ORFEUS-II Far-Ultraviolet Observations of 3C273: 1. Interstellar and Intergalactic Absorption Lines

We present the first intermediate-resolution (lambda / 3000) spectrum of the bright quasi-stellar object 3C273 at wavelengths between 900 and 1200 A. Observations were performed with the Berkeley spectrograph aboard the ORFEUS-SPAS II mission. We detect Lyman beta counterparts to previously-identified intergalactic Lyman-alpha features at cz = 19900, 1600, and 1000 km/s; counterparts to other putative Lyman-alpha clouds along the sight line are below our detection limit. The strengths of the two very low redshift Lyman-beta features, which are believed to arise in Virgo intracluster gas, exceed preflight expectations, suggesting that the previous determination of the cloud parameters may underestimate the true column densities. A curve-of-growth analysis sets a minimum H I column density of 4 E14/cm^2 for the 1600 km/s cloud. We find marginally significant evidence for Galactic H_2 along the sight line, with a total column density of about 1 E15/cm^2. We detect the stronger interstellar O VI doublet member unambiguously; the weaker member is blended with other features. If the Doppler b value for O VI is comparable to that determined for N V then the O VI column density is 7 +/- 2 E14/cm^2, significantly above the only previous estimate. The O VI / N V ratio is about 10, consistent with the low end of the range observed in the disk. Additional interstellar species detected for the first time toward 3C273 (at modest statistical significance) include P II, Fe III, Ar I, and S III.Comment: LaTeX file, 11 pages, 4 encapsulated PostScript figures. Uses aaspp4.sty and astrobib.sty. (Astrobib is available from http://www.stsci.edu/software/TeX.html .) The ORFEUS telescope is described at http://sag-www.ssl.berkeley.edu/orfeus/ . To appear in ApJ (Letters

Asthma Prevalence, Knowledge, and Perceptions among Secondary School Pupils in Rural and Urban Costal Districts in Tanzania.

Asthma is a common chronic disease of childhood that is associated with significant morbidity and mortality. We aimed to estimate the prevalence of asthma among secondary school pupils in urban and rural areas of coast districts of Tanzania. The study also aimed to describe pupils' perception towards asthma, and to assess their knowledge on symptoms, triggers, and treatment of asthma. A total of 610 pupils from Ilala district and 619 pupils from Bagamoyo district formed the urban and rural groups, respectively. Using a modified International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, a history of "diagnosed" asthma or the presence of a wheeze in the previous 12 months was obtained from all the studied pupils, along with documentation of their perceptions regarding asthma. Pupils without asthma or wheeze in the prior 12 months were subsequently selected and underwent a free running exercise testing. A >= 20% decrease in the post-exercise Peak Expiratory Flow Rate (PEFR) values was the criterion for diagnosing exercise-induced asthma. The mean age of participants was 16.8 (+/-1.8) years. The prevalence of wheeze in the past 12 months was 12.1% in Bagamoyo district and 23.1% in Ilala district (p < 0.001). Self-reported asthma was found in 17.6% and 6.4% of pupils in Ilala and Bagamoyo districts, respectively (p < 0.001). The prevalence of exercise-induced asthma was 2.4% in Bagamoyo, and 26.3% in Ilala (P < 0.002). In both districts, most information on asthma came from parents, and there was variation in symptoms and triggers of asthma reported by the pupils. Non-asthmatic pupils feared sleeping, playing, and eating with their asthmatic peers. The prevalence rates of self-reported asthma, wheezing in the past 12 months, and exercise-induced asthma were significantly higher among urban than rural pupils. Although bronchial asthma is a common disease, pupils' perceptions about asthma were associated with fear of contact with their asthmatic peers in both rural and urban schools

Hepatic FoxOs link insulin signaling with plasma lipoprotein metabolism through an apolipoprotein M/sphingosine-1-phosphate pathway

Multiple beneficial cardiovascular effects of HDL depend on sphingosine-1-phosphate (S1P). S1P associates with HDL by binding to apolipoprotein M (ApoM). Insulin resistance is a major driver of dyslipidemia and cardiovascular risk. However, the mechanisms linking alterations in insulin signaling with plasma lipoprotein metabolism are incompletely understood. The insulin-repressible FoxO transcription factors mediate key effects of hepatic insulin action on glucose and lipoprotein metabolism. This work tested whether hepatic insulin signaling regulates HDL-S1P and aimed to identify the underlying molecular mechanisms. We report that insulin-resistant, nondiabetic individuals had decreased HDL-S1P levels, but no change in total plasma S1P. This also occurred in insulin-resistant db/db mice, which had low ApoM and a specific reduction of S1P in the HDL fraction, with no change in total plasma S1P levels. Using mice lacking hepatic FoxOs (L-FoxO1,3,4), we found that hepatic FoxOs were required for ApoM expression. Total plasma S1P levels were similar to those in controls, but S1P was nearly absent from HDL and was instead increased in the lipoprotein-depleted plasma fraction. This phenotype was restored to normal by rescuing ApoM in L-FoxO1,3,4 mice. Our findings show that insulin resistance in humans and mice is associated with decreased HDL-associated S1P. Our study shows that hepatic FoxO transcription factors are regulators of the ApoM/S1P pathway

Newly qualified doctors' views about whether their medical school had trained them well: questionnaire surveys

A survey of newly qualified doctors in the UK in 2000/2001 found that 42% of them felt unprepared for their first year of employment in clinical posts. We report on how UK qualifiers' preparedness has changed since then, and on the impact of course changes upon preparedness. Methods Postal questionnaires were sent to all doctors who qualified from UK medical schools, in their first year of clinical work, in 2003 (n = 4257) and 2005 (n = 4784); and findings were compared with those in 2000/2001 (n = 5330). The response rates were 67% in 2000/2001, 65% in 2003, and 43% in 2005. The outcome measure was the percentage of doctors agreeing with the statement "My experience at medical school has prepared me well for the jobs I have undertaken so far". Results In the 2000/2001 survey 36.3% strongly agreed or agreed with the statement, as did 50.3% in the 2003 survey and 58.5% in 2005 (chi-squared test for linear trend: χ2 = 259.5; df = 1; p < 0.001). Substantial variation in preparedness between doctors from different medical schools, reported in the first survey, was still present in 2003 and 2005. Between 1998 and 2006 all UK medical schools updated their courses. Within each cohort a significantly higher percentage of the respondents from schools with updated courses felt well prepared. Conclusion UK medical schools are now training doctors who feel better prepared for work than in the past. Some of the improvement may be attributable to curricular change

Bacterial porin disrupts mitochondrial membrane potential and sensitizes host cells to apoptosis

The bacterial PorB porin, an ATP-binding beta-barrel protein of pathogenic Neisseria gonorrhoeae, triggers host cell apoptosis by an unknown mechanism. PorB is targeted to and imported by host cell mitochondria, causing the breakdown of the mitochondrial membrane potential (delta psi m). Here, we show that PorB induces the condensation of the mitochondrial matrix and the loss of cristae structures, sensitizing cells to the induction of apoptosis via signaling pathways activated by BH3-only proteins. PorB is imported into mitochondria through the general translocase TOM but, unexpectedly, is not recognized by the SAM sorting machinery, usually required for the assembly of beta-barrel proteins in the mitochondrial outer membrane. PorB integrates into the mitochondrial inner membrane, leading to the breakdown of delta psi m. The PorB channel is regulated by nucleotides and an isogenic PorB mutant defective in ATP-binding failed to induce delta psi m loss and apoptosis, demonstrating that dissipation of delta psi m is a requirement for cell death caused by neisserial infection

Assessment of the Introductory Transportation Engineering Course and the General Transportation Engineering Curriculum

Transportation engineering is a critical subdiscipline of the civil engineering profession as indicated by its inclusion on the Fundamentals of Engineering Examination, its overlap with other specialty areas of civil engineering, and as recognized by the Transportation Research Board, Institute of Transportation Engineers, and the American Society of Civil Engineers. With increasing transportation workforce needs, low numbers of students entering the ‘pipeline’, and limited hours within undergraduate civil engineering programs, it is important to ensure civil engineering students receive adequate preparation and exposure to career opportunities in the transportation engineering field. As such, investigations into the status of transportation engineering within civil engineering programs and specifically the introductory transportation engineering course are essential for understanding the implications to the profession. This paper presents a review of relevant literature and findings from a new survey of ABET-accredited civil engineering programs that yielded 84 responses. The survey indicates that 88 percent of responding programs teach an introductory course in transportation engineering, and 79 percent require it in their undergraduate programs. There is significant variation in the structure of the introductory course (number of credit hours, lab requirements, etc.), and common responses regarding improvements that could be made include adding labs, requiring a second course, and broadening course content. In addition, nearly 15 percent of instructors teaching the introductory course did not have a primary focus in transportation engineering. This finding should be investigated further, given that this course may be an undergraduate civil engineering student’s only exposure to the profession.This is an author's peer-reviewed final manuscript, as accepted by the publisher. The published article is copyrighted by the Transportation Research Board of the National Academies and can be found at: https://doi.org/10.3141/2328-0

Predictive Analytics in Practice: A Novel Simulation Application for Addressing Patient Flow Challenges in Today&apos;s Emergency Departments

Abstract Objectives: To develop a flexible software application that uses predictive analytics to enable emergency department (ED) decision-makers in virtually any environment to predict the effects of operational interventions and enhance continual process improvement efforts. To demonstrate the ability of the application&apos;s core simulation model to recreate and predict sitespecific patient flow in two very different EDs: a large academic center and a freestanding ED. To describe how the application was used by a freestanding ED medical director to match ED resources to patient demand. Methods: The application was developed through a public-private partnership between University of Florida Health and Roundtable Analytics, Inc., supported by a National Science Foundation Small Business Technology Transfer (STTR) grant. The core simulation technology was designed to be quickly adaptable to any ED using data routinely collected by most electronic health record systems. To demonstrate model accuracy, Monte Carlo studies were performed to predict the effects of management interventions in two distinct ED settings. At one ED, the medical director conducted simulation studies to evaluate the sustainability of the current staffing strategy and inform his decision to implement specific interventions that better match ED resources to patient demand. After implementation of one intervention, the fidelity of the model&apos;s predictions was evaluated. Results: A flexible, cloud-based software application enabling ED decision-makers to predict the effects of operational decisions was developed and deployed at two qualitatively distinct EDs. The application accurately recreated each ED&apos;s throughput and faithfully predicted the effects of specific management interventions. At one site, the application was used to identify when increasing arrivals will dictate that the current staffing strategy will be less effective than an alternative strategy. As actual arrivals approached this point, decision-makers used the application to simulate a variety different interventions; this directly informed their decision to implement a new strategy. The observed outcomes resulting from this intervention fell within the range of predictions from the model. Conclusion: This application overcomes technical barriers that have made simulation modeling inaccessible to key decision-makers in emergency departments. Using this technology, ED managers with no programming experience can conduct customized simulation studies regardless of their ED&apos;s volume and complexity. In two very different case studies, the fidelity of the application was established and the application was shown to have a direct positive effect on patient flow. The effective use of simulation modeling promises to replace inefficient trial-anderror approaches and become a useful and accessible tool for healthcare managers challenged to make operational decisions in environments of increasingly scarce resources

The effects of hip muscle strengthening on knee load, pain, and function in people with knee osteoarthritis: a protocol for a randomised, single-blind controlled trial

BACKGROUND: Lower limb strengthening exercises are an important component of the treatment for knee osteoarthritis (OA). Strengthening the hip abductor and adductor muscles may influence joint loading and/or OA-related symptoms, but no study has evaluated these hypotheses directly. The aim of this randomised, single-blind controlled trial is to determine whether hip abductor and adductor muscle strengthening can reduce knee load and improve pain and physical function in people with medial compartment knee OA. METHODS/DESIGN: 88 participants with painful, radiographically confirmed medial compartment knee OA and varus alignment will be recruited from the community and randomly allocated to a hip strengthening or control group using concealed allocation stratified by disease severity. The hip strengthening group will perform 6 exercises to strengthen the hip abductor and adductor muscles at home 5 times per week for 12 weeks. They will consult with a physiotherapist on 7 occasions to be taught the exercises and progress exercise resistance. The control group will be requested to continue with their usual care. Blinded follow up assessment will be conducted at 12 weeks after randomisation. The primary outcome measure is the change in the peak external knee adduction moment measured during walking. Questionnaires will assess changes in pain and physical function as well as overall perceived rating of change. An intention-to-treat analysis will be performed using linear regression modelling and adjusting for baseline outcome values and other demographic characteristics. DISCUSSION: Results from this trial will contribute to the evidence regarding the effect of hip strengthening on knee loads and symptoms in people with medial compartment knee OA. If shown to reduce the knee adduction moment, hip strengthening has the potential to slow disease progression. TRIAL REGISTRATION: Australia New Zealand Clinical Trials Registry ACTR12607000001493

SLI-1 Cbl Inhibits the Engulfment of Apoptotic Cells in C. elegans through a Ligase-Independent Function

The engulfment of apoptotic cells is required for normal metazoan development and tissue remodeling. In Caenorhabditis elegans, two parallel and partially redundant conserved pathways act in cell-corpse engulfment. One pathway, which includes the small GTPase CED-10 Rac and the cytoskeletal regulator ABI-1, acts to rearrange the cytoskeleton of the engulfing cell. The CED-10 Rac pathway is also required for proper migration of the distal tip cells (DTCs) during the development of the C. elegans gonad. The second pathway includes the receptor tyrosine kinase CED-1 and might recruit membranes to extend the surface of the engulfing cell. Cbl, the mammalian homolog of the C. elegans E3 ubiquitin ligase and adaptor protein SLI-1, interacts with Rac and Abi2 and modulates the actin cytoskeleton, suggesting it might act in engulfment. Our genetic studies indicate that SLI-1 inhibits apoptotic cell engulfment and DTC migration independently of the CED-10 Rac and CED-1 pathways. We found that the RING finger domain of SLI-1 is not essential to rescue the effects of SLI-1 deletion on cell migration, suggesting that its role in this process is ubiquitin ligase-independent. We propose that SLI-1 opposes the engulfment of apoptotic cells via a previously unidentified pathway.National Cancer Institute (U.S.) (Award K08CA104890