Intimal hyperplasia following implantation of helical-centreline and straight-centreline stents in common carotid arteries in healthy pigs: influence of intraluminal flow

Intimal hyperplasia (IH) is a leading cause of obstruction of vascular interventions, including arterial stents, bypass grafts and arteriovenous grafts and fistulae. Proposals to account for arterial stent-associated IH include wall damage, low wall shear stress (WSS), disturbed flow and, although not widely recognized, wall hypoxia. The common non-planarity of arterial geometry and flow, led us to develop a bare-metal, nitinol, self-expanding stent with three-dimensional helical-centreline geometry. This was deployed in one common carotid artery of healthy pigs, with a straight-centreline, but otherwise identical (conventional) stent deployed contralaterally. Both stent types deformed the arteries, but the helical-centreline device additionally deformed them helically and caused swirling of intraluminal flow. At sacrifice, one month post stent deployment, histology revealed significantly less IH in the helical-centreline than straight-centreline stented vessels. Medial cross-sectional area was not significantly different in helical-centreline than straight-centreline stented vessels. By contrast, luminal cross-sectional area was significantly larger in helical-centreline than straight-centreline stented vessels. Mechanisms considered to account for those results include enhanced intraluminal WSS and enhanced intraluminal blood–vessel wall mass transport, including of oxygen, in the helical-centreline stented vessels. Consistent with the latter proposal, adventitial microvessel density was lower in the helical-centreline stented than straight-centreline stented vessels

Emplacement of inflated Pāhoehoe flows in the Naude’s Nek Pass, Lesotho remnant, Karoo continental flood basalt province: use of flow-lobe tumuli in understanding flood basalt emplacement

Physical volcanological features are presented for a 710-m-thick section, of the Naude’s Nek Pass, within the lower part of the Lesotho remnant of the Karoo Large Igneous Province. The section consists of inflated pāhoehoe lava with thin, impersistent sedimentary interbeds towards the base. There are seven discreet packages of compound and hummocky pāhoehoe lobes containing flow-lobe tumuli, making up approximately 50% of the section. Approximately 45% of the sequence consists of 14 sheet lobes, between 10 and 52-m-thick. The majority of the sheet lobes are in two packages indicating prolonged periods of lava supply capable of producing thick sheet lobes. The other sheet lobes are as individual lobes or pairs, within compound flows, suggesting brief increases in lava supply rate. We suggest, contrary to current belief, that there is no evidence that compound flows are proximal to source and sheet lobes (simple flows) are distal to source and we propose that the presence of flow-lobe tumuli in compound flows could be an indicator that a flow is distal to source. We use detailed, previously published, studies of the Thakurvadi Formation (Deccan Traps) as an example. We show that the length of a lobe and therefore the sections that are ‘medial or distal to source’ are specific to each individual lobe and are dependent on the lava supply of each eruptive event, and as such flow lobe tumuli can be used as an indicator of relative distance from source

Serratamolide is a hemolytic factor produced by Serratia marcescens

Serratia marcescens is a common contaminant of contact lens cases and lenses. Hemolytic factors of S. marcescens contribute to the virulence of this opportunistic bacterial pathogen. We took advantage of an observed hyper-hemolytic phenotype of crp mutants to investigate mechanisms of hemolysis. A genetic screen revealed that swrW is necessary for the hyper-hemolysis phenotype of crp mutants. The swrW gene is required for biosynthesis of the biosurfactant serratamolide, previously shown to be a broad-spectrum antibiotic and to contribute to swarming motility. Multicopy expression of swrW or mutation of the hexS transcription factor gene, a known inhibitor of swrW expression, led to an increase in hemolysis. Surfactant zones and expression from an swrW-transcriptional reporter were elevated in a crp mutant compared to the wild type. Purified serratamolide was hemolytic to sheep and murine red blood cells and cytotoxic to human airway and corneal limbal epithelial cells in vitro. The swrW gene was found in the majority of contact lens isolates tested. Genetic and biochemical analysis implicate the biosurfactant serratamolide as a hemolysin. This novel hemolysin may contribute to irritation and infections associated with contact lens use. © 2012 Shanks et al

Carbon budget for 1.5 and 2oC targets lowered by natural wetland and permafrost feedbacks

Methane emissions from natural wetlands and carbon release from permafrost thaw have a positive feedback on climate, yet are not represented in most state-of-the-art climate models. Furthermore, a fraction of the thawed permafrost carbon is released as methane, enhancing the combined feedback strength. We present simulations with an intermediate complexity climate model which follow prescribed global warming pathways to stabilisation at 1.5°C or 2.0°C above pre-industrial levels by the year 2100, and that incorporates a state-of-the-art global land surface model with updated descriptions of wetland and permafrost carbon release. We demonstrate that the climate feedbacks from those two processes are substantial. Specifically, permissible anthropogenic fossil fuel CO2 emission budgets are reduced by 17-23% (47-56 GtC) for stabilisation at 1.5°C, and 9-13% (52-57 GtC) for 2.0°C stabilisation. In our simulations these feedback processes respond faster at temperatures below 1.5°C, and the differences between the 1.5°C and 2°C targets are disproportionately small. This key finding is due to our interest in transient emission pathways to the year 2100 and does not consider the longer term implications of these feedback processes. We conclude that natural feedback processes from wetlands and permafrost must be considered in assessments of transient emission pathways to limit global warming

Does strabismus surgery improve quality and mood, and what factors influence this?

Aims To establish the impact of adult strabismus surgery on clinical and psychosocial well-being and determine who experiences the greatest benefit from surgery and how one could intervene to improve quality of life post-surgery. Methods A longitudinal study, with measurements taken pre-surgery and at 3 and 6 months post-surgery. All participants completed the AS-20 a disease specific quality of life scale, along with measures of mood, strabismus and appearance-related beliefs and cognitions and perceived social support. Participants also underwent a full orthoptic assessment at their preoperative visit and again 3 months postoperatively. Clinical outcomes of surgery were classified as success, partial success or failure, using the largest angle of deviation, diplopia and requirement for further therapy. Results 210 participants took part in the study. Strabismus surgery led to statistically significant improvements in psychosocial and functional quality of life. Those whose surgery was deemed a partial success did however experience a deterioration in quality of life. A combination of clinical variables, high expectations, and negative beliefs about the illness and appearance pre-surgery were significant predictors of change in quality of life from pre- to post-surgery. Conclusions Strabismus surgery leads to significant improvements in quality of life up to 6 months postoperatively. There are however a group of patients who do not experience these benefits. A series of clinical and psychosocial factors have now been identified, which will enable clinicians to identify patients who may be vulnerable to poorer outcomes post-surgery and allow for the development of interventions to improve quality of life after surgery

Practical nutritional recovery strategies for elite soccer players when limited time separates repeated matches

Specific guidelines that aim to facilitate the recovery of soccer players from the demands of training and a congested fixture schedule are lacking; especially in relation to evidence-based nutritional recommendations. The importance of repeated high level performance and injury avoidance while addressing the challenges of fixture scheduling, travel to away venues, and training commitments requires a strategic and practically feasible method of implementing specific nutritional strategies. Here we present evidence-based guidelines regarding nutritional recovery strategies within the context of soccer. An emphasis is placed on providing practically applicable guidelines for facilitation of recovery when multiple matches are played within a short period of time (i.e. 48 h). Following match-play, the restoration of liver and muscle glycogen stores (via consumption of ~1.2 gkg-1h-1 of carbohydrate) and augmentation of protein synthesis (via ~40 g of protein) should be prioritised in the first 20 minutes of recovery. Daily intakes of 6-10 gkg-1 body mass of carbohydrate are recommended when limited time separates repeated matches while daily protein intakes of >1.5 gkg-1 body mass should be targeted; possibly in the form of multiple smaller feedings (e.g., 6 x 20-40 g). At least 150% of the body mass lost during exercise should be consumed within 1 h and electrolytes added such that fluid losses are ameliorated. Strategic use of protein, leucine, creatine, polyphenols and omega-3 supplements could also offer practical means of enhancing post-match recovery. Keywords: soccer, nutrition, recovery, polyphenols, omega-3, creatine, fixture, congestio

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Dengue in Thailand and Cambodia: An Assessment of the Degree of Underrecognized Disease Burden Based on Reported Cases

Dengue is a major public health problem especially in tropical and subtropical countries of Asia and Latin-America. An effective dengue vaccine is not yet available, but several vaccine candidates are currently being evaluated in clinical trials. Accurate country-level incidence data are crucial to assess the cost-effectiveness of such vaccines and will assist policy-makers in making vaccine introduction decisions. Existing national surveillance systems are often passive and are designed to monitor trends and to detect disease outbreaks. Our analyses of data from prospectively followed cohorts with laboratory confirmation of dengue cases show that, in Thailand and Cambodia, dengue incidence is underrecognized by more than 8-fold. The magnitude of the outpatient burden caused by dengue is not assessed or reflected by the national surveillance data. We estimate that a median of more than 340,000 symptomatic dengue virus infections occurred annually in children less than 15 years of age in Thailand in Cambodia between 2003 and 2007

Chapter 11: Challenges in and Principles for Conducting Systematic Reviews of Genetic Tests used as Predictive Indicators

In this paper, we discuss common challenges in and principles for conducting systematic reviews of genetic tests. The types of genetic tests discussed are those used to 1). determine risk or susceptibility in asymptomatic individuals; 2). reveal prognostic information to guide clinical management in those with a condition; or 3). predict response to treatments or environmental factors. This paper is not intended to provide comprehensive guidance on evaluating all genetic tests. Rather, it focuses on issues that have been of particular concern to analysts and stakeholders and on areas that are of particular relevance for the evaluation of studies of genetic tests. The key points include:The general principles that apply in evaluating genetic tests are similar to those for other prognostic or predictive tests, but there are differences in how the principles need to be applied or the degree to which certain issues are relevant.A clear definition of the clinical scenario and an analytic framework is important when evaluating any test, including genetic tests.Organizing frameworks and analytic frameworks are useful constructs for approaching the evaluation of genetic tests.In constructing an analytic framework for evaluating a genetic test, analysts should consider preanalytic, analytic, and postanalytic factors; such factors are useful when assessing analytic validity.Predictive genetic tests are generally characterized by a delayed time between testing and clinically important events.Finding published information on the analytic validity of some genetic tests may be difficult. Web sites (FDA or diagnostic companies) and gray literature may be important sources.In situations where clinical factors associated with risk are well characterized, comparative effectiveness reviews should assess the added value of using genetic testing along with known factors compared with using the known factors alone.For genome-wide association studies, reviewers should determine whether the association has been validated in multiple studies to minimize both potential confounding and publication bias. In addition, reviewers should note whether appropriate adjustments for multiple comparisons were used

Tumor to normal single-cell mRNA comparisons reveal a pan-neuroblastoma cancer cell

Neuroblastoma is a childhood cancer that resembles developmental stages of the neural crest. It is not established what developmental processes neuroblastoma cancer cells represent. Here, we sought to reveal the phenotype of neuroblastoma cancer cells by comparing cancer (n = 19,723) with normal fetal adrenal single-cell transcriptomes (n = 57,972). Our principal finding was that the neuroblastoma cancer cell resembled fetal sympathoblasts, but no other fetal adrenal cell type. The sympathoblastic state was a universal feature of neuroblastoma cells, transcending cell cluster diversity, individual patients, and clinical phenotypes. We substantiated our findings in 650 neuroblastoma bulk transcriptomes and by integrating canonical features of the neuroblastoma genome with transcriptional signals. Overall, our observations indicate that a pan-neuroblastoma cancer cell state exists, which may be attractive for novel immunotherapeutic and targeted avenues