Analysis of a 290-Year Net Accumulation Time Series from Mt. Logan, Yukon

A 102.5-m mechanically continuous firn and ice core sequence retrieved from the Northwest Col of Mt. Logan (latitude 60°30\u27N; longitude 140°35\u27W; site location 5340 m a.s.l.) in the Yukon Territory, Canada, has been analyzed continuously for stable isotopes, pH and liquid electrolytic conductivity. Specific sections of the core have been analyzed for total β-activity (0-22 m) and trace ion concentrations (across major volcanic events) in order to date the core. In the lower half of the core, nitrate and some other ionic species are used to identify annual increments except between AD 1693 and AD 1720 and between AD 1729 and AD 1735 where only average annual increments are given. Annual increments were converted to water equivalents, then corrected for ice flow thinning as well as for origin, since a significant net accumulation gradient exists across the borehole site. The time series was subjected to cross correlation analysis, using instrumental data for the last 80 years, and to spectral analyses, using a 250-year sequence

The power of interdependence: Linking health systems, communities, and health professions educational programs to better meet the needs of patients and populations

Promoting optimal health outcomes for diverse patients and populations requires the acknowledgement and strengthening of interdependent relationships between health professions education programs, health systems, and the communities they serve. Educational programs must recognize their role as integral components of a larger system. Educators must strive to break down silos and synergize efforts to foster a health care workforce positioned for collaborative, equitable, community-oriented practice. Sharing interprofessional and interinstitutional strategies can foster wide propagation of educational innovation while accommodating local contexts. This paper outlines how member schools of the American Medical Association Accelerating Change in Medical Education Consortium leveraged interdependence to accomplish transformative innovations catalyzed by systems thinking and a community of innovation

And then there were four: a study of UK market concentration - causes, consequences and the scope for market adjustment

While concentration measures are a good indicator of market structure, the link with competitiveness is more complex than often assumed. In particular, the modern theory of industrial organisation makes no clear statement regarding the impact of concentration on competition - the focus of this paper is concentration and no inferences are made about competitive aspects of the market. The extent and nature of concentration within the UK listed company audit market as at April, 2002 and, pro forma, after the collapse of Andersen is documented and analysed in detail (by firm, market segment and industry sector). The largest four firms held 90 per cent of the market (based on audit fees) in 2002, rising to 96 per cent with the demise of Andersen. A single firm, Pricewaterhouse-Coopers, held 70 per cent or more of the share of six out of 38 industry sectors, with a share of 50 per cent up to 70 per cent in a further seven sectors. The provision of non-audit services (NAS) by incumbent auditors is also considered. As at April 2002, the average ratio of non-audit fees (paid to auditor) to audit fees was 208 per cent, and exceeded 300 per cent in seven sectors. It is likely, however, that disposals by firms of their management consultancy and outsource firms, combined with the impact of the Smith Report on audit committees will serve to reduce these ratios. Another finding is that audit firms with expertise in a particular sector appeared to earn significantly higher nonaudit fees from their audit clients in that sector. The paper thus provides a solid empirical basis for debate. The subsequent discussion considers the implications for companies and audit firms of the high level of concentration in the current regulatory climate, where no direct regulatory intervention is planned

Stable isotope analysis of soft tissues from mummified human remains

Mummies are faunal remains that include the preservation of soft tissues, such as skin, muscle, nails and hair as well as bone. These soft tissues are generally rich in collagen or keratin proteins and thus provide potentially suitable material for stable isotope studies. When preserved, such tissues can provide high-resolution information about the diet and migration of humans in the weeks and months before death. Hair, nails and soft tissue provide short-term (months) dietary information in contrast to bone which will represent 5–20 years of dietary history prior to death, depending on the bone analysed. Such high-resolution data can answer questions on the season of death, seasonality of food resources and the movement and relocation of people. This review begins with a summary of the most common isotope techniques (13C/12C, 15N/14N) and the tissues concerned, followed by an analysis of the key questions that have been addressed using these methods. Until relatively recently work has focused on bulk protein isotope analysis, but in the last 10 years this has been expanded to on-line compound-specific amino acid analysis and to a wider variety of isotopes (18O/16O, 2H/1H and 34S/32S) and these applications are also discussed

Endotypes of difficult-to-control asthma in inner-city African American children

African Americans have higher rates of asthma prevalence, morbidity, and mortality in comparison with other racial groups. We sought to characterize endotypes of childhood asthma severity in African American patients in an inner-city pediatric asthma population. Baseline blood neutrophils, blood eosinophils, and 38 serum cytokine levels were measured in a sample of 235 asthmatic children (6–17 years) enrolled in the NIAID (National Institute of Allergy and Infectious Diseases)-sponsored Asthma Phenotypes in the Inner City (APIC) study (ICAC (Inner City Asthma Consortium)-19). Cytokines were quantified using a MILLIPLEX panel and analyzed on a Luminex analyzer. Patients were classified as Easy-to-Control or Difficult-to-Control based on the required dose of controller medications over one year of prospective management. A multivariate variable selection procedure was used to select cytokines associated with Difficult-to-Control versus Easy-to-Control asthma, adjusting for age, sex, blood eosinophils, and blood neutrophils. In inner-city African American children, 12 cytokines were significant predictors of Difficult-to-Control asthma (n = 235). CXCL-1, IL-5, IL-8, and IL-17A were positively associated with Difficult-to-Control asthma, while IL-4 and IL-13 were positively associated with Easy-to-Control asthma. Using likelihood ratio testing, it was observed that in addition to blood eosinophils and neutrophils, serum cytokines improved the fit of the model. In an inner-city pediatric population, serum cytokines significantly contributed to the definition of Difficult-to-Control asthma endotypes in African American children. Mixed responses characterized by TH2 (IL-5) and TH17-associated cytokines were associated with Difficult-to-Control asthma. Collectively, these data may contribute to risk stratification of Difficult-to-Control asthma in the African American population

Realizing autonomy in responsive relationships

The goal of this article is to augment the ethical discussion among nurses with the findings from empirical research on autonomy of older adults with type 2 diabetes mellitus. There are many factors influencing autonomy. These include: health conditions, treatment, knowledge, experience and skills, personal approach as well as familial patterns, type of relationship, life history and social context. Fifteen older adults with type 2 diabetes mellitus were interviewed in a nurse-led diabetes clinic. These participants perceive three processes which support autonomy in responsive relationships: preserving patterns of concern and interaction, nurturing collaborative responsibilities and being closely engaged in trustful and helpful family relations. People with diabetes realize autonomy in various responsive relationships in their unique life context. Next, we performed a literature review of care ethics and caring in nursing with regard to relational autonomy. We classified the literature in five strands of care: attitude-oriented, dialogue-oriented, activity-oriented, relationship-oriented and life-oriented. According to our respondents, autonomy in responsive relationships is fostered when patient, nurses, professionals of the health team and family members carry out care activities supported by a relational attitude of care. They can best realize autonomy in relationships with others when several essential aspects of care and caring are present in their lives. Therefore, we advocate a comprehensive approach to care and caring

BCL11A enhancer edited hematopoietic stem cells persist in rhesus monkeys without toxicity

Gene editing of the erythroid-specific BCL11A enhancer in hematopoietic stem and progenitor cells (HSPCs) from sickle cell disease (SCD) patients induces fetal hemoglobin (HbF) without detectable toxicity as assessed by mouse xenotransplant. Here, we evaluated autologous engraftment and HbF induction potential of erythroid-specific BCL11A enhancer edited HSPCs in four non-human primates. We utilized a single guide RNA (sgRNA) with identical human and rhesus target sequences to disrupt a GATA1 binding site at the BCL11A +58 erythroid enhancer. Cas9 protein and sgRNA ribonucleoprotein complex (RNP) was electroporated into rhesus HSPCs, followed by autologous infusion after myeloablation. We found that gene edits persisted in peripheral blood (PB) and bone marrow (BM) for up to 101 weeks similarly for BCL11A enhancer or control locus (AAVS1) targeted cells. Biallelic BCL11A enhancer editing resulted in robust gamma-globin induction, with the highest levels observed during stress erythropoiesis. Indels were evenly distributed across PB and BM lineages. Off-target edits were not observed. Non-homologous end-joining repair alleles were enriched in engrafting HSCs. In summary, we find that edited HSCs can persist for at least 101 weeks post-transplant, and biallelic edited HSCs provide substantial HbF levels in PB red blood cells, together supporting further clinical translation of this approach