Limiting inter-annual variation in total allowable catch strategies. An application to ICES roundfish stocks

This study evaluated through simulation management strategy that stabilise catch levels by setting bounds on the inter-annual variability in Total Allowable Catches (TACs). An integrated modelling approach was used, which modelled both the ‘real’ and observed systems and the interactions between all system components. The modelling framework therefore allowed evaluation of the robustness of candidate management strategies to both the intrinsic properties of the systems, and the ability to observe, monitor, assess and control them. Strategies were evaluated in terms of level of risk (measured as the probability of spawning stock biomass falling below the biomass limit reference level for the stock) and cumulative yield. The simulation approach used provides a powerful tool for the examination of the performance of candidate management strategies. It has shown that better management is not necessarily going to be achieved by improving the assessement, since even with a perfect assessment (where the simulated working group knew stock status perfectly) stocks may crash at fishing levels that standard stochastic projections would suggest were safe. Also explicitly modelling the assessment process can result in quite different outcomes than those predicted by the simple projection traditionally used by stock assessment working groups. This is because the simple projection assumes that the status of the stock in the current year is known without error and that the target fishing mortality can be achieved without error. However, in practice the assessment is based on last years data and the effect of any management measure on SSB is only manifest, following the implementation of the quota, at the end of the following year. The choice of target and fishing mortality levels and minimum stock levels results from ICES interpretation of the precautionary approach. This lead to the definition of fishing mortality and biomass reference points that are intended to prevent over-fishing and to trigger recovery plans when a stock is overfished respectively. Although, fishing mortality and biomass reference points were originally intended to be independent, a fishing mortality level implies a corresponding biomass level. In the case of saithe a fishing mortality of 0.40 (i.e. the FPA level) would drive the stock to Blim, suggesting that the choice of biomass and target reference points are not consistent for this stock

Limiting inter-annual variation in total allowable catch strategies. An application to ICES roundfish stocks

This study evaluated through simulation management strategy that stabilise catch levels by setting bounds on the inter-annual variability in Total Allowable Catches (TACs). An integrated modelling approach was used, which modelled both the ‘real’ and observed systems and the interactions between all system components. The modelling framework therefore allowed evaluation of the robustness of candidate management strategies to both the intrinsic properties of the systems, and the ability to observe, monitor, assess and control them. Strategies were evaluated in terms of level of risk (measured as the probability of spawning stock biomass falling below the biomass limit reference level for the stock) and cumulative yield. The simulation approach used provides a powerful tool for the examination of the performance of candidate management strategies. It has shown that better management is not necessarily going to be achieved by improving the assessement, since even with a perfect assessment (where the simulated working group knew stock status perfectly) stocks may crash at fishing levels that standard stochastic projections would suggest were safe. Also explicitly modelling the assessment process can result in quite different outcomes than those predicted by the simple projection traditionally used by stock assessment working groups. This is because the simple projection assumes that the status of the stock in the current year is known without error and that the target fishing mortality can be achieved without error. However, in practice the assessment is based on last years data and the effect of any management measure on SSB is only manifest, following the implementation of the quota, at the end of the following year. The choice of target and fishing mortality levels and minimum stock levels results from ICES interpretation of the precautionary approach. This lead to the definition of fishing mortality and biomass reference points that are intended to prevent over-fishing and to trigger recovery plans when a stock is overfished respectively. Although, fishing mortality and biomass reference points were originally intended to be independent, a fishing mortality level implies a corresponding biomass level. In the case of saithe a fishing mortality of 0.40 (i.e. the FPA level) would drive the stock to Blim, suggesting that the choice of biomass and target reference points are not consistent for this stock

FLUXNET: A New Tool to Study the Temporal and Spatial Variability of Ecosystem-Scale Carbon Dioxide, Water Vapor, and Energy Flux Densities

FLUXNET is a global network of micrometeorological flux measurement sites that measure the exchanges of carbon dioxide, water vapor, and energy between the biosphere and atmosphere. At present over 140 sites are operating on a long–term and continuous basis. Vegetation under study includes temperate conifer and broadleaved (deciduous and evergreen) forests, tropical and boreal forests, crops, grasslands, chaparral, wetlands, and tundra. Sites exist on five continents and their latitudinal distribution ranges from 70°N to 30°S. FLUXNET has several primary functions. First, it provides infrastructure for compiling, archiving, and distributing carbon, water, and energy flux measurement, and meteorological, plant, and soil data to the science community. (Data and site information are available online at the FLUXNET http://www–eosdis.ornl.gov/FLUXNET/.) Second, the project supports calibration and flux intercomparison activities. This activity ensures that data from the regional networks are intercomparable. And third, FLUXNET supports the synthesis, discussion, and communication of ideas and data by supporting project scientists, workshops, and visiting scientists. The overarching goal is to provide information for validating computations of net primary productivity, evaporation, and energy absorption that are being generated by sensors mounted on the NASA Terra satellite. Data being compiled by FLUXNET are being used to quantify and compare magnitudes and dynamics of annual ecosystem carbon and water balances, to quantify the response of stand–scale carbon dioxide and water vapor flux densities to controlling biotic and abiotic factors, and to validate a hierarchy of soil–plant–atmosphere trace gas exchange models. Findings so far include 1) net CO2 exchange of temperate broadleaved forests increases by about 5.7 g C m–2 day–1 for each additional day that the growing season is extended; 2) the sensitivity of net ecosystem CO2 exchange to sunlight doubles if the sky is cloudy rather than clear; 3) the spectrum of CO2 flux density exhibits peaks at timescales of days, weeks, and years, and a spectral gap exists at the month timescale; 4) the optimal temperature of net CO2 exchange varies with mean summer temperature; and 5) stand age affects carbon dioxide and water vapor flux densities

Can fisheries-induced evolution shift reference points for fisheries management?

Biological reference points are important tools for fisheries management. Reference points are not static, butmay change when a population's environment or the population itself changes. Fisheries-induced evolution is one mechanism that can alter population characteristics, leading to "shifting" reference points by modifying the underlying biological processes or by changing the perception of a fishery system. The former causes changes in "true" reference points, whereas the latter is caused by changes in the yardsticks used to quantify a system's status. Unaccounted shifts of either kind imply that reference points gradually lose their intended meaning. This can lead to increased precaution, which is safe, but potentially costly. Shifts can also occur in more perilous directions, such that actual risks are greater than anticipated. Our qualitative analysis suggests that all commonly used reference points are susceptible to shifting through fisheries-induced evolution, including the limit and "precautionary" reference points for spawning-stock biomass, B-lim and B-pa, and the target reference point for fishing mortality, F-0.1. Our findings call for increased awareness of fisheries-induced changes and highlight the value of always basing reference points on adequately updated information, to capture all changes in the biological processes that drive fish population dynamics

End of life care in sub-Saharan Africa: a systematic review of the qualitative literature

<p>Abstract</p> <p>Background</p> <p>End of life (EoL) care in sub-Saharan Africa still lacks the sound evidence-base needed for the development of effective, appropriate service provision. It is essential to make evidence from all types of research available alongside clinical and health service data, to ensure that EoL care is ethical and culturally appropriate. This article aims to synthesize qualitative research on EoL care in sub-Saharan Africa to inform policy, practice and further research. It seeks to identify areas of existing research; describe findings specifically relevant to the African context; and, identify areas lacking evidence.</p> <p>Methods</p> <p>Relevant literature was identified through eight electronic databases: AMED, British Nursing Index & Archive, CINAHL, EMBASE, IBSS, MEDLINE, PsycINFO, and the Social Sciences Citation Index; and hand searches. Inclusion criteria were: published qualitative or mixed-method studies in sub-Saharan Africa, about EoL care. Study quality was assessed using a standard grading scale. Relevant data including findings and practice recommendations were extracted and compared in tabular format.</p> <p>Results</p> <p>Of the 407 articles initially identified, 51 were included in the qualitative synthesis. Nineteen came from South Africa and the majority (38) focused on HIV/AIDS. Nine dealt with multiple or unspecified conditions and four were about cancer. Study respondents included health professionals, informal carers, patients, community members and bereaved relatives. Informal carers were typically women, the elderly and children, providing total care in the home, and lacking support from professionals or the extended family. Twenty studies focused on home-based care, describing how programmes function in practice and what is needed to make them effective. Patients and carers were reported to prefer institutional care but this needs to be understood in context. Studies focusing on culture discussed good and bad death, culture-specific approaches to symptoms and illness, and the bereavement process.</p> <p>Conclusions</p> <p>The data support or complement the findings from quantitative research. The review prompts a reconsideration of the assumption that in Africa the extended family care for the sick, and that people prefer home-based care. The review identifies areas relevant for a research agenda on socio-cultural issues at the EoL in sub-Saharan Africa.</p

Bioinformatics tools for cancer metabolomics

It is well known that significant metabolic change take place as cells are transformed from normal to malignant. This review focuses on the use of different bioinformatics tools in cancer metabolomics studies. The article begins by describing different metabolomics technologies and data generation techniques. Overview of the data pre-processing techniques is provided and multivariate data analysis techniques are discussed and illustrated with case studies, including principal component analysis, clustering techniques, self-organizing maps, partial least squares, and discriminant function analysis. Also included is a discussion of available software packages

Symptom-based stratification of patients with primary Sjögren's syndrome: multi-dimensional characterisation of international observational cohorts and reanalyses of randomised clinical trials

Background Heterogeneity is a major obstacle to developing effective treatments for patients with primary Sjögren's syndrome. We aimed to develop a robust method for stratification, exploiting heterogeneity in patient-reported symptoms, and to relate these differences to pathobiology and therapeutic response. Methods We did hierarchical cluster analysis using five common symptoms associated with primary Sjögren's syndrome (pain, fatigue, dryness, anxiety, and depression), followed by multinomial logistic regression to identify subgroups in the UK Primary Sjögren's Syndrome Registry (UKPSSR). We assessed clinical and biological differences between these subgroups, including transcriptional differences in peripheral blood. Patients from two independent validation cohorts in Norway and France were used to confirm patient stratification. Data from two phase 3 clinical trials were similarly stratified to assess the differences between subgroups in treatment response to hydroxychloroquine and rituximab. Findings In the UKPSSR cohort (n=608), we identified four subgroups: Low symptom burden (LSB), high symptom burden (HSB), dryness dominant with fatigue (DDF), and pain dominant with fatigue (PDF). Significant differences in peripheral blood lymphocyte counts, anti-SSA and anti-SSB antibody positivity, as well as serum IgG, κ-free light chain, β2-microglobulin, and CXCL13 concentrations were observed between these subgroups, along with differentially expressed transcriptomic modules in peripheral blood. Similar findings were observed in the independent validation cohorts (n=396). Reanalysis of trial data stratifying patients into these subgroups suggested a treatment effect with hydroxychloroquine in the HSB subgroup and with rituximab in the DDF subgroup compared with placebo. Interpretation Stratification on the basis of patient-reported symptoms of patients with primary Sjögren's syndrome revealed distinct pathobiological endotypes with distinct responses to immunomodulatory treatments. Our data have important implications for clinical management, trial design, and therapeutic development. Similar stratification approaches might be useful for patients with other chronic immune-mediated diseases. Funding UK Medical Research Council, British Sjogren's Syndrome Association, French Ministry of Health, Arthritis Research UK, Foundation for Research in Rheumatology

SBML Level 3: an extensible format for the exchange and reuse of biological models

Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction-based models and packages that extend the core with features suited to other model types including constraint-based models, reaction-diffusion models, logical network models, and rule-based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single-cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570