The role of spatial and temporal radiation deposition in inertial fusion chambers: the case of HiPER¿

The first wall armour for the reactor chamber of HiPER will have to face short energy pulses of 5 to 20 MJ mostly in the form of x-rays and charged particles at a repetition rate of 5–10 Hz. Armour material and chamber dimensions have to be chosen to avoid/minimize damage to the chamber, ensuring the proper functioning of the facility during its planned lifetime. The maximum energy fluence that the armour can withstand without risk of failure, is determined by temporal and spatial deposition of the radiation energy inside the material. In this paper, simulations on the thermal effect of the radiation–armour interaction are carried out with an increasing definition of the temporal and spatial deposition of energy to prove their influence on the final results. These calculations will lead us to present the first values of the thermo-mechanical behaviour of the tungsten armour designed for the HiPER project under a shock ignition target of 48 MJ. The results will show that only the crossing of the plasticity limit in the first few micrometres might be a threat after thousands of shots for the survivability of the armour

Inferring cost of transport from whole-body kinematics in three sympatric turtle species with different locomotor habits

Chelonians are mechanically unusual vertebrates as an exoskeleton limits their body wall mobility. They generallymove slowly on land and have aquatic or semi-aquatic lifestyles. Somewhat surprisingly, the limitedexperimental work that has been done suggests that their energetic cost of transport (CoT) are relatively low.This study examines the mechanical evidence for CoT in three turtle species that have differing degrees ofterrestrial activity. Our results show that Apolone travels faster than the other two species, and that Chelydra hashigher levels of yaw. All the species show poor mean levels of energy recovery, and, whilst there is considerablevariation, never show the high levels of energy recovery seen in cursorial quadrupeds. The mean mechanical CoTis 2 to 4 times higher than is generally seen in terrestrial animals. We therefore find no mechanical support for alow CoT in these species. This study illustrates the need for research on a wider range of chelonians to discoverwhether there are indeed general trends in mechanical and metabolic energy costs

Generalized Brans-Dicke cosmology in the presence of matter and dark energy

We study the Generalized Brans-Dicke cosmology in the presence of matter and dark energy. Of particular interest for a constant Brans-Dicke parameter, the de Sitter space has also been investigated.Comment: 9 page

Expanding indication of padeliporfin (WST11) vascular-targeted photodynamic therapy: results of prostate cancer Latin-American multicenter study

OBJECTIVES: To explore the proportion of patients with higher risk localized prostate cancer (PCa) that would become safely biopsy negative 12 months after non-thermal focal therapy with padeliporfin vascular-targeted photodynamic therapy (VTP). METHODS: Multicenter study in a scenario of prostate-specific antigen (PSA) ≤20ng/ml and variable PCa target volumes Gleason pattern 3 or low-volume secondary Gleason pattern 4, all patients received VTP, consisting of intravenous 4mg/kg padeliporfin activated by light-diffusing fibers in the prostate. The prostate was biopsied at baseline, months 6 and 12, PSA, patient-reported functional outcomes and quality of life (QoL) questionnaires were recorded at baseline, months 3, 6, and 12 and adverse events (AE) throughout the study. RESULTS: In the intention-to-treat population (n=81), the proportion of patients with negative biopsies at month 12 was 74% (60/81 patients; 95% CI: 63.1%,83.2%). In the per-protocol population, the proportion was 79% (58/73 patients; 95% CI: 68.4%,88.0%). Questionnaire results indicated a slight improvement in urinary function and limited deterioration in sexual function. No difference in QoL was observed over time. A total of 42/81 (52%) patients reported mild or moderate and 4 of 81 (4.9%) experienced serious AE, all resolved without sequelae. No phototoxicity, cardiovascular event, fistula or prolonged urinary incontinence, secondary cancer or death was reported. CONCLUSIONS: Results support the efficacy, safety, and QoL associated with padeliporfin focal treatment for low/intermediate risk localized PCa

Incidence and clinical relevance of non-small cell lung cancer lymph node micro-metastasis detected by staging endobronchial ultrasound-guided transbronchial needle aspiration

Background: Approximately twenty percent of lymph node (LN) negative non-small cell lung cancer (NSCLC) patients who undergo curative intent surgery have pan-cytokeratin immunohistochemistry (IHC)-detectable occult micro-metastases (MMs) in resected LNs. The presence of the MMs in NSCLC is associated worsened outcomes. As a substantial proportion of NSCLC LN staging is conducted using endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), we sought to determine the frequency of detection of occult MMs in EBUS-TBNA specimens and to evaluate the impact of MMs on progression-free and overall survival. Methods: We performed retrospective IHC staining for pan-cytokeratin of EBUS-TBNA specimens previously deemed negative by a cytopathologist based on conventional hematoxylin and eosin staining. The results were correlated with clinical variables, including survival outcomes. Results: Of 887 patients screened, 44 patients were identified meeting inclusion criteria with sufficient additional tissue for testing. With respect to the time of the EBUS-TBNA procedure, 52% of patients were clinical stage I, 34% clinical stage II, and clinical 14% stage IIIa NSCLC. Three patients (6.8%) were found to have cytokeratin positive MMs. All 3 MMs detected were at N2 LN stations. The presence of MMs was associated with significantly decreased progression-free (median 210 vs. 1,293 days, P=0.0093) and overall survival (median 239 vs. 1,120 days, P=0.0357). Conclusions: Occult LN MMs can be detected in EBUS-TBNA specimens obtained during staging examinations and are associated with poor clinical outcomes. If prospectively confirmed, these results have significant implications for EBUS-TBNA specimen analyses and possibly for the NSCLC staging paradigm

Efficacy and Safety of Nivolumab Plus Ipilimumab in Patients With Advanced Hepatocellular Carcinoma Previously Treated With Sorafenib The CheckMate 040 Randomized Clinical Trial

IMPORTANCE Most patients with hepatocellular carcinoma (HCC) are diagnosed with advanced disease not eligible for potentially curative therapies; therefore, new treatment options are needed. Combining nivolumab with ipilimumab may improve clinical outcomes compared with nivolumab monotherapy. OBJECTIVE To assess efficacy and safety of nivolumab plus ipilimumab in patients with advanced HCC who were previously treated with sorafenib. DESIGN, SETTING, AND PARTICIPANTS CheckMate 040 is a multicenter, open-label, multicohort, phase 1/2 study. In the nivolumab plus ipilimumab cohort, patients were randomized between January 4 and September 26, 2016. Treatment group information was blinded after randomization. Median follow-up was 30.7 months. Data cutoff for this analysis was January 2019. Patients were recruited at 31 centers in 10 countries/territories in Asia, Europe, and North America. Eligible patients had advanced HCC (with/without hepatitis B or C) previously treated with sorafenib. A total of 148 patients were randomized (50 to arm A and 49 each to arms B and C). INTERVENTIONS Patients were randomized 1:1:1 to either nivolumab 1 mg/kg plus ipilimumab 3 mg/kg, administered every 3 weeks (4 doses), followed by nivolumab 240 mg every 2 weeks (arm A); nivolumab 3 mg/kg plus ipilimumab 1 mg/kg, administered every 3 weeks (4 doses), followed by nivolumab 240 mg every 2 weeks (arm B); or nivolumab 3 mg/kg every 2 weeks plus ipilimumab 1 mg/kg every 6 weeks (arm C). MAIN OUTCOMES AND MEASURES Coprimary end points were safety, tolerability, and objective response rate. Duration of response was also measured (investigator assessed with the Response Evaluation Criteria in Solid Tumors v1.1). RESULTS Of 148 total participants, 120 were male (81%). Median (IQR) age was 60 (52.5-66.5). At data cutoff (January 2019), the median follow-up was 30.7 months (IQR, 29.9-34.7). Investigator-assessed objective response rate was 32% (95% CI, 20%-47%) in arm A, 27% (95% CI, 15%-41%) in arm B, and 29% (95% CI, 17%-43%) in arm C. Median (range) duration of response was not reached (8.3-33.7+) in arm A and was 15.2 months (4.2-29.9+) in arm B and 21.7 months (2.8-32.7+) in arm C. Any-grade treatment-related adverse events were reported in 46 of 49 patients (94%) in arm A, 35 of 49 patients (71%) in arm B, and 38 of 48 patients (79%) in arm C; there was 1 treatment-related death (arm A; grade 5 pneumonitis). CONCLUSIONS AND RELEVANCE In this randomized clinical trial, nivolumab plus ipilimumab had manageable safety, promising objective response rate, and durable responses. The arm A regimen (4 doses nivolumab 1 mg/kg plus ipilimumab 3 mg/kg every 3 weeks then nivolumab 240 mg every 2 weeks) received accelerated approval in the US based on the results of this study. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0165887

Tension between SN and BAO: current status and future forecasts

Using real and synthetic Type Ia SNe (SNeIa) and baryon acoustic oscillations (BAO) data representing current observations forecasts, this paper investigates the tension between those probes in the dark energy equation of state (EoS) reconstruction considering the well known CPL model and Wang's low correlation reformulation. In particular, here we present simulations of BAO data from both the the radial and transverse directions. We also explore the influence of priors on Omega_m and Omega_b on the tension issue, by considering 1-sigma deviations in either one or both of them. Our results indicate that for some priors there is no tension between a single dataset (either SNeIa or BAO) and their combination (SNeIa+BAO). Our criterion to discern the existence of tension (sigma-distance) is also useful to establish which is the dataset with most constraining power; in this respect SNeIa and BAO data switch roles when current and future data are considered, as forecasts predict and spectacular quality improvement on BAO data. We also find that the results on the tension are blind to the way the CPL model is addressed: there is a perfect match between the original formulation and that by the low correlation optimized, but the errors on the parameters are much narrower in all cases of our exhaustive exploration, thus serving the purpose of stressing the convenience of this reparametrization.Comment: 21 pages, under review in JCA

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

Utilization of COVID-19 Treatments and Clinical Outcomes among Patients with Cancer: A COVID-19 and Cancer Consortium (CCC19) Cohort Study.

Among 2,186 U.S. adults with invasive cancer and laboratory-confirmed SARS-CoV-2 infection, we examined the association of COVID-19 treatments with 30-day all-cause mortality and factors associated with treatment. Logistic regression with multiple adjustments (e.g., comorbidities, cancer status, baseline COVID-19 severity) was performed. Hydroxychloroquine with any other drug was associated with increased mortality versus treatment with any COVID-19 treatment other than hydroxychloroquine or untreated controls; this association was not present with hydroxychloroquine alone. Remdesivir had numerically reduced mortality versus untreated controls that did not reach statistical significance. Baseline COVID-19 severity was strongly associated with receipt of any treatment. Black patients were approximately half as likely to receive remdesivir as white patients. Although observational studies can be limited by potential unmeasured confounding, our findings add to the emerging understanding of patterns of care for patients with cancer and COVID-19 and support evaluation of emerging treatments through inclusive prospective controlled trials. SIGNIFICANCE: Evaluating the potential role of COVID-19 treatments in patients with cancer in a large observational study, there was no statistically significant 30-day all-cause mortality benefit with hydroxychloroquine or high-dose corticosteroids alone or in combination; remdesivir showed potential benefit. Treatment receipt reflects clinical decision-making and suggests disparities in medication access.This article is highlighted in the In This Issue feature, p. 1426