ALBERT

Description: Conducting numerous, rapid, and reliable PCR tests for SARS-CoV-2 is essential for our ability to monitor and control the current COVID-19 pandemic. Here, we tested the sensitivity and efficiency of SARS-CoV-2 detection in clinical samples collected directly into a mix of lysis buffer and RNA preservative, thus inactivating the virus immediately after sampling. We tested 79 COVID-19 patients and 20 healthy controls. We collected two samples (nasopharyngeal swabs) from each participant: one swab was inserted into a test tube with Viral Transport Medium (VTM), following the standard guideline used as the recommended method for sample collection; the other swab was inserted into a lysis buffer supplemented with nucleic acid stabilization mix (coined NSLB). We found that RT-qPCR tests of patients were significantly more sensitive with NSLB sampling, reaching detection threshold 2.1±0.6 (Mean±SE) PCR cycles earlier then VTM samples from the same patient. We show that this improvement is most likely since NSLB samples are not diluted in lysis buffer before RNA extraction. Re-extracting RNA from NSLB samples after 72 hours at room temperature did not affect the sensitivity of detection, demonstrating that NSLB allows for long periods of sample preservation without special cooling equipment. We also show that swirling the swab in NSLB and discarding it did not reduce sensitivity compared to retaining the swab in the tube, thus allowing improved automation of COVID-19 tests. Overall, we show that using NSLB instead of VTM can improve the sensitivity, safety, and rapidity of COVID-19 tests at a time most needed.

Description: 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.

Description: There is an emerging consensus that achieving global tuberculosis control targets will require more proactive case finding approaches than are currently used in high-incidence settings. Household contact tracing (HHCT), for which households of newly diagnosed cases are actively screened for additional infected individuals is a potentially efficient approach to finding new cases of tuberculosis, however randomized trials assessing the population-level effects of such interventions in settings with sustained community transmission have shown mixed results. One potential explanation for this is that household transmission is responsible for a variable proportion of population-level tuberculosis burden between settings. For example, transmission is more likely to occur in households in settings with a lower tuberculosis burden and where individuals mix preferentially in local areas, compared with settings with higher disease burden and more dispersed mixing. To better understand the relationship between endemic incidence levels, social mixing, and the impact of HHCT, we developed a spatially explicit model of coupled household and community transmission. We found that the impact of HHCT was robust across settings of varied incidence and community contact patterns. In contrast, we found that the effects of community contact tracing interventions were sensitive to community contact patterns. Our results suggest that the protective benefits of HHCT are robust and the benefits of this intervention are likely to be maintained across epidemiological settings.

Description: We examined whether activating independent or interdependent self-construal modulates attention shifting in response to group gaze cues. European Canadians (Study 1) and East Asian Canadians (Study 2) primed with independence vs. interdependence completed a multi-gaze cueing task with a central face gazing left or right, flanked by multiple background faces that either matched or mismatched the direction of the foreground gaze. Results showed that European Canadians (Study 1) mostly ignored background gaze cues and were uninfluenced by the self-construal primes. However, East Asian Canadians (Study 2), who have cultural backgrounds relevant to both independence and interdependence, showed different attention patterns by prime: those primed with interdependence were more distracted by mismatched (vs. matched) background gaze cues, whereas there was no change for those primed with independence. These findings suggest activating an interdependent self-construal modulates social attention mechanisms to attend broadly, but only for those who may find these representations meaningful.

Description: This study investigates the microbiological and immunological basis underlying the efficacy of electron beam-inactivated immune modulators. The underlying hypothesis is that exposure to eBeam-based ionization reactions inactivate microorganisms without modifying their antigenic properties and thereby creating immune modulators. The immunological correlates of protection induced by such eBeam based Salmonella Typhimurium (EBST) immune modulators in dendritic cell (DC) (in vitro) and mice (in vivo) models were assessed. The EBST stimulated innate pro inflammatory response (TNFα) and maturation (MHC-II, CD40, CD80 and CD86) of DC. Immuno-stimulatory potential of EBST was on par with both a commercial Salmonella vaccine, and live Salmonella cells. The EBST cells did not multiply under permissive in vitro and in vivo conditions. However, EBST cells remained metabolically active. EBST immunized mice developed Salmonella-specific CD4+ T-cells that produced the Th1 cytokine IFNγ at a level similar to that induced by the live attenuated vaccine (AroA- ST) formulation. The EBST retained stable immunogenic properties for several months at room temperature, 4°C, and -20°C as well as after lyophilization. Therefore, such eBeam-based immune modulators have potential as vaccine candidates since they offer the safety of a “killed” vaccine, while retaining the immunogenicity of an “attenuated” vaccine. The ability to store eBeam based immune modulators at room temperature without loss of potency is also noteworthy.

Description: Background A major earthquake in Israel is inevitable. Individual risk perceptions and preparedness can mitigate harm and save lives. The gap between the public’s concerns and those of experts is reflected in their differential perceptions regarding the components that influence the occurrence of an earthquake in Israel. Whereas the public believes that geographic location is the critical variable, the experts note additional variables that need to be considered. Common knowledge regarding the risks of earthquake occurrence in Israel is based on a distinction between high and low-risk areas, such that the closer a residential area is to the Great Rift Valley, the higher the risk that an earthquake will occur. Objectives To examine the variables affecting public preparedness in Israel (effective communication agent (communicator), high and low earthquake risk areas) and the degree to which experts’ knowledge contradicts respondents’ common knowledge. Methods The study used a mixed-methods approach combining qualitative and quantitative research. The first stage included in-depth interviews with earthquake experts (n = 19). The second stage consisted of an experiment conducted among a representative sample of the public (n = 834). Results Most people believe that geographical location constitutes the main risk factor for earthquakes in Israel. Yet experts claim that additional variables affect earthquake intensity and damage: building strength, earthquake magnitude, distance from earthquake epicenter, soil type, and interaction between these four. The study found that knowledge of expert information affects public willingness to prepare. The direction of this influence depends on participants’ risk perceptions regarding residential area and on degree of consistency with common knowledge. In low-risk areas, added knowledge increased willingness to prepare whereas in high-risk areas this knowledge decreased willingness. Conclusion To turn expert information into common knowledge and to increase earthquake preparedness, the authorities must educate the public to generate a new public preparedness norm.

Description: Objective Numerous adverse prenatal exposures have been individually associated with risk for psychiatric illness in the offspring. However, such exposures frequently co-occur, raising questions about their cumulative impact. We evaluated effects of cumulative adverse prenatal exposure burden on psychopathology risk in school-aged children. Methods Using baseline surveys from the U.S.-based Adolescent Brain and Cognitive Development (ABCD) Study (7,898 non-adopted, unrelated children from 21 sites, age 9–10, and their primary caregivers), we examined 8 retrospectively-reported adverse prenatal exposures in relation to caregiver-reported total and subscale Child Behavior Checklist (CBCL) scores. We also assessed cumulative effects of these factors on CBCL total as a continuous measure, as well as on odds of clinically significant psychopathology (CBCL total ≥60), in both the initial set and a separate ABCD sample comprising an additional 696 sibling pairs. Analyses were conducted before and after adjustment for 14 demographic and environmental covariates. Results In minimally and fully adjusted models, 6 exposures (unplanned pregnancy; maternal alcohol, marijuana, and tobacco use early in pregnancy; pregnancy complications; and birth complications) independently associated with significant but small increases in CBCL total score. Among these 6, none increased the odds of crossing the threshold for clinically significant symptoms by itself. However, odds of exceeding this threshold became significant with 2 exposures (OR = 1.86, 95% CI 1.47–2.36), and increased linearly with each level of exposure (OR = 1.39, 95% CI 1.31–1.47), up to 3.53-fold for ≥4 exposures versus none. Similar effects were observed in confirmatory analysis among siblings. Within sibling pairs, greater discordance for exposure load associated with greater CBCL total differences, suggesting that results were not confounded by unmeasured family-level effects. Conclusion Children exposed to multiple common, adverse prenatal events showed dose-dependent increases in broad, clinically significant psychopathology at age 9–10. Fully prospective studies are needed to confirm and elaborate upon this pattern.

Description: The physical basis of consciousness remains one of the most elusive concepts in current science. One influential conjecture is that consciousness is to do with some form of causality, measurable through information. The integrated information theory of consciousness (IIT) proposes that conscious experience, filled with rich and specific content, corresponds directly to a hierarchically organised, irreducible pattern of causal interactions; i.e. an integrated informational structure among elements of a system. Here, we tested this conjecture in a simple biological system (fruit flies), estimating the information structure of the system during wakefulness and general anesthesia. Consistent with this conjecture, we found that integrated interactions among populations of neurons during wakefulness collapsed to isolated clusters of interactions during anesthesia. We used classification analysis to quantify the accuracy of discrimination between wakeful and anesthetised states, and found that informational structures inferred conscious states with greater accuracy than a scalar summary of the structure, a measure which is generally championed as the main measure of IIT. In stark contrast to a view which assumes feedforward architecture for insect brains, especially fly visual systems, we found rich information structures, which cannot arise from purely feedforward systems, occurred across the fly brain. Further, these information structures collapsed uniformly across the brain during anesthesia. Our results speak to the potential utility of the novel concept of an “informational structure” as a measure for level of consciousness, above and beyond simple scalar values.

Description: Biomineralization is the process by which organisms use minerals to harden their tissues and provide them with physical support. Biomineralizing cells concentrate the mineral in vesicles that they secret into a dedicated compartment where crystallization occurs. The dynamics of vesicle motion and the molecular mechanisms that control it, are not well understood. Sea urchin larval skeletogenesis provides an excellent platform for investigating the kinetics of mineral-bearing vesicles. Here we used lattice light-sheet microscopy to study the three-dimensional (3D) dynamics of calcium-bearing vesicles in the cells of normal sea urchin embryos and of embryos where skeletogenesis is blocked through the inhibition of Vascular Endothelial Growth Factor Receptor (VEGFR). We developed computational tools for displaying 3D-volumetric movies and for automatically quantifying vesicle dynamics. Our findings imply that calcium vesicles perform an active diffusion motion in both, calcifying (skeletogenic) and non-calcifying (ectodermal) cells of the embryo. The diffusion coefficient and vesicle speed are larger in the mesenchymal skeletogenic cells compared to the epithelial ectodermal cells. These differences are possibly due to the distinct mechanical properties of the two tissues, demonstrated by the enhanced f-actin accumulation and myosinII activity in the ectodermal cells compared to the skeletogenic cells. Vesicle motion is not directed toward the biomineralization compartment, but the vesicles slow down when they approach it, and probably bind for mineral deposition. VEGFR inhibition leads to an increase of vesicle volume but hardly changes vesicle kinetics and doesn’t affect f-actin accumulation and myosinII activity. Thus, calcium vesicles perform an active diffusion motion in the cell of the sea urchin embryo, with diffusion length and speed that inversely correlate with the strength of the actomyosin network. Overall, our studies provide an unprecedented view of calcium vesicle 3D-dynamics and point toward cytoskeleton remodeling as an important effector of the motion of mineral-bearing vesicles.

Description: The aim of this study was to evaluate the impact on muscle strength, aerobic fitness and body composition, of replacing the physical education (PE) class of Colombian adolescents with resistance or aerobic training. 120 tanner stage 3 adolescents attending a state school were randomized to resistance training, aerobic training, or a control group who continued to attend a weekly 2- hour PE class for 16 weeks. The resistance training and aerobic training groups participated in twice weekly supervised after-school exercise sessions of 〈 1 hour instead of their PE class. Sum of skinfolds, lean body mass (bioelectrical impedance analysis), muscular strength (6 repetition maximum (RM)) bench press, lateral pulldown and leg press) and estimated cardiorespiratory fitness (multistage 20 meter shuttle run) were assessed at pre and post intervention. Complete data were available for n = 40 of the resistance training group, n = 40 of the aerobic training group and n = 30 PE (controls). Resistance training attenuated increases in sum of skinfolds compared with controls (d = 0.27, [0.09–0.36]). We found no significant effect on lean body mass. Resistance training produced a positive effect on muscle strength compared with both controls (d = 0.66 [.49-.86]) and aerobic training (d = 0.55[0.28–0.67]). There was a positive effect of resistance training on cardiorespiratory fitness compared with controls (d = 0.04 [-0.10–0.12]) but not compared with aerobic training (d = 0.24 [0.10–0.36]). Replacing a 2-hour PE class with two 1 hour resistance training sessions attenuated gains in subcutaneous adiposity, and enhanced muscle strength and aerobic fitness development in Colombian youth, based on a median attendance of approximately 1 session a week. Further research to assess whether adequate stimuli for the development of muscular fitness exists within current physical education provision is warranted.