ALBERT

Beschreibung: Organic and organometallic reactants in aqueous electrolytes, being composed of earth-abundant elements, are promising redox active candidates for cost-effective organic redox flow batteries (ORFBs). Various compounds of ferrocene and methyl viologen have been examined as promising redox actives for this application. Herein, we examined the influence of the electrolyte pH and the salt anion on model redox active organic cations, bis((3-trimethylammonio) propyl)- ferrocene dichloride (BTMAP-Fc) and bis(3-trimethylammonio) propyl viologen tetrachloride (BTMAP-Vi), which have exhibited excellent cycling stability and capacity retention at ≥1.00 M concentration [E. S. Beh, et al. ACS Energy Lett. 2, 639–644 (2017)]. We examined the solvation shell around BTMAP-Fc and BTMAP-Vi at acidic and neutral pH with SO42-, Cl−, and CH3SO3− counterions and elucidated their impact on cation diffusion coefficient, first electron transfer rate constant, and thereby the electrochemical Thiele modulus. The electrochemical Thiele modulus was found to be exponentially correlated with the solvent reorganizational energy (λ) in both neutral and acidic pH. Thus, λ is proposed as a universal descriptor and selection criteria for organic redox flow battery electrolyte compositions. In the specific case of the BTMAP-Fc/BTMAP-Vi ORFB, low pH electrolytes with methanesulfonate or chloride counterions were identified as offering the best balance of transport and kinetic requirements.

Beschreibung: When displayed on erythrocytes, peptides and proteins can drive antigen-specific immune tolerance. Here, we investigated a straightforward approach based on erythrocyte binding to promote antigen-specific tolerance to both peptides and proteins. We first identified a robust erythrocyte-binding ligand. A pool of one million fully d-chiral peptides was injected into mice, blood cells were isolated, and ligands enriched on these cells were identified using nano-liquid chromatography–tandem mass spectrometry. One round of selection yielded a murine erythrocyte-binding ligand with an 80 nM apparent dissociation constant, Kd. We modified an 83-kDa bacterial protein and a peptide antigen derived from ovalbumin (OVA) with the identified erythrocyte-binding ligand. An administration of the engineered bacterial protein led to decreased protein-specific antibodies in mice. Similarly, mice given the engineered OVA-derived peptide had decreased inflammatory anti-OVA CD8+ T cell responses. These findings suggest that our tolerance-induction strategy is applicable to both peptide and protein antigens and that our in vivo selection strategy can be used for de novo discovery of robust erythrocyte-binding ligands.

Beschreibung: Platinum group elements (PGE) are considered to be very poorly soluble in aqueous fluids in most natural hydrothermal–magmatic contexts and industrial processes. Here, we combined in situ X-ray absorption spectroscopy and solubility experiments with atomistic and thermodynamic simulations to demonstrate that the trisulfur radical ion S3•− forms very stable and soluble complexes with both PtII and PtIV in sulfur-bearing aqueous solution at elevated temperatures (∼300 °C). These Pt-bearing species enable (re)mobilization, transfer, and focused precipitation of platinum up to 10,000 times more efficiently than any other common inorganic ligand, such as hydroxide, chloride, sulfate, or sulfide. Our results imply a far more important contribution of sulfur-bearing hydrothermal fluids to PGE transfer and accumulation in the Earth’s crust than believed previously. This discovery challenges traditional models of PGE economic concentration from silicate and sulfide melts and provides new possibilities for resource prospecting in hydrothermal shallow crust settings. The exceptionally high capacity of the S3•− ion to bind platinum may also offer new routes for PGE selective extraction from ore and hydrothermal synthesis of noble metal nanomaterials.

Beschreibung: Objectives N-Terminal pro Brain Natriuretic Peptide (NT-proBNP) is a diagnostic marker for heart failure and a prognostic factor for cardiovascular disease (CVD). The aim of this study was to examine the association of socioeconomic position (SEP) with NT-proBNP while assessing sex-differences and the impact of CVD risk factors and prevalent CVD on the association. Methods Baseline data of 4598 participants aged 45–75 years of the Heinz Nixdorf Recall Study were used. Income and education were used as SEP indicators. Age- and sex-adjusted linear regression models were fitted to calculate effect size estimates and 95% confidence intervals (95%-CIs) for the total effect of SEP indicators on NT-proBNP, while potential mediation was assessed by additionally accounting for traditional CVD risk factors (i.e., systolic blood pressure, HDL cholesterol, LDL cholesterol, diabetes, anti-hypertensive medication, lipid-lowering medication, BMI, current smoking). Education and income were included separately in the models. Results With an age- and sex-adjusted average change in NT-proBNP of -6.47% (95%-CI: -9.91; -2.91) per 1000€, the association between income and NT-proBNP was more pronounced compared to using education as a SEP indicator (-0.80% [95%-CI: -1.92; 0.32] per year of education). Sex-stratified results indicated stronger associations in men (-8.43% [95%-CI: -13.21; -3.38] per 1000€; -1.63% [95%-CI: -3.23; -0.001] per year of education) compared to women (-5.10% [95%-CI: -9.82; -0.01] per 1000€; -1.04% [95%-CI: -2.59; 0.50] per year of education). After adjusting for CVD risk factors some of the observed effect size estimates were attenuated, while the overall association between SEP indicators and NT-proBNP was still indicated. The exclusion of participants with prevalent coronary heart disease or stroke did not lead to a substantial change in the observed associations. Conclusions In the present study associations of education and income with NT-proBNP were observed in a population-based study sample. Only parts of the association were explained by traditional CVD risk factors, while there were substantial sex-differences in the strength of the observed association. Overt coronary heart disease or stroke did not seem to trigger the associations.

Beschreibung: The maned wolf (Chrysocyon brachyurus) is an induced ovulator. Though the mechanism of ovulation induction remains unknown, it is suspected to be urinary chemical signals excreted by males. This study assessed volatile organic compounds (VOCs) in weekly urine samples across 5 months from 13 maned wolves (6 intact males, 1 neutered male, 6 females) with the goal of identifying VOCs that are differentially expressed across sex, reproductive status, and pairing status. Solid-phase microextraction (SPME) and gas chromatography-mass spectrometry (GC-MS) were used to extract and separate VOCs that were identified via spectral matching with authentic standards, with spectral libraries, or with new software that further matches molecular fragment structures with mass spectral peaks. Two VOCs were present across all 317 urine samples: 2,5-dimethyl pyrazine and 2-methyl-6-(1-propenyl)-pyrazine. Fifteen VOCs differed significantly (Adj. P 〈 0.001 and |log2 fold change| 〉2.0) between intact males and females. Using partial least squares-discriminant analysis, the compounds with the highest importance to the sex classification were delta-decalactone, delta-dodecalactone, and bis(prenyl) sulfide. Sixty-two VOCs differed between intact males and the neutered male. Important classifier compounds were 3-ethyl 2,5-dimethyl pyrazine, 2-methyl-6-(1-propenyl)-pyrazine, and tetrahydro-2-isopentyl-5-propyl furan. Several VOCs established as important here have been implicated in reproductive communication in other mammals. This study is the most robust examination of differential expression in the maned wolf thus far and provides the most comprehensive analysis of maned wolf urinary VOCs to date, increasing the sample size substantially over previous chemical communication studies in this species. New data analysis software allowed for the identification of compounds in the hormone-producing mevalonate pathway which were previously unreported in maned wolf urine. Several putative semiochemicals were identified as good candidates for behavioral bioassays to determine their role in maned wolf reproduction, and specifically in ovulation induction.

Beschreibung: Background Patients admitted to intensive care units (ICU) are at an increased risk of developing immobility related complications. Physiotherapists are challenged to employ preventive and rehabilitative strategies to combat these effects. Passive limb range of motion (PROM) exercises- a part of early mobilization-aid in maintaining joint range of motion and functional muscle strength and forms a part of treatment for patients in ICU. However, there is a lack of evidence on practice of PROM exercises on patients admitted to ICU in the United Arab Emirates (UAE). This study aimed at exploring practices regarding the same in UAE. Methods This survey, conducted from January 2021 to February 2021 in College of Physiotherapy, Sharjah University studied practice of physiotherapists in the intensive care units. Physiotherapists currently working in ICU completed an online questionnaire composed of forty-two questions about physiotherapy service provision, assessment and intervention in the intensive care units. Results 33 physiotherapists completed the survey. 66.6% of respondents routinely assessed PROM for all the patients in ICU referred for physiotherapy. 84.8% of them assessed all the joints. More than half of the respondents (57.8%) reported that they administered PROM regularly to all the patients. According to 63.6% respondents, maintaining joint range of motion was the main reason for performing PROM. Responses pertaining to sets and repetitions of PROM were variable ranging from 1–6 sets and from 3 to 30 repetitions. Personal experience, resources/financial consideration and research findings were found to have influence on the practice. Conclusions PROM was found to be one of the frequently used mobilization techniques administered by physiotherapists in the intensive care units and was mostly performed after assessment. Maintaining joint range of motion was the main aim for performing PROM. Variability was found in the sets and repetitions of PROM administered. Various factors influenced the practice of PROM.

Beschreibung: The role the mammary epithelial circadian clock plays in gland development and lactation is unknown. We hypothesized that mammary epithelial clocks function to regulate mammogenesis and lactogenesis, and propose the core clock transcription factor BMAL1:CLOCK regulates genes that control mammary epithelial development and milk synthesis. Our objective was to identify transcriptional targets of BMAL1 in undifferentiated (UNDIFF) and lactogen differentiated (DIFF) mammary epithelial cells (HC11) using ChIP-seq. Ensembl gene IDs with the nearest transcriptional start site to ChIP-seq peaks were explored as potential targets, and represented 846 protein coding genes common to UNDIFF and DIFF cells and 2773 unique to DIFF samples. Genes with overlapping peaks between samples (1343) enriched cell-cell adhesion, membrane transporters and lipid metabolism categories. To functionally verify targets, an HC11 line with Bmal1 gene knocked out (BMAL1-KO) using CRISPR-CAS was created. BMAL1-KO cultures had lower cell densities over an eight-day growth curve, which was associated with increased (p

Beschreibung: Objectives N-benzoyl-DL-arginine peptidase (trypsin-like peptidase) is specifically produced by certain strains of periodontitis-associated bacteria. We aimed to examine the effectiveness of an objectively quantified trypsin-like peptidase activity assay (TLP-AA) for detecting severe periodontitis. Methods The study population included 347 adults (108 men and 239 women; average age, 43.3 years) who underwent a full-mouth periodontal examination. Specimens for the TLP-AA were obtained using tongue swabs. Using a color reader, the TLP-AA results were obtained as a* values, with higher positive a* values indicating an increased intense enzymatic activity. The predictive validity of the TLP-AA results for severe periodontitis was assessed using receiver operating characteristic curve analysis and the periodontitis case definition provided by the Centers for Disease Control and Prevention/American Academy of Periodontology as the gold standard. Furthermore, multivariable logistic regression analyses were performed to predict severe periodontitis using the TLP-AA results and health characteristics, as the exposure variables. Results Severe periodontitis was observed in 5.2% of the participants. TLP-AA had high diagnostic accuracy for severe periodontitis, with an area under the curve of 0.83 (95% confidence interval [CI]: 0.75–0.92). The cut-off score for the a* value that best differentiated individuals with severe periodontitis was 0.09, with a sensitivity of 83% and specificity of 77%. Multivariable logistic regression analyses revealed that the TLP-AA results were significantly associated with severe periodontitis after adjusting for health characteristics (adjusted odds ratios: 1.90 [95% CI: 1.37–2.62] for the a* value). Conclusions Objectively quantified TLP-AA results are potentially useful for detecting severe periodontitis in epidemiological surveillance.

Beschreibung: Introduction Suicidality is a risk of a person committing suicide often characterized by suicidal ideation, intent or attempts. Despite the high burden of suicidality among individuals living with HIV and HAIDS, there is paucity of data on the impact of suicidality on clinical (such as CD4 counts and HIV disease progression) and behavioural outcomes (such as adherence to HIV Medications). Cross-sectional investigations of these associations are often complicated by bidirectional causal relationships and hence the need for longitudinal study designs. We conducted a cohort study to determine the impact of suicidality on clinical and behavioural outcomes among adults living with HIV/AIDS in Uganda. Materials and methods We conducted the study among 1099 ART naïve adults living with HIV/AIDS in Uganda. Data were collected at three time points: baseline, 6 and 12 months. Multiple regression and discrete time survival models were used to determine the relationship between suicidality and indices of HIV outcomes. Results Majority of the participants were female and the participant mean age was 35 years. Most of them (73%) had primary or no formal education. The proportion of participants with suicidality decreased from 2.9% at baseline to roughly 1% both at month 6 and month 12. Of the investigated clinical and behavioural outcomes, baseline suicidality only had a negative impact on missing a dose of ART where the odds of missing a dose of ART were 8.25 (95% CI 2.45–27.71, p〉0.01) times higher for participants with suicidality compared to those without suicidality. The following outcomes were not significantly impacted by baseline suicidality: HIV clinical stage, CD4 count and risky sexual behaviour. Conclusions The fact that baseline suicidality significantly negatively impacted ART adherence calls for the incorporation of psychosocial interventions to target indices of psychological distress such as suicidality to improve HIV related outcomes.

Beschreibung: Gram-negative bacteria take up the essential ion Fe3+ as ferric-siderophore complexes through their outer membrane using TonB-dependent transporters. However, the subsequent route through the inner membrane differs across many bacterial species and siderophore chemistries and is not understood in detail. Here, we report the crystal structure of the inner membrane protein FoxB (from Pseudomonas aeruginosa) that is involved in Fe-siderophore uptake. The structure revealed a fold with two tightly bound heme molecules. In combination with in vitro reduction assays and in vivo iron uptake studies, these results establish FoxB as an inner membrane reductase involved in the release of iron from ferrioxamine during Fe-siderophore uptake.

Beschreibung: Background The COVID-19 vaccination campaign in the US has been immensely successful in vaccinating those who are receptive, further increases in vaccination rates however will require more innovative approaches to reach those who remain hesitant. Developing vaccination strategies that are modelled on what people want could further increase uptake. Methods and findings To inform COVID-19 vaccine distribution strategies that are aligned with public preferences we conducted a discrete choice experiment among the US public (N = 2,895) between March 15 to March 22, 2021. We applied sampling weights, evaluated mean preferences using mixed logit models, and identified latent class preference subgroups. On average, the public prioritized ease, preferring single to two dose vaccinations (mean preference: -0.29; 95%CI: -0.37 to -0.20), vaccinating once rather than annually (mean preference: -0.79; 95%CI: -0.89 to -0.70) and reducing waiting times at vaccination sites. Vaccine enforcement reduced overall vaccine acceptance (mean preference -0.20; 95%CI: -0.30 to -0.10), with a trend of increasing resistance to enforcement with increasing vaccine hesitancy. Latent class analysis identified four distinct preference phenotypes: the first prioritized inherent “vaccine features” (46.1%), the second were concerned about vaccine “service delivery” (8.8%), a third group desired “social proof” of vaccine safety and were susceptible to enforcement (13.2%), and the fourth group were “indifferent” to vaccine and service delivery features and resisted enforcement (31.9%). Conclusions This study identifies several critical insights for the COVID-19 public health response. First, identifying preference segments is essential to ensure that vaccination services meet the needs of diverse population subgroups. Second, making vaccination easy and promoting autonomy by simplifying services and offering the public choices (where feasible) may increase uptake in those who remain deliberative. And, third vaccine mandates have the potential to increase vaccination rates in susceptible groups but may simultaneously promote control aversion and resistance in those who are most hesitant.

Beschreibung: Mountains are reservoirs for a tremendous biodiversity which was fostered by a suite of factors acting in concert throughout evolutionary times. These factors can be climatic, geological, or biotic, but the way they combine through time to generate diversity remains unknown. Here, we investigate these factors as correlates of diversification of three closely related sections of Gentiana in the European Alpine System. Based upon phylogenetic approaches coupled with divergence dating and ancestral state reconstructions, we attempted to identify the role of bedrock preferences, chromosome numbers coupled with relative genome sizes estimates, as well as morphological features through time. We also investigated extant climatic preferences using a heavily curated set of occurrence records individually selected for superior precision, and quantified rates of climatic niche evolution in each section. We found that a number of phylogenetic incongruences derail the identification of correlates of diversification, yet a number of patterns persist regardless of the topology considered. All the studied correlates are likely to have contributed to the diversification of Gentiana in Europe, however, their respective importance varied through time and across clades. Chromosomal variation and divergence of climatic preferences appear to correlate with diversification throughout the evolution of European Gentiana (Oligocene to present), whereas shifts in bedrock preferences appear to have been more defining during recent diversification (Pliocene). Overall, a complex interaction among climatic, geological and biotic attributes appear to have supported the diversification of Gentiana across the mountains of Europe, which based upon phylogenetic as well as other evidence, was probably also bolstered by hybridization.

Beschreibung: Introduction The single-leg heel raise test (SLHR) is commonly used in clinical settings to approximate plantar flexor strength, yet this is neither validated nor supported physiologically. The purposes of this study were to: determine (1) associations between SLHR repetitions, maximal plantar flexor strength, and reductions in strength; and (2) whether sex differences exist in performance of the SLHR. Methods Twenty-eight young, healthy participants (14 males,14 females, 19–30 years) performed repeated single-leg heel raises to task failure. Pre- and post-task measures included maximal voluntary isometric contractions (MVIC), and voluntary activation and contractile properties of the plantar flexor muscles, assessed using peripheral electrical stimulation of the tibial nerve. Surface electromyography was recorded for the medial and lateral gastrocnemius, soleus, and anterior tibialis muscles. Results The SLHR resulted in 20.5% reductions in MVIC torque (p

Beschreibung: We consider a nonlinear autonomous system of N≫1 degrees of freedom randomly coupled by both relaxational (“gradient”) and nonrelaxational (“solenoidal”) random interactions. We show that with increased interaction strength, such systems generically undergo an abrupt transition from a trivial phase portrait with a single stable equilibrium into a topologically nontrivial regime of “absolute instability” where equilibria are on average exponentially abundant, but typically, all of them are unstable, unless the dynamics is purely gradient. When interactions increase even further, the stable equilibria eventually become on average exponentially abundant unless the interaction is purely solenoidal. We further calculate the mean proportion of equilibria that have a fixed fraction of unstable directions.

Beschreibung: Humans and nonhuman animals display conformist as well as anticonformist biases in cultural transmission. Whereas many previous mathematical models have incorporated constant conformity coefficients, empirical research suggests that the extent of (anti)conformity in populations can change over time. We incorporate stochastic time-varying conformity coefficients into a widely used conformity model, which assumes a fixed number n of “role models” sampled by each individual. We also allow the number of role models to vary over time (nt). Under anticonformity, nonconvergence can occur in deterministic and stochastic models with different parameter values. Even if strong anticonformity may occur, if conformity or random copying (i.e., neither conformity nor anticonformity) is expected, there is convergence to one of the three equilibria seen in previous deterministic models of conformity. Moreover, this result is robust to stochastic variation in nt. However, dynamic properties of these equilibria may be different from those in deterministic models. For example, with random conformity coefficients, all equilibria can be stochastically locally stable simultaneously. Finally, we study the effect of randomly changing weak selection. Allowing the level of conformity, the number of role models, and selection to vary stochastically may produce a more realistic representation of the wide range of group-level properties that can emerge under (anti)conformist biases. This promises to make interpretation of the effect of conformity on differences between populations, for example those connected by migration, rather difficult. Future research incorporating finite population sizes and migration would contribute added realism to these models.

Beschreibung: Stream temperature science and management is rapidly shifting from single-metric driven approaches to multi-metric, thermal regime characterizations of streamscapes. Given considerable investments in recovery of cold-water fisheries (e.g., Pacific salmon and other declining native species), understanding where cold water is likely to persist, and how cold-water thermal regimes vary, is critical for conservation. California’s unique position at the southern end of cold-water ecosystems in the northern hemisphere, variable geography and hydrology, and extensive flow regulation requires a systematic approach to thermal regime classification. We used publicly available, long-term (〉 8 years) stream temperature data from 77 sites across California to model their thermal regimes, calculate three temperature metrics, and use the metrics to classify each regime with an agglomerative nesting algorithm. Then, we assessed the variation in each class and considered underlying physical or anthropogenic factors that could explain differences between classes. Finally, we considered how different classes might fit existing criteria for cool- or cold-water thermal regimes, and how those differences complicate efforts to manage stream temperature through regulation. Our results demonstrate that cool- and cold-water thermal regimes vary spatially across California. Several salient findings emerge from this study. Groundwater-dominated streams are a ubiquitous, but as yet, poorly explored class of thermal regimes. Further, flow regulation below dams imposes serial discontinuities, including artificial thermal regimes on downstream ecosystems. Finally, and contrary to what is often assumed, California reservoirs do not contain sufficient cold-water storage to replicate desirable, reach-scale thermal regimes. While barriers to cold-water conservation are considerable and the trajectory of cold-water species towards extinction is dire, protecting reaches that demonstrate resilience to climate warming remains worthwhile.

Beschreibung: This paper investigated the appropriate specifications of Engel curves for non-food expenditure categories and estimated the deprivation indices of non-food needs in rural areas using a semi parametric examination of the presence of saturation points. The study used the extended partial linear model (EPLM) and adopted two estimation methods—the double residual estimator and differencing estimator—to obtain flexible shapes across different expenditure categories and estimate equivalence scales. We drew on data of the Egyptian Household Income, Expenditure, and Consumption Survey (HIEC). Our paper provides empirical evidence that the rankings of most non-food expenditure categories is of rank three at most. Rural households showed high economies of scale in non-food consumption, with child’s needs accounting for only 10% of adult’s non-food needs. Based on semi-parametrically estimated consumption behavior, the tendency of non-food expenditure categories to saturate did not emerge. While based on parametrically estimated consumption behavior, rural areas exhibited higher deprivation indices in terms of health and education expenditure categories, which indicates the need to design specific programs economically targeting such vulnerable households.

Beschreibung: Menzerath’s law is a quantitative linguistic law which states that, on average, the longer is a linguistic construct, the shorter are its constituents. In contrast, Menzerath-Altmann’s law (MAL) is a precise mathematical power-law-exponential formula which expresses the expected length of the linguistic construct conditioned on the number of its constituents. In this paper, we investigate the anatomy of MAL for constructs being word tokens and constituents being syllables, measuring its length in graphemes. First, we derive the exact form of MAL for texts generated by the memoryless source with three emitted symbols, which can be interpreted as a monkey typing model or a null model. We show that this null model complies with Menzerath’s law, revealing that Menzerath’s law itself can hardly be a criterion of complexity in communication. This observation does not apply to the more precise Menzerath-Altmann’s law, which predicts an inverted regime for sufficiently range constructs, i.e., the longer is a word, the longer are its syllables. To support this claim, we analyze MAL on data from 21 languages, consisting of texts from the Standardized Project Gutenberg. We show the presence of the inverted regime, not exhibited by the null model, and we demonstrate robustness of our results. We also report the complicated distribution of syllable sizes with respect to their position in the word, which might be related with the emerging MAL. Altogether, our results indicate that Menzerath’s law—in terms of correlations—is a spurious observation, while complex patterns and efficiency dynamics should be rather attributed to specific forms of Menzerath-Altmann’s law.

Beschreibung: Temperate grassland soils store significant amounts of carbon (C). Estimating how much livestock grazing and manuring can influence grassland soil organic carbon (SOC) is key to improve greenhouse gas grassland budgets. The Rothamsted Carbon (RothC) model, although originally developed and parameterized to model the turnover of organic C in arable topsoil, has been widely used, with varied success, to estimate SOC changes in grassland under different climates, soils, and management conditions. In this paper, we hypothesise that RothC-based SOC predictions in managed grasslands under temperate moist climatic conditions can be improved by incorporating small modifications to the model based on existing field data from diverse experimental locations in Europe. For this, we described and evaluated changes at the level of: (1) the soil water function of RothC, (2) entry pools accounting for the degradability of the exogenous organic matter (EOM) applied (e.g., ruminant excreta), (3) the month-on-month change in the quality of C inputs coming from plant residues (i.e above-, below-ground plant residue and rhizodeposits), and (4) the livestock trampling effect (i.e., poaching damage) as a common problem in areas with higher annual precipitation. In order to evaluate the potential utility of these changes, we performed a simple sensitivity analysis and tested the model predictions against averaged data from four grassland experiments in Europe. Our evaluation showed that the default model’s performance was 78% and whereas some of the modifications seemed to improve RothC SOC predictions (model performance of 95% and 86% for soil water function and plant residues, respectively), others did not lead to any/or almost any improvement (model performance of 80 and 46% for the change in the C input quality and livestock trampling, respectively). We concluded that, whereas adding more complexity to the RothC model by adding the livestock trampling would actually not improve the model, adding the modified soil water function and plant residue components, and at a lesser extent residues quality, could improve predictability of the RothC in managed grasslands under temperate moist climatic conditions.

Beschreibung: Usutu virus (USUV) is an emerging arbovirus in Europe that has been increasingly identified in asymptomatic humans and donated blood samples and is a cause of increased incidents of neuroinvasive human disease. Treatment or prevention options for USUV disease are currently nonexistent, the result of a lack of understanding of the fundamental elements of USUV pathogenesis. Here, we report two structures of the mature USUV virus, determined at a resolution of 2.4 Å, using single-particle cryogenic electron microscopy. Mature USUV is an icosahedral shell of 180 copies of envelope (E) and membrane (M) proteins arranged in the classic herringbone pattern. However, unlike previous reports of flavivirus structures, we observe virus subpopulations and differences in the fusion loop disulfide bond. Presence of a second, unique E glycosylation site could elucidate host interactions, contributing to the broad USUV tissue tropism. The structures provide a basis for exploring USUV interactions with glycosaminoglycans and lectins, the role of the RGD motif as a receptor, and the inability of West Nile virus therapeutic antibody E16 to neutralize the mature USUV strain SAAR-1776. Finally, we identify three lipid binding sites and predict key residues that likely participate in virus stability and flexibility during membrane fusion. Our findings provide a framework for the development of USUV therapeutics and expand the current knowledge base of flavivirus biology.

Beschreibung: The success of unmanned car, an emerging tool of transportation with so many advantages, depends to a large extent on its user acceptability. Potential designers are both the decision makers of driverless car design and the users of driverless cars. This study aims to explore the influencing factors of the potential designers’ intention to use unmanned cars. Based on the theory of Technology Acceptance Model (TAM), this study further expanded the TAM by incorporating perceived trust, perceived enjoyment and self-efficacy, so as to explain and predict potential designers’ intention to use unmanned cars. The questionnaire is determined through theoretical literature, pre-tests, etc., and the Structural Equation Model is used to analyze the data of 202 valid survey samples to investigate the influencing factors of the willingness to use unmanned vehicles. The results show that potential designers’ intention to use unmanned cars is positively affected by perceived trust, perceived enjoyment, perceived usefulness and perceived ease of use, and perceived trust has a positive effect on perceived ease of use, self-efficacy and perceived ease of use also have a positive effect on perceived usefulness. The findings of this study can provide designers and developers of unmanned cars, policy makers and implementers with guidance in the follow-up design, policy formulation and advertising of unmanned cars.

Beschreibung: Global value chains are formed through value-added trade, and some regions promote economic integration by concluding regional trade agreements to promote these chains. However, it has not been established to quantitatively assess the scope and extent of economic integration involving various sectors in multiple countries. In this study, we used the World Input–Output Database to create a cross-border sector-wise network of trade in value-added (international value-added network) covering the period of 2000–2014 and evaluated them using network science methods. By applying Infomap to the international value-added network, we confirmed two regional communities: Europe and the Pacific Rim. We applied Helmholtz–Hodge decomposition to the value-added flows within the region into potential and circular flows, and clarified the annual evolution of the potential and circular relationships between countries and sectors. The circular flow component of the decomposition was used to define an economic integration index. Findings confirmed that the degree of economic integration in Europe declined sharply after the economic crisis in 2009 to a level lower than that in the Pacific Rim. The European economic integration index recovered in 2011 but again fell below that of the Pacific Rim in 2013. Moreover, sectoral economic integration indices suggest what Europe depends on Russia in natural resources makes the European economic integration index unstable. On the other hand, the indices of the Pacific Rim suggest the steady economic integration index of the Pacific Rim captures the stable global value chains from natural resources to construction and manufactures of motor vehicles and high-tech products.

Beschreibung: Background COPD and asthma exacerbations result in many emergency department admissions. Not all treatments are successful, often leading to hospital readmissions. Aims We sought to develop predictive models for exacerbation treatment outcome in a cohort of exacerbating asthma and COPD patients presenting to the emergency department. Methods Treatment failure was defined as the need for additional systemic corticosteroids (SCS) and/or antibiotics, hospital readmissison or death within 30 days of initial emergency department visit. We performed univariate analysis comparing characteristics of patients either given or not given SCS at exacerbation and of patients who succeeded versus failed treatment. Patient demographics, medications and exacerbation symptoms, physiology and biology were available. We developed multivariate random forest models to identify predictors of SCS prescription and for predicting treatment failure. Results Data were available for 81 patients, 43 (53%) of whom failed treatment. 64 (79%) of patients were given SCS. A random forest model using presence of wheeze at exacerbation and blood eosinophil percentage predicted SCS prescription with area under receiver operating characteristic curve (AUC) 0.69. An 11 variable random forest model (which included medication, previous exacerbations, symptoms and quality of life scores) could predict treatment failure with AUC 0.81. A random forest model using just the two best predictors of treatment failure, namely, visual analogue scale for breathlessness and sputum purulence, predicted treatment failure with AUC 0.68. Conclusion Prediction of exacerbation treatment outcome can be achieved via supervised machine learning combining different predictors at exacerbation. Validation of our predictive models in separate, larger patient cohorts is required.

Beschreibung: Regulation systems for fluid-driven soft robots predominantly consist of inflexible and bulky components. These rigid structures considerably limit the adaptability and mobility of these robots. Soft valves in various forms for fluidic actuators have been developed, primarily fluidically or electrically driven. However, fluidic soft valves require external pressure sources that limit robot locomotion. State-of-the-art electrostatic valves are unable to modulate pressure beyond 3.5 kPa with a sufficient flow rate (〉6 mL⋅min−1). In this work, we present an electrically powered soft valve for hydraulic actuators with mesoscale channels based on a different class of ultrahigh-power density dynamic dielectric elastomer actuators. The dynamic dielectric elastomer actuators (DEAs) are actuated at 500 Hz or above. These DEAs generate 300% higher blocked force compared with the dynamic DEAs in previous works and their loaded power density reaches 290 W⋅kg−1 at operating conditions. The soft valves are developed with compact (7 mm tall) and lightweight (0.35 g) dynamic DEAs, and they allow effective control of up to 51 kPa of pressure and a 40 mL⋅min−1 flow rate with a response time less than 0.1 s. The valves can also tune flow rates based on their driving voltages. Using the DEA soft valves, we demonstrate control of hydraulic actuators of different volumes and achieve independent control of multiple actuators powered by a single pressure source. This compact and lightweight DEA valve is capable of unprecedented electrical control of hydraulic actuators, showing the potential for future onboard motion control of soft fluid-driven robots.

Beschreibung: Metapopulation capacity provides an analytic tool to quantify the impact of landscape configuration on metapopulation persistence, which has proven powerful in biological conservation. Yet surprisingly few efforts have been made to apply this approach to multispecies systems. Here, we extend metapopulation capacity theory to predict the persistence of trophically interacting species. Our results demonstrate that metapopulation capacity could be used to predict the persistence of trophic systems such as prey–predator pairs and food chains in fragmented landscapes. In particular, we derive explicit predictions for food chain length as a function of metapopulation capacity, top-down control, and population dynamical parameters. Under certain assumptions, we show that the fraction of empty patches for the basal species provides a useful indicator to predict the length of food chains that a fragmented landscape can support and confirm this prediction for a host–parasitoid interaction. We further show that the impact of habitat changes on biodiversity can be predicted from changes in metapopulation capacity or approximately by changes in the fraction of empty patches. Our study provides an important step toward a spatially explicit theory of trophic metacommunities and a useful tool for predicting their responses to habitat changes.

Beschreibung: Introduction The concept of death is abstract, complex and has a number of meanings. Thus, its understanding and the approach taken to it depend, to a large extent, on aspects such as age, culture, training and religion. Nursing students have regular contact with the process of death and so it is of great interest to understand the attitudes they have towards it. As we live in a plural society it is even more interesting to not only understand the attitudes of Spanish students but, also, those of students coming from other countries. In the present article, we seek to identify and compare the attitudes held by nursing degree students at Hekima-Santé University (Senegal) and the University of Huelva (Spain) about end of life processes. The study identifies elements that condition attitudes and coping with death, whilst considering curricular differences with regards to specific end of life training. Method A descriptive, cross-sectional and multi-center study was conducted. The overall sample (N = 142) was divided into groups: Hekima-Santé University (Dakar, Senegal) and the University of Huelva (Huelva, Spain). The measurement instruments used were an ad-hoc questionnaire and Bugen´s Coping with Death Scale. Results Statistically significant differences (p = 0.005, 95%CI) were found in relation to overall Bugen Scale scores. We can confirm that specialized end of life training (University of Huelva, Spain) did not lead to better coping when compared with a population whose academic curriculum did not provide specific training and who engaged in more religious practices (Hekima-Santé University, Senegal). Conclusions In cultures where religion not only influences the spiritual dimension of the individual, but acts in the ethical and moral system and consequently in the economic, educational and family sphere, the accompaniment at the end of life transcends the formative plane. Considering the plural society in which we live, the training that integrates the Degree in Nursing with regard to the care of the final process, must be multidimensional in which spirituality and faith are integrated, working emotional and attentional skills, as well as cultural competence strategies in this process.

Beschreibung: Introduction Absenteeism of frontline health workers in public sector facilities is widespread in low-income countries. There is little quantitative evidence on how health worker absenteeism influences patient treatment seeking behavior, though low public sector utilization and heavy reliance on the informal sector are well documented in low-income settings. Methods Using a unique panel dataset covering health facilities and households over a 10-month period in Uganda, we investigate the extent to which health worker absenteeism (defined as zero health workers present at a health facility) impacts patient care seeking behavior, testing, and treatment. Results We find high rates of health worker absenteeism at public sector health facilities, with most of the absenteeism occurring at lower level public health clinics. On average, no health worker was present in 42% of all days monitored in lowest level public health clinics, whereas this number was less than 5% in high level public hospitals and private facilities. In our preferred empirical model with household fixed effects, we find that health worker absenteeism reduces the odds that a patient seeks care in the public sector (OR = 0.65, 95% CI = 0.44–0.95) and receives malaria testing (OR = 0.73, 95% CI = 0.53–0.99) and increases the odds of paying out-of-pocket for treatment (OR = 1.41, 95% CI = 1.10–1.80). The estimated differences in care-seeking are larger for children under-five than for the overall study population. Conclusions The impact of health worker absenteeism on the quality of care received as well as the financial burden faced by households in sub-Saharan Africa is substantial.

Beschreibung: Braiding of topological structures in complex matter fields provides a robust framework for encoding and processing information, and it has been extensively studied in the context of topological quantum computation. In living systems, topological defects are crucial for the localization and organization of biochemical signaling waves, but their braiding dynamics remain unexplored. Here, we show that the spiral wave cores, which organize the Rho-GTP protein signaling dynamics and force generation on the membrane of starfish egg cells, undergo spontaneous braiding dynamics. Experimentally measured world line braiding exponents and topological entropy correlate with cellular activity and agree with predictions from a generic field theory. Our analysis further reveals the creation and annihilation of virtual quasi-particle excitations during defect scattering events, suggesting phenomenological parallels between quantum and living matter.

Beschreibung: Malaria is still a global health problem. Plasmodium is a single-cell protozoan parasite that causes malaria and is transmitted to humans through the female Anopheles mosquito. The previous study showed that Sonchus arvensis L. callus has antiplasmodial activity. Several treatments are needed for callus quality improvement for antimalarial compound production. This study aimed to examine the effect of dolomite [CaMg(CO3)2] on growth (morpho-anatomical structure and biomass), secondary metabolite production, and in vitro antiplasmodial activity of S. arvensis L. callus. In this study, leaf explants were grown in Murashige and Skoog medium with a combination of 2,4-dichlorophenoxyacetic acid (2,4-D, one mg/L) and 6-benzyl amino purine (BAP, 0.5 mg/L) with dolomite (50, 75, 100, 150, and 200 mg/L). The 21 days callus ethanolic and methanolic extract were analyzed by gas chromatography-mass spectrometry (GC-MS) and thin-layer chromatography (TLC). The antiplasmodial test was performed on a blood culture infected with Plasmodium falciparum strain 3D7 using the Rieckmann method. The results showed that dolomite significantly affected callus growth, metabolite profile, and in vitro antiplasmodial activity. Dolomite (150 mg/L) showed the highest biomass (0.590 ± 0.136 g fresh weight and 0.074 ± 0.008 g dry weight). GC-MS analysis detected four compounds from callus ethanolic extract. Pelargonic acid, decanoic acid, and hexadecanoic acid were major compounds. One new terpenoid compound is based on TLC analysis. S. arvensis L. callus has antiplasmodial activity with the IC50 value of 5.037 μg/mL. It was three times lower than leaf methanolic extract and five times lower than leaf ethanolic extract.

Beschreibung: Linear Parameter Varying (LPV) systems and their control have gained attraction recently as they approximate nonlinear systems with higher order than ordinary linear systems. On the other hand, time delay is an inherent part of various real-life applications. A supervisory control structure is proposed in this paper for LPV systems subject to time delays. In the proposed control structure, a supervisor selects the most suitable controller from a bank of controllers; which desires to enhance the performance of closed-loop system in contrast with using a single robust controller. The analysis is based on the celebrated Smith predictor for time delay compensation and we provide a sufficient condition to assure the stability of the closed-loop switched system in terms of dwell time. Simulations on blood pressure control of hypertension patients in postoperative scenario are used to exemplify the effectiveness of the utilized technique. The operating region of the system is partitioned into five smaller operating regions to construct corresponding robust controllers and perform hysteresis switching amongst them. Simulation results witnessed that the proposed control scheme demonstrated a pressure undershoot less than the desired value of 10 mmHg while the Mean Arterial Pressure (MAP) remains within ±5 mmHg of the desired value.

Beschreibung: Background Assessing fitness to drive and predicting driving cessation remains a challenge for primary care physicians using standard screening procedures. The objective of this study was to prospectively evaluate the properties of neuropsychological screening tests, including the Trail Making Test (TMT), Clock Drawing Test (CDT), Montreal Cognitive Assessment (MoCA), Useful Field of View (UFOV), and Timed Up and Go (TUG) test, in predicting driving cessation for health reasons in drivers older than 70 years of age. Design and methods This prospective cohort study, with a median follow-up of 4 years for drivers of 70 years old or older with an active driving license in Switzerland, included 441 participants from a driving refresher course dedicated to volunteer senior drivers. Cases were drivers reported in the national driving registry who lost their license following a health-related accident, who were reported as unfit to drive by their physician or voluntarily ceased driving for health reasons. Survival analysis was used to measure the hazard ratio of driving cessation by adjusting for age and sex and to evaluate the predictive value of combining 3 or more positive tests in predicting driving cessation during a 4-year follow-up. Results A total of 1738 person-years were followed-up in the cohort, with 19 (4.3%) having ceased driving for health reasons. We found that participants with a TMT-A 〈 54 sec and TMT-B 〈 150 sec at baseline had a significantly lower cumulative hazard of driving cessation in 4 years than those with slower performance (adjusted HR 3, 95% CI: 1.16–7.78, p = 0.023). Participants who performed a CDT ≥ 5 had a significantly lower cumulative hazard of driving cessation (adjusted HR 2.89, 95% CI: 1.01–7.71, p = 0.033). Similarly, an MoCA score ≥ 26, TUG test

Beschreibung: Host genetic background is a significant driver of the variability in neurological responses to viral infection. Here, we leverage the genetically diverse Collaborative Cross (CC) mouse resource to better understand how chronic infection by Theiler’s Murine Encephalomyelitis Virus (TMEV) elicits diverse clinical and morphologic changes in the central nervous system (CNS). We characterized the TMEV-induced clinical phenotype responses, and associated lesion distributions in the CNS, in six CC mouse strains over a 90 day infection period. We observed varying degrees of motor impairment in these strains, as measured by delayed righting reflex, paresis, paralysis, seizures, limb clasping, ruffling, and encephalitis phenotypes. All strains developed neuroparenchymal necrosis and mineralization in the brain, primarily localized to the hippocampal regions. Two of the six strains presented with axonal degeneration with myelin loss of the nerve roots in the lumbar spinal cord. Moreover, we statistically correlated lesion distribution with overall frequencies of clinical phenotypes and phenotype progression to better understand how and where TMEV targets the CNS, based on genetic background. Specifically, we assessed lesion distribution in relation to the clinical progression of these phenotypes from early to late TMEV disease, finding significant relationships between progression and lesion distribution. Finally, we identified quantitative trait loci associated with frequency of lesions in a particular brain region, revealing several loci of interest for future study: lysosomal trafficking regulator (Lyst) and nidogen 1 (Nid1). Together, these results indicate that the genetic background influences the type and severity of clinical phenotypes, phenotypic resilience to TMEV, and the lesion distribution across strains.

Beschreibung: Plant pathogens are responsible for the annual yield loss of crops worldwide and pose a significant threat to global food security. A necessary prelude to many plant disease epidemics is the short-range dispersal of spores, which may generate several disease foci within a field. New information is needed on the mechanisms of plant pathogen spread within and among susceptible plants. Here, we show that self-propelled jumping dew droplets, working synergistically with low wind flow, can propel spores of a fungal plant pathogen (wheat leaf rust) beyond the quiescent boundary layer and disperse them onto neighboring leaves downwind. An array of horizontal water-sensitive papers was used to mimic healthy wheat leaves and showed that up to 25 spores/h may be deposited on a single leaf downwind of the infected leaf during a single dew cycle. These findings reveal that a single dew cycle can disperse copious numbers of fungal spores to other wheat plants, even in the absence of rain splash or strong gusts of wind.

Beschreibung: In the field of Differential Evolution (DE), a number of measures have been used to enhance algorithm. However, most of the measures need revision for fitting ensemble of different combinations of DE operators—ensemble DE algorithm. Meanwhile, although ensemble DE algorithm may show better performance than each of its constituent algorithms, there still exists the possibility of further improvement on performance with the help of revised measures. In this paper, we manage to implement measures into Ensemble of Differential Evolution Variants (EDEV). Firstly, we extend the collecting range of optional external archive of JADE—one of the constituent algorithm in EDEV. Then, we revise and implement the Event-Triggered Impulsive (ETI) control. Finally, Linear Population Size Reduction (LPSR) is used by us. Then, we obtain Improved Ensemble of Differential Evolution Variants (IEDEV). In our experiments, good performers in the CEC competitions on real parameter single objective optimization among population-based metaheuristics, state-of-the-art DE algorithms, or up-to-date DE algorithms are involved. Experiments show that our IEDEV is very competitive.

Beschreibung: Against the background of the speed-accuracy trade-off, we explored whether the Pace of Life can be used to identify heterogeneity in the strategy to place more weight on either fast or accurate accomplishments. The Pace of Life approaches an individual’s exposure to time and is an intensively studied concept in the evolutionary biology research. Albeit overall rarely, it is increasingly used to understand human behavior and may fulfill many criteria of a personal trait. In a controlled laboratory environment, we measured the participants’ Pace of Life, as well as their performance on a real-effort task. In the real-effort task, the participants had to encode words, whereby each word encoded correctly was associated with a monetary reward. We found that individuals with a faster Pace of Life accomplished more tasks in total. At the same time, they were less accurate and made more mistakes (in absolute terms) than those with a slower Pace of Life. Thus, the Pace of Life seems to be useful to identify an individual’s stance on the speed-accuracy continuum. In our specific task, placing more weight on speed instead of accuracy paid off: Individuals with a faster Pace of Life were ultimately more successful (with regard to their monetary revenue).

Beschreibung: Predatory mites in the family Phytoseiidae (Acari: Mesostigmata) are of great importance as biological control agents of pest mites and other arthropods. Correct identification of species is crucial to implement effective biological control of target pests. Here, we provide re-descriptions of seven phytoseiid mite species collected from citrus orchards in Florida. The several important morphological features including dorsal setae lengths, dorsal solenostomes, shape of calyx of spermatheca, chelicera dentition, measurements, and shape of macrosetae on legs currently used to discriminate phytoseiid species were missing in the original descriptions and re-descriptions of these species. Additionally, we observed the presence of a previously unnoted taxonomically important character on Proprioseius meridionalis Chant. Therefore, the re-description was essential for further diagnosis of this species. Accordingly, the validity of the presence/absence of this structure as a diagnostic character to separate species groups in the genus Proprioseius should be re-considered. Furthermore, Typhlodromalus peregrinus, a species for which a series of morphological variations are reported in previous descriptions, is re-described and illustrated from Clermont, Florida, a location very close (10 km) to its type location (Minneola), and the leaves of type host citrus. The macrosetae StIV was knobbed apically in all our specimens of T. peregrinus indicating invalidity of sharp-pointed or knobbed StIV to separate this species from a closely related species, T. aripo De Leon. These re-descriptions and species are important to utilizing authentic and promising candidates for biological control.

Beschreibung: How are eyes and head adapted to meet the demands of visual exploration in different tasks and environments? In two studies, we measured the horizontal movements of the eyes (using mobile eye tracking in Studies 1 and 2) and the head (using inertial sensors in Study 2) while participants completed a walking task and a search and retrieval task in a large, outdoor environment. We found that the spread of visual exploration was greater while searching compared with walking, and this was primarily driven by increased movement of the head as opposed to the eyes. The contributions of the head to gaze shifts of different eccentricities was greater when searching compared to when walking. Findings are discussed with respect to understanding visual exploration as a motor action with multiple degrees of freedom.

Beschreibung: Background We hypothesized that a decrease in frequency of controlled breaths during biphasic positive airway pressure (BIVENT), associated with an increase in spontaneous breaths, whether pressure support (PSV)-assisted or not, would mitigate lung and diaphragm damage in mild experimental acute respiratory distress syndrome (ARDS). Materials and methods Wistar rats received Escherichia coli lipopolysaccharide intratracheally. After 24 hours, animals were randomly assigned to: 1) BIVENT-100+PSV0%: airway pressure (Phigh) adjusted to VT = 6 mL/kg and frequency of controlled breaths (f) = 100 bpm; 2) BIVENT-50+PSV0%: Phigh adjusted to VT = 6 mL/kg and f = 50 bpm; 3) BIVENT-50+PSV50% (PSV set to half the Phigh reference value, i.e., PSV50%); or 4) BIVENT-50+PSV100% (PSV equal to Phigh reference value, i.e., PSV100%). Positive end-expiratory pressure (Plow) was equal to 5 cmH2O. Nonventilated animals were used for lung and diaphragm histology and molecular biology analysis. Results BIVENT-50+PSV0%, compared to BIVENT-100+PSV0%, reduced the diffuse alveolar damage (DAD) score, the expression of amphiregulin (marker of alveolar stretch) and muscle atrophy F-box (marker of diaphragm atrophy). In BIVENT-50 groups, the increase in PSV (BIVENT-50+PSV50% versus BIVENT-50+PSV100%) yielded better lung mechanics and less alveolar collapse, interstitial edema, cumulative DAD score, as well as gene expressions associated with lung inflammation, epithelial and endothelial cell damage in lung tissue, and muscle ring finger protein 1 (marker of muscle proteolysis) in diaphragm. Transpulmonary peak pressure (Ppeak,L) and pressure–time product per minute (PTPmin) at Phigh were associated with lung damage, while increased spontaneous breathing at Plow did not promote lung injury. Conclusion In the ARDS model used herein, during BIVENT, the level of PSV and the phase of the respiratory cycle in which the inspiratory effort occurs affected lung and diaphragm damage. Partitioning of inspiratory effort and transpulmonary pressure in spontaneous breaths at Plow and Phigh is required to minimize VILI.

Beschreibung: Small RNAs (sRNAs) encompass a great variety of molecules of different kinds, such as microRNAs, small interfering RNAs, Piwi-associated RNA, among others. These sRNAs have a wide range of activities, which include gene regulation, protection against virus, transposable element silencing, and have been identified as a key actor in determining the development of the cell. Small RNA sequencing is thus routinely used to assess the expression of the diversity of sRNAs, usually in the context of differentially expression, where two conditions are compared. Tools that detect differentially expressed microRNAs are numerous, because microRNAs are well documented, and the associated genes are well defined. However, tools are lacking to detect other types of sRNAs, which are less studied, and whose precursor RNA is not well characterized. We present here a new method, called srnadiff, which finds all kinds of differentially expressed sRNAs. To the extent of our knowledge, srnadiff is the first tool that detects differentially expressed sRNAs without the use of external information, such as genomic annotation or additional sequences of sRNAs.

Beschreibung: In order to eliminate COVID-19, many countries provided vaccinations. However, success depends on peoples’ knowledge levels and rates of acceptance. But, previous research on this topic is currently lacking in Bangladesh. This cross-sectional study aimed at to investigate Bangladeshi peoples’ knowledge, acceptance, and perception of challenges regarding COVID-19 vaccines. Quantitative data were collected using an online survey (n = 1975) and face-to-face interviews (n = 2200) with a pre-tested structured questionnaire. In addition, seven open-ended interviews were conducted with health experts regarding challenges of vaccination. Binary logistic regression analyses were conducted to assess the association between explanatory and dependent variables. Effect size was estimated to understand the magnitude of relationship between two variables. Of 4175 respondents, 92.6% knew about COVID-19 vaccines, while only 37.4% believed vaccines to be effective in controlling COVID-19. Nearly 46% of respondents believed that COVID-19 vaccines have side-effects, and 16.4% of respondents believed that side-effects could be life-threatening. Only 60.5% of respondents indicated that they would receive the COVID-19 vaccine. Out of 1650 respondents (39.5%) who did not intend to receive the vaccine, 948 (57.4%) believed that they would be naturally protected. Regressions results indicated that men had higher rates of knowledge regarding the vaccine. In addition, rural respondents demonstrated lower knowledge regarding the vaccine. Furthermore, education had a significant association with knowledge of COVID-19 vaccines. Respondents with university education had more knowledge regarding the vaccine (Odds ratio, OR = 29.99; 95% confidence interval, CI 11.40–78.90, effect size 1.88; p = 0.01) and correct dosage (OR 27.34; 95% CI 15.25–49.00, effect size 1.83; p = 0.01). However, women (OR 1.16; 95% CI 0.96–1.40, effect size 0.08) and rural (OR 1.24; 95% CI 1.07–1.44, effect size 0.12; p = 0.01) respondents were more enthusiastic regarding receiving the COVID-19 vaccine. Higher educated respondents showed higher probability of receiving the vaccine. Those who believed in the effectiveness of the COVID-19 vaccine were 11.57 times more interested (OR 11.57; 95% CI 8.92–15.01, effect size 1.35; p = 0.01) in receiving the vaccine. Open-ended interviews identified several challenges toward successful COVID-19 vaccination. Mass awareness creation, uninterrupted supply, equitable distribution, and sectoral coordination were suggested to achieve at least 70% immunization across the country.

Beschreibung: Replicability takes on special meaning when researching phenomena that are embedded in space and time, including phenomena distributed on the surface and near surface of the Earth. Two principles, spatial dependence and spatial heterogeneity, are generally characteristic of such phenomena. Various practices have evolved in dealing with spatial heterogeneity, including the use of place-based models. We review the rapidly emerging applications of artificial intelligence to phenomena distributed in space and time and speculate on how the principle of spatial heterogeneity might be addressed. We introduce a concept of weak replicability and discuss possible approaches to its measurement.

Beschreibung: Introduction Burnout syndrome is common among medical students, but findings about the gender differences in burnout are not consistent. The aim of this study was to assess high risk of burnout syndrome among medical students at one University in Serbia, by gender. Method A cross-sectional study was conducted at the Faculty of Medical Sciences, University of Kragujevac in 2014. The Maslach Burnout Inventory—Student Survey was used for assessment of burnout level. A questionnaire on basic socio-demographic characteristics (age, gender, marital status, habits, etc.) and academic performance (year of study, cumulative total average grade, length of study, housing, study financing, etc.) was used. The study included a total of 760 medical students (760/836 medical students; participation rate: 90.9%). Logistic regression analysis was used to determine odds ratios (OR) with 95% confidence intervals (95% CI). Results Significant gender differences were detected in prevalence of high risk of burnout syndrome (male students– 19.0% vs. female students– 12.8%, p = 0.024). A significant independent predictor of high risk for burnout syndrome in male medical students was study year (p for trend = 0.011), while in female medical students–study year (p for trend = 0.002) and use of sedatives (adjusted OR = 5.74, 95% CI = 1.96–16.77, p = 0.001). Conclusion Our results indicate the need to assess the risk of burnout syndrome at the very beginning of medical studies, in order to more effectively control the modifiable risk factors.

Beschreibung: The inability of adult mammalian cardiomyocytes to proliferate underpins the development of heart failure following myocardial injury. Although the newborn mammalian heart can spontaneously regenerate for a short period of time after birth, this ability is lost within the first week after birth in mice, partly due to increased mitochondrial reactive oxygen species (ROS) production which results in oxidative DNA damage and activation of DNA damage response. This increase in ROS levels coincides with a postnatal switch from anaerobic glycolysis to fatty acid (FA) oxidation by cardiac mitochondria. However, to date, a direct link between mitochondrial substrate utilization and oxidative DNA damage is lacking. Here, we generated ROS-sensitive fluorescent sensors targeted to different subnuclear compartments (chromatin, heterochromatin, telomeres, and nuclear lamin) in neonatal rat ventricular cardiomyocytes, which allowed us to determine the spatial localization of ROS in cardiomyocyte nuclei upon manipulation of mitochondrial respiration. Our results demonstrate that FA utilization by the mitochondria induces a significant increase in ROS detection at the chromatin level compared to other nuclear compartments. These results indicate that mitochondrial metabolic perturbations directly alter the nuclear redox status and that the chromatin appears to be particularly sensitive to the prooxidant effect of FA utilization by the mitochondria.

Beschreibung: Interactions of electronic and vibrational degrees of freedom are essential for understanding excited-states relaxation pathways of molecular systems at interfaces and surfaces. Here, we present the development of interface-specific two-dimensional electronic–vibrational sum frequency generation (2D-EVSFG) spectroscopy for electronic–vibrational couplings for excited states at interfaces and surfaces. We demonstrate this 2D-EVSFG technique by investigating photoexcited interface-active (E)-4-((4-(dihexylamino) phenyl)diazinyl)-1-methylpyridin-1- lum (AP3) molecules at the air–water interface as an example. Our 2D-EVSFG experiments show strong vibronic couplings of interfacial AP3 molecules upon photoexcitation and subsequent relaxation of a locally excited (LE) state. Time-dependent 2D-EVSFG experiments indicate that the relaxation of the LE state, S2, is strongly coupled with two high-frequency modes of 1,529.1 and 1,568.1 cm−1. Quantum chemistry calculations further verify that the strong vibronic couplings of the two vibrations promote the transition from the S2 state to the lower excited state S1. We believe that this development of 2D-EVSFG opens up an avenue of understanding excited-state dynamics related to interfaces and surfaces.

Beschreibung: Background Comorbidities are associated with increased mortality among patients receiving long-term kidney replacement therapy (KRT). However, it is not known whether primary kidney disease modifies the effect of comorbidities on KRT patients’ survival. Methods An incident cohort of all patients (n = 8696) entering chronic KRT in Finland in 2000–2017 was followed until death or end of 2017. All data were obtained from the Finnish Registry for Kidney Diseases. Information on comorbidities (coronary artery disease, peripheral vascular disease, left ventricular hypertrophy, heart failure, cerebrovascular disease, malignancy, obesity, underweight, and hypertension) was collected at the start of KRT. The main outcome measure was relative risk of death according to comorbidities analyzed in six groups of primary kidney disease: type 2 diabetes, type 1 diabetes, glomerulonephritis (GN), polycystic kidney disease (PKD), nephrosclerosis, and other or unknown diagnoses. Kaplan-Meier estimates and Cox regression were used for survival analyses. Results In the multivariable model, heart failure increased the risk of death threefold among PKD and GN patients, whereas in patients with other kidney diagnoses the increased risk was less than twofold. Obesity was associated with worse survival only among GN patients. Presence of three or more comorbidities increased the age- and sex-adjusted relative risk of death 4.5-fold in GN and PKD patients, but the increase was only 2.5-fold in patients in other diagnosis groups. Conclusions Primary kidney disease should be considered when assessing the effect of comorbidities on survival of KRT patients as it varies significantly according to type of primary kidney disease.

Beschreibung: In this study, we use molecular genetic approaches to clarify the role of the Hedgehog (Hh) pathway in regulating the blood–brain/spinal cord barrier (BBB) in the adult mouse central nervous system (CNS). Our work confirms and extends prior studies to demonstrate that astrocytes are the predominant cell type in the adult CNS that transduce Hh signaling, revealed by the expression of Gli1, a target gene of the canonical pathway that is activated in cells receiving Hh, and other key pathway transduction components. Gli1+ (Hh-responsive) astrocytes are distributed in specific regions of the CNS parenchyma, including layers 4/5/6 of the neocortex, hypothalamus, thalamus, and spinal cord, among others. Notably, although BBB properties in endothelial cells are normally regulated by both paracellular and transcellular mechanisms, conditional inactivation of Hh signaling in astrocytes results in transient, region-specific BBB defects that affect transcytosis but not paracellular diffusion. These findings stand in contrast to prior studies that implicated astrocytes as a source of Sonic hedgehog that limited extravasation via both mechanisms [J. I. Alvarez et al., Science 334, 1727–1731 (2011)]. Furthermore, using three distinct Cre driver lines as well as pharmacological approaches to inactivate Hh-pathway transduction globally in CNS astrocytes, we find that these specific BBB defects are only detected in the rostral hypothalamus and spinal cord but not the cortex or other regions where Gli1+ astrocytes are found. Together, our data show that Gli1+ Hh-responsive astrocytes have regionally distinct molecular and functional properties and that the pathway is required to maintain BBB properties in specific regions of the adult mammalian CNS.

Beschreibung: New-generation migrant workers in Chinese cities are struggling with a lack of urban resources, such as capital, skills, and relationships. To cope with the pressure of these resource constraints, new-generation migrant workers obtain urban development opportunities through resource bricolage. Based on a questionnaire survey of 365 new-generation migrant workers, we used a multiple regression analysis to study the mechanism underlying the effects of resource bricolage on the city integration of new-generation migrant workers. There were four findings: (1) resource bricolage had a significant positive effect on career growth and city integration; (2) career growth had a mediation effect on the relationship between resource bricolage and city integration; (3) environmental dynamism had a positive moderating effect on the relationship between resource bricolage and city integration for new-generation migrant workers; and (4) resource bricolage and environmental dynamism had a moderating effect on city integration through the mediation effect of career growth. The results suggest that resource bricolage promotes the career growth of new-generation migrant workers and further promotes their city integration, and that the environmental dynamism faced by workers is the external condition for promoting integration through resource bricolage. The study emphasizes the importance of resource bricolage in new-generation migrant workers’ city integration.

Beschreibung: Vessel-based sonar systems that focus on the water column provide valuable information on the distribution of underwater marine organisms, but such data are expensive to collect and limited in their spatiotemporal coverage. Satellite data, however, are widely available across large regions and provide information on surface ocean conditions. If satellite data can be linked to subsurface sonar measurements, it may be possible to predict marine life over broader spatial regions with higher frequency using satellite observations. Here, we use random forest models to evaluate the potential for predicting a sonar-derived proxy for subsurface biomass as a function of satellite imagery in the California Current Ecosystem. We find that satellite data may be useful for prediction under some circumstances, but across a range of sonar frequencies and depths, overall model performance was low. Performance in spatial interpolation tasks exceeded performance in spatial and temporal extrapolation, suggesting that this approach is not yet reliable for forecasting or spatial extrapolation. We conclude with some potential limitations and extensions of this work.

Beschreibung: The area of tropical secondary forests is increasing rapidly, but data on the physical and biological structure of the canopies of these forests are limited. To obtain such data and to measure the ontogeny of canopy structure during tropical rainforest succession, we studied patch-scale (5 m2) canopy structure in three areas of 18–36 year-old secondary forest in Costa Rica, and compared the results to data from old-growth forest at the same site. All stands were sampled with a stratified random design with complete harvest from ground level to the top of the canopy from a modular portable tower. All canopies were organized into distinct high- and low-leaf-density layers (strata), and multiple strata developed quickly with increasing patch height. The relation of total Leaf Area Index (LAI, leaf area per area of ground) to patch canopy height, the existence of distinct high and low leaf- density layers (strata and free air spaces), the depth and LAI of the canopy strata and free air spaces, and the relation of the number of strata to patch canopy height were remarkably constant across the entire successional gradient. Trees were the most important contributor to LAI at all stages, while contribution of palm LAI increased through succession. We hypothesize that canopy physical structure at the patch scale is driven by light competition and discuss how this hypothesis could be tested. That canopy physical structure was relatively independent of the identity of the species present suggests that canopy physical structure may be conserved even as canopy floristics shift due to changing climate.

Beschreibung: Visual perception in football (“soccer” in the U.S.) is increasingly becoming a key area of interest for researchers and practitioners. This exploratory case study investigated a sub-set of visual perception, namely visual exploratory scanning. The aim of this study was to examine the scanning of four elite football midfield players in an 11 vs. 11 real-game environment using mobile eye-tracking technology. More specifically, we measured the duration and information (number of teammates and opponents) of the players’ scanning behavior. The results showed that the players’ scanning duration was influenced by the ball context and the action undertaken with the ball at the moment of scan initiation. Furthermore, fixations were found in only 2.3% of the scans. Additionally, the results revealed that the stop point is the most information-rich part of a scan and that the players had more opponents than teammates inside their video frame during scans. Practical applications and further research recommendations are presented.

Beschreibung: Digital mobility assessment using wearable sensor systems has the potential to capture walking performance in a patient’s natural environment. It enables monitoring of health status and disease progression and evaluation of interventions in real-world situations. In contrast to laboratory settings, real-world walking occurs in non-conventional environments and under unconstrained and uncontrolled conditions. Despite the general understanding, there is a lack of agreed definitions about what constitutes real-world walking, impeding the comparison and interpretation of the acquired data across systems and studies. The goal of this study was to obtain expert-based consensus on specific aspects of real-world walking and to provide respective definitions in a common terminological framework. An adapted Delphi method was used to obtain agreed definitions related to real-world walking. In an online survey, 162 participants from a panel of academic, clinical and industrial experts with experience in the field of gait analysis were asked for agreement on previously specified definitions. Descriptive statistics was used to evaluate whether consent (〉 75% agreement as defined a priori) was reached. Of 162 experts invited to participate, 51 completed all rounds (31.5% response rate). We obtained consensus on all definitions (“Walking” 〉 90%, “Purposeful” 〉 75%, “Real-world” 〉 90%, “Walking bout” 〉 80%, “Walking speed” 〉 75%, “Turning” 〉 90% agreement) after two rounds. The identification of a consented set of real-world walking definitions has important implications for the development of assessment and analysis protocols, as well as for the reporting and comparison of digital mobility outcomes across studies and systems. The definitions will serve as a common framework for implementing digital and mobile technologies for gait assessment and are an important link for the transition from supervised to unsupervised gait assessment.

Beschreibung: Introduction Hypertension (HT) is a major non-communicable disease worldwide and a growing global public health problem. Although several studies have investigated the independent associations of neck circumference (NC) and hypertension, no such studies have been conducted among the Thai population. Aim This study aims to identify risk factors associated with hypertension, which may be used to predict HT among asymptomatic adults residing in a remote rural community in central Thailand. Method 1,084 adults were included in this community-based cross-sectional study by a population-based total survey. The participants were included those who had been living in 6 villages in the rural community in the central area of Thailand. Anthropometric information, NC, body composition indexes such as waist circumference and blood pressure were measured. Logistic regression models were fitted to calculate the multi-variable adjusted prevalence and the association of NC with HT. Result The prevalence of HT among adults in the rural community was 27.7% (95% CI: 25.0–30.3). Of the 300 adults with HT, 164 participants (54.7%) were found within the unawareness HT category. We found that associated factors with HT were included larger neck circumference both continuous and categorical (≥ 37.5 in male, ≥ 32.5 in female), pre-existing diabetes mellitus, male, and higher body mass index. Conclusion Almost one-third of participants in the remote rural areas presented hypertension. NC was associated with HT independent from other risk factors. NC is a simple and useful anthropometric index to identify HT in rural Thai adults.

Beschreibung: This is a protocol of a review paper, and there is no abstract. This review is part of a doctoral project that aims to develop a discrete event simulation model to predict how many adolescents may become hypertensive in adulthood. We will use data from the Brazilian study of cardiovascular risks in adolescents, called ERICA (Portuguese acronym). This study may help promote adherence to disease prevention protocols.

Beschreibung: Mycobacterium tuberculosis (Mtb) infects one-quarter of the world’s population. Mtb and HIV coinfections enhance the comorbidity of tuberculosis (TB) and AIDS, accounting for one-third of all AIDS-associated mortalities. Humoral antibody to Mtb correlates with TB susceptibility, and engineering of Mtb antibodies may lead to new diagnostics and therapeutics. The characterization and validation of functional immunoglobulin (Ig) variable chain (IgV) sequences provide a necessary first step towards developing therapeutic antibodies against pathogens. The virulence-associated Mtb antigens SodA (Superoxide Dismutase), KatG (Catalase), PhoS1/PstS1 (regulatory factor), and GroES (heat shock protein) are potential therapeutic targets but lacked IgV sequence characterization. Putative IgV sequences were identified from the mRNA of hybridomas targeting these antigens and isotype-switched into a common immunoglobulin fragment crystallizable region (Fc region) backbone, subclass IgG2aκ. Antibodies were validated by demonstrating recombinant Ig assembly and secretion, followed by the determination of antigen-binding specificity using ELISA and immunoblot assay.

Beschreibung: Evidence suggests that non-binary people have poorer mental and physical health outcomes, compared with people who identify within the gender binomial (man/woman). Research on the impact of the COVID-19 pandemic on mental health has been conducted worldwide in the last few months. It has however overlooked gender diversity. The aim of our study was to explore social and health-related factors associated with mental health (anxiety and depression) among people who do not identify with the man/woman binomial during COVID-19 lockdown in Spain. A cross-sectional study with online survey, aimed at the population residing in Spain during lockdown, was conducted. Data were collected between the 8th of April until the 28th of May 2020, the time period when lockdown was implemented in Spain. Mental health was measured using the Generalised Anxiety Disorder 7-item (GAD-7) scale for anxiety, and the Patient Health Questionnaire (PHQ-9) for depression. The survey included the question: Which sex do you identify with? The options “Man”, “Woman”, “Non-binary” and “I do not identify” were given. People who answered one of the last two options were selected for this study. Multivariate regression logistic models were constructed to evaluate the associations between sociodemographic, social and health-related factors, anxiety and depression. Out of the 7125 people who participated in the survey, 72 (1%) identified as non-binary or to not identify with another category. People who do not identify with the man/woman binomial (non-binary/I do not identify) presented high proportions of anxiety (41.7%) and depression (30.6%). Poorer mental health was associated with social-employment variables (e.g., not working before the pandemic) and health-related variables (e.g., poor or regular self-rated health). These findings suggest that social inequities, already experienced by non-binary communities before the pandemic, may deepen due to the COVID-19 pandemic.

Beschreibung: In everyday life, we group and subdivide time to understand the sensory environment surrounding us. Organizing time in units, such as diurnal rhythms, phrases, and beat patterns, is fundamental to behavior, speech, and music. When listening to music, our perceptual system extracts and nests rhythmic regularities to create a hierarchical metrical structure that enables us to predict the timing of the next events. Foot tapping and head bobbing to musical rhythms are observable evidence of this process. In the special case of polyrhythms, at least two metrical structures compete to become the reference for these temporal regularities, rendering several possible beats with which we can synchronize our movements. While there is general agreement that tempo, pitch, and loudness influence beat perception in polyrhythms, we focused on the yet neglected influence of beat subdivisions, i.e., the least common denominator of a polyrhythm ratio. In three online experiments, 300 participants listened to a range of polyrhythms and tapped their index fingers in time with the perceived beat. The polyrhythms consisted of two simultaneously presented isochronous pulse trains with different ratios (2:3, 2:5, 3:4, 3:5, 4:5, 5:6) and different tempi. For ratios 2:3 and 3:4, we additionally manipulated the pitch of the pulse trains. Results showed a highly robust influence of subdivision grouping on beat perception. This was manifested as a propensity towards beats that are subdivided into two or four equally spaced units, as opposed to beats with three or more complex groupings of subdivisions. Additionally, lower pitched pulse trains were more often perceived as the beat. Our findings suggest that subdivisions, not beats, are the basic unit of beat perception, and that the principle underlying the binary grouping of subdivisions reflects a propensity towards simplicity. This preference for simple grouping is widely applicable to human perception and cognition of time.

Beschreibung: Objectives Eradicated infectious diseases like smallpox can re-emerge through accident or the designs of bioterrorists, and cause heavy casualties. Presently, the populace is largely susceptible as only a small percentage is vaccinated, and their immunity is likely to have waned. And when the disease re-emerges, the susceptible individuals may be manipulated by disinformation on Social Media to refuse vaccines. Thus, a combination of countermeasures consisting of antiviral drugs and vaccines and a range of policies for their application need to be investigated. Opinions regarding whether to receive vaccines evolve over time through social exchanges via networks that overlap with but are not identical to the disease propagation networks. These couple the spread of the biological and information contagion and necessitate a joint investigation of the two. Methods We develop a computationally tractable metapopulation epidemiological model that captures the joint spatio-temporal evolution of an infectious disease (e.g., smallpox, COVID-19) and opinion dynamics. Results Considering smallpox, the computations based on the model show that opinion dynamics have a substantial impact on the fatality count. Towards understanding how perpetrators are likely to seed the infection, we identify a) the initial distribution of infected individuals that maximize the overall fatality count; and b) which habitation structures are more vulnerable to outbreaks. We assess the relative efficacy of different countermeasures and conclude that a combination of vaccines and drugs minimize the fatalities, and by itself, drugs reduce fatalities more than the vaccine. Accordingly, we assess the impact of increase in the supply of drugs and identify the most effective among a collection of policies for administering of drugs for various parameter combinations. Many of the observed patterns are stable to variations of a diverse set of parameters. Conclusions Our findings provide a quantitative foundation for various important elements of public health discourse that have largely been conducted qualitatively.

Beschreibung: Introduction Improving hypertension management is a national priority that can decrease morbidity and mortality. Evidence-based hypertension management guidelines advocate self-measured BP (SMBP), but widespread implementation of SMBP is lacking. The purpose of this study was to describe the perspective of primary care physicians (PCPs) on SMBP to identify the barriers and facilitators for implementing SMBP. Methods We collected data from PCPs from a large health system using semi-structured interviews based on the Theoretical Domains Framework (TDF). Responses were recorded, transcribed, and qualitatively analyzed into three overarching TDF domains based on the Behavior Change Wheel (BCW): 1) Motivation 2) Opportunity and 3) Capabilities. The sample size was based on theme saturation. Results All 17 participating PCPs believed that SMBP is a useful, but underutilized tool. Although individual practices varied, most physicians felt that the increased data points from SMBP allowed for better hypertension management. Most felt that overcoming existing barriers would be difficult, but identified several facilitators: physician support of SMBP, the possibility of having other trained health professionals to assist with SMBP and patient education; improving patient engagement and empowerment with SMBP, and the interest of the health system in using technology to improve hypertension management. Conclusion PCPs believe that SMBP can improve hypertension management. There are numerous barriers and facilitators for implementing SMBP. Successful implementation in clinical practice will require implementation strategies targeted at increasing patient acceptability and reducing physician workload. This may need a radical change in the current methods of managing hypertension.

Beschreibung: Background The mid-life emergence of higher levels of total cholesterol (TC) for women than for men has been observed in different Western and Asian populations. The aim of this study was to investigate whether there is evidence of this in Vietnam and, if so, whether it can be explained by ageing, by body size and fatness, or by socio-demographic characteristics and behavioural factors. Methods Participants (n = 14706, 50.9% females) aged 25–64 years were selected by multi-stage stratified cluster sampling from eight provinces each representing one of the eight geographical regions of Vietnam. Measurements were made using the World Health Organization STEPS protocols. Linear regression was used to assess the independent contributions of potential explanatory factors to mean levels of TC. Data were analysed using complex survey methods. Results Men and women had similar mean levels of body mass index (BMI), and men had modestly higher mean levels of waist circumference (WC), in each 5-year age category. The mean TC of women increased more or less continuously across the age range but with a step-up at age 50 years to reach higher concentrations on average than those of their male counterparts. The estimated step-up was not eliminated by adjustment for anthropometric indices including BMI or WC, or by adjustment for socio-demographic characteristics or behavioural factors. The estimated step-up was least for women with the greatest weight. Conclusion There is a marked step-up in TC at age 50 years for Vietnamese women that cannot be explained by their age, or by their body fatness or its distribution, or by their socio-demographic characteristics or behavioural factors, and which results in greater mean levels of TC for middle-aged women than for their male counterparts in Vietnam.

Beschreibung: Corrections applied by the visual system, like size constancy, provide us with a coherent and stable perspective from ever-changing retinal images. In the present experiment we investigated how willing adults are to examine their own vision as if it were an uncorrected 2D image, much like a photograph. We showed adult participants two lines on a wall, both of which were the same length but one was closer to the participant and hence appeared visually longer. Despite the instruction to base their judgements on appearance specifically, approximately half of the participants judged the lines to appear the same. When they took a photo of the lines and were asked how long they appeared in the image their responses shifted; now the closer line appeared longer. However, when they were asked again about their own view they reverted to their original response. These results suggest that many adults are resistant to imagining their own vision as if it were a flat image. We also place these results within the context of recent views on visual perspective-taking.

Beschreibung: Geometry in materials is a key concept which can determine material behavior in ordering, frustration, and fragmentation. More specifically, the behavior of interacting degrees of freedom subject to arbitrary geometric constraints has the potential to be used for engineering materials with exotic phase behavior. While advances in lithography have allowed for an experimental exploration of geometry on ordering that has no precedent in nature, many of these methods are low throughput or the underlying dynamics remain difficult to observe directly. Here, we introduce an experimental system that enables the study of interacting many-body dynamics by exploiting the physics of multidroplet evaporation subject to two-dimensional spatial constraints. We find that a high-energy initial state of this system settles into frustrated, metastable states with relaxation on two timescales. We understand this process using a minimal dynamical model that simulates the overdamped dynamics of motile droplets by identifying the force exerted on a given droplet as being proportional to the two-dimensional vapor gradients established by its neighbors. Finally, we demonstrate the flexibility of this platform by presenting experimental realizations of droplet−lattice systems representing different spin degrees of freedom and lattice geometries. Our platform enables a rapid and low-cost means to directly visualize dynamics associated with complex many-body systems interacting via long-range interactions. More generally, this platform opens up the rich design space between geometry and interactions for rapid exploration with minimal resources.

Beschreibung: In most bacteriophages, genome transport across bacterial envelopes is carried out by the tail machinery. In viruses of the Podoviridae family, in which the tail is not long enough to traverse the bacterial wall, it has been postulated that viral core proteins assembled inside the viral head are translocated and reassembled into a tube within the periplasm that extends the tail channel. Bacteriophage T7 infects Escherichia coli, and despite extensive studies, the precise mechanism by which its genome is translocated remains unknown. Using cryo-electron microscopy, we have resolved the structure of two different assemblies of the T7 DNA translocation complex composed of the core proteins gp15 and gp16. Gp15 alone forms a partially folded hexamer, which is further assembled upon interaction with gp16 into a tubular structure, forming a channel that could allow DNA passage. The structure of the gp15–gp16 complex also shows the location within gp16 of a canonical transglycosylase motif involved in the degradation of the bacterial peptidoglycan layer. This complex docks well in the tail extension structure found in the periplasm of T7-infected bacteria and matches the sixfold symmetry of the phage tail. In such cases, gp15 and gp16 that are initially present in the T7 capsid eightfold-symmetric core would change their oligomeric state upon reassembly in the periplasm. Altogether, these results allow us to propose a model for the assembly of the core translocation complex in the periplasm, which furthers understanding of the molecular mechanism involved in the release of T7 viral DNA into the bacterial cytoplasm.

Beschreibung: Despite widespread yearly vaccination, influenza leads to significant morbidity and mortality across the globe. To make a more broadly protective influenza vaccine, it may be necessary to elicit antibodies that can activate effector functions in immune cells, such as antibody-dependent cellular cytotoxicity (ADCC). There is growing evidence supporting the necessity for ADCC in protection against influenza and herpes simplex virus (HSV), among other infectious diseases. An HSV-2 strain lacking the essential glycoprotein D (gD), was used to create ΔgD-2, which is a highly protective vaccine against lethal HSV-1 and HSV-2 infection in mice. It also elicits high levels of IgG2c antibodies that bind FcγRIV, a receptor that activates ADCC. To make an ADCC-eliciting influenza vaccine, we cloned the hemagglutinin (HA) gene from an H1N1 influenza A strain into the ΔgD-2 HSV vector. Vaccination with ΔgD-2::HAPR8 was protective against homologous influenza challenge and elicited an antibody response against HA that inhibits hemagglutination (HAI+), is predominantly IgG2c, strongly activates FcγRIV, and protects against influenza challenge following passive immunization of naïve mice. Prior exposure of mice to HSV-1, HSV-2, or a replication-defective HSV-2 vaccine (dl5-29) does not reduce protection against influenza by ΔgD-2::HAPR8. This vaccine also continues to elicit protection against both HSV-1 and HSV-2, including high levels of IgG2c antibodies against HSV-2. Mice lacking the interferon-α/β receptor and mice lacking the interferon-γ receptor were also protected against influenza challenge by ΔgD-2::HAPR8. Our results suggest that ΔgD-2 can be used as a vaccine vector against other pathogens, while also eliciting protective anti-HSV immunity.

Beschreibung: Purpose We sought to evaluate changes of mean peripapillary choroidal thickness (PCT) and subfoveal choroidal thickness (SFCT) over 12 months in patients with unilateral central retinal vein occlusion (CRVO). Methods Our retrospective, observational study included 19 patients with treatment-naïve, unilateral CRVO who completed at least 12 months of follow-up period. Mean PCT and mean SFCT in CRVO-affected eyes and unaffected contralateral eyes were measured at each follow-up visit, and then compared. Differences between baseline and 12 months (ΔSFCT and ΔPCT) and percentage changes (ΔSFCT or ΔPCT/baseline×100%) were determined. We also investigated the predictive factors for visual outcome in the CRVO-affected eyes. Results In the CRVO-affected eyes, mean PCT was 146.7±41.9 μm at baseline, and 106.5±24.2 μm at 12 months (P 〈 0.001). Mean PCT of the contralateral eyes was 129.8±42.6 μm at baseline and 124.6±39.7 μm at 12 months (P = 0.089). Mean SFCT of CRVO-affected eyes was 225.8±77.9 μm at baseline, and 199.4±66.6 μm at 12 months (P = 0.009). Mean SFCT of the contralateral eyes was 218.4±83.0 μm at baseline, and 208.4±78.1 μm at 12 months (P = 0.089). Δ PCT was -41.6±25.3 μm in the CRVO-affected eyes, and -5.2±5.8 μm in the contralateral eyes (P

Beschreibung: Background Right ventricular (RV) systolic strain has recently demonstrated prognostic value in various cardiovascular diseases. Despite this, the reference range including the lower limit of normal (LLN) and factors associated with RV strain measurements are not well-established. This meta-analysis aimed to determine the mean and LLN of two- (2D) and three-dimensional (3D) right ventricular global (RVGLS), free wall (RVFWLS) and interventricular septal wall (IVSLS) longitudinal strains in healthy individuals and factors that affect strain measurements. Methods In this meta-analysis, Pubmed, Embase and Cochrane databases were searched until 31 July 2020 for eligible studies reporting RVGLS, RVFWLS and/or IVSLS in at least 30 healthy subjects. We pooled the means and LLNs of RV strains by two- (2D) and three- (3D) dimensional echocardiography, and performed meta-regression analyses. Results From 788 articles screened, 45 eligible studies totaling 4439 healthy subjects were eligible for analysis. Pooled means and LLNs with 95% confidence intervals for 2D- RV strains were RVGLS -23.4% (-24.2%, -22.6%) and -16.4% (-17.3%, -15.5%) in 27 studies; RVFWLS -26.9% (-28.0%, -25.9%) and -18.0% (-19.2%, -16.9%) in 32 studies; and IVSLS –20.4% (-22.0%, -18.9%) and -11.5% (-13.6%, -9.6%) in 10 studies, and similar results for 3D- RV strains. Right ventricular fractional area change and vendor software were associated with 2D-RVGLS and RVFWLS means and LLNs. Conclusion We reported the pooled means and LLNs of RV systolic strains in healthy subjects, to define thresholds for abnormal, borderline and normal strains. Important factors associated with RV systolic strains include right ventricular fractional area change and vendor software.

Beschreibung: In the case of a fire, the choice of exit in the highway tunnel is strictly limited by fire location, which seriously affects the evacuation time. A spontaneous or disorderly exit choice might result in a decreased evacuation efficiency and utilization rate of exits. In this paper, we propose a strategy to obtain the optimal exit choice based on fire location during highway tunnel evacuations. In our strategy, first, the vehicle distributions and locations of evacuating occupants are determined in the traffic simulation program VISSIM. The evacuation simulation software BuildingEXODUS is employed to obtain the corresponding parameters of the evacuation process and analyze the impacts of different fire locations on the evacuation time. During the analysis, the optimal productivity statistics (OPS) is selected as the evaluation index. Then, the feature points of the crowding occupants are captured by the fuzzy c-means (FCM) cluster algorithm. Next, based on the feature points, the relationship between the location of the fire and boundary of the optimal exit choice under the optimal OPS is obtained through the polynomial regression model. It is found that the R-squared(R2) and sum of squares for error (SSE) of the polynomial regression model, reflecting the accuracy estimation, are 98.02% and 2.79×10−4, respectively. Moreover, different fire locations impact the evacuation time of tunnel entrance and evacuation passageway. This paper shows that the location of the fire and boundary of optimal exit choice have a negative linear correlation. Taking the fire 110 m away from the evacuation passageway as an example, the OPS of our strategy can be decreased by 35.6% when compared with no strategies. Our proposed strategy could be applied to determine the location of variable evacuation signs to help evacuating occupants make optimal exit choices.

Beschreibung: Background The aim of this study was to understand how physical activity and sedentary behaviour levels of pregnant women with gestational diabetes in the UK have been affected by COVID-19. Methods An online survey exploring physical activity and sedentary behaviour levels of pregnant women with gestational diabetes during COVID-19 was distributed through social media platforms. Women who had been pregnant during the COVID-19 outbreak and had gestational diabetes, were resident in the UK, were 18 years old or over and could understand written English were invited to take part. Results A total of 724 women accessed the survey, 553 of these met the eligibility criteria and took part in the survey. Sedentary time increased for 79% of the women during the pandemic. Almost half of the women (47%) were meeting the physical activity guidelines pre COVID-19 during their pregnancy, this dropped to 23% during the COVID-19 pandemic. Fear of leaving the house due to COVID-19 was the most commonly reported reason for the decline. Significant associations were found between meeting the physical activity guidelines during COVID-19 and educational attainment, fitness equipment ownership and knowledge of how to exercise safely in pregnancy. Conclusions and implications These results show the impact of COVID-19 on physical activity and sedentary behaviour levels and highlight the need for targeted public health initiatives as the pandemic continues and for future lockdowns. Women with gestational diabetes need to know how it is safe and beneficial to them to engage in physical activity and ways to do this from their homes if fear of leaving the house due to COVID-19 is a barrier for them. Online physical activity classes provided by certified trainers in physical activity for pregnant women may help them remain active when face-to-face appointments are reduced and limited additional resources are available.

Beschreibung: It is a well-known feature of social protection systems that not all persons who are entitled to social benefits also claim these benefits. The costs people face when claiming benefits is considered an important cause of this phenomenon of non-take-up. In this paper, we developed and examined the psychometric properties of a new scale, the Claiming Cost Scale (CCS), which measures three dimensions of costs associated with claiming benefits. A multi-phase instrument development method was performed to develop the instrument. The item pool was generated based on a literature review, and presented to academic experts (n = 9) and experts by experience (n = 5) to assess content and face validity. In a second stage, centrality and dispersion, construct validity, convergent and divergent validity, and internal reliability of the instrument were tested. These analyses were based on two samples (n = 141 and n = 1265) of individuals living in low-income households in Belgium. Nine items were retained, which represent three factors (Information costs, Process costs and Stigma). The confirmatory factor analysis proved adequate model fitness. Both convergent and divergent validity were good, and internal consistency was adequate, with Cronbach’s alpha ranging between .73 and .87. The findings showed that the CCS is a valid and reliable instrument for assessing the costs potential beneficiaries face when claiming benefits. Consisting of only nine items, the scale can be easily implemented in large-scale survey research or used in day-to-day work of service providers who are interested in understanding non-take-up of their service.

Beschreibung: The COVID-19 pandemic has had a major impact on professional sports, notably, forcing the National Hockey League to hold its 2020 playoffs in empty arenas. This provided an unprecedented opportunity to study how crowds may influence penalties awarded by referees in an ecological context. Using data from playoff games played during the COVID-19 pandemic and the previous 5 years (n = 547), we estimate the number of penalties called by referees depending on whether or not spectators were present. The results show an interaction between a team’s status (home; away) and the presence or absence of crowds. Post-hoc analyses reveal that referees awarded significantly more penalties to the away team compared to the home team when there is a crowd present. However, when there are no spectators, the number of penalties awarded to the away and home teams are not significantly different. In order to generalize these results, we took advantage of the extension of the pandemic and the unusual game setting it provided to observe the behavior of referees during the 2020–2021 regular season. Again, using data from the National Hockey League (n = 1639), but also expanding our sample to include Canadian Hockey League games (n = 1709), we also find that the advantage given to the home team by referees when in front of a crowd fades in the absence of spectators. These findings provide new evidence suggesting that social pressure does have an impact on referees’ decision-making, thus contributing to explain the phenomenon of home advantage in professional ice hockey.

Beschreibung: Metabolism should drive demography by determining the rates of both biological work and resource demand. Long-standing “rules” for how metabolism should covary with demography permeate biology, from predicting the impacts of climate change to managing fisheries. Evidence for these rules is almost exclusively indirect and in the form of among-species comparisons, while direct evidence is exceptionally rare. In a manipulative field experiment on a sessile marine invertebrate, we created experimental populations that varied in population size (density) and metabolic rate, but not body size. We then tested key theoretical predictions regarding relationships between metabolism and demography by parameterizing population models with lifetime performance data from our field experiment. We found that populations with higher metabolisms had greater intrinsic rates of increase and lower carrying capacities, in qualitative accordance with classic theory. We also found important departures from theory—in particular, carrying capacity declined less steeply than predicted, such that energy use at equilibrium increased with metabolic rate, violating the long-standing axiom of energy equivalence. Theory holds that energy equivalence emerges because resource supply is assumed to be independent of metabolic rate. We find this assumption to be violated under real-world conditions, with potentially far-reaching consequences for the management of biological systems.

Beschreibung: In the Paleozoic era, more than 400 Ma, a number of insect groups continued molting after forming functional wings. Today, however, flying insects stop molting after metamorphosis when they become fully winged. The only exception is the mayflies (Paleoptera, Ephemeroptera), which molt in the subimago, a flying stage between the nymph and the adult. However, the identity and homology of the subimago still is underexplored. Debate remains regarding whether this stage represents a modified nymph, an adult, or a pupa like that of butterflies. Another relevant question is why mayflies have the subimago stage despite the risk of molting fragile membranous wings. These questions have intrigued numerous authors, but nonetheless, clear answers have not yet been found. By combining morphological studies, hormonal treatments, and molecular analysis in the mayfly Cloeon dipterum, we found answers to these old questions. We observed that treatment with a juvenile hormone analog in the last nymphal instar stimulated the expression of the Kr-h1 gene and reduced that of E93, which suppress and trigger metamorphosis, respectively. The regulation of metamorphosis thus follows the MEKRE93 pathway, as in neopteran insects. Moreover, the treatment prevented the formation of the subimago. These findings suggest that the subimago must be considered an instar of the adult mayfly. We also observed that the forelegs dramatically grow between the last nymphal instar, the subimago, and the adult. This necessary growth spread over the last two stages could explain, at least in part, the adaptive sense of the subimago.

Beschreibung: Wind power forecasting plays a key role in the design and maintenance of wind power generation which can directly help to enhance environment resilience. Offshore wind power forecasting has become more challenging due to their operation in a harsh and multi-faceted environment. In this paper, the data generated from offshore wind turbines are used for power forecasting purposes. First, fragmented data is filtered and Deep Auto-Encoding is used to select high dimensional features. Second, a mixture of the CNN and LSTM models is used to train prominent wind features and further improve forecasting accuracy. Finally, the CNN-LSTM deep learning hybrid model is fine-tuned with various parameters for reliable forecasting of wind energy on three different offshore Windfarms. A state-of-the-art comparison against existing models is presented based on root mean square error (RMSE) and mean absolute error (MAE) respectively. The forecasting analyses indicate that the proposed CNN-LSTM strategy is quite successful for offshore wind turbines by retaining the lowest RMSE and MAE along with high forecasting accuracy. The experimental findings will be helpful to design environment resilient energy transition pathways.

Beschreibung: T helper (Th)17 cells are considered to contribute to inflammatory mechanisms in diseases such as multiple sclerosis (MS). However, the discussion persists regarding their true role in patients. Here, we visualized central nervous system (CNS) inflammatory processes in models of MS live in vivo and in MS brains and discovered that CNS-infiltrating Th17 cells form prolonged stable contact with oligodendrocytes. Strikingly, compared to Th2 cells, direct contact with Th17 worsened experimental demyelination, caused damage to human oligodendrocyte processes, and increased cell death. Importantly, we found that in comparison to Th2 cells, both human and murine Th17 cells express higher levels of the integrin CD29, which is linked to glutamate release pathways. Of note, contact of human Th17 cells with oligodendrocytes triggered release of glutamate, which induced cell stress and changes in biosynthesis of cholesterol and lipids, as revealed by single-cell RNA-sequencing analysis. Finally, exposure to glutamate decreased myelination, whereas blockade of CD29 preserved oligodendrocyte processes from Th17-mediated injury. Our data provide evidence for the direct and deleterious attack of Th17 cells on the myelin compartment and show the potential for therapeutic opportunities in MS.

Beschreibung: Industrial waste salt is classified as hazardous waste to the environment. The organic impurity and its occurrence in industrial waste salt affect the salt resource utilization. In this paper, composition quantitative analysis, XRD, TG-DSC, SEM/FIB-SEM coupled with EDS, FTIR, XPS and GC-Ms were chosen to investigate the organic impurity and its occurrence in industrial waste salt. The organic impurities owe small proportion (1.77%) in the specimen and exhibit weak thermal stability within the temperature of 600°C. A clear definition of organic impurity, including 11 kinds of organic compounds, including aldehyde, benzene and its derivatives etc., were detected in the industrial waste salt. These organic impurities, owing (C-O/C-O-C, C-OH/C = O, C–C/CHx/C = C etc.)-containing function group substance, are mainly distributed both on the surface and inside of the salt particles. Meanwhile, the organic substance may combine with metal cations (Ni2+, Mg2+, Cu2+ etc.) through functional groups, such as hydroxide, carbonyl etc., which increases its stability in the industrial waste salt. These findings provide comprehensive information for the resource utilization of industrial waste salt from chemical industry etc.

Beschreibung: Background Low resting heart rate (RHR) and low systolic blood pressure (SBP) are associated with criminal behavior. However, knowledge is lacking about their predictive value for reoffending. Aim We aimed to examine associations of RHR and SBP with reoffending in a large population-based sample. Methods We conducted a cohort study of all convicted male conscripts born in Sweden 1958–1990 (N = 407,533). We obtained data by linking Swedish population-based registers. Predictor variables were RHR and SBP, measured at conscription which was mandatory until 2010 for men at age 18. The outcome variable was reoffending, defined as criminal convictions (any crime, violent crime and non-violent crime), obtained from the National Crime Register. We used survival analyses to test for associations of RHR and SBP with reoffending, adjusting for pertinent covariates such as socioeconomic status, height, weight and physical energy capacity. Results In fully adjusted Cox regression models, men with lower RHR (≤60 bpm) had higher risk of reoffending (any crime: HR = 1.17, 95% CI: 1.14, 1.19, violent crime: HR = 1.23, 95% CI: 1.17, 1.29, non-violent crime: HR = 1.16, 95% CI: 1.14, 1.19), compared to men with higher RHR (≥ 82 bpm). Men with lower SBP (≤80 mmHg) had higher risk of reoffending (any crime: HR = 1.19, 95% CI: 1.17, 1.21, violent crime: HR = 1.16, 95% CI: 1.12, 1.20, non-violent crime: HR = 1.20, 95% CI: 1.18, 1.22), compared to men with higher SBP (≥138 mmHg). Conclusions Low autonomic arousal is associated with increased risk of reoffending. RHR and SBP should be investigated further as potential predictors for reoffending as they each may have predictive value in risk assessment protocols.

Beschreibung: Background Longitudinal studies examining the life trajectories of young people after they have exited homelessness have identified concerns with persistent social and economic exclusion, struggles to shake off identities of homelessness, and housing instability. This pilot study sought to explore the feasibility of improving socioeconomic inclusion outcomes by bolstering identity capital (sense of purpose and control, self-efficacy and self-esteem) among young people who had experienced homelessness. Methods Nineteen individuals (aged 18–26) who had transitioned out of homelessness within the past three years participated in a six-week, six-session program focused on building identity capital. The study employed a mixed method prospective cohort hybrid design with an intervention group (Group One) and a delayed intervention comparison group (Group Two). Participants were interviewed every three months until nine months post-intervention. Results None of the youth who began the intervention dropped out of the program, with the exception of one participant who moved across the country and was unable to continue. Immediately after participating in the intervention, Group One had statistically significant improvements (p 〈 .05) and large to very large effect sizes in self-esteem (d = 1.16) and physical community integration (d = 1.79) compared to changes in Group Two over the same period, which had not yet begun the intervention. In the pooled analysis, small to moderate effect sizes in hopelessness, physical community integration, and self-esteem were observed at all post-intervention time points. Notably, at six- and nine-months post-intervention, statistically significant improvements (p 〈 .05) and moderate effect sizes in hopelessness (d = -0.73 and d = -0.60 respectively) and self-esteem (d = 0.71 and d = 0.53 respectively) were observed. Youth shared they appreciated the normalizing (vs. pathologizing) of strategies they needed to learn and spoke of the importance of framing new skills as something one needs “to have a better life” vs. “to get better.” Conclusions These early findings signal that targeting identity capital is feasible and may be a promising approach to incorporate into a more complex intervention that includes housing, education, and employment supports to help youth transition out of homelessness. Future research could build on these findings through a sufficiently powered randomized controlled trial.

Beschreibung: The article applies a GIS based approach to the study of the spread of the cult of Asclepius, the Greco-Roman healing god, during the Roman period. It explores the role of soldiers and physicians in the spatial dissemination of the cult along the transportation network of Roman roads in the border provinces of Britannia, Germania Superior and Inferior, Raetia, Noricum, Pannonia Superior and Inferior, Moesia Superior and Inferior, and Dacia. These provinces were selected as a suitable area for quantitative GIS exploration because they were all on the outer border of the Roman Empire, had a significant military presence, and there is a representative amount of inscriptions attested that can be used as proxies for the spatial occurrence of the three measured variables: the cult of Asclepius, Roman soldiers, and Roman physicians. After establishing by means of spatial proximity analysis that the cult of Asclepius occurred frequently in the context of the Roman army, the article proposes and quantitatively evaluates a more specific hypothesis; i.e., that the spatial occurrences of Roman physicians in inscriptions are a relevant predictor for the spatial occurrences of the worship of Asclepius in the environment of the Roman army because of the shared focus between physicians and the cult of Asclepius—health and medicine. The highly significant results of the statistical analysis reveal a positive trend in the spatial relationships between Roman physicians and the worship of Asclepius in the context of the Roman army in the majority of provinces of interest, thus supporting the proposed hypothesis. The results presented in the article demonstrate the potential of the GIS approach in testing assumptions produced by traditional scholarship and in nuancing our understanding of a specific process of cultural spread.

Beschreibung: The most effective method of the fruit harvesting is the mechanical harvest. The frequency spectrum of different testing positions on a Ginkgo biloba tree under the impact excitation was tested in the laboratory. The acceleration responses under the harmonic excitation were measured at the frequency of the peak and trough points in the frequency spectrum curves. Results of this research indicate that the frequency spectrum presented the consistency on the same branch but distinction among different branches. There was a correspondence between the frequency spectrum characteristics and the vibration responses. The vibration responses could be strengthened at the resonant frequency. Merely, the acceleration responses at low frequency were very weak. At higher frequency, the vibration responses were strong but presented different characteristics among different branches. The acceleration response on the trunk was always the weakest. On the same branch, the dynamic responses presented the similar characteristics and the acceleration amplitude increased gradually as the testing position was located away from the excitation point on the trunk. Among different branches, the strongest dynamic response appeared at different frequencies. Our results indicate that it was difficult to induce the strong vibration response of all the branches at the single frequency during the practical mechanical harvesting of fruits.

Beschreibung: Background Immunization with radiation-attenuated sporozoites (RAS) by mosquito bites provides 〉90% sterile protection against Plasmodium falciparum malaria in humans. We conducted a clinical trial based on data from previous RAS clinical trials that suggested that 800–1200 infected bites should induce ~50% protective vaccine efficacy (VE) against controlled human malaria infection (CHMI) administered three weeks after the final immunization. Two cohorts were immunized separately. VE was 55% in Cohort 1 but 90% in Cohort 2, the cohort that received a higher first dose and a reduced (fractional) fifth dose. Immune responses were better boosted by the fractional fifth dose in Cohort 2 and suggested the importance of the fractional fifth dose for increased protection in Cohort 2 responses. Three protected subjects were later boosted and were protected suggesting that protection could be extended to at least 67 weeks. Methods The ex vivo FluoroSpot assay was used to measure peripheral IFN-γ, IL2, and IFN-γ+IL2 responses to PfNF54 sporozoites and malaria antigens CSP, AMA1, TRAP, and CelTOS using pools of synthetic overlapping 15mer peptides spanning each antigen. Results There was no correlation between IFN-γ, IL2, and IFN-γ+IL2 responses to sporozoites and protection, but fold-increases between post-4th and post-5th responses greater than 1.0 occurred mostly in protected subjects. IFN-γ and IL2 responses to TRAP, CelTOS and CSP occurred only in protected subjects. Peripheral IFN-γ, IL2, and IFN-γ+IL2 responses were short-lived and low by 27 weeks post-CHMI but were restored by boosting. Conclusions These studies highlight the importance of vaccine dose and schedule for vaccine efficacy, and suggest that CSP, TRAP, AMA1 and CelTOS may be targets of protective immunity. The correlation between fold-increases in responses and protection should be explored in other vaccine trials. Trial registration ClinicalTrials.gov NCT01994525.

Beschreibung: Introduction Corneal transplantation is the only treatment option for corneal blindness to restore sight. However, there is a disproportionate imbalance between the demand and supply of corneal tissue in Ethiopia. This is because accessing corneal tissue is reliant on people who are willing to donate corneas after death. Objective This study aimed to assess the proportion of willingness to donate cornea and associated factors among adult patients attending at University of Gondar comprehensive and specialized hospital. Method Institutional based cross-sectional study was conducted from July 13 to July 28, 2020, through a face-to-face interview. A total of 451 samples were selected using systematic random sampling. The data were entered into Epidemiological information version 7 and exported to statistical package for social science version 20 for formal analysis. Variables with a P-value of 〈 0.20 in a bi-variable logistic regression were entered into the multivariable logistic regression and those variables with a p-value of 〈 0.05 were taken as statistically significant. The strength of association was shown using the odds ratio with a 95% confidence interval. Result A total of 408 adults participated in this study with a response rate of 90% and the proportion of willingness to donate cornea was 179(43.90%). Participants who had a religious belief in Christianity (AOR = 3.23 (95% CI: 1.09–9.57)) and good knowledge about corneal donation (AOR = 5.45(95%CI: 2.69–11.18)) were positively associated with the willingness of corneal donation. On the other side, the age group above 43 years (AOR = 0.31(95% CI: 0.11–0.89) was negatively associated with the willingness of corneal donation. Conclusion The proportion of willingness to donate cornea 43.9% among participants attending Gondar University Comprehensive and Specialized Hospital. Age group greater than 43 years, religion of Christianity and good knowledge were associated with the willingness of corneal donation.

Beschreibung: Dietary homogenization has progressed worldwide due to westernization and the globalization of food production systems. We investigated dietary heterogeneity in South Korea by examining the spatial distribution of carbon (C), nitrogen (N), and sulfur (S) isotope ratios using 264 human hair samples. Overall, variation in isotope values was small, indicating low dietary heterogeneity. We detected differences in δ13C, δ15N, and δ34S values between administrative provinces and metropolitan cities; inter-regional differences were typically 〈 1 ‰. Values of δ34S were significantly lower in hair samples from inland regions relative to those from coastal locations, and a similar pattern was observed in δ15N values. Understanding geographic variation in δ34S and δ15N values in human hair is useful for provenancing humans in South Korea.

Beschreibung: Natural vision is a dynamic and continuous process. Under natural conditions, visual object recognition typically involves continuous interactions between ocular motion and visual contrasts, resulting in dynamic retinal activations. In order to identify the dynamic variables that participate in this process and are relevant for image recognition, we used a set of images that are just above and below the human recognition threshold and whose recognition typically requires 〉2 s of viewing. We recorded eye movements of participants while attempting to recognize these images within trials lasting 3 s. We then assessed the activation dynamics of retinal ganglion cells resulting from ocular dynamics using a computational model. We found that while the saccadic rate was similar between recognized and unrecognized trials, the fixational ocular speed was significantly larger for unrecognized trials. Interestingly, however, retinal activation level was significantly lower during these unrecognized trials. We used retinal activation patterns and oculomotor parameters of each fixation to train a binary classifier, classifying recognized from unrecognized trials. Only retinal activation patterns could predict recognition, reaching 80% correct classifications on the fourth fixation (on average, ∼2.5 s from trial onset). We thus conclude that the information that is relevant for visual perception is embedded in the dynamic interactions between the oculomotor sequence and the image. Hence, our results suggest that ocular dynamics play an important role in recognition and that understanding the dynamics of retinal activation is crucial for understanding natural vision.

Beschreibung: Two independent structures of the proton-pumping, respiratory cytochrome bo3 ubiquinol oxidase (cyt bo3) have been determined by cryogenic electron microscopy (cryo-EM) in styrene–maleic acid (SMA) copolymer nanodiscs and in membrane scaffold protein (MSP) nanodiscs to 2.55- and 2.19-Å resolution, respectively. The structures include the metal redox centers (heme b, heme o3, and CuB), the redox-active cross-linked histidine–tyrosine cofactor, and the internal water molecules in the proton-conducting D channel. Each structure also contains one equivalent of ubiquinone-8 (UQ8) in the substrate binding site as well as several phospholipid molecules. The isoprene side chain of UQ8 is clamped within a hydrophobic groove in subunit I by transmembrane helix TM0, which is only present in quinol oxidases and not in the closely related cytochrome c oxidases. Both structures show carbonyl O1 of the UQ8 headgroup hydrogen bonded to D75I and R71I. In both structures, residue H98I occupies two conformations. In conformation 1, H98I forms a hydrogen bond with carbonyl O4 of the UQ8 headgroup, but in conformation 2, the imidazole side chain of H98I has flipped to form a hydrogen bond with E14I at the N-terminal end of TM0. We propose that H98I dynamics facilitate proton transfer from ubiquinol to the periplasmic aqueous phase during oxidation of the substrate. Computational studies show that TM0 creates a channel, allowing access of water to the ubiquinol headgroup and to H98I.

Beschreibung: Canonical Wnt signaling plays critical roles in development and tissue renewal by regulating β-catenin target genes. Recent evidence showed that β-catenin–independent Wnt signaling is also required for faithful execution of mitosis. However, the targets and specific functions of mitotic Wnt signaling still remain uncharacterized. Using phosphoproteomics, we identified that Wnt signaling regulates the microtubule depolymerase KIF2A during mitosis. We found that Dishevelled recruits KIF2A via its N-terminal and motor domains, which is further promoted upon LRP6 signalosome formation during cell division. We show that Wnt signaling modulates KIF2A interaction with PLK1, which is critical for KIF2A localization at the spindle. Accordingly, inhibition of basal Wnt signaling leads to chromosome misalignment in somatic cells and pluripotent stem cells. We propose that Wnt signaling monitors KIF2A activity at the spindle poles during mitosis to ensure timely chromosome alignment. Our findings highlight a function of Wnt signaling during cell division, which could have important implications for genome maintenance, notably in stem cells.

Beschreibung: Plants employ sensor–helper pairs of NLR immune receptors to recognize pathogen effectors and activate immune responses. Yet, the subcellular localization of NLRs pre- and postactivation during pathogen infection remains poorly understood. Here, we show that NRC4, from the “NRC” solanaceous helper NLR family, undergoes dynamic changes in subcellular localization by shuttling to and from the plant–pathogen haustorium interface established during infection by the Irish potato famine pathogen Phytophthora infestans. Specifically, prior to activation, NRC4 accumulates at the extrahaustorial membrane (EHM), presumably to mediate response to perihaustorial effectors that are recognized by NRC4-dependent sensor NLRs. However, not all NLRs accumulate at the EHM, as the closely related helper NRC2 and the distantly related ZAR1 did not accumulate at the EHM. NRC4 required an intact N-terminal coiled-coil domain to accumulate at the EHM, whereas the functionally conserved MADA motif implicated in cell death activation and membrane insertion was dispensable for this process. Strikingly, a constitutively autoactive NRC4 mutant did not accumulate at the EHM and showed punctate distribution that mainly associated with the plasma membrane, suggesting that postactivation, NRC4 may undergo a conformation switch to form clusters that do not preferentially associate with the EHM. When NRC4 is activated by a sensor NLR during infection, however, NRC4 forms puncta mainly at the EHM and, to a lesser extent, at the plasma membrane. We conclude that following activation at the EHM, NRC4 may spread to other cellular membranes from its primary site of activation to trigger immune responses.

Beschreibung: Magellanic penguins (Spheniscus magellanicus) disperse widely during winter and are a major consumer of marine resources over the Patagonian Shelf. Magellanic penguins were equipped with geolocators at Martillo Island in late February- early March 2017 and recaptured at the beginning of the next breeding season to recover the devices and to collect blood samples for stable carbon (δ13C) and nitrogen (δ15N) isotope analysis. We evaluated their whole winter dispersal and their trophic niche by sex during the last month of the winter dispersal. Also, we evaluated their spatial overlap with bottom trawl and shrimp fisheries using data from satellite fisheries monitoring. Penguins dispersed northwards up to 42°S and showed latitudinal spatial segregation between sexes during May to August (females were located further north than males). In contrast, during the last month of the winter dispersal females were located more southerly and showed lower trophic position than males. Also, females did not dive as deep as males during winter. We found high overlap between both fisheries and penguin’s spatial use in regions with documented interaction. However, no sex-specific statistical differences with fisheries overlap were found. Our results highlight the importance of understanding the spatial domains of each sex and assessment of their potential conflicts with bottom trawl fishery and shrimp fishery during the winter period.

Beschreibung: The impacts of COVID-19 on travel demand, traffic congestion, and traffic safety are attracting heated attention. However, the influence of the pandemic on electric bike (e-bike) safety has not been investigated. This paper fills the research gap by analyzing how COVID-19 affects China’s e-bike safety based on a province-level dataset containing e-bike safety metrics, socioeconomic information, and COVID-19 cases from 2017 to 2020. Multi-output regression models are adopted to investigate the overall impact of COVID-19 on e-bike safety in China. Clustering-based regression models are used to examine the heterogeneous effects of COVID-19 and the other explanatory variables in different provinces/municipalities. This paper confirms the high relevance between COVID-19 and the e-bike safety condition in China. The number of COVID-19 cases has a significant negative effect on the number of e-bike fatalities/injuries at the country level. Moreover, two clusters of provinces/municipalities are identified: one (cluster 1) with lower and the other (cluster 2 that includes Hubei province) higher number of e-bike fatalities/injuries. In the clustering-based regressions, the absolute coefficients of the COVID-19 feature for cluster 2 are much larger than those for cluster 1, indicating that the pandemic could significantly reduce e-bike safety issues in provinces with more e-bike fatalities/injuries.

Beschreibung: Background Malnutrition is highly prevalent in HIV-exposed perinatally uninfected infants (HEUs) increasing the risk of morbidity and mortality throughout the life course. We set out to compare the effect of postnatal exposure to maternal antiretroviral therapy (mART) in breastmilk versus infant Nevirapine prophylaxis (iNVP) on somatic growth of HEUs in the randomized PROMISE trial. Methods and findings We randomized 2431 mothers with HIV and their 2444 HEUs from six African countries and India 6–14 days after delivery to mART or iNVP for prevention of breastmilk HIV transmission. The mART regimen contained tenofovir/emtricitabine (99%) plus lopinavir/ritonavir. Infant growth parameters were compared at postnatal week 10, 26, 74 and 104 using World Health Organization (WHO) z-scores for length-for-age (LAZ), weight-for-age (WAZ), and head circumference-for-age (HCAZ). Week 26 LAZ was the primary endpoint measure. Student T-tests compared mean LAZ, WAZ, and HCAZ; estimated mean and 95% confidence interval (CI) are presented. Maternal and infant baseline characteristics were comparable between study arms. The estimated median breastfeeding duration was 70 weeks. After a mean follow-up of 88 weeks, mean LAZ and WAZ were below the WHO reference population mean at all timepoints, whereas mean HCAZ was not. The mART and iNVP arms did not differ for the primary outcome measure of LAZ at week 26 (p-value = 0.39; estimated mean difference (95%CI) of -0.05 (-0.18, 0.07)) or any of the other secondary growth outcome measures or timepoints (all p-values≥0.16). Secondary analyses of the primary outcome measure adjusting for week 0 LAZ and other covariates did not change these results (all p-values≥0.09). However, infants assigned to mART were more likely to have stunting compared to iNVP infants at week 26 (odds ratio (95% CI): 1.28 (1.05, 1.57)). Conclusions In HEUs, growth effects from postnatal exposure to mART compared to iNVP were comparable for measures on length, weight and head circumference with no clinically relevant differences between the groups. Despite breastfeeding into the second year of life, length and weight were below reference population means at all ages in both arms. Further investment is needed to optimize postnatal growth of infants born to women with HIV. Clinical trial registration ClinicalTrials.gov number NCT01061151.

Beschreibung: Sterile α motif domain-containing protein 9-like (SAMD9L) is encoded by a hallmark interferon-induced gene with a role in controlling virus replication that is not well understood. Here, we analyze SAMD9L function from the perspective of human mutations causing neonatal-onset severe autoinflammatory disease. Whole-genome sequencing of two children with leukocytoclastic panniculitis, basal ganglia calcifications, raised blood inflammatory markers, neutrophilia, anemia, thrombocytopaenia, and almost no B cells revealed heterozygous de novo SAMD9L mutations, p.Asn885Thrfs*6 and p.Lys878Serfs*13. These frameshift mutations truncate the SAMD9L protein within a domain a region of homology to the nucleotide-binding and oligomerization domain (NOD) of APAF1, ∼80 amino acids C-terminal to the Walker B motif. Single-cell analysis of human cells expressing green fluorescent protein (GFP)-SAMD9L fusion proteins revealed that enforced expression of wild-type SAMD9L repressed translation of red fluorescent protein messenger RNA and globally repressed endogenous protein translation, cell autonomously and in proportion to the level of GFP-SAMD9L in each cell. The children’s truncating mutations dramatically exaggerated translational repression even at low levels of GFP-SAMD9L per cell, as did a missense Arg986Cys mutation reported recurrently as causing ataxia pancytopenia syndrome. Autoinflammatory disease associated with SAMD9L truncating mutations appears to result from an interferon-induced translational repressor whose activity goes unchecked by the loss of C-terminal domains that may normally sense virus infection.

Beschreibung: Introduction WHO has recommended using Robson’s Ten Group Classification System (TGCS) to monitor and analyze CD rates. Its failure to take some maternal and organizational factors into account, however, could limit the interpretation of CD rate comparisons, because it may contribute to variations in hospital CD rates. Objective To study the contribution of maternal socioeconomic and clinical characteristics and hospital organizational factors to the variation in CD rates when using Robson’s ten-group classification system for CD rate comparisons. Methods This prospective, observational, population-based study included all deliveries at a gestational age 〉 24 weeks at the 10 hospitals of the French MYPA perinatal network in the Paris area. CD rates were calculated for each TGCS group in each hospital. Interhospital variations in these rates were investigated with hierarchical logistic regression models to quantify the variation explained by differences in patient and hospital characteristics when the TGCS is considered. Variations in CD rates between hospitals were estimated with median odds ratios (MOR) to express interhospital variance on the standard odds ratio scale. The percentage of variation explained by TGCS and maternal and hospital characteristics was also calculated. Results The global CD rate was 24.0% (interhospital range: 17–32%). CD rates within each TGCS group differed significantly between hospitals (P40 years), severe preeclampsia, and two organizational factors: hospital status (private maternities) and the deliveries per staff member per 24 hours. The MOR in the empty model was 1.27 and did not change after taking the TGCS into account. Adding maternal characteristics and hospital organizational factors lowered the MOR to 1.14 and reduced the variation between hospital CD rates by 70%. Conclusion Maternal characteristics and hospital factors are needed to address variation in CD rates among the TGCS groups. Therefore, comparisons of these rates that do not consider these factors should be interpreted carefully.

Beschreibung: Natural killer T (NKT) cells detect lipids presented by CD1d. Most studies focus on type I NKT cells that express semi-invariant αβ T cell receptors (TCR) and recognize α-galactosylceramides. However, CD1d also presents structurally distinct lipids to NKT cells expressing diverse TCRs (type II NKT cells), but our knowledge of the antigens for type II NKT cells is limited. An early study identified a nonlipidic NKT cell agonist, phenyl pentamethyldihydrobenzofuransulfonate (PPBF), which is notable for its similarity to common sulfa drugs, but its mechanism of NKT cell activation remained unknown. Here, we demonstrate that a range of pentamethylbenzofuransulfonates (PBFs), including PPBF, activate polyclonal type II NKT cells from human donors. Whereas these sulfa drug–like molecules might have acted pharmacologically on cells, here we demonstrate direct contact between TCRs and PBF-treated CD1d complexes. Further, PBF-treated CD1d tetramers identified type II NKT cell populations expressing αβTCRs and γδTCRs, including those with variable and joining region gene usage (TRAV12-1–TRAJ6) that was conserved across donors. By trapping a CD1d–type II NKT TCR complex for direct mass-spectrometric analysis, we detected molecules that allow the binding of CD1d to TCRs, finding that both selected PBF family members and short-chain sphingomyelin lipids are present in these complexes. Furthermore, the combination of PPBF and short-chain sphingomyelin enhances CD1d tetramer staining of PPBF-reactive T cell lines over either molecule alone. This study demonstrates that nonlipidic small molecules, which resemble sulfa drugs implicated in systemic hypersensitivity and drug allergy reactions, are targeted by a polyclonal population of type II NKT cells in a CD1d-restricted manner.