The shock process and light element production in supernovae envelopes

Detailed hydrodynamic modeling of the passage of supernova shocks through the hydrogen envelopes of blue and red progenitor stars was carried out to explore the sensitivity to model conditions of light element production (specifically Li-7 and B-11) which was noted by Dearborn, Schramm, Steigman and Truran (1989) (DSST). It is found that, for stellar models with M is less than or approximately 100 M solar mass, current state of the art supernova shocks do not produce significant light element yields by hydrodynamic processes alone. The dependence of this conclusion on stellar models and on shock strengths is explored. Preliminary implications for Galactic evolution of lithium are discussed, and it is suspected that intermediate mass red giant stars may be the most consistent production site for lithium

Health Status After Cancer: Does It Matter Which Hospital You Belong To?

Background Survival rates are widely used to compare the quality of cancer care. However, the extent to which cancer survivors regain full physical or cognitive functioning is not captured by this statistic. To address this concern we introduce post-diagnosis employment as a supplemental measure of the quality of cancer care. Methods This study is based on individual level data from the Norwegian Cancer Registry (n = 46,720) linked with data on labor market outcomes and socioeconomic status from Statistics Norway. We study variation across Norwegian hospital catchment areas (n = 55) with respect to survival and employment five years after cancer diagnosis. To handle the selection problem, we exploit the fact that cancer patients in Norway (until 2001) have been allocated to local hospitals based on their place of residence. Results We document substantial differences across catchment areas with respect to patients' post-diagnosis employment rates. Conventional quality indicators based on survival rates indicate smaller differences. The two sets of indicators are only moderately correlated. Conclusions This analysis shows that indicators based on survival and post-diagnosis employment may capture different parts of the health status distribution, and that using only one of them to capture quality of care may be insufficient

Nationwide Survival Benefit after Implementation of First-Line Immunotherapy for Patients with Advanced NSCLC—Real World Efficacy

SIMPLE SUMMARY: The expected change in overall survival (OS) in patients with advanced non-small cell lung cancer (NSCLC) after the clinical implementation of immune checkpoint inhibitor therapy (ICI) has not been substantially investigated in large real-world cohorts outside randomized controlled trials (RCTs). In this nationwide study, we compared OS before and after the implementation of ICI and found that 3-year OS tripled from 6% to 18%. Patients receiving ICI had a lower OS than demonstrated in RCTs, except for patients with performance status (PS) 0. More than a fifth of the patients progressed early within the first six ICI cycles. Adverse prognostic factors were PS ≥ 1 and metastases to the bone and liver. ABSTRACT: Background The selection of patients with non-small cell lung cancer (NSCLC) for immune checkpoint inhibitor (ICI) treatment remains challenging. This real-world study aimed to compare the overall survival (OS) before and after the implementation of ICIs, to identify OS prognostic factors, and to assess treatment data in first-line (1L) ICI-treated patients without epidermal growth factor receptor mutation or anaplastic lymphoma kinase translocation. Methods Data from the Danish NSCLC population initiated with 1L palliative antineoplastic treatment from 1 January 2013 to 1 October 2018, were extracted from the Danish Lung Cancer Registry (DLCR). Long-term survival and median OS pre- and post-approval of 1L ICI were compared. From electronic health records, additional clinical and treatment data were obtained for ICI-treated patients from 1 March 2017 to 1 October 2018. Results The OS was significantly improved in the DLCR post-approval cohort (n = 2055) compared to the pre-approval cohort (n = 1658). The 3-year OS rates were 18% (95% CI 15.6–20.0) and 6% (95% CI 5.1–7.4), respectively. On multivariable Cox regression, bone (HR = 1.63) and liver metastases (HR = 1.47), performance status (PS) 1 (HR = 1.86), and PS ≥ 2 (HR = 2.19) were significantly associated with poor OS in ICI-treated patients. Conclusion OS significantly improved in patients with advanced NSCLC after ICI implementation in Denmark. In ICI-treated patients, PS ≥ 1, and bone and liver metastases were associated with a worse prognosis

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Identification and Characterization of Novel Mutations in the Human Gene Encoding the Catalytic Subunit Calpha of Protein Kinase A (PKA)

The genes PRKACA and PRKACB encode the principal catalytic (C) subunits of protein kinase A (PKA) Cα and Cβ, respectively. Cα is expressed in all eukaryotic tissues examined and studies of Cα knockout mice demonstrate a crucial role for Cα in normal physiology. We have sequenced exon 2 through 10 of PRKACA from the genome of 498 Norwegian donors and extracted information about PRKACA mutations from public databases. We identified four interesting nonsynonymous point mutations, Arg45Gln, Ser109Pro, Gly186Val, and Ser263Cys, in the Cα1 splice variant of the kinase. Cα variants harboring the different amino acid mutations were analyzed for kinase activity and regulatory (R) subunit binding. Whereas mutation of residues 45 and 263 did not alter catalytic activity or R subunit binding, mutation of Ser109 significantly reduced kinase activity while R subunit binding was unaltered. Mutation of Cα Gly186 completely abrogated kinase activity and PKA type I but not type II holoenzyme formation. Gly186 is located in the highly conserved DFG motif of Cα and mutation of this residue to Val was predicted to result in loss of binding of ATP and Mg2+, which may explain the kinetic inactivity. We hypothesize that individuals born with mutations of Ser109 or Gly186 may be faced with abnormal development and possibly severe disease

Experimental Demonstration of Attosecond Pump-Probe Spectroscopy with an X-ray Free-Electron Laser

Pump-probe experiments with sub-femtosecond resolution are the key to understanding electronic dynamics in quantum systems. Here we demonstrate the generation and control of sub-femtosecond pulse pairs from a two-colour X-ray free-electron laser (XFEL). By measuring the delay between the two pulses with an angular streaking diagnostic, we characterise the group velocity of the XFEL and demonstrate control of the pulse delay down to 270 as. We demonstrate the application of this technique to a pump-probe measurement in core-excited para-aminophenol. These results demonstrate the ability to perform pump-probe experiments with sub-femtosecond resolution and atomic site specificity.Comment: 55 pages, main manuscript (5 figures) + supplementary materials (25 figures), 30 figures total. Submitted to Nature Photonic

Artificial Nightlight Alters the Predator–Prey Dynamics of an Apex Carnivore

Artificial nightlight is increasingly recognized as an important environmental disturbance that influences the habitats and fitness of numerous species. However, its effects on wide‐ranging vertebrates and their interactions remain unclear. Light pollution has the potential to amplify land‐use change, and as such, answering the question of how this sensory stimulant affects behavior and habitat use of species valued for their ecological roles and economic impacts is critical for conservation and land‐use planning. Here, we combined satellite‐derived estimates of light pollution, with GPS‐data from cougars Puma concolor (n = 56), mule deer Odocoileus hemionus (n = 263) and locations of cougar‐killed deer (n = 1562 carcasses), to assess the effects of light exposure on mammal behavior and predator–prey relationships across wildland–urban gradients in the southwestern United States. Our results indicate that deer used the anthropogenic environments to access forage and were more active at night than their wildland conspecifics. Despite higher nightlight levels, cougars killed deer at the wildland–urban interface, but hunted them in the relatively darkest locations. Light had the greatest effect of all covariates on where cougars killed deer at the wildland–urban interface. Both species exhibited functional responses to light pollution at fine scales; individual cougars and deer with less light exposure increasingly avoided illuminated areas when exposed to greater radiance, whereas deer living in the wildland–urban interface selected elevated light levels. We conclude that integrating estimates of light pollution into ecological studies provides crucial insights into how the dynamic human footprint can alter animal behavior and ecosystem function across spatial scales