Corrections to Hawking-like Radiation for a Friedmann-Robertson-Walker Universe

Recently, a Hamilton-Jacobi method beyond semiclassical approximation in black hole physics was developed by \emph{Banerjee} and \emph{Majhi}\cite{beyond0}. In this paper, we generalize their analysis of black holes to the case of Friedmann-Robertson-Walker (FRW) universe. It is shown that all the higher order quantum corrections in the single particle action are proportional to the usual semiclassical contribution. The corrections to the Hawking-like temperature and entropy of apparent horizon for FRW universe are also obtained. In the corrected entropy, the area law involves logarithmic area correction together with the standard inverse power of area term.Comment: 10 pages, no figures, comments are welcome; v2: references added and some typoes corrected, to appear in Euro.Phys.J.C; v3:a defect corrected. We thank Dr.Elias Vagenas for pointing out a defect of our pape

The spatial coverage of dairy cattle urine patches in an intensively grazed pasture system

Accurate field data on the paddock area affected by cow urine depositions are critical to the estimation and modelling of nitrogen (N) losses and N management in grazed pasture systems. A new technique using survey-grade global positioning system (GPS) technology was developed to precisely measure the paddock spatial area coverage, diversity and distribution of dairy cattle urine patches in grazed paddocks over time. A 4-year study was conducted on the Lincoln University Dairy Farm (LUDF), Canterbury, New Zealand, from 2003 to 2007. Twelve field plots, each 100m² in area, were established on typical grazing areas of the farm. All urine and dung deposits within the plots were visually identified, the pasture response area (radius) measured and position marked with survey-grade GPS. The plots were grazed as part of the normal grazing rotation of the farm and urine and dung deposits measured at 12-week intervals. The data were collated using spatial (GIS) software and an assessment of annual urine patch coverage and spatial distribution was made. Grazing intensities ranged from 17645 to 30295 cow grazing h/ha/yr. Mean annual areas of urine patches ranged from 0·34 to 0·40m² (4-year mean 0·37±0·009m²), with small but significant variation between years and seasons. Mean annual urine patch numbers were 6240±124 patches/ha/yr. The mean proportional area coverage for a single sampling event or season was 0·058 and the mean proportional annual urine patch coverage was 0·232±0·0071. There was a strong linear relationship between annual cow grazing h/ha and urine patch numbers/ha (R²=0·69) and also annual urine patch area coverage (R²=0·77). Within the stocking densities observed in this study, an annual increase of 10 000 cow grazing h/ha increased urine patch numbers by 1800 urine patches/ha/yr and annual urine patch area coverage by 0·07. This study presents new quantitative data on urine patch size, numbers and the spatial coverage of patches on a temporal basis

Thermodynamics Inducing Massive Particles' Tunneling and Cosmic Censorship

By calculating the change of entropy, we prove that the first law of black hole thermodynamics leads to the tunneling probability of massive particles through the horizon, including the tunneling probability of massive charged particles from the Reissner-Nordstr\"om black hole and the Kerr-Newman black hole. Novelly, we find the trajectories of massive particles are close to that of massless particles near the horizon, although the trajectories of massive charged particles may be affected by electromagnetic forces. We show that Hawking radiation as massive particles tunneling does not lead to violation of the weak cosmic-censorship conjecture

Thermodynamics in f(R)f(R) gravity in the Palatini formalism

We investigate thermodynamics of the apparent horizon in $f(R)$ gravity in the Palatini formalism with non-equilibrium and equilibrium descriptions. We demonstrate that it is more transparent to understand the horizon entropy in the equilibrium framework than that in the non-equilibrium one. Furthermore, we show that the second law of thermodynamics can be explicitly verified in both phantom and non-phantom phases for the same temperature of the universe outside and inside the apparent horizon.Comment: 20 pages, no figure, accepted in JCA

A laboratory-based scoring system predicts early treatment in Rai 0 chronic lymphocytic leukemia

We present a laboratory-based prognostic calculator (designated CRO score) to risk stratify treatment-free survival in early stage (Rai 0) chronic lymphocytic leukemia developed using a training-validation model in a series of 1,879 cases from Italy, the United Kingdom and the United States. By means of regression analysis, we identified five prognostic variables with weighting as follows: deletion of the short arm of chromosome 17 and unmutated immunoglobulin heavy chain gene status, 2 points; deletion of the long arm of chromosome 11, trisomy of chromosome 12, and white blood cell count>32.0x103/microliter, 1 point. Low, intermediate and high-risk categories were established by recursive partitioning in a training cohort of 478 cases, and then validated in four independent cohorts of 144/395/540/322 cases, as well as in the composite validation cohort. Concordance indices were 0.75 in the training cohort and ranged from 0.63 to 0.74 in the four validation cohorts (0.69 in the composite validation cohort). These findings advocate potential application of our novel prognostic calculator to better stratify early-stage chronic lymphocytic leukemia, and aid case selection in risk-adapted treatment for early disease. Furthermore, they support immunocytogenetic analysis in Rai 0 chronic lymphocytic leukemia being performed at the time of diagnosis to aid prognosis and treatment, particularly in today's chemo-free era

Static Spherically Symmetric Solutions in F(R) Gravity

A Lagrangian derivation of the Equation of Motion (EOM) for static spherically symmetric metrics in F(R) modified gravity is presented. For a large class of metrics, our approach permits to reduce the EOM to a single equation and we show how it is possible to construct exact solutions in $F(R)$-gravity. All known exact solutions are recovered. We also exibit a new non trivial solution with non constant Ricci scalar.Comment: 8 pages, published version, some references added, a minor modificatio

Unruh--DeWitt detectors in spherically symmetric dynamical space-times

In the present paper, Unruh--DeWitt detectors are used in order to investigate the issue of temperature associated with a spherically symmetric dynamical space-times. Firstly, we review the semi-classical tunneling method, then we introduce the Unruh--DeWitt detector approach. We show that for the generic static black hole case and the FRW de Sitter case, making use of peculiar Kodama trajectories, semiclassical and quantum field theoretic techniques give the same standard and well known thermal interpretation, with an associated temperature, corrected by appropriate Tolman factors. For a FRW space-time interpolating de Sitter space with the Einstein--de Sitter universe (that is a more realistic situation in the frame of $\Lambda$CDM cosmologies), we show that the detector response splits into a de Sitter contribution plus a fluctuating term containing no trace of Boltzmann-like factors, but rather describing the way thermal equilibrium is reached in the late time limit. As a consequence, and unlike the case of black holes, the identification of the dynamical surface gravity of a cosmological trapping horizon as an effective temperature parameter seems lost, at least for our co-moving simplified detectors. The possibility remains that a detector performing a proper motion along a Kodama trajectory may register something more, in which case the horizon surface gravity would be associated more likely to vacuum correlations than to particle creation.Comment: 19 pages, to appear on IJTP. arXiv admin note: substantial text overlap with arXiv:1101.525

Addition of nintedanib or placebo to neoadjuvant gemcitabine and cisplatin in locally advanced muscle-invasive bladder cancer (NEOBLADE) : a double-blind, randomised, phase 2 trial

Background Recurrence is common after neoadjuvant chemotherapy and radical treatment for muscle-invasive bladder cancer. We investigated the effect of adding nintedanib to neoadjuvant chemotherapy on response and survival in muscle-invasive bladder cancer. Methods NEOBLADE was a parallel-arm, double-blind, randomised, placebo-controlled, phase 2 trial of neoadjuvant gemcitabine and cisplatin chemotherapy with nintedanib or placebo in locally advanced muscle-invasive bladder cancer. Patients aged 18 years or older, with an Eastern Cooperative Oncology Group performance status of 0–1, were recruited from 15 hospitals in the UK. Patients were randomly assigned (1:1) to nintedanib or placebo using permuted blocks with random block sizes of two or four, stratified by centre and glomerular filtration rate. Treatments were allocated using an interactive web-based system, and patients and investigators were masked to treatment allocation throughout the study. Patients received oral nintedanib (150 mg or 200 mg twice daily for 12 weeks) or placebo, in addition to usual neoadjuvant chemotherapy with intravenous gemcitabine 1000 mg/m2 on days 1 and 8 and intravenous cisplatin 70 mg/m2 on day 1 of a 3-weekly cycle. The primary endpoint was pathological complete response rate, assessed at cystectomy or at day 8 of cycle 3 (plus or minus 7 days) if cystectomy did not occur. Primary analyses were done in the intention-to-treat population. The trial is registered with EudraCT, 2012-004895-01, and ISRCTN, 56349930, and has completed planned recruitment. Findings Between Dec 4, 2014, and Sept 3, 2018, 120 patients were recruited and were randomly allocated to receive nintedanib (n=57) or placebo (n=63). The median follow-up for the study was 33·5 months (IQR 14·0–44·0). Pathological complete response in the intention-to-treat population was reached in 21 (37%) of 57 patients in the nintedanib group and 20 (32%) of 63 in the placebo group (odds ratio [OR] 1·25, 70% CI 0·84–1·87; p=0·28). Grade 3 or worse toxicities were observed in 53 (93%) of 57 participants who received nintedanib and 50 (79%) of 63 patients in the placebo group (OR 1·65, 95% CI 0·74–3·65; p=0·24). The most common grade 3 or worse adverse events were thromboembolic events (17 [30%] of 57 patients in the nintedanib group vs 13 [21%] of 63 patients in the placebo group [OR 1·63, 95% CI 0·71–3·76; p=0·29]) and decreased neutrophil count (22 [39%] in the nintedanib group vs seven [11%] in the placebo group [5·03, 1·95–13·00; p=0·0006]). 45 treatment-related serious adverse events occurred in the nintedanib group and 43 occurred in the placebo group. One treatment-related death occurred in the placebo group, which was due to myocardial infarction. Interpretation The addition of nintedanib to chemotherapy was safe but did not improve the rate of pathological complete response in muscle-invasive bladder cancer

Recent Randomized Trials of Antithrombotic Therapy for Patients With COVID-19: JACC State-of-the-Art Review

Endothelial injury and microvascular/macrovascular thrombosis are common pathophysiological features of coronavirus disease-2019 (COVID-19). However, the optimal thromboprophylactic regimens remain unknown across the spectrum of illness severity of COVID-19. A variety of antithrombotic agents, doses, and durations of therapy are being assessed in ongoing randomized controlled trials (RCTs) that focus on outpatients, hospitalized patients in medical wards, and patients critically ill with COVID-19. This paper provides a perspective of the ongoing or completed RCTs related to antithrombotic strategies used in COVID-19, the opportunities and challenges for the clinical trial enterprise, and areas of existing knowledge, as well as data gaps that may motivate the design of future RCTs. © 2021 American College of Cardiology Foundatio

Intermediate versus standard-dose prophylactic anticoagulation and statin therapy versus placebo in critically-ill patients with COVID-19: Rationale and design of the INSPIRATION/INSPIRATION-S studies

Background: Microvascular and macrovascular thrombotic events are among the hallmarks of coronavirus disease 2019 (COVID-19). Furthermore, the exuberant immune response is considered an important driver of pulmonary and extrapulmonary manifestations of COVID-19. The optimal management strategy to prevent thrombosis in critically-ill patients with COVID-19 remains unknown. Methods: The Intermediate versus Standard-dose Prophylactic anticoagulation In cRitically-ill pATIents with COVID-19: An opeN label randomized controlled trial (INSPIRATION) and INSPIRATION-statin (INSPIRATION-S) studies test two independent hypotheses within a randomized controlled trial with 2 � 2 factorial design. Hospitalized critically-ill patients with reverse transcription polymerase chain reaction confirmed COVID-19 will be randomized to intermediate-dose versus standard dose prophylactic anticoagulation. The 600 patients undergoing this randomization will be screened and if meeting the eligibility criteria, will undergo an additional double-blind stratified randomization to atorvastatin 20 mg daily versus matching placebo. The primary endpoint, for both hypotheses will be tested for superiority and includes a composite of adjudicated acute arterial thrombosis, venous thromboembolism (VTE), use of extracorporeal membrane oxygenation, or all-cause death within 30 days from enrollment. Key secondary endpoints include all-cause mortality, adjudicated VTE, and ventilator-free days. Key safety endpoints include major bleeding according to the Bleeding Academic Research Consortium definition and severe thrombocytopenia (platelet count 3 times upper normal limit and clinically-diagnosed myopathy. The primary analyses will be performed in the modified intention-to-treat population. Results will be tested in exploratory analyses across key subgroups and in the intention-to-treat and per-protocol cohorts. Conclusions: INSPIRATION and INSPIRATON-S studies will help address clinically-relevant questions for antithrombotic therapy and thromboinflammatory therapy in critically-ill patients with COVID-19. © 2020 Elsevier Lt