The Detection of a 3.5-h Period in the Classical Nova Velorum 1999 (V382 Vel) and the Long Term Behavior of the Nova Light Curve

We present CCD photometry, light curve and time series analysis of the classical nova V382 Vel (N Vel 1999). The source was observed for 2 nights in 2000, 21 nights in 2001 and 7 nights in 2002 using clear filters. We report the detection of a distinct period in the light curve of the nova P=0.146126(18) d (3.5 h). The period is evident in all data sets, and we interpret it as the binary period of the system. We also measured an increase in the amplitude modulation of the optical light (in magnitude) by more than 55% from 2000 to 2001 and about 64% from 2001 to 2002. The pulse profiles in 2001 show deviations from a pure sinusoidal shape which progressively become more sinusoidal by 2002. The main cause of the variations in 2001 and 2002 can be explained with the occultation of the accretion disk by the secondary star. We interpret the observed deviations from a pure sinusoidal shape as additional flux resulting from the aspect variations of the irradiated face of the secondary star.Comment: 16 pages and 4 figures, accepted as it stands to be published in the Astronomical Journal (AJ

Cerebello-Thalamo-Cortical Network Dynamics in the Harmaline Rodent Model of Essential Tremor

This is the final version. Available on open access from Frontiers Media via the DOI in this recordData Availability Statement: The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.Essential Tremor (ET) is a common movement disorder, characterised by a posture or movement-related tremor of the upper limbs. Abnormalities within cerebellar circuits are thought to underlie the pathogenesis of ET, resulting in aberrant synchronous oscillatory activity within the thalamo-cortical network leading to tremors. Harmaline produces pathological oscillations within the cerebellum, and a tremor that phenotypically resembles ET. However, the neural network dynamics in cerebellar-thalamo-cortical circuits in harmaline-induced tremor remains unclear, including the way circuit interactions may be influenced by behavioural state. Here, we examined the effect of harmaline on cerebello-thalamo-cortical oscillations during rest and movement. EEG recordings from the sensorimotor cortex and local field potentials (LFP) from thalamic and medial cerebellar nuclei were simultaneously recorded in awake behaving rats, alongside measures of tremor using EMG and accelerometery. Analyses compared neural oscillations before and after systemic administration of harmaline (10 mg/kg, I.P), and coherence across periods when rats were resting vs. moving. During movement, harmaline increased the 9-15 Hz behavioural tremor amplitude and increased thalamic LFP coherence with tremor. Medial cerebellar nuclei and cerebellar vermis LFP coherence with tremor however remained unchanged from rest. These findings suggest harmaline-induced cerebellar oscillations are independent of behavioural state and associated changes in tremor amplitude. By contrast, thalamic oscillations are dependent on behavioural state and related changes in tremor amplitude. This study provides new insights into the role of cerebello-thalamo-cortical network interactions in tremor, whereby neural oscillations in thalamocortical, but not cerebellar circuits can be influenced by movement and/or behavioural tremor amplitude in the harmaline model.Medical Research Council (MRC)Biotechnology and Biological Sciences Research Council (BBSRC

Penetrance estimates for BRCA1, BRCA2 (also applied to Lynch syndrome) based on presymptomatic testing: a new unbiased method to assess risk?

PURPOSE: The identification of BRCA1, BRCA2 or mismatch repair (MMR) pathogenic gene variants in familial breast/ovarian/colorectal cancer families facilitates predictive genetic testing of at-risk relatives. However, controversy still exists regarding overall lifetime risks of cancer in individuals testing positive. METHODS: We assessed the penetrance of BRCA1, BRCA2, MLH1 and MSH2 mutations in men and women using Bayesian calculations based on ratios of positive to negative presymptomatic testing by 10-year age cohorts. Mutation position was also assessed for BRCA1/BRCA2. RESULTS: Using results from 2264 presymptomatic tests in first-degree relatives (FDRs) of mutation carriers in BRCA1 and BRCA2 and 646 FDRs of patients with MMR mutations, we assessed overall associated cancer penetrance to age of 68 years as 73% (95% CI 61% to 82%) for BRCA1, 60% (95% CI 49% to 71%) for BRCA2, 95% (95% CI 76% to 99%) for MLH1% and 61% (95% CI 49% to 76%) for MSH2. There was no evidence for significant penetrance for males in BRCA1 or BRCA2 families and males had equivalent penetrance to females with Lynch syndrome. Mutation position and degree of family history influenced penetrance in BRCA2 but not BRCA1. CONCLUSION: We describe a new method for assessing penetrance in cancer-prone syndromes. Results are in keeping with published prospective series and present modern-day estimates for overall disease penetrance that bypasses retrospective series biases

Pathogenic germline variants in patients with features of hereditary renal cell carcinoma: Evidence for further locus heterogeneity.

Inherited renal cell carcinoma (RCC) is associated with multiple familial cancer syndromes but most individuals with features of non-syndromic inherited RCC do not harbor variants in the most commonly tested renal cancer predisposition genes (CPGs). We investigated whether undiagnosed cases might harbor mutations in CPGs that are not routinely tested for by testing 118 individuals with features suggestive of inherited RCC (family history of RCC, two or more primary RCC aged <60 years, or early onset RCC ≤46 years) for the presence of pathogenic variants in a large panel of CPGs. All individuals had been prescreened for pathogenic variants in the major RCC genes. We detected pathogenic or likely pathogenic (P/LP) variants of potential clinical relevance in 16.1% (19/118) of individuals, including P/LP variants in BRIP1 (n = 4), CHEK2 (n = 3), MITF (n = 1), and BRCA1 (n = 1). Though the power to detect rare variants was limited by sample size the frequency of truncating variants in BRIP1, 4/118, was significantly higher than in controls (P = 5.92E-03). These findings suggest that the application of genetic testing for larger inherited cancer gene panels in patients with indicators of a potential inherited RCC can increase the diagnostic yield for P/LP variants. However, the clinical utility of such a diagnostic strategy requires validation and further evaluation and in particular, confirmation of rarer RCC genotype-phenotype associations is required

Measurement of telescope transmission using a Collimated Beam Projector

With the increasingly large number of type Ia supernova being detected by current-generation survey telescopes, and even more expected with the upcoming Rubin Observatory Legacy Survey of Space and Time, the precision of cosmological measurements will become limited by systematic uncertainties in flux calibration rather than statistical noise. One major source of systematic error in determining SNe Ia color evolution (needed for distance estimation) is uncertainty in telescope transmission, both within and between surveys. We introduce here the Collimated Beam Projector (CBP), which is meant to measure a telescope transmission with collimated light. The collimated beam more closely mimics a stellar wavefront as compared to flat-field based instruments, allowing for more precise handling of systematic errors such as those from ghosting and filter angle-of-incidence dependence. As a proof of concept, we present CBP measurements of the StarDICE prototype telescope, achieving a standard (1 sigma) uncertainty of 3 % on average over the full wavelength range measured with a single beam illumination

The relationship between shame, perfectionism and Anorexia Nervosa: a grounded theory study

Objectives The aim of this study was to explore the potential relationship between shame, perfectionism and Anorexia Nervosa (AN) and their impact on recovery from AN. Method Semi-structured interviews were conducted with 11 people currently accessing services for AN. Interviews were transcribed and analysed using constructivist-grounded theory methodology. Results A model was developed which found a vicious cycle between shame and perfectionism. Participants tried to alleviate their feelings of shame by striving for perfectionism, however failing caused them more shame. Participants who disclosed childhood trauma believed their shame preceded their perfectionism. Participants who did not disclose trauma either believed their perfectionism preceded shame or they were unsure of which occurred first. Participants' responses suggested the following pathways from perfectionism to AN: needing goals; the need for a perfect life including a perfect body and AN being something they could be perfect at. The pathways identified between shame and AN entailed mechanisms via which AN could be used to escape shame, either by seeking pride through AN, seeking to numb shame through AN, seeking to escape body shame and punishing the self. AN was found to feed back into shame in two ways: when people had AN they felt ashamed when they broke their dietary rules, and also simultaneously people felt ashamed of their AN as they were not able to recover. Shame and perfectionism influenced one another in a cyclical pattern, in which shame drove perfectionism and not attaining high standards led to shame. Shame and perfectionism also impacted on recovery in several ways. AN functioned to numb participants' emotions, becoming part of their identity over time. AN also brought respite from a constant striving towards perfectionism. The need for a perfect recovery also influenced their motivation to engage in treatment, and fear of a return of strong emotions was another deterrent to recovery. Conclusion The findings of this paper show perfectionism and shame to both be important in the aetiology and maintenance of AN and to have an impact on recovery from AN

The simulation of mineral dust in the United Kingdom Earth System Model UKESM1

Mineral dust plays an important role in Earth system models and is linked to many components, including atmospheric wind speed, precipitation and radiation, surface vegetation cover and soil properties and oceanic biogeochemical systems. In this paper, the dust scheme in the first configuration of the United Kingdom Earth System Model UKESM1 is described, and simulations of dust and its radiative effects are presented and compared with results from the parallel coupled atmosphere–ocean general circulation model (GCM) HadGEM3-GC3.1. Not only changes in the driving model fields but also changes in the dust size distribution are shown to lead to considerable differences to the present-day dust simulations and to projected future changes. UKESM1 simulations produce a present-day, top-of-the-atmosphere (ToA) dust direct radiative effect (DRE – defined as the change in downward net flux directly due to the presence of dust) of 0.086 W m−2 from a dust load of 19.5 Tg. Under climate change pathways these values decrease considerably. In the 2081–2100 mean of the Shared Socioeconomic Pathway SSP5–8.45 ToA DRE reaches 0.048 W m−2 from a load of 15.1 Tg. In contrast, in HadGEM3-GC3.1 the present-day values of −0.296 W m−2 and 15.0 Tg are almost unchanged at −0.289 W m−2 and 14.5 Tg in the 2081–2100 mean. The primary mechanism causing the differences in future dust projections is shown to be the vegetation response, which dominates over the direct effects of warming in our models. Though there are considerable uncertainties associated with any such estimates, the results presented demonstrate both the importance of the size distribution for dust modelling and also the necessity of including Earth system processes such as interactive vegetation in dust simulations for climate change studies

The Persistent Problem: Inequality, Difference, and the Challenge of Development

This report highlights the complex, multidimensional nature of inequality in the era of globalization. It documents that despite the impressive strides by nations like China and India, absolute inequality between the richest and poorest countries is greater than ever before in history. It demonstrates that the rise of China and India creates a new dimension to the persistent problem of inequality

Coronary CT Angiography and 5-Year Risk of Myocardial Infarction.

BACKGROUND: Although coronary computed tomographic angiography (CTA) improves diagnostic certainty in the assessment of patients with stable chest pain, its effect on 5-year clinical outcomes is unknown. METHODS: In an open-label, multicenter, parallel-group trial, we randomly assigned 4146 patients with stable chest pain who had been referred to a cardiology clinic for evaluation to standard care plus CTA (2073 patients) or to standard care alone (2073 patients). Investigations, treatments, and clinical outcomes were assessed over 3 to 7 years of follow-up. The primary end point was death from coronary heart disease or nonfatal myocardial infarction at 5 years. RESULTS: The median duration of follow-up was 4.8 years, which yielded 20,254 patient-years of follow-up. The 5-year rate of the primary end point was lower in the CTA group than in the standard-care group (2.3% [48 patients] vs. 3.9% [81 patients]; hazard ratio, 0.59; 95% confidence interval [CI], 0.41 to 0.84; P=0.004). Although the rates of invasive coronary angiography and coronary revascularization were higher in the CTA group than in the standard-care group in the first few months of follow-up, overall rates were similar at 5 years: invasive coronary angiography was performed in 491 patients in the CTA group and in 502 patients in the standard-care group (hazard ratio, 1.00; 95% CI, 0.88 to 1.13), and coronary revascularization was performed in 279 patients in the CTA group and in 267 in the standard-care group (hazard ratio, 1.07; 95% CI, 0.91 to 1.27). However, more preventive therapies were initiated in patients in the CTA group (odds ratio, 1.40; 95% CI, 1.19 to 1.65), as were more antianginal therapies (odds ratio, 1.27; 95% CI, 1.05 to 1.54). There were no significant between-group differences in the rates of cardiovascular or noncardiovascular deaths or deaths from any cause. CONCLUSIONS: In this trial, the use of CTA in addition to standard care in patients with stable chest pain resulted in a significantly lower rate of death from coronary heart disease or nonfatal myocardial infarction at 5 years than standard care alone, without resulting in a significantly higher rate of coronary angiography or coronary revascularization. (Funded by the Scottish Government Chief Scientist Office and others; SCOT-HEART ClinicalTrials.gov number, NCT01149590 .)