Project description:1. The prevalence of phylogenetic niche conservatism (PNC) in nature is still a conflicting issue. Disagreement arises from confusion over its precise definition and the variety of approaches to measure its prevalence. Recent work highlighted that common measures of PNC strongly depend on the assumptions of the underlying model of niche evolution. However, this warning has not been well recognized in the applied literature and questionable approaches are still frequently applied. 2. The aim of this paper is to draw attention to the assumptions underlying commonly applied simple measures of PNC. We used a series of simulations to illustrate how misleading results can be if assumptions of niche evolution are violated, that the violation of assumptions is a common phenomenon and that testing assumptions requires in-depth pre-test. 3. We conclude that the seemingly simple measures of PNC, such as phylogenetic sign6al and evolutionary rate, are not so easy to apply if one accounts for the necessity to test model assumptions. In addition, these measures can be difficult to interpret. The common assumption that strong phylogenetic signal indicates PNC will be often invalid. In addition, the interpretation of some measures, e.g. the conclusion that evolutionary rate is slow enough to indicate PNC, requires a comparison with another clade, another trait or well-developed null model assumptions and thus additional data. 4. We suggest that studies investigating PNC should always compare alternative evolutionary models, and that model comparisons should in particular include flexible niche evolution models such as multiple-optima OU models, although these are computational intensive. These models are directly inherited from the concept of macro-evolutionary adaptive landscape, and can indicate PNC either by relative few peak shifts or by narrow peaks in the adaptive landscape. A test of PNC thus requires comparing these parameters of the macroevolutionary landscape between clades or time periods. 5. The general prevalence of PNC in nature should be evaluated only based on studies keeping up to the high standards of communicating the used definition of PNC, testing the assumptions made in the modelling approaches and including newly developed models in a model comparison approach.
Project description:To date, the diagnoses of Parkinson syndromes are based on clinical examination. Therefore, these specific diagnoses are made, when the neuropathological process is already advanced. However, disease modification or neuroprotection, is considered to be most effective before marked neurodegeneration has occurred. In recent years, early clinical or prodromal stages of Parkinson syndromes came into focus. Moreover, subtypes of distinct diseases will allow predictions of the individual course of the diseases more precisely. Thereby, patients will be enrolled into clinical trials with more specific disease entities and endpoints. Furthermore, novel fluid and imaging biomarkers that allow biochemical diagnoses are under development. These will lead to earlier diagnoses and earlier therapy in the future as consequence. Furthermore, therapeutic approaches will take the underlying neuropathological process of neurodegenerative Parkinson syndromes more specific into account. Specifically, future therapies will target the aggregation of aggregation-prone proteins such as alpha-synuclein and tau, the degradation of pathological aggregates, and the spreading of pathological protein aggregates throughout the brain. Many of these approaches are already in (pre)clinical development. In addition, anti-inflammatory approaches are in development. Furthermore, drug-repurposing is a feasible approach to shorten the developmental process of new drugs.
Project description:Clinical studies with cellular therapies using tolerance-inducing cells, such as tolerogenic antigen-presenting cells (tolAPC) and regulatory T cells (Treg) for the prevention of transplant rejection and the treatment of autoimmune diseases have been expanding the last decade. In this perspective, we will summarize the current perspectives of the clinical application of both tolAPC and Treg, and will address future directions and the importance of immunomonitoring in clinical studies that will result in progress in the field.
Project description:Machine Learning (ML) methods have been proposed in the academic literature as alternatives to statistical ones for time series forecasting. Yet, scant evidence is available about their relative performance in terms of accuracy and computational requirements. The purpose of this paper is to evaluate such performance across multiple forecasting horizons using a large subset of 1045 monthly time series used in the M3 Competition. After comparing the post-sample accuracy of popular ML methods with that of eight traditional statistical ones, we found that the former are dominated across both accuracy measures used and for all forecasting horizons examined. Moreover, we observed that their computational requirements are considerably greater than those of statistical methods. The paper discusses the results, explains why the accuracy of ML models is below that of statistical ones and proposes some possible ways forward. The empirical results found in our research stress the need for objective and unbiased ways to test the performance of forecasting methods that can be achieved through sizable and open competitions allowing meaningful comparisons and definite conclusions.
Project description:Soil is one of the most complex systems on Earth, functioning at the interface between the lithosphere, biosphere, hydrosphere, and atmosphere and generating a multitude of functions. Moreover, soil constitutes the belowground environment from which plants capture water and nutrients. Despite their great importance, soil properties are often not sufficiently considered in other disciplines, especially in spatial studies of plant distributions. Most soil properties are available as point data and, to be used in spatial analyses, need to be generalised over entire regions (i.e. digital soil mapping). Three categories of statistical approaches can be used for such purpose: geostatistical approaches (GSA), predictive-statistical approaches (PSA), and hybrid approaches (HA) that combine the two previous ones. How then to choose the best approach in a given soil study context? Does it depend on the soil properties to be spatialized, the study area's characteristics, and/or the availability of soil data? The main aims of this study was to review the use of these three approaches to derive maps of soil properties in relation to the soil parameters, the study area characteristics, and the number of soil samples. We evidenced that the approaches that tend to show the best performance for spatializing soil properties were not necessarily the ones most used in practice. Although PSA was the most widely used, it tended to be outperformed by HA in many cases, but the latter was far less used. However, as the study settings were not always properly described and not all situations were represented in the set of papers analysed, more comparative studies would be needed across a wider range of regions, soil properties, and spatial scales to provide robust conclusions on the best spatialization methods in a specific context.
Project description:Africa along side with south-east Asia are the epicentres of emerging and epidemic prone-infectious diseases and megacity biosecurity threat scenarios. Massive mobility and reluctance in the populations exposed to epidemic and emerging prone-infectious diseases coupled by a weak health system made disease alert and control measures difficult to implement. The investigation of virus detection and persistence in semen across a range of emerging viruses is useful for clinical and public health reasons, in particular for viruses that lead to high mortality or morbidity rates or to epidemics. Innovating built facility to safely treat patients with highly pathogenic infectious diseases is urgently need, not only to prevent the spread of infection from patients to healthcare workers but also to offer provision of relatively invasive organ support, whenever considered appropriate, without posing additional risk to staff. Despite multiple challenges, the need to conduct research during epidemics is inevitable, and candidate products must continue undergoing rigorous trials. Preparedness including management of complex humanitarian crises with community distrust is a cornerstone in response to high consequence emerging infectious disease outbreaks and imposes strengthening of the public health response infrastructure and emergency outbreak systems in high-risk regions.
Project description:Almost 30 years have passed since the first publication reporting regeneration of transformed peach plants. Nevertheless, the general applicability of genetic transformation of this species has not yet been established. Many strategies have been tested in order to obtain an efficient peach transformation system. Despite the amount of time and the efforts invested, the lack of success has significantly limited the utility of peach as a model genetic system for trees, despite its relatively short generation time; small, high-quality genome; and well-studied genetic resources. Additionally, the absence of efficient genetic transformation protocols precludes the application of many biotechnological tools in peach breeding programs. In this review, we provide an overview of research on regeneration and genetic transformation in this species and summarize novel strategies and procedures aimed at producing transgenic peaches. Promising future approaches to develop a robust peach transformation system are discussed, focusing on the main bottlenecks to success including the low efficiency of A. tumefaciens-mediated transformation, the low level of correspondence between cells competent for transformation and those that have regenerative competence, and the high rate of chimerism in the few shoots that are produced following transformation.
Project description:Neighbourhood socioeconomic status (NSES) has been identified as a determinant of mental health. In this study, we aimed to quantify how many cases of common mental health problems could be prevented by increasing NSES in the most socioeconomically deprived neighbourhoods in Rotterdam, the Netherlands, and how the increases in NSES would affect mental health inequalities. We used publicly available data for conducting a quantitative Health Impact Assessment (HIA) of two counterfactual policy scenarios. In Scenario 1, we set the NSES to the Rotterdam median score for all neighbourhoods which were below the Rotterdam median. In Scenario 2, we set the NSES score to the Dutch national average socioeconomic status score for the neighbourhoods that were below the national average. We estimated that Scenario 1 could prevent 5847 (95% CI, 2700-7999) or 10.7% of annual cases of common mental health problems, and Scenario 2 could prevent 10 713 (95% CI, 4875-14 799) or 19.6% of annual cases in Rotterdam while also reducing mental health inequalities between neighbourhoods in both scenarios. Given the substantial improvements in population mental health that enhanced neighbourhood socioeconomic conditions would bring, policy implementation is urgently needed.
Project description:IntroductionSexually transmitted infections (STIs) remain prevalent and are increasing in several populations. Appropriate STI diagnosis is crucial to prevent the transmission and sequelae of untreated infection. We reviewed the diagnostic accuracy of syndromic case management and existing point-of-care tests (POCTs), including those in the pipeline, to diagnose STIs in resource-constrained settings.MethodsWe prioritized updating the systematic review and meta-analysis of the diagnostic accuracy of vaginal discharge from 2001 to 2015 to include studies until 2018. We calculated the absolute effects of different vaginal flowcharts and the diagnostic performance of POCTs on important outcomes. We searched the peer-reviewed literature for previously conducted systematic reviews and articles from 1990 to 2018 on the diagnostic accuracy of syndromic management of vaginal and urethral discharge, genital ulcer and anorectal infections. We conducted literature reviews from 2000 to 2018 on the existing POCTs and those in the pipeline.Results and discussionsThe diagnostic accuracy of urethral discharge and genital ulcer disease syndromes is relatively adequate. Asymptomatic Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG) infections limit the use of vaginal discharge and anorectal syndromes. The pooled diagnostic accuracy of vaginal syndromic case management for CT/NG is low, resulting in high numbers of overtreatment and missed treatment. The absolute effect of POCTs was reduced overtreatment and missed treatment. Findings of the reviews on syndromic case management underscored the need for low-cost and accurate POCTs for the identification, first, of CT/NG, and, second, of Mycoplasma genitalium (MG) and Trichomonas vaginalis (TV) and NG and MG resistance/susceptibility testing. Near-patient POCT molecular assays for CT/NG/TV are commercially available. The prices of these POCTs remain the barrier for uptake in resource-constrained settings. This is driving the development of lower cost solutions.ConclusionsThe WHO syndromic case management guidelines should be updated to raise the quality of STI management through the integration of laboratory tests. STI screening strategies are needed to address asymptomatic STIs. POCTs that are accurate, rapid, simple and affordable are urgently needed in resource-constrained settings to support the uptake of aetiological diagnosis and treatment.
Project description:Encouragingly, global rates of new tuberculosis (TB) cases have been falling since 2005, in line with the Millennium Development Goal targets; however, cases of multidrug-resistant (MDR-) and extensively drug-resistant TB (XDR-TB) have been increasing. Fifteen of the world's 27 high MDR- and XDR-TB burden countries are in the World Health Organization (WHO) European Region, of which 10 are in Eastern Europe (including Baltic and Caucasus countries). To address the MDR- and XDR-TB situation in the WHO European Region, a Consolidated Action Plan to Prevent and Combat M/XDR-TB (2011-2015) was developed for all 53 Member States and implemented in 2011. Since the implementation of the Action Plan, the proportion of MDR-TB appears largely to have levelled off among bacteriologically confirmed TB cases in high-burden countries with universal or near universal (>95%) first-line drug susceptibility testing (DST). The treatment success rate, however, continues to decrease. A contributing factor is the substantial proportion of MDR-TB cases that are additionally resistant to either a fluoroquinolone, a second-line injectable agent or both (XDR-TB); high-burden country proportions range from 12.6% to 80.4%. Proportions of XDR-TB range from 5% to 24.8%. Despite much progress in Eastern Europe, critical challenges remain as regards access to appropriate treatment regimens; patient hospitalisation; scale-up of laboratory capacity, including the use of rapid diagnostics and second-line DST; vulnerable populations; human resources; and financing. Solutions to these challenges are aligned with the Post-2015 Global TB strategy. As a first step, the global strategy should be adapted at regional and country levels to serve as a framework for immediate actions as well as longer-term ways forward.