The brain's kryptonite : overview of punctate white matter lesions in neonates

With increasing advances in the field of medical brain imaging, the known spectrum of white matter lesions hasexpanded, and we can now assess the presence of punctate white matter lesions (PWML). These focal smalllesions are quite frequently detected in the preterm infant and in full-term infants with congenital heart mal-formations with, some studies reporting a link between these lesions and adverse long-term outcomes. Theetiology of PWML has sparked a lot of questions over the years, some of which still remain unanswered. Thisnarrative review will bring an overview of current knowledge and their significant clinical importance in thenewborn brain

HIV pre-exposure prophylaxis services, provision, and delivery in the European treatment network of HIV, hepatitis and global emerging infectious diseases (NEAT ID)

Objectives: We conducted a survey to evaluate HIV pre-exposure prophylaxis (PrEP) practices in a European clinical research network on HIV, hepatitis, and global infectious diseases (NEAT ID). Methods: An online survey comprising 22 questions was sent via a secure electronic tool to the investigating physician of each of the 342 NEAT ID study centres across 15 European countries in November 2020. Results: In total, 50 sites from 12 countries responded (15% response rate). Most sites were in Western Europe, two were in Poland, and one was in Hungary. Of the responding sites, 45 provided PrEP services for a total of 27 416 PrEP users, with 1361 new PrEP initiators each month. These centres supplied PrEP for men who have sex with men (100%), people who inject drugs (84%), sex workers (84%), women (62%), and transgender women (31%). PrEP persistence after 1 year was >90%, 75%–90%, and 40%–75% in 17, 24, and 4 centres, respectively. In total, 32/45 (71%) centres reported strong community-based organization commitment at their site, and 15/45 (33%) centres developed task-shifting processes to deliver PrEP through nurses (11/15), pharmacists (5/15), and key-population peers (2/15). The biggest barriers to implementation of PrEP were low awareness of and knowledge about PrEP (47%), unwillingness to disclose sexual identity or at-risk behaviour (36%), and lack of administrative support (29%). Of the 45 centres, 32 (71%) have already been involved in PrEP research and 43 (96%) were interested in participating in such studies. Conclusions: The few NEAT ID centres that responded to the survey showed disparities in PrEP deployment and practices despite a common interest in participating in research in this field.</p

ImmunoPET helps predicting the efficacy of antibody-drug conjugates targeting TENB2 and STEAP1

The efficacy of antibody-drug conjugates (ADCs) targeted to solid tumors depends on biological processes that are hard to monitor in vivo. Zr-89-immunoPET of the ADC antibodies could help understand the performance of ADCs in the clinic by confirming the necessary penetration, binding, and internalization. This work studied monomethyl auristatin E (MMAE) ADCs against two targets in metastatic castration-resistant prostate cancer, TENB2 and STEAP1, in four patient-derived tumor models (LuCaP35V, LuCaP70, LuCaP77, LuCaP96.1). Three aspects of ADC biology were measured and compared: efficacy was measured in tumor growth inhibition studies; target expression was measured by immunohistochemistry and flow cytometry; and tumor antibody uptake was measured with In-111-mAbs and gamma counting or with Zr-89-immunoPET. Within each model, the mAb with the highest tumor uptake showed the greatest potency as an ADC. Sensitivity between models varied, with the LuCaP77 model showing weak efficacy despite high target expression and high antibody uptake. Ex vivo analysis confirmed the in vivo results, showing a correlation between expression, uptake and ADC efficacy. We conclude that Zr-89-immunoPET data can demonstrate which ADC candidates achieve the penetration, binding, and internalization necessary for efficacy in tumors sensitive to the toxic payload

Weak Gravitational Lensing with COSMOS: Galaxy Selection and Shape Measurements

With a primary goal of conducting precision weak-lensing measurements from space, the COSMOS survey has imaged the largest contiguous area observed by Hubble Space Telescope to date, using the Advanced Camera for Surveys (ACS). This is the first paper in a series in which we describe our strategy for addressing the various technical challenges in the production of weak-lensing measurements from COSMOS data. We first construct a source catalog from 575 ACS/WFC tiles (1.64 deg^2) subsampled at a pixel scale of 0.03". Defects and diffraction spikes are carefully removed, leaving a total of 1.2 × 10^6 objects to a limiting magnitude of F814W = 26.5. This catalog is made publicly available. Multiwavelength follow-up observations of the COSMOS field provide photometric redshifts for 73% of the source galaxies in the lensing catalog. We analyze and discuss the COSMOS redshift distribution and show broad agreement with other surveys to z ~ 1. Our next step is to measure the shapes of galaxies and correct them for the distortion induced by the time-varying ACS point-spread function and for charge transfer efficiency (CTE) effects. Simulated images are used to derive the shear susceptibility factors that are necessary in transforming shape measurements into unbiased shear estimators. For every galaxy we derive a shape measurement error and utilize this quantity to extract the intrinsic shape noise of the galaxy sample. Interestingly, our results indicate that intrinsic shape noise varies little with size, magnitude, or redshift. Representing a number density of 66 galaxies per arcmin^2, the final COSMOS weak-lensing catalog contains 3.9 × 10^5 galaxies with accurate shape measurements. The properties of the COSMOS weak-lensing catalog described throughout this paper will provide key input numbers for the preparation and design of next-generation wide field space missions

Global guidance on environmental life cycle impact assessment indicators: Progress and case study

International audiencePurpose: The life cycle impact assessment (LCIA) guidance flagship project of the United Nations Environment Programme (UNEP)/Society of Environmental Toxicology and Chemistry (SETAC) Life Cycle Initiative aims at providing global guidance and building scientific consensus on environmental LCIA indicators. This paper presents the progress made since 2013, preliminary results obtained for each impact category and the description of a rice life cycle assessment (LCA) case study designed to test and compare LCIA indicators. Methods: The effort has been focused in a first stage on impacts of global warming, fine particulate matter emissions, water use and land use, plus cross-cutting issues and LCA-based footprints. The paper reports the process and progress and specific results obtained in the different task forces (TFs). Additionally, a rice LCA case study common to all TF has been developed. Three distinctly different scenarios of producing and cooking rice have been defined and underlined with life cycle inventory data. These LCAs help testing impact category indicators which are being developed and/or selected in the harmonisation process. The rice LCA case study further helps to ensure the practicality of the finally recommended impact category indicators. Results and discussion: The global warming TF concludes that analysts should explore the sensitivity of LCA results to metrics other than GWP. The particulate matter TF attained initial guidance of how to include health effects from PM2.5 exposures consistently into LCIA. The biodiversity impacts of land use TF suggests to consider complementary metrics besides species richness for assessing biodiversity loss. The water use TF is evaluating two stress-based metrics, AWaRe and an alternative indicator by a stakeholder consultation. The cross-cutting issues TF agreed upon maintaining disability-adjusted life years (DALY) as endpoint unit for the safeguard subject 'human health'. The footprint TF defined main attributes that should characterise all footprint indicators. 'Rice cultivation' and 'cooking' stages of the rice LCA case study contribute most to the environmental impacts assessed. Conclusions: The results of the TF will be documented in white papers and some published in scientific journals. These white papers represent the input for the Pellston workshop', taking place in Valencia, Spain, from 24 to 29 January 2016, where best practice, harmonised LCIA indicators and an update on the general LCIA framework will be discussed and agreed on. With the diversity in results and the multi-tier supply chains, the rice LCA case study is well suited to test candidate recommended indicators and to ensure their applicability in common LCA case studies

Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

Exploring South Africa's southern frontier : a 20-year vision for polar research through the South African National Antarctic Programme

Antarctica, the sub-Antarctic islands and surrounding Southern Ocean are regarded as one of the planet’s last remaining wildernesses, ‘insulated from threat by [their] remoteness and protection under the Antarctic Treaty System’. Antarctica encompasses some of the coldest, windiest and driest habitats on earth. Within the Southern Ocean, sub-Antarctic islands are found between the Sub-Antarctic Front to the north and the Polar Front to the south. Lying in a transition zone between warmer subtropical and cooler Antarctic waters, these islands are important sentinels from which to study climate change. A growing body of evidence now suggests that climatically driven changes in the latitudinal boundaries of these two fronts define the islands’ short- and long-term atmospheric and oceanic circulation patterns. Consequently, sub-Antarctic islands and their associated terrestrial and marine ecosystems offer ideal natural laboratories for studying ecosystem response to change. For example, a recent study indicates that the shift in the geographical position of the oceanic fronts has disrupted inshore marine ecosystems, with a possible impact on top predators. Importantly, biotic responses are variable as indicated by different population trends of these top predators. When studied collectively, these variations in species’ demographic patterns point to complex spatial and temporal changes within the broader sub-Antarctic ecosystem, and invite further examination of the interplay between extrinsic and intrinsic drivers.http://www.sajs.co.zaam2017GeneticsMammal Research InstituteZoology and Entomolog

Tracking development assistance for health and for COVID-19: a review of development assistance, government, out-of-pocket, and other private spending on health for 204 countries and territories, 1990-2050

Background The rapid spread of COVID-19 renewed the focus on how health systems across the globe are financed, especially during public health emergencies. Development assistance is an important source of health financing in many low-income countries, yet little is known about how much of this funding was disbursed for COVID-19. We aimed to put development assistance for health for COVID-19 in the context of broader trends in global health financing, and to estimate total health spending from 1995 to 2050 and development assistance for COVID-19 in 2020. Methods We estimated domestic health spending and development assistance for health to generate total health-sector spending estimates for 204 countries and territories. We leveraged data from the WHO Global Health Expenditure Database to produce estimates of domestic health spending. To generate estimates for development assistance for health, we relied on project-level disbursement data from the major international development agencies' online databases and annual financial statements and reports for information on income sources. To adjust our estimates for 2020 to include disbursements related to COVID-19, we extracted project data on commitments and disbursements from a broader set of databases (because not all of the data sources used to estimate the historical series extend to 2020), including the UN Office of Humanitarian Assistance Financial Tracking Service and the International Aid Transparency Initiative. We reported all the historic and future spending estimates in inflation-adjusted 2020 US$, 2020 US$ per capita, purchasing-power parity-adjusted US$per capita, and as a proportion of gross domestic product. We used various models to generate future health spending to 2050. Findings In 2019, health spending globally reached$8. 8 trillion (95% uncertainty interval UI] 8.7-8.8) or $1132 (1119-1143) per person. Spending on health varied within and across income groups and geographical regions. Of this total,$40.4 billion (0.5%, 95% UI 0.5-0.5) was development assistance for health provided to low-income and middle-income countries, which made up 24.6% (UI 24.0-25.1) of total spending in low-income countries. We estimate that $54.8 billion in development assistance for health was disbursed in 2020. Of this,$13.7 billion was targeted toward the COVID-19 health response. $12.3 billion was newly committed and$1.4 billion was repurposed from existing health projects. $3.1 billion (22.4$2.4 billion (17.9%) was for supply chain and logistics. Only $714.4 million (7.7$1519 (1448-1591) per person in 2050, although spending across countries is expected to remain varied. Interpretation Global health spending is expected to continue to grow, but remain unequally distributed between countries. We estimate that development organisations substantially increased the amount of development assistance for health provided in 2020. Continued efforts are needed to raise sufficient resources to mitigate the pandemic for the most vulnerable, and to help curtail the pandemic for all. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd