Impaired receptor-mediated endocytosis by the asialoglycoprotein receptor in ethanol-fed mice: implications for studying the role of this receptor in alcoholic apoptosis

During receptor-mediated endocytosis (RME), extracellular molecules are internalized after being recognized and bound to specific cell surface receptors. In previous studies of the asialoglycoprotein receptor (ASGPR) in rats, we showed that ethanol impairs RME at multiple ASGPR sites. Ethanol administration has been shown to increase apoptosis, and we demonstrated increased sensitization to apoptotic induction in hepatocytes from ethanol-fed rats. Although a physiological role for the ASGPR has not been identified, investigators have shown its involvement in the uptake/clearance of apoptotic cells in vitvo. This suggests a potential role for the ASGPR in the removal of apoptotic cells, and the recent availability of an ASGPR-deficient mouse strain provides an excellent opportunity to examine the role of the ASGPR during ethanol impairment. In this study, we examined ethanol-impaired RME in mice and began the characterization of ASGPR-deficient mice for use in ethanol studies. Similar to our findings with rats, ligand binding, internalization, and degradation were decreased 45-50% in hepatocytes from ethanol-fed wild-type mice. In ASGPR-deficient mice, these parameters did not vary among the chow-fed, pair-fed control, or ethanol groups and were negligible compared with those of wild-type mice. TUNEL analysis of liver sections showed an ethanol-induced increase in apoptotic bodies in all mouse strains with a significant difference in the receptor-deficient mice. Further, the livers of ASGPR-deficient mice had three times more apoptotic bodies, in all feeding groups, compared with wild-type mice. These results support the use of the ASGPR-deficient mouse model for studying ethanol-induced liver injury, specifically ethanol-induced apoptosis

Complications among colorectal cancer survivors: SF-6D preference-weighted quality of life scores

Background Societal preference-weighted health-related quality of life (HRQOL) scores enable comparing multi-dimensional health states across diseases and treatments for research and policy. Objective To assess the effects of living with a permanent intestinal stoma, compared to a major bowel resection, among colorectal cancer (CRC) survivors. Research Design Cross-sectional multivariate linear regression analysis to explain preference-weighted HRQOL scores. Subjects Six-hundred-forty CRC survivors (≥5 years) from three group-model HMOs; ostomates and non-ostomates with colorectal resections for CRC were matched on gender, age (±5 years), time since diagnosis, and tumor site (rectum vs. colon). Measures SF-6D scoring system applied to Medical Outcomes Study Short Form-36 version 2 (SF-36v2); City of Hope Quality of Life-Ostomy (mCOH-QOL-O); Charlson-Deyo comorbidity index. Methods Survey of CRC survivors linked to respondents’ clinical data extracted from HMO files. Results Response rate was 52%. Ostomates and non-ostomates had similar sociodemographic characteristics. Mean SF-6D score was 0.69 for ostomates, compared to 0.73 for non-ostomates (p <.001), but other factors explained this difference. Complications of initial cancer surgery, and prior-year comorbidity burden and hospital use were negatively associated with SF-6D scores, while household income was positively associated. Conclusions CRC survivors’ SF-6D scores were not associated with living with a permanent ostomy after other factors were taken into account. Surgical complications, comorbidities, and metastatic disease lowered the preference-weighted HRQOL of CRC survivors with and without ostomies. Further research to understand and reduce late complications from CRC surgeries as well as associated depression is warranted

Federal Land Management Agencies: Background on Land and Resource Management

This report provides an overview of how federal lands and resources are managed, the agencies that manage the lands, the authorities under which these lands are managed, and some of the issues associated with federal land management

The Lick AGN Monitoring Project: Reverberation Mapping of Optical Hydrogen and Helium Recombination Lines

We have recently completed a 64-night spectroscopic monitoring campaign at the Lick Observatory 3-m Shane telescope with the aim of measuring the masses of the black holes in 12 nearby (z < 0.05) Seyfert 1 galaxies with expected masses in the range ~10^6-10^7M_sun and also the well-studied nearby active galactic nucleus (AGN) NGC 5548. Nine of the objects in the sample (including NGC 5548) showed optical variability of sufficient strength during the monitoring campaign to allow for a time lag to be measured between the continuum fluctuations and the response to these fluctuations in the broad Hbeta emission, which we have previously reported. We present here the light curves for the Halpha, Hgamma, HeII 4686, and HeI 5876 emission lines and the time lags for the emission-line responses relative to changes in the continuum flux. Combining each emission-line time lag with the measured width of the line in the variable part of the spectrum, we determine a virial mass of the central supermassive black hole from several independent emission lines. We find that the masses are generally consistent within the uncertainties. The time-lag response as a function of velocity across the Balmer line profiles is examined for six of the AGNs. Finally we compare several trends seen in the dataset against the predictions from photoionization calculations as presented by Korista & Goad. We confirm several of their predictions, including an increase in responsivity and a decrease in the mean time lag as the excitation and ionization level for the species increases. Further confirmation of photoionization predictions for broad-line gas behavior will require additional monitoring programs for these AGNs while they are in different luminosity states. [abridged]Comment: 37 pages, 18 figures and 15 tables, accepted for publication in the Astrophysical Journa

Complementary and conventional medicine: a concept map

BACKGROUND: Despite the substantive literature from survey research that has accumulated on complementary and alternative medicine (CAM) in the United States and elsewhere, very little research has been done to assess conceptual domains that CAM and conventional providers would emphasize in CAM survey studies. The objective of this study is to describe and interpret the results of concept mapping with conventional and CAM practitioners from a variety of backgrounds on the topic of CAM. METHODS: Concept mapping, including free sorts, ratings, and multidimensional scaling was used to organize conceptual domains relevant to CAM into a visual "cluster map." The panel consisted of CAM providers, conventional providers, and university faculty, and was convened to help formulate conceptual domains to guide the development of a CAM survey for use with United States military veterans. RESULTS: Eight conceptual clusters were identified: 1) Self-assessment, Self-care, and Quality of Life; 2) Health Status, Health Behaviors; 3) Self-assessment of Health; 4) Practical/Economic/ Environmental Concerns; 5) Needs Assessment; 6) CAM vs. Conventional Medicine; 7) Knowledge of CAM; and 8) Experience with CAM. The clusters suggest panelists saw interactions between CAM and conventional medicine as a critical component of the current medical landscape. CONCLUSIONS: Concept mapping provided insight into how CAM and conventional providers view the domain of health care, and was shown to be a useful tool in the formulation of CAM-related conceptual domains

Is late-life dependency increasing or not? A comparison of the Cognitive Function and Ageing Studies (CFAS)

Background: Little is known about how the proportions of dependency states have changed between generational cohorts of older people. We aimed to estimate years lived in different dependency states at age 65 years in 1991 and 2011, and new projections of future demand for care. Methods: In this population-based study, we compared two Cognitive Function and Ageing Studies (CFAS I and CFAS II) of older people (aged ≥65 years) who were permanently registered with a general practice in three defined geographical areas (Cambridgeshire, Newcastle, and Nottingham; UK). These studies were done two decades apart (1991 and 2011). General practices provided lists of individuals to be contacted and were asked to exclude those who had died or might die over the next month. Baseline interviews were done in the community and care homes. Participants were stratified by age, and interviews occurred only after written informed consent was obtained. Information collected included basic sociodemographics, cognitive status, urinary incontinence, and self-reported ability to do activities of daily living. CFAS I was assigned as the 1991 cohort and CFAS II as the 2011 cohort, and both studies provided prevalence estimates of dependency in four states: high dependency (24-h care), medium dependency (daily care), low dependency (less than daily), and independent. Years in each dependency state were calculated by Sullivan's method. To project future demands for social care, the proportions in each dependency state (by age group and sex) were applied to the 2014 England population projections. Findings: Between 1991 and 2011, there were significant increases in years lived from age 65 years with low dependency (1·7 years [95% CI 1·0-2·4] for men and 2·4 years [1·8-3·1] for women) and increases with high dependency (0·9 years [0·2-1·7] for men and 1·3 years [0·5-2·1] for women). The majority of men's extra years of life were spent independent (36·3%) or with low dependency (36·3%) whereas for women the majority were spent with low dependency (58·0%), and only 4·8% were independent. There were substantial reductions in the proportions with medium and high dependency who lived in care homes, although, if these dependency and care home proportions remain constant in the future, further population ageing will require an extra 71 215 care home places by 2025. Interpretation: On average older men now spend 2·4 years and women 3·0 years with substantial care needs, and most will live in the community. These findings have considerable implications for families of older people who provide the majority of unpaid care, but the findings also provide valuable new information for governments and care providers planning the resources and funding required for the care of their future ageing populations. Funding: Medical Research Council (G9901400) and (G06010220), with support from the National Institute for Health Research Comprehensive Local research networks in West Anglia and Trent, UK, and Neurodegenerative Disease Research Network in Newcastle, UK

Enhanced relapse prevention for bipolar disorder – ERP trial. A cluster randomised controlled trial to assess the feasibility of training care coordinators to offer enhanced relapse prevention for bipolar disorder

BACKGROUND: Bipolar Disorder (BD) is a common and severe form of mental illness characterised by repeated relapses of mania or depression. Pharmacotherapy is the main treatment currently offered, but this has only limited effectiveness. A recent Cochrane review has reported that adding psycho-social interventions that train people to recognise and manage the early warning signs of their relapses is effective in increasing time to recurrence, improving social functioning and in reducing hospitalisations. However, the review also highlights the difficulties in offering these interventions within standard mental health services due to the need for highly trained therapists and extensive input of time. There is a need to explore the potential for developing Early Warning Sign (EWS) interventions in ways that will enhance dissemination. METHODS AND DESIGN: This article describes a cluster-randomised trial to assess the feasibility of training care coordinators (CCs) in community mental health teams (CMHTs) to offer Enhanced Relapse Prevention (ERP) to people with Bipolar Disorder. CMHTs in the North West of England are randomised to either receive training in ERP and to offer this to their clients, or to continue to offer treatment as usual (TAU). The main aims of the study are (1) to determine the acceptability of the intervention, training and outcome measures (2) to assess the feasibility of the design as measured by rates of recruitment, retention, attendance and direct feedback from participants (3) to estimate the design effect of clustering for key outcome variables (4) to estimate the effect size of the impact of the intervention on outcome. In this paper we provide a rationale for the study design, briefly outline the ERP intervention, and describe in detail the study protocol. DISCUSSION: This information will be useful to researchers attempting to carry out similar feasibility assessments of clinical effectiveness trials and in particular cluster randomised controlled trials

Expert consensus and recommendations on safety criteria for active mobilization of mechanically ventilated critically ill adults

Introduction: The aim of this study was to develop consensus recommendations on safety parameters for mobilizing adult, mechanically ventilated, intensive care unit (ICU) patients. Methods: A systematic literature review was followed by a meeting of 23 multidisciplinary ICU experts to seek consensus regarding the safe mobilization of mechanically ventilated patients. Results: Safety considerations were summarized in four categories: respiratory, cardiovascular, neurological and other. Consensus was achieved on all criteria for safe mobilization, with the exception being levels of vasoactive agents. Intubation via an endotracheal tube was not a contraindication to early mobilization and a fraction of inspired oxygen less than 0.6 with a percutaneous oxygen saturation more than 90% and a respiratory rate less than 30 breaths/minute were considered safe criteria for in- and out-of-bed mobilization if there were no other contraindications. At an international meeting, 94 multidisciplinary ICU clinicians concurred with the proposed recommendations. Conclusion: Consensus recommendations regarding safety criteria for mobilization of adult, mechanically ventilated patients in the ICU have the potential to guide ICU rehabilitation whilst minimizing the risk of adverse events