Relationship between plasma fibroblast growth factor-23 concentration and survival time in cats with chronic kidney disease

BACKGROUND: Fibroblast growth factor‐23 (FGF‐23) and parathyroid hormone (PTH) are commonly increased in cats with azotemic chronic kidney disease (CKD). Both are predictors of survival time in human patients, but these relationships have not previously been examined in the cat. OBJECTIVES: To investigate the relationship between plasma FGF‐23 and PTH concentrations at diagnosis of CKD in cats with survival time and with disease progression over 12 months. ANIMALS: 214 azotemic, client‐owned cats (≥9 years). METHODS: Retrospective study: Biochemical and urinary variables at diagnosis of azotemic CKD, including plasma FGF‐23 and PTH concentrations were assessed as predictors of survival time (all‐cause mortality) using Cox regression, and as predictors of CKD progression over 12 months using logistic regression. RESULTS: In the final multivariable Cox regression model, survival was negatively associated with plasma creatinine (P = .002) and FGF‐23 concentrations (P = .014), urine protein‐to‐creatinine ratio (P < .001) and age (P < .001). Survival was positively associated with PCV (P = .004). In the final multivariable logistic regression model, independent predictors of CKD progression included logFGF‐23 and age. Neither plasma phosphate nor PTH was found to be an independent predictor of survival time or of CKD progression. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma FGF‐23 concentration is a novel prognostic indicator in cats with CKD, independent of other factors including plasma creatinine and phosphate concentrations. Further work is required to assess if FGF‐23 contributes directly to CKD progression, but regardless these findings may make FGF‐23 a useful biomarker for predicting poorer outcomes in cats with CKD

Ethical issues in the use of in-depth interviews: literature review and discussion

This paper reports a literature review on the topic of ethical issues in in-depth interviews. The review returned three types of article: general discussion, issues in particular studies, and studies of interview-based research ethics. Whilst many of the issues discussed in these articles are generic to research ethics, such as confidentiality, they often had particular manifestations in this type of research. For example, privacy was a significant problem as interviews sometimes probe unexpected areas. For similar reasons, it is difficult to give full information of the nature of a particular interview at the outset, hence informed consent is problematic. Where a pair is interviewed (such as carer and cared-for) there are major difficulties in maintaining confidentiality and protecting privacy. The potential for interviews to harm participants emotionally is noted in some papers, although this is often set against potential therapeutic benefit. As well as these generic issues, there are some ethical issues fairly specific to in-depth interviews. The problem of dual role is noted in many papers. It can take many forms: an interviewer might be nurse and researcher, scientist and counsellor, or reporter and evangelist. There are other specific issues such as taking sides in an interview, and protecting vulnerable groups. Little specific study of the ethics of in-depth interviews has taken place. However, that which has shows some important findings. For example, one study shows participants are not averse to discussing painful issues provided they feel the study is worthwhile. Some papers make recommendations for researchers. One such is that they should consider using a model of continuous (or process) consent rather than viewing consent as occurring once, at signature, prior to the interview. However, there is a need for further study of this area, both philosophical and empirical

A kinematic study of Open Clusters: implications for their origin

The Galactic population of open clusters provides an insight into star formation in the Galaxy. The open cluster catalogue by Dias et al.(2002b) is a rich source of data, including kinematic information. This large sample made it possible to carry out a systematic analysis of 481 open cluster orbits, using parameters based on orbit eccentricity and separation from the Galactic plane. These two parameters may be indicative of origin, and we find them to be correlated. We also find them to be correlated with metallicity, another parameter suggested elsewhere to be a marker for origin in that high values of any of these two parameters generally indicates a low metallicity ([Fe/H] Solar$<-$0.2 dex). The resulting analysis points to four open clusters in the catalogue being of extra-Galactic origin by impact of high velocity cloud on the disk: Berkeley21, 32, 99, and Melotte66, with a possible further four due to this origin (NGC2158, 2420, 7789, IC1311). A further three may be due to Galactic globular cluster impact on the disk i.e of internal Galactic origin (NGC6791, 1817, and 7044).Comment: 14 pages, 816 figures, accepted for publication in MNRAS 14-May-201

Galaxy density profiles and shapes -- I. simulation pipeline for lensing by realistic galaxy models

Studies of strong gravitational lensing in current and upcoming wide and deep photometric surveys, and of stellar kinematics from (integral-field) spectroscopy at increasing redshifts, promise to provide valuable constraints on galaxy density profiles and shapes. However, both methods are affected by various selection and modelling biases, whch we aim to investigate in a consistent way. In this first paper in a series we develop a flexible but efficient pipeline to simulate lensing by realistic galaxy models. These galaxy models have separate stellar and dark matter components, each with a range of density profiles and shapes representative of early-type, central galaxies without significant contributions from other nearby galaxies. We use Fourier methods to calculate the lensing properties of galaxies with arbitrary surface density distributions, and Monte Carlo methods to compute lensing statistics such as point-source lensing cross-sections. Incorporating a variety of magnification bias modes lets us examine different survey limitations in image resolution and flux. We rigorously test the numerical methods for systematic errors and sensitivity to basic assumptions. We also determine the minimum number of viewing angles that must be sampled in order to recover accurate orientation-averaged lensing quantities. We find that for a range of non-isothermal stellar and dark matter density profiles typical of elliptical galaxies, the combined density profile and corresponding lensing properties are surprisingly close to isothermal around the Einstein radius. The converse implication is that constraints from strong lensing and/or stellar kinematics, which are indeed consistent with isothermal models near the Einstein radius, cannot trivially be extrapolated to smaller and larger radii.Comment: 31 pages, 15 figures; paper II at arXiv:0808.2497; accepted for publication in MNRAS; PDF file with full resolution figures at http://www.sns.ias.edu/~glenn/paper1.pd

Process evaluation for complex interventions in primary care: understanding trials using the normalization process model

Background: the Normalization Process Model is a conceptual tool intended to assist in understanding the factors that affect implementation processes in clinical trials and other evaluations of complex interventions. It focuses on the ways that the implementation of complex interventions is shaped by problems of workability and integration.Method: in this paper the model is applied to two different complex trials: (i) the delivery of problem solving therapies for psychosocial distress, and (ii) the delivery of nurse-led clinics for heart failure treatment in primary care.Results: application of the model shows how process evaluations need to focus on more than the immediate contexts in which trial outcomes are generated. Problems relating to intervention workability and integration also need to be understood. The model may be used effectively to explain the implementation process in trials of complex interventions.Conclusion: the model invites evaluators to attend equally to considering how a complex intervention interacts with existing patterns of service organization, professional practice, and professional-patient interaction. The justification for this may be found in the abundance of reports of clinical effectiveness for interventions that have little hope of being implemented in real healthcare setting

Structural analysis of MDM2 RING separates degradation from regulation of p53 transcription activity

MDM2–MDMX complexes bind the p53 tumor-suppressor protein, inhibiting p53's transcriptional activity and targeting p53 for proteasomal degradation. Inhibitors that disrupt binding between p53 and MDM2 efficiently activate a p53 response, but their use in the treatment of cancers that retain wild-type p53 may be limited by on-target toxicities due to p53 activation in normal tissue. Guided by a novel crystal structure of the MDM2–MDMX–E2(UbcH5B)–ubiquitin complex, we designed MDM2 mutants that prevent E2–ubiquitin binding without altering the RING-domain structure. These mutants lack MDM2's E3 activity but retain the ability to limit p53′s transcriptional activity and allow cell proliferation. Cells expressing these mutants respond more quickly to cellular stress than cells expressing wild-type MDM2, but basal p53 control is maintained. Targeting the MDM2 E3-ligase activity could therefore widen the therapeutic window of p53 activation in tumors

Wheat-barley hybridization – the last forty years

Abstract Several useful alien gene transfers have been reported from related species into wheat (Triticum aestivum), but very few publications have dealt with the development of wheat/barley (Hordeum vulgare) introgression lines. An overview is given here of wheat 9 barley hybridization over the last forty years, including the development of wheat 9 barley hybrids, and of addition and translocation lines with various barley cultivars. A short summary is also given of the wheat 9 barley hybrids produced with other Hordeum species. The meiotic pairing behaviour of wheat 9 barley hybrids is presented, with special regard to the detection of wheat– barley homoeologous pairing using the molecular cytogenetic technique GISH. The effect of in vitro multiplication on the genome composition of intergeneric hybrids is discussed, and the production and characterization of the latest wheat/barley translocation lines are presented. An overview of the agronomical traits (b-glucan content, earliness, salt tolerance, sprouting resistance, etc.) of the newly developed introgression lines is given. The exploitation and possible use of wheat/barley introgression lines for the most up-to-date molecular genetic studies (transcriptome analysis, sequencing of flow-sorted chromosomes) are also discussed

Ethnic Inequalities in Mortality: The Case of Arab-Americans

BACKGROUND: Although nearly 112 million residents of the United States belong to a non-white ethnic group, the literature about differences in health indicators across ethnic groups is limited almost exclusively to Hispanics. Features of the social experience of many ethnic groups including immigration, discrimination, and acculturation may plausibly influence mortality risk. We explored life expectancy and age-adjusted mortality risk of Arab-Americans (AAs), relative to non-Arab and non-Hispanic Whites in Michigan, the state with the largest per capita population of AAs in the US. METHODOLOGY/PRINCIPAL FINDINGS: Data were collected about all deaths to AAs and non-Arab and non-Hispanic Whites in Michigan between 1990 and 2007, and year 2000 census data were collected for population denominators. We calculated life expectancy, age-adjusted all-cause, cause-specific, and age-specific mortality rates stratified by ethnicity and gender among AAs and non-Arab and non-Hispanic Whites. Among AAs, life expectancies among men and women were 2.0 and 1.4 years lower than among non-Arab and non-Hispanic White men and women, respectively. AA men had higher mortality than non-Arab and non-Hispanic White men due to infectious diseases, chronic diseases, and homicide. AA women had higher mortality than non-Arab and non-Hispanic White women due to chronic diseases. CONCLUSIONS/SIGNIFICANCE: Despite better education and higher income, AAs have higher age-adjusted mortality risk than non-Arab and non-Hispanic Whites, particularly due to chronic diseases. Features specific to AA culture may explain some of these findings

Measurements of the transverse-momentum-dependent cross sections of J /ψ production at mid-rapidity in proton+proton collisions at s =510 and 500 GeV with the STAR detector

We present measurements of the differential cross sections of inclusive J/ψ meson production as a function of transverse momentum (pTJ/ψ) using the μ+μ- and e+e- decay channels in proton+proton collisions at center-of-mass energies of 510 and 500 GeV, respectively, recorded by the STAR detector at the Relativistic Heavy Ion Collider. The measurement from the μ+μ- channel is for