Asia-Pacific International Center of Excellence in Malaria Research: Maximizing Impact on Malaria Control Policy and Public Health in Cambodia and Papua New Guinea

The Asia-Pacific International Center of Excellence in Malaria Research (ICEMR) was funded in 2016 to conduct a coordinated set of field and in-depth biological studies in Cambodia and Papua New Guinea (PNG), in sites that span the range of transmission intensities currently found in the Asia-Pacific regions. The overall objective is to gain an understanding of key parasite, human host, and vector factors involved in maintaining transmission in the face of intensified control and elimination programs, and to develop novel approaches to identify and target residual transmission foci. In this article, we will describe how the ICEMR program was designed to address key knowledge gaps and priority areas for the malaria control programs in each country. In PNG, partners have worked together on two consecutive ICEMR grants (2009-2016 and 2017-2024) and we present a case study of the partnership and engagement approach that has led to stronger coordination of research activities and integration with program, informing country-level strategic planning and prioritization of control activities. In both settings, the ICEMR program has generated insights into transmission foci, risk factors for ongoing transmission, highlighting the hidden burden of vivax malaria, and the need for additional complementary vector control tools. Finally, we will summarize the emerging research questions and priority areas-namely surveillance, vivax malaria, new vector control tools, and community/health systems-oriented approaches-where further tool development and implementation research have been identified as being needed to guide policy

Connecting the Persistent Identifier Ecosystem: Building the Technical and Human Infrastructure for Open Research

The persistent identifier (PID) landscape extends to cover objects, individuals and organisations engaged in the process of research. Established services such as DataCite, Crossref, ORCID and ISNI are providing a foundation for a trusted ecosystem and a new generation of services. Scalable identifier systems will support researchers and capture research activity in a holistic way, across the entire lifecycle. Challenges remain – siloed services are not interoperable; important types of objects are not adequately covered, many processes remain manual, and adoption, while strong, is not consistent across disciplines. This article draws on the work of the EU-funded THOR project to take stock of the current state of interoperability across the PID landscape and to discuss the next steps towards an integrated research record. Examples illustrate how this interconnectivity is facilitated technically, as well as social and human challenges in fostering adoption. User stories highlight how this network of persistent identifier services is facilitating good practice in open research and where its limitations lie

Variation in photosynthetic traits related to access to water in semiarid Australian woody species

© 2017 CSIRO. Low soil water content can limit photosynthesis by reducing stomatal conductance. Here, we explore relationships among traits pertaining to carbon uptake and pre-dawn leaf water potential (as an index of soil water availability) across eight species found in semiarid central Australia. We found that as pre-dawn leaf water potential declined, stomatal limitations to photosynthesis increased, as did foliar nitrogen, which enhanced photosynthesis. Nitrogen-fixing Acacia species had higher foliar nitrogen concentrations compared with non-nitrogen fixing species, although there was considerable variability of traits within the Acacia genus. From principal component analysis we found that the most dissimilar species was Acacia aptaneura Maslin&J.E.Reid compared with both Eucalyptus camaldulensis Dehnh. and Corymbia opaca. (D.J.Carr & S.G.M.Carr)K.D.Hill&L.A.S.Johnson, having both the largest foliar N content, equal largest leaf mass per area and experiencing the lowest pre-dawn water potential of all species. A. aptaneura has shallow roots and grows above a hardpan that excludes access to groundwater, in contrast to E. camaldulensis and C. opaca, which are known to access groundwater. We conclude that ecohydrological niche separation is an important factor driving the variability of within-biome traits related to carbon gain. These observations have important implications for global vegetation models, which are parameterised with many of the traits measured here, but are often limited by data availability

Whole-genome sequencing reveals host factors underlying critical COVID-19

Altres ajuts: Department of Health and Social Care (DHSC); Illumina; LifeArc; Medical Research Council (MRC); UKRI; Sepsis Research (the Fiona Elizabeth Agnew Trust); the Intensive Care Society, Wellcome Trust Senior Research Fellowship (223164/Z/21/Z); BBSRC Institute Program Support Grant to the Roslin Institute (BBS/E/D/20002172, BBS/E/D/10002070, BBS/E/D/30002275); UKRI grants (MC_PC_20004, MC_PC_19025, MC_PC_1905, MRNO2995X/1); UK Research and Innovation (MC_PC_20029); the Wellcome PhD training fellowship for clinicians (204979/Z/16/Z); the Edinburgh Clinical Academic Track (ECAT) programme; the National Institute for Health Research, the Wellcome Trust; the MRC; Cancer Research UK; the DHSC; NHS England; the Smilow family; the National Center for Advancing Translational Sciences of the National Institutes of Health (CTSA award number UL1TR001878); the Perelman School of Medicine at the University of Pennsylvania; National Institute on Aging (NIA U01AG009740); the National Institute on Aging (RC2 AG036495, RC4 AG039029); the Common Fund of the Office of the Director of the National Institutes of Health; NCI; NHGRI; NHLBI; NIDA; NIMH; NINDS.Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care or hospitalization after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes-including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)-in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease