Explore the vast range of titles available.

Degraded by shear stress, loss of high-molecular-weight multimers of von Willebrand factor (VWF) correlates strongly with pressure gradient in aortic stenosis (AS) and obstructive hypertrophic cardiomyopathy (HC). We assessed VWF tests before and after interventions in HC and contrasted the severity of abnormalities in HC to patients with AS, mitral regurgitation, and left ventricular assist devices. Ninety patients with median (interquartile range) age 66 (53 to 72) years, 51% men, with HC had assessments of 3 VWF parameters and B-type natriuretic peptide before and after 26 discreet medical/pacing interventions, 22 alcohol septal ablations, and 28 ventricular septal myectomies. VWF multimers were abnormal in 87% of patients with obstructive HC versus 48% of patients with latent obstruction (p = 0.0001). VWF measurements correlated with peak instantaneous left ventricular outflow tract gradient, Spearman ρ 0.51 to 0.61, p <0.0001. For B-type natriuretic peptide, correlation with left ventricular outflow tract gradient was weaker, ρ = 0.37, p = 0.0005, but stronger with septal thickness or mitral E/e'. In pre-/post-medical treatment of HC, VWF multimers were abnormal in 73%/68% of patients, p = 0.74; pre-/post-septal ablation 74%/26%, p = 0.0035; and pre-/post-septal myectomy 75%/0%, p <0.0001. In obstructive HC, the degree VWF multimer loss was greater than in severe AS or severe mitral regurgitation and overlapped that seen in left ventricular assist devices. In conclusion, VWF activity indexes were predictably abnormal in patients with HC with resting obstruction to a degree where bleeding could be anticipated, accurately reflected gradient changes after intervention, and demonstrated complete normalization after septal myectomy.

We describe a case of intraoperative diagnosis and successful deferred percutaneous closure of a patent foramen ovale (PFO) in the clinical setting of acute refractory hypoxemic respiratory failure and new-onset ischemic stroke in an elderly patient after coronary artery bypass graft. Perioperative morbidity (i.e. severe hypoxemia, worsening right ventricular dysfunction, and embolic stroke) that is potentially related to intraoperatively diagnosed PFO during cardiac surgery can complicate management in the Intensive Care Unit and perhaps affect the patient's outcome. Although the PFO closure can be challenging in the clinical setting of hypoxemic respiratory failure and stroke following cardiac surgery, it can be a reasonable perioperative option.

OBJECTIVE:The aim of the study was to declare a call to action to improve mental health in the workplace. METHODS:We convened a public health summit and assembled an Advisory Council consisting of experts in the field of occupational health and safety, workplace wellness, and public policy to offer recommendations for action steps to improve health and well-being of workers. RESULTS:The Advisory Council narrowed the list of ideas to four priority projects. CONCLUSIONS:The recommendations for action include developing a mental health in the workplace (1) “how to” guide, (2) scorecard, (3) recognition program, and (4) executive training.

Bloodless evolution The cornea is one of the few tissues in the body with no blood vessels flowing through it. This blood-vessel-free island is often used to test anti-angiogenic therapies for cancer, arthritis, atherosclerosis, diabetes and other diseases driven by pathological angiogenesis. This lack of blood vessels is remarkable because of the highly vascular nature of the surrounding tissues; doubly remarkable because the cornea has now been found to contain large amounts of the potent angiogenic molecule VEGF-A (vascular endothelial growth factor). This discovery has led to a finding that could be important in terms of drug design: a VEGF-A trap known as soluble VEGFR-1 is also present in the cornea and is singly responsible for the absence of blood vessels there. Intriguingly, the few known organisms that have a vascularized cornea (manatees, mutant mice, and some aniridia patients with Pax6 mutations) are all deficient in corneal soluble VEGFR-1. Corneal avascularity—the absence of blood vessels in the cornea—is required for optical clarity and optimal vision, and has led to the cornea being widely used for validating pro- and anti-angiogenic therapeutic strategies for many disorders 1 , 2 , 3 , 4 . But the molecular underpinnings of the avascular phenotype have until now remained obscure 5 , 6 , 7 , 8 , 9 , 10 and are all the more remarkable given the presence in the cornea of vascular endothelial growth factor (VEGF)-A, a potent stimulator of angiogenesis, and the proximity of the cornea to vascularized tissues. Here we show that the cornea expresses soluble VEGF receptor-1 (sVEGFR-1; also known as sflt-1) and that suppression of this endogenous VEGF-A trap 11 by neutralizing antibodies, RNA interference or Cre-lox-mediated gene disruption abolishes corneal avascularity in mice. The spontaneously vascularized corneas of corn1 and Pax6 +/- mice 12 , 13 and Pax6 +/- patients with aniridia 14 are deficient in sflt-1, and recombinant sflt-1 administration restores corneal avascularity in corn1 and Pax6 +/- mice. Manatees, the only known creatures uniformly to have vascularized corneas 15 , do not express sflt-1, whereas the avascular corneas of dugongs, also members of the order Sirenia, elephants, the closest extant terrestrial phylogenetic relatives of manatees, and other marine mammals (dolphins and whales) contain sflt-1, indicating that it has a crucial, evolutionarily conserved role. The recognition that sflt-1 is essential for preserving the avascular ambit of the cornea can rationally guide its use as a platform for angiogenic modulators, supports its use in treating neovascular diseases, and might provide insight into the immunological privilege of the cornea.

A prospective, 4-year cohort study of children born in an urban slum in northeastern Brazil was undertaken to elucidate the epidemiology of Cryptosporidium infection in an endemic setting, describe factors associated with Cryptosporidium-associated persistent diarrhea, and clarify the importance of copathogens in symptomatic cryptosporidiosis. A total of 1476 episodes of diarrhea, accounting for 7581 days of illness (5.25 episodes/child-year), were recorded: of these, 102 episodes (6.9%) were persistent. Cryptosporidium oocysts were identified in 7.4% of all stools, and they were found more frequently in children with persistent diarrhea (16.5%) than in those with acute (8.4%) or no (4.0%) diarrhea (P < .001). Low-birth-weight children and those living in densely crowded subdivisions were at greater risk for symptomatic infection. Disease course was highly variable and was not associated with the presence of copathogens. Recurrent Cryptosporidium infection and relapsing diarrhea associated with it were moderately common. In light of these data, the applicability of the current World Health Organization diarrheal definitions to Cryptosporidium-associated diarrheal episodes may need to be reconsidered.

To evaluate the impact of Cryptosporidium infection on diarrheal disease burden and nutrition status, a nested case-control study was done among children who were followed from birth in Fortaleza, Brazil. The diarrhea history and growth records of 43 children with a symptomatic diarrhea episode of cryptosporidiosis (case-children) were compared with those of 43 age-matched controls with no history of cryptosporidiosis. After Cryptosporidium infection, case-children ⩽1 year old experienced an excessive and protracted (nearly 2 years) diarrheal disease burden. Case-children ⩽1 year old with no history of diarrhea prior to their Cryptosporidium infection also experienced a subsequent increased diarrheal disease burden with an associated decline in growth. Control subjects experienced no change in their diarrhea burden over time. This study suggests that an episode of symptomatic Cryptosporidium infection in children ⩽1 year of age is a marker for increased diarrhea morbidity.

We conducted a feasibility study to examine whether a paediatric patient at a regional hospital could be assessed by an ear, nose and throat (ENT) specialist via videoconference, therefore saving at least one journey to the tertiary hospital for a preadmission appointment. A video-otoscope was used with standard videoconference equipment, and realtime images were transmitted at a bandwidth of 384 kbit/s. In all, 1 3 telepaediatric ENT clinics were conducted between November 2003 and April 2005, and 98 consultations were facilitated for 64 patients. The main reasons for referral were recurrent tonsillitis (25%) and obstructive sleep apnoea (23%). Of the 64 patients examined by telemedicine, 42 (66%) were recommended for surgery and placed on the surgical waiting list. About 12 patients (19%) required travel to the tertiary centre for further investigations and tests not available locally, while four patients (6%) were reviewed via videoconference during a scheduled clinic. Six patients (9%) required no further follow-up after their initial telepaediatric consultation. Videoconferencing is an effective method of assessing ENT conditions of paediatric patients and for pre-screening potential surgical admissions to a tertiary hospital. Careful consideration of a number of economic and logistical factors needs to be made before large investments are made to expand the service.

A Companion to Cultural Geography brings together original contributions from 35 distinguished international scholars to provide a critical overview of this dynamic and influential field of study. * Provides accessible overviews of key themes, debates and controversies from a variety of historical and theoretical vantage points * Charts significant changes in cultural geography in the twentieth century as well as the principal approaches that currently animate work in the field * A valuable resource not just for geographers but also those working in allied fields who wish to get a clear understanding of the contribution geography is making to cross-disciplinary debates

While the green revolution adapted a handful of crops to homogenous and high-input industrialized agriculture, much of the global population still relies on local food production from low-input smallholder farms that grow highly variable crop cultivars. The high diversity of the grain and bioenergy crop sorghum 1–4, and many other crops that were not homogenized during the green revolution 5, not only provides the raw materials for breeders to make substantial gains in cultivar improvement, but also constrains breeding efforts due to highly specialized locally adapted plant phenotypes 6. Here, we construct a 33-member pangenome and identify trait-associated variants in 1,988 cultivars and landraces. We then apply these resources to explore the complex interplay between historical contingency, ongoing adaptation, and the potential for future gains through climate-aware genome-enabled breeding. Specifically, our analyses conclusively demonstrate that multiple nested, deeply diverged, and previously uncharacterized structural variants in the domestication gene SHATTERING1 distinguish the previously established multicentric origin of sorghum. We then apply landscape genomics tests to reveal how gene flow, adaptation, and secondary contact created the complex genetic mosaic in current global breeding networks. Further analysis of climate-gene associations highlights candidate loci underlying adaptation, including the biosynthetic gene cluster for the cyanogenic glucoside dhurrin. Combined, the pangenome-informed variants developed here will enable both trait discovery and subsequent marker assays to accelerate breeding and provide a framework for similar applications in other diverse and non-model crops.