Diagnosis of antiphospholipid syndrome in routine clinical practice.

The updated international consensus criteria for definite antiphospholipid syndrome (APS) are useful for scientific clinical studies. However, there remains a need for diagnostic criteria for routine clinical use. We audited the results of routine antiphospholipid antibodies (aPLs) in a cohort of 193 consecutive patients with aPL positivity-based testing for lupus anticoagulant (LA), IgG and IgM anticardiolipin (aCL) and anti-ß(2)glycoprotein-1 antibodies (aß(2)GPI). Medium/high-titre aCL/aβ(2)GPI was defined as >99th percentile. Low-titre aCL/aβ(2)GPI positivity (>95(th )< 99(th) percentile) was considered positive for obstetric but not for thrombotic APS. One hundred of the 145 patients fulfilled both clinical and laboratory criteria for definite APS. Twenty-six women with purely obstetric APS had persistent low-titre aCL and/or aβ(2)GPI. With the inclusion of these patients, 126 of the 145 patients were considered to have APS. Sixty-seven out of 126 patients were LA-negative, of whom 12 had aCL only, 37 had aβ(2)GPI only and 18 positive were for both. The omission of aCL or aβ(2)GPI testing from investigation of APS would have led to a failure to diagnose APS in 9.5% and 29.4% of patients, respectively. Our data suggest that LA, aCL and aβ(2)GPI testing are all required for the accurate diagnosis of APS and that low-titre antibodies should be included in the diagnosis of obstetric APS

"Integrity and the corruption debate in sport: where is the integrity?

Research question: The paper is based on the contention that ‘integrity’ is a significantly under-theorised and under-conceptualised value within sports particularly in its use by a range of organisations fighting corruption in sport, which constitute what can be termed the ‘sports integrity industry’. The ‘sports integrity industry’ reveals: different narratives about integrity amongst the different groups; a lack of integration between the different views of integrity in sport; and the danger of imposing a corporate model of (behavioural-based) integrity. Research methods: The approach adopted in the research is two-fold. Initially, a brief examination will be made of the use of the term integrity by a range of bodies within Europe and wider internationally as part of the sports integrity industry. This identifies different level of depth and sophistication of the meanings given to the term. The second part of the paper clears the conceptual ground, examining the different philosophical and psychological views of integrity. Results and findings: This analysis will distinguish moral and behavioural integrity and examine the theoretical basis for the different understandings of integrity that have been developed in literature around business and public sector activities. The paper concludes that as far as effective engagement with corruption, sport needs to look beyond its own experience and be conscious of the wider debate concerning integrity. Implications: There is an urgent need for the development of the concept and practice of integrity and effective governance in sport that recognises the inherent integrity of sport itself; personal integrity; organisational integrity and procedural integrity in sports events

The role of mindfulness in distress and quality of life for men with advanced prostate cancer.

OBJECTIVE: To examine the extent to which mindfulness skills influence psychological distress and health-related quality of life (HRQOL) in men with metastatic or castration-resistant biochemical progression of prostate cancer. PATIENTS AND METHODS: A cross-sectional survey of 190 men (46 % response; mean age 71 years, SD = 8.7, range 40-91 years) with advanced prostate cancer, assessed psychological and cancer-specific distress, HRQOL. Mindfulness skills were assessed as potential predictors of adjustment outcomes. RESULTS: Overall, 39 % of men reported high psychological distress. One third had accessed psychological support previously although only 10 % were under current psychological care. One quarter had accessed a prostate cancer support group in the past six months. Higher HRQOL and lower cancer-specific and global psychological distress were related to non-judging of inner experience (p < 0.001). Higher HRQOL and lower psychological distress were related to acting with awareness (p < 0.001). Lower distress was also related to higher non-reactivity to inner experience and a lower level of observing (p < 0.05). CONCLUSIONS: Men with advanced prostate cancer are at risk of poor psychological outcomes. Psychological flexibility may be a promising target for interventions to improve adjustment outcomes in this patient group. CLINICAL TRIAL REGISTRY: Trial Registration: ACTRN12612000306819

Allocating the Burdens of Climate Action: Consumption-Based Carbon Accounting and the Polluter-Pays Principle

Action must be taken to combat climate change. Yet, how the costs of climate action should be allocated among states remains a question. One popular answer—the polluter-pays principle (PPP)—stipulates that those responsible for causing the problem should pay to address it. While intuitively plausible, the PPP has been subjected to withering criticism in recent years. It is timely, following the Paris Agreement, to develop a new version: one that does not focus on historical production-based emissions but rather allocates climate burdens in proportion to each state’s annual consumption-based emissions. This change in carbon accounting results in a fairer and more environmentally effective principle for distributing climate duties

Stochastic population growth in spatially heterogeneous environments

Classical ecological theory predicts that environmental stochasticity increases extinction risk by reducing the average per-capita growth rate of populations. To understand the interactive effects of environmental stochasticity, spatial heterogeneity, and dispersal on population growth, we study the following model for population abundances in $n$ patches: the conditional law of $X_{t+dt}$ given $X_t=x$ is such that when $dt$ is small the conditional mean of $X_{t+dt}^i-X_t^i$ is approximately $[x^i\mu_i+\sum_j(x^j D_{ji}-x^i D_{ij})]dt$, where $X_t^i$ and $\mu_i$ are the abundance and per capita growth rate in the $i$-th patch respectivly, and $D_{ij}$ is the dispersal rate from the $i$-th to the $j$-th patch, and the conditional covariance of $X_{t+dt}^i-X_t^i$ and $X_{t+dt}^j-X_t^j$ is approximately $x^i x^j \sigma_{ij}dt$. We show for such a spatially extended population that if $S_t=(X_t^1+...+X_t^n)$ is the total population abundance, then $Y_t=X_t/S_t$, the vector of patch proportions, converges in law to a random vector $Y_\infty$ as $t\to\infty$, and the stochastic growth rate $\lim_{t\to\infty}t^{-1}\log S_t$ equals the space-time average per-capita growth rate \sum_i\mu_i\E[Y_\infty^i] experienced by the population minus half of the space-time average temporal variation \E[\sum_{i,j}\sigma_{ij}Y_\infty^i Y_\infty^j] experienced by the population. We derive analytic results for the law of $Y_\infty$, find which choice of the dispersal mechanism $D$ produces an optimal stochastic growth rate for a freely dispersing population, and investigate the effect on the stochastic growth rate of constraints on dispersal rates. Our results provide fundamental insights into "ideal free" movement in the face of uncertainty, the persistence of coupled sink populations, the evolution of dispersal rates, and the single large or several small (SLOSS) debate in conservation biology.Comment: 47 pages, 4 figure

A performance evaluation of a novel human recombinant tissue factor prothrombin time reagent (Revohem (TM) PT)

Summary Introduction A new prothrombin time reagent (Revohem™ PT) based on recombinant human tissue factor produced by the silkworm-baculovirus expression system was tested. The aim of this study was to compare the performance of the new PT reagent with two widely used routine PT reagents. Methods All testing was performed on a Sysmex CS-5100 coagulometer. Revohem™ PT was tested for imprecision and stability using normal and abnormal lyophilized commercial control plasmas. Comparability was assessed with two widely used reagents: one containing recombinant human tissue factor (Reagent A) and the other a human placental thromboplastin (Reagent B) using a wide range of normal and abnormal plasmas and analyser-specific ISI values. Results Excellent between-day imprecision was obtained for Revohem™ PT (CV <1.0%) and acceptable open-vial on-board stability over 7 days. There was good agreement between methods in samples from patients with liver disease and patients receiving warfarin and no significant differences between methods with increasing INR values. Both recombinant reagents suffered less interference from lupus anticoagulant than the placental thromboplastin. Revohem™ PT had similar sensitivity to reagents A and B for FII, V, VII and X deficiency and demonstrated dose responsiveness to dabigatran, apixaban and rivaroxaban with steeper response curves than the comparison reagents. Conclusion Revohem™ PT showed comparable or improved performance relative to two widely used reagents and is suitable for use in warfarin control, detection of inherited factor II, V, VII and X deficiency and assessment of liver disease coagulopathy

Policy Coherence in US Tobacco Control: Beyond FDA Regulation

Joshua Yang and Thomas Novotny explore whether the US government can develop and implement a coherent policy agenda to reduce tobacco-related morbidity and mortality

A major genetic locus in <i>Trypanosoma brucei</i> is a determinant of host pathology

The progression and variation of pathology during infections can be due to components from both host or pathogen, and/or the interaction between them. The influence of host genetic variation on disease pathology during infections with trypanosomes has been well studied in recent years, but the role of parasite genetic variation has not been extensively studied. We have shown that there is parasite strain-specific variation in the level of splenomegaly and hepatomegaly in infected mice and used a forward genetic approach to identify the parasite loci that determine this variation. This approach allowed us to dissect and identify the parasite loci that determine the complex phenotypes induced by infection. Using the available trypanosome genetic map, a major quantitative trait locus (QTL) was identified on T. brucei chromosome 3 (LOD = 7.2) that accounted for approximately two thirds of the variance observed in each of two correlated phenotypes, splenomegaly and hepatomegaly, in the infected mice (named &lt;i&gt;TbOrg1&lt;/i&gt;). In addition, a second locus was identified that contributed to splenomegaly, hepatomegaly and reticulocytosis (&lt;i&gt;TbOrg2&lt;/i&gt;). This is the first use of quantitative trait locus mapping in a diploid protozoan and shows that there are trypanosome genes that directly contribute to the progression of pathology during infections and, therefore, that parasite genetic variation can be a critical factor in disease outcome. The identification of parasite loci is a first step towards identifying the genes that are responsible for these important traits and shows the power of genetic analysis as a tool for dissecting complex quantitative phenotypic traits

Statistical challenges in the development and evaluation of marker-based clinical tests

Exciting new technologies for assessing markers in human specimens are now available to evaluate unprecedented types and numbers of variations in DNA, RNA, proteins, or biological structures such as chromosomes. These markers, whether viewed individually, or collectively as a 'signature', have the potential to be useful for disease risk assessment, screening, early detection, prognosis, therapy selection, and monitoring for therapy effectiveness or disease recurrence. Successful translation from basic research findings to clinically useful test requires basic, translational, and regulatory sciences and a collaborative effort among individuals with varied types of expertise including laboratory scientists, technology developers, clinicians, statisticians, and bioinformaticians. The focus of this commentary is the many statistical challenges in translational marker research, specifically in the development and validation of marker-based tests that have clinical utility for therapeutic decision-making