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IMPORTANCE: Among kidney transplant recipients, Black patients continue to have worse graft function and reduced patient and graft survival. Better understanding of different phenotypes and subgroups of Black kidney transplant recipients may help the transplant community to identify individualized strategies to improve outcomes among these vulnerable groups. OBJECTIVE: To cluster Black kidney transplant recipients in the US using an unsupervised machine learning approach. DESIGN, SETTING, AND PARTICIPANTS: This cohort study performed consensus cluster analysis based on recipient-, donor-, and transplant-related characteristics in Black kidney transplant recipients in the US from January 1, 2015, to December 31, 2019, in the Organ Procurement and Transplantation Network/United Network for Organ Sharing database. Each cluster’s key characteristics were identified using the standardized mean difference, and subsequently the posttransplant outcomes were compared among the clusters. Data were analyzed from June 9 to July 17, 2021. EXPOSURE: Machine learning consensus clustering approach. MAIN OUTCOMES AND MEASURES: Death-censored graft failure, patient death within 3 years after kidney transplant, and allograft rejection within 1 year after kidney transplant. RESULTS: Consensus cluster analysis was performed for 22 687 Black kidney transplant recipients (mean [SD] age, 51.4 [12.6] years; 13 635 men [60%]), and 4 distinct clusters that best represented their clinical characteristics were identified. Cluster 1 was characterized by highly sensitized recipients of deceased donor kidney retransplants; cluster 2, by recipients of living donor kidney transplants with no or short prior dialysis; cluster 3, by young recipients with hypertension and without diabetes who received young deceased donor transplants with low kidney donor profile index scores; and cluster 4, by older recipients with diabetes who received kidneys from older donors with high kidney donor profile index scores and extended criteria donors. Cluster 2 had the most favorable outcomes in terms of death-censored graft failure, patient death, and allograft rejection. Compared with cluster 2, all other clusters had a higher risk of death-censored graft failure and death. Higher risk for rejection was found in clusters 1 and 3, but not cluster 4. CONCLUSIONS AND RELEVANCE: In this cohort study using an unsupervised machine learning approach, the identification of clinically distinct clusters among Black kidney transplant recipients underscores the need for individualized care strategies to improve outcomes among vulnerable patient groups.

Additional file 2: Appendix 2. Health care providers semi-structured interview guide.

Additional file 1: Appendix 1. PARENT semi-structured interview guide.

Additional file 3.

Aging is commonly associated with chronic low-grade inflammation and hypertension but it is unknown whether a cause-effect relationship exists between them. We compared the sensitivity of young adult (8-12 w) and aged (23-31 mo) male C57Bl6J mice to develop hypertension in response to a slow-pressor dose of angiotensin II (Ang II; 0.28 mg/kg/d; 28 d). In young mice, the pressor response to Ang II was gradual and increased to 142±8 mmHg over 28 d. However, in aged mice, Ang II promptly increased SBP and reached 155±12 mmHg by 28 d. Aging increased renal but not brain expression of Ang II receptors (At1ar and At2r) and elevated AT1R:AT2R expression ratio in mesenteric artery. Maximal contractile responses of mesenteric arteries to Ang II were enhanced in aged mice and were not affected by L-NAME, indomethacin or tempol. Mesenteric arteries and thoracic aortae from aged mice exhibited higher Nox2-dependent superoxide production. Despite having higher renal expression of Nlrp3, Casp-1 and Il-1β, Ang II-induced hypertension (SBP: 139±7 mmHg) was unaffected by co-infusion of the NLRP3 inflammasome inhibitor, MCC950 (10 mg/kg/d; SBP: 145±10 mmHg). Thus, increased vascular AT1R:AT2R expression, rather than NLRP3 inflammasome activation, may contribute to enhanced responses to Ang II in aging.

Carbon offset programs are critical in the fight against climate change. One emerging threat to the long-term stability and viability of forest carbon offset projects is wildfires, which can release large amounts of carbon and limit the efficacy of associated offsetting credits. However, analysis of wildfire risk to forest carbon projects is challenging because existing models for forecasting long-term fire risk are limited in predictive accuracy. Therefore, we propose an explainable artificial intelligence (XAI) model trained on 7 million global satellite wildfire observations. Validation results suggest substantial potential for high resolution, enhanced accuracy projections of global wildfire risk, and the model outperforms the U.S. National Center for Atmospheric Research's leading fire model. Applied to a collection of 190 global forest carbon projects, we find that fire exposure is projected to increase 55% [37-76%] by 2080 under a mid-range scenario (SSP2-4.5). Our results indicate the large wildfire carbon project damages seen in the past decade are likely to become more frequent as forests become hotter and drier. In response, we hope the model can support wildfire managers, policymakers, and carbon market analysts to preemptively quantify and mitigate long-term permanence risks to forest carbon projects., Comment: 6 pages, 5 figures. Published in ICLR 2023 Workshop: Tackling Climate Change with Machine Learning

Molecular organic fluorophores are currently used in organic light-emitting diodes, though non-emissive triplet excitons generated in devices incorporating conventional fluorophores limit the efficiency. This limit can be overcome in materials that have intramolecular charge-transfer excitonic states and associated small singlet-triplet energy separations; triplets can then be converted to emissive singlet excitons resulting in efficient delayed fluorescence. However, the mechanistic details of the spin interconversion have not yet been fully resolved. We report transient electron spin resonance studies that allow direct probing of the spin conversion in a series of delayed fluorescence fluorophores with varying energy gaps between local excitation and charge-transfer triplet states. The observation of distinct triplet signals, unusual in transient electron spin resonance, suggests that multiple triplet states mediate the photophysics for efficient light emission in delayed fluorescence emitters. We reveal that as the energy separation between local excitation and charge-transfer triplet states decreases, spin interconversion changes from a direct, singlet-triplet mechanism to an indirect mechanism involving intermediate states.

Molecular organic fluorophores are currently used in organic light-emitting diodes, though non-emissive triplet excitons generated in devices incorporating conventional fluorophores limit the efficiency. This limit can be overcome in materials that have intramolecular charge-transfer excitonic states and associated small singlet-triplet energy separations; triplets can then be converted to emissive singlet excitons resulting in efficient delayed fluorescence. However, the mechanistic details of the spin interconversion have not yet been fully resolved. We report transient electron spin resonance studies that allow direct probing of the spin conversion in a series of delayed fluorescence fluorophores with varying energy gaps between local excitation and charge-transfer triplet states. The observation of distinct triplet signals, unusual in transient electron spin resonance, suggests that multiple triplet states mediate the photophysics for efficient light emission in delayed fluorescence emitters. We reveal that as the energy separation between local excitation and charge-transfer triplet states decreases, spin interconversion changes from a direct, singlet-triplet mechanism to an indirect mechanism involving intermediate states.

Molecular organic fluorophores are currently used in organic light-emitting diodes, though non-emissive triplet excitons generated in devices incorporating conventional fluorophores limit the efficiency. This limit can be overcome in materials that have intramolecular charge-transfer excitonic states and associated small singlet-triplet energy separations; triplets can then be converted to emissive singlet excitons resulting in efficient delayed fluorescence. However, the mechanistic details of the spin interconversion have not yet been fully resolved. We report transient electron spin resonance studies that allow direct probing of the spin conversion in a series of delayed fluorescence fluorophores with varying energy gaps between local excitation and charge-transfer triplet states. The observation of distinct triplet signals, unusual in transient electron spin resonance, suggests that multiple triplet states mediate the photophysics for efficient light emission in delayed fluorescence emitters. We reveal that as the energy separation between local excitation and charge-transfer triplet states decreases, spin interconversion changes from a direct, singlet-triplet mechanism to an indirect mechanism involving intermediate states.

Increasing numbers of compatible pairs are choosing to enter paired exchange programs, but motivations, outcomes, and system-level effects of participation are not well described. Using a linkage of the Scientific Registry of Transplant Recipients and National Kidney Registry, we compared outcomes of traditional (originally incompatible) recipients to originally compatible recipients using the Kaplan-Meier method. We identified 154 compatible pairs. Most pairs sought to improve HLA matching. Compared to the original donor, actual donors were younger (39 vs. 50years, p&nbsp

Supplemental material, sj-docx-1-pmj-10.1177_02692163221105599 for Measuring quality of dying, death and end-of-life care for children and young people: A scoping review of available tools by Catriona R Mayland, Katy A Sunderland, Matthew Cooper, Paul Taylor, Philip A Powell, Lucy Zeigler, Vicki Cox, Constance Gilman, Nicola Turner, Kate Flemming and Lorna K Fraser in Palliative Medicine

Additional file 1. Interview question guide parent.

Additional file 4. Semi-structured interview guide for healthcare provider.

Additional file 3. Healthcare provider focus group guide.

Additional file 7. Telephone follow-up at 6-12 weeks post discharge.

Additional file 6. Medical record audit checklist form.

Additional file 5. Semi-structured interview guide for healthcare providers.

Additional file 2. Semi-structured interview guide for healthcare provider.

Additional file 1. Home Exercise Programme.

This paper consists of two parts, namely, “Is the Landscape of the Problem of Evil at an Impasse?” and “A Pragmatic Argument against Reliance in God to Prevent Horrendous Evils.” The first part of this paper completes an analysis of formulations around the problem of evil, analysis of logical and evidential arguments from evil, and analysis of theist responses to the problem of evil. Within the first part, I establish that certain arguments from evil are not valid, so they will not convince the theist. In response to those which are however, the theist does not convince the atheist to abandon the problem of evil. Sceptical theism allows the theist to remain unconvinced by the problem of evil and immune to any evidential argument from evil. Due to colliding atheist and theist principles, there is an impasse in the debate. The second part of this paper aims to take a more pragmatic approach to the problem of evil. Rather than focusing on debate and conjecture within the landscape of the problem of evil, this paper seeks to establish a common idea that theists and atheists will be able to hold. Both atheists and theists seek to eliminate evil. Within the second part of the paper, I establish that reliance in God alone to prevent horrendous evils is an unreasonable action. I do this through an analysis and application of pragmatism and Humean thought to the problem of evil. The application is largely based around naturalist background assumptions which atheists and theists will all hold, and how these assumptions inform us of what actions may be reasonable and unreasonable.

Molecular organic fluorophores are currently used in organic light-emitting diodes, though non-emissive triplet excitons generated in devices incorporating conventional fluorophores limit the efficiency. This limit can be overcome in materials that have intramolecular charge-transfer excitonic states and associated small singlet-triplet energy separations; triplets can then be converted to emissive singlet excitons resulting in efficient delayed fluorescence. However, the mechanistic details of the spin interconversion have not yet been fully resolved. We report transient electron spin resonance studies that allow direct probing of the spin conversion in a series of delayed fluorescence fluorophores with varying energy gaps between local excitation and charge-transfer triplet states. The observation of distinct triplet signals, unusual in transient electron spin resonance, suggests that multiple triplet states mediate the photophysics for efficient light emission in delayed fluorescence emitters. We reveal that as the energy separation between local excitation and charge-transfer triplet states decreases, spin interconversion changes from a direct, singlet-triplet mechanism to an indirect mechanism involving intermediate states.

Molecular organic fluorophores are currently used in organic light-emitting diodes, though non-emissive triplet excitons generated in devices incorporating conventional fluorophores limit the efficiency. This limit can be overcome in materials that have intramolecular charge-transfer excitonic states and associated small singlet-triplet energy separations; triplets can then be converted to emissive singlet excitons resulting in efficient delayed fluorescence. However, the mechanistic details of the spin interconversion have not yet been fully resolved. We report transient electron spin resonance studies that allow direct probing of the spin conversion in a series of delayed fluorescence fluorophores with varying energy gaps between local excitation and charge-transfer triplet states. The observation of distinct triplet signals, unusual in transient electron spin resonance, suggests that multiple triplet states mediate the photophysics for efficient light emission in delayed fluorescence emitters. We reveal that as the energy separation between local excitation and charge-transfer triplet states decreases, spin interconversion changes from a direct, singlet-triplet mechanism to an indirect mechanism involving intermediate states.

Molecular organic fluorophores are currently used in organic light-emitting diodes, though non-emissive triplet excitons generated in devices incorporating conventional fluorophores limit the efficiency. This limit can be overcome in materials that have intramolecular charge-transfer excitonic states and associated small singlet-triplet energy separations; triplets can then be converted to emissive singlet excitons resulting in efficient delayed fluorescence. However, the mechanistic details of the spin interconversion have not yet been fully resolved. We report transient electron spin resonance studies that allow direct probing of the spin conversion in a series of delayed fluorescence fluorophores with varying energy gaps between local excitation and charge-transfer triplet states. The observation of distinct triplet signals, unusual in transient electron spin resonance, suggests that multiple triplet states mediate the photophysics for efficient light emission in delayed fluorescence emitters. We reveal that as the energy separation between local excitation and charge-transfer triplet states decreases, spin interconversion changes from a direct, singlet-triplet mechanism to an indirect mechanism involving intermediate states.

Natural Flood Management (NFM) seeks to utilise natural processes within the landscape to reduce flood risk and is increasingly being viewed as a sustainable, cost effective, and complementary addition to flood defence infrastructure. One NFM measure is to increase the proportion of forested lands within catchments draining to the communities at risk. Tree cover has good potential to reduce flood risk by increasing canopy evaporation, enhancing below and above ground flood storage and slowing the flow of water towards streams. However, the extent to which these mechanisms are superior for forestry, compared to other land uses, and how they vary throughout the year and for different forest types remains difficult to predict, which is a major gap in our ability to quantify how forest cover can help reduce flood risk. Here, we present a study that utilises LoRaWAN, a developing wireless sensor network technology, to provide real time collection of canopy interception and streamflow data at the Pennal catchment in Wales, UK. LoRaWAN is an emerging Low Power Wide Area Network (LPWAN) protocol designed for Internet of Things (IoT) applications. The capability of LoRaWAN to operate under harsh attenuation and interference conditions make it well suited to the forest catchment area which is characterised by dense vegetation and varied topography. This study will utilise a network of tipping bucket rain gauges and stream flow monitors distributed in different forest types and densities. The rain gauges and water level monitors are the end devices (IoT things) in the network which perform a direct communication with LoRaWAN Gateways, from which the data is ‘pushed’ to a server for storing and assimilation. The data will be used to develop and validate a coupled canopy and soil hydrology model. This will guide forest management and aid in quantifying the effects of natural flood management techniques, initially within the Pennal catchment, with a view to expanding to the regional scale.

Additional file 2. STROBE statement. Checklist of reporting guidelines for observational studies (cross-sectional).

Additional file 1. Detailed description of multiple imputation.

We study supercritical $O(d)$-equivariant biharmonic maps with a focus on $d = 5$, where $d$ is the dimension of the domain. We give a characterisation of non-trivial equivariant biharmonic maps from $\mathbf{R}^5$ into $S^5$ as heteroclinic orbits of an associated dynamical system. Moreover, we prove the existence of such non-trivial equivariant biharmonic maps. Finally, in stark contrast to the harmonic map analogue, we show the existence of an equivariant biharmonic map from $B^5(0, 1)$ into $S^5$ that winds around $S^5$ infinitely many times.

Additional file 4: Table S2. Mean difference in allostatic load between those exposed and unexposed to racial discrimination, within and between class comparisons.

Global resource flows and indicators for emerging challenges relevant to the realization of sustainable development goals are of high interest for research on sustainable development and geopolitics. Such complex sets of information require advanced methodological approaches that enable effective communication of data and participatory data exploration. To address this need, we present ResFlow, an interactive web-based application for the visualization and exploration of flow data, in particular for analysing resource flows between countries. ResFlow visualizes resource flows to and from countries using 3D arcs and provides tailored interaction and filtering techniques to facilitate flexible exploration of the data at hand., EuroVis 2020 - Posters, Posters, 9, 11, Carlo Navarra, Karin Eliasson, Jesper Karjalainen, Lotten Wiréhn, Matthew Cooper, and Tina S. Neset, CCS Concepts: Human-centered computing -->Geographic visualization

Additional file 3: Table S1. Complete cases and imputed values for individual biomarkers and allostatic load risk index.

We evaluate several augmentations to the choropleth map to convey additional information, including glyphs, 3D, cartograms, juxtaposed maps, and shading methods. While choropleth maps are a common method used to represent societal data, with multivariate data they can impede as much as improve understanding. In particular large, low population density regions often dominate the map and can mislead the viewer as to the message conveyed. Our results highlight the potential of 3D choropleth maps as well as the low accuracy of choropleth map tasks with multivariate data. We also introduce and evaluate popcharts, four techniques designed to show the density of population at a very fine scale on top of choropleth maps. All the data, results, and scripts are available from https://osf.io/8rxwg/.

Ostreococcus tauri, a picoeukaryotic alga that contributes significantly to primary production in oligotrophic waters, has a highly streamlined genome, lacking the genetic capacity to grow without the vitamins thiamine (B1) and cobalamin (B12). Here we demonstrate that the B12 and B1 auxotrophy of O. tauri can be alleviated by co-culturing with a heterotrophic bacterial partner Dinoroseobacter shibae, a member of the Rhodobacteraceae family of alpha-proteobacteria, genera of which are frequently found associated with marine algae. D. shibae lacks the complete pathway to synthesise three other B-vitamins: niacin (B3), biotin (B7), and p-aminobenzoic acid (a precursor for folate, B9), and the alga is in turn able to satisfy the reciprocal vitamin requirements of its bacterial partner in a stable long-term co-culture. Bioinformatics searches of 197 representative marine bacteria with sequenced genomes identified just nine species that had a similar combination of traits (ability to make vitamin B12, but missing one or more genes for niacin and biotin biosynthesis enzymes), all of which were from the Rhodobacteraceae. Further analysis of 70 species from this family revealed the majority encoded the B12 pathway, but only half were able to make niacin, and fewer than 13% biotin. These characteristics may have either contributed to or resulted from the tendency of members of this lineage to adopt lifestyles in close association with algae. This study provides a nuanced view of bacterial-phytoplankton interactions, emphasising the complexity of the sources, sinks and dynamic cycling between marine microbes of these important organic micronutrients.

All data and codes used to produce the results reported in the manuscript "Seasonal evolution of supraglacial lakes and rivers on the southwest Greenland Ice Sheet".

Additional file 1: Comparison of estimates from imputation and complete case analysis. (DOCX 16 kb)

Klebsiella pneumoniae frequently harbour multidrug resistance and current methodologies are struggling to rapidly discern feasible antibiotics to treat these infections. While rapid DNA sequencing has been proposed for prediction of resistance profile; the role of rapid RNA sequencing has yet to be fully explored. The MinION sequencer can sequence native DNA and RNA in real-time, providing an opportunity to contrast the utility of DNA and RNA for prediction of drug susceptibility. This study interrogated the genome and transcriptome of four extensively drug-resistant (XDR) K. pneumoniae clinical isolates. The majority of acquired resistance (≥75%) resided on plasmids including several megaplasmids (≥100 kbp). DNA sequencing identified most resistance genes (≥70%) within 2 hours of sequencing. Direct RNA sequencing (with a ∼6x slower pore translocation) was able to identify ≥35% of resistance genes, including aminoglycoside, β-lactam, trimethoprim and sulphonamide and also quinolone, rifampicin, fosfomycin and phenicol in some isolates, within 10 hours of sequencing. Polymyxin-resistant isolates showed a heightened transcription of phoPQ (≥2-fold) and the pmrHFIJKLM operon (≥8-fold). Expression levels estimated from direct RNA sequencing displayed strong correlation (Pearson: 0.86) compared to qRT-PCR across 11 resistance genes. Overall, MinION sequencing rapidly detected the XDR K. pneumoniae resistome and direct RNA sequencing revealed differential expression of these genes.

The practice of kidney paired donation (KPD) is expanding annually, offering the opportunity for live donor kidney transplant to more patients. We sought to identify if voluntary KPD networks such as the National Kidney Registry (NKR) were selecting or attracting a narrower group of donors or recipients compared with national registries. For this purpose, we merged data from the NKR database with the Scientific Registry of Transplant Recipients (SRTR) database, from February 14, 2008, to February 14, 2017, encompassing the first 9 years of the NKR. Compared with all United Network for Organ Sharing (UNOS) live donor transplant patients (49 610), all UNOS living unrelated transplant patients (23 319), and all other KPD transplant patients (4236), the demographic and clinical characteristics of NKR transplant patients (2037) appear similar to contemporary national trends. In particular, among the NKR patients, there were a significantly (P 80%), female recipients (45.9% vs 37.6%), black recipients (18.2% vs 13%), and those on public insurance (49.7% vs 41.8%) compared with controls. These results support the need for greater sharing and larger pool sizes, perhaps enhanced by the entry of compatible pairs and even chains initiated by deceased donors, to unlock more opportunities for those harder-to-match pairs.

Small global positioning system (GPS) trackers are now routinely used to study the movement and behaviour of birds at sea. If the birds rest on the water they become “drifters of opportunity” and can be used to give information about surface currents. In this paper, we use a small data set from satellite-tracked razorbills (Alca torda) in the Irish Sea to test the potential of this idea for measuring tidal currents. Razorbills regularly rest on the sea overnight and their tracks at this time are consistent with their drifting with the tidal flows and changing direction as the flood turns to ebb and vice versa. Data from 4 years (2011–2014) have been binned in a geographical grid and analysed to give the variation of current over a mean tidal cycle in each grid element. A map of maximum current speed is consistent with a numerical model of the tidal currents in the region. The root mean square difference between observed maximum speed and that predicted by the model is 0.15 m s−1, about 15 % of typical current speeds in the area. The divergence between bird-track speed and model prediction increases in regions of the fastest tidal currents. The method clearly has its limitations, but the results of this study show that tagged birds resting on the sea have potential to provide relatively inexpensive quantitative information about surface tidal currents over an extended geographical area.

Tutorials are one of the most fundamental means of conveying knowledge. Ideally when the task involves physical or digital objects, tutorials not only describe each step with text or via audio narration but show it as well using photos or animation. In most cases, online tutorial authors capture media from handheld mobile devices to compose these documents, but increasingly they use wearable devices as well. In this work, we explore the full life-cycle of online tutorial creation and viewing using head-mounted capture and displays. We developed a media-capture tool for Google Glass that requires minimal attention to the capture device and instead allows the author to focus on creating the tutorial's content rather than its capture. The capture tool is coupled with web-based authoring tools for creating annotatable videos and multimedia documents. In a study comparing standalone (camera on tripod) versus wearable capture (Google Glass) as well as two types of multimedia representation for authoring tutorials, we show that tutorial authors have a preference for wearable capture devices, especially when recording activities involving larger objects in non-desktop environments. Authors preferred document-based multimedia tutorials because they are more straightforward to compose and the step-based structure translates more directly to explaining a procedure. In addition, we explored using head-mounted displays for accessing tutorials in comparison to lightweight computing devices such as tablets. Our study included tutorials recorded with the same capture methods as in our access study. We found that although authors preferred head-mounted capture, tutorial consumers preferred video recorded by a camera on tripod that provides a more stable image of the workspace.

Supplemental material for A randomised, controlled clinical trial of narrowband UVB phototherapy for clinically isolated syndrome: The PhoCIS study by Prue H Hart, Anderson P Jones, Stephanie Trend, Lilian Cha, Marzena J Fabis-Pedrini, Matthew N Cooper, Catherine d’Este, Sian Geldenhuys, William M Carroll, Scott N Byrne, David R Booth, Judith M Cole, Robyn M Lucas and Allan G Kermode in Multiple Sclerosis Journal – Experimental, Translational and Clinical

Vancomycin was bactericidal against Clostridium difficile at eightfold the minimum inhibitory concentration (MIC) using a traditional minimum bactericidal concentration (MBC) assay. However, at higher concentrations up to 64 × MIC, vancomycin displayed a paradoxical “more-drug-kills-less” Eagle effect against C. difficile. To overcome challenges associated with performing the labor-intensive agar-based MBC method under anaerobic growth conditions, we investigated an alternative more convenient ATP-bioluminescence assay to assess the Eagle effect in C. difficile. The commercial BacTiter-GloTM assay is a homogenous method to determine bacterial viability based on quantification of bacterial ATP as a marker for metabolic activity. The ATP-bioluminescence assay was advantageous over the traditional MBC-type assay in detecting the Eagle effect because it reduced assay time and was simple to perform; measurement of viability could be performed in less than 10 min outside of the anaerobic chamber. Using this method, we found C. difficile survived clinically relevant, high concentrations of vancomycin (up to 2048 μg/mL). In contrast, C. difficile did not survive high concentrations of metronidazole or fidaxomicin. The Eagle effect was also detected for telavancin, but not for teicoplanin, dalbavancin, oritavancin, or ramoplanin. All four pathogenic strains of C. difficile tested consistently displayed Eagle effect resistance to vancomycin, but not metronidazole or fidaxomicin. These results suggest that Eagle effect resistance to vancomycin in C. difficile could be more prevalent than previously appreciated, with potential clinical implications. The ATP-Bioluminescence assay can thus be used as an alternative to the agar-based MBC assay to characterize the Eagle effect against a variety of antibiotics, at a wide-range of concentrations, with much greater throughput. This may facilitate improved understanding of Eagle effect resistance and promote further research to understand potential clinical relevance.

Blood pressure is a heritable trait influenced by several biological pathways and responsive to environmental stimuli. Over one billion people worldwide have hypertension (≥140 mm Hg systolic blood pressure or ≥90 mm Hg diastolic blood pressure). Even small increments in blood pressure are associated with an increased risk of cardiovascular events. This genome-wide association study of systolic and diastolic blood pressure, which used a multi-stage design in 200,000 individuals of European descent, identified sixteen novel loci: six of these loci contain genes previously known or suspected to regulate blood pressure (GUCY1A3-GUCY1B3, NPR3-C5orf23, ADM, FURIN-FES, GOSR2, GNAS-EDN3); the other ten provide new clues to blood pressure physiology. A genetic risk score based on 29 genome-wide significant variants was associated with hypertension, left ventricular wall thickness, stroke and coronary artery disease, but not kidney disease or kidney function. We also observed associations with blood pressure in East Asian, South Asian and African ancestry individuals. Our findings provide new insights into the genetics and biology of blood pressure, and suggest potential novel therapeutic pathways for cardiovascular disease prevention. ispartof: Nature vol:478 issue:7367 pages:103-109 ispartof: location:England status: published

The Community for Open Antimicrobial Drug Discovery (CO-ADD) is a not-for-profit, collaborative approach to discovering new antibiotics. We access novel chemical diversity from academic synthetic chemists, who collectively possess millions of untested compounds with chemical diversity that lie outside commercial collections. We perform high-throughput antimicrobial screening of pure compounds derived from both synthetic and natural sources free of charge. The resulting data can be used by participants for publication, patenting and development purposes, and is fed back into the research community through an open-access database after a 2-year period during which information is kept confidential to the provider. CO-ADD is fundamentally asking two questions: can the community work together to address the global threat of antimicrobial resistance; and are there as yet undiscovered, novel antimicrobial compounds already present within our diverse global chemistry community?

Top 20 most abundant CAZy categories within â Ca. Homeothermaceaeâ as a percentage of total genes with CAZy annotation in each genome. (DOCX 17 kb)

â Ca. Homeothermaceaeâ population genome properties. (DOCX 19 kb)

SusCD-like genes present in â Ca. Homeothermaceaeâ genomes. (DOCX 17 kb)