Emergence of human immunodeficiency virus-1 drug resistance during the 3-month World Health Organization-recommended enhanced adherence counseling period in the CART-1 cohort study

Background: In resource-limited settings, the World Health Organization recommends enhanced adherence counseling (EAC) for individuals with an unsuppressed human immunodeficiency virus (HIV)-1 viral load (VL) and to remeasure VL after 3 months to avoid unnecessary regimen switches. In cases in which this follow-up VL remains unsuppressed, a regimen switch is indicated. We aimed to assess levels of HIV-1 drug resistance before and after the EAC period among people with ongoing viremia (>/=80 c/mL) after EAC. Methods: We included adult participants of the CART-1 cohort study conducted in Lesotho who had a VL >/=80 c/mL after EAC. Paired plasma samples (before and after EAC) were analyzed by next-generation sequencing. We assessed the prevalence of resistance-associated mutations and viral susceptibility scores to each participant's antiretroviral therapy (ART) regimen (range, 0-3; 3 indicates complete susceptibility). Results: Among 93 participants taking nonnucleoside reverse-transcriptase inhibitor-based ART with an initial VL >/=1000 copies/mL who received a follow-up VL test after EAC, 76 still had a VL >/=80 copies/mL after EAC, and paired samples were available for 57 of 76. The number of individuals without full susceptibility to any drug in their regimen increased from 31 of 57 (54.4%) before to 36 of 57 (63.2%) after EAC. Median susceptibility scores dropped from 0.5 (interquartile range [IQR] = 0.25-) to 0.25 (IQR = 0.25-1) during the EAC period (P = .16). Conclusions: Despite high levels of resistance before EAC, we observed a slight decline in susceptibility scores after EAC. The risk of further accumulation of resistance during EAC has to be balanced against the benefit of avoiding unnecessary switches in those with spontaneous resuppression after EAC

Similar but different: Integrated phylogenetic analysis of Austrian and Swiss HIV-1 sequences reveal differences in transmission patterns of the local HIV-1 epidemics.

OBJECTIVES Phylogenetic analyses of two or more countries allow to detect differences in transmission dynamics of local HIV-1 epidemics beyond differences in demographic characteristics. METHODS A maximum-likelihood phylogenetic tree was built using pol-sequences of the Swiss HIV Cohort Study (SHCS) and the Austrian HIV Cohort Study (AHIVCOS), with international background sequences. Three types of phylogenetic cherries (clusters of size 2) were analyzed further: 1) Domestic cherries, 2) International cherries and 3) SHCS/AHIVCOS-cherries. Transmission group and ethnicities observed within the cherries were compared to the respective distribution expected from a random distribution of patients on the phylogeny. RESULTS The demographic characteristics of the AHIVCOS (included patients: 3'141) and the SHCS (included patients: 12'902) are very similar. In the AHIVCOS, 36.5% of the patients were in domestic cherries, 8.3% in international cherries, and 7.0% in SHCS/AHIVCOS cherries. Similarly, in the SHCS, 43.0% of the patients were in domestic cherries, 8.2% in international cherries, and 1.7% in SHCS/AHIVCOS cherries. While international cherries in the SHCS were dominated by heterosexuals (HET) with MSM being underrepresented, the opposite was the case for the AHIVCOS. In both cohorts, cherries with one patient belonging to the transmission group intravenous drug user (IDU) and the other one non-IDU were underrepresented. CONCLUSION In both cohorts, international HIV transmission plays a major role in the local epidemics, mostly driven by MSM in the AHIVOS, and by HET in the SHCS, highlighting the importance of international collaborations to understand global HIV transmission links on the way to eliminate HIV

A global analysis of Y-chromosomal haplotype diversity for 23 STR loci

In a worldwide collaborative effort, 19,630 Y-chromosomes were sampled from 129 different populations in 51 countries. These chromosomes were typed for 23 short-tandem repeat (STR) loci (DYS19, DYS389I, DYS389II, DYS390, DYS391, DYS392, DYS393, DYS385ab, DYS437, DYS438, DYS439, DYS448, DYS456, DYS458, DYS635, GATAH4, DYS481, DYS533, DYS549, DYS570, DYS576, and DYS643) and using the PowerPlex Y23 System (PPY23, Promega Corporation, Madison, WI). Locus-specific allelic spectra of these markers were determined and a consistently high level of allelic diversity was observed. A considerable number of null, duplicate and off-ladder alleles were revealed. Standard single-locus and haplotype-based parameters were calculated and compared between subsets of Y-STR markers established for forensic casework. The PPY23 marker set provides substantially stronger discriminatory power than other available kits but at the same time reveals the same general patterns of population structure as other marker sets. A strong correlation was observed between the number of Y-STRs included in a marker set and some of the forensic parameters under study. Interestingly a weak but consistent trend toward smaller genetic distances resulting from larger numbers of markers became apparent.Fil: Corach, Daniel. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Caputo, Mariela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Servicio de Huellas Digitales Genéticas; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marino, Miguel Eduardo. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Laboratorio de Analisis de ADN; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Purps, Josephine. Charité-Universitätsmedizin; AlemaniaFil: Siegert, Sabine. University of Cologne; AlemaniaFil: Willuweit, Sascha. Charité-Universitätsmedizin; AlemaniaFil: Nagy, Marion. Charité-Universitätsmedizin; AlemaniaFil: Alves, Cíntia. Universidad de Porto; PortugalFil: Salazar, Renato. Universidad de Porto; PortugalFil: Angustia, Sheila M. T.. Philippine National Police Crime Laboratory; FilipinasFil: Santos, Lorna H.. Philippine National Police Crime Laboratory; FilipinasFil: Anslinger, Katja. Universitat Genzentrum Der Ludwing-maximilians; AlemaniaFil: Bayer, Birgit. Universitat Genzentrum Der Ludwing-maximilians; AlemaniaFil: Ayub, Qasim. The Wellcome Trust Sanger Institute; Reino UnidoFil: Wei, Wei. The Wellcome Trust Sanger Institute; Reino UnidoFil: Xue, Yali. The Wellcome Trust Sanger Institute; Reino UnidoFil: Tyler Smith, Chris. The Wellcome Trust Sanger Institute; Reino UnidoFil: Baeta Bafalluy, Miriam. Universidad de Zaragoza; EspañaFil: Martínez Jarreta, Begoña. Universidad de Zaragoza; EspañaFil: Egyed, Balazs. Eotvos University, Budapest; ArgentinaFil: Balitzki, Beate. Universidad de Basilea; SuizaFil: Tschumi, Sibylle. Universidad de Basilea; SuizaFil: Ballard, David. King; Reino UnidoFil: Syndercombe Court, Denise. King; Reino UnidoFil: Barrantes, Xinia. Poder Judicial, Forensic Sciences Department; Costa RicaFil: Bäßler, Gerhard. Landeskriminalamt Baden-Württemberg; AlemaniaFil: Berger, Burkhard. Universidad de Innsbruck; AustriaFil: Niederstätter, Haral. Universidad de Innsbruck; AustriaFil: Parson, Walther. Universidad de Innsbruck; Austria. University Park; Estados UnidosFil: Davis, Carey. Department of Molecular and Medical Genetics; Estados Unidos. Institute of Applied Genetics; Estados UnidosFil: Furfuro, Sandra. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Laboratorio de Análisis de ADN; ArgentinaFil: Locarno, Laura. Universidad Nacional de Cuyo. Facultad de Ciencias Médicas. Laboratorio de Análisis de ADN; Argentin

Different Requirement for Wnt/β-Catenin Signaling in Limb Regeneration of Larval and Adult Xenopus

BACKGROUND:In limb regeneration of amphibians, the early steps leading to blastema formation are critical for the success of regeneration, and the initiation of regeneration in an adult limb requires the presence of nerves. Xenopus laevis tadpoles can completely regenerate an amputated limb at the early limb bud stage, and the metamorphosed young adult also regenerates a limb by a nerve-dependent process that results in a spike-like structure. Blockage of Wnt/β-catenin signaling inhibits the initiation of tadpole limb regeneration, but it remains unclear whether limb regeneration in young adults also requires Wnt/β-catenin signaling. METHODOLOGY/PRINCIPAL FINDINGS:We expressed heat-shock-inducible (hs) Dkk1, a Wnt antagonist, in transgenic Xenopus to block Wnt/β-catenin signaling during forelimb regeneration in young adults. hsDkk1 did not inhibit limb regeneration in any of the young adult frogs, though it suppressed Wnt-dependent expression of genes (fgf-8 and cyclin D1). When nerve supply to the limbs was partially removed, however, hsDkk1 expression blocked limb regeneration in young adult frogs. Conversely, activation of Wnt/β-catenin signaling by a GSK-3 inhibitor rescued failure of limb-spike regeneration in young adult frogs after total removal of nerve supply. CONCLUSIONS/SIGNIFICANCE:In contrast to its essential role in tadpole limb regeneration, our results suggest that Wnt/β-catenin signaling is not absolutely essential for limb regeneration in young adults. The different requirement for Wnt/β-catenin signaling in tadpoles and young adults appears to be due to the projection of nerve axons into the limb field. Our observations suggest that nerve-derived signals and Wnt/β-catenin signaling have redundant roles in the initiation of limb regeneration. Our results demonstrate for the first time the different mechanisms of limb regeneration initiation in limb buds (tadpoles) and developed limbs (young adults) with reference to nerve-derived signals and Wnt/β-catenin signaling

A global synthesis reveals biodiversity-mediated benefits for crop production

Human land use threatens global biodiversity and compromises multiple ecosystem functions critical to food production. Whether crop yield-related ecosystem services can be maintained by a few dominant species or rely on high richness remains unclear. Using a global database from 89 studies (with 1475 locations), we partition the relative importance of species richness, abundance, and dominance for pollination; biological pest control; and final yields in the context of ongoing land-use change. Pollinator and enemy richness directly supported ecosystem services in addition to and independent of abundance and dominance. Up to 50% of the negative effects of landscape simplification on ecosystem services was due to richness losses of service-providing organisms, with negative consequences for crop yields. Maintaining the biodiversity of ecosystem service providers is therefore vital to sustain the flow of key agroecosystem benefits to society

Nurse forecasting in Europe (RN4CAST): Rationale, design and methodology

Contains fulltext : 97171.pdf (postprint version ) (Open Access)BACKGROUND: Current human resources planning models in nursing are unreliable and ineffective as they consider volumes, but ignore effects on quality in patient care. The project RN4CAST aims innovative forecasting methods by addressing not only volumes, but quality of nursing staff as well as quality of patient care. METHODS/DESIGN: A multi-country, multilevel cross-sectional design is used to obtain important unmeasured factors in forecasting models including how features of hospital work environments impact on nurse recruitment, retention and patient outcomes. In each of the 12 participating European countries, at least 30 general acute hospitals were sampled. Data are gathered via four data sources (nurse, patient and organizational surveys and via routinely collected hospital discharge data). All staff nurses of a random selection of medical and surgical units (at least 2 per hospital) were surveyed. The nurse survey has the purpose to measure the experiences of nurses on their job (e.g. job satisfaction, burnout) as well as to allow the creation of aggregated hospital level measures of staffing and working conditions. The patient survey is organized in a sub-sample of countries and hospitals using a one-day census approach to measure the patient experiences with medical and nursing care. In addition to conducting a patient survey, hospital discharge abstract datasets will be used to calculate additional patient outcomes like in-hospital mortality and failure-to-rescue. Via the organizational survey, information about the organizational profile (e.g. bed size, types of technology available, teaching status) is collected to control the analyses for institutional differences.This information will be linked via common identifiers and the relationships between different aspects of the nursing work environment and patient and nurse outcomes will be studied by using multilevel regression type analyses. These results will be used to simulate the impact of changing different aspects of the nursing work environment on quality of care and satisfaction of the nursing workforce. DISCUSSION: RN4CAST is one of the largest nurse workforce studies ever conducted in Europe, will add to accuracy of forecasting models and generate new approaches to more effective management of nursing resources in Europe

The interplay of landscape composition and configuration: new pathways to manage functional biodiversity and agroecosystem services across Europe

Managing agricultural landscapes to support biodiversity and ecosystem services is a key aim of a sustainable agriculture. However, how the spatial arrangement of crop fields and other habitats in landscapes impacts arthropods and their functions is poorly known. Synthesising data from 49 studies (1515 landscapes) across Europe, we examined effects of landscape composition (% habitats) and configuration (edge density) on arthropods in fields and their margins, pest control, pollination and yields. Configuration effects interacted with the proportions of crop and non‐crop habitats, and species’ dietary, dispersal and overwintering traits led to contrasting responses to landscape variables. Overall, however, in landscapes with high edge density, 70% of pollinator and 44% of natural enemy species reached highest abundances and pollination and pest control improved 1.7‐ and 1.4‐fold respectively. Arable‐dominated landscapes with high edge densities achieved high yields. This suggests that enhancing edge density in European agroecosystems can promote functional biodiversity and yield‐enhancing ecosystem services

A global synthesis reveals biodiversity-mediated benefits for crop production

Human land use threatens global biodiversity and compromises multiple ecosystem functions critical to food production. Whether crop yield-related ecosystem services can be maintained by a few dominant species or rely on high richness remains unclear. Using a global database from 89 studies (with 1475 locations), we partition the relative importance of species richness, abundance, and dominance for pollination; biological pest control; and final yields in the context of ongoing land-use change. Pollinator and enemy richness directly supported ecosystem services in addition to and independent of abundance and dominance. Up to 50% of the negative effects of landscape simplification on ecosystem services was due to richness losses of service-providing organisms, with negative consequences for crop yields. Maintaining the biodiversity of ecosystem service providers is therefore vital to sustain the flow of key agroecosystem benefits to society. [Abstract copyright: Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).

Crop pests and predators exhibit inconsistent responses to surrounding landscape composition

The idea that noncrop habitat enhances pest control and represents a win–win opportunity to conserve biodiversity and bolster yields has emerged as an agroecological paradigm. However, while noncrop habitat in landscapes surrounding farms sometimes benefits pest predators, natural enemy responses remain heterogeneous across studies and effects on pests are inconclusive. The observed heterogeneity in species responses to noncrop habitat may be biological in origin or could result from variation in how habitat and biocontrol are measured. Here, we use a pest-control database encompassing 132 studies and 6,759 sites worldwide to model natural enemy and pest abundances, predation rates, and crop damage as a function of landscape composition. Our results showed that although landscape composition explained significant variation within studies, pest and enemy abundances, predation rates, crop damage, and yields each exhibited different responses across studies, sometimes increasing and sometimes decreasing in landscapes with more noncrop habitat but overall showing no consistent trend. Thus, models that used landscape-composition variables to predict pest-control dynamics demonstrated little potential to explain variation across studies, though prediction did improve when comparing studies with similar crop and landscape features. Overall, our work shows that surrounding noncrop habitat does not consistently improve pest management, meaning habitat conservation may bolster production in some systems and depress yields in others. Future efforts to develop tools that inform farmers when habitat conservation truly represents a win–win would benefit from increased understanding of how landscape effects are modulated by local farm management and the biology of pests and their enemies

Children's encounters with things: schooling the body

This article draws on work around matter and the material in order to examine how (extra)ordinary “things” are used to (re)produce formulaic and predictable performances within the context of an early years classroom. Using ethnographic data I focus on a series of encounters where oscillations between (in)animate objects and the child work at schooling the body. I also note how the “work” of things constitutes a point of tension where on the one hand they are implicated in discourses of normalization yet simultaneously work at “othering.” The article also argues that despite their coercive propensities children’s relationships with and through material things can open up possibilities for dislocating sedimented pedagogical practices where “something else” becomes possible