Constraints on Transport Models for Galactic Cosmic Rays and their Implications for the Anomalous Positron Abundance

While supernova remnants account for most of the cosmic rays in the Galaxy, they do not produce essential amounts of antimatter. The predicted amount of positrons, which are assumed to be purely secondary produced by cosmic ray interactions, cannot explain the measurements from PAMELA and very recently from AMS-02. In this work current cosmic ray transport models are investigated and the transport related uncertainty on the expected secondary positron flux is quantified

Racial Differences in the Use of Adjuvant Chemotherapy for Breast Cancer in a Large Urban Integrated Health System

Background. Racial differences in breast cancer survival may be in part due to variation in patterns of care. To better understand factors influencing survival disparities, we evaluated patterns of receipt of adjuvant chemotherapy among 2,234 women with invasive, nonmetastatic breast cancer treated at the Henry Ford Health System (HFHS) from 1996 through 2005. Methods. Sociodemographic and clinical information were obtained from linked datasets from the HFHS, Metropolitan Detroit Cancer Surveillance Systems, and U.S. Census. Comorbidity was measured using the Charlson comorbidity index (CCI), and economic deprivation was categorized using a neighborhood deprivation index. Results. African American (AA) women were more likely than whites to have advanced tumors with more aggressive clinical features, to have more comorbidity and to be socioeconomically deprived. While in the unadjusted model, AAs were more likely to receive chemotherapy (odds ratio (OR) 1.22, 95% confidence interval (CI) 1.02–1.46) and to have a delay in receipt of chemotherapy beyond 60 days (OR 1.68, 95% CI, 1.26–1.48), after multivariable adjustment there were no racial differences in receipt (odds ratio (OR) 1.02, 95% confidence interval (CI) 0.73–1.43), or timing of chemotherapy (OR 1.18, 95 CI, 0.8–1.74). Conclusions. Societal factors and not race appear to have an impact on treatment delay among African American women with early breast cancer

Racial Differences in the Use of Adjuvant Chemotherapy for Breast Cancer in a Large Urban Integrated Health System

Background. Racial differences in breast cancer survival may be in part due to variation in patterns of care. To better understand factors influencing survival disparities, we evaluated patterns of receipt of adjuvant chemotherapy among 2,234 women with invasive, nonmetastatic breast cancer treated at the Henry Ford Health System (HFHS) from 1996 through 2005. Methods. Sociodemographic and clinical information were obtained from linked datasets from the HFHS, Metropolitan Detroit Cancer Surveillance Systems, and U.S. Census. Comorbidity was measured using the Charlson comorbidity index (CCI), and economic deprivation was categorized using a neighborhood deprivation index. Results. African American (AA) women were more likely than whites to have advanced tumors with more aggressive clinical features, to have more comorbidity and to be socioeconomically deprived. While in the unadjusted model, AAs were more likely to receive chemotherapy (odds ratio (OR) 1.22, 95% confidence interval (CI) 1.02-1.46) and to have a delay in receipt of chemotherapy beyond 60 days (OR 1.68, 95% CI, 1.26-1.48), after multivariable adjustment there were no racial differences in receipt (odds ratio (OR) 1.02, 95% confidence interval (CI) 0.73-1.43), or timing of chemotherapy (OR 1.18, 95 CI,. Conclusions. Societal factors and not race appear to have an impact on treatment delay among African American women with early breast cancer. Background Despite improvements in available options for breast cancer treatment, there continues to be a considerable gap in survival between African American (AA) and white women with breast cancer Adjuvant chemotherapy and hormonal therapy have had a dramatic impact on breast cancer survival, and in order to optimize longevity, it is critical for patients to receive treatment according to standard clinical guidelines International Journal of Breast Cancer Previous reports on patterns of care have indicated that AA women are less likely to receive standard breast cancer treatment compared with white women We hypothesized that racial disparities in breast cancer survival may be at least in part due to differences in the receipt of standard adjuvant chemotherapy as defined by national treatment guidelines. In order to address this question, we evaluated patterns of breast cancer care provided at the Henry Ford Health System (HFHS), a large integrated health system serving southeastern MI. The goal of this study was to assess patterns of adjuvant chemotherapy administration among women with invasive, nonmetastatic breast cancer comparing AA and white women, and focusing on receipt of standard chemotherapy, duration of treatment, and timing of treatment in relationship to diagnosis. Methods Study Design. This study consisted of a descriptive analysis of adjuvant chemotherapy received by AA and white women diagnosed with invasive, nonmetastatic breast cancer at the HFHS between January 1, 1996 and December 31, 2005. HFHS is a large urban integrated health system located in southeast Michigan founded in 1915 to provide for the health care needs of the city of Detroit and surrounding metropolitan area. HFHS currently consists of 5 hospitals, anchored by Henry Ford Hospital, a 903 bed tertiary care, research and teaching facility; and 36 ambulatory care facilities including 5 sites located within the city of Detroit, and 31 sites located in Wayne (outside of Detroit), Macomb, Oakland, and Washtenaw counties. A single lifetime medical record number (MRN) is used throughout the system to provide continuity of record keeping and medical care. For the purposes of this project, patient sociodemographic, clinical, and treatment information was derived through analyses of linked datasets using the HFHS administrative databases, the Metropolitan Detroit Cancer Surveillance System (MDCSS), and the U.S. Census Bureau. The MDCSS is home for the Detroit SEER registry, which registers all cancers of residents from Wayne, Oakland, and Macomb counties. In the current study, case records were matched from the SEER and HFHS databases using MRN, social security number (SSN), last name, and date of birth. Records that matched for only one variable were manually reviewed to look for character or punctuation errors in other nonmatched fields. Matching resulted in 3,630 record matches. We excluded matches with unknown American Joint Cancer Committee (AJCC) stage (n = 51); first breast surgery at another institution (n = 147); history of a prior malignancy within 6 months of breast cancer diagnosis (n = 52); duplicate records (n = 3); histology code indicating non-breast origin (n = 1); stage IV disease (n = 978), other race (n = 45); no definitive breast surgery (n = 52); and receipt of neoadjuvant chemotherapy (n = 67). These exclusions resulted in a study population of 2,234 (61.5%) white and AA women treated for invasive, nonmetastatic breast cancer at the HFHS. Measurement of Variables. Detailed information on breast cancer treatment, clinical, and socio-demographic data were derived from the HFHS and SEER database and information on neighborhood-level economic deprivation (see deprivation index below) was obtained form the U.S. Census Bureau. All primary breast surgery consisting of lumpectomy (partial mastectomy) or mastectomy (modified radical mastectomy, radical mastectomy, or simple mastectomy) and standard axillary lymph node dissection was performed at the HFHS. Guidelines from the National Comprehensive Cancer Network (NCCN) corresponding to the years of diagnosis were used to define standard adjuvant chemotherapy treatment recommendations according to AJCC stage Patient and clinical characteristics included race (from the medical record listing), age at diagnosis, tumor size, lymph node positivity, histology, grade, and estrogen and progesterone receptor (ER and PR) status. Insurance status was available from the HFHS records and was classified based on the most frequent insurance charged for each treatment visit, and categorized into 3 groups (private, Medicare, and other, including uninsured). Comorbidity was assessed using the Charlson comorbidity index (CCI) a prospectively verified method for classifying comorbid medical conditions which could affect the risk of mortality in longitudinal studies Statistical Analysis. The clinical and sociodemographic characteristics of AA and white women with invasive, nonmetastatic breast cancer were compared by chi-square tests for categorical variables and Student's t-tests for continuous variables. Separate analyses were conducted to determine racial differences in the use of standard chemotherapy (yes versus no), timing of chemotherapy as determined by the date of diagnosis and the date of chemotherapy initiation (dichotomized using the sample median, 60 days) for cases where detailed chemotherapy records were available and completion of standard chemotherapy (i.e., completing the NCCN recommended number of cycles of treatment). Odds ratios (ORs) for receipt of chemotherapy for AA versus white women and 95% confidence intervals (CIs) were estimated using unconditional logistic regression analyses. Race, age at diagnosis, tumor size, lymph node positivity, hormone receptor status, tumor grade, CCI, deprivation index, and insurance status were assessed individually and in multivariable adjusted models. Unconditional logistic regression was also used to estimate the odds of beginning chemotherapy within 60 days of the date of diagnosis. The analyses consisted of three models, first adjusting for clinical factors only (race, age, tumor size, lymph node positivity, hormone receptor status, tumor grade, and CCI), second adjusting for societal factors (race, deprivation index, and insurance status), and third adjusting for all listed variables. The purpose of performing three different models was to determine whether clinical versus societal factors had a greater impact on racial differences in receipt of adjuvant chemotherapy or in timing of chemotherapy. All regression models were run with and without a clustering correction for census tract. Results There were no significant racial differences in age at diagnosis adjuvant chemotherapy for AA women compared with white women. The average time from diagnosis to initiation of chemotherapy for white women was 67.9 days (S.D. 38.6) compared to 73.2 (S.D. 36.4) for AA women, P = 0.049. When time to adjuvant chemotherapy was stratified at 60 days (the sample median), white women were more likely to be treated prior to 60 days (55%) compared to AA women (43%), P < 0.001. Discussion While breast cancer survival rates continue to improve over time http://seer.cancer.gov/csr/1975 2008/, there remains a marked discrepancy in survival by race, Strengths of this study include the inclusion of women enrolled in a large integrated urban heath care system which provides uniform access to high-quality medical care. In addition, the linked HFHS and SEER database allowed for availability of detailed and accurate clinical, demographic, and treatment data including details on adjuvant chemotherapy received. Our measure of socioeconomic deprivation was a sophisticated measure developed through the linkage with U.S. Census data, however, the derived deprivation index was not based on factors specific to the individual patient such as income, education, or family support, and may therefore be subject to misclassification. In conclusion, race had no direct impact on receipt of adjuvant chemotherapy or timing of chemotherapy among a cohort of women treated at a large urban integrated health care system in Detroit. The fact that AA women were more likely to receive adjuvant chemotherapy in the unadjusted model was largely explained by the more advanced stage at diagnosis among AAs that suggests the need for better screening and access to early treatment interventions. Delay in receipt of chemotherapy among AA women was largely explained by societal factors which likely have a direct effect on access to care. However, the delay was on average less than one week and may not have had significant clinical impact. Nevertheless, it serves to remind health care providers of the importance of making health care accessible to all

Extreme weather and climate in Europe

This report describes the current scientific knowledge of extreme weather and climate events in Europe for the following variables: temperature, precipitation, hail, and drought (with the following types of drought: meteorological, hydrological and soil moisture). The content summarises key literature drawn from peer reviewed journals and other sources (business and government reports), and builds upon the synthesised results presented in international assessments such as IPCC reports. It describes the recorded observations and modelled projections for extreme events including definitions, frequency, trends, spatial and temporal distribution. The report also presents an overview of the indices used to characterise extreme events as well as their main uses, before going on to describe the datasets where they are recorded, and provides information on the strengths and weaknesses of the indices and the datasets. Extra consideration is given to indices that are relevant to socio-economic impacts resulting from climate change and relevant statistical techniques for analysing extreme events. Observed changes in global climate and extreme events provide the context to the changes in extreme events observed in Europe, which are described for much of the 20th century. Modelled projections of extreme events are also given, under different emissions scenarios and time horizons, including results from regional models covering the European domain, such as EURO-CORDEX. The report is written for climate scientists, climate researchers and experts who use climate information in a professional role. There are four case studies (Appendix 2) which provide an anatomy of different recent European extreme weather/climate events including meteorological impacts and synoptic context. Observed global temperature trends show the number of warm extremes has increased and number of cool extremes has decreased over the last 100 years, and the length and frequency of summer heat waves has increased during the last century. In Europe these trends are most pronounced in the last 40 years although regional variations exist. For Europe, 2014 was the warmest year on record, although it had fewer hot days than recent years. Under future climate change with continued warming, the number of heat waves is projected to increase, along with their duration and intensity. Under all emissions scenarios, summers like the hot summer experienced in 2003 will become commonplace by the 2040s. The global trend in precipitation is generally for wetter conditions over the 20th century although changes are less temporally and spatially coherent than those observed for temperature. The general trend in precipitation for Europe in the 20th century is of increases over northern Europe and decreases over southern Europe. Extreme precipitation is becoming more intense and more frequent in Europe, especially in central and eastern Europe in winter, often resulting in greater and more frequent flooding. Since 1950 winter wet spells increased in duration in northern Europe and reduced in southern Europe, while summer wet spells became shorter in northern and eastern Europe. An increasing proportion of total rainfall is observed to fall on heavy rainfall days. Extreme precipitation (including short intense convective or longer duration frontal types) demonstrates complex variability and lacks a robust spatial pattern. Climate models project that events currently considered extreme are expected to occur more frequently in the future. For example a 1-in-20 year annual maximum daily precipitation amount is likely to become a 1-in-5 to 1-in-15 year event by the end of the 21st century in many parts of Europe. There are few ground based hail observation networks, so satellite measurements and weather models are used to identify hail forming conditions. In Europe most extreme hail events occur in the summer over Central Europe and the Alps where convective energy is greatest. Intense hail events are linked to increases in convective energy in the atmosphere observed over the last 30 years. Hailstorm projection studies, although limited to France, northern Italy and Germany, show increases in the convective conditions that lead to hail and some areas show a rise in damage days although this is not statistically significant. Recent severe droughts include Italy (1997-2002), the Baltic countries 2005-2009, the European heatwave of summer 2003, and the widespread European drought of 2011. The 1950s were prone to long, intense, Europe-wide meteorological and hydrological droughts. In northern and eastern Europe the highest drought frequency and severity was from the early 1950s to the mid-1970s. Southern and Western Europe (especially the Mediterranean) show the highest drought frequency and severity since 1990. There has been a small but continuous increase of the European areas prone to drought from the 1980s to the early 2010s. Regional climate models project a decrease in summer precipitation until 2100 of 17%. Dry periods are expected to occur 3 times more often at the end of this century and to last longer by 1 to 3 days compared to the period of 1971-2000. There is significant uncertainty associated with future projections of drought, with climate variability being the dominant source of uncertainty in observed and projected soil moisture drough

Setting new priorities for nursing research: The updated Swiss Nursing Research Agenda—a systematic, participative approach

Aim To identify current key areas for nursing research in Switzerland, we revised the Swiss Research Agenda for Nursing (SRAN) initially published in 2008. Background By developing a research agenda, nursing researchers internationally prioritize and cluster relevant topics within the research community. The process should be collaborative and systematic to provide credible information for decisionmakers in health care research, policy, and practice. Sources of Evidence After a participative, systematic, and critical evaluation within and outside of the Swiss Association for Nursing Science, the updated SRAN 2019–2029 defines four research priorities (new models of care, nursing care interventions, work and care environment, and quality of care and patient safety) and four transversal themes (organization of research, research methodologies, research in health care policy and public health perspectives). Conclusion Adding to other national nursing research agendas, the categories are organized in a framework of key research priorities and transversal themes. They relate to the importance of global and local foci of research as well as challenges in health care services and policy systems. The agenda is an important prerequisite for enhancing the influence of nursing research in Switzerland and provides guidance for the next decade.Implications for Nursing PracticeThe revised agenda ensures that research projects target key knowledge gaps and the discipline's core questions in respective countries.Implications for Health PolicyNursing research should inform and influence health policy on all institutional and political levels. Therefore, the integration of public health perspectives in research is one of the most important new aspects of SRAN 2019–2029

Testing for pharmacogenomic predictors of ppRNFL thinning in individuals exposed to vigabatrin

BACKGROUND: The anti-seizure medication vigabatrin (VGB) is effective for controlling seizures, especially infantile spasms. However, use is limited by VGB-associated visual field loss (VAVFL). The mechanisms by which VGB causes VAVFL remains unknown. Average peripapillary retinal nerve fibre layer (ppRNFL) thickness correlates with the degree of visual field loss (measured by mean radial degrees). Duration of VGB exposure, maximum daily VGB dose, and male sex are associated with ppRNFL thinning. Here we test the hypothesis that common genetic variation is a predictor of ppRNFL thinning in VGB exposed individuals. Identifying pharmacogenomic predictors of ppRNFL thinning in VGB exposed individuals could potentially enable safe prescribing of VGB and broader use of a highly effective drug. METHODS: Optical coherence topography (OCT) and GWAS data were processed from VGB-exposed individuals (n = 71) recruited through the EpiPGX Consortium. We conducted quantitative GWAS analyses for the following OCT measurements: (1) average ppRNFL, (2) inferior quadrant, (3) nasal quadrant, (4) superior quadrant, (5) temporal quadrant, (6) inferior nasal sector, (7) nasal inferior sector, (8) superior nasal sector, and (9) nasal superior sector. Using the summary statistics from the GWAS analyses we conducted gene-based testing using VEGAS2. We conducted nine different PRS analyses using the OCT measurements. To determine if VGB-exposed individuals were predisposed to having a thinner RNFL, we calculated their polygenic burden for retinal thickness. PRS alleles for retinal thickness were calculated using published summary statistics from a large-scale GWAS of inner retinal morphology using the OCT images of UK Biobank participants. RESULTS: The GWAS analyses did not identify a significant association after correction for multiple testing. Similarly, the gene-based and PRS analyses did not reveal a significant association that survived multiple testing. CONCLUSION: We set out to identify common genetic predictors for VGB induced ppRNFL thinning. Results suggest that large-effect common genetic predictors are unlikely to exist for ppRNFL thinning (as a marker of VAVFL). Sample size was a limitation of this study. However, further recruitment is a challenge as VGB is rarely used today because of this adverse reaction. Rare variants may be predictors of this adverse drug reaction and were not studied here

Demonstration of the temporal matter-wave Talbot effect for trapped matter waves

We demonstrate the temporal Talbot effect for trapped matter waves using ultracold atoms in an optical lattice. We investigate the phase evolution of an array of essentially non-interacting matter waves and observe matter-wave collapse and revival in the form of a Talbot interference pattern. By using long expansion times, we image momentum space with sub-recoil resolution, allowing us to observe fractional Talbot fringes up to 10th order.Comment: 17 pages, 7 figure

Azimuthal anisotropy at RHIC: the first and fourth harmonics

We report the first observations of the first harmonic (directed flow, v_1), and the fourth harmonic (v_4), in the azimuthal distribution of particles with respect to the reaction plane in Au+Au collisions at the Relativistic Heavy Ion Collider (RHIC). Both measurements were done taking advantage of the large elliptic flow (v_2) generated at RHIC. From the correlation of v_2 with v_1 it is determined that v_2 is positive, or {\it in-plane}. The integrated v_4 is about a factor of 10 smaller than v_2. For the sixth (v_6) and eighth (v_8) harmonics upper limits on the magnitudes are reported.Comment: 6 pages with 3 figures, as accepted for Phys. Rev. Letters The data tables are at http://www.star.bnl.gov/central/publications/pubDetail.php?id=3

Major Surface Glycoproteins of Insect Forms of Trypanosoma brucei Are Not Essential for Cyclical Transmission by Tsetse

Procyclic forms of Trypanosoma brucei reside in the midgut of tsetse flies where they are covered by several million copies of glycosylphosphatidylinositol-anchored proteins known as procyclins. It has been proposed that procyclins protect parasites against proteases and/or participate in tropism, directing them from the midgut to the salivary glands. There are four different procyclin genes, each subject to elaborate levels of regulation. To determine if procyclins are essential for survival and transmission of T. brucei, all four genes were deleted and parasite fitness was compared in vitro and in vivo. When co-cultured in vitro, the null mutant and wild type trypanosomes (tagged with cyan fluorescent protein) maintained a near-constant equilibrium. In contrast, when flies were infected with the same mixture, the null mutant was rapidly overgrown in the midgut, reflecting a reduction in fitness in vivo. Although the null mutant is patently defective in competition with procyclin-positive parasites, on its own it can complete the life cycle and generate infectious metacyclic forms. The procyclic form of T. brucei thus differs strikingly from the bloodstream form, which does not tolerate any perturbation of its variant surface glycoprotein coat, and from other parasites such as Plasmodium berghei, which requires the circumsporozoite protein for successful transmission to a new host