16th International Congress on Antiphospholipid Antibodies Task Force Report on Antiphospholipid Syndrome Treatment Trends

Antiphospholipid syndrome (APS), an acquired autoimmune thrombophilia, is characterised by thrombosis and/or pregnancy morbidity in association with persistent antiphospholipid antibodies. The 16th International Congress on Antiphospholipid Antibodies Task Force on APS Treatment Trends reviewed the current status with regard to existing and novel treatment trends for APS, which is the focus of this Task Force report. The report addresses current treatments and developments since the last report, on the use of direct oral anticoagulants in patients with APS, antiplatelet agents, adjunctive therapies (hydroxychloroquine, statins and vitamin D), targeted treatment including rituximab, belimumab, and anti-TNF agents, complement inhibition and drugs based on peptides of beta-2-glycoprotein I. In addition, the report summarises potential new players, including coenzyme Q10, adenosine receptor agonists and adenosine potentiation. In each case, the report provides recommendations for clinicians, based on the current state of the art, and suggests a clinical research agenda. The initiation and development of appropriate clinical studies requires a focus on devising suitable outcome measures, including a disease activity index, an optimal damage index, and a specific quality of life index

The structure of the PapD-PapGII pilin complex reveals an open and flexible P5 pocket

P pili are hairlike polymeric structures that mediate binding of uropathogenic Escherichia coli to the surface of the kidney via the PapG adhesin at their tips. PapG is composed of two domains: a lectin domain at the tip of the pilus followed by a pilin domain that comprises the initial polymerizing subunit of the 1,000-plus-subunit heteropolymeric pilus fiber. Prior to assembly, periplasmic pilin domains bind to a chaperone, PapD. PapD mediates donor strand complementation, in which a beta strand of PapD temporarily completes the pilin domain's fold, preventing premature, nonproductive interactions with other pilin subunits and facilitating subunit folding. Chaperone-subunit complexes are delivered to the outer membrane usher where donor strand exchange (DSE) replaces PapD's donated beta strand with an amino-terminal extension on the next incoming pilin subunit. This occurs via a zip-in-zip-out mechanism that initiates at a relatively accessible hydrophobic space termed the P5 pocket on the terminally incorporated pilus subunit. Here, we solve the structure of PapD in complex with the pilin domain of isoform II of PapG (PapGIIp). Our data revealed that PapGIIp adopts an immunoglobulin fold with a missing seventh strand, complemented in parallel by the G1 PapD strand, typical of pilin subunits. Comparisons with other chaperone-pilin complexes indicated that the interactive surfaces are highly conserved. Interestingly, the PapGIIp P5 pocket was in an open conformation, which, as molecular dynamics simulations revealed, switches between an open and a closed conformation due to the flexibility of the surrounding loops. Our study reveals the structural details of the DSE mechanism

Data-driven quality improvement program to prevent hospitalisation and improve care of people living with coronary heart disease: Protocol for a process evaluation

Background: Practice-level quality improvement initiatives using rapidly advancing technology offers a multidimensional approach to reduce cardiovascular disease burden. For the “QUality improvement in primary care to prevent hospitalisations and improve Effectiveness and efficiency of care for people Living with heart disease” (QUEL) cluster randomised controlled trial, a 12-month quality improvement intervention was designed for primary care practices to use data and implement progressive changes using “Plan, Do, Study, Act” cycles within their practices with training in a series of interactive workshops. This protocol aims to describe the systematic methods to conduct a process evaluation of the data-driven intervention within the QUEL study. Methods: A mixed-method approach will be used to conduct the evaluation. Quantitative data collected throughout the intervention period, via surveys and intervention materials, will be used to (1) identify the key elements of the intervention and how, for whom and in what context it was effective; (2) determine if the intervention is delivered as intended; and (3) describe practice engagement, commitment and capacity associated with various intervention components. Qualitative data, collected via semi-structured interviews and open-ended questions, will be used to gather in-depth understanding of the (1) satisfaction, utility, barriers and enablers; (2) acceptability, uptake and feasibility, and (3) effect of the COVID-19 pandemic on the implementation of the intervention. Conclusion: Findings from the evaluation will provide new knowledge on the implementation of a complex, multi-component intervention at practice-level using their own electronic patient data to enhance secondary prevention of cardiovascular disease. Trial registration: Australian New Zealand Clinical Trials Registry (ANZCTR) number ACTRN12619001790134

Estimating the Associations between Big Five Personality Traits, Testosterone, and Cortisol

OBJECTIVE: Hormones are often conceptualized as biological markers of individual differences and have been associated with a variety of behavioral indicators and characteristics, such as mating behavior or acquiring and maintaining dominance. However, before researchers create strong theoretical models for how hormones modulate individual and social behavior, information on how hormones are associated with dominant models of personality is needed. Although there have been some studies attempting to quantify the associations between personality traits, testosterone, and cortisol, there are many inconsistencies across these studies. METHODS: In this registered report, we examined associations between testosterone, cortisol, and Big Five personality traits. We aggregated 25 separate samples to yield a single sample of 3964 (50.3% women; 27.7% of women were on hormonal contraceptives). Participants completed measures of personality and provided saliva samples for testosterone and cortisol assays. RESULTS: The results from multi-level models and meta-analyses revealed mostly weak, non-significant associations between testosterone or cortisol and personality traits. The few significant effects were still very small in magnitude (e.g., testosterone and conscientiousness: r = −0.05). A series of moderation tests revealed that hormone-personality associations were mostly similar in men and women, those using hormonal contraceptives or not, and regardless of the interaction between testosterone and cortisol (i.e., a variant of the dual-hormone hypothesis). CONCLUSIONS: Altogether, we did not detect many robust associations between Big Five personality traits and testosterone or cortisol. The findings are discussed in the context of biological models of personality and the utility of examining heterogeneity in hormone-personality associations

Two Bee-Pollinated Plant Species Show Higher Seed Production when Grown in Gardens Compared to Arable Farmland

Background Insect pollinator abundance, in particular that of bees, has been shown to be high where there is a super-abundance of floral resources; for example in association with mass-flowering crops and also in gardens where flowering plants are often densely planted. Since land management affects pollinator numbers, it is also likely to affect the resultant pollination of plants growing in these habitats. We hypothesised that the seed or fruit set of two plant species, typically pollinated by bumblebees and/or honeybees might respond in one of two ways: 1) pollination success could be reduced when growing in a floriferous environment, via competition for pollinators, or 2) pollination success could be enhanced because of increased pollinator abundance in the vicinity. Methodology/Principal Findings We compared the pollination success of experimental plants of Glechoma hederacea L. and Lotus corniculatus L. growing in gardens and arable farmland. On the farms, the plants were placed either next to a mass-flowering crop (oilseed rape, Brassica napus L. or field beans, Vicia faba L.) or next to a cereal crop (wheat, Triticum spp.). Seed set of G. hederacea and fruit set of L. corniculatus were significantly higher in gardens compared to arable farmland. There was no significant difference in pollination success of G. hederacea when grown next to different crops, but for L. corniculatus, fruit set was higher in the plants growing next to oilseed rape when the crop was in flower. Conclusions/Significance The results show that pollination services can limit fruit set of wild plants in arable farmland, but there is some evidence that the presence of a flowering crop can facilitate their pollination (depending on species and season). We have also demonstrated that gardens are not only beneficial to pollinators, but also to the process of pollination

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

Atlantic Ocean influence on a shift in European climate in the 1990s

European climate exhibits variability on a wide range of timescales. Understanding the nature and drivers of this variability is an essential step in developing robust climate predictions and risk assessments. The Atlantic Ocean has been suggested as an important driver of variability in European climate on decadal timescales1, but the importance of this influence in recent decades has been unclear, partly because of difficulties in separating the influence of the Atlantic Ocean from other contributions, for example, from the tropical Pacific Ocean and the stratosphere. Here we analyse four data sets derived from observations to show that, during the 1990s, there was a substantial shift in European climate towards a pattern characterized by anomalously wet summers in northern Europe, and hot, dry, summers in southern Europe, with related shifts in spring and autumn. These changes in climate coincided with a substantial warming of the North Atlantic Ocean, towards a state last seen in the 1950s. The patterns of European climate change in the 1990s are consistent with earlier changes attributed to the influence of the North Atlantic Ocean, and provide compelling evidence that the Atlantic Ocean was the key driver. Our results suggest that the recent pattern of anomalies in European climate will persist as long as the North Atlantic Ocean remains anomalously warm

Alcohol policy enforcement and changes in student drinking rates in a statewide public college system: a follow-up study

<p>Abstract</p> <p>Background</p> <p>Heavy alcohol use among U.S. college students is a major contributor to young adult morbidity and mortality. The aim of this study was to examine whether college alcohol policy enforcement levels predict changes in student drinking and related behaviors in a state system of public colleges and universities, following a system-wide change to a stricter policy.</p> <p>Methods</p> <p>Students and administrators at 11 Massachusetts public colleges/universities completed surveys in 1999 (N of students = 1252), one year after the policy change, and again in 2001 (N = 1074). We calculated policy enforcement scores for each school based on the reports of deans of students, campus security chiefs, and students, and examined the correlations between perceived enforcement levels and the change in student drinking rates over the subsequent two year period, after weighting the 2001 data to adjust for demographic changes in the student body.</p> <p>Results</p> <p>Overall rates of any past-30-days drinking, heavy episodic drinking, and usual heavy drinking among past-30-days drinkers were all lower in 2001 compared to 1999. School-level analyses (N = 11) found deans' baseline reports of stricter enforcement were strongly correlated with subsequent declines in heavy episodic drinking (Pearson's r = -0.73, p = 0.011). Moreover, consistently high enforcement levels across time, as reported by deans, were associated with greater declines in heavy episodic drinking. Such relationships were not found for students' and security chiefs' reports of enforcement. Marijuana use did not rise during this period of decline in heavy drinking.</p> <p>Conclusions</p> <p>Study findings suggest that stronger enforcement of a stricter alcohol policy may be associated with reductions in student heavy drinking rates over time. An aggressive enforcement stance by deans may be an important element of an effective college alcohol policy.</p