Prior events predict cerebrovascular and coronary outcomes in the PROGRESS trial

<p><b>Background and Purpose:</b> The relationship between baseline and recurrent vascular events may be important in the targeting of secondary prevention strategies. We examined the relationship between initial event and various types of further vascular outcomes and associated effects of blood pressure (BP)–lowering.</p> <p><b>Methods:</b> Subsidiary analyses of the Perindopril Protection Against Recurrent Stroke Study (PROGRESS) trial, a randomized, placebo-controlled trial that established the benefits of BP–lowering in 6105 patients (mean age 64 years, 30% female) with cerebrovascular disease, randomly assigned to either active treatment (perindopril for all, plus indapamide in those with neither an indication for, nor a contraindication to, a diuretic) or placebo(s).</p> <p><b>Results:</b> Stroke subtypes and coronary events were associated with 1.5- to 6.6-fold greater risk of recurrence of the same event (hazard ratios, 1.51 to 6.64; P=0.1 for large artery infarction, P<0.0001 for other events). However, 46% to 92% of further vascular outcomes were not of the same type. Active treatment produced comparable reductions in the risk of vascular outcomes among patients with a broad range of vascular events at entry (relative risk reduction, 25%; P<0.0001 for ischemic stroke; 42%, P=0.0006 for hemorrhagic stroke; 17%, P=0.3 for coronary events; P homogeneity=0.4).</p> <p><b>Conclusions:</b> Patients with previous vascular events are at high risk of recurrences of the same event. However, because they are also at risk of other vascular outcomes, a broad range of secondary prevention strategies is necessary for their treatment. BP–lowering is likely to be one of the most effective and generalizable strategies across a variety of major vascular events including stroke and myocardial infarction.</p&gt

Dynamical density functional theory for the evaporation of droplets of nanoparticle suspension

We develop a lattice gas model for the drying of droplets of a nanoparticle suspension on a planar surface, using dynamical density functional theory (DDFT) to describe the time evolution of the solvent and nanoparticle density profiles. The DDFT assumes a diffusive dynamics but does not include the advective hydrodynamics of the solvent, so the model is relevant to highly viscous or near to equilibrium systems. Nonetheless, we see an equivalent of the coffee-ring stain effect, but in the present model it occurs for thermodynamic rather the fluid-mechanical reasons. The model incorporates the effect of phase separation and vertical density variations within the droplet and the consequence of these on the nanoparticle deposition pattern on the surface. We show how to include the effect of slip or no-slip at the surface and how this is related to the receding contact angle. We also determine how the equilibrium contact angle depends on the microscopic interaction parameters.Comment: 35 pages, 10 figure

Bronchiectasis insanity:Doing the same thing over and over again and expecting different results?

Bronchiectasis is an increasingly common disease with a significant impact on quality of life and morbidity of affected patients. It is also a very heterogeneous disease with numerous different underlying etiologies and presentations. Most treatments for bronchiectasis are based on low-quality evidence; consequently, no treatments have been approved by the US Food and Drug Administration or the European Medicines Agency for the treatment of bronchiectasis. The last several years have seen numerous clinical trials in which the investigational agent, thought to hold great promise, did not demonstrate a clinically or statistically significant benefit. This commentary will review the likely reasons for these disappointing results and a potential approach that may have a greater likelihood of defining evidence-based treatment for bronchiectasis

Research ethics committees: agents of research policy?

The purpose of this commentary is to describe the unintended effects ethics committees may have on research and to analyse the regulatory and administrative problems of clinical trials. DISCUSSION: The Finnish law makes an arbitrary distinction between medical research and other health research, and the European Union's directive for good clinical trials further differentiates drug trials. The starting point of current rules is that clinical trials are lesser in the interest of patients and society than routine health care. However, commercial interests are not considered unethical. The contrasting procedures in research and normal health care may tempt physicians to continue introducing innovations into practice by relying on unsystematic and uncontrolled observations. Tedious and bureaucratic rules may lead to the disappearance of trials initiated by researchers. Trying to accommodate the special legislative requirements for new drug trials into more complex interventions may result in poor designs with unreliable results and increased costs. Meanwhile, current legal requirements may undermine the morale of ethics committee members. CONCLUSION: The aims and the quality of the work of ethics committees should be evaluated, and a reformulation of the EU directive on good clinical trials is needed. Ethical judgement should consider the specific circumstance of each trial, and ethics committees should not foster poor research for legal reasons

Impact of Model Choice When Studying the Relationship Between Blood Pressure Variability and Risk of Stroke Recurrence

Long-term blood pressure variability (BPV), an increasingly recognized vascular risk factor, is challenging to analyze. The objective was to assess the impact of BPV modeling on its estimated effect on the risk of stroke. We used data from a secondary stroke prevention trial, PROGRESS (Perindopril Protection Against Stroke Study), which included 6105 subjects. The median number of blood pressure (BP) measurements was 12 per patient and 727 patients experienced a first stroke recurrence over a mean follow-up of 4.3 years. Hazard ratios (HRs) of BPV were estimated from 6 proportional hazards models using different BPV modeling for comparison purposes. The 3 commonly used methods first derived SD of BP measures observed over a given period of follow-up and then used it as a fixed covariate in a Cox model. The 3 more advanced modeling accounted for changes in BP or BPV over time in a single-stage analysis. While the 3 commonly used methods produced contradictory results (for a 5 mmHg increase in BPV, HR=0.75 [95% CI, 0.68-0.82], HR=0.99 [0.91-1.08], HR=1.19 [1.10-1.30]), the 3 more advanced modeling resulted in a similar moderate positive association (HR=1.08 [95% CI, 0.99-1.17]), whether adjusted for BP at randomization or mean BP over the follow-up. The method used to assess BPV strongly affects its estimated effect on the risk of stroke, and should be chosen with caution. Further methodological developments are needed to account for the dynamics of both BP and BPV over time, to clarify the specific role of BPV

Clinical examination for hyperlinear palms to determine filaggrin genotype:a diagnostic test accuracy study

BackgroundPalmar hyperlinearity is a feature of ichthyosis vulgaris, the monogenic skin disorder caused by FLG loss-of-function mutations.ObjectiveTo investigate how well the presence or absence of hyperlinear palms (HLP) detect FLG genotype in children.MethodsSTARD criteria are used to report this diagnostic accuracy study. Phenotype and genotype data (four most prevalent FLG null mutations) were obtained from a total of 3656 children in three studies: the UK CLOTHES trial (children 1–5 years with moderate–severe atopic eczema); UK BEEP trial (2 year olds at high risk of developing atopic eczema); UK-Irish eczema case collection (0–16 year olds with atopic eczema). All participants included in analyses of HLP as the index test and FLG genotype as the reference were of white European ancestry.ResultsThirty-two percent of participants (1159/3656) had FLG null mutation(s) and 37% (1347/3656) had HLP. In 13% (464/3656), HLP was recorded as ‘unsure’ or not recorded. The sensitivity and specificity of HLP for detecting FLG mutations in each of the studies was: 67% (95% CI 55–78%) and 75% (67–82%) in CLOTHES; 46% (36–55%) and 89% (86–91%) in BEEP; 72% (68–75%) and 60% (57–62%) in the UK-Irish case collection. Positive and negative likelihood ratios were: 2.73 (1.95–3.81) and 0.44 (0.31–0.62) in CLOTHES; 4.02 (2.99–5.40) and 0.61 (0.52–0.73) in BEEP; 1.79 (1.66–1.93) and 0.47 (0.42–0.53) in the UK-Irish collection.DiscussionTrained observers were able to define palmar hyperlinearity in the majority (3191/3656, 87%) of cases. The presence of HLP is not a reliable sign to detect FLG mutations, but the absence of HLP excludes FLG null genotype with a reasonable degree of certainty

LXR\u3csup\u3eTM\u3c/sup\u3e White Clover: Development of Transgenic White Clover (\u3cem\u3eTrifolium Repens\u3c/em\u3e) with Delayed Leaf Senescence

Leaf senescence is a type of programmed cell death characterized by loss of chlorophyll, lipids, protein, and RNA. Cytokinins are a class of plant hormones that play roles in many aspects of plant growth and development, including leaf senescence, apical dominance, the formation and activity of shoot meristems, nutrient mobilization, seed germination, and pathogen responses. They also appear to mediate a number of light- regulated processes, such as de-etiolation and chloroplast differentiation. It is known that the concentrations of endogenous cytokinins decline in plant tissues as senescence progresses. This observation provides the opportunity to manipulate the senescence program in transgenic plants to enhance biomass and seed production, through the regulated expression of cytokinin biosynthesis genes

RevManHAL: towards automatic text generation in systematic reviews

Background: Systematic reviews are a key part of healthcare evaluation. They involve important painstaking but repetitive work. A major producer of systematic reviews, the Cochrane Collaboration, employs Review Manager (RevMan) programme—a software which assists reviewers and produces XML-structured files. This paper describes an add-on programme (RevManHAL) which helps auto-generate the abstract, results and discussion sections of RevMan-generated reviews in multiple languages. The paper also describes future developments for RevManHAL. Methods: RevManHAL was created in Java using NetBeans by a programmer working full time for 2 months. Results: The resulting open-source programme uses editable phrase banks to envelop text/numbers from within the prepared RevMan file in formatted readable text of a chosen language. In this way, considerable parts of the review’s ‘abstract’, ‘results’ and ‘discussion’ sections are created and a phrase added to ‘acknowledgements’. Conclusion: RevManHAL’s output needs to be checked by reviewers, but already, from our experience within the Cochrane Schizophrenia Group (200 maintained reviews, 900 reviewers), RevManHAL has saved much time which is better employed thinking about the meaning of the data rather than restating them. Many more functions will become possible as review writing becomes increasingly automated