Not all light transmission aggregation assays are created equal: qualitative differences between light transmission and 96-well plate aggregometry.

In this short article, submitted as part of the review on platelet function testing, we illustrate the quantitative and qualitative differences between classical light transmission aggregometry (LTA) and 96-well plate aggregometry. We show that responses to platelet agonists and antagonists differ depending upon the method of aggregation testing. For example, in 96-well aggregometry, responses to collagen are strongly inhibited by P2Y12 receptor antagonists while in LTA they are much less affected. Furthermore, we explore the importance of differences in the mechanical environment upon platelet aggregation. We emphasize that LTA and 96-well aggregometry are not interchangeable assays. These two assays are best used as complementary tests to explore platelet function in depth

18F-FDG PET/MRI for staging and interim response assessment in pediatric and adolescent Hodgkin lymphoma: a prospective study with 18F-FDG PET/CT as reference standard

Rationale: Treatment regimens for pediatric Hodgkin's lymphoma (HL) depend on accurate staging and treatment response assessment, based on accurate disease distribution and metabolic activity depiction. With the aim of radiation dose reduction, we compared the diagnostic performance of 18F-FDG PET/MR to a 18F-FDG PET/CT reference standard for staging and response assessment. Methods: Twenty-four patients (mean age 15.4 years, range 8-19.5 years) with histologically proven HL were prospectively and consecutively recruited in 2015 and 2016, undergoing both 18F-FDG PET/CT and 18F-FDG PET/MRI at initial staging (N n = 24) and at response assessment (N n = 21). Diagnostic accuracy of 18F-FDG PET/MRI for both nodal and extra-nodal disease was compared to 18F-FDG PET/CT, which was considered as the reference standard. Discrepancies were retrospectively classified as perceptual or technical errors and 18F-FDG PET/MRI and 18F-FDG PET/CT were corrected by removing perceptual error. Agreement with Ann-Arbor staging and Deauville grading was also assessed. Results: For nodal and extranodal sites combined, corrected staging 18F-FDG PET/MRI sensitivity was 100% (95% confidence interval (CI) 96.7%-100%), specificity 99.5% (95%CI 98.3%-99.9%). Corrected response assessment 18F-FDG PET/MRI sensitivity was 83.3% (95%CI 36.5%-99.1%), specificity 100% (95%CI 99.2%-100%). Modified Ann-Arbor staging agreement between F18-FDG PET/CT and 18F-FDG PET/MRI was perfect (k = 1.0, P = 0.000). Deauville grading agreement between 18F-FDG PET/MRI and 18F-FDG PET/CT was excellent (k = 0.835, P = 0.000). Conclusion:18F-FDG PET/MRI is a promising alternative to 18F-FDG PET/CT for staging and response assessment in children with Hodgkin lymphoma

Evolutionary connectionism: algorithmic principles underlying the evolution of biological organisation in evo-devo, evo-eco and evolutionary transitions

The mechanisms of variation, selection and inheritance, on which evolution by natural selection depends, are not fixed over evolutionary time. Current evolutionary biology is increasingly focussed on understanding how the evolution of developmental organisations modifies the distribution of phenotypic variation, the evolution of ecological relationships modifies the selective environment, and the evolution of reproductive relationships modifies the heritability of the evolutionary unit. The major transitions in evolution, in particular, involve radical changes in developmental, ecological and reproductive organisations that instantiate variation, selection and inheritance at a higher level of biological organisation. However, current evolutionary theory is poorly equipped to describe how these organisations change over evolutionary time and especially how that results in adaptive complexes at successive scales of organisation (the key problem is that evolution is self-referential, i.e. the products of evolution change the parameters of the evolutionary process). Here we first reinterpret the central open questions in these domains from a perspective that emphasises the common underlying themes. We then synthesise the findings from a developing body of work that is building a new theoretical approach to these questions by converting well-understood theory and results from models of cognitive learning. Specifically, connectionist models of memory and learning demonstrate how simple incremental mechanisms, adjusting the relationships between individually-simple components, can produce organisations that exhibit complex system-level behaviours and improve the adaptive capabilities of the system. We use the term “evolutionary connectionism” to recognise that, by functionally equivalent processes, natural selection acting on the relationships within and between evolutionary entities can result in organisations that produce complex system-level behaviours in evolutionary systems and modify the adaptive capabilities of natural selection over time. We review the evidence supporting the functional equivalences between the domains of learning and of evolution, and discuss the potential for this to resolve conceptual problems in our understanding of the evolution of developmental, ecological and reproductive organisations and, in particular, the major evolutionary transitions

Dose-response association between moderate to vigorous physical activity and incident morbidity and mortality for individuals with a different cardiovascular health status: A cohort study among 142,493 adults from the Netherlands.

BACKGROUND: Moderate to vigorous physical activity (MVPA) is strongly associated with risk reductions of noncommunicable diseases and mortality. Cardiovascular health status may influence the benefits of MVPA. We compare the association between MVPA and incident major adverse cardiovascular events (MACE) and mortality between healthy individuals, individuals with elevated levels of cardiovascular risk factors (CVRF), and cardiovascular disease (CVD). METHODS AND FINDINGS: A cohort study was performed in the 3 northern provinces of the Netherlands, in which data were collected between 2006 and 2018, with a median follow-up of 6.8 years (Q25 5.7; Q75 7.9). A total of 142,493 participants of the Lifelines Cohort Study were stratified at baseline as (1) healthy; (2) CVRF; or (3) CVD. Individuals were categorized into "inactive" and 4 quartiles of least (Q1) to most (Q4) active based on self-reported MVPA volumes. Primary outcome was a composite of incident MACE and all-cause mortality during follow-up. Cox regression was used to estimate hazard ratios (HRs), 95% confidence intervals (CIs) and P values. The main analyses were stratified on baseline health status and adjusted for age, sex, income, education, alcohol consumption, smoking, protein, fat and carbohydrate intake, kidney function, arrhythmias, hypothyroid, lung disease, osteoarthritis, and rheumatoid arthritis. The event rates were 2.2% in healthy individuals (n = 2,485 of n = 112,018), 7.9% in those with CVRF (n = 2,214 of n = 27,982) and 40.9% in those with CVD (n = 1,019 of n = 2,493). No linear association between MVPA and all-cause mortality or MACE was found for healthy individuals (P = 0.36) and individuals with CVRF (P = 0.86), but a linear association was demonstrated for individuals with CVD (P = 0.04). Adjusted HRs in healthy individuals were 0.81 (95% CI 0.64 to 1.02, P = 0.07), 0.71 (95% CI 0.56 to 0.89, P = 0.004), 0.72 (95% CI 0.57 to 0.91, P = 0.006), and 0.76 (95% CI 0.60 to 0.96, P = 0.02) for MVPA Q1 to Q4, respectively, compared to inactive individuals. In individuals with CVRF, HRs were 0.69 (95% CI 0.57 to 0.82, P < 0.001), 0.66 (95% CI 0.55 to 0.80, P < 0.001), 0.64 (95% CI 0.53 to 0.77, P < 0.001), and 0.69 (95% CI 0.57 to 0.84, P < 0.001) for MVPA Q1 to Q4, respectively, compared to inactive individuals. Finally, HRs for MVPA Q1 to Q4 compared to inactive individuals were 0.80 (95% CI 0.62 to 1.03, P = 0.09), 0.82 (95% CI 0.63 to 1.06, P = 0.13), 0.74 (95% CI 0.57 to 0.95, P = 0.02), and 0.70 (95% CI 0.53 to 0.93, P = 0.01) in CVD patients. Leisure MVPA was associated with the most health benefits, nonleisure MVPA with little health benefits, and occupational MVPA with no health benefits. Study limitations include its observational nature, self-report data about MVPA, and potentially residual confounding despite extensive adjustment for lifestyle risk factors and health-related factors. CONCLUSIONS: MVPA is beneficial for reducing adverse outcomes, but the shape of the association depends on cardiovascular health status. A curvilinear association was found in healthy and CVRF individuals with a steep risk reduction at low to moderate MVPA volumes and benefits plateauing at high(er) MVPA volumes. CVD patients demonstrated a linear association, suggesting a constant reduction of risk with higher volumes of MVPA. Therefore, individuals with CVDs should be encouraged that "more is better" regarding MVPA. These findings may help to optimize exercise prescription to gain maximal benefits of a physically active lifestyle

Camels and Climate Resilience: Adaptation in Northern Kenya

In the drylands of Africa, pastoralists have been facing new challenges, including those related to environmental shocks and stresses. In northern Kenya, under conditions of reduced rainfall and more frequent droughts, one response has been for pastoralists to focus increasingly on camel herding. Camels have started to be kept at higher altitudes and by people who rarely kept camels before. The development has been understood as a climate change adaptation strategy and as a means to improve climate resilience. Since 2003, development organizations have started to further the trend by distributing camels in the region. Up to now, little has been known about the nature of, reasons for, or ramifications of the increased reliance on camels. The paper addresses these questions and concludes that camels improve resilience in this dryland region, but only under certain climate change scenarios, and only for some groups.This study was funded by The Royal Geographical Society with Institute of British Geographers Thesiger-Oman Fellowship

Early recognition of coeliac disease through community pharmacies: A proof of concept study

Setting: 15 community pharmacies in the UK Objective: Proof of concept study to test the use of community pharmacies for active case finding of patients with coeliac disease. Method: Customers accessing over-the counter and prescription medicines indicated in the treatment of possible symptoms of coeliac disease over a six month period were offered a free point of care test. All patients were given advice regarding the test results and those who tested positive were advised to make an appointment with their general practitioner. Patients and pharmacists involved in service provision were asked to complete a satisfaction survey. Pharmacists were additionally invited to undertake interviews to better understand their views on the service. Main outcome measures: Feasibility of service, acceptability to stakeholders and proportion testing positive for coeliac disease. Results: Of the 551 individuals tested, 52 (9.4%) tested positive. 277 (50.3%) were tested for accessing irritable bowel syndrome treatment, 142 (25.8%) due to presenting for diarrhoea. The proportion of patients testing positive with different symptoms or for different treatments were similar. Of 43 customers who returned the satisfaction survey, all would recommend the service to others, believing the community pharmacy to be a suitable location. Community pharmacists believed that it enabled them to improve relationships with their customers and that medical practices were receptive to the service. Conclusion: This proof of concept study has shown that community pharmacies using a point of care test can effectively recognise and refer patients for confirmatory coeliac disease testing with high levels of customer and service provider satisfaction

Use of reconstituted metabolic networks to assist in metabolomic data visualization and mining

Metabolomics experiments seldom achieve their aim of comprehensively covering the entire metabolome. However, important information can be gleaned even from sparse datasets, which can be facilitated by placing the results within the context of known metabolic networks. Here we present a method that allows the automatic assignment of identified metabolites to positions within known metabolic networks, and, furthermore, allows automated extraction of sub-networks of biological significance. This latter feature is possible by use of a gap-filling algorithm. The utility of the algorithm in reconstructing and mining of metabolomics data is shown on two independent datasets generated with LC–MS LTQ-Orbitrap mass spectrometry. Biologically relevant metabolic sub-networks were extracted from both datasets. Moreover, a number of metabolites, whose presence eluded automatic selection within mass spectra, could be identified retrospectively by virtue of their inferred presence through gap filling

The science of clinical practice: disease diagnosis or patient prognosis? Evidence about "what is likely to happen" should shape clinical practice.

BACKGROUND: Diagnosis is the traditional basis for decision-making in clinical practice. Evidence is often lacking about future benefits and harms of these decisions for patients diagnosed with and without disease. We propose that a model of clinical practice focused on patient prognosis and predicting the likelihood of future outcomes may be more useful. DISCUSSION: Disease diagnosis can provide crucial information for clinical decisions that influence outcome in serious acute illness. However, the central role of diagnosis in clinical practice is challenged by evidence that it does not always benefit patients and that factors other than disease are important in determining patient outcome. The concept of disease as a dichotomous 'yes' or 'no' is challenged by the frequent use of diagnostic indicators with continuous distributions, such as blood sugar, which are better understood as contributing information about the probability of a patient's future outcome. Moreover, many illnesses, such as chronic fatigue, cannot usefully be labelled from a disease-diagnosis perspective. In such cases, a prognostic model provides an alternative framework for clinical practice that extends beyond disease and diagnosis and incorporates a wide range of information to predict future patient outcomes and to guide decisions to improve them. Such information embraces non-disease factors and genetic and other biomarkers which influence outcome. SUMMARY: Patient prognosis can provide the framework for modern clinical practice to integrate information from the expanding biological, social, and clinical database for more effective and efficient care

Nautilus at Risk – Estimating Population Size and Demography of Nautilus pompilius

The low fecundity, late maturity, long gestation and long life span of Nautilus suggest that this species is vulnerable to over-exploitation. Demand from the ornamental shell trade has contributed to their rapid decline in localized populations. More data from wild populations are needed to design management plans which ensure Nautilus persistence. We used a variety of techniques including capture-mark-recapture, baited remote underwater video systems, ultrasonic telemetry and remotely operated vehicles to estimate population size, growth rates, distribution and demographic characteristics of an unexploited Nautilus pompilius population at Osprey Reef (Coral Sea, Australia). We estimated a small and dispersed population of between 844 and 4467 individuals (14.6–77.4 km−2) dominated by males (83∶17 male∶female) and comprised of few juveniles (<10%).These results provide the first Nautilid population and density estimates which are essential elements for long-term management of populations via sustainable catch models. Results from baited remote underwater video systems provide confidence for their more widespread use to assess efficiently the size and density of exploited and unexploited Nautilus populations worldwide