Risk factors for hospital admission with RSV bronchiolitis in England: a population-based birth cohort study.

OBJECTIVE: To examine the timing and duration of RSV bronchiolitis hospital admission among term and preterm infants in England and to identify risk factors for bronchiolitis admission. DESIGN: A population-based birth cohort with follow-up to age 1 year, using the Hospital Episode Statistics database. SETTING: 71 hospitals across England. PARTICIPANTS: We identified 296618 individual birth records from 2007/08 and linked to subsequent hospital admission records during the first year of life. RESULTS: In our cohort there were 7189 hospital admissions with a diagnosis of bronchiolitis, 24.2 admissions per 1000 infants under 1 year (95%CI 23.7-24.8), of which 15% (1050/7189) were born preterm (47.3 bronchiolitis admissions per 1000 preterm infants (95% CI 44.4-50.2)). The peak age group for bronchiolitis admissions was infants aged 1 month and the median was age 120 days (IQR = 61-209 days). The median length of stay was 1 day (IQR = 0-3). The relative risk (RR) of a bronchiolitis admission was higher among infants with known risk factors for severe RSV infection, including those born preterm (RR = 1.9, 95% CI 1.8-2.0) compared with infants born at term. Other conditions also significantly increased risk of bronchiolitis admission, including Down's syndrome (RR = 2.5, 95% CI 1.7-3.7) and cerebral palsy (RR = 2.4, 95% CI 1.5-4.0). CONCLUSIONS: Most (85%) of the infants who are admitted to hospital with bronchiolitis in England are born at term, with no known predisposing risk factors for severe RSV infection, although risk of admission is higher in known risk groups. The early age of bronchiolitis admissions has important implications for the potential impact and timing of future active and passive immunisations. More research is needed to explain why babies born with Down's syndrome and cerebral palsy are also at higher risk of hospital admission with RSV bronchiolitis

Physician Executive Leadership: Student-Led Curriculum to Fill Gaps in Traditional Medical Education

Students at Sidney Kimmel Medical College (SKMC) have identified a gap in the traditional medical curriculum surrounding topics such as telehealth, the patient experience, health policy, medical malpractice, and health care entrepreneurship and innovation, and in response have initiated a student-centered, student-led, student-driven program called Physician Executive Leadership (PEL). PEL provides students with a variety of avenues to engage with these topics, such as lectures from leaders in each of these fields, easy access to weekly news articles on current events in health care, targeted review sessions on the US health care system, and the opportunity to voice and develop ideas through an online publication. To identify the gaps in medical education PEL is best suited to fill, we administered a survey to 174 students at Sidney Kimmel Medical College.The survey contained 20 multiple-choice questions to assess general knowledge on health insurance and reimbursement, health care policy and reform, and care quality and patient experience. It also included a subjective self-assessment of students’ understanding of and interest in these topics. Overall, we found that although the traditional medical school curriculum improved students\u27 understanding of these topics from year to year, it is not sufficient on it\u27s own: on average, students failed to achieve a passing score of 70% in any of the categories tested. Further illustrating the importance of this program, students self-identified a gap between their current level of understanding and what they want to know. Please visit our website www.physicianexecutiveleadership.com to learn more!https://jdc.jefferson.edu/pel/1000/thumbnail.jp

Understanding needle-related distress in children with cystic fibrosis

Objective. To explore the nature and management of needle-related distress in children and adolescents with cystic fibrosis (CF). Design. Qualitative study using semi-structured interviews. Methods. Fourteen child–parent dyads took part. Children (5 male; 9 female) had a mean age of 12.4 years (range 7–17) and were mostly diagnosed with CF at birth (N= 11). Frequency of needle procedures ranged from once to six times a year. Parents (3 male; 11 female) had a mean age of 41.5 years and were from a variety of socio-economic backgrounds. Interviews were transcribed and analysed using thematic analysis. Results. Most participants identified previous needle experiences and pain as related to their needle anxiety. Over half of parents and children considered ‘taking control’ to be the optimum coping strategy. The majority of parents and children thought inhaled nitrous oxide gas during needle procedures was helpful in managing needle-related distress. Parent and staff influences on needle-related distress are also examined. Conclusions. Needle-related distress in children with CF has a substantial impact on children and their parents, and may lead to management problems and treatment refusal. Psychological and pharmacological interventions could reduce distress and aid management

Vasculogenic Mimicry: Role of melanoma differentiation associated gene-9/syntenin

Malignant melanoma (MM) is the most aggressive skin cancer and the most frequent skin disorder in Caucasians. MM is associated with aggressive and progressive disease states, leading to major cancer-related morbidity and mortality. Recent investigations identify a new non-angiogenesis-dependent pathway vasculogenic mimicry (VM), which is considered a cancer hallmark that can independently facilitate tumor neovascularization by the formation of fluid-conducting and vascular endothelial cells. MM cells undergoing VM can dedifferentiate into numerous cellular phenotypes and acquire endothelial-like features, resulting in the formation of the de novo matrix-rich vascular-like network, such as plasma and red blood cells. The co-generation of endothelial cells, channels, laminar structures, and heparin sulfate proteoglycans are the main pathophysiological characteristics of VM in human melanoma patients. In highly aggressive melanoma cells downregulation of vascular endothelial cadherin and upregulation of ECM components promote the perfusion of the VM pathway. We investigated whether mda-9/syntenin, a pro-metastatic gene, affects VM in MM. The expression of mda-9/syntenin was modulated using gain-of-function and loss-of-function strategies to determine its potential role in VM. Downregulation of mda-9/syntenin in aggressive melanoma cells decreases VM, while over expressing mda-9/syntenin in immortalized melanoma cells increases VM. These findings shed light on a novel role and molecular mechanism of action of mda-9/syntenin in VM, which may contribute significantly to the metastatic phenotype of these aggressive cancers.https://scholarscompass.vcu.edu/gradposters/1137/thumbnail.jp

The dilemma of arranged marriages in people with epilepsy. An expert group appraisal

INTRODUCTION: Matrimony remains a challenging psychosocial problem confronting people with epilepsy (PWE). People with epilepsy are less likely to marry; however, their marital prospects are most seriously compromised in arranged marriages. AIMS: The aim of this study was to document marital prospects and outcomes in PWE going through arranged marriage and to propose optimal practices for counseling PWE contemplating arranged marriage. METHODS: A MEDLINE search and literature review were conducted, followed by a cross-disciplinary meeting of experts to generate consensus. RESULTS: People with epilepsy experience high levels of felt and enacted stigma in arranged marriages, but the repercussions are heavily biased against women. Hiding epilepsy is common during marital negotiations but may be associated with poor medication adherence, reduced physician visits, and poor marital outcome. Although divorce rates are generally insubstantial in PWE, divorce rates appear to be higher in PWE undergoing arranged marriages. In these marriages, hiding epilepsy during marital negotiations is a risk factor for divorce. CONCLUSIONS: In communities in which arranged marriages are common, physicians caring for PWE are best-equipped to counsel them about their marital prospects. Marital plans and aspirations should be discussed with the family of the person with epilepsy in a timely and proactive manner. The benefits of disclosing epilepsy during marital negotiations should be underscored

Postconditioning inhibits myocardial apoptosis during prolonged reperfusion via a JAK2-STAT3-Bcl-2 pathway

<p>Abstract</p> <p>Background</p> <p>Postconditioning (PostC) inhibits myocardial apoptosis after ischemia-reperfusion (I/R) injury. The JAK2-STAT3 pathway has anti-apoptotic effects and plays an essential role in the late protection of preconditioning. Our aim was to investigate the anti-apoptotic effect of PostC after prolonged reperfusion and the role of the JAK2-STAT3 pathway in the anti-apoptotic effect of PostC.</p> <p>Methods</p> <p>Wistar rats were subjected to 30 minutes ischemia and 2 or 24 hours (h) reperfusion, with or without PostC (three cycles of 10 seconds reperfusion and 10 seconds reocclusion at the onset of reperfusion). Separate groups of rats were treated with a JAK2 inhibitor (AG490) or a PI3K inhibitor (wortmannin) 5 minutes before PostC. Immunohistochemistry was used to analyze Bcl-2 protein levels after reperfusion. mRNA levels of Bcl-2 were detected by qRT-PCR. TTC staining was used to detect myocardial infarction size. Myocardial apoptosis was evaluated by TUNEL staining. Western-blot was used to detect p-STAT3 and p-Akt levels after reperfusion.</p> <p>Results</p> <p>There was more myocardial apoptosis at 24 h <it>vs </it>2 h after reperfusion in all groups. PostC significantly reduced myocardial apoptosis and elevated Bcl-2 levels at both 2 and 24 hours after reperfusion. PostC increased p-STAT3 and p-Akt levels after reperfusion. Administration of AG490 reduced p-STAT3 and p-Akt levels and attenuated the anti-apoptotic effect of PostC. Wortmannin also reduced p-Akt levels and attenuated the anti-apoptotic effect of PostC but had no effect on p-STAT3 levels. AG490 abrogated the up-regulation of Bcl-2 by PostC.</p> <p>Conclusion</p> <p>PostC may reduce myocardial apoptosis during prolonged reperfusion via a JAK2-STAT3-Bcl-2 pathway. As a downstream target of JAK2 signaling, activation of PI3K/Akt pathway may be necessary in the protection of PostC.</p

Memory in quantum dot blinking

The photoluminescence intermittency (blinking) of quantum dots is interesting because it is an easily-measured quantum process whose transition statistics cannot be explained by Fermi's Golden Rule. Commonly, the transition statistics are power-law distributed, implying that quantum dots possess at least trivial memories. By investigating the temporal correlations in the blinking data, we demonstrate with high statistical confidence that quantum dot blinking data has non-trivial memory, which we define to be statistical complexity greater than one. We show that this memory cannot be discovered using the transition distribution. We show by simulation that this memory does not arise from standard data manipulations. Finally, we conclude that at least three physical mechanisms can explain the measured non-trivial memory: 1) Storage of state information in the chemical structure of a quantum dot; 2) The existence of more than two intensity levels in a quantum dot; and 3) The overlap in the intensity distributions of the quantum dot states, which arises from fundamental photon statistics.Comment: Added supplementary quantum dot plots in source director

Scaphoid Waist Internal Fixation for Fractures Trial (SWIFFT) protocol : a pragmatic multi-centre randomised controlled trial of cast treatment versus surgical fixation for the treatment of bi-cortical, minimally displaced fractures of the scaphoid waist in adults

BACKGROUND: A scaphoid fracture is the most common type of carpal fracture affecting young active people. The optimal management of this fracture is uncertain. When treated with a cast, 88 to 90 % of these fractures unite; however, for the remaining 10-12 % the non-union almost invariably leads to arthritis. The alternative is surgery to fix the scaphoid with a screw at the outset. METHODS/DESIGN: We will conduct a randomised controlled trial (RCT) of 438 adult patients with a "clear" and "bicortical" scaphoid waist fracture on plain radiographs to evaluate the clinical effectiveness and cost-effectiveness of plaster cast treatment (with fixation of those that fail to unite) versus early surgical fixation. The plaster cast treatment will be immobilisation in a below elbow cast for 6 to 10 weeks followed by mobilisation. If non-union is confirmed on plain radiographs and/or Computerised Tomogram at 6 to 12 weeks, then urgent surgical fixation will be performed. This is being compared with immediate surgical fixation with surgeons using their preferred technique and implant. These treatments will be undertaken in trauma units across the United Kingdom. The primary outcome and end-point will be the Patient Rated Wrist Evaluation (a patient self-reported assessment of wrist pain and function) at 52 weeks and also measured at 6, 12, 26 weeks and 5 years. Secondary outcomes include an assessment of radiological union of the fracture; quality of life; recovery of wrist range and strength; and complications. We will also qualitatively investigate patient experiences of their treatment. DISCUSSION: Scaphoid fractures are an important public health problem as they predominantly affect young active individuals in the more productive working years of their lives. Non-union, if untreated, can lead to arthritis which can disable patients at a very young age. There is a rapidly increasing trend for immediate surgical fixation of these fractures but there is insufficient evidence from existing RCTs to support this. The SWIFFT Trial is a rigorously designed and adequately powered study which aims to contribute to the evidence-base to inform clinical decisions for the treatment of this common fracture in adults. TRIAL REGISTRATION: The trial is registered with the International Standard Randomised Controlled Trial Register ( ISRCTN67901257 ). Date registration assigned was 13/02/2013

Using random forest and decision tree models for a new vehicle prediction approach in computational toxicology

yesDrug vehicles are chemical carriers that provide beneficial aid to the drugs they bear. Taking advantage of their favourable properties can potentially allow the safer use of drugs that are considered highly toxic. A means for vehicle selection without experimental trial would therefore be of benefit in saving time and money for the industry. Although machine learning is increasingly used in predictive toxicology, to our knowledge there is no reported work in using machine learning techniques to model drug-vehicle relationships for vehicle selection to minimise toxicity. In this paper we demonstrate the use of data mining and machine learning techniques to process, extract and build models based on classifiers (decision trees and random forests) that allow us to predict which vehicle would be most suited to reduce a drug’s toxicity. Using data acquired from the National Institute of Health’s (NIH) Developmental Therapeutics Program (DTP) we propose a methodology using an area under a curve (AUC) approach that allows us to distinguish which vehicle provides the best toxicity profile for a drug and build classification models based on this knowledge. Our results show that we can achieve prediction accuracies of 80 % using random forest models whilst the decision tree models produce accuracies in the 70 % region. We consider our methodology widely applicable within the scientific domain and beyond for comprehensively building classification models for the comparison of functional relationships between two variables