241 research outputs found

    Gravitational Waves from Gravitational Collapse

    Get PDF
    Gravitational wave emission from the gravitational collapse of massive stars has been studied for more than three decades. Current state of the art numerical investigations of collapse include those that use progenitors with realistic angular momentum profiles, properly treat microphysics issues, account for general relativity, and examine non--axisymmetric effects in three dimensions. Such simulations predict that gravitational waves from various phenomena associated with gravitational collapse could be detectable with advanced ground--based and future space--based interferometric observatories.Comment: 68 pages including 13 figures; revised version accepted for publication in Living Reviews in Relativity (http://www.livingreviews.org

    Studies of a co-chaperone of the androgen receptor, FKBP52, as candidate for hypospadias

    Get PDF
    BACKGROUND: Hypospadias is a common inborn error of the male urethral development, for which the aetiology is still elusive. Polymorphic variants in genes involved in the masculinisation of male genitalia, such as the androgen receptor, have been associated with some cases of hypospadias. Co-regulators of the androgen receptor start being acknowledged as possible candidates for hormone-resistance instances, which could account for hypospadias. One such molecule, the protein FKBP52, coded by the FKBP4 gene, has an important physiological role in up-regulating androgen receptor activity, an essential step in the development of the male external genitalia. The presence of hypospadias in mice lacking fkbp52 encouraged us to study the sequence and the expression of FKBP4 in boys with isolated hypospadias. PATIENTS AND METHODS: The expression of FKBP52 in the genital skin of boys with hypospadias and in healthy controls was tested by immunohistochemistry. Mutation screening in the FKBF4 gene was performed in ninety-one boys with non syndromic hypospadias. Additionally, two polymorphisms were typed in a larger cohort. RESULTS: Immunohistochemistry shows epithelial expression of FKBP52 in the epidermis of the penile skin. No apparent difference in the FKBP52 expression was detected in healthy controls, mild or severe hypospadias patients. No sequence variants in the FKBP4 gene have implicated in hypospadias in our study. CONCLUSION: FKBP52 is likely to play a role in growth and development of the male genitalia, since it is expressed in the genital skin of prepubertal boys; however alterations in the sequence and in the expression of the FKBP4 gene are not a common cause of non-syndromic hypospadias

    21-Hydroxylase Genotyping in Australasian Patients with Congenital Adrenal Hyperplasia

    Get PDF
    Mutations in CYP21 (21-hydroxylase) lead to congenital adrenal hyperplasia (CAH). We genotyped 26 probands with CAH by PCR-sequencing the entire CYP21 gene. 25/26 had homozygous or compound heterozygous mutations. The frequencies of mutations were similar to other populations with deletion/hybrid, 12 G splice and 1172N the most common. Five patients with a 1172N allele predicting simple-virilising CAH had a salt-wasting phenotype. Two other probands also had a more severe phenotype than predicted by genotype. Two families had both non-classic and salt-wasting phenotypes arising from combinations of three deleterious alleles. Two novel CYP21 alleles were detected: D106N and a large deletion encompassing CYP21 and adjacent pseudogene. Two rare CYP21 alleles were also found. Three of these four novel/rare alleles were only detected as a result of sequencing the entire CYP21 gene. Entire CYP21 sequencing will increase the number of mutations detected in CAH, and in combination with functional studies should contribute a greater understanding of phenotype-genotype correlations.

    10-Year cardiovascular event risks for women who experienced hypertensive disorders in late pregnancy: the HyRAS study

    Get PDF
    ABSTRACT: BACKGROUND: Cardiovascular disease is the cause of death in 32% of women in the Netherlands. Prediction of an individual's risk for cardiovascular disease is difficult, in particular in younger women due to low sensitive and specific tests for these women. 10% to 15% of all pregnancies are complicated by hypertensive disorders, the vast majority of which develop only after 36 weeks of gestation. Preeclampsia and cardiovascular disease in later life show both features of "the metabolic syndrome" and atherosclerosis. Hypertensive disorders in pregnancy and cardiovascular disease may develop by common pathophysiologic pathways initiated by similar vascular risk factors. Vascular damage occurring during preeclampsia or gestational hypertension may contribute to the development of future cardiovascular disease, or is already present before pregnancy. At present clinicians do not systematically aim at the possible cardiovascular consequences in later life after a hypertensive pregnancy disorder at term. However, screening for risk factors after preeclampsia or gestational hypertension at term may give insight into an individual's cardiovascular risk profile. METHODS: Women with a history of preeclampsia or gestational hypertension will be invited to participate in a cohort study 2,5 years after delivery. Participants will be screened for established modifiable cardiovascular risk indicators. The primary outcome is the 10-year cardiovascular event risk. Secondary outcomes include differences in cardiovascular parameters, SNP's in glucose metabolism, and neonatal outcome. DISCUSSION: This study will provide evidence on the potential health gains of a modifiable cardiovascular risk factor screening program for women whose pregnancy was complicated by hypertension or preeclampsia. The calculation of individual 10-year cardiovascular event risks will allow identification of those women who will benefit from primary prevention by tailored interventions, at a relatively young age. Trail registration The HYPITAT trial is registered in the clinical trial register as ISRCTN08132825

    Increasing the Depth of Current Understanding: Sensitivity Testing of Deep-Sea Larval Dispersal Models for Ecologists

    Get PDF
    Larval dispersal is an important ecological process of great interest to conservation and the establishment of marine protected areas. Increasing numbers of studies are turning to biophysical models to simulate dispersal patterns, including in the deep-sea, but for many ecologists unassisted by a physical oceanographer, a model can present as a black box. Sensitivity testing offers a means to test the models' abilities and limitations and is a starting point for all modelling efforts. The aim of this study is to illustrate a sensitivity testing process for the unassisted ecologist, through a deep-sea case study example, and demonstrate how sensitivity testing can be used to determine optimal model settings, assess model adequacy, and inform ecological interpretation of model outputs. Five input parameters are tested (timestep of particle simulator (TS), horizontal (HS) and vertical separation (VS) of release points, release frequency (RF), and temporal range (TR) of simulations) using a commonly employed pairing of models. The procedures used are relevant to all marine larval dispersal models. It is shown how the results of these tests can inform the future set up and interpretation of ecological studies in this area. For example, an optimal arrangement of release locations spanning a release area could be deduced; the increased depth range spanned in deep-sea studies may necessitate the stratification of dispersal simulations with different numbers of release locations at different depths; no fewer than 52 releases per year should be used unless biologically informed; three years of simulations chosen based on climatic extremes may provide results with 90% similarity to five years of simulation; and this model setup is not appropriate for simulating rare dispersal events. A step-by-step process, summarising advice on the sensitivity testing procedure, is provided to inform all future unassisted ecologists looking to run a larval dispersal simulation

    Nutrient intakes related to osteoporotic fractures in men and women – The Brazilian Osteoporosis Study (BRAZOS)

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Adequate nutrition plays an important role in bone mass accrual and maintenance and has been demonstrated as a significant tool for the prevention of fractures in individuals with osteoporosis.</p> <p>Objective</p> <p>The aim of the present study was to evaluate bone health-related nutrients intake and its association with osteoporotic fractures in a representative sample of 2344 individuals aged 40 years or older in Brazil.</p> <p>Methods</p> <p>In a transversal population-based study, a total of 2420 individuals over 40 years old were evaluated from March to April 2006. Participants were men and women from all socio-economic classes and education levels living around the Brazilian territory Individuals responded a questionnaire including self reported fractures as well a 24-hour food recall. Nutrient intakes were evaluated by Nutrition Data System for Research software (NDSR, University of Minnesota, 2007). Low trauma fracture was defined as that resulting of a fall from standing height or less. Nutrient intakes adequacies were performed by using the DRI's proposed values. Statistical analysis comprises Oneway ANCOVA adjusted by age and use of nutritional supplements and multiple logistic regression. SAS software was used for statistical analysis.</p> <p>Results</p> <p>Fractures was reported by 13% of men and 15% of women. Women with fractures presented significantly higher calcium, phosphorus and magnesium intakes. However, in all regions and socio-economical levels mean intakes of bone related nutrients were below the recommended levels. It was demonstrated that for every 100 mg/phosphorus increase the risk of fractures by 9% (OR 1.09; IC95% 1.05–1.13, p < 0.001).</p> <p>Conclusion</p> <p>The results demonstrated inadequacies in bone related nutrients in our population as well that an increase in phosphorus intake is related to bone fractures.</p

    Implementing a stepped-care approach in primary care: results of a qualitative study

    Get PDF
    Contains fulltext : 108260.pdf (publisher's version ) (Open Access)BACKGROUND: Since 2004, 'stepped-care models' have been adopted in several international evidence-based clinical guidelines to guide clinicians in the organisation of depression care. To enhance the adoption of this new treatment approach, a Quality Improvement Collaborative (QIC) was initiated in the Netherlands. METHODS: Alongside the QIC, an intervention study using a controlled before-and-after design was performed. Part of the study was a process evaluation, utilizing semi-structured group interviews, to provide insight into the perceptions of the participating clinicians on the implementation of stepped care for depression into their daily routines. Participants were primary care clinicians, specialist clinicians, and other healthcare staff from eight regions in the Netherlands. Analysis was supported by the Normalisation Process Theory (NPT). RESULTS: The introduction of a stepped-care model for depression to primary care teams within the context of a depression QIC was generally well received by participating clinicians. All three elements of the proposed stepped-care model (patient differentiation, stepped-care treatment, and outcome monitoring), were translated and introduced locally. Clinicians reported changes in terms of learning how to differentiate between patient groups and different levels of care, changing antidepressant prescribing routines as a consequence of having a broader treatment package to offer to their patients, and better working relationships with patients and colleagues. A complex range of factors influenced the implementation process. Facilitating factors were the stepped-care model itself, the structured team meetings (part of the QIC method), and the positive reaction from patients to stepped care. The differing views of depression and depression care within multidisciplinary health teams, lack of resources, and poor information systems hindered the rapid introduction of the stepped-care model. The NPT constructs 'coherence' and 'cognitive participation' appeared to be crucial drivers in the initial stage of the process. CONCLUSIONS: Stepped care for depression is received positively in primary care. While it is difficult for the implementation of a full stepped-care approach to occur within a short time frame, clinicians can make progress towards achieving a stepped-care approach, particularly within the context of a QIC. Creating a shared understanding within multidisciplinary teams of what constitutes depression, reaching a consensus about the content of depression care, and the division of tasks are important when addressing the implementation process

    Engaging community pharmacists in the primary prevention of cardiovascular disease: protocol for the Pharmacist Assessment of Adherence, Risk and Treatment in Cardiovascular Disease (PAART CVD) pilot study

    Get PDF
    Background: Cardiovascular disease (CVD) is the leading cause of death globally. Community pharmacist intervention studies have demonstrated clinical effectiveness for improving several leading individual CVD risk factors. Primary prevention strategies increasingly emphasise the need for consideration of overall cardiovascular risk and concurrent management of multiple risk factors. It is therefore important to demonstrate the feasibility of multiple risk factor management by community pharmacists to ensure continued currency of their role.Methods/Design: This study will be a longitudinal pre- and post-test pilot study with a single cohort of up to 100 patients in ten pharmacies. Patients aged 50-74 years with no history of heart disease or diabetes, and taking antihypertensive or lipid-lowering medicines, will be approached for participation. Assessment of cardiovascular risk, medicines use and health behaviours will be undertaken by a research assistant at baseline and following the intervention (6 months). Validated interview scales will be used where available. Baseline data will be used by accredited medicines management pharmacists to generate a report for the treating community pharmacist. This report will highlight individual patients&rsquo; overall CVD risk and individual risk factors, as well as identifying modifiablehealth behaviours for risk improvement and suggesting treatment and behavioural goals. The treating community pharmacist will use this information to finalise and implement a treatment plan in conjunction with the patient and their doctor. Community pharmacists will facilitate patient improvements in lifestyle, medicines adherence, and medicines management over the course of five counselling sessions with monthly intervals. The primary outcome will be the change to average overall cardiovascular risk, assessed using the Framingham risk equation.Discussion: This study will assess the feasibility of implementing holistic primary CVD prevention programs into community pharmacy, one of the most accessible health services in most developed countries.<br /

    Physician attitude toward depression care interventions: Implications for implementation of quality improvement initiatives

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Few individuals with depression treated in the primary care setting receive care consistent with clinical treatment guidelines. Interventions based on the chronic care model (CCM) have been promoted to address barriers and improve the quality of care. A current understanding of barriers to depression care and an awareness of whether physicians believe interventions effectively address those barriers is needed to enhance the success of future implementation.</p> <p>Methods</p> <p>We conducted semi-structured interviews with 23 primary care physicians across the US regarding their experience treating patients with depression, barriers to care, and commonly promoted CCM-based interventions. Themes were identified from interview transcripts using a grounded theory approach.</p> <p>Results</p> <p>Six barriers emerged from the interviews: difficulty diagnosing depression, patient resistance, fragmented mental health system, insurance coverage, lack of expertise, and competing demands and other responsibilities as a primary care provider. A number of interventions were seen as helpful in addressing these barriers – including care managers, mental health integration, and education – while others received mixed reviews. Mental health consultation models received the least endorsement. Two systems-related barriers, the fragmented mental health system and insurance coverage limitations, appeared incompletely addressed by the interventions.</p> <p>Conclusion</p> <p>CCM-based interventions, which include care managers, mental health integration, and patient education, are most likely to be implemented successfully because they effectively address several important barriers to care and are endorsed by physicians. Practices considering the adoption of interventions that received less support should educate physicians about the benefit of the interventions and attend to physician concerns prior to implementation. A focus on interventions that address systems-related barriers is needed to overcome all barriers to care.</p

    Biogeographic distributions of neotropical trees reflect their directly measured drought tolerances

    Get PDF
    High levels of species diversity hamper current understanding of how tropical forests may respond to environmental change. In the tropics, water availability is a leading driver of the diversity and distribution of tree species, suggesting that many tropical taxa may be physiologically incapable of tolerating dry conditions, and that their distributions along moisture gradients can be used to predict their drought tolerance. While this hypothesis has been explored at local and regional scales, large continental-scale tests are lacking. We investigate whether the relationship between drought-induced mortality and distributions holds continentally by relating experimental and observational data of drought-induced mortality across the Neotropics to the large-scale bioclimatic distributions of 115 tree genera. Across the different experiments, genera affiliated to wetter climatic regimes show higher drought-induced mortality than dry-affiliated ones, even after controlling for phylogenetic relationships. This pattern is stronger for adult trees than for saplings or seedlings, suggesting that the environmental filters exerted by drought impact adult tree survival most strongly. Overall, our analysis of experimental, observational, and bioclimatic data across neotropical forests suggests that increasing moisture-stress is indeed likely to drive significant changes in floristic composition
    corecore