Behavioral modeling of zinc-oxide, thin-film, field-effect transistors and the design of pixel driver, analog amplifier, and low-noise RF amplifier circuits

Zinc-oxide (ZnO) is of great interest due to transparent properties, high breakdown voltages, and low cost. Behavioral modeling is presented in this dissertation to model ZnO thin-film field-effect transistor (FET) drain current versus gate-source overdrive voltage. Initial findings show that in “strong inversion,” saturation, the drain current equation reveals a quartic-law dependency on gate-source overdrive voltage instead of square-law dependency seen in complementary metal-oxide semiconductor (CMOS) with no mobility reduction effects. This is postulated to result from the ZnO mobility showing a square-law increase with gate-source overdrive voltage. A “strong inversion,” saturation model having ±1.6% deviation from measured data is created in verilog-A to simulate and design circuits. Circuits include a fabricated and measured pixel driver circuit sinking 28 µA of current while only having a gate area of 20 µm2. This ZnO thin-film FET pixel driver is believed to have the highest current density reported at the time of this writing. Also, the first known ZnO thin-film FET analog amplifier is analytically designed for a gain of 3 V/V at 10 kHz while drawing only 8 µA of supply current. Finally, the first known ZnO thin-film FET low-noise RF amplifier is designed, utilizing scattering parameters measured at the Air Force Research Laboratory on a device with minimum channel length of 1.25 µm. This amplifier has a small-signal gain of 12.6 dB at 13.56 MHz, and a current drain of 268.4 mA at a drain voltage of 13 V

Impact of earthquakes on agriculture during the Roman–Byzantine period from pollen records of the Dead Sea laminated sediment

The Dead Sea region holds the archives of a complex relationship between an ever-changing nature and ancient civilisations. Regional pollen diagrams show a Roman–Byzantine period standing out in the recent millennia by its wetter climate that allowed intensive arboriculture. During that period, the Dead Sea formed laminites that display mostly a seasonal character. A multidisciplinary study focused on two earthquakes, 31 BC and AD 363, recorded as seismites in the Ze’elim gully A unit III which has been well dated by radiocarbon in a previous study. The sampling of the sediment was done at an annual resolution starting from a few years before and finishing a decade after each earthquake. A clear drop in agricultural indicators (especially Olea and cereals) is shown. These pollen indicators mostly reflect human activities in the Judean Hills and coastal oases. Agriculture was disturbed in large part of the rift valley where earthquake damage affected irrigation and access to the fields. It took 4 to 5 yr to resume agriculture to previous conditions. Earthquakes must be seen as contributors to factors damaging societies. If combined with other factors such as climatic aridification, disease epidemics and political upheaval, they may lead to civilisation collapse

Mutations in splicing factor genes are a major cause of autosomal dominant retinitis pigmentosa in Belgian families

Purpose : Autosomal dominant retinitis pigmentosa (adRP) is characterized by an extensive genetic heterogeneity, implicating 27 genes, which account for 50 to 70% of cases. Here 86 Belgian probands with possible adRP underwent genetic testing to unravel the molecular basis and to assess the contribution of the genes underlying their condition. Methods : Mutation detection methods evolved over the past ten years, including mutation specific methods (APEX chip analysis), linkage analysis, gene panel analysis (Sanger sequencing, targeted next-generation sequencing or whole exome sequencing), high-resolution copy number screening (customized microarray-based comparative genomic hybridization). Identified variants were classified following American College of Medical Genetics and Genomics (ACMG) recommendations. Results : Molecular genetic screening revealed mutations in 48/86 cases (56%). In total, 17 novel pathogenic mutations were identified: four missense mutations in RHO, five frameshift mutations in RP1, six mutations in genes encoding spliceosome components (SNRNP200, PRPF8, and PRPF31), one frameshift mutation in PRPH2, and one frameshift mutation in TOPORS. The proportion of RHO mutations in our cohort (14%) is higher than reported in a French adRP population (10.3%), but lower than reported elsewhere (16.5-30%). The prevalence of RP1 mutations (10.5%) is comparable to other populations (3.5%-10%). The mutation frequency in genes encoding splicing factors is unexpectedly high (altogether 19.8%), with PRPF31 the second most prevalent mutated gene (10.5%). PRPH2 mutations were found in 4.7% of the Belgian cohort. Two families (2.3%) have the recurrent NR2E3 mutation p.(Gly56Arg). The prevalence of the recurrent PROM1 mutation p.(Arg373Cys) was higher than anticipated (3.5%). Conclusions : Overall, we identified mutations in 48 of 86 Belgian adRP cases (56%), with the highest prevalence in RHO (14%), RP1 (10.5%) and PRPF31 (10.5%). Finally, we expanded the molecular spectrum of PRPH2, PRPF8, RHO, RP1, SNRNP200, and TOPORS-associated adRP by the identification of 17 novel mutations

The burden of legionnaires’ disease in Belgium, 2013 to 2017

Background: Legionnaires’ disease (LD) is a severe bacterial infection causing pneumonia. Surveillance commonly underestimates the true incidence as not all cases are laboratory confirmed and reported to public health authorities. The aim of this study was to present indicators for the impact of LD in Belgium between 2013 and 2017 and to estimate its true burden in the Belgian population in 2017, the most recent year for which the necessary data were available. Methods: Belgian hospital discharge data, data from three infectious disease surveillance systems (mandatory notification, sentinel laboratories and the national reference center), information on reimbursed diagnostic tests from the Belgian National Institute for Health and Disability Insurance and mortality data from the Belgian statistical office were used. To arrive at an estimate of the total number of symptomatic cases in Belgium, we defined a surveillance pyramid and estimated a multiplication factor to account for LD cases not captured by surveillance. The multiplication factor was then applied to the pooled number of LD cases reported by the three surveillance systems. This estimate was the basis for our hazard- and incidence-based Disability-Adjusted Life Years (DALYs) calculation. To account for uncertainty in the estimations of the DALYs and the true incidence, we used Monte Carlo simulations with 10,000 iterations. Results: We found an average of 184 LD cases reported by Belgian hospitals annually (2013–2017), the majority of which were male (72%). The surveillance databases reported 215 LD cases per year on average, 11% of which were fatal within 90 days after diagnosis. The estimation of the true incidence in the community yielded 2674 (95% Uncertainty Interval [UI]: 2425–2965) cases in 2017. LD caused 3.05 DALYs per case (95%UI: 1.67–4.65) and 8147 (95%UI: 4453–12,426) total DALYs in Belgium in 2017, which corresponds to 71.96 (95%UI: 39.33–109.75) DALYs per 100,000 persons. Conclusions: This analysis revealed a considerable burden of LD in Belgium that is vastly underestimated by surveillance data. Comparison with other European DALY estimates underlines the impact of the used data sources and methodological approaches on burden estimates, illustrating that national burden of disease studies remain essential

Surveillance of ARV safety in pregnancy and breastfeeding: towards a new framework

INTRODUCTION: As new antiretrovirals (ARVs), including long‐acting ARVs for treatment and prevention, are approved and introduced, surveillance during pregnancy must become the safety net for evaluating birth outcomes, especially those that are rare and require large numbers of observations. Historically, drug pharmacovigilance in pregnancy has been limited and fragmented between different data sources, resulting in inadequate data to assess risk. The International Maternal Pediatric Adolescent AIDS Clinical Trials Network and World Health Organization convened a Workshop which reviewed strengths and weaknesses of existing programs and discussed an improved framework to integrate existing safety data sources and promote harmonization and digitalization. DISCUSSION: This paper highlights that although robust sources of safety data and surveillance programs exist, key challenges remain, including unknown denominators, reporting bias, under‐reporting (e.g. in voluntary registries), few data sources from resource‐limited settings (most are in North America and Europe), incomplete or inaccurate data (e.g. within routine medical records). However, recent experiences (e.g. with safety signals) and current innovations (e.g. electronic record use in resource‐limited settings and defining adverse outcomes) provide momentum and building blocks for a new framework for active surveillance of ARV safety in pregnancy. A public health approach should be taken using data from existing sources, including registries of pregnancy ARV exposure and birth defects; observational surveillance and cohort studies; clinical trials; and real‐world databases. Key facilitators are harmonization and standardization of outcomes, sharing of materials and tools, and data linkages between programs. Other key facilitators include the development of guidance to estimate sample size and duration of surveillance, ensuring strategic geographic diversity, bringing partners together to share information and engaging the community of women living with HIV. CONCLUSIONS: Looking ahead, critical steps to safely introduce new ARVs include (1) adopting harmonized standards for measuring adverse maternal, birth and infant outcomes; (2) establishing surveillance centres of excellence in areas with high HIV prevalence with harmonized data collection and optimized electronic health records linking maternal/infant data; and (3) creating targets and evaluation goals for reporting progress on implementation and quality of surveillance in pregnancy. The platform will be leveraged to ensure that appropriate contributions and strategic actions by relevant stakeholders are implemented

Animal board invited review: Risks of zoonotic disease emergence at the interface of wildlife and livestock systems.

The ongoing coronavirus disease 19s pandemic has yet again demonstrated the importance of the human-animal interface in the emergence of zoonotic diseases, and in particular the role of wildlife and livestock species as potential hosts and virus reservoirs. As most diseases emerge out of the human-animal interface, a better understanding of the specific drivers and mechanisms involved is crucial to prepare for future disease outbreaks. Interactions between wildlife and livestock systems contribute to the emergence of zoonotic diseases, especially in the face of globalization, habitat fragmentation and destruction and climate change. As several groups of viruses and bacteria are more likely to emerge, we focus on pathogenic viruses of the Bunyavirales, Coronaviridae, Flaviviridae, Orthomyxoviridae, and Paramyxoviridae, as well as bacterial species including Mycobacterium sp., Brucella sp., Bacillus anthracis and Coxiella burnetii. Noteworthy, it was difficult to predict the drivers of disease emergence in the past, even for well-known pathogens. Thus, an improved surveillance in hotspot areas and the availability of fast, effective, and adaptable control measures would definitely contribute to preparedness. We here propose strategies to mitigate the risk of emergence and/or re-emergence of prioritized pathogens to prevent future epidemics

Effets de l’environnement de vie sur les associations entre déterminants individuels et santé périnatale en Wallonie (Belgique)

Résumé L’association entre les caractéristiques individuelles des mères et la prématurité ou le faible poids à la naissance, tout comme l’effet de l’environnement de vie sur la santé périnatale ont fait l’objet de nombreux travaux. Plus rares sont les études qui se sont penchées sur l’effet que l’environnement de vie pouvait avoir sur l’association entre ces caractéristiques individuelles et la santé périnatale. Dans cet article, nous adoptons une perspective multi-niveaux pour prendre en compte conjointement l’effet de l’environnement de vie et les déterminants individuels des mères sur deux indicateurs de santé périnatale, la prématurité et le faible poids à la naissance en Wallonie. Les analyses portent sur 147 718 naissances vivantes uniques issues de mères qui résidaient en Wallonie de 2010 à 2013. Les variables indépendantes principales sont le niveau d’instruction, le statut professionnel et l’état de cohabitation des mères. Les variables dépendantes sont la prématurité et le faible poids à la naissance. Un indice synthétique des conditions de bien-être (ICBE) est utilisé pour décrire l’environnement de vie et mis en relation avec la prématurité et le faible poids à la naissance grâce à des modèles de régression logistique multivariables à un et plusieurs niveaux. La fréquence de la prématurité et du faible poids s’avère plus élevée dans les communes avec un environnement de vie défavorisé. Les mères ayant un faible niveau d’instruction, n’ayant pas d’activité professionnelle ou déclarant vivre seule courent par ailleurs un risque plus élevé d’accoucher prématurément ou d’avoir un enfant de faible poids à la naissance. Dans les analyses multi-niveaux, les mesures d’association entre les variables socio-économiques de la mère et les deux variables dépendantes restent identiques aux mesures d’association observées dans les régressions classiques. Les conditions de bien-être dans une commune, mesurées par l’ICBE, n’ont pas d’effet additionnel sur les associations entre les caractéristiques socio-économiques de la mère et la prématurité ou le faible poids à la naissance. Abstract The association between the individual characteristics of mothers, preterm birth or low birth weight and the impact of the living environment on perinatal health have been widely studied. Far fewer studies have examined the way the living environment can influence the association between characteristics and perinatal health. In this paper, we adopt a multi-level analysis to simultaneously study the effects of the living environment and the individual characteristics of the mothers on preterm birth and low-birth weight in Wallonia. The study population consists of 147’718 single live births to mothers who resided in Wallonia and delivered between 2010 and 2013. The main independent variables are the mothers’s level of education, their occupational and cohabitation status. The dependent variables are preterm birth and low birth weight. A synthetic index of Well-being condition (ICBE) is used to describe living conditions. The association between these conditions, preterm birth and low birth weight is quantified through multilevel logistic regression models adjusted for mothers’ characteristics. Preterm birth and low birth weight rates are higher in municipalities with a poor living environment. Non-working, single mothers or with low levels of education are at higher risk of delivering a preterm or low birth weight baby. In the multilevel analyses, the association between the socio-economic variables and the two dependent variables is similar to the one observed in the classical regressions (one level-analysis). Well-Being conditions, measured through ICBE, have no additional effect on the association between individual socio-economic characteristics of the mother, preterm birth or low birth weight.&nbsp

18-Month Effectiveness of Short-Course Antiretroviral Regimens Combined with Alternatives to Breastfeeding to Prevent HIV Mother-to-Child Transmission

OBJECTIVE: We assessed the 18-month effectiveness of short-course (sc) antiretroviral peripartum regimens combined with alternatives to prolonged breastfeeding to prevent mother-to-child transmission (MTCT) of HIV-1 in Abidjan, Côte d'Ivoire. METHODOLOGY: HIV-1 infected pregnant women received from >/=32-36 weeks of gestation scZidovudine (ZDV)+/-Lamivudine (3TC)+single-dose Nevirapine (sdNVP) at delivery within the ANRS 1201/1202 DITRAME-Plus cohort (2001-2003). Neonates received a sdNVP+7-day ZDV prophylaxis. Two infant-feeding interventions were systematically offered free of charge: formula-feeding or exclusive shortened breastfeeding with early cessation from four months. The reference group was the ANRS 049a DITRAME cohort (1994-2000) exposed to scZDV from 36 weeks, then to prolonged breastfeeding. Pediatric HIV infection was defined by a positive plasma HIV-1 RNA at any age, or if aged >/=18 months, a positive HIV-1 serology. Turnbull estimates of cumulative transmission risks (CTR) and effectiveness (HIV-free survival) were compared by exposure group using a Cox model. FINDINGS: Among 926 live-born children enrolled, 107 (11.6%) were HIV-infected at 18 months. CTRs were 22.3% (95% confidence interval[CI]:16-30%) in the 238 ZDV long-term breastfed reference group, 15.9% (CI:10-27%) in the 169 ZDV+sdNVP shortened breastfed group; 9.4% (CI:6-14%) in the 195 ZDV+sdNVP formula-fed group; 6.8% (CI:4-11%) in the 198 ZDV+3TC+sdNVP shortened breastfed group, and 5.6% (CI:2-10%) in the 126 ZDV+3TC+sdNVP formula-fed group. Each combination had a significantly higher effectiveness than the ZDV long-term breastfed group except for ZDV+sdNVP shortened breastfed children, ranging from 51% (CI:20-70%) for ZDV+sdNVP formula fed children to 63% (CI:40-80%) for ZDV+3TC+NVPsd shortened breastfed children, after adjustment for maternal eligibility for antiretroviral therapy (ART), home delivery and low birth-weight. Substantial MTCT risk reductions are reachable in Africa, even in short-term breastfed children. The two sc antiretroviral combinations associated to any of the two infant feeding interventions, formula-feeding and shortened breastfeeding, reduce significantly MTCT with long-term benefit until age 18 months and without increasing mortality

The three pillars of natural product dereplication. Alkaloids from the bulbs of Urceolina peruviana (C. Presl) J.F. Macbr. as a preliminary test case

open access articleThe role and importance of the identification of natural products are first discussed in the perspective of the study of secondary metabolites. The rapid identification of already reported compounds, or structural dereplication, is recognized as a key element in natural product chemistry. The biological taxonomy of metabolite producing organisms, the knowledge of metabolite molecular structures, and the availability of metabolite spectroscopic signatures are considered as the three pillars of structural dereplication. The role and the construction of databases is illustrated by references to the KNApSAcK, UNPD, CSEARCH, and COCONUT databases, and by the importance of calculated taxonomic and spectroscopic data as substitutes for missing or lost original ones. Two NMR-based tools, the PNMRP database that derives from UNPD, and KnapsackSearch, a database generator that provides taxonomically focused libraries of compounds, are proposed to the community of natural product chemists. The study of the alkaloids from Urceolina peruviana, a plant from the Andes used in traditional medicine for antibacterial and anticancer actions, has given the opportunity to test different approaches to dereplication, favoring the use of publicly available data sources