eModeration: Contextualising online learning in undergraduate nurse education

The wide availability of flexible, mixed-mode methods of course delivery to nursing students places increased demands on the skills and adaptability of nurse educators. The rapid uptake of computer-moderated learning, in particular, has required educators to reconsider some of their long-established pedagogical beliefs and practices which, over time, have faithfully sustained face-to-face teaching in classrooms. Inevitably, a certain degree of pedagogical adjustment is required when teaching online to ensure that the qualities of educational processes are consonant with expected learning outcomes. This paper discusses these important aspects, together with strategies that can help optimise educational practice, with a view to improve the delivery of Web-based courses

Enhanced activation of an amino-terminally truncated isoform of the voltage-gated proton channel HVCN1 enriched in malignant B cells

The final published version can be found here: http://dx.doi.org/10.1073/pnas.1411390111M.C. is the recipient of a Bennett Fellowship from Leukaemia and Lymphoma Research (ref. 12002). M.A.B. is supported by a GlaxoSmithKline Oncology–Biotechnology and Biological Sciences Research Council Collaborative Awards in Science and Engineering PhD studentship. This work was supported by National Institutes of Health Grants GM087507 and GM102336 (to T.E.D.)

Excess mortality in patients with advanced chronic hepatitis C treated with long-term peginterferon

Chronic hepatitis C virus infection can cause chronic liver disease, cirrhosis and liver cancer. The Hepatitis C Antiviral Long-term Treatment against Cirrhosis (HALT-C) Trial was a prospective, randomized controlled study of long-term, low-dose peginterferon therapy in patients with advanced chronic hepatitis C who failed to respond to a previous course of optimal antiviral therapy. The aim of this follow-up analysis is to describe the frequency and causes of death among this cohort of patients. Deaths occurring during and after the HALT-C Trial were reviewed by a committee of investigators to determine the cause of death and to categorize each death as liver- or nonliver-related and as related or not to complications of peginterferon. Rates of liver transplantation were also assessed. Over a median of 5.7 years, 122 deaths occurred among 1,050 randomized patients (12%), of which 76 were considered liver-related (62%) and 46 nonliver-related (38%); 74 patients (7%) underwent liver transplantation. At 7 years the cumulative mortality rate was higher in the treatment compared to the control group (20% versus 15%, P = 0.049); the primary difference in mortality was in patients in the fibrosis compared to the cirrhosis stratum (14% versus 7%, P = 0.01); comparable differences were observed when liver transplantation was included. Excess mortality, emerging after 3 years of treatment, was related largely to nonliver-related death; liver-related mortality was similar in the treatment and control groups. No specific cause of death accounted for the excess mortality and only one death was suspected to be a direct complication of peginterferon. Conclusion: Long-term maintenance peginterferon in patients with advanced chronic hepatitis C is associated with an excess overall mortality, which was primarily due to nonliver-related causes among patients with bridging fibrosis. (H EPATOLOGY 2011;)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83750/1/24169_ftp.pd

Outcome of sustained virological responders with histologically advanced chronic hepatitis C

Retrospective studies suggest that subjects with chronic hepatitis C and advanced fibrosis who achieve a sustained virological response (SVR) have a lower risk of hepatic decompensation and hepatocellular carcinoma (HCC). In this prospective analysis, we compared the rate of death from any cause or liver transplantation, and of liver-related morbidity and mortality, after antiviral therapy among patients who achieved SVR, virologic nonresponders (NR), and those with initial viral clearance but subsequent breakthrough or relapse (BT/R) in the HALT-C (Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis) Trial. Laboratory and/or clinical outcome data were available for 140 of the 180 patients who achieved SVR. Patients with nonresponse (NR; n = 309) or who experienced breakthrough or relapse (BT/R; n = 77) were evaluated every 3 months for 3.5 years and then every 6 months thereafter. Outcomes included death, liver-related death, liver transplantation, decompensated liver disease, and HCC. Median follow-up for the SVR, BT/R, and NR groups of patients was 86, 85, and 79 months, respectively. At 7.5 years, the adjusted cumulative rate of death/liver transplantation and of liver-related morbidity/mortality in the SVR group (2.2% and 2.7%, respectively) was significantly lower than that of the NR group (21.3% and 27.2%, P < 0.001 for both) but not the BT/R group (4.4% and 8.7%). The adjusted hazard ratio (HR) for time to death/liver transplantation (HR = 0.17, 95% confidence interval [CI] = 0.06-0.46) or development of liver-related morbidity/mortality (HR = 0.15, 95% CI = 0.06-0.38) or HCC (HR = 0.19, 95% CI = 0.04-0.80) was significant for SVR compared to NR. Laboratory tests related to liver disease severity improved following SVR. Conclusion: Patients with advanced chronic hepatitis C who achieved SVR had a marked reduction in death/liver transplantation, and in liver-related morbidity/mortality, although they remain at risk for HCC. (H EPATOLOGY 2010;)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/78047/1/23744_ftp.pd

The Glial Regenerative Response to Central Nervous System Injury Is Enabled by Pros-Notch and Pros-NFκB Feedback

Organisms are structurally robust, as cells accommodate changes preserving structural integrity and function. The molecular mechanisms underlying structural robustness and plasticity are poorly understood, but can be investigated by probing how cells respond to injury. Injury to the CNS induces proliferation of enwrapping glia, leading to axonal re-enwrapment and partial functional recovery. This glial regenerative response is found across species, and may reflect a common underlying genetic mechanism. Here, we show that injury to the Drosophila larval CNS induces glial proliferation, and we uncover a gene network controlling this response. It consists of the mutual maintenance between the cell cycle inhibitor Prospero (Pros) and the cell cycle activators Notch and NFκB. Together they maintain glia in the brink of dividing, they enable glial proliferation following injury, and subsequently they exert negative feedback on cell division restoring cell cycle arrest. Pros also promotes glial differentiation, resolving vacuolization, enabling debris clearance and axonal enwrapment. Disruption of this gene network prevents repair and induces tumourigenesis. Using wound area measurements across genotypes and time-lapse recordings we show that when glial proliferation and glial differentiation are abolished, both the size of the glial wound and neuropile vacuolization increase. When glial proliferation and differentiation are enabled, glial wound size decreases and injury-induced apoptosis and vacuolization are prevented. The uncovered gene network promotes regeneration of the glial lesion and neuropile repair. In the unharmed animal, it is most likely a homeostatic mechanism for structural robustness. This gene network may be of relevance to mammalian glia to promote repair upon CNS injury or disease

Variants in interferon-alpha pathway genes and response to pegylated interferon-Alpha2a plus ribavirin for treatment of chronic hepatitis C virus infection in the hepatitis C antiviral long-term treatment against cirrhosis trial

Combination treatment with pegylated-interferon-alpha (PEG IFN-Α) and ribavirin, the current recommended therapy for chronic hepatitis C virus (HCV) infection, results in a sustained virological response (SVR) in only about half of patients. Because genes involved in the interferon-alpha pathway may affect antiviral responses, we analyzed the relationship between variants in these genes and SVR among participants in the Hepatitis C Antiviral Long-Term treatment Against Cirrhosis (HALT-C) trial. Patients had advanced chronic hepatitis C that had previously failed to respond to interferon-based treatment. Participants were treated with peginterferon-Α2a and ribavirin during the trial. Subjects with undetectable HCV RNA at week 72 were considered to have had an SVR. Subjects with detectable HCV RNA at week 20 were considered nonresponders. We used TaqMan assays to genotype 56 polymorphisms found in 13 genes in the interferon-alpha pathway. This analysis compares genotypes for participants with an SVR to nonresponders. The primary analysis was restricted to European American participants because a priori statistical power was low among the small number (n = 131) of African American patients. We used logistic regression to control the effect of other variables that are associated with treatment response. Among 581 European American patients, SVR was associated with IFNAR1 IVS1-22G (adjusted odds ratio, 0.57; P = 0.02); IFNAR2 Ex2-33C (adjusted odds ratio, 2.09; P = 0.02); JAK1 IVS22+112T (adjusted odds ratio, 1.66; P = 0.04); and ADAR Ex9+14A (adjusted odds ratio, 1.67; P = 0.03). For the TYK2 -2256A promoter region variant, a borderline association was present among European American participants (OR, 1.51; P = 0.05) and a strong relationship among African American patients; all 10 with SVR who were genotyped for TYK2 -2256 carried the A variant compared with 68 of 120 (57%) nonresponders ( P = 0.006). Conclusion: Genetic polymorphisms in the interferon-Α pathway may affect responses to antiviral therapy of chronic hepatitis C. (H EPATOLOGY 2009.)Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/63061/1/22877_ftp.pd

The Fire and Tree Mortality Database, for Empirical Modeling of Individual Tree Mortality After Fire

Wildland fires have a multitude of ecological effects in forests, woodlands, and savannas across the globe. A major focus of past research has been on tree mortality from fire, as trees provide a vast range of biological services. We assembled a database of individual-tree records from prescribed fires and wildfires in the United States. The Fire and Tree Mortality (FTM) database includes records from 164,293 individual trees with records of fire injury (crown scorch, bole char, etc.), tree diameter, and either mortality or top-kill up to ten years post-fire. Data span 142 species and 62 genera, from 409 fires occurring from 1981-2016. Additional variables such as insect attack are included when available. The FTM database can be used to evaluate individual fire-caused mortality models for pre-fire planning and post-fire decision support, to develop improved models, and to explore general patterns of individual fire-induced tree death. The database can also be used to identify knowledge gaps that could be addressed in future research

Peptide YY ablation in mice leads to the development of hyperinsulinaemia and obesity

Aims/hypothesis. Obese people exhibit reduced circulating peptide YY (PYY) levels, but it is unclear whether this is a consequence or cause of obesity. We therefore investigated the effect of Pyy ablation on energy homeostasis. Methods. Body composition, i.p. glucose tolerance, food intake and hypothalamic neuropeptide expression were determined in Pyy knock-out and wild-type mice on a normal or high-fat diet. Results. Pyy knock-out significantly increased bodyweight and increased fat mass by 50% in aged females on a normal diet. Male chow-fed Pyy −/− mice were resistant to obesity but became significantly fatter and glucose-intolerant compared with wild-types when fed a high-fat diet. Pyy knock-out animals exhibited significantly elevated fasting or glucose-stimulated serum insulin concentrations vs wild-types, with no increase in basal or fasting-induced food intake. Pyy knock-out decreased or had no effect on neuropeptide Y expression in the arcuate nucleus of the hypothalamus, and significantly increased proopiomelanocortin expression in this region. Male but not female knock-outs exhibited significantly increased growth hormone-releasing hormone expression in the ventromedial hypothalamus and significantly elevated serum IGF-I and testosterone levels. This sex difference in activation of the hypothalamo–pituitary somatotrophic axis by Pyy ablation may contribute to the resistance of chow-fed male knock-outs to late-onset obesity. Conclusions/interpretation. PYY signalling is important in the regulation of energy balance and glucose homeostasis, possibly via regulation of insulin release. Therefore reduced PYY levels may predispose to the development of obesity, particularly with ageing or under conditions of high-fat feeding

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin