ALBERT

Description: Background Drug coated balloons (DCB) with paclitaxel (Ptx) dose of 2–3.5 μg/mm2 balloon surface inhibit restenosis with different effectiveness and duration of success. A clinical dose finding study is not known for any of the currently marketed products. The aim of the present preclinical trial was to investigate a novel DCB coated with 6 μg Ptx/mm2 in a porcine model. Methods and results The current study investigated a DCB with a novel, modified iopromide based matrix with 6 μg Ptx/mm2. Drug transfer to the vessel wall of peripheral arteries was compared with a dose of 3 μg Ptx/mm2 and two fully overlapping DCB with 3 μg Ptx/mm2, each. Ptx concentration in the vessel wall after drug transfer was about twice as high for balloons with 6 μg/mm2 (1957±1472 μg/g) and two overlapping DCB with 3 μg Ptx/mm2, each (1287±619 μg/g) compared to a single balloon with 3 μg Ptx/mm2, (787±738 μg/g), with statistical significant differences for 1x6 μg/mm2 vs. 1x3 μg/mm2 (p = 0.017) but not for 2x3 μg/mm2 vs. 1x3 μg/mm2 (p = 0.184) and 1x6 μg/mm2 vs. 2x3 μg/mm2 (p = 0.178). The proportion of residual Ptx on balloon after treatment was similar for all groups between 6±1% and 10±3% of dose on balloon. Conclusion The dose of 6 μg Ptx/mm2 was successfully as well as reproducibly coated on conventional balloon catheters. Increased Ptx on balloons resulted in increased drug concentration in the vessel wall. A single balloon with 6 μg Ptx/mm2 seems to provide double dose compared to 3 μg Ptx/mm2, facilitates the procedure, and may reduce medico-economic cost compared to the use of two standard DCB.

Description: Despite the often emphasized importance of water awareness, and notwithstanding the fact that calls for increasing public awareness are becoming commonplace, most studies do not define the concept, let alone operationalise it into measurable units. This is, however, essential to measure and evaluate efforts related to water awareness such as public campaigns, customer communication and behavioural interventions. To address this gap, we conceptualise, operationalise and assess tap water awareness, hereby differentiating between cognitive awareness (head), affectional awareness (heart), and behavioural awareness (hands). In parallel, we also differentiate between tap water quality, quantity and system. By building on a variety of contemporary conceptual insights in literature and a series of expert interviews, an assessment framework is developed. A cohesive set of nine awareness components are identified and operationalised into a set of tangible questions which are put to the test in a large-scale online survey (n = 1003) in the Netherlands, applying both a traditional and modern segmentation approach based on four types of perspectives (‘quality & health concerned’, ‘aware & committed’, ‘egalitarian & solidary’, and ‘down to earth & confident’). Based on the analysis of the results of the first empirical application of our tap water awareness assessment framework, we conclude that—with a score 53.5 points out of 100—tap water awareness in the Netherlands shows ample room for improvement. Interestingly, most significant variations in awareness are generally not related to sociodemographic factors but rather apply to the four customer perspectives on drinking water that are based on people’s subjective views and preferences.

Description: We evaluated phytochemical composition, antibacterial, antifungal, anti-oxidant and cytotoxic properties of aqueous (water) and organic extracts (methanol, ethyl acetate and n-hexane) of Chenopodium glaucum. Highest phenolic content 45 mg gallic acid equivalents (GAE)/g d.w was found in aqueous extract followed by ethyl acetate (41mg GAE/g d.w) and methanol extract (34.46 mg GAE/g d.w). Antibacterial potential of aqueous and organic extracts of C. glaucum was examined against Acinetobacter baumannii, Klebsiella pneumoniae, Escherichia coli and Staphylococcus epidermidis. The aqueous, methanolic, ethyl acetate, and n-hexane extract showed antibacterial activity against A. baumannii, K. pneumoniae, E. coli and S. epidermidis. However, against A. baumannii significantly higher inhibition zone (19 mm and 18.96 mm respectively) was shown by ethyl acetate and methanol extracts. Aqueous extract possessed highest growth inhibition (11 mm) against E. coli. Aqueous, ethyl acetate and methanol extracts showed 9 mm, 10 mm, and 10.33 mm zone of inhibition against the K. pneumoniae. For antifungal activity, the extracts were less effective against Aspergillus niger but showed strong antifungal activity against Aspergillus flavus (A. flavus). The antioxidant activity was measured as DPPH (2, 2-diphenyl-1-picrylhydrazyl), H2O2 and ABTS (2, 2’-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) scavenging activity of free radicals. All the organic extracts of C. glaucum possessed ABTS, DPPH and H2O2 scavenging properties. The highest cytotoxic activity measured as half maximal inhibitory concentration (IC50) against human lungs carcinoma cells was recorded for methanolic (IC50 = 16 μg/mL) and n-hexane (IC50 = 25 μg/mL) extracts, respectively. The Gas chromatography–mass spectrometry (GC-MS) analysis showed 4 major and 26 minor compounds in n-hexane extract and 4 major and 7 minor compounds in methanol extract of the C. glaucum. It is concluded that aqueous and organic extracts of C. glaucum would be potential therapeutic agents and could be exploited on a pilot scale to treat human pathogenic diseases.

Description: Sign Language (SL) is a continuous and complex stream of multiple body movement features. That raises the challenging issue of providing efficient computational models for the description and analysis of these movements. In the present paper, we used Principal Component Analysis (PCA) to decompose SL motion into elementary movements called principal movements (PMs). PCA was applied to the upper-body motion capture data of six different signers freely producing discourses in French Sign Language. Common PMs were extracted from the whole dataset containing all signers, while individual PMs were extracted separately from the data of individual signers. This study provides three main findings: (1) although the data were not synchronized in time across signers and discourses, the first eight common PMs contained 94.6% of the variance of the movements; (2) the number of PMs that represented 94.6% of the variance was nearly the same for individual as for common PMs; (3) the PM subspaces were highly similar across signers. These results suggest that upper-body motion in unconstrained continuous SL discourses can be described through the dynamic combination of a reduced number of elementary movements. This opens up promising perspectives toward providing efficient automatic SL processing tools based on heavy mocap datasets, in particular for automatic recognition and generation.

Description: In self-reports, socially desirable responding threatens the validity of prevalence estimates for sensitive personal attitudes and behaviors. Indirect questioning techniques such as the crosswise model attempt to control for the influence of social desirability bias. The crosswise model has repeatedly been found to provide more valid prevalence estimates than direct questions. We investigated whether crosswise model estimates are also less susceptible to deliberate faking than direct questions. To this end, we investigated the effect of “fake good” instructions on responses to direct and crosswise model questions. In a sample of 1,946 university students, 12-month prevalence estimates for a sensitive road traffic behavior were higher and thus presumably more valid in the crosswise model than in a direct question. Moreover, “fake good” instructions severely impaired the validity of the direct questioning estimates, whereas the crosswise model estimates were unaffected by deliberate faking. Participants also reported higher levels of perceived confidentiality and a lower perceived ease of faking in the crosswise model compared to direct questions. Our results corroborate previous studies finding the crosswise model to be an effective tool for counteracting the detrimental effects of positive self-presentation in surveys on sensitive issues.

Description: Urbanisation alters landscapes, introduces wildlife to novel stressors, and fragments habitats into remnant ‘islands’. Within these islands, isolated wildlife populations can experience genetic drift and subsequently suffer from inbreeding depression and reduced adaptive potential. The Western tiger snake (Notechis scutatus occidentalis) is a predator of wetlands in the Swan Coastal Plain, a unique bioregion that has suffered substantial degradation through the development of the city of Perth, Western Australia. Within the urban matrix, tiger snakes now only persist in a handful of wetlands where they are known to bioaccumulate a suite of contaminants, and have recently been suggested as a relevant bioindicator of ecosystem health. Here, we used genome-wide single nucleotide polymorphism (SNP) data to explore the contemporary population genomics of seven tiger snake populations across the urban matrix. Specifically, we used population genomic structure and diversity, effective population sizes (Ne), and heterozygosity-fitness correlations to assess fitness of each population with respect to urbanisation. We found that population genomic structure was strongest across the northern and southern sides of a major river system, with the northern cluster of populations exhibiting lower heterozygosities than the southern cluster, likely due to a lack of historical gene flow. We also observed an increasing signal of inbreeding and genetic drift with increasing geographic isolation due to urbanisation. Effective population sizes (Ne) at most sites were small (〈 100), with Ne appearing to reflect the area of available habitat rather than the degree of adjacent urbanisation. This suggests that ecosystem management and restoration may be the best method to buffer the further loss of genetic diversity in urban wetlands. If tiger snake populations continue to decline in urban areas, our results provide a baseline measure of genomic diversity, as well as highlighting which ‘islands’ of habitat are most in need of management and protection.

Description: Metabolic syndrome (MetS) is highly prevalent worldwide. In the United States, estimates show that more than 30% of the adult population has MetS. MetS consists of multiple phenotypes, including obesity, dyslipidemia, and impaired glucose tolerance. Therefore, identifying the molecular mechanisms to explain this complex disease is critical for diagnosing and treating MetS. We previously showed 70 increased genes and 20 decreased genes in whole blood in MetS participants. The present study aimed to identify blood-based DNA methylation biomarkers in non-MetS versus MetS participants. The present study analyzed whole blood DNA samples from 184 adult participants of Latino descent from the Arizona Insulin Resistance (AIR) registry. We used the National Cholesterol Education Program Adult Treatment Panel III (NCEP: ATP III) criteria to identify non-MetS (n = 110) and MetS (n = 74) participants. We performed whole blood methylation analysis on select genes: ATP Synthase, H+ Transporting mitochondrial F1 Complex, Epsilon Subunit (ATP5E), Cytochrome C Oxidase Subunit VIc (COX6C), and Ribosomal Protein L9 (RPL9). The pyrosequencing analysis was a targeted approach focusing on the promoter region of each gene that specifically captured CpG methylation sites. In MetS participants, we showed decreased methylation in two CpG sites in COX6C and three CpG sites in RPL9, all p 〈 0.05 using the Mann-Whitney U test. There were no ATP5E CpG sites differently methylated in the MetS participants. Furthermore, while adjusting for age, gender, and smoking status, logistic regression analysis reaffirmed the associations between MetS and mean methylation within COX6C and RPL9 (both p 〈 0.05). In addition, Spearman’s correlation revealed a significant inverse relationship between the previously published gene expression data and methylation data for RPL9 (p 〈 0.05). In summary, these results highlight potential blood DNA methylation biomarkers for the MetS phenotype. However, future validation studies are warranted to strengthen our findings.

Description: Population-based genomic screening is at the forefront of a new approach to disease prevention. Yet the lack of diversity in genome wide association studies and ongoing debates about the appropriate use of racial and ethnic categories in genomics raise key questions about the translation of genomic knowledge into clinical practice. This article reports on an ethnographic study of a large pragmatic clinical trial of breast cancer screening called WISDOM (Women Informed to Screen Depending On Measures of Risk). Our ethnography illuminates the challenges of using race or ethnicity as a risk factor in the implementation of precision breast cancer risk assessment. Our analysis provides critical insights into how categories of race, ethnicity and ancestry are being deployed in the production of genomic knowledge and medical practice, and key challenges in the development and implementation of novel Polygenic Risk Scores in the research and clinical applications of this emerging science. Specifically, we show how the conflation of social and biological categories of difference can influence risk prediction for individuals who exist at the boundaries of these categories, affecting the perceptions and practices of scientists, clinicians, and research participants themselves. Our research highlights the potential harms of practicing genomic medicine using under-theorized and ambiguous categories of race, ethnicity, and ancestry, particularly in an adaptive, pragmatic trial where research findings are applied in the clinic as they emerge. We contribute to the expanding literature on categories of difference in post-genomic science by closely examining the implementation of a large breast cancer screening study that aims to personalize breast cancer risk using both common and rare genomic markers.

Description: Purpose To investigate the postoperative course of patients who explanted a diffractive bifocal intraocular lens (IOL) due to waxy vision and implanted with an extended depth of focus IOL. Methods This study evaluated 29 eyes of 25 patients who underwent diffractive bifocal IOL explantation followed by TECNIS Symfony® implantation because of dissatisfaction due to waxy vision at the Takabatake West Eye Clinic between January 2018 and November 2019. The indication criteria for this surgery were patients with uncorrected distance visual acuity of 0.05 logMAR or better, without eye diseases that may affect visual function, and no dissatisfactions about photic phenomena. We investigated patient demographics, uncorrected and corrected visual acuity, manifest refraction, contrast sensitivity, subjective symptoms, time to IOL explantation, explanted IOL type, and spectacle independence. Results The time to the IOL exchange after the initial IOL implantation was 55.3 ± 50.4 days (range: 14–196 days). The logMAR corrected distance visual acuity before and after IOL exchange were −0.13 ± 0.06 and −0.14 ± 0.06, respectively (p = 0.273). After IOL exchange surgery, the area under log contrast sensitivity function increased significantly from 1.07 ± 0.12 to 1.21 ± 0.12 (p 〈 0.001), and the waxy vision symptoms improved. The spectacle independence rate at the last visit was 88.0%. Conclusion For patients who complain of waxy vision despite good visual acuity after diffractive bifocal IOL implantation, exchange to extended depth of focus IOL was considered one of the useful surgical options.

Description: Ocean-going ships were key to rising maritime economies of the Early Modern period, and understanding how they were built is critical to grasp the challenges faced by shipwrights and merchant seafarers. Shipwreck timbers hold material evidence of the dynamic interplay of wood supplies, craftmanship, and evolving ship designs that helped shape the Early Modern world. Here we present the results of dendroarchaeological research carried out on Batavia’s wreck timbers, currently on display at the Western Australian Shipwrecks Museum in Fremantle. Built in Amsterdam in 1628 CE and wrecked on its maiden voyage in June 1629 CE in Western Australian waters, Batavia epitomises Dutch East India Company (Verenigde Oostindische Compagnie, or VOC) shipbuilding. In the 17th century, the VOC grew to become the first multinational trading enterprise, prompting the rise of the stock market and modern capitalism. Oak (Quercus sp.) was the preferred material for shipbuilding in northern and western Europe, and maritime nations struggled to ensure sufficient supplies to meet their needs and sustain their ever-growing mercantile fleets and networks. Our research illustrates the compatibility of dendrochronological studies with musealisation of shipwreck assemblages, and the results demonstrate that the VOC successfully coped with timber shortages in the early 17th century through diversification of timber sources (mainly Baltic region, Lübeck hinterland in northern Germany, and Lower Saxony in northwest Germany), allocation of sourcing regions to specific timber products (hull planks from the Baltic and Lübeck, framing elements from Lower Saxony), and skillful woodworking craftmanship (sapwood was removed from all timber elements). These strategies, combined with an innovative hull design and the use of wind-powered sawmills, allowed the Dutch to produce unprecedented numbers of ocean-going ships for long-distance voyaging and interregional trade in Asia, proving key to their success in 17th-century world trade.