Single-cell RNA transcriptome landscape of hepatocytes and non-parenchymal cells in healthy and NAFLD mouse liver

Nonalcoholic fatty liver disease (NAFLD) is a global health-care problem with limited therapeutic options. To obtain a cellular resolution of pathogenesis, 82,168 single-cell transcriptomes (scRNA-seq) across different NAFLD stages were profiled, identifying hepatocytes and 12 other non-parenchymal cell (NPC) types. scRNA-seq revealed insights into the cellular and molecular mechanisms of the disease. We discovered a dual role for hepatic stellate cells in gene expression regulation and in the potential to trans-differentiate into myofibroblasts. We uncovered distinct expression profiles of Kupffer cells versus monocyte-derived macrophages during NAFLD progression. Kupffer cells showed stronger immune responses, while monocyte-derived macrophages demonstrated a capability for differentiation. Three chimeric NPCs were identified including endothelial-chimeric stellate cells, hepatocyte-chimeric endothelial cells, and endothelial-chimeric Kupffer cells. Our work identified unanticipated aspects of mouse with NAFLD at the single-cell level and advanced the understanding of cellular heterogeneity in NAFLD livers

Measuring the context of care in an Australian acute care hospital: a nurse survey

BACKGROUND: This study set out to achieve three objectives: to test the application of a context assessment tool in an acute hospital in South Australia; to use the tool to compare context in wards that had undergone an evidence implementation process with control wards; and finally to test for relationships between demographic variables (in particular experience) of nurses being studied (n = 422) with the dimensions of context. METHODS: The Alberta Context Tool (ACT) was administered to all nursing staff on six control and six intervention wards. A total of 217 (62%) were returned (67% from the intervention wards and 56% from control wards). Data were analysed using Stata (v9). The effect of the intervention was analysed using nested (hierarchical) analysis of variance; relationships between nurses' experience and context was examined using canonical correlation analysis. RESULTS: Results confirmed the adaptation and fit of the ACT to one acute care setting in South Australia. There was no difference in context scores between control and intervention wards. However, the tool identified significant variation between wards in many of the dimensions of context. Though significant, the relationship between nurses' experience and context was weak, suggesting that at the level of the individual nurse, few factors are related to context. CONCLUSIONS: Variables operating at the level of the individual showed little relationship with context. However, the study indicated that some dimensions of context (e.g., leadership, culture) vary at the ward level, whereas others (e.g., structural and electronic resources) do not. The ACT also raised a number of interesting speculative hypotheses around the relationship between a measure of context and the capability and capacity of staff to influence it.Timothy J. Schultz and Alison L. Kitso

A comparative study on gene-set analysis methods for assessing differential expression associated with the survival phenotype

Abstract Background Many gene-set analysis methods have been previously proposed and compared through simulation studies and analysis of real datasets for binary phenotypes. We focused on the survival phenotype and compared the performances of Gene Set Enrichment Analysis (GSEA), Global Test (GT), Wald-type Test (WT) and Global Boost Test (GBST) methods in a simulation study and on two ovarian cancer data sets. We considered two versions of GSEA by allowing different weights: GSEA1 uses equal weights, yielding results similar to the Kolmogorov-Smirnov test; while GSEA2's weights are based on the correlation between genes and the phenotype. Results We compared GSEA1, GSEA2, GT, WT and GBST in a simulation study with various settings for the correlation structure of the genes and the association parameter between the survival outcome and the genes. Simulation results indicated that GT, WT and GBST consistently have higher power than GSEA1 and GSEA2 across all scenarios. However, the power of the five tests depends on the combination of correlation structure and association parameter. For the ovarian cancer data set, using the FDR threshold of q Conclusion Simulation studies and a real data example indicate that GT, WT and GBST tend to have high power, whereas GSEA1 and GSEA2 have lower power. We also found that the power of the five tests is much higher when genes are correlated than when genes are independent, when survival is positively associated with genes. It seems that there is a synergistic effect in detecting significant gene sets when significant genes have within-class correlation and the association between survival and genes is positive or negative (i.e., one-direction correlation).</p

Developing country consumers’ acceptance of biofortified foods: a synthesis

The success of biofortified staple crops depends on whether they are accepted and consumed by target populations. In the past 8 years, several studies were undertaken to understand consumers’ acceptance of foods made with biofortified staple crops. Consumer acceptance is measured in terms of their sensory evaluation and economic valuation of biofortified varieties vis-à-vis conventional ones. These studies apply expert sensory panel and hedonic trait analyses methods adopted from food sciences literature, as well as various preference elicitation methods (including experimental auctions, revealed choice experiments, and stated choice experiments) adopted from experimental economics literature. These studies also test the impact of various levers on consumers’ evaluation and valuation for biofortified foods. These levers include (i) nutrition information and the media through which such information is conveyed; (ii) the length and content of nutrition information; (iii) different branding options; (iv) the nature (national or international) of the branding/certification agency that is endorsing the biofortified staple food; and (v) the nature (national or international) of the agency that is delivering the biofortified staple food. This paper brings together evidence on consumer acceptance of biofortified crops on 5 crops across 7 countries in Africa, Asia and Latin America. The results of these studies are expected to aid in the development of biofortified crops that consumers like, as well as in the development of appropriate marketing and consumer awareness or information campaigns to encourage the switch in consumption from traditional staples to biofortified ones

Assessment of variation in the alberta context tool: the contribution of unit level contextual factors and specialty in Canadian pediatric acute care settings

Background: There are few validated measures of organizational context and none that we located are parsimonious and address modifiable characteristics of context. The Alberta Context Tool (ACT) was developed to meet this need. The instrument assesses 8 dimensions of context, which comprise 10 concepts. The purpose of this paper is to report evidence to further the validity argument for ACT. The specific objectives of this paper are to: (1) examine the extent to which the 10 ACT concepts discriminate between patient care units and (2) identify variables that significantly contribute to between-unit variation for each of the 10 concepts. Methods: 859 professional nurses (844 valid responses) working in medical, surgical and critical care units of 8 Canadian pediatric hospitals completed the ACT. A random intercept, fixed effects hierarchical linear modeling (HLM) strategy was used to quantify and explain variance in the 10 ACT concepts to establish the ACT’s ability to discriminate between units. We ran 40 models (a series of 4 models for each of the 10 concepts) in which we systematically assessed the unique contribution (i.e., error variance reduction) of different variables to between-unit variation. First, we constructed a null model in which we quantified the variance overall, in each of the concepts. Then we controlled for the contribution of individual level variables (Model 1). In Model 2, we assessed the contribution of practice specialty (medical, surgical, critical care) to variation since it was central to construction of the sampling frame for the study. Finally, we assessed the contribution of additional unit level variables (Model 3). Results: The null model (unadjusted baseline HLM model) established that there was significant variation between units in each of the 10 ACT concepts (i.e., discrimination between units). When we controlled for individual characteristics, significant variation in the 10 concepts remained. Assessment of the contribution of specialty to between-unit variation enabled us to explain more variance (1.19% to 16.73%) in 6 of the 10 ACT concepts. Finally, when we assessed the unique contribution of the unit level variables available to us, we were able to explain additional variance (15.91% to 73.25%) in 7 of the 10 ACT concepts. Conclusion: The findings reported here represent the third published argument for validity of the ACT and adds to the evidence supporting its use to discriminate patient care units by all 10 contextual factors. We found evidence of relationships between a variety of individual and unit-level variables that explained much of this between-unit variation for each of the 10 ACT concepts. Future research will include examination of the relationships between the ACT’s contextual factors and research utilization by nurses and ultimately the relationships between context, research utilization, and outcomes for patients

Augmented acquisition of cocaine self-administration and altered brain glucose metabolism in adult female but not male rats exposed to a cannabinoid agonist during adolescence

Marijuana consumption during adolescence has been proposed to be a stepping stone for adult cocaine addiction. However, experimental evidence for this hypothesis is missing. In this work we chronically injected male and female Wistar rats with either the cannabinoid agonist CP 55,940 (CP; 0.4 mg/kg) or its corresponding vehicle. Adult acquisition (seven 30 min daily sessions) and maintenance (fourteen 2 h daily sessions) of cocaine self administration (1 mg/kg), food reinforced operant learning under conditions of normal (ad libitum access to food), and high motivation (food restriction schedule) were measured. Additionally, brain metabolic activity was analyzed by means of [18F] fluorodeoxyglucose positron emission tomography. During the acquisition phase, female CP treated rats showed a higher rate of cocaine self administration as compared to vehicle treated females and males; no differences were found between both male groups. This effect disappeared in the maintenance phase. Moreover, no differences among groups were evident in the food reinforced operant task, pointing to the cocaine specific nature of the effect seen in self administration rather than a general change in reward processing. Basal brain metabolic activity also changed in CP treated females when compared to their vehicle treated counterparts with no differences being found in the males; more specifically we observed a hyper activation of the frontal cortex and a hypo activation of the amygdalo entorhinal cortex. Our results suggest that a chronic exposure to cannabinoids during adolescence alters the susceptibility to acquire cocaine self administration, in a sex specific fashion. This increased susceptibility could be related to thechanges in brain metabolic activity induced by cannabinoids during adolescenceThis work was supported by Grants FIS G03/05 (Red de Trastornos Adictivos), BSO2001-1099, FIS 01-05-01, Plan Nacional sobre Drogas (PNSD) 2001–2003, PNSD 2004–2007, GR-SAL/0260/2004 to EA and Grants INT/2012/ 2002, CB06/01/0079, and CENIT (2006–2009) to MDPublicad

Multi-level analysis of electronic health record adoption by health care professionals: A study protocol

<p>Abstract</p> <p>Background</p> <p>The electronic health record (EHR) is an important application of information and communication technologies to the healthcare sector. EHR implementation is expected to produce benefits for patients, professionals, organisations, and the population as a whole. These benefits cannot be achieved without the adoption of EHR by healthcare professionals. Nevertheless, the influence of individual and organisational factors in determining EHR adoption is still unclear. This study aims to assess the unique contribution of individual and organisational factors on EHR adoption in healthcare settings, as well as possible interrelations between these factors.</p> <p>Methods</p> <p>A prospective study will be conducted. A stratified random sampling method will be used to select 50 healthcare organisations in the Quebec City Health Region (Canada). At the individual level, a sample of 15 to 30 health professionals will be chosen within each organisation depending on its size. A semi-structured questionnaire will be administered to two key informants in each organisation to collect organisational data. A composite adoption score of EHR adoption will be developed based on a Delphi process and will be used as the outcome variable. Twelve to eighteen months after the first contact, depending on the pace of EHR implementation, key informants and clinicians will be contacted once again to monitor the evolution of EHR adoption. A multilevel regression model will be applied to identify the organisational and individual determinants of EHR adoption in clinical settings. Alternative analytical models would be applied if necessary.</p> <p>Results</p> <p>The study will assess the contribution of organisational and individual factors, as well as their interactions, to the implementation of EHR in clinical settings.</p> <p>Conclusions</p> <p>These results will be very relevant for decision makers and managers who are facing the challenge of implementing EHR in the healthcare system. In addition, this research constitutes a major contribution to the field of knowledge transfer and implementation science.</p

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700