HYPER-RESPONSIVENESS OF ALDOSTERONE TO METOCLOPRAMIDE IN ALDOSTERONISM

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73101/1/j.1365-2265.1982.tb02761.x.pd

The resultant on compact Riemann surfaces

We introduce a notion of resultant of two meromorphic functions on a compact Riemann surface and demonstrate its usefulness in several respects. For example, we exhibit several integral formulas for the resultant, relate it to potential theory and give explicit formulas for the algebraic dependence between two meromorphic functions on a compact Riemann surface. As a particular application, the exponential transform of a quadrature domain in the complex plane is expressed in terms of the resultant of two meromorphic functions on the Schottky double of the domain.Comment: 44 page

Race and delays in breast cancer treatment across the care continuum in the Carolina Breast Cancer Study

Background: After controlling for baseline disease factors, researchers have found that black women have worse breast cancer survival, and this suggests that treatment differences may contribute to poorer outcomes. Delays in initiating and completing treatment are one proposed mechanism. Methods: Phase 3 of the Carolina Breast Cancer Study involved a large, population-based cohort of women with incident breast cancer. For this analysis, we included black women (n = 1328) and white women (n = 1331) with stage I to III disease whose treatment included surgery with or without adjuvant therapies. A novel treatment pathway grouping was used to benchmark the treatment duration (surgery only, surgery plus chemotherapy, surgery plus radiation, or all 3). Models controlled for the treatment pathway, age, and tumor characteristics and for demographic factors related to health care access. Exploratory analyses of the association between delays and cancer recurrence were performed. Results: In fully adjusted analyses, blacks had 1.73 times higher odds of treatment initiation more than 60 days after their diagnosis in comparison with whites (odds ratio [OR], 1.73; 95% confidence interval [CI], 1.04-2.90). Black race was also associated with a longer treatment duration. Blacks were also more likely to be in the highest quartile of treatment duration (OR, 1.69; 95% CI, 1.41-2.02), even after adjustments for demographic and tumor characteristics (OR, 1.31; 95% CI, 1.04-1.64). A nonsignificant trend toward a higher recurrence risk was observed for patients with delayed initiation (hazard ratio, 1.44; 95% CI, 0.89-2.33) or the longest duration (hazard ratio, 1.17; 95% CI, 0.87-1.59). Conclusions: Black women more often had delayed treatment initiation and a longer duration than whites receiving similar treatment. Interventions that target access barriers may be needed to improve timely delivery of care

Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance

AbstractMany different definitions for multidrug-resistant (MDR), extensively drug-resistant (XDR) and pandrug-resistant (PDR) bacteria are being used in the medical literature to characterize the different patterns of resistance found in healthcare-associated, antimicrobial-resistant bacteria. A group of international experts came together through a joint initiative by the European Centre for Disease Prevention and Control (ECDC) and the Centers for Disease Control and Prevention (CDC), to create a standardized international terminology with which to describe acquired resistance profiles in Staphylococcus aureus, Enterococcus spp., Enterobacteriaceae (other than Salmonella and Shigella), Pseudomonas aeruginosa and Acinetobacter spp., all bacteria often responsible for healthcare-associated infections and prone to multidrug resistance. Epidemiologically significant antimicrobial categories were constructed for each bacterium. Lists of antimicrobial categories proposed for antimicrobial susceptibility testing were created using documents and breakpoints from the Clinical Laboratory Standards Institute (CLSI), the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the United States Food and Drug Administration (FDA). MDR was defined as acquired non-susceptibility to at least one agent in three or more antimicrobial categories, XDR was defined as non-susceptibility to at least one agent in all but two or fewer antimicrobial categories (i.e. bacterial isolates remain susceptible to only one or two categories) and PDR was defined as non-susceptibility to all agents in all antimicrobial categories. To ensure correct application of these definitions, bacterial isolates should be tested against all or nearly all of the antimicrobial agents within the antimicrobial categories and selective reporting and suppression of results should be avoided

Integrating Biology and Access to Care in Addressing Breast Cancer Disparities: 25 Years’ Research Experience in the Carolina Breast Cancer Study

Purpose of Review: To review research on breast cancer mortality disparities, emphasizing research conducted in the Carolina Breast Cancer Study, with a focus on challenges and opportunities for integration of tumor biology and access characteristics across the cancer care continuum. Recent Findings: Black women experience higher mortality following breast cancer diagnosis, despite lower incidence compared to white women. Biological factors, such as stage at diagnosis and breast cancer subtypes, play a role in these disparities. Simultaneously, social, behavioral, environmental, and access to care factors are important. However, integrated studies of biology and access are challenging and it is uncommon to have both data types available in the same study population. The central emphasis of phase 3 of the Carolina Breast Cancer Study, initiated in 2008, was to collect rich data on biology (including germline and tumor genomics and pathology) and health care access in a diverse study population, with the long-term goal of defining intervention opportunities to reduce disparities across the cancer care continuum. Summary: Early and ongoing research from CBCS has identified important interactions between biology and access, leading to opportunities to build greater equity. However, sample size, population-specific relationships among variables, and complexities of treatment paths along the care continuum pose important research challenges. Interdisciplinary teams, including experts in novel data integration and causal inference, are needed to address gaps in our understanding of breast cancer disparities

Endocrine Therapy Nonadherence and Discontinuation in Black and White Women

Background: Differential use of endocrine therapy (ET) by race may contribute to breast cancer outcome disparities, but racial differences in ET behaviors are poorly understood. Methods: Women aged 20-74 years with a first primary, stage I-III, hormone receptor-positive (HR+) breast cancer were included. At 2 years postdiagnosis, we assessed nonadherence, defined as not taking ET every day or missing more than two pills in the past 14 days, discontinuation, and a composite measure of underuse, defined as either missing pills or discontinuing completely. Using logistic regression, we evaluated the relationship between race and nonadherence, discontinuation, and overall underuse in unadjusted, clinically adjusted, and socioeconomically adjusted models. Results: A total of 1280 women were included; 43.2% self-identified as black. Compared to white women, black women more often reported nonadherence (13.7% vs 5.2%) but not discontinuation (10.0% vs 10.7%). Black women also more often reported the following: hot flashes, night sweats, breast sensitivity, and joint pain; believing that their recurrence risk would not change if they stopped ET; forgetting to take ET; and cost-related barriers. In multivariable analysis, black race remained statistically significantly associated with nonadherence after adjusting for clinical characteristics (adjusted odds ratio = 2.72, 95% confidence interval = 1.75 to 4.24) and after adding socioeconomic to clinical characteristics (adjusted odds ratio = 2.44, 95% confidence interval = 1.50 to 3.97) but was not independently associated with discontinuation after adjustment. Low recurrence risk perception and lack of a shared decision making were strongly predictive of ET underuse across races. Conclusions: Our results highlight important racial differences in ET-Adherence behaviors, perceptions of benefits/harms, and shared decision making that may be targeted with culturally tailored interventions

Health promotion: results of focus groups with African-American men

http://dx.doi.org/10.1016/j.jomh.2010.11.00

Innovations in suicide prevention research (INSPIRE): a protocol for a population-based case–control study

Background Suicide deaths have been increasing for the past 20 years in the USA resulting in 45 979 deaths in 2020, a 29% increase since 1999. Lack of data linkage between entities with potential to implement large suicide prevention initiatives (health insurers, health institutions and corrections) is a barrier to developing an integrated framework for suicide prevention. Objectives Data linkage between death records and several large administrative datasets to (1) estimate associations between risk factors and suicide outcomes, (2) develop predictive algorithms and (3) establish long-term data linkage workflow to ensure ongoing suicide surveillance. Methods We will combine six data sources from North Carolina, the 10th most populous state in the USA, from 2006 onward, including death certificate records, violent deaths reporting system, large private health insurance claims data, Medicaid claims data, University of North Carolina electronic health records and data on justice involved individuals released from incarceration. We will determine the incidence of death from suicide, suicide attempts and ideation in the four subpopulations to establish benchmarks. We will use a nested case–control design with incidence density-matched population-based controls to (1) identify short-term and long-term risk factors associated with suicide attempts and mortality and (2) develop machine learning-based predictive algorithms to identify individuals at risk of suicide deaths. Discussion We will address gaps from prior studies by establishing an in-depth linked suicide surveillance system integrating multiple large, comprehensive databases that permit establishment of benchmarks, identification of predictors, evaluation of prevention efforts and establishment of long-term surveillance workflow protocols

The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics

TBCRC 048: Phase II Study of Olaparib for Metastatic Breast Cancer and Mutations in Homologous Recombination-Related Genes

PURPOSE Olaparib, a poly (ADP-ribose) polymerase (PARP) inhibitor (PARPi), is approved for the treatment of human epidermal growth factor receptor 2 (HER2)–negative metastatic breast cancer (MBC) in germline (g)BRCA1/2 mutation carriers. Olaparib Expanded, an investigator-initiated, phase II study, assessed olaparib response in patients with MBC with somatic (s)BRCA1/2 mutations or g/s mutations in homologous recombination (HR)–related genes other than BRCA1/2. METHODS Eligible patients had MBC with measurable disease and germline mutations in non-BRCA1/2 HR-related genes (cohort 1) or somatic mutations in these genes or BRCA1/2 (cohort 2). Prior PARPi, platinum-refractory disease, or progression on more than two chemotherapy regimens (metastatic setting) was not allowed. Patients received olaparib 300 mg orally twice a day until progression. A single-arm, two-stage design was used. The primary endpoint was objective response rate (ORR); the null hypothesis (# 5% ORR) would be rejected within each cohort if there were four or more responses in 27 patients. Secondary endpoints included clinical benefit rate and progression-free survival (PFS). RESULTS Fifty-four patients enrolled. Seventy-six percent had estrogen receptor–positive HER2-negative disease. Eighty-seven percent had mutations in PALB2, sBRCA1/2, ATM, or CHEK2. In cohort 1, ORR was 33% (90% CI, 19% to 51%) and in cohort 2, 31% (90% CI, 15% to 49%). Confirmed responses were seen only with gPALB2 (ORR, 82%) and sBRCA1/2 (ORR, 50%) mutations. Median PFS was 13.3 months (90% CI, 12 months to not available/computable [NA]) for gPALB2 and 6.3 months (90% CI, 4.4 months to NA) for sBRCA1/ 2 mutation carriers. No responses were observed with ATM or CHEK2 mutations alone. CONCLUSION PARP inhibition is an effective treatment for patients with MBC and gPALB2 or sBRCA1/2 mutations, significantly expanding the population of patients with breast cancer likely to benefit from PARPi beyond gBRCA1/2 mutation carriers. These results emphasize the value of molecular characterization for treatment decisions in MBC