Interface-tuned epoxy/clay nanocomposites

Though interface has been known for a critical role in determining the properties of conventional composites, its role in polymer nanocomposites is still fragmented and in its infancy. This study synthesized a series of epoxy/clay nanocomposites with different interface strength by using three types of modifiers: ethanolamine (denoted ETH), Jeffamine� M2070 (M27) and Jeffamine� XTJ502 (XTJ). XTJ created a strong interface between clay layers and matrix because it bridged the layers with matrix by a chemical reaction as proved by Fourier transform infrared spectroscopy; M27 produced an interme-diate interface strength due to the molecular entanglement between grafted M27 chains and matrix molecules; the interface made by ETH was weak because neither chemical bridging nor molecular entanglement was involved. The studies of mechanical and thermal properties and morphology at a wide range of magnification show that the strong interface promoted the highest level of exfoliation and dispersion of clay layers, and achieved the most increment in Young’s modulus, fracture toughness and glass transition temperature (Tg) of matrix. With w1.3 wt% clay, the critical strain energy release rate G1c of neat epoxy improved from 179.0 to 384.7 J/m, 115% improvement and Tg enhanced from 93.7 to 99.

CO depletion in ATLASGAL-selected high-mass clumps

In the low-mass regime, it is found that the gas-phase abundances of C-bearing molecules in cold starless cores rapidly decrease with increasing density. Here the molecules tend to stick to the grains, forming ice mantles. We study CO depletion in the TOP100 sample of the ATLASGAL survey, and investigate its correlation with evolutionary stage and with the physical parameters of the sources. We use low-J emission lines of CO isotopologues and the dust continuum emission to infer the depletion factor fD. RATRAN one-dimensional models were also used to determine fD and to investigate the presence of depletion above a density threshold. The isotopic ratios and optical depth were derived with a Bayesian approach. We find a significant number of clumps with a large CO depletion, up to ∼20. Larger values are found for colder clumps, thus for earlier evolutionary phases. For massive clumps in the earliest stages of evolution we estimate the radius of the region where CO depletion is important to be a few tenths of a pc. CO depletion in high-mass clumps seems to behave as in the low-mass regime, with less evolved clumps showing larger values for the depletion than their more evolved counterparts, and increasing for denser sources

Predicting range shifts of African apes under global change scenarios

Aim: Modelling African great ape distribution has until now focused on current or past conditions, while future scenarios remain scarcely explored. Using an ensemble forecasting approach, we predicted changes in taxon-specific distribution under future scenarios of climate, land use and human populations for (1) areas outside protected areas (PAs) only (assuming complete management effectiveness of PAs), (2) the entire study region and (3) interspecies range overlap. Location: Tropical Africa. Methods: We compiled occurrence data (n = 5,203) on African apes from the IUCN A.P.E.S. database and extracted relevant climate-, habitat- and human-related predictors representing current and future (2050) conditions to predict taxon-specific range change under a best- and a worst-case scenario, using ensemble forecasting. Results: The predictive performance of the models varied across taxa. Synergistic interactions between predictors are shaping African ape distribution, particularly human-related variables. On average across taxa, a range decline of 50% is expected outside PAs under the best scenario if no dispersal occurs (61% in worst scenario). Otherwise, an 85% range reduction is predicted to occur across study regions (94% worst). However, range gains are predicted outside PAs if dispersal occurs (52% best, 21% worst), with a slight increase in gains expected across study regions (66% best, 24% worst). Moreover, more than half of range losses and gains are predicted to occur outside PAs where interspecific ranges overlap. Main Conclusions: Massive range decline is expected by 2050, but range gain is uncertain as African apes will not be able to occupy these new areas immediately due to their limited dispersal capacity, migration lag and ecological constraints. Given that most future range changes are predicted outside PAs, Africa\u27s current PA network is likely to be insufficient for preserving suitable habitats and maintaining connected ape populations. Thus, conservation planners urgently need to integrate land use planning and climate change mitigation measures at all decision-making levels both in range countries and abroad

Development of the Preferred Components for Co-Design in Research Guideline and Checklist: Protocol for a Scoping Review and a Modified Delphi Process

Background: There is increasing evidence that co-design can lead to more engaging, acceptable, relevant, feasible, and even effective interventions. However, no guidance is provided on the specific designs and associated methods or methodologies involved in the process. We propose the development of the Preferred Components for Co-design in Research (PRECISE) guideline to enhance the consistency, transparency, and quality of reporting co-design studies used to develop complex health interventions. Objective: The aim is to develop the first iteration of the PRECISE guideline. The purpose of the PRECISE guideline is to improve the consistency, transparency, and quality of reporting on studies that use co-design to develop complex health interventions. Methods: The aim will be achieved by addressing the following objectives: to review and synthesize the literature on the models, theories, and frameworks used in the co-design of complex health interventions to identify their common elements (components, values or principles, associated methods and methodologies, and outcomes); and by using the results of the scoping review, prioritize the co-design components, values or principles, associated methods and methodologies, and outcomes to be included in the PRECISE guideline. Results: The project has been funded by the Canadian Institutes of Health Research. Conclusions: The collective results of this project will lead to a ready-to-implement PRECISE guideline that outlines a minimum set of items to include when reporting the co-design of complex health interventions. The PRECISE guideline will improve the consistency, transparency, and quality of reports of studies. Additionally, it will include guidance on how to enact or enable the values or principles of co-design for meaningful and collaborative solutions (interventions). PRECISE might also be used by peer reviewers and editors to improve the review of manuscripts involving co-design. Ultimately, the PRECISE guideline will facilitate more efficient use of new results about complex health intervention development and bring better returns on research investments

SARS-CoV-2 susceptibility and COVID-19 disease severity are associated with genetic variants affecting gene expression in a variety of tissues

Variability in SARS-CoV-2 susceptibility and COVID-19 disease severity between individuals is partly due to genetic factors. Here, we identify 4 genomic loci with suggestive associations for SARS-CoV-2 susceptibility and 19 for COVID-19 disease severity. Four of these 23 loci likely have an ethnicity-specific component. Genome-wide association study (GWAS) signals in 11 loci colocalize with expression quantitative trait loci (eQTLs) associated with the expression of 20 genes in 62 tissues/cell types (range: 1:43 tissues/gene), including lung, brain, heart, muscle, and skin as well as the digestive system and immune system. We perform genetic fine mapping to compute 99% credible SNP sets, which identify 10 GWAS loci that have eight or fewer SNPs in the credible set, including three loci with one single likely causal SNP. Our study suggests that the diverse symptoms and disease severity of COVID-19 observed between individuals is associated with variants across the genome, affecting gene expression levels in a wide variety of tissue types

Triple therapy with artemether-lumefantrine plus amodiaquine versus artemether-lumefantrine alone for artemisinin-resistant, uncomplicated falciparum malaria: an open-label, randomised, multicentre trial

Background: Late treatment failures after artemisinin-based combination therapies (ACTs) for falciparum malaria have increased in the Greater Mekong subregion in southeast Asia. Addition of amodiaquine to artemether-lumefantrine could provide an efficacious treatment for multidrug-resistant infections. Methods: We conducted an open-label, randomised trial at five hospitals or health centres in three locations (western Cambodia, eastern Cambodia, and Vietnam). Eligible participants were male and female patients aged 2-65 years with uncomplicated Plasmodium falciparum malaria. Patients were randomly allocated (1:1 in blocks of eight to 12) to either artemether-lumefantrine alone (dosed according to WHO guidelines) or artemether-lumefantrine plus amodiaquine (10 mg base per kg/day), both given orally as six doses over 3 days. All received a single dose of primaquine (0·25 mg/kg) 24 h after the start of study treatment to limit transmission of the parasite. Parasites were genotyped, identifying artemisinin resistance. The primary outcome was Kaplan-Meier 42-day PCR-corrected efficacy against recrudescence of the original parasite, assessed by intent-to-treat. Safety was a secondary outcome. This completed trial is registered at ClinicalTrials.gov (NCT03355664). Findings: Between March 18, 2018, and Jan 30, 2020, 310 patients received randomly allocated treatment; 154 received artemether-lumefantrine alone and 156 received artemether-lumefantrine plus amodiaquine. Parasites from 305 of these patients were genotyped. 42-day PCR-corrected treatment efficacy was noted in 151 (97%, 95% CI 92-99) of 156 patients with artemether-lumefantrine plus amodiaquine versus 146 (95%, 89-97) of 154 patients with artemether-lumefantrine alone; hazard ratio (HR) for recrudescence 0·6 (95% CI 0·2-1·9, p=0·38). Of the 13 recrudescences, 12 were in 174 (57%) of 305 infections with pfkelch13 mutations indicating artemisinin resistance, for which 42-day efficacy was noted in 89 (96%) of 93 infections with artemether-lumefantrine plus amodiaquine versus 73 (90%) of 81 infections with artemether-lumefantrine alone; HR for recrudescence 0·44 (95% CI 0·14-1·40, p=0·17). Artemether-lumefantrine plus amodiaquine was generally well tolerated, but the number of mild (grade 1-2) adverse events, mainly gastrointestinal, was greater in this group compared with artemether-lumefantrine alone (vomiting, 12 [8%] with artemether-lumefantrine plus amodiaquine vs three [2%] with artemether-lumefantrine alone, p=0·03; and nausea, 11 [7%] with artemether-lumefantrine plus amodiaquine vs three [2%] with artemether-lumefantrine alone, p=0·05). Early vomiting within 1 h of treatment, requiring retreatment, occurred in no patients of 154 with artemether-lumefantrine alone versus five (3%) of 156 with artemether-lumefantrine plus amodiaquine, p=0·06. Bradycardia (≤54 beats/min) of any grade was noted in 59 (38%) of 154 patients with artemether-lumefantrine alone and 95 (61%) of 156 with artemether-lumefantrine plus amodiaquine, p=0·0001. Interpretation: Artemether-lumefantrine plus amodiaquine provides an alternative to artemether-lumefantrine alone as first-line treatment for multidrug-resistant P falciparum malaria in the Greater Mekong subregion, and could prolong the therapeutic lifetime of artemether-lumefantrine in malaria-endemic populations

Quantitative estimates of glacial refugia for chimpanzees (Pan troglodytes) since the Last Interglacial (120,000 BP).

Paleoclimate reconstructions have enhanced our understanding of how past climates have shaped present-day biodiversity. We hypothesize that the geographic extent of Pleistocene forest refugia and suitable habitat fluctuated significantly in time during the late Quaternary for chimpanzees (Pan troglodytes). Using bioclimatic variables representing monthly temperature and precipitation estimates, past human population density data, and an extensive database of georeferenced presence points, we built a model of changing habitat suitability for chimpanzees at fine spatio-temporal scales dating back to the Last Interglacial (120,000 BP). Our models cover a spatial resolution of 0.0467° (approximately 5.19 km2 grid cells) and a temporal resolution of between 1000 and 4000 years. Using our model, we mapped habitat stability over time using three approaches, comparing our modeled stability estimates to existing knowledge of Afrotropical refugia, as well as contemporary patterns of major keystone tropical food resources used by chimpanzees, figs (Moraceae), and palms (Arecacae). Results show habitat stability congruent with known glacial refugia across Africa, suggesting their extents may have been underestimated for chimpanzees, with potentially up to approximately 60,000 km2 of previously unrecognized glacial refugia. The refugia we highlight coincide with higher species richness for figs and palms. Our results provide spatio-temporally explicit insights into the role of refugia across the chimpanzee range, forming the empirical foundation for developing and testing hypotheses about behavioral, ecological, and genetic diversity with additional data. This methodology can be applied to other species and geographic areas when sufficient data are available

A first update on mapping the human genetic architecture of COVID-19

peer reviewe

COVID-19 symptoms at hospital admission vary with age and sex: results from the ISARIC prospective multinational observational study

Background: The ISARIC prospective multinational observational study is the largest cohort of hospitalized patients with COVID-19. We present relationships of age, sex, and nationality to presenting symptoms. Methods: International, prospective observational study of 60 109 hospitalized symptomatic patients with laboratory-confirmed COVID-19 recruited from 43 countries between 30 January and 3 August 2020. Logistic regression was performed to evaluate relationships of age and sex to published COVID-19 case definitions and the most commonly reported symptoms. Results: ‘Typical’ symptoms of fever (69%), cough (68%) and shortness of breath (66%) were the most commonly reported. 92% of patients experienced at least one of these. Prevalence of typical symptoms was greatest in 30- to 60-year-olds (respectively 80, 79, 69%; at least one 95%). They were reported less frequently in children (≤ 18 years: 69, 48, 23; 85%), older adults (≥ 70 years: 61, 62, 65; 90%), and women (66, 66, 64; 90%; vs. men 71, 70, 67; 93%, each P < 0.001). The most common atypical presentations under 60 years of age were nausea and vomiting and abdominal pain, and over 60 years was confusion. Regression models showed significant differences in symptoms with sex, age and country. Interpretation: This international collaboration has allowed us to report reliable symptom data from the largest cohort of patients admitted to hospital with COVID-19. Adults over 60 and children admitted to hospital with COVID-19 are less likely to present with typical symptoms. Nausea and vomiting are common atypical presentations under 30 years. Confusion is a frequent atypical presentation of COVID-19 in adults over 60 years. Women are less likely to experience typical symptoms than men