Local Field effects on the radiative lifetime of emitters in surrounding media: virtual- or real-cavity model?

For emitters embedded in media of various refractive indices, different macroscopic or microscopic theoretical models predict different dependencies of the spontaneous emission lifetime on refractive index. Among those models are the two most promising models: the virtual-cavity model and the real-cavity model. It is a priori not clear which model is more relevant for a given situation. By close analysis of the available experimental results and examining the assumptions underlying the two models, we reach a consistent interpretation of the experimental results and give the criteria which model should apply for a given situation.Comment: 12 pages with 4 figure

Post-Transcriptional Dysregulation by miRNAs Is Implicated in the Pathogenesis of Gastrointestinal Stromal Tumor [GIST]

peer-reviewedIn contrast to adult mutant gastrointestinal stromal tumors [GISTs], pediatric/wild-type GISTs remain poorly understood overall, given their lack of oncogenic activating tyrosine kinase mutations. These GISTs, with a predilection for gastric origin in female patients, show limited response to therapy with tyrosine kinase inhibitors and generally pursue a more indolent course, but still may prove fatal. Defective cellular respiration appears to underpin tumor development in these wild-type cases, which as a group lack expression of succinate dehydrogenase [SDH] B, a surrogate marker for respiratory chain metabolism. Yet, only a small subset of the wild-type tumors show mutations in the genes coding for the SDH subunits [SDHx]. To explore additional pathogenetic mechanisms in these wild-type GISTs, we elected to investigate posttranscriptional regulation of these tumors by conducting microRNA (miRNA) profiling of a mixed cohort of 73 cases including 18 gastric pediatric wild-type, 25 (20 gastric, 4 small bowel and 1 retroperitoneal) adult wild-type GISTs and 30 gastric adult mutant GISTs. By this approach we have identified distinct signatures for GIST subtypes which correlate tightly with clinico-pathological parameters. A cluster of miRNAs on 14q32 show strikingly different expression patterns amongst GISTs, a finding which appears to be explained at least in part by differential allelic methylation of this imprinted region. Small bowel and retroperitoneal wild-type GISTs segregate with adult mutant GISTs and express SDHB, while adult wildtype gastric GISTs are dispersed amongst adult mutant and pediatric wild-type cases, clustering in this situation on the basis of SDHB expression. Interestingly, global methylation analysis has recently similarly demonstrated that these wild-type, SDHB-immunonegative tumors show a distinct pattern compared with KIT and PDGFRA mutant tumors, which as a rule do express SDHB. All cases with Carney triad within our cohort cluster together tightly.Funding was obtained from the Medical Research Charities Group (http://www.mrcg.ie/) and Health Research Board of Ireland (http://www.hrb.ie) (MO’S), The Children’s Medical and Research Foundation (http://www.cmrf.org) (MO’S), the GIST Cancer Awareness Foundation [GCAF] (http://www. gistawareness.org/)(MO’S), and research grants from the Life Raft Group (http://www.liferaftgroup.org/)(MD-R) and from the Fonds voor Wetenschappelijk Onderzoek Vlaanderen (http://www.fwo.be/)(grant # G.0286.05 MD-R)

Relativistic stars with a linear equation of state: analogy with classical isothermal spheres and black holes

We complete our previous investigation concerning the structure and the stability of "isothermal" spheres in general relativity. This concerns objects that are described by a linear equation of state $P=q\epsilon$ so that the pressure is proportional to the energy density. In the Newtonian limit $q\to 0$, this returns the classical isothermal equation of state. We consider specifically a self-gravitating radiation (q=1/3), the core of neutron stars (q=1/3) and a gas of baryons interacting through a vector meson field (q=1). We study how the thermodynamical parameters scale with the size of the object and find unusual behaviours due to the non-extensivity of the system. We compare these scaling laws with the area scaling of the black hole entropy. We also determine the domain of validity of these scaling laws by calculating the critical radius above which relativistic stars described by a linear equation of state become dynamically unstable. For photon stars, we show that the criteria of dynamical and thermodynamical stability coincide. Considering finite spheres, we find that the mass and entropy as a function of the central density present damped oscillations. We give the critical value of the central density, corresponding to the first mass peak, above which the series of equilibria becomes unstable. Finally, we extend our results to d-dimensional spheres. We show that the oscillations of mass versus central density disappear above a critical dimension d_{crit}(q). For Newtonian isothermal stars (q=0) we recover the critical dimension d_{crit}=10. For the stiffest stars (q=1) we find d_{crit}=9 and for a self-gravitating radiation (q=1/d) we find d_{crit}=9.96404372... very close to 10. Finally, we give analytical solutions of relativistic isothermal spheres in 2D gravity.Comment: A minor mistake in calculation has been corrected in the second version (v2

Multicentre, non-interventional study to assess the profile of patients with uncontrolled rhinitis prescribed a novel formulation of azelastine hydrochloride and fluticasone propionate in a single spray in routine clinical practice in the UK

OBJECTIVE: The aims of this study were (1) to characterise the type of patient prescribed MP-AzeFlu (Dymista, a novel formulation of azelastine hydrochloride, fluticasone propionate and excipients in a single spray) in real life in the UK and physicians' reasons for prescribing it and (2) to quantify the personal and societal burden of allergic rhinitis (AR) in the UK prior to MP-AzeFlu prescription. DESIGN, SETTING AND PARTICIPANTS: This multicentre, non-interventional study enrolled patients (n=193) with moderate-to-severe AR and acute symptoms who were eligible to receive treatment with MP-AzeFlu according to its licensed indications. Information was gathered on patient demographics, AR history and symptom severity, symptomatology and AR treatments in the previous calendar year (prior to MP-AzeFlu prescription). Physicians also recorded the number of previous AR visits, specific reasons for these visits and their reason for prescribing MP-AzeFlu. RESULTS: Most patients had seasonal AR either alone (10.4%) or in combination with perennial AR (35.2%), but many had AR of unknown origin (35.8%). Prior to MP-AzeFlu prescription, patients reported troublesome symptoms (78.2%) and sleep disturbance (64.8%), with congestion considered the most bothersome (54.4%) and ocular symptoms reported by 68.4% of patients. The most frequent reason for MP-AzeFlu prescription was that other therapies were not sufficient in the past (78.8%) or not sufficient to treat acute symptoms (16.1%). 79.3% of patients reported using ≥2 AR therapies in the past year. An average of 1.6 (SD 1.9) doctor visits due to AR were reported prior to MP-AzeFlu prescription. CONCLUSIONS: In the UK, MP-AzeFlu was prescribed for individuals (≥12 years) with moderate/severe AR irrespective of (1) previous AR treatment (mono or multiple), (2) previous or likely treatment failure, (3) phenotype, (4) number of previous physician visits for AR and (5) for the relief of both acute symptoms and in anticipation of allergen exposure

Is 8:30 a.m. Still Too Early to Start School? A 10:00 a.m. School Start Time Improves Health and Performance of Students Aged 13-16.

While many studies have shown the benefits of later school starts, including better student attendance, higher test scores, and improved sleep duration, few have used starting times later than 9:00 a.m. Here we report on the implementation and impact of a 10 a.m. school start time for 13 to 16-year-old students. A 4-year observational study using a before-after-before (A-B-A) design was carried out in an English state-funded high school. School start times were changed from 8:50 a.m. in study year 0, to 10 a.m. in years 1-2, and then back to 8:50 a.m. in year 3. Measures of student health (absence due to illness) and academic performance (national examination results) were used for all students. Implementing a 10 a.m. start saw a decrease in student illness after 2 years of over 50% (p < 0.0005 and effect size: Cohen's d = 1.07), and reverting to an 8:50 a.m. start reversed this improvement, leading to an increase of 30% in student illness (p < 0.0005 and Cohen's d = 0.47). The 10:00 a.m. start was associated with a 12% increase in the value-added number of students making good academic progress (in standard national examinations) that was significant (<0.0005) and equivalent to 20% of the national benchmark. These results show that changing to a 10:00 a.m. high school start time can greatly reduce illness and improve academic performance. Implementing school start times later than 8:30 a.m., which may address the circadian delay in adolescents' sleep rhythms more effectively for evening chronotypes, appears to have few costs and substantial benefits

Efficacy of once-daily tiotropium Respimat in adults with asthma at GINA Steps 2-5

Tiotropium Respimat is an efficacious add-on to maintenance treatment in patients with symptomatic asthma. Currently, the Global Initiative for Asthma (GINA) strategy recommends tiotropium for patients at Steps 4–5. To assess the clinical benefits of tiotropium Respimat across asthma severities, GINA Steps 2–5, a post hoc analysis of five double-blind trials (12–48-weeks; patients aged 18–75 years) investigated the effect of tiotropium Respimat, 5 μg or 2.5 μg, versus placebo, on peak forced expiratory volume in 1 s (FEV1) within 3 h post-dose (FEV1(0–3h)) response, and Asthma Control Questionnaire-7 (ACQ-7) responder rate. GINA step grouping was based on patients’ background treatment regimen. Baseline characteristics of patients (N = 2926) were balanced between treatments. Tiotropium Respimat showed consistent improvements in lung function across GINA steps; placebo-corrected peak FEV1(0–3h) improvements after tiotropium Respimat 5 μg and 2.5 μg were: Step 2 (Week 8), 135 mL (95% confidence interval: 84, 187) and 155 mL (103, 206); Step 3 (Week 24), 187 mL (139, 235) and 235 mL (187, 283); Step 4 (Week 24), 111 mL (63, 159) and 181 mL (35, 326); Step 5 (Week 24; 5 μg only), 164 mL (5, 323). Asthma control improved with tiotropium Respimat versus placebo, showing statistical significance (nominal P value) with tiotropium Respimat 5 μg at Step 4 (odds ratio 1.36 [1.03, 1.78]). Safety profiles were similar between treatments. In conclusion, tiotropium Respimat add-on therapy improves lung function, and may improve asthma control, in adults across disease severities.</p

Risks and Benefits of Preexposure and Postexposure Smallpox Vaccination1

This article presents a model and decision criteria for evaluating a person’s risk of pre- or postexposure smallpox vaccination in light of serious vaccine-related adverse events (death, postvaccine encephalitis and progressive vaccinia). Even at a 1-in-10 risk of 1,000 initial smallpox cases, a person in a population of 280 million has a greater risk for serious vaccine-related adverse events than a risk for smallpox. For a healthcare worker to accept preexposure vaccination, the risk for contact with an infectious smallpox case-patient must be >1 in 100, and the probability of 1,000 initial cases must be >1 in 1,000. A member of an investigation team would accept preexposure vaccination if his or her anticipated risk of contact is 1 in 2.5 and the risk of attack is assumed to be >1 in 16,000. The only circumstances in which postexposure vaccination would not be accepted are the following: if vaccine efficacy were <1%, the risk of transmission were <1%, and (simultaneously) the risk for serious vaccine-related adverse events were >1 in 5,000

Tiotropium Respimat® add-on therapy to inhaled corticosteroids in patients with symptomatic asthma improves clinical outcomes regardless of baseline characteristics

BACKGROUND: Despite currently available therapies and detailed treatment guidelines, many patients with asthma remain symptomatic. Tiotropium delivered by the soft mist inhaler Respimat®, as add-on therapy to medium-dose inhaled corticosteroids (ICS), has been shown to improve lung function and asthma control in patients with symptomatic moderate asthma. OBJECTIVE: To determine whether the efficacy of tiotropium Respimat® in asthma differs by patients' study baseline characteristics. METHODS: Two replicate Phase III, randomized, double-blind, placebo-controlled, parallel-group studies (MezzoTinA-asthma®; NCT01172808 and NCT01172821) of once-daily tiotropium Respimat 5 μg and 2.5 μg add-on to ICS were conducted in patients with symptomatic asthma despite treatment with medium-dose ICS with or without additional controllers. Subgroup analyses of peak forced expiratory volume in 1 s (FEV1), trough FEV1, risk of severe asthma exacerbation and Asthma Control Questionnaire responder rate were performed to determine whether results were influenced by patients' baseline characteristics. RESULTS: In this analysis, 523 patients received placebo while 517 and 519 patients received the 5 μg and 2.5 μg dose of tiotropium Respimat, respectively. The magnitude of the improvements in lung function and asthma control, as well as the reduced risk of severe exacerbation with both doses of tiotropium Respimat versus placebo, was independent of a broad range of baseline characteristics. CONCLUSIONS: Once-daily tiotropium Respimat as add-on to ICS is a beneficial treatment option for patients with asthma who remain symptomatic despite at least medium-dose ICS, regardless of baseline characteristics