Providing nutritious and environmentally sustainable food to all people at all times is one of the greatest challenges currently facing society. This problem is particularly acute in Africa where an ...estimated one in four people still lack adequate food to sustain an active and healthy life. In this study, we consider the potential impact of future population growth and climate change on food security in Africa, looking ahead to 2050. A modelling framework termed FEEDME (Food Estimation and Export for Diet and Malnutrition Evaluation) was used which was characterized to model the impacts of future climate changes (utilizing the Intergovernmental Panel on Climate Change Special Report on Emissions Scenarios projections) and projected population growth on food availability and subsequent undernourishment prevalence in 44 African countries. Our results indicate that projected rapid population growth will be the leading cause of food insecurity and widespread undernourishment across Africa. Very little to no difference in undernourishment projections were found when we examined future scenarios with and without the effects of climate change, suggesting population growth is the dominant driver of change. Various adaptation options are discussed, such as closing the yield gap via sustainable intensification and increasing imports through trade and aid agreements. These strategies are likely to be critical in preventing catastrophic future food insecurity.
A new conceptual framework is presented for the assessment of the impacts of environmental change drivers on ecosystem service provision and the policy and management responses that would derive from ...the valuation of these impacts. The Framework for Ecosystem Service Provision (FESP), is based on an interpretation of the widely-used Drivers-Pressures-State-Impact-Response (DPSIR) framework. FESP differs from the DPSIR by offering clarity in the definitions of the various DPSIR components as well as introducing novel elements of relevance to the ecosystem service approach. The value of a common framework lies in making the comparison across competing services accessible and clear as well as highlighting the conflicts and trade-offs between not only multiple ecosystem services, but also multiple service beneficiaries. The framework is explicit, for example, in recognising as state variables not only the attributes of the Ecosystem Service Providers (ESPs), but also the attributes of the Ecosystem Service Beneficiaries (ESBs). That a service depends as much on the attributes of the people whose well-being benefits from the service as on the attributes of the biology providing the service is an important step in integrated social-ecological thinking. FESP also identifies the mechanisms of either mitigation or adaptation to the environmental change problem through the effect of these response strategies on specific pressure or state variables. In this way, FESP can contribute to the policies and strategies that are used to support conservation management. This paper describes the principles of FESP and presents some indicative examples of its practical implementation.
Modelling strategies for predicting the potential impacts of climate change on the natural distribution of species have often focused on the characterization of a species' bioclimate envelope. A ...number of recent critiques have questioned the validity of this approach by pointing to the many factors other than climate that play an important part in determining species distributions and the dynamics of distribution changes. Such factors include biotic interactions, evolutionary change and dispersal ability. This paper reviews and evaluates criticisms of bioclimate envelope models and discusses the implications of these criticisms for the different modelling strategies employed. It is proposed that, although the complexity of the natural system presents fundamental limits to predictive modelling, the bioclimate envelope approach can provide a useful first approximation as to the potentially dramatic impact of climate change on biodiversity. However, it is stressed that the spatial scale at which these models are applied is of fundamental importance, and that model results should not be interpreted without due consideration of the limitations involved. A hierarchical modelling framework is proposed through which some of these limitations can be addressed within a broader, scale-dependent context.
Developmental and cancer models show Wnt/β-catenin-dependent signaling mediates diverse phenotypic outcomes in the pancreas that are dictated by context, duration and strength of activation. While ...generally assumed to be pro-tumorigenic, it is unclear to what extent dysregulation of Wnt/β-catenin signaling impacts tumor progression in pancreatic adenocarcinoma (PDAC). In the present study, Wnt/β-catenin activity was characterized across a spectrum of PDAC cell lines and primary tumors. Reporter and gene expression-based assays revealed wide heterogeneity in Wnt/β-catenin transcriptional activity across PDAC cell lines and patient tumors, as well as variable responsiveness to exogenous Wnt ligand stimulation. An experimentally generated, pancreas-specific gene expression signature of Wnt/β-catenin transcriptional activation was used to stratify pathway activation across a cohort of resected, early-stage PDAC tumors (N=41). In this cohort, higher Wnt/β-catenin activation was found to significantly correlate with lymphvascular invasion and worse disease-specific survival (median survival time 20.3 versus 43.9 months, log-rank P=0.03). Supporting the importance of Wnt ligand in mediating autocrine Wnt signaling, Wnt/β-catenin activity was significantly inhibited in PDAC cell lines by WLS gene silencing and the small-molecule inhibitor IWP-2, both of which functionally block Wnt ligand processing and secretion. Transcriptional profiling revealed elevated expression of WNT7B occurred in PDAC cell lines with high levels of cell autonomous Wnt/β-catenin activity. Gene-knockdown studies in AsPC-1 and HPAF-2 cell lines confirmed WNT7B-mediated cell autonomous Wnt/β-catenin activation, as well as an anchorage-independent growth phenotype. Our findings indicate WNT7B can serve as a primary determinant of differential Wnt/β-catenin activation in PDAC. Disrupting the interaction between Wnt ligands and their receptors may be a particularly suitable approach for therapeutic modulation of Wnt/β-catenin signaling in PDAC and other cancer contexts where Wnt activation is mediated by ligand expression rather than mutations in canonical pathway members.
A model, A Spatial Evaluation of Climate Impact on the Envelope of Species (SPECIES), is presented which has been developed to evaluate the impacts of climate change on the bioclimatic envelope of ...plant species in Great Britain. SPECIES couples an artificial neural network with a climate–hydrological process model. The hybrid model has been successfully trained to estimate current species distributions using climate and soils data at the European scale before application at a finer resolution national scale. Using this multi-scale approach ensures encapsulation of the full extent of future climate scenarios within Great Britain without extrapolating outside of the model's training dataset. Application of the model to 32 plant species produced a mean Pearson correlation coefficient of 0.841 and a mean Kappa statistic of 0.772 between observed and simulated distributions. Simulations of four climate change scenarios revealed that changes to suitable climate space in Great Britain is highly species dependent and that distribution changes may be multidirectional and temporally non-linear. Analysis of the SPECIES results suggests that the neural network methodology can provide a feasible alternative to more classical spatial statistical techniques.
Summary
We describe the collection of cohorts together with the analysis plan for an update of the fracture risk prediction tool FRAX with respect to current and novel risk factors. The resource ...comprises 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures.
Introduction
The availability of the fracture risk assessment tool FRAX® has substantially enhanced the targeting of treatment to those at high risk of fracture with FRAX now incorporated into more than 100 clinical osteoporosis guidelines worldwide. The aim of this study is to determine whether the current algorithms can be further optimised with respect to current and novel risk factors.
Methods
A computerised literature search was performed in PubMed from inception until May 17, 2019, to identify eligible cohorts for updating the FRAX coefficients. Additionally, we searched the abstracts of conference proceedings of the American Society for Bone and Mineral Research, European Calcified Tissue Society and World Congress of Osteoporosis. Prospective cohort studies with data on baseline clinical risk factors and incident fractures were eligible.
Results
Of the 836 records retrieved, 53 were selected for full-text assessment after screening on title and abstract. Twelve cohorts were deemed eligible and of these, 4 novel cohorts were identified. These cohorts, together with 60 previously identified cohorts, will provide the resource for constructing an updated version of FRAX comprising 2,138,428 participants with a follow-up of approximately 20 million person-years and 116,117 documented incident major osteoporotic fractures. For each known and candidate risk factor, multivariate hazard functions for hip fracture, major osteoporotic fracture and death will be tested using extended Poisson regression. Sex- and/or ethnicity-specific differences in the weights of the risk factors will be investigated. After meta-analyses of the cohort-specific beta coefficients for each risk factor, models comprising 10-year probability of hip and major osteoporotic fracture, with or without femoral neck bone mineral density, will be computed.
Conclusions
These assembled cohorts and described models will provide the framework for an updated FRAX tool enabling enhanced assessment of fracture risk (PROSPERO (CRD42021227266)).
This paper presents the results of a search for brown dwarfs in the Upper Scorpius Association using data from the UKIRT Infrared Deep Sky Survey (UKIDSS) Galactic Cluster Survey. Candidate young ...brown dwarfs were first chosen by their position in colour magnitude diagrams with further selection based on proper motions to ensure Upper Scorpius membership. Proper motions were derived by comparing UKIDSS and Two Micron All Sky Survey (2MASS) data. Using that method we identify 19 new brown dwarfs in the southern part of the association. In addition there are up to eight likely members with slightly higher dispersion velocity. The ratio of brown dwarfs to stars was found to be consistent with other areas in Upper Scorpius. It was also found to be similar to other results from young clusters with OB associations, and lower than those without, suggesting the brown dwarf formation rate may be a function of environment.
A modelling framework for studying the combined effects of climate and land-cover changes on the distribution of species is presented. The model integrates land-cover data into a correlative ...bioclimatic model in a scale-dependent hierarchical manner, whereby Artificial Neural Networks are used to characterise species' climatic requirements at the European scale and land-cover requirements at the British scale. The model has been tested against an alternative non-hierarchical approach and has been applied to four plant species in Britain: Rhynchospora alba, Erica tetralix, Salix herbacea and Geranium sylvaticum. Predictive performance has been evaluated using Cohen's Kappa statistic and the area under the Receiver Operating Characteristic curve, and a novel approach to identifying thresholds of occurrence which utilises three levels of confidence has been applied. Results demonstrate reasonable to good predictive performance for each species, with the main patterns of distribution simulated at both 10 km and 1 km resolutions. The incorporation of land-cover data was found to significantly improve purely climate-driven predictions for R. alba and E. tetralix, enabling regions with suitable climate but unsuitable land-cover to be identified. The study thus provides an insight into the roles of climate and land-cover as determinants of species' distributions and it is demonstrated that the modelling approach presented can provide a useful framework for making predictions of distributions under scenarios of changing climate and land-cover type. The paper confirms the potential utility of multi-scale approaches for understanding environmental limitations to species' distributions, and demonstrates that the search for environmental correlates with species' distributions must be addressed at an appropriate spatial scale. Our study contributes to the mounting evidence that hierarchical schemes are characteristic of ecological systems.
The use of Mendelian randomization (MR) in epidemiology has increased considerably in recent years, with a subsequent increase in systematic reviews of MR studies. We conducted a systematic review of ...tools designed for assessing risk of bias and/or quality of evidence in MR studies and a review of systematic reviews of MR studies.
We systematically searched MEDLINE, Embase, the Web of Science, preprints servers and Google Scholar for articles containing tools for assessing, conducting and/or reporting MR studies. We also searched for systematic reviews and protocols of systematic reviews of MR studies. From eligible articles we collected data on tool characteristics and content, as well as details of narrative description of bias assessment.
Our searches retrieved 2464 records to screen, from which 14 tools, 35 systematic reviews and 38 protocols were included in our review. Seven tools were designed for assessing risk of bias/quality of evidence in MR studies and evaluation of their content revealed that all seven tools addressed the three core assumptions of instrumental variable analysis, violation of which can potentially introduce bias in MR analysis estimates.
We present an overview of tools and methods to assess risk of bias/quality of evidence in MR analysis. Issues commonly addressed relate to the three standard assumptions of instrumental variables analyses, the choice of genetic instrument(s) and features of the population(s) from which the data are collected (particularly in two-sample MR), in addition to more traditional non-MR-specific epidemiological biases. The identified tools should be tested and validated for general use before recommendations can be made on their widespread use. Our findings should raise awareness about the importance of bias related to MR analysis and provide information that is useful for assessment of MR studies in the context of systematic reviews.
Background
How the physical metrics, especially physical intensity, and possession interact with each other, and subsequently combine to influence performance remains opaque. Therefore, we ...investigated the interrelationship of possession, physical metrics, and team performance in elite soccer.
Methods
Four seasons of a top European league were used to derive 80 team league performances (points), together with possession and physical data. Physical metrics were absolute distances (m) during the whole match and ball‐in‐play, and rates of distance covered (m⋅min−1) as the index of physical intensity, notably when in‐possession/out‐of‐possession, in total and within five speed categories. Interrelationships of possession, physical metrics, possession, and performance were assessed with Pearson's correlations and mediation analysis.
Results
Overall possession (r = 0.794) and time out‐of‐possession within the defensive third (r = −0.797) were most strongly correlated with performance. The strong relationships between in‐possession distances and performance appeared coincidental due to greater time in‐possession. Physical intensity had a complex relationship with possession and performance, with opposite relationships according to possession status: lower physical intensity when in‐possession and higher physical intensity when out‐of‐possession were associated with possession and performance. Mediation analysis revealed the direct, independent importance of possession for team performance; however, the association of physical intensity with performance was largely (>79%) mediated by possession.
Conclusion
Based on these findings, we propose a novel model of the interrelationships between possession, physical intensity, and performance, whereby higher possession is the largest, direct contributor toward enhanced team performance, with lower physical intensity in‐possession a consequence of higher possession, but greater physical intensity when out‐of‐possession a cause of increased possession.
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