Identification and Risk-Stratification of Problem Alcohol Drinkers with Minor Trauma in the Emergency Department

BACKGROUND: Brief alcohol intervention may improve outcomes for injury patients with hazardous drinking but is less effective with increased severity of alcohol involvement. This study evaluated a brief method for detecting problem drinking in minor trauma patients and differentiating hazardous drinkers from those with more severe alcohol problems.METHODS: Subjects included 60 minor trauma patients in an academic urban emergency department (ED) who had consumed any amount of alcohol in the prior month. Screening and risk stratification involved the use of a heavy-drinking-day screening item and the Rapid Alcohol Problems Screen (RAPS). We compared the heavy-drinking-day item to past-month alcohol use, as obtained by validated self-reporting methods, and measured the percentage of carbohydrate-deficient transferrin (%CDT) to assess the accuracy of self-reporting. The Alcohol Dependence Scale (ADS) was administered to gauge the severity of alcohol involvement and compared to the RAPS.RESULTS: Eighty percent of the subjects endorsed at least one heavy drinking day in the past year, and all patients who exceeded recommended weekly drinking limits endorsed at least one heavy drinking day. Among those with at least one heavy drinking day, 58% had a positive RAPS result. Persons with no heavy drinking days (n=12) had a median ADS of 0.5 (range 0 to 3). RAPS-negative persons with heavy drinking days (n=20) had a median ADS of 2 (range 0 to 8). RAPS-positive persons with heavy drinking days (n=28) had a median ADS of 8 (range 1 to 43).CONCLUSION: A heavy-drinking-day item is useful for detecting hazardous drinking patterns, and the RAPS is useful for differentiating more problematic drinkers who may benefit from referral from those more likely to respond to a brief intervention. This represents a time-sensitive approach for risk-stratifying non-abstinent injury patients prior to ED discharge. [West J Emerg Med. 2010 May;11(2):133-7.

The Parkes Observatory Pulsar Data Archive

The Parkes pulsar data archive currently provides access to 144044 data files obtained from observations carried out at the Parkes observatory since the year 1991. Around 10^5 files are from surveys of the sky, the remainder are observations of 775 individual pulsars and their corresponding calibration signals. Survey observations are included from the Parkes 70cm and the Swinburne Intermediate Latitude surveys. Individual pulsar observations are included from young pulsar timing projects, the Parkes Pulsar Timing Array and from the PULSE@Parkes outreach program. The data files and access methods are compatible with Virtual Observatory protocols. This paper describes the data currently stored in the archive and presents ways in which these data can be searched and downloaded.Comment: Accepted by PAS

The experience of international nursing students studying for a PhD in the U.K: A qualitative study

<p>Abstract</p> <p>Background</p> <p>Educating nurses to doctoral level is an important means of developing nursing capacity globally. There is an international shortage of doctoral nursing programmes, hence many nurses seek their doctorates overseas. The UK is a key provider of doctoral education for international nursing students, however, very little is known about international doctoral nursing students' learning experiences during their doctoral study. This paper reports on a national study that sought to investigate the learning expectations and experiences of overseas doctoral nursing students in the UK.</p> <p>Methods</p> <p>Semi-structured qualitative interviews were conducted in 2008/09 with 17 international doctoral nursing students representing 9 different countries from 6 different UK universities. Data were analysed thematically. All 17 interviewees were enrolled on 'traditional' 3 year PhD programmes and the majority (15/17) planned to work in higher education institutions back in their home country upon graduation.</p> <p>Results</p> <p>Studying for a UK PhD involved a number of significant transitions, including adjusting to a new country/culture, to new pedagogical approaches and, in some cases, to learning in a second language. Many students had expected a more structured programme of study, with a stronger emphasis on professional nursing issues as well as research - akin to the professional doctorate. Students did not always feel well integrated into their department's wider research environment, and wanted more opportunities to network with their UK peers. A good supervision relationship was perceived as the most critical element of support in a doctoral programme, but good relationships were sometimes difficult to attain due to differences in student/supervisor expectations and in approaches to supervision. The PhD was perceived as a difficult and stressful journey, but those nearing the end reflected positively on it as a life changing experience in which they had developed key professional and personal skills.</p> <p>Conclusions</p> <p>Doctoral programmes need to ensure that structures are in place to support international students at different stages of their doctoral journey, and to support greater local-international student networking. Further research is needed to investigate good supervision practice and the suitability of the PhD vis a vis other doctoral models (e.g. the professional doctorate) for international nursing students.</p

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

The fitness for the Ageing Brain Study II (FABS II): protocol for a randomized controlled clinical trial evaluating the effect of physical activity on cognitive function in patients with Alzheimer's disease

Background: Observational studies have documented a potential protective effect of physical exercise in older adults who are at risk for developing Alzheimer's disease. The Fitness for the Ageing Brain II (FABS II) study is a multicentre randomized controlled clinical trial (RCT) aiming to determine whether physical activity reduces the rate of cognitive decline among individuals with Alzheimer's disease. This paper describes the background, objectives of the study, and an overview of the protocol including design, organization and data collection methods

Heterologous expression of cytotoxic sesquiterpenoids from the medicinal mushroom Lignosus rhinocerotis in yeast

Background: Genome mining facilitated by heterologous systems is an emerging approach to access the chemical diversity encoded in basidiomycete genomes. In this study, three sesquiterpene synthase genes, GME3634, GME3638, and GME9210, which were highly expressed in the sclerotium of the medicinal mushroom Lignosus rhinocerotis, were cloned and heterologously expressed in a yeast system. Results: Metabolite profile analysis of the yeast culture extracts by GC-MS showed the production of several sesquiterpene alcohols (C 15 H 26 O), including cadinols and germacrene D-4-ol as major products. Other detected sesquiterpenes include selina-6-en-4-ol, ß-elemene, ß-cubebene, and cedrene. Two purified major compounds namely (+)-torreyol and a-cadinol synthesised by GME3638 and GME3634 respectively, are stereoisomers and their chemical structures were confirmed by 1 H and 13 C NMR. Phylogenetic analysis revealed that GME3638 and GME3634 are a pair of orthologues, and are grouped together with terpene synthases that synthesise cadinenes and related sesquiterpenes. (+)-Torreyol and a-cadinol were tested against a panel of human cancer cell lines and the latter was found to exhibit selective potent cytotoxicity in breast adenocarcinoma cells (MCF7) with IC 50 value of 3.5 ± 0.58 µg/ml while a-cadinol is less active (IC 50 = 18.0 ± 3.27 µg/ml). Conclusions: This demonstrates that yeast-based genome mining, guided by transcriptomics, is a promising approach for uncovering bioactive compounds from medicinal mushrooms

Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution

Immune evasion is a hallmark of cancer. Losing the ability to present neoantigens through human leukocyte antigen (HLA) loss may facilitate immune evasion. However, the polymorphic nature of the locus has precluded accurate HLA copy-number analysis. Here, we present loss of heterozygosity in human leukocyte antigen (LOHHLA), a computational tool to determine HLA allele-specific copy number from sequencing data. Using LOHHLA, we find that HLA LOH occurs in 40% of non-small-cell lung cancers (NSCLCs) and is associated with a high subclonal neoantigen burden, APOBEC-mediated mutagenesis, upregulation of cytolytic activity, and PD-L1 positivity. The focal nature of HLA LOH alterations, their subclonal frequencies, enrichment in metastatic sites, and occurrence as parallel events suggests that HLA LOH is an immune escape mechanism that is subject to strong microenvironmental selection pressures later in tumor evolution. Characterizing HLA LOH with LOHHLA refines neoantigen prediction and may have implications for our understanding of resistance mechanisms and immunotherapeutic approaches targeting neoantigens. Video Abstract [Figure presented] Development of the bioinformatics tool LOHHLA allows precise measurement of allele-specific HLA copy number, improves the accuracy in neoantigen prediction, and uncovers insights into how immune escape contributes to tumor evolution in non-small-cell lung cancer

Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function

Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes