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The Green Edge initiative was developed to investigate the processes controlling the primary productivity and fate of organic matter produced during the Arctic phytoplankton spring bloom (PSB) and to determine its role in the ecosystem. Two field campaigns were conducted in 2015 and 2016 at an ice camp located on landfast sea ice southeast of Qikiqtarjuaq Island in Baffin Bay (67.4797∘ N, 63.7895∘ W). During both expeditions, a large suite of physical, chemical and biological variables was measured beneath a consolidated sea-ice cover from the surface to the bottom (at 360 m depth) to better understand the factors driving the PSB. Key variables, such as conservative temperature, absolute salinity, radiance, irradiance, nutrient concentrations, chlorophyll a concentration, bacteria, phytoplankton and zooplankton abundance and taxonomy, and carbon stocks and fluxes were routinely measured at the ice camp. Meteorological and snow-relevant variables were also monitored. Here, we present the results of a joint effort to tidy and standardize the collected datasets, which will facilitate their reuse in other Arctic studies. The dataset is available at https://doi.org/10.17882/59892 (Massicotte et al., 2019a).

Abstract Tracking trajectories of body size in children provides insight into chronic disease risk. One measure of pediatric body size is body mass index (BMI), a function of height and weight. Errors in measuring height or weight may lead to incorrect assessment of BMI. Yet childhood measures of height and weight extracted from electronic medical records often include values which seem biologically implausible in the context of a growth trajectory. Removing biologically implausible values reduces noise in the data, and thus increases the ease of modeling associations between exposures and childhood BMI trajectories, or between childhood BMI trajectories and subsequent health conditions. We developed open-source algorithms (available on github) for detecting and removing biologically implausible values in pediatric trajectories of height and weight. A Monte Carlo simulation experiment compared the sensitivity, specificity and speed of our algorithms to three published algorithms. The comparator algorithms were selected because they used trajectory information, had open-source code, and had published verification studies. Simulation inputs were derived from longitudinal epidemiological cohorts. Our algorithms had higher specificity, with similar sensitivity and speed, when compared to the three published algorithms. The results suggest that our algorithms should be adopted for cleaning longitudinal pediatric growth data.

Abstract Networks throughout physics and biology leverage spatiotemporal dynamics for computation. However, the connection between structure and computation remains unclear. Here, we study a complex-valued neural network (cv-NN) with linear interactions and phase-delays. We report the cv-NN displays sophisticated spatiotemporal dynamics, which we then use, in combination with a nonlinear readout, for computation. The cv-NN can instantiate dynamics-based logic gates, encode short-term memories, and mediate secure message passing through a combination of interactions and phase-delays. The computations in this system can be fully described in an exact, closed-form mathematical expression. Finally, using direct intracellular recordings of neurons in slices from neocortex, we demonstrate that computations in the cv-NN are decodable by living biological neurons as the nonlinear readout. These results demonstrate that complex-valued linear systems can perform sophisticated computations, while also being exactly solvable. Taken together, these results open future avenues for design of highly adaptable, bio-hybrid computing systems that can interface seamlessly with other neural networks.

Background: Studies show a high prevalence of osteoporosis and fracture risk in kidney transplant candidates and recipients. However, little is known about the prevalence of osteoporosis among transplant recipients and candidates living with HIV.Objective: To determine the prevalence of osteopenia and osteoporosis and investigate the socio-demographic and nutritional factors associated with BMD in HIV-positive transplant candidates and recipients from an HIV-positive donor.Methods: In this cross-sectional study, 20 HIV- positive transplant recipients and 36 transplant candidates on haemodialysis (HD) and awaiting transplantation had BMD and body composition measured by dual-energy X-ray absorptiometry (DEXA). Vitamin D status was measured using serum 25-hydroxyvitamin D [25(OH)D]. Dietary Vitamin D and calcium intake was obtained from a single 24-hour recall.Results: Participants were mainly black African (92.9%), male (55.4%) with a mean age of 43.8 ± 8.3 years. Serum 25(OH)D levels were low for the group as a whole, with a mean of 22.04 ± 12.74 ng/ml. Osteoporosis was more prevalent amongst transplant recipients (20.0%) than transplant candidates (13.9%). Conversely, osteopenia was present amongst transplant candidates (27.8%). T-scores strongly correlated positively, with lean mass and BMD of the spine (r = 0.707, p = 0.007), and moderately, with each side of the total hip BMD (r = 0.455, p = 0.007 and r = 0.420, p = 0.007). There was a significant positive association between dietary calcium and all BMD sites in transplant recipients only.Conclusion: The prevalence of osteoporosis was similar, and in some cases, lower than in transplant recipients elsewhere. Lean mass was positively associated with BMD, and in transplant recipients, dietary calcium intake was positively associated with BMD emphasising the role of diet and exercise in preserving BMD.

Measurements of dissolved organic carbon (DOC), nitrogen (DON), and phosphorus (DOP) concentrations are used to characterize the dissolved organic matter (DOM) pool and are important components of biogeochemical cycling in the coastal ocean. Here, we present the first edition of a global database (CoastDOM v1; available at https://doi.org/10.1594/PANGAEA.964012, Lønborg et al., 2023) compiling previously published and unpublished measurements of DOC, DON, and DOP in coastal waters. These data are complemented by hydrographic data such as temperature and salinity and, to the extent possible, other biogeochemical variables (e.g. chlorophyll a, inorganic nutrients) and the inorganic carbon system (e.g. dissolved inorganic carbon and total alkalinity). Overall, CoastDOM v1 includes observations of concentrations from all continents. However, most data were collected in the Northern Hemisphere, with a clear gap in DOM measurements from the Southern Hemisphere. The data included were collected from 1978 to 2022 and consist of 62 338 data points for DOC, 20 356 for DON, and 13 533 for DOP. The number of measurements decreases progressively in the sequence DOC > DON > DOP, reflecting both differences in the maturity of the analytical methods and the greater focus on carbon cycling by the aquatic science community. The global database shows that the average DOC concentration in coastal waters (average ± standard deviation (SD): 182±314 µmol C L−1; median: 103 µmol C L−1) is 13-fold higher than the average coastal DON concentration (13.6±30.4 µmol N L−1; median: 8.0 µmol N L−1), which is itself 39-fold higher than the average coastal DOP concentration (0.34±1.11 µmol P L−1; median: 0.18 µmol P L−1). This dataset will be useful for identifying global spatial and temporal patterns in DOM and will help facilitate the reuse of DOC, DON, and DOP data in studies aimed at better characterizing local biogeochemical processes; closing nutrient budgets; estimating carbon, nitrogen, and phosphorous pools; and establishing a baseline for modelling future changes in coastal waters.

To design the next generations of wind turbines, engineers from the wind energy industry must now have access to new numerical tools, allowing the high-fidelity simulation of complex physical phenomena and thus a further calibration of lower-order models. For instance, the rotors of offshore wind turbines, whose diameters can now exceed 200 m, are highly flexible and fluid–structure interactions cannot be neglected any longer. Accordingly, this paper presents a new aero-servo-elastic solver designed to perform high-fidelity large-eddy simulation (LES) of wind turbines, as well as of rotor–wake interactions classically occurring in wind farms. In this framework, the turbine blades are modeled as flexible actuator lines. In terms of operating parameters (rotation speed and pitch angles) and power output, the solver is first validated against field data from the Westermost Rough offshore wind farm, for three different operation points. A very good agreement between the numerical results and field data is obtained. To push the validation further, additional results are compared to those given by a certified aero-servo-elastic solver used in the industry, which relies on a blade element momentum (BEM) method. The internal loads throughout the first blade and the deflections at the tip are studied in detail, and some discrepancies are observed. Of a reasonable amplitude overall, those are legitimately related to intrinsic modeling differences between the two solvers.

Background. HIV‐infected kidney transplant recipients with COVID‐19 are at increased risk of acute illness and death owing to their underlying comorbidities and chronic immunosuppression. Objectives. To describe the incidence, clinical presentation and course of COVID‐19, vaccination status, and SARS‐CoV‐2 antibody positivity rate among HIV‐infected‐to‐HIV‐infected kidney transplant recipients in South Africa (SA). Methods. This retrospective study reports on rates of SARS‐CoV‐2 infection, COVID‐19 and mortality among SA HIV‐infected kidney transplant recipients who received organs from HIV‐infected donors (HIV positive to HIV positive), before and after vaccination. Patient demographics, clinical presentation, course, management and disease outcomes were analysed. Antibody serology tests were performed between May and September 2022. Results. Among 39 HIV‐positive‐to‐HIV‐positive transplant recipients, 11 cases of COVID‐19 were diagnosed from March 2020 to September 2022. Six patients (55%) required hospitalisation, of whom 3 were admitted to a high‐care unit or intensive care unit. Two patients required mechanical ventilation, and 2 received acute dialysis. One patient was declined access to intensive care. Four patients (10%) died of COVID‐19 pneumonia. All the COVID‐19‐positive patients had at least one comorbidity. Vaccination data were available for 24 patients, of whom 5 had refused SARS‐CoV‐2 vaccination. SARS‐CoV‐2 antibody data were available for 20 patients; 4 vaccinated patients had a negative nucleocapsid protein antibody test and a positive spike protein antibody test, suggesting vaccination‐acquired immunity. The remaining 16 patients demonstrated immunity that was probably due to COVID infection, and of these, 14 were also vaccinated. Of the 11 COVID‐19 cases, only 1 was observed after vaccination. Conclusion. In our case series, ~10% of the HIV‐positive‐to‐HIV‐positive transplant recipients died of COVID‐19 pneumonia. This mortality rate appears higher than figures reported in other transplant cohorts. However, it is likely that the actual number of cases of SARS‐CoV‐2 infection was much higher, as the study only included polymerase chain reaction‐confirmed cases. It remains unclear whether HIV infection, transplant or the combination of the two drives poorer outcomes, and larger studies adjusting for important demographic and biological factors may isolate these effects.

Iron and manganese are poorly soluble elements in oxic and alkaline solutions, whereas they are much more soluble under anoxic conditions. As a result, the formation of authigenic mineral phases rich in Fe and/or Mn has traditionally been viewed as diagnostic of global or local anoxic conditions. Here we reveal that some specific cyanobacteria of very small size (< 2 µm, i.e., picocyanobacteria) can biomineralize abundant, authigenic Fe(III)-, Mn(IV)- and Si-rich amorphous phases under oxic conditions in an alkaline lake in Mexico. The resulting biominerals cluster as small globules arranged as rings around the division septum of cyanobacterial cells. These rings are enveloped within an organic, likely polysaccharidic envelope and are partially preserved, at least morphologically, upon sedimentation. Based on their 16S rDNA sequence, these cyanobacteria were affiliated with the Synechococcales order. The high Fe and Mn enrichment of the biominerals questions the systematic inference of anoxic conditions based on their detection. Moreover, this process scavenges iron from the water column, an overlooked biological contribution to the Fe cycle. Finally, it reveals a new case of controlled biomineralization of Si-rich phases by bacteria.

The dissolved organic carbon (DOC) reservoir plays a critical role in the C cycle of marine and freshwater environments because of its size and implication in many biogeochemical reactions. Although it is poorly constrained, its importance in ancient Earth's C cycles is also commonly invoked. Yet DOC is rarely quantified and characterized in modern stratified analogues. In this study, we investigated the DOC reservoirs of four redox-stratified alkaline crater lakes in Mexico. We analyzed the concentrations and isotopic compositions of DOC throughout the four water columns and compared them with existing data on dissolved inorganic and particulate organic C reservoirs (DIC and POC). The four lakes have high DOC concentrations with great variability between and within the lakes (averaging 2 ± 4 mM; 1 SD, n=28; i.e., from ∼ 15 to 160 times the amount of POC). The δ13CDOC signatures also span a broad range of values from −29.3 ‰ to −8.7 ‰ (with as much as 12.5 ‰ variation within a single lake). The prominent DOC peaks (up to 21 mM), together with their associated isotopic variability, are interpreted as reflecting oxygenic and/or anoxygenic primary productivity through the release of excess fixed carbon in three of the lakes (Alberca de los Espinos, La Preciosa, and Atexcac). By contrast, the variability of [DOC] and δ13CDOC in the case of Lake Alchichica is mainly explained by the partial degradation of organic matter and the accumulation of DOC in anoxic waters. The DOC records detailed metabolic functions such as active DIC-uptake and DIC-concentrating mechanisms, which cannot be inferred from DIC and POC analyses alone but which are critical to the understanding of carbon fluxes from the environment to the biomass. Extrapolating our results to the geological record, we suggest that anaerobic oxidation of DOC may have caused the very negative C isotope excursions in the Neoproterozoic. It is, however, unlikely that a large oceanic DOC reservoir could overweigh the entire oceanic DIC reservoir. This study demonstrates how the analysis of DOC in modern systems deepens our understanding of the C cycle in stratified environments and helps to set boundary conditions for the Earth's past oceans.

Redox-stratified water columns are a prevalent feature of the Earth's history, and ongoing environmental changes tend to promote a resurgence of such settings. Studying modern redox-stratified environments has improved our understanding of biogeochemical processes and element cycling in such water columns. These settings are associated with peculiar carbon biogeochemical cycling, owing to a layered distribution of biological processes in relation to oxidant availability. Metabolisms from distinct biogeochemical layers are diverse and may differently imprint the sedimentological record. Paired carbon isotope compositions of organic matter and carbonates, which are commonly used to characterize these ecological dynamics, can thus vary from one stratified environment to another. Changes in the organic/inorganic carbon sources and mass balance can further complicate the isotopic message in stratified environments. Better understanding of these multifaceted carbon isotope signals requires further evaluation of how the processes occurring in redox-stratified water columns are transferred to the sediments. We therefore characterized and compared the isotopic signatures of dissolved inorganic carbon (DIC), carbonate, and organic matter reservoirs at different depths in the water column and upper sediments of four stratified Mexican lakes that follow a gradient of alkalinity and salinity. Comparing these systems shows strong diversity in the carbon isotope signals of the water column and sediments. Differences in inorganic carbon isotope signatures arise primarily from the size of the DIC reservoir, buffering the expression of redox-dependent biological processes as alkalinity increases. Combining this isotopic dataset with water column physicochemical parameters allows us to identify oxygenic photosynthesis and aerobic respiration in the four lakes studied, while anoxygenic photosynthesis is evidenced in only two of them. Sedimentary organic matter does not originate from the same water column layers in the four lakes, highlighting the ecological variability that can stem from different stratified water columns and how it is transferred or not to the sedimentary record. The least alkaline lake shows higher isotopic variability and signatures typical of methanogenesis in the sediment porewaters. This metabolism, however, does not leave diagnostic isotopic signatures in the sedimentary archives (organic matter and carbonates), underlining the fact that even when alkalinity does not strongly buffer the inorganic carbon reservoir, a comprehensive picture of the active biogeochemical carbon cycling is not necessarily transferred to the geological record.

Abstract We present a dataset of structural relaxations of bulk ternary transition metal dichalcogenides (TMDs) computed via plane-wave density functional theory (DFT). We examined combinations of up to two chalcogenides with seven transition metals from groups 4–6 in octahedral (1T) or trigonal prismatic (2H) coordination. The full dataset consists of 672 unique stoichiometries, with a total of 50,337 individual configurations generated during structural relaxation. Our motivations for building this dataset are (1) to develop a training set for the generation of machine and deep learning models and (2) to obtain structural minima over a range of stoichiometries to support future electronic analyses. We provide the dataset as individual VASP xml files as well as all configurations encountered during relaxations collated into an ASE database with the corresponding total energy and atomic forces. In this report, we discuss the dataset in more detail and highlight interesting structural and electronic features of the relaxed structures.

Abstract Although superficially similar to data from clinical research, data extracted from electronic health records may require fundamentally different approaches for model building and analysis. Because electronic health record data is designed for clinical, rather than scientific use, researchers must first provide clear definitions of outcome and predictor variables. Yet an iterative process of defining outcomes and predictors, assessing association, and then repeating the process may increase Type I error rates, and thus decrease the chance of replicability, defined by the National Academy of Sciences as the chance of “obtaining consistent results across studies aimed at answering the same scientific question, each of which has obtained its own data.”[1] In addition, failure to account for subgroups may mask heterogeneous associations between predictor and outcome by subgroups, and decrease the generalizability of the findings. To increase chances of replicability and generalizability, we recommend using a stratified split sample approach for studies using electronic health records. A split sample approach divides the data randomly into an exploratory set for iterative variable definition, iterative analyses of association, and consideration of subgroups. The confirmatory set is used only to replicate results found in the first set. The addition of the word ‘stratified’ indicates that rare subgroups are oversampled randomly by including them in the exploratory sample at higher rates than appear in the population. The stratified sampling provides a sufficient sample size for assessing heterogeneity of association by testing for effect modification by group membership. An electronic health record study of the associations between socio-demographic factors and uptake of hepatic cancer screening, and potential heterogeneity of association in subgroups defined by gender, self-identified race and ethnicity, census-tract level poverty and insurance type illustrates the recommended approach.

Coastal wetlands are vulnerable to accelerated sea-level rise, yet knowledge about their extent and distribution is often limited. We developed a land cover classification of wetlands in the coastal plains of the southern United States along the Gulf of Mexico (Texas, Louisiana, Mississippi, Alabama, and Florida) using 6161 very-high (2 m per pixel) resolution WorldView-2 and WorldView-3 satellite images from 2012 to 2015. Area extent estimations were obtained for the following vegetated classes: marsh, scrub, grass, forested upland, and forested wetland, located in elevation brackets between 0 and 10 m above sea level at 0.1 m intervals. Sea-level trends were estimated for each coastal state using tide gauge data collected over the period 1983–2021 and projected for 2100 using the trend estimated over that period. These trends were considered conservative, as sea level rise in the region accelerated between 2010 and 2021. Estimated losses in vegetation area due to sea level rise by 2100 are projected to be at least 12,587 km2, of which 3224 km2 would be coastal wetlands. Louisiana is expected to suffer the largest losses in vegetation (80%) and coastal wetlands (75%) by 2100. Such high-resolution coastal mapping products help to guide adaptation plans in the region, including planning for wetland conservation and coastal development.

Postpartum haemorrhage is the leading cause of preventable maternal mortality in South Africa. In a significant breakthrough in the management of PPH, the E-MOTIVE trial found that a multifaceted health service intervention reduced severe PPH after vaginal delivery by 60% in 78 hospitals in Nigeria, Kenya, Tanzania and SA. The E-MOTIVE approach comprises objective blood loss measurement monitored every 15 minutes during the first hour after delivery to detect PPH early and trigger a bundle of first-line treatments, including massaging the uterus, oxytocin infusion, tranexamic acid infusion, intravenous crystalloid fluids, examination for the cause, emptying the bladder and, if necessary, escalation of care. E-MOTIVE was integrated into the existing Essential Steps in Managing Obstetric Emergencies algorithm. Certain research-related elements of the trial setting cannot be replicated in routine practice. Therefore, we need to develop local strategies to ensure the essential clinical elements of the intervention are implemented. Potential strategies include incorporating the E-MOTIVE principles into national guidelines, ongoing training strategies and ensuring all facilities are equipped with necessary medication, equipment and delegations. This breakthrough intervention provides hope for women in SA, and requires a purposeful, co-ordinated implementation strategy on a national scale to reach all levels of the health service.

Background: Breast magnetic resonance imaging (MRI) is an important imaging tool for the management of breast cancer patients and for screening women at high risk for breast cancer. Objectives: To examine long-term trends in the distribution of histologic diagnoses obtained from MRI-guided breast biopsies. Design: Retrospective analysis. Methods: We retrospectively reviewed the distribution of histologic diagnoses of MRI-guided breast biopsies from 2004 to 2019. All cases underwent central pathology review and lesions were classified based on the most prominent histologic finding present. Magnetic resonance imaging features were extracted from radiology reports when available and correlated with pathology diagnoses. Results: Four hundred ninety-four MRI-guided biopsies were performed on 440 patients; overall, 73% of biopsies were benign and 27% were malignant. The annual percentages of benign and malignant diagnoses remained similar throughout the 16-year period. Of the benign entities commonly identified, the percentage of benign papillary and sclerosing lesions detected in the benign biopsies increased significantly (13% in 2004-2011 vs 31% in 2012-2019, P = .03). The mean size of malignant lesions was larger than benign lesions (30.1 mm compared with 14.2 mm, P = .045); otherwise, there were no distinguishing radiologic features between benign and malignant lesions. Conclusion: The specificity of breast MRI remained constant over a 16-year period; however, there was a shift in the distribution of benign diagnoses with increased detection and biopsy of benign papillary and sclerosing lesions. Monitoring the distribution of breast MRI biopsy diagnoses over time with radiology-pathology correlation might improve the suboptimal specificity of breast MRI.

Abstract Stratifying breast cancer into specific molecular or histologic subtypes aids in therapeutic decision-making and predicting outcomes; however, these subtypes may not be as distinct as previously thought. Patients with luminal-like, estrogen receptor (ER)-expressing tumors have better prognosis than patients with more aggressive, triple-negative or basal-like tumors. There is, however, a subset of luminal-like tumors that express lower levels of ER, which exhibit more basal-like features. We have found that breast tumors expressing lower levels of ER, traditionally considered to be luminal-like, represent a distinct subset of breast cancer characterized by the emergence of basal-like features. Lineage tracing of low-ER tumors in the MMTV-PyMT mouse mammary tumor model revealed that basal marker-expressing cells arose from normal luminal epithelial cells, suggesting that luminal-to-basal plasticity is responsible for the evolution and emergence of basal-like characteristics. This plasticity allows tumor cells to gain a new lumino-basal phenotype, thus leading to intratumoral lumino-basal heterogeneity. Single-cell RNA sequencing revealed SOX10 as a potential driver for this plasticity, which is known among breast tumors to be almost exclusively expressed in triple-negative breast cancer (TNBC) and was also found to be highly expressed in low-ER tumors. These findings suggest that basal-like tumors may result from the evolutionary progression of luminal tumors with low ER expression.

Abstract Background When evaluating the impact of environmental exposures on human health, study designs often include a series of repeated measurements. The goal is to determine whether populations have different trajectories of the environmental exposure over time. Power analyses for longitudinal mixed models require multiple inputs, including clinically significant differences, standard deviations, and correlations of measurements. Further, methods for power analyses of longitudinal mixed models are complex and often challenging for the non-statistician. We discuss methods for extracting clinically relevant inputs from literature, and explain how to conduct a power analysis that appropriately accounts for longitudinal repeated measures. Finally, we provide careful recommendations for describing complex power analyses in a concise and clear manner. Methods For longitudinal studies of health outcomes from environmental exposures, we show how to [1] conduct a power analysis that aligns with the planned mixed model data analysis, [2] gather the inputs required for the power analysis, and [3] conduct repeated measures power analysis with a highly-cited, validated, free, point-and-click, web-based, open source software platform which was developed specifically for scientists. Results As an example, we describe the power analysis for a proposed study of repeated measures of per- and polyfluoroalkyl substances (PFAS) in human blood. We show how to align data analysis and power analysis plan to account for within-participant correlation across repeated measures. We illustrate how to perform a literature review to find inputs for the power analysis. We emphasize the need to examine the sensitivity of the power values by considering standard deviations and differences in means that are smaller and larger than the speculated, literature-based values. Finally, we provide an example power calculation and a summary checklist for describing power and sample size analysis. Conclusions This paper provides a detailed roadmap for conducting and describing power analyses for longitudinal studies of environmental exposures. It provides a template and checklist for those seeking to write power analyses for grant applications.

Abstract Plant‐imposed, fitness‐reducing sanctions against less‐beneficial symbionts have been documented for rhizobia, mycorrhizal fungi, and fig wasps. Although most of our examples are for rhizobia, we argue that the evolutionary persistence of mutualism in any symbiosis would require such sanctions, if there are multiple symbiont genotypes per host plant. We therefore discuss methods that could be used to develop and assess crops with stricter sanctions. These include methods to screen strains for greater mutualism as resources to identify crop genotypes that impose stronger selection for mutualism. Single‐strain experiments that measure costs as well as benefits have shown that diversion of resources by rhizobia can reduce nitrogen‐fixation efficiency (N per C) and that some legumes can increase this efficiency by manipulating their symbionts. Plants in the field always host multiple strains with possible synergistic interactions, so benefits from different strains might best be compared by regressing plant growth or yield on each strain's abundance in a mixture. However, results from this approach have not yet been published. To measure legacy effects of stronger sanctions on future crops, single‐genotype test crops could be planted in a field that recently had replicated plots with different genotypes of the sanction‐imposing crop. Enhancing agricultural benefits from symbiosis may require accepting tradeoffs that constrained past natural selection, including tradeoffs between current and future benefits.

Abstract Background Recent studies demonstrated that failure of achieving pharmacodynamic targets of commonly used antibiotics is common in critically ill patients. Therapeutic drug monitoring (TDM) can contribute to optimize the exposure of beta-lactams and ciprofloxacin. While evidence for TDM of these antibiotics is growing, translation into clinical implementation remains limited. Therefore, perceived barriers and facilitators are important for implementing TDM in this population. The primary aim of this study was to identify healthcare professionals’ barriers and facilitators for the implementation of TDM of beta-lactams and ciprofloxacin in Dutch intensive care units (ICU). Methods We conducted a nationwide cross-sectional online survey among healthcare professionals (HCPs) involved in antibiotic treatment of ICU patients. An adapted version of the Measurement Instrument for Determinants of Innovations was sent out. Items were considered barriers when ≥ 20% of participants responded with a negative answer. If ≥ 80% of the participants responded with a positive answer, the item was considered a facilitator. Results Sixty-four HCPs completed the survey, of which 14 were from academic hospitals, 25 from general hospitals, and 25 from teaching hospitals. Most participants were hospital pharmacists (59%) or medical specialists (23%). Eleven barriers and four facilitators for implementation of TDM of beta-lactams were identified; 17 barriers for TDM of ciprofloxacin and no facilitators. The most important barriers were a lack of conclusive evidence, organizational support, and low availability of assays. Additional barriers were a lack of consensus on which specific patients to apply TDM and which pharmacodynamic targets to use. Identified facilitators for beta-lactam TDM implementation are low complexity and high task perception, combined with the perception that TDM is important to prevent side effects and to adequately treat infections. Twenty-eight percent of participants reported that flucloxacillin could be analyzed in their hospital. Assay availability of other beta-lactams and ciprofloxacin was lower (3–17%). Conclusion Several barriers were identified that could obstruct the implementation of TDM of beta-lactams and ciprofloxacin in the ICU. In particular, education, clear guidelines, and organizational support should be considered when creating tailored implementation strategies. Finally, evidence of beneficial clinical outcomes on TDM of beta-lactams and ciprofloxacin can enhance further implementation.

Abstract Background Opioid use has increased globally in the recent decade. Although pain remains a significant problem among older adults, susceptibility to opioid-related harms highlights the importance of careful opioid therapy monitoring on individual and societal levels. We aimed to describe the trends of prescription opioid utilisation among residents aged ≥65 in all Nordic countries during 2009–2018. Methods We conducted cross-sectional measurements of opioid utilisation in 2009–2018 from nationwide registers of dispensed drugs in Denmark, Finland, Iceland, Norway, and Sweden. The measures included annual opioid prevalence, defined daily doses (DDDs) per 1000 inhabitants per day (DIDs), and morphine milligram equivalents (MMEs) per user per day. Results From 2009 to 2018, an average of 808,584 of adults aged ≥65 used opioids yearly in all five countries; an average annual prevalence of 17.0%. During this time period, the prevalence decreased in Denmark, Norway, and Sweden due to declining codeine and/or tramadol use. Iceland had the highest opioid prevalence in 2009 (30.2%), increasing to 31.7% in 2018. In the same period, DIDs decreased in all five countries, and ranged from 28.3 in Finland to 58.5 in Denmark in 2009, and from 23.0 in Finland to 54.6 in Iceland in 2018. MMEs/user/day ranged from 4.4 in Iceland to 19.6 in Denmark in 2009, and from 4.6 in Iceland to 18.8 in Denmark in 2018. In Finland, Norway, and Sweden, MMEs/user/day increased from 2009 to 2018, mainly due to increasing oxycodone utilisation. Conclusions The stable or decreasing opioid utilisation prevalence among a majority of older adults across the Nordic countries coincides with an increase in treatment intensity in 2009–2018. We found large cross-national differences despite similarities across the countries’ cultures and healthcare systems. For the aged population, national efforts should be placed on improving pain management and monitoring future trends of especially oxycodone utilisation.

Background. South Africa (SA) is one of the most financially unequal countries in the world. This situation is highlighted by disparate access to healthcare, particularly provision of kidney replacement therapy (KRT). Unlike the private sector, public sector access to KRT is highly rationed, and patient selection is based on suitability for transplantation and capacity. Objectives. To investigate the state of the KRT service in Eastern Cape Province, SA, by analysing access to and provision of KRT in the province for individuals with end-stage kidney disease, as well as disparities between the private and public healthcare systems. Methods. This was a retrospective descriptive study to examine KRT provision and temporal trends in the Eastern Cape. Data were obtained from the South African Renal Registry and the National Transplant Waiting List. KRT provision was compared between the three main referral centres, in Gqeberha (formerly Port Elizabeth), East London and Mthatha, and between the private and public healthcare systems. Results. There were 978 patients receiving KRT in the Eastern Cape, with an overall treatment rate of 146 per million population (pmp). The treatment rate for the private sector was 1 435 pmp, compared with 49 pmp in the public sector. Patients treated in the private sector were older at initiation of KRT (52 v. 34 years), and more likely to be male, to be HIV positive, and to receive haemodialysis as their KRT modality. Peritoneal dialysis was more commonly used in Gqeberha and East London as the first and subsequent KRT modality, compared with Mthatha. There were no patients from Mthatha on the transplant waiting list. There were no waitlisted HIV-positive patients in the public sector in East London, compared with 16% of the public sector patients in Gqeberha. The kidney transplant prevalence rate was 58 pmp in the private sector and 19 pmp in the public sector, with a combined prevalence of 22 pmp, constituting 14.9% of all patients on KRT. We estimated the shortfall of KRT provision in the public sector to be ~8 606 patients. Conclusion. Patients in the private sector were 29 times more likely to access KRT than their public sector counterparts, who were on average 18 years younger at initiation of KRT, probably reflecting selection bias in an overburdened public health system. Transplantation rates were low in both sectors, and lowest in Mthatha. A large public sector KRT provision gap exists in the Eastern Cape and needs to be addressed urgently.

Abstract Synthesis research in ecology and environmental science improves understanding, advances theory, identifies research priorities, and supports management strategies by linking data, ideas, and tools. Accelerating environmental challenges increases the need to focus synthesis science on the most pressing questions. To leverage input from the broader research community, we convened a virtual workshop with participants from many countries and disciplines to examine how and where synthesis can address key questions and themes in ecology and environmental science in the coming decade. Seven priority research topics emerged: (1) diversity, equity, inclusion, and justice (DEIJ), (2) human and natural systems, (3) actionable and use‐inspired science, (4) scale, (5) generality, (6) complexity and resilience, and (7) predictability. Additionally, two issues regarding the general practice of synthesis emerged: the need for increased participant diversity and inclusive research practices; and increased and improved data flow, access, and skill‐building. These topics and practices provide a strategic vision for future synthesis in ecology and environmental science.

Long-term wave action, sea level rise, climate change, human activities, pollutants, sea surface temperature SST, are causative factors for deterioration and changes in natural ecosystems. The current study aims to assess environmental deterioration that disturbs turtles and their nesting grounds at Wadi El Gemal National Park (WGNP), using modern remote sensing techniques and ecological investigations. Nesting area mapping and change detection were found to be precise and clear in the current investigation. The true nests recorded from WGNP during the current survey were Wadi El Gemal Delta (3), Torfa (10), Elshiekha Sabieha (2), Hankorab (14), Umm Alabas, Wadi El Gemal Island (1) and Syial Island (1). The concentration of some heavy metals in eggshells were positively correlated with their concentrations in sand (p ≤ 0.01), while heavy metals in nesting sands were negatively correlated with grain size (p

Abstract Background The Living Evidence Map Project at the Norwegian Institute of Public Health (NIPH) gives an updated overview of research results and publications. As part of NIPH’s mandate to inform evidence-based infection prevention, control and treatment, a large group of experts are continously monitoring, assessing, coding and summarising new COVID-19 publications. Screening tools, coding practice and workflow are incrementally improved, but remain largely manual. Results This paper describes how deep learning methods have been employed to learn classification and coding from the steadily growing NIPH COVID-19 dashboard data, so as to aid manual classification, screening and preprocessing of the rapidly growing influx of new papers on the subject. Our main objective is to make manual screening scalable through semi-automation, while ensuring high-quality Evidence Map content. Conclusions We report early results on classifying publication topic and type from titles and abstracts, showing that even simple neural network architectures and text representations can yield acceptable performance.

Organ and tissue donation depends on non-transplant clinicians to identify and timeously refer potential donors and to counsel families compassionately about the prognosis at end of life. Organ donation referral is often felt to be beyond the capacity of district-level hospital services. In this case series, we report on four referrals from a geographically remote, public sector district-level hospital, and review the identification, referral and consent process of potential donors after brain death, and also donors after circulatory death. For the one successfully consented donor we report on the donor work-up and management, and the outcome of the organ recovery and organ allocation process.

Drain-associated intracerebral infections are life-threatening emergencies. Their treatment is challenging due to the limited penetration of antibiotics to the site of infection, resulting in potentially inadequate exposure. The emergence of multidrug-resistant pathogens might force the use of off-label intrathecal (IT) doses of antibiotics. We reviewed the literature on general aspects determining intrathecal dosing regimen, using pharmacometric knowledge. We summarised clinical experience with IT doses of antibiotics that are usually not used intrathecally, as well as the outcome of the cases and concentrations reached in the cerebrospinal fluid (CSF). Factors determining the IT regimen are the size of the ventricle system and the CSF drainage volume. With regard to pharmacometrics, pharmacokinetic/pharmacodynamic indices are likely similar to those in non-cerebral infections. The following number (N) of cases were described: benzylpenicillin (>50), ampicillin (1), ceftazidime (2), cephaloridine (56), ceftriaxone (1), cefotiam (1), meropenem (57), linezolid (1), tigecycline (15), rifampicin (3), levofloxacin (2), chloramphenicol (3) and daptomycin (8). Many side effects were reported for benzylpenicillin in the 1940–50s, but for the other antibiotics, when administered correctly, all side effects were minor and reversible. These data might help when choosing an IT dosing regimen in case there is no alternative option due to antimicrobial resistance.

Objective: To determine body composition (BC) and the correlation, if any, between indices measured by anthropometry and dual-energy X-ray absorptiometry (DEXA). Design: Cross-sectional descriptive. Setting: National sample of HIV-positive patients on the ‘positive-to-positive’ kidney transplant programme, South Africa. Methodology: 34 participants categorised as (i) HIV-positive transplant recipients from an HIV-positive donor (n = 16); and (ii) HIV-positive transplant candidates on the waiting list to receive a kidney from an HIV-positive donor (n = 18). Pearson's coefficient was used to correlate anthropometry with DEXA. Outcome measures: Body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were compared with DEXA-derived percentage body fat (%BF), truncal fat (TF) and visceral adipose tissue (VAT). Mid arm muscle circumference (MAMC) was correlated with DEXA lean indices namely lean mass (LM), lean mass index (LMI) and appendicular lean mass index (ALMI). Results: Pearson's correlation coefficient between BMI and %BF was strong (r = 0.773, p

Abstract Gastrointestinal symptoms (GIS) are common in kidney transplant candidates and recipients and may be worsened by HIV. Objective: To determine the frequency and severity of GIS in HIV-positive kidney transplant recipients from HIV-positive donors, and those waiting to receive one. A GIS rating scale (GSRS) was completed by 76 participants at baseline and at 6 months. GIS frequency was defined as having at least one symptom (GSRS > 1). Severity was indicated by the GSRS score. Transplant candidates: GIS frequency was 88.9% and 86.3% at baseline and 6 months respectively. Indigestion was the most frequent (79.6% and 66.7% at baseline and 6 months), and severe GIS (GSRS 2.3). Women reported global mean (p = 0.030) severity significantly more than men. Transplant recipients: GIS frequency was 95.2% and 76.2% at baseline and 6 months respectively. At both assessment points, indigestion occurred most frequently (85.7% and 61.9% respectively). Highest GSRS was reported for indigestion at baseline (2.33) and at 6 months (1.33). Waist circumference (WC) was positively associated with the severity of constipation GSRS. GIS are common in both groups, especially indigestions. WC in transplant recipients should be monitored.

Sammendrag Covid-19-pandemien og påfølgende smittevernstiltak, samfunnsnedstengning, arbeidsledighet og usikkerhet rammet hele befolkningen i 2020. Det er uklart i hvilken grad og på hvilken måte pandemien har fått konsekvenser for utsatte barn og unge, for eksempel når det gjelder mishandling. Vi utførte en hurtig kartleggingsoversikt, som er en type systematisk kunnskapsoppsummering, med forenklede metodiske steg relativt til standard fremgangsmåte i en full systematisk oversikt. Etter et omfattende litteratursøk i flere internasjonale databaser inkluderte vi sju studier. Fem av disse var registerstudier fra USA som målte innrapportert eller anmeldt mishandling eller igangsatte barnevernssaker. Studiene viste en klar nedgang etter covid-19, sammenlignet med tidligere år. Forfatterne refererer til annen forskning som kan tyde på at nedgangen ikke skyldes faktisk lavere forekomst av mishandling, men i stedet manglende oppdagelse og rapportering. Forfatterne peker videre på muligheten for at det har vært en økning i mishandling, gitt pandemiens belastninger på familiene når det gjelder økonomi, arbeid og stress. Det er ennå ikke sikkert om denne trenden ses i Norge, men beslutningstakere og tjenesteutøvere i kontakt med barn og unge bør være aktsomme overfor situasjonen.

Introduction: Protein binding can diminish the pharmacological effect of beta-lactam antibiotics. Only the free fraction has an antibacterial effect. The aim of this systematic literature review was to give an overview of the current knowledge of protein binding of cephalosporins in human body fluids as well as to describe patient characteristics influencing the level of protein binding.Method: A systematic literature search was performed in Embase, Medline ALL, Web of Science Core Collection and the Cochrane Central Register of Controlled Trials with the following search terms: “protein binding,” “beta-lactam antibiotic,” and “body fluid.” Only studies were included where protein binding was measured in humans in vivo.Results: The majority of studies reporting protein binding were performed in serum or plasma. Other fluids included pericardial fluid, blister fluid, bronchial secretion, pleural exudate, wound exudate, cerebrospinal fluid, dialysate, and peritoneal fluid. Protein binding differs between diverse cephalosporins and between different patient categories. For cefazolin, ceftriaxone, cefpiramide, and cefonicid a non-linear pattern in protein binding in serum or plasma was described. Several patient characteristics were associated with low serum albumin concentrations and were found to have lower protein binding compared to healthy volunteers. This was for critically ill patients, dialysis patients, and patients undergoing cardiopulmonary bypass during surgery. While mean/median percentages of protein binding are lower in these patient groups, individual values may vary considerably. Age is not likely to influence protein binding by itself, however limited data suggest that lower protein binding in newborns. Obesity was not correlated with altered protein binding.Discussion/Conclusion: Conclusions on protein binding in other body fluids than blood cannot be drawn due to the scarcity of data. In serum and plasma, there is a large variability in protein binding per cephalosporin and between different categories of patients. Several characteristics were identified which lead to a lower protein binding. The finding that some of the cephalosporins display a non-linear pattern of protein binding makes it even more difficult to predict the unbound concentrations in individual patients. Taken all these factors, it is recommended to measure unbound concentrations to optimize antibiotic exposure in individual patients.Systematic Review Registration: PROSPERO, identifier (CRD42021252776).

Abstract The evolutionary stability of mutualistic interactions involving multiple partners requires “sanctioning”–the ability to influence the fitness of each partner based on its respective contribution. Sanctions must be sensitive to even small differences if even slightly less‐beneficial partners could gain a fitness advantage by diverting resources away from the mutualistic service toward their own reproductive fitness. Here, we test whether legume hosts sanction even mediocre N2‐fixing rhizobial strains by influencing either nodule growth (which limits rhizobial cell numbers) or carbon accumulation (polyhydroxybutryate or PHB) per rhizobial cell. We also test whether sanctions depend on the availability of less‐expensive nitrogen alternatives, either as nitrate or coinoculation with a more‐efficient isogenic strain. We found that nitrate eliminated differences in nodule size between the mediocre and more‐efficient strains, suggesting that host sanctions were compromised. However, nitrate additions also decreased PHB accumulation by the mediocre strain, which may eliminate any fitness advantages of diverting resources from N2 fixation. Coinoculation with a more‐efficient strain could also compromise host sanctions if reduction in fitness from smaller nodules does not offset the potential fitness gain from greater PHB accumulation that we observed in the mediocre strain. Hence, a host's ability to sanction mediocre strains depends not only on alternative sources of nitrogen but also the relative importance of different components of rhizobial fitness.

Abstract Background Critically ill patients undergo extensive physiological alterations that will have impact on antibiotic pharmacokinetics. Up to 60% of intensive care unit (ICU) patients meet the pharmacodynamic targets of beta-lactam antibiotics, with only 30% in fluoroquinolones. Not reaching these targets might increase the chance of therapeutic failure, resulting in increased mortality and morbidity, and antibiotic resistance. The DOLPHIN trial was designed to demonstrate the added value of therapeutic drug monitoring (TDM) of beta-lactam and fluoroquinolones in critically ill patients in the ICU. Methods A multi-centre, randomised controlled trial (RCT) was designed to assess the efficacy and cost-effectiveness of model-based TDM of beta-lactam and fluoroquinolones. Four hundred fifty patients will be included within 24 months after start of inclusion. Eligible patients will be randomly allocated to either study group: the intervention group (active TDM) or the control group (non-TDM). In the intervention group dose adjustment of the study antibiotics (cefotaxime, ceftazidime, ceftriaxone, cefuroxime, amoxicillin, amoxicillin with clavulanic acid, flucloxacillin, piperacillin with tazobactam, meropenem, and ciprofloxacin) on day 1, 3, and 5 is performed based upon TDM with a Bayesian model. The primary outcome will be ICU length of stay. Other outcomes amongst all survival, disease severity, safety, quality of life after ICU discharge, and cost effectiveness will be included. Discussion No trial has investigated the effect of early TDM of beta-lactam and fluoroquinolones on clinical outcome in critically ill patients. The findings from the DOLPHIN trial will possibly lead to new insights in clinical management of critically ill patients receiving antibiotics. In short, to TDM or not to TDM? Trial registration EudraCT number: 2017–004677-14. Sponsor protocol name: DOLPHIN. Registered 6 March 2018 . Protocol Version 6, Protocol date: 27 November 2019.

The Intergovernmental Science-Policy Platform on Biodiversity and Ecosystem Services(IPBES) strengthens the science-policy interface by producing scientific assessments on biodiversity and ecosystem services to inform policy. IPBES fosters knowledge exchange across disciplines, between researchers and other knowledge holders, practitioners, societal actors and decision makers working at different geographic scales. A number of avenues for participation of stakeholders across the four functions if IPBES exist. Stakeholders come from diverse backgrounds, including Indigenous Peoples and local communities, businesses, and non-governmental organization. They represent multiple sources of information, data, knowledge, and perspectives on biodiversity. Stakeholder engagement in IPBES seeks to 1. communicate, disseminate, and implement the findings of IPBES products; 2. Develop guidelines for biodiversity conservation within member countries; and 3. create linkages between global policy and local actors – all key to the implementation of global agreements on biodiversity. This paper reflects on the role of stakeholders in the first work programme of IPBES (2014–2018). It provides an overview of IPBES processes and products relevant to stakeholders, examines the motivation of stakeholders to engage with IPBES, and explores reflections by the authors (all active participants on the platform) for improved stakeholder engagement and contributions to future work of the platform.

Increasingly, eDNA is being used to infer ecological interactions. Here the authors sample eDNA over 18 months in a marine environment and use co-occurrence network analyses to infer potential interactions among organisms from microbes to mammals, testing how they change over time in response to oceanographic factors.

Accurate and up-to-date maps of coastal bathymetry are fundamental for coastal resource management, commercial and military navigation, and aquaculture, among many applications. Existing methods for bathymetry mapping require intensive and costly field surveys or targeted aerial captures, neither of which are easily or affordably replicated for repeat mapping and change monitoring. Satellite-derived bathymetry (SDB), however, offers the potential to map shallow water bodies repeatedly and efficiently with high spatial and temporal resolution (i.e., daily-weekly at 5 m or better). One challenge to large-scale implementation of SDB lies in the automated derivation of inherent water column properties such that they may be accurately compensated for across a variety of depth and substrate conditions. Here we present an algorithm that leverages WorldView (Maxar/Digital GlobeTM) satellite imagery to map the entire 3700 km2 Florida Keys (USA) island chain at 2-meter resolution without the need for any in-situ data collections. Preprocessing included radiometric calibration, atmospheric correction, automated deglinting, and automated detection of optically deep water, which was then used to estimate chlorophyll-a concentration assuming that the study area is primarily comprised of Case-I water (i.e., those where the optical signal is dominated by water, Chlorophyll-a in phytoplankton, and properties that vary in proportion to Chlorophyll-a concentration). Estimating Chlorophyll-a concentration allowed us to calculate the appropriate tuning coefficients used in a spectral band ratio equation for estimating bathymetry. The entire process was fully automated from ingestion of Level-1B image to bathymetry raster output. Mapping the Florida Keys from Key Largo to Key West required 34 WorldView images and was completed in approximately 27 min for an average processing time of 47 s per image using a single GPU core (i.e., supercomputing resources were not needed). After combining the products (mosaicking) in ArcMap, the wall-to-wall bathymetry map was validated against a LiDAR-derived bathymetry model with over 600,000 points; results show an RMSE of 1.95 m over depths from 0 to 15 m.

We introduce an analytical approach that allows predictions and mechanistic insights into the dynamics of nonlinear oscillator networks with heterogeneous time delays. We demonstrate that time delays shape the spectrum of a matrix associated with the system, leading to the emergence of waves with a preferred direction. We then create analytical predictions for the specific spatiotemporal patterns observed in individual simulations of time-delayed Kuramoto networks. This approach generalizes to systems with heterogeneous time delays at finite scales, which permits the study of spatiotemporal dynamics in a broad range of applications.

Understanding the sensitivity of a system's behavior with respect to parameter changes is essential for many applications. This sensitivity may be desired—for instance, in the brain, where a large repertoire of different dynamics, particularly different synchronization patterns, is crucial—or may be undesired—for instance, in power grids, where disruptions to synchronization may lead to blackouts. In this paper, we show that networks of coupled phase oscillators with nonlinear interactions can acquire a very large and complicated sensitivity to changes made in either their units' parameters or in their connections. Even modifications made to a parameter of a single unit can radically alter the global dynamics of the network in an unpredictable manner. This occurs over a wide parameter region, around the network's transitions to phase synchronization. We argue that this is a widespread phenomenon that can be expected in real-world systems, extending even beyond networks of oscillators.

The number of pharmacokinetic (PK) models of meropenem is increasing. However, the daily role of these PK models in the clinic remains unclear, especially for critically ill patients. Therefore, we evaluated the published meropenem models on real-world ICU data to assess their suitability for use in clinical practice. All models were built in NONMEM and evaluated using prediction and simulation-based diagnostics for the ability to predict the subsequent meropenem concentrations without plasma concentrations (a priori), and with plasma concentrations (a posteriori), for use in therapeutic drug monitoring (TDM). Eighteen PopPK models were included for evaluation. The a priori fit of the models, without the use of plasma concentrations, was poor, with a prediction error (PE)% of the interquartile range (IQR) exceeding the ±30% threshold. The fit improved when one to three concentrations were used to improve model predictions for TDM purposes. Two models were in the acceptable range with an IQR PE% within ±30%, when two or three concentrations were used. The role of PK models to determine the starting dose of meropenem in this population seems limited. However, certain models might be suitable for TDM-based dose adjustment using two to three plasma concentrations.

Maintaining healthy, productive ecosystems in the face of pervasive and accelerating human impacts including climate change requires globally coordinated and sustained observations of marine biodiversity. Global coordination is predicated on an understanding of the scope and capacity of existing monitoring programs, and the extent to which they use standardized, interoperable practices for data management. Global coordination also requires identification of gaps in spatial and ecosystem coverage, and how these gaps correspond to management priorities and information needs. We undertook such an assessment by conducting an audit and gap analysis from global databases and structured surveys of experts. Of 371 survey respondents, 203 active, long-term (>5 years) observing programs systematically sampled marine life. These programs spanned about 7% of the ocean surface area, mostly concentrated in coastal regions of the United States, Canada, Europe, and Australia. Seagrasses, mangroves, hard corals, and macroalgae were sampled in 6% of the entire global coastal zone. Two-thirds of all observing programs offered accessible data, but methods and conditions for access were highly variable. Our assessment indicates that the global observing system is largely uncoordinated which results in a failure to deliver critical information required for informed decision-making such as, status and trends, for the conservation and sustainability of marine ecosystems and provision of ecosystem services. Based on our study, we suggest four key steps that can increase the sustainability, connectivity and spatial coverage of biological Essential Ocean Variables in the global ocean: (1) sustaining existing observing programs and encouraging coordination among these; (2) continuing to strive for data strategies that follow FAIR principles (findable, accessible, interoperable, and reusable); (3) utilizing existing ocean observing platforms and enhancing support to expand observing along coasts of developing countries, in deep ocean basins, and near the poles; and (4) targeting capacity building efforts. Following these suggestions could help create a coordinated marine biodiversity observing system enabling ecological forecasting and better planning for a sustainable use of ocean resources.

For decades, flucloxacillin has been used to treat methicillin-susceptible Staphylococcus aureus (MSSA). Little is still known about its pharmacodynamics (PD). The present study aimed to determine the pharmacokinetic (PK)/PD index and the PD-index value minimally required for efficacy. MICs of 305 MSSA isolates were measured to determine the wild-type distribution. The PD of 8 S. aureus, 1 S. pyogenes, and 1 S. agalactiae isolates were evaluated in a neutropenic murine thigh infection model. Two S. aureus isolates were used in a dose-fractionation study and a dose–response analysis was performed additionally in the in vivo model. Data were analyzed with a population PK and sigmoid maximum effect model. The end of the wild-type distribution was 1 mg/L. The percentage of time the unbound concentration was above MIC (%fT > MIC) was best correlated with efficacy. For S. aureus, median %fT > 0.25 × MIC required for 1-log reduction was 15%. The value for S. pyogenes was 10%fT > MIC and for S. agalactiae 22%fT > 0.25xMIC for a 1-log reduction. The effect of flucloxacillin reached a 2-log reduction of S. aureus at 20%fT > 0.25xMIC and also for S. pyogenes and S. agalactiae, a reduction was reached. These data may serve to optimize dosing regimens currently used in humans.

Successful management and mitigation of marine challenges depends on cooperation and knowledge sharing which often occurs across culturally diverse geographic regions. Global ocean science collaboration is therefore essential for developing global solutions. Building effective global research networks that can enable collaboration also need to ensure inter- and transdisciplinary research approaches to tackle complex marine socio-ecological challenges. To understand the contribution of interdisciplinary global research networks to solving these complex challenges, we use the Integrated Marine Biosphere Research (IMBeR) project as a case study. We investigated the diversity and characteristics of 1,827 scientists from 11 global regions who were attendees at different IMBeR global science engagement opportunities since 2009. We also determined the role of social science engagement in natural science based regional programmes (using key informants) and identified the potential for enhanced collaboration in the future. Event attendees were predominantly from western Europe, North America, and East Asia. But overall, in the global network, there was growing participation by females, students and early career researchers, and social scientists, thus assisting in moving toward interdisciplinarity in IMBeR research. The mainly natural science oriented regional programmes showed mixed success in engaging and collaborating with social scientists. This was mostly attributed to the largely natural science (i.e., biological, physical) goals and agendas of the programmes, and the lack of institutional support and push to initiate connections with social science. Recognising that social science research may not be relevant to all the aims and activities of all regional programmes, all researchers however, recognised the (potential) benefits of interdisciplinarity, which included broadening scientists’ understanding and perspectives, developing connections and interlinkages, and making science more useful. Pathways to achieve progress in regional programmes fell into four groups: specific funding, events to come together, within-programme-reflections, and social science champions. Future research programmes should have a strategic plan to be truly interdisciplinary, engaging natural and social sciences, as well as aiding early career professionals to actively engage in such programmes.

We derive a noncentral [Formula: see text] power approximation for the Kenward and Roger test. We use a method of moments approach to form an approximate distribution for the Kenward and Roger scaled Wald statistic, under the alternative. The result depends on the approximate moments of the unscaled Wald statistic. Via Monte Carlo simulation, we demonstrate that the new power approximation is accurate for cluster randomized trials and longitudinal study designs. The method retains accuracy for small sample sizes, even in the presence of missing data. We illustrate the method with a power calculation for an unbalanced group-randomized trial in oral cancer prevention.

Wetlands are the second-most valuable natural resource on Earth but have declined by approximately 70 % since 1900. Restoration and conservation efforts have succeeded in some areas through establishment of refuges where anthropogenic impacts are minimized. However, these areas are still prone to wetland damage caused by natural disasters. Severe storms such as Hurricane Irma, which made landfall as a Category 3 hurricane in southwest Florida (USA) on September 11, 2017, can cause the destruction of mangroves and other wetland habitat. Multispectral images from commercial satellites provide a means to assess the extent of the damage to different wetland habitat types with high spatial resolution (2 m pixels or finer) over large areas. Using such images presents a number of challenges, including deriving consistent and accurate classification of wetland and non-wetland vegetation. Machine learning methods have demonstrated high-accuracy mapping capabilities on small spatial scales, but require a large amount of robust training data. Meanwhile, ambitious efforts to map larger areas at finer resolutions may use hundreds of thousands of images, and therefore encounter Big-Data processing challenges. Large-scale efforts face the dilemma of adopting traditional mapping methods that may lend themselves to Big Data analytics but may result in accuracies that are inferior to new methods, or move to machine learning methods, which require robust training data. Given these considerations, we describe a version of the traditional Decision Tree (DT) approach and compare two common machine learning methods to derive land cover classes using a WorldView-2 image collected on November 12, 2018 to include one growing season after Hurricane Irma affected this area. Specifically, we compared the Support Vector Machine [SVM] and Neural Network [NN] methods, trained and validated with separate ground-truth datasets collected during a robust field campaign. Overall accuracies were only marginally different (85 % NN vs 83 % each DT and SVM), but healthy mangroves were more accurately identified with the DT (91 % vs 88 % NN and 86 % SVM), and degraded mangroves were more accurately identified with NN (62 % vs 57 % NN and 38 % DT). These results, combined with their respective training requirements, have implications for the direction with which large-scale high-resolution mapping of coastal habitats proceeds.

Background: Ectopic fat deposition in obesity is associated with organ dysfunction; however, little is known about fat deposition within the lymphatic system and associated lymphatic dysfunction. Methods: One hundred fifty-five women who underwent routine screening mammography before and after a Roux-en-y gastric bypass or a sleeve gastrectomy were retrospectively reviewed and after excluding women without visible nodes both before and after bariatric surgery, 84 patients were included in the final analysis. Axillary lymph node size, patient weight in kilograms, body mass index, and a diagnosis of hypertension, type 2 diabetes, and dyslipidemia were evaluated before and after surgery. Binary linear regression models and Fischer’s exact test were used to evaluate the relationship between the size of fat-infiltrated axillary lymph nodes, patient age, change in patient weight, and diagnosis of hypertension, type 2 diabetes, and dyslipidemia. Results: Fat-infiltrated axillary lymph nodes demonstrated a statistically significant decrease in size after bariatric surgery with a mean decrease of 4.23 mm (95% CI: 3.23 to 5.2, p < 0.001). The resolution of dyslipidemia was associated with a decrease in lymph node size independent of weight loss (p = 0.006). Conclusions: Mammographically visualized fat-infiltrated axillary lymph nodes demonstrated a statistically significant decrease in size after bariatric surgery. The decrease in lymph node size was significantly associated with the resolution of dyslipidemia, independent of weight loss, age, and type of surgery.

Abstract Background A high prevalence of colistin resistance among E. cloacae isolates in two intensive care units (ICU) (of 16 and 6 beds) using selective digestive decontamination (SDD) since 1990 instigated a retrospective and prospective investigation to quantify the role of clonal transmission. SDD is topical application of colistin and tobramycin and systemic use of cefotaxime during the first days of ICU-admission. Methods Multi-resistant E. cloacae (MREb) was defined as ESBL production and/or tobramycin non-susceptibility and/or colistin non-susceptibility. Incidence of acquisition and prevalence of carriage with MREb was determined from microbiological culture results. Results Colistin-resistant E. cloacae was first detected in November 2009 and carriage was demonstrated in 141 patients until October 2014. Mean incidence of MREb acquisition was 4.61 and 1.86 per 1000 days at risk in ICUs 1 and 2, respectively, and the mean monthly prevalence of MREb in both ICUs was 7.0 and 3.1%, respectively, without a discernible trend in time. Conversion rates from carriage of colistin-susceptible to resistant E. cloacae were 0.20 and 0.13 per 1000 patient days, respectively. Whole genome sequencing of 149 isolates revealed eight clusters, with the number of SNPs of the largest two clusters ranging between 0 and 116 for cluster 1 (n = 49 isolates), and 0 and 27 for cluster 2 (n = 36 isolates), among isolates derived between 2009 and 2014. Conclusions This study demonstrates a stable low-level endemicity of MREb in two Dutch ICUs with prolonged use of SDD, which was characterized by the persistent presence of two clusters, suggesting incidental clonal transmission.

Population pharmacokinetic modeling and simulation (M&S) are used to improve antibiotic dosing. Little is known about the differences in parametric and nonparametric M&S. Our objectives were to compare (1) the external validation of parametric and nonparametric models of imipenem in critically ill patients and (2) the probability of target attainment (PTA) calculations using simulations of both models. The M&S software used was NONMEM 7.2 (parametric) and Pmetrics 1.5.2 (nonparametric). The external predictive performance of both models was adequate for eGFRs ≥ 78 mL/min but insufficient for lower eGFRs, indicating that the models (developed using a population with eGFR ≥ 60 mL/min) could not be extrapolated to lower eGFRs. Simulations were performed for three dosing regimens and three eGFRs (90, 120, 150 mL/min). Fifty percent of the PTA results were similar for both models, while for the other 50% the nonparametric model resulted in lower MICs. This was explained by a higher estimated between-subject variability of the nonparametric model. Simulations indicated that 1000 mg q6h is suitable to reach MICs of 2 mg/L for eGFRs of 90–120 mL/min. For MICs of 4 mg/L and for higher eGFRs, dosing recommendations are missing due to largely different PTA values per model. The consequences of the different modeling approaches in clinical practice should be further investigated.

Abstract Background Persistent high-risk human papillomavirus (HR-HPV) infection is associated with the development of anogenital cancers, particularly in men living with HIV (MLWH). We describe the prevalence of anogenital HPV infection, abnormal anal cytology and anogenital warts (AGWs) in MLWH in Johannesburg, and explore whether HPV infection and receipt of antiretroviral treatment is associated with detection of abnormal anal cytology and AGWs. Methods We enrolled a cohort of 304 sexually-active MLWH ≥18 years, who completed a questionnaire and physical examination. Genital swabs were collected from all men and intra-anal swabs from 250 (82%). Swabs were tested for HPV DNA and genotypes, and anal smears graded using the Bethesda classification. Factors associated with anogenital disease were assessed by logistic regression models. Results Two thirds were receiving antiretroviral treatment, for a median 33 months (IQR = 15–58) and 54% were HIV-virologically suppressed. Only 5% reported ever having sex with men. Among 283 genital swabs with valid results, 79% had any HPV, 52% had HR-HPV and 27% had >1 HR-HPV infection. By comparison, 39% of the 227 valid intra-anal swabs had detectable HPV, 25% had any HR-HPV and 7% >1 HR infection. While most anal smears were normal (51%), 20% had ASCUS and 29% were LSIL. No cases had HSIL or cancer. Infection with >1 HR type (adjusted OR [aOR] = 2.39; 95%CI = 1.02–5.58) and alpha-9 types (aOR = 3.98; 95%CI = 1.42–11.16) were associated with having abnormal cytology. Prevalence of AGWs was 12%. Infection with any LR type (aOR = 41.28; 95%CI = 13.57–125.62), >1 LR type (aOR = 4.14; 95%CI = 1.60–10.69), being

In Fiji, like most Pacific Island countries, there have been numerous reports of degradation of coastal resources, including adverse changes in abundance and stock distribution of numerous aquatic species associated with the coastal habitat. To develop effective management plans, assessment of existing coastal resources is pertinent. High spatial resolution satellite imagery, combined with geographic information systems allow for efficient and synoptic mapping of coastal resources to provide a baseline for developing effective and improved management plans. The purpose of this study was to develop a baseline habitat map of the intertidal benthic cover in Komave Village, Coral Coast, Sigatoka, Fiji. Resource mapping was based on high resolution (2 m) WorldView-2 imagery. Ground-truthing was attained by means of on-site data logging of the intertidal resources, image capturing and GPS recording. Based on these records, the benthic cover was classified into seven classes: ‘coral,’ ‘algae,’ ‘brown algae,’ ‘volcanic rocks,’ ‘sand and gravel,’ ‘sea grass,’ and ‘bare.’ Ground referencing points were randomly assigned for either supervised classification training or accuracy assessment. A community participatory research approach was used to conduct interviews to assimilate information on fishing sites and coastal land use activities. This exercise explored the social-ecological approach in natural resource management and how it can become an important tool in coastal conservation practices. The coastal resource map generated through this study serves as a baseline for monitoring the status and spatial distribution of the coastal resources in Komave. Annual mapping of the resources and enrichment of maps along with iterative village consultation will enable managers to develop and gauge the effectiveness of coastal management plans. This high resolution map is particularly relevant to Fiji as it is the first of its kind for the country. This work also serves to reduce the global information gap of coastal resource status for Fiji.