Hypersonic Separated Flows About "Tick" Configurations With Sensitivity to Model Design

This paper presents computational results obtained by applying the direct simulation Monte Carlo (DSMC) method for hypersonic nonequilibrium flow about "tick-shaped" model configurations. These test models produces a complex flow where the nonequilibrium and rarefied aspects of the flow are initially enhanced as the flow passes over an expansion surface, and then the flow encounters a compression surface that can induce flow separation. The resulting flow is such that meaningful numerical simulations must have the capability to account for a significant range of rarefaction effects; hence the application of the DSMC method in the current study as the flow spans several flow regimes, including transitional, slip, and continuum. The current focus is to examine the sensitivity of both the model surface response (heating, friction and pressure) and flowfield structure to assumptions regarding surface boundary conditions and more extensively the impact of model design as influenced by leading edge configuration as well as the geometrical features of the expansion and compression surfaces. Numerical results indicate a strong sensitivity to both the extent of the leading edge sharpness and the magnitude of the leading edge bevel angle. Also, the length of the expansion surface for a fixed compression surface has a significant impact on the extent of separated flow

Darbepoetin alfa given every 1 or 2 weeks alleviates anaemia associated with cancer chemotherapy.

In part A of this study, patients were randomised to cohorts receiving darbepoetin alfa at doses of 0.5 to 8.0 m.c.g x kg(-1) x wk(-1) or to a control group receiving epoetin alfa at an initial dose of 150 U x kg(-1) three times weekly. In part B, the cohorts were darbepoetin alfa 3.0 to 9.0 m.c.g x kg(-1) every 2 weeks or epoetin alfa, initial dose 40 000 U x wk(-1). Safety was assessed by adverse events, changes in blood pressure, and formation of antibodies to darbepoetin alfa. Efficacy was assessed by several haematologic endpoints, including change in haemoglobin from baseline. The adverse event profile of darbepoetin alfa was similar to that of epoetin alfa. No relationship between the rapidity of haemoglobin response and any adverse event was observed. No antibodies to darbepoetin alfa were detected. Higher doses of darbepoetin alfa increased the proportion of patients with a haemoglobin response and decreased the median time to response. The overall dose of darbepoetin alfa required to produce a mean increase in haemoglobin does not increase when the dosing interval is increased from 1 to 2 weeks. Therapy with darbepoetin alfa is safe and effective in producing a dose-related increase in haemoglobin levels in patients with cancer receiving chemotherapy

Irish inquiry reports relating to perinatal deaths and pregnancy loss services

Aims: External inquiries are carried out following specific adverse events in healthcare, many in maternity care; to identify issues and make recommendations to improve standards of care. Methods: Ten publically-available national inquiry reports published between 2005-2018 relating to pregnancy loss services, were reviewed by 2 clinicians, separately, examining the content and recommendations from each report. Results: A total of 258 recommendations were made in 9 reports (90%). Five inquiries (50%) clearly stated that affected families were involved and four (40%) involved affected clinical staff. In 9 reports (90%) recommendations included: increase workforce staffing and/or training, strengthen clinical governance, enhance adverse incident management and comprehensive data collection e.g. maternity outcomes. Only two inquiry reports (20%) stated that feedback was sought from key stakeholders prior to publication. Conclusion: A collaborative and standardised inquiry process involving and supporting all persons affected as well as key stakeholders would ensure that all relevant issues are identified, recommendations are implemented and essential lessons are learned

The prognostic role of circulating tumor cells (CTCs) in lung cancer

© 2018 Kapeleris, Kulasinghe, Warkiani, Vela, Kenny, O'Byrne and Punyadeera. Lung cancer affects over 1. 8 million people worldwide and is the leading cause of cancer related mortality globally. Currently, diagnosis of lung cancer involves a combination of imaging and invasive biopsies to confirm histopathology. Non-invasive diagnostic techniques under investigation include "liquid biopsies" through a simple blood draw to develop predictive and prognostic biomarkers. A better understanding of circulating tumor cell (CTC) dissemination mechanisms offers promising potential for the development of techniques to assist in the diagnosis of lung cancer. Enumeration and characterization of CTCs has the potential to act as a prognostic biomarker and to identify novel drug targets for a precision medicine approach to lung cancer care. This review will focus on the current status of CTCs and their potential diagnostic and prognostic utility in this setting

Risk of new onset diabetes mellitus in patients with asthma or COPD taking inhaled corticosteroids

SummaryBackgroundA recent case-controlled study reported an increased risk of diabetes mellitus in patients treated with inhaled corticosteroids for asthma or COPD, versus age-matched controls.ObjectiveThe purpose of the current study was to evaluate whether there was an increased risk of new onset diabetes mellitus or hyperglycaemia among patients with asthma or COPD treated with inhaled corticosteroids.MethodsA retrospective analysis evaluated all double-blind, placebo-controlled, trials in patients ≥4 years of age involving budesonide or budesonide/formoterol in asthma (26 trials; budesonide: n = 9067; placebo: n = 5926), and in COPD (8 trials; budesonide: n = 4616; non-ICS: n = 3643). A secondary dataset evaluated all double-blind, controlled trials in asthma involving the use of inhaled corticosteroids (60 trials; budesonide: n = 33,496; fluticasone: n = 2773).ResultsIn the primary asthma dataset, the occurrence of diabetes mellitus/hyperglycaemia adverse events (AEs) was 0.13% for budesonide and 0.13% for placebo (HR 0.98 [95% CI: 0.38–2.50], p = 0.96) and serious adverse events (SAEs) was 0% for budesonide and 0.05% for placebo. In the secondary dataset, the occurrence of diabetes/hyperglycaemia as AE and SAE was 0.19% and 0.03%, respectively. In the COPD dataset, the occurrence of diabetes mellitus/hyperglycaemia AEs was 1.3% for budesonide and 1.2% for non-ICS (HR 0.99 [95% CI: 0.67–1.46], p = 0.96) and SAEs was 0.1% for budesonide and 0.03% for non-ICS.Conclusion and clinical relevanceTreatment with inhaled corticosteroids in patients with asthma or COPD was not associated with increased risk of new onset diabetes mellitus or hyperglycaemia

Generalised Apery numbers modulo 9

Whilst locoregional control of head and neck cancers (HNCs) has improved over the last four decades, long-term survival has remained largely unchanged. A possible reason for this is that the rate of distant metastasis has not changed. Such disseminated disease is reflected in measurable levels of cancer cells in the blood of HNC patients, referred to as circulating tumour cells (CTCs). Numerous marker-independent techniques have been developed for CTC isolation and detection. Recently, microfluidics-based platforms have come to the fore to avoid molecular bias. In this pilot, proof of concept study, we evaluated the use of the spiral microfluidic chip for CTC enrichment and subsequent detection in HNC patients. CTCs were detected in 13/24 (54%) HNC patients, representing both early to late stages of disease. Importantly, in 7/13 CTC-positive patients, CTC clusters were observed. This is the first study to use spiral microfluidics technology for CTC enrichment in HNC

Statement by Eric Mehnert and Rhonda Decontie collected by Rachel George on December 5, 2014

This is the author accepted manuscript. The final version is available from the Society for Neuroscience via the DOI in this recordFertility critically depends on the gonadotropin-releasing hormone (GnRH) pulse generator, a neural construct comprised of hypothalamic neurons co-expressing kisspeptin, neurokoinin-B and dynorphin. Here, using mathematical modelling and in-vivo optogenetics we reveal for the first time how this neural construct initiates and sustains the appropriate ultradian frequency essential for reproduction. Prompted by mathematical modelling, we show experimentally using female estrous mice that robust pulsatile release of luteinizing hormone, a proxy for GnRH, emerges abruptly as we increase the basal activity of the neuronal network using continuous low frequency optogenetic stimulation. Further increase in basal activity markedly increases pulse frequency and eventually leads to pulse termination. Additional model predictions that pulsatile dynamics emerge from non-linear positive and negative feedback interactions mediated through neurokinin-B and dynorphin signaling respectively are confirmed neuropharmacologically. Our results shed light on the long-elusive GnRH pulse generator offering new horizons for reproductive health and wellbeing.SIGNIFICANCE STATEMENTThe gonadotropin-releasing hormone (GnRH) pulse generator controls the pulsatile secretion of the gonadotropic hormones LH and FSH and is critical for fertility. The hypothalamic arcuate kisspeptin neurons are thought to represent the GnRH pulse generator, since their oscillatory activity is coincident with LH pulses in the blood; a proxy for GnRH pulses. However, the mechanisms underlying GnRH pulse generation remain elusive. We developed a mathematical model of the kisspeptin neuronal network and confirmed its predictions experimentally, showing how LH secretion is frequency-modulated as we increase the basal activity of the arcuate kisspeptin neurons in-vivo using continuous optogenetic stimulation. Our model provides a quantitative framework for understanding the reproductive neuroendocrine system and opens new horizons for fertility regulation.Engineering and Physical Sciences Research Council (EPSRC)Medical Research Council (MRC)Biotechnology and Biological Sciences Research Council (BBSRC

Drug Use as Boundary Play: A Qualitative Exploration of Gay Circuit Parties

Research findings have revealed that gay circuit parties may be locations that are disproportionately responsible for the increasing rates of many STIs/HIV among gay/bisexual men. Theories have been put forth that this may be the case because circuit parties are locales of prevalent drug use and unsafe sex. To explore the relationship between these two phenomena, in-depth qualitative interviews were undertaken with 17 men who (1) have sex with other men, (2) attended gay circuit parties in Montréal, Canada, in 2007. These revealed that drugs (including alcohol) were used intentionally to engage in unsafe sex, and then to justify this behavior after the fact. This process we called boundary play