Evolution of the number of accreting white dwarfs with shell nuclear burning and of occurrence rate of SN Ia

We analyze temporal evolution of the number of accreting white dwarfs with shell hydrogen burning in semidetached and detached binaries. We consider a stellar system in which star formation lasts for 10 Gyr with a constant rate, as well as a system in which the same amount of stars is formed in a single burst lasting for 1 Gyr. Evolution of the number of white dwarfs is confronted to the evolution of occurrence rate of events that usually are identified with SN Ia or accretion-induced collapses, i.e. with accumulation of Chandrasekhar mass by a white dwarf or a merger of a pair of CO white dwarfs with total mass not lower than the Chandrasekhar one. In the systems with a burst of star formation, at $t=$10 Gyr observed supersoft X-ray sources, most probably, are not precursors of SN Ia. The same is true for an overwhelming majority of the sources in the systems with constant star formation rate. In the systems of both kinds mergers of white dwarfs is the dominant SN Ia scenario. In symbiotic binaries, accreting CO-dwarfs do not accumulate enough mass for SN Ia explosion, while ONeMg-dwarfs finish their evolution by an accretion-induced collapse with formation of a neutron star.Comment: 11 pages, 2 figures, accepted by Astronomy Letter

Phase 1 study of chemoradiotherapy combined with nivolumab +/- Ipilimumab for the curative treatment of muscle-invasive bladder cancer

Background: Muscle-invasive bladder cancer (MIBC) has a poor prognosis. Chemoradiotherapy (CRT) in selected patients has comparable results to radical cystectomy. Results of neoadjuvant immune checkpoint inhibitors (ICIs) before radical cystectomy are promising. We hypothesize that ICI concurrent to CRT (iCRT) is safe and may improve treatment outcomes. Objective: To determine the safety of iCRT for MIBC. Design, setting, and participants: This multicenter, phase 1b, open-label, dose-escalation study determined the safety of CRT with three ICI regimens in patients with nonmetastatic (T2-4aN0-1) MIBC. Twenty-six patients received mitomycin C/capecitabine and 20 x 2.75 Gy to the bladder. Tolerability was evaluated in a cohort of up to ten patients. If two or fewer out of the first six patients or three or fewer of ten patients experienced dose-limiting toxicity (DLT), accrual continued in the next cohort. Intervention: Patients received nivolumab 480 mg (NIVO480), nivolumab 3 mg/kg and ipilimumab 1 mg/kg (NIVO3 + IPI1), or nivolumab 1 mg/kg and ipilimumab 3 mg/kg (IPI3 + NIVO1). Outcome measurements and statistical analysis: The primary endpoint was safety. Secondary objectives were response rate, disease-free survival, metastatic-free survival (MFS), and overall survival (OS). Results and limitations: In the NIVO480 cohort, no patients experienced DLT. The NIVO3 + IPI1 2 patients experienced DLT, thrombocytopenia (grade 4), and asystole (grade 5). IPI3 + NIVO1 was discontinued after three out of six patients experienced DLT. Clinically significant adverse events (AEs) of grade >= 3 occurred in zero, three, and five patients in the NIVO480, NIVO3 + IPI1, and IPI3 + NIVO1 groups, respectively. The most common AEs were immune related and gastrointestinal. MFS and OS were 90% at 2 yr for NIVO480 and 90% at 1 yr for NIVO3 + IPI1. Limitations include the absence of a centralized pathology and radiology review, and a lack of biomarker analysis. Conclusions: In this dose-finding study of iCRT, the regimens of nivolumab monotherapy and nivolumab 3 mg/kg with ipilimumab 1 mg/kg have acceptable toxicity. Patient summary: We tested the safety of a new bladder-sparing treatment modality for muscle-invasive bladder cancer patients, combiningimmunecheckpoint inhibitors simultaneously with chemoradiotherapy. We report that two regimens, nivolumab monotherapy and nivolumab 3 mg/kg with ipilimumab 1 mg/kg, are safe and can be used in phase 3 trials

An assessment of best practices of extreme weather insurance and directions for a more resilient society

Extreme weather resilience has been defined as being based on three pillars: resistance (the ability to lower impacts), recovery (the ability to bounce back), and adaptive capacity (the ability to learn and improve). These resilience pillars are important both before and after the occurrence of extreme weather events. Extreme weather insurance can influence these pillars of resilience depending on how particular insurance mechanisms are structured. We explore how the lessons learnt from the current best insurance practices can improve resilience to extreme weather events. We employ an extensive inventory of private property and agricultural crop insurance mechanisms to conduct a multi-criteria analysis of insurance market outcomes. We draw conclusions regarding the patterns in the best practice from six European countries to increase resilience. We suggest that requirements to buy a bundle extreme weather event insurance with general insurance packages are strengthened and supported with structures to financing losses through public-private partnerships. Moreover, support for low income households through income vouchers could be provided. Similarly, for the agricultural sector we propose moving towards comprehensive crop yield insurance linked to general agricultural subsidies. In both cases a nationally representative body can coordinate the various stakeholders into acting in concert

Genome-wide meta-analysis of variant-by-diuretic interactions as modulators of lipid traits in persons of European and African ancestry

Hypertension (HTN) is a significant risk factor for cardiovascular morbidity and mortality. Metabolic abnormalities, including adverse cholesterol and triglycerides (TG) profiles, are frequent comorbid findings with HTN and contribute to cardiovascular disease. Diuretics, which are used to treat HTN and heart failure, have been associated with worsening of fasting lipid concentrations. Genome-wide meta-analyses with 39,710 European-ancestry (EA) individuals and 9925 African-ancestry (AA) individuals were performed to identify genetic variants that modify the effect of loop or thiazide diuretic use on blood lipid concentrations. Both longitudinal and cross sectional data were used to compute cohort-specific interaction results, which were then combined through meta-analysis in each ancestry. These ancestry-specific results were further combined through trans-ancestry meta-analysis. Analysis of EA data identified two genome-wide significant (p < 5 × 10−8) loci with single nucleotide variant (SNV)-loop diuretic interaction on TG concentrations (including COL11A1). Analysis of AA data identified one genome-wide significant locus adjacent to BMP2 with SNV-loop diuretic interaction on TG concentrations. Trans-ancestry analysis strengthened evidence of association for SNV-loop diuretic interaction at two loci (KIAA1217 and BAALC). There were few significant SNV-thiazide diuretic interaction associations on TG concentrations and for either diuretic on cholesterol concentrations. Several promising loci were identified that may implicate biologic pathways that contribute to adverse metabolic side effects from diuretic therapy

Astronomical Distance Determination in the Space Age: Secondary Distance Indicators

The formal division of the distance indicators into primary and secondary leads to difficulties in description of methods which can actually be used in two ways: with, and without the support of the other methods for scaling. Thus instead of concentrating on the scaling requirement we concentrate on all methods of distance determination to extragalactic sources which are designated, at least formally, to use for individual sources. Among those, the Supernovae Ia is clearly the leader due to its enormous success in determination of the expansion rate of the Universe. However, new methods are rapidly developing, and there is also a progress in more traditional methods. We give a general overview of the methods but we mostly concentrate on the most recent developments in each field, and future expectations. © 2018, The Author(s)

Genome-wide meta-analysis of variant-by-diuretic interactions as modulators of lipid traits in persons of European and African ancestry

Hypertension (HTN) is a significant risk factor for cardiovascular morbidity and mortality. Metabolic abnormalities, including adverse cholesterol and triglycerides (TG) profiles, are frequent comorbid findings with HTN and contribute to cardiovascular disease. Diuretics, which are used to treat HTN and heart failure, have been associated with worsening of fasting lipid concentrations. Genome-wide meta-analyses with 39,710 European-ancestry (EA) individuals and 9925 African-ancestry (AA) individuals were performed to identify genetic variants that modify the effect of loop or thiazide diuretic use on blood lipid concentrations. Both longitudinal and cross sectional data were used to compute cohort-specific interaction results, which were then combined through meta-analysis in each ancestry. These ancestry-specific results were further combined through trans-ancestry meta-analysis. Analysis of EA data identified two genome-wide significant (p < 5 × 10−8) loci with single nucleotide variant (SNV)-loop diuretic interaction on TG concentrations (including COL11A1). Analysis of AA data identified one genome-wide significant locus adjacent to BMP2 with SNV-loop diuretic interaction on TG concentrations. Trans-ancestry analysis strengthened evidence of association for SNV-loop diuretic interaction at two loci (KIAA1217 and BAALC). There were few significant SNV-thiazide diuretic interaction associations on TG concentrations and for either diuretic on cholesterol concentrations. Several promising loci were identified that may implicate biologic pathways that contribute to adverse metabolic side effects from diuretic therapy

Has the Rate of CD4 Cell Count Decline before Initiation of Antiretroviral Therapy Changed over the Course of the Dutch HIV Epidemic among MSM?

Introduction:Studies suggest that the HIV-1 epidemic in the Netherlands may have become more virulent, leading to faster disease progression if untreated. Analysis of CD4 cell count decline before antiretroviral therapy (ART) initiation, a surrogate marker for disease progression, may be hampered by informative censoring as ART initiation is more likely with a steeper CD4 cell count decline.Methods:Development of CD4 cell count from 9 to 48 months after seroconversion was analyzed using a mixed-effects model and 2 models that jointly modeled CD4 cell counts and time to censoring event (start ART

Transformation with the sun

This research document is the result of an investigation on the subject of the use of the sun in the transformation of an existing building. The report is written as an informative document. The study has a generic character, which means that the research will be useful for others who are dealing with a transformation of existing buildings in a bioclimatic way.Lab 09Architectural EngineeringArchitectur

The role of the EORTC pathologist in clinical trials: achievements and perspectives. European Organisation for Research and Treatment of Cancer.

Item does not contain fulltextThe role of the pathologist in clinical trials (CT) is focused on three activities: pathology review, translational research, and participation in scientific committees. The primary goal of pathology review in CT is the quality control (QC) of the diagnosis and prognostic parameters. Important contributions have been achieved in the context of QC for CT such as new classifications of diseases or identification of new prognostic markers that are now widely used. Telematics implemented in some EORTC groups markedly facilitate the pathology review. The pathologist has a key-role in translational research for the identification of new targets in tissue specimens that may eventually lead to new therapeutics and for the understanding of the mechanisms involved in tumour progression. The gap between individualised prognosis and therapeutical possibilities has been considerably reduced by the development of drugs targeted on specific molecular defects. The paradigm of this is the treatment of stromal tumours by STI-571. For proper selection of patients to be treated, information on the expression of the molecules involved is needed, which is well suited for pathologists. The access to tissue resources from patients included in CT is a major goal to enhance translational research, both for brand institution and CT organisations. Active involvement of pathologists in scientific committees and interactions with the pharmaceutical industry is mandatory for an optimal design of CT protocols. In addition, translational research is a resource-consuming activity that necessitates an adequate financial flow to create a proper infrastructure at least for sponsored trials to the participating pathology departments and committees