Systematic comparison of ranking aggregation methods for gene lists in experimental results.

MOTIVATION: A common experimental output in biomedical science is a list of genes implicated in a given biological process or disease. The gene lists resulting from a group of studies answering the same, or similar, questions can be combined by ranking aggregation methods to find a consensus or a more reliable answer. Evaluating a ranking aggregation method on a specific type of data before using it is required to support the reliability since the property of a dataset can influence the performance of an algorithm. Such evaluation on gene lists is usually based on a simulated database because of the lack of a known truth for real data. However, simulated datasets tend to be too small compared to experimental data and neglect key features, including heterogeneity of quality, relevance and the inclusion of unranked lists. RESULTS: In this study, a group of existing methods and their variations that are suitable for meta-analysis of gene lists are compared using simulated and real data. Simulated data were used to explore the performance of the aggregation methods as a function of emulating the common scenarios of real genomic data, with various heterogeneity of quality, noise level and a mix of unranked and ranked data using 20 000 possible entities. In addition to the evaluation with simulated data, a comparison using real genomic data on the SARS-CoV-2 virus, cancer (non-small cell lung cancer) and bacteria (macrophage apoptosis) was performed. We summarize the results of our evaluation in a simple flowchart to select a ranking aggregation method, and in an automated implementation using the meta-analysis by information content algorithm to infer heterogeneity of data quality across input datasets. AVAILABILITY AND IMPLEMENTATION: The code for simulated data generation and running edited version of algorithms: https://github.com/baillielab/comparison_of_RA_methods. Code to perform an optimal selection of methods based on the results of this review, using the MAIC algorithm to infer the characteristics of an input dataset, can be downloaded here: https://github.com/baillielab/maic. An online service for running MAIC: https://baillielab.net/maic. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Graphia: A platform for the graph-based visualisation and analysis of high dimensional data.

Graphia is an open-source platform created for the graph-based analysis of the huge amounts of quantitative and qualitative data currently being generated from the study of genomes, genes, proteins metabolites and cells. Core to Graphia's functionality is support for the calculation of correlation matrices from any tabular matrix of continuous or discrete values, whereupon the software is designed to rapidly visualise the often very large graphs that result in 2D or 3D space. Following graph construction, an extensive range of measurement algorithms, routines for graph transformation, and options for the visualisation of node and edge attributes are available, for graph exploration and analysis. Combined, these provide a powerful solution for the interpretation of high-dimensional data from many sources, or data already in the form of a network or equivalent adjacency matrix. Several use cases of Graphia are described, to showcase its wide range of applications in the analysis biological data. Graphia runs on all major desktop operating systems, is extensible through the deployment of plugins and is freely available to download from https://graphia.app/.

Stem cell-derived porcine macrophages as a new platform for studying host-pathogen interactions.

BACKGROUND: Infectious diseases of farmed and wild animals pose a recurrent threat to food security and human health. The macrophage, a key component of the innate immune system, is the first line of defence against many infectious agents and plays a major role in shaping the adaptive immune response. However, this phagocyte is a target and host for many pathogens. Understanding the molecular basis of interactions between macrophages and pathogens is therefore crucial for the development of effective strategies to combat important infectious diseases. RESULTS: We explored how porcine pluripotent stem cells (PSCs) can provide a limitless in vitro supply of genetically and experimentally tractable macrophages. Porcine PSC-derived macrophages (PSCdMs) exhibited molecular and functional characteristics of ex vivo primary macrophages and were productively infected by pig pathogens, including porcine reproductive and respiratory syndrome virus (PRRSV) and African swine fever virus (ASFV), two of the most economically important and devastating viruses in pig farming. Moreover, porcine PSCdMs were readily amenable to genetic modification by CRISPR/Cas9 gene editing applied either in parental stem cells or directly in the macrophages by lentiviral vector transduction. CONCLUSIONS: We show that porcine PSCdMs exhibit key macrophage characteristics, including infection by a range of commercially relevant pig pathogens. In addition, genetic engineering of PSCs and PSCdMs affords new opportunities for functional analysis of macrophage biology in an important livestock species. PSCs and differentiated derivatives should therefore represent a useful and ethical experimental platform to investigate the genetic and molecular basis of host-pathogen interactions in pigs, and also have wider applications in livestock.

Efficient CRISPR/Cas9 genome editing in a salmonid fish cell line using a lentivirus delivery system.

BACKGROUND: Genome editing is transforming bioscience research, but its application to non-model organisms, such as farmed animal species, requires optimisation. Salmonids are the most important aquaculture species by value, and improving genetic resistance to infectious disease is a major goal. However, use of genome editing to evaluate putative disease resistance genes in cell lines, and the use of genome-wide CRISPR screens is currently limited by a lack of available tools and techniques. RESULTS: In the current study, we developed an optimised protocol using lentivirus transduction for efficient integration of constructs into the genome of a Chinook salmon (Oncorhynchus tshwaytcha) cell line (CHSE-214). As proof-of-principle, two target genes were edited with high efficiency in an EGFP-Cas9 stable CHSE cell line; specifically, the exogenous, integrated EGFP and the endogenous RIG-I locus. Finally, the effective use of antibiotic selection to enrich the successfully edited targeted population was demonstrated. CONCLUSIONS: The optimised lentiviral-mediated CRISPR method reported here increases possibilities for efficient genome editing in salmonid cells, in particular for future applications of genome-wide CRISPR screens for disease resistance.

Pleiotropic Impacts of Macrophage and Microglial Deficiency on Development in Rats with Targeted Mutation of the Csf1r Locus.

We have produced Csf1r-deficient rats by homologous recombination in embryonic stem cells. Consistent with the role of Csf1r in macrophage differentiation, there was a loss of peripheral blood monocytes, microglia in the brain, epidermal Langerhans cells, splenic marginal zone macrophages, bone-associated macrophages and osteoclasts, and peritoneal macrophages. Macrophages of splenic red pulp, liver, lung, and gut were less affected. The pleiotropic impacts of the loss of macrophages on development of multiple organ systems in rats were distinct from those reported in mice. Csf1r-/- rats survived well into adulthood with postnatal growth retardation, distinct skeletal and bone marrow abnormalities, infertility, and loss of visceral adipose tissue. Gene expression analysis in spleen revealed selective loss of transcripts associated with the marginal zone and, in brain regions, the loss of known and candidate novel microglia-associated transcripts. Despite the complete absence of microglia, there was little overt phenotype in brain, aside from reduced myelination and increased expression of dopamine receptor-associated transcripts in striatum. The results highlight the redundant and nonredundant functions of CSF1R signaling and of macrophages in development, organogenesis, and homeostasis.

Real-time video counselling for smoking cessation.

BACKGROUND: Real-time video communication software such as Skype and FaceTime transmits live video and audio over the Internet, allowing counsellors to provide support to help people quit smoking. There are more than four billion Internet users worldwide, and Internet users can download free video communication software, rendering a video counselling approach both feasible and scalable for helping people to quit smoking. OBJECTIVES: To assess the effectiveness of real-time video counselling delivered individually or to a group in increasing smoking cessation, quit attempts, intervention adherence, satisfaction and therapeutic alliance, and to provide an economic evaluation regarding real-time video counselling. SEARCH METHODS: We searched the Cochrane Tobacco Addiction Group Specialised Register, CENTRAL, MEDLINE, PubMed, PsycINFO and Embase to identify eligible studies on 13 August 2019. We searched the World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov to identify ongoing trials registered by 13 August 2019. We checked the reference lists of included articles and contacted smoking cessation researchers for any additional studies. SELECTION CRITERIA: We included randomised controlled trials (RCTs), randomised trials, cluster RCTs or cluster randomised trials of real-time video counselling for current tobacco smokers from any setting that measured smoking cessation at least six months following baseline. The real-time video counselling intervention could be compared with a no intervention control group or another smoking cessation intervention, or both. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data from included trials, assessed the risk of bias and rated the certainty of the evidence using the GRADE approach. We performed a random-effects meta-analysis for the primary outcome of smoking cessation, using the most stringent measure of smoking cessation measured at the longest follow-up. Analysis was based on the intention-to-treat principle. We considered participants with missing data at follow-up for the primary outcome of smoking cessation to be smokers. MAIN RESULTS: We included two randomised trials with 615 participants. Both studies delivered real-time video counselling for smoking cessation individually, compared with telephone counselling. We judged one study at unclear risk of bias and one study at high risk of bias. There was no statistically significant treatment effect for smoking cessation (using the strictest definition and longest follow-up) across the two included studies when real-time video counselling was compared to telephone counselling (risk ratio (RR) 2.15, 95% confidence interval (CI) 0.38 to 12.04; 2 studies, 608 participants; I2 = 66%). We judged the overall certainty of the evidence for smoking cessation as very low due to methodological limitations, imprecision in the effect estimate reflected by the wide 95% CIs and inconsistency of cessation rates. There were no significant differences between real-time video counselling and telephone counselling reported for number of quit attempts among people who continued to smoke (mean difference (MD) 0.50, 95% CI -0.60 to 1.60; 1 study, 499 participants), mean number of counselling sessions completed (MD -0.20, 95% CI -0.45 to 0.05; 1 study, 566 participants), completion of all sessions (RR 1.13, 95% CI 0.71 to 1.79; 1 study, 43 participants) or therapeutic alliance (MD 1.13, 95% CI -0.24 to 2.50; 1 study, 398 participants). Participants in the video counselling arm were more likely than their telephone counselling counterparts to recommend the programme to a friend or family member (RR 1.06, 95% CI 1.01 to 1.11; 1 study, 398 participants); however, there were no between-group differences on satisfaction score (MD 0.70, 95% CI -1.16 to 2.56; 1 study, 29 participants). AUTHORS' CONCLUSIONS: There is very little evidence about the effectiveness of real-time video counselling for smoking cessation. The existing research does not suggest a difference between video counselling and telephone counselling for assisting people to quit smoking. However, given the very low GRADE rating due to methodological limitations in the design, imprecision of the effect estimate and inconsistency of cessation rates, the smoking cessation results should be interpreted cautiously. High-quality randomised trials comparing real-time video counselling to telephone counselling are needed to increase the confidence of the effect estimate. Furthermore, there is currently no evidence comparing real-time video counselling to a control group. Such research is needed to determine whether video counselling increases smoking cessation.

A survey of the prevalence of modifiable health risk behaviours among carers of people with a mental illness.

BACKGROUND: Family carers provide significant support to people with a mental illness; yet may experience poor mental and physical health themselves. Among limited research addressing the physical health of carers, studies of carers of people with dementia and young people with psychosis suggest increased risk of chronic diseases in conjunction with higher levels of potentially modifiable lifestyle risk behaviours. This exploratory study, conducted with carers of people with various mental illnesses, aimed to determine: carer prevalence of health risk behaviours (inadequate fruit and vegetable consumption, inadequate physical activity, harmful alcohol consumption, and tobacco smoking); interest in changing 'at risk' behaviours; and potential associations of socio-demographic characteristics with risk status and interest in change. METHODS: A cross-sectional survey was conducted among family carers of people with a mental illness (N = 144) residing in New South Wales, Australia. Analyses explored risk behaviour prevalence and interest in change, and associations with socio-demographic variables. RESULTS: Inadequate fruit and vegetable consumption was most prevalent (74.8%), followed by engaging in inadequate amounts of physical activity (57.6%); harmful alcohol consumption (36.3%) and smoking (11.8%). The majority of carers were interested in improving 'at risk' behaviours (56.3-89.2%), with the exception of alcohol consumption (41.5%). Previously or never married participants were more likely to consume inadequate amounts of fruits and/or vegetables compared to those married or cohabiting (Odds Ratio [OR]: 4.1, 95% Confidence Interval [CI]: 1.3-12.9, p = .02). Carers in the workforce were more likely to be engaging in inadequate physical activity (OR: 2.6, 95% CI: 1.2-5.7, p = .02); and male participants were more likely to engage in harmful alcohol consumption (OR: 2.9, 95% CI: 1.1-7.9, p = .03). Working carers were approximately five times more likely to report interest in improving their alcohol consumption (OR: 5.1, 95% CI: 1.3-20.5, p = .02) compared to those not currently in the workforce. CONCLUSIONS: Results suggest high engagement in health risk behaviours among carers of people with a mental illness, particularly with regards to harmful alcohol consumption. Findings suggest a need to develop and implement chronic disease prevention strategies. Further research with larger representative samples is needed to confirm findings.

Strategies to improve the implementation of workplace-based policies or practices targeting tobacco, alcohol, diet, physical activity and obesity.

BACKGROUND: Given the substantial period of time adults spend in their workplaces each day, these provide an opportune setting for interventions addressing modifiable behavioural risk factors for chronic disease. Previous reviews of trials of workplace-based interventions suggest they can be effective in modifying a range of risk factors including diet, physical activity, obesity, risky alcohol use and tobacco use. However, such interventions are often poorly implemented in workplaces, limiting their impact on employee health. Identifying strategies that are effective in improving the implementation of workplace-based interventions has the potential to improve their effects on health outcomes. OBJECTIVES: To assess the effects of strategies for improving the implementation of workplace-based policies or practices targeting diet, physical activity, obesity, tobacco use and alcohol use.Secondary objectives were to assess the impact of such strategies on employee health behaviours, including dietary intake, physical activity, weight status, and alcohol and tobacco use; evaluate their cost-effectiveness; and identify any unintended adverse effects of implementation strategies on workplaces or workplace staff. SEARCH METHODS: We searched the following electronic databases on 31 August 2017: CENTRAL; MEDLINE; MEDLINE In Process; the Campbell Library; PsycINFO; Education Resource Information Center (ERIC); Cumulative Index to Nursing and Allied Health Literature (CINAHL); and Scopus. We also handsearched all publications between August 2012 and September 2017 in two speciality journals: Implementation Science and Journal of Translational Behavioral Medicine. We conducted searches up to September 2017 in Dissertations and Theses, the WHO International Clinical Trials Registry Platform, and the US National Institutes of Health Registry. We screened the reference lists of included trials and contacted authors to identify other potentially relevant trials. We also consulted experts in the field to identify other relevant research. SELECTION CRITERIA: Implementation strategies were defined as strategies specifically employed to improve the implementation of health interventions into routine practice within specific settings. We included any trial with a parallel control group (randomised or non-randomised) and conducted at any scale that compared strategies to support implementation of workplace policies or practices targeting diet, physical activity, obesity, risky alcohol use or tobacco use versus no intervention (i.e. wait-list, usual practice or minimal support control) or another implementation strategy. Implementation strategies could include those identified by the Effective Practice and Organisation of Care (EPOC) taxonomy such as quality improvement initiatives and education and training, as well as other strategies. Implementation interventions could target policies or practices directly instituted in the workplace environment, as well as workplace-instituted efforts encouraging the use of external health promotion services (e.g. gym membership subsidies). DATA COLLECTION AND ANALYSIS: Review authors working in pairs independently performed citation screening, data extraction and 'Risk of bias' assessment, resolving disagreements via consensus or a third reviewer. We narratively synthesised findings for all included trials by first describing trial characteristics, participants, interventions and outcomes. We then described the effect size of the outcome measure for policy or practice implementation. We performed meta-analysis of implementation outcomes for trials of comparable design and outcome. MAIN RESULTS: We included six trials, four of which took place in the USA. Four trials employed randomised controlled trial (RCT) designs. Trials were conducted in workplaces from the manufacturing, industrial and services-based sectors. The sample sizes of workplaces ranged from 12 to 114. Workplace policies and practices targeted included: healthy catering policies; point-of-purchase nutrition labelling; environmental supports for healthy eating and physical activity; tobacco control policies; weight management programmes; and adherence to guidelines for staff health promotion. All implementation interventions utilised multiple implementation strategies, the most common of which were educational meetings, tailored interventions and local consensus processes. Four trials compared an implementation strategy intervention with a no intervention control, one trial compared different implementation interventions, and one three-arm trial compared two implementation strategies with each other and a control. Four trials reported a single implementation outcome, whilst the other two reported multiple outcomes. Investigators assessed outcomes using surveys, audits and environmental observations. We judged most trials to be at high risk of performance and detection bias and at unclear risk of reporting and attrition bias.Of the five trials comparing implementation strategies with a no intervention control, pooled analysis was possible for three RCTs reporting continuous score-based measures of implementation outcomes. The meta-analysis found no difference in standardised effects (standardised mean difference (SMD) -0.01, 95% CI -0.32 to 0.30; 164 participants; 3 studies; low certainty evidence), suggesting no benefit of implementation support in improving policy or practice implementation, relative to control. Findings for other continuous or dichotomous implementation outcomes reported across these five trials were mixed. For the two non-randomised trials examining comparative effectiveness, both reported improvements in implementation, favouring the more intensive implementation group (very low certainty evidence). Three trials examined the impact of implementation strategies on employee health behaviours, reporting mixed effects for diet and weight status (very low certainty evidence) and no effect for physical activity (very low certainty evidence) or tobacco use (low certainty evidence). One trial reported an increase in absolute workplace costs for health promotion in the implementation group (low certainty evidence). None of the included trials assessed adverse consequences. Limitations of the review included the small number of trials identified and the lack of consistent terminology applied in the implementation science field, which may have resulted in us overlooking potentially relevant trials in the search. AUTHORS' CONCLUSIONS: Available evidence regarding the effectiveness of implementation strategies for improving implementation of health-promoting policies and practices in the workplace setting is sparse and inconsistent. Low certainty evidence suggests that such strategies may make little or no difference on measures of implementation fidelity or different employee health behaviour outcomes. It is also unclear if such strategies are cost-effective or have potential unintended adverse consequences. The limited number of trials identified suggests implementation research in the workplace setting is in its infancy, warranting further research to guide evidence translation in this setting.

Availability of food and beverage items on school canteen menus and association with items purchased by children of primary-school age.

OBJECTIVE: To (i) describe the proportion of foods and beverages available on school canteen menus classified as having high ('green'), moderate ('amber') or low ('red') nutritional value; (ii) describe the proportion of these items purchased by students; and (iii) examine the association between food and beverage availability on school canteen menus and food and beverage purchasing by students. DESIGN: A cross-sectional study was conducted as part of a larger randomised controlled trial (RCT). SETTING: A nested sample of fifty randomly selected government schools from the Hunter New England region of New South Wales, Australia, who had participated in an RCT of an intervention to improve the availability of healthy foods sold from school canteens, was approached to participate. SUBJECTS: School principals, canteen managers and students. RESULTS: The average proportion of green, amber and red items available on menus was 47·9, 47·4 and 4·7 %, respectively. The average proportion of green, amber and red items purchased by students was 30·1, 61·8 and 8·1 %, respectively. There was a significant positive relationship between the availability and purchasing of green (R 2=0·66), amber (R 2=0·57) and red menu items (R 2=0·61). In each case, a 1 % increase in the availability of items in these categories was associated with a 1·21, 1·35 and 1·67 % increase in purchasing of items of high, moderate and low nutritional value, respectively. CONCLUSIONS: The findings provide support for school-based policies to improve the relative availability of healthy foods for sale in these settings.

Association of emergency department albuterol dispensing with pediatric asthma revisits and readmissions.

INTRODUCTION: Although pediatric asthma continues to be a highly studied disease, data to suggest clear strategies to decrease asthma related revisits or readmissions is lacking. The purpose of our study was to assess the effect of emergency department (ED) direct dispensing of beta-agonist metered dose inhalers on pediatric asthma ED revisit and readmission rates. METHODS: We conducted a retrospective cohort study of pediatric patients discharged from the pediatric ED with a diagnosis of asthma. Our primary outcome measured the rate of asthma revisits to the ED or admissions to the hospital within 28 days. Logistic regression analysis was used to assess ED beta-agonist MDI dispensing and revisit and/or readmission as the outcome. RESULTS: A total of 853 patients met eligibility for inclusion in the study, with 657 enrolled in the Baseline group and 196 enrolled in the ED-MDI group. The Baseline group experienced a revisit and readmission rate of 7.0% (46/657) versus 2.6% (5/196) in the ED-MDI group, (p = 0.026). ED direct dispensing of MDIs was found to be independently associated with a decreased risk of revisit or readmission (odds ratio 0.37; 95% confidence interval 0.14-0.95). CONCLUSIONS: In our study, ED direct dispensing of beta-agonist MDIs resulted in a reduction in 28-day revisit and readmission to the hospital. Further studies should be performed to evaluate the economic impact of reducing these revisits and readmissions against the costs of maintaining a dispensing program. Our findings may support modification of asthma programs to include dispensing MDIs from the emergency department.

Intestinal expression of Fas and Fas ligand is upregulated by bacterial signaling through TLR4 and TLR5, with activation of Fas modulating intestinal TLR-mediated inflammation.

TLRs play an important role in mediating intestinal inflammation and homeostasis. Fas is best studied in terms of its function in apoptosis, but recent studies demonstrate that Fas signaling may mediate additional functions such as inflammation. The role of Fas, and the Fas ligand (FasL), in the intestine is poorly understood. The aim of this study was to evaluate potential cross-talk between TLRs and Fas/FasL system in intestinal epithelial cells (IECs). IECs were stimulated with TLR ligands, and expression of Fas and FasL was investigated. Treatment with TLR4 and TLR5 ligands, but not TLR2 and 9 ligands, increased expression of Fas and FasL in IECs in vitro. Consistent with this finding, expression of intestinal Fas and FasL was reduced in vivo in the epithelium of TLR4 knockout (KO), 5KO, and germ-free mice, but not in TLR2KO mice. Modulating Fas signaling using agonistic anti-Fas augmented TLR4- and TLR5-mediated TNF-α and IL-8 production by IECs. In addition, suppression of Fas in IECs reduced the ability of TLR4 and TLR5 ligands and the intestinal pathogens Salmonella typhimurium and Listeria monocytogenes to induce the expression of IL-8. In conclusion, this study demonstrates that extensive cross-talk in IECs occurs between the Fas and TLR signaling pathways, with the FasL/Fas system playing a role in TLR-mediated inflammatory responses in the intestine.

A pilot, multisite, randomized controlled trial of a self-directed coping skills training intervention for couples facing prostate cancer: accrual, retention, and data collection issues.

PURPOSE: To examine the acceptability of the methods used to evaluate Coping-Together, one of the first self-directed coping skill intervention for couples facing cancer, and to collect preliminary efficacy data. METHODS: Forty-two couples, randomized to a minimal ethical care (MEC) condition or to Coping-Together, completed a survey at baseline and 2 months after, a cost diary, and a process evaluation phone interview. RESULTS: One hundred seventy patients were referred to the study. However, 57 couples did not meet all eligibility criteria, and 51 refused study participation. On average, two to three couples were randomized per month, and on average it took 26 days to enrol a couple in the study. Two couples withdrew from MEC, none from Coping-Together. Only 44 % of the cost diaries were completed, and 55 % of patients and 60 % of partners found the surveys too long, and this despite the follow-up survey being five pages shorter than the baseline one. Trends in favor of Coping-Together were noted for both patients and their partners. CONCLUSIONS: This study identified the challenges of conducting dyadic research, and a number of suggestions were put forward for future studies, including to question whether distress screening was necessary and what kind of control group might be more appropriate in future studies.

Prevalence and correlates of current smoking among medical oncology outpatients.

BACKGROUND: Continued smoking following a cancer diagnosis has adverse impacts on cancer treatment and puts individuals at risk of secondary cancers. Data on the prevalence and correlates of smoking among cancer patients are critical for successfully targeting smoking cessation interventions. AIMS: To explore among a sample of medical oncology outpatients (a) the prevalence of self-reported current smoking and (b) the demographic and psychosocial factors associated with self-reported smoking. METHODS: A heterogeneous sample of cancer patients aged 18 years or over was recruited from 1 of 11 medical oncology treatment centres across Australia. Patients completed a survey assessing the following: smoking status; socio-demographic, disease and treatment characteristics; time since diagnosis; anxiety; and depression. Factors associated with self-reported smoking were examined using a univariate and multivariate mixed-effects logistic regression. RESULTS: A total of 1379 patients returned surveys and 1338 were included in the analysis. The prevalence of current smoking was 10.9% (n = 146). After adjusting for treatment centre, patients aged 65 years and older and those without health concession cards were significantly less likely to smoke. Patients diagnosed with lung cancer and those without private health insurance were more likely to smoke. DISCUSSION: A minority of cancer patients reported continued smoking at an average time of 13 months post-diagnosis. Patients, who are younger, have been diagnosed with lung cancer and have lower socioeconomic status are at-risk groups and represent important targets for smoking cessation advice and intervention. Copyright © 2015 John Wiley & Sons, Ltd.

Couples coping with cancer: exploration of theoretical frameworks from dyadic studies.

OBJECTIVE: A diagnosis of cancer and subsequent treatment are distressing not only for the person directly affected, but also for their intimate partner. The aim of this review is to (a) identify the main theoretical frameworks underpinning research addressing dyadic coping among couples affected by cancer, (b) summarise the evidence supporting the concepts described in these theoretical frameworks, and (c) examine the similarities and differences between these theoretical perspectives. METHODS: A literature search was undertaken to identify descriptive studies published between 1990 and 2013 (English and French) that examined the interdependence of patients' and partners' coping, and the impact of coping on psychosocial outcomes. Data were extracted using a standardised form and reviewed by three of the authors. RESULTS: Twenty-three peer-reviewed manuscripts were identified, from which seven theoretical perspectives were derived: Relationship-Focused Coping, Transactional Model of Stress and Coping, Systemic-Transactional Model (STM) of dyadic coping, Collaborative Coping, Relationship Intimacy model, Communication models, and Coping Congruence. Although these theoretical perspectives emphasised different aspects of coping, a number of conceptual commonalities were noted. CONCLUSION: This review identified key theoretical frameworks of dyadic coping used in cancer. Evidence indicates that responses within the couple that inhibit open communication between partner and patient are likely to have an adverse impact on psychosocial outcomes. Models that incorporate the interdependence of emotional responses and coping behaviours within couples have an emerging evidence base in psycho-oncology and may have greatest validity and clinical utility in this setting.

Identification of TLR10 as a key mediator of the inflammatory response to Listeria monocytogenes in intestinal epithelial cells and macrophages.

Listeria monocytogenes is a Gram-positive bacterium that can cause septicemia and meningitis. TLRs are central receptors of the innate immune system that drive inflammatory responses to invading microbes such as L. monocytogenes. Although intestinal epithelial cells (IECs) represent the initial point of entry used by L. monocytogenes for infection, the innate immune response to L. monocytogenes in these cells has been poorly characterized to date. The aim of this study was to determine which TLRs are involved in mediating the immune response to L. monocytogenes in IECs. We performed an RNA interference screen of TLRs 1-10 in the HT-29 IEC cell line and observed the most significant reduction in chemokine output following silencing of TLR10. This effect was also observed in the macrophage cell line THP-1. The chemokines CCL20, CCL1, and IL-8 were reduced following knockdown of TLR10. Silencing of TLR10 resulted in increased viability of L. monocytogenes in both HT-29 and THP-1 cells. TLR10 was found to be predominantly expressed intracellularly in epithelia, and activation required viable L. monocytogenes. NF-κB activation was seen to require TLR2 in addition to TLR10. Taken together, these data indicate novel roles for TLR10 in sensing pathogenic infection in both the epithelium and macrophages and have identified L. monocytogenes as a source of ligand for the orphan receptor TLR10.

The effects of an electronic order set on vancomycin dosing in the ED.

OBJECTIVE: The objective of the study was to assess the impact of a computer physician order entry (CPOE) electronic order set on appropriate vancomycin dosing in the emergency department (ED). METHODS: We conducted a retrospective study examining ED dosing of vancomycin before and after the implementation of an electronic weight-based vancomycin order set. Preimplementation and postimplementation patient records were analyzed between the dates of June 1st and August 31st 2010 for the pre-CPOE group and January 1st to March 31st 2013 for the post-CPOE group. STATISTICAL ANALYSIS: χ(2) analysis, Fisher exact test, and t tests were performed with a 2-sided P value <.05 denoting statistical significance, where appropriate. RESULTS: A total of 597 patients were included in the study, with 220 in the pre-CPOE group and 377 in the post-CPOE group. The use of the electronic order set resulted in a 21.9% increase (P < .05) in appropriate dosing with 67.4% (254/377) of post-CPOE vancomycin doses considered appropriate vs 45.5% (100/220) in the pre-CPOE group. In critically ill patients, there was a 16.3% increase in appropriate dosing with 44.7% (38/85) in the post-CPOE group compared with 28.4% (19/67) in the pre-CPOE group. CONCLUSION: The implementation of an electronic order set increased the percentage of ED patients receiving appropriate initial vancomycin doses. The impact of increasing compliance to vancomycin guidelines is in accordance with stewardship principles that promote optimization of antimicrobial dosing based on individual patient characteristics. More studies are needed to assess the relationship between appropriate vancomycin loading doses in the ED and therapeutic outcomes.

Missed opportunities: general practitioner identification of their patients' smoking status.

BACKGROUND: In order to provide smoking cessation support to their patients in line with clinical practice guidelines, general practitioners must first ascertain whether their patients' use tobacco. This study examined (i) the sensitivity, specificity, positive predictive value and negative predictive value of general practitioner detection of smoking, and (ii) the general practitioner and patient characteristics associated with detection of tobacco use. METHODS: Eligible patients completed a touchscreen computer survey while waiting for an appointment with their general practitioner. Patients self-reported demographic characteristics, medical history, and current smoking status. Following the patient's consultation, their general practitioner was asked to indicate whether the patient was a current smoker (yes/no/unsure/not applicable). Smoking prevalence, sensitivity, specificity, positive predictive value and negative predictive values (with 95% confidence intervals) were calculated using patient self-report of smoking status as the gold standard. Generalised estimating equations were used to examine the general practitioner and patient characteristics associated with detection of tobacco use. RESULTS: Fifty-one general practitioners and 1,573 patients in twelve general practices participated. Patient self-report of smoking was 11.3% compared to general practitioner estimated prevalence of 9.5%. Sensitivity of general practitioner assessment was 66% [95% CI 59-73] while specificity was 98% [95% CI 97-98]. Positive predictive value was 78% [95% CI 71-85] and negative predictive value was 96% [95% CI 95-97]. No general practitioner factors were associated with detection of smoking. Patients with a higher level of education or who responded 'Other' were less likely to be detected as smokers than patients who had completed a high school or below level of education. CONCLUSION: Despite the important role general practitioners play in providing smoking cessation advice and support, a substantial proportion of general practitioners do not know their patient's smoking status. This represents a significant missed opportunity in the provision of preventive healthcare. Electronic waiting room assessments may assist general practitioners in improving the identification of smokers.

Tracing innate immune defences along the path of Listeria monocytogenes infection.

The pathogenic gram-positive bacteria, Listeria monocytogenes is a facultative infectious intracellular pathogen that causes listeriosis. Effective elimination of infection is dependent upon a functioning innate immune system and activation of inflammatory responses by pathogen recognition receptors (PRRs). In this review, we trace the route of L. monocytogenes invasion as it disseminates from the intestinal epithelium, through the bloodstream of the host, to the liver and spleen. Along this route, we highlight the diverse, region specific, innate defences in place throughout the course of infection. We provide an overview of recent advances in our knowledge of key innate immune defences against L. monocytogenes, focusing on the PRRs in various cell types known to be critical in the detection of this pathogen.

A chromosome-scale Mytilus edulis genome assembly for aquaculture, marine ecology, and evolution.

The smooth-shelled blue mussel, Mytilus edulis is part of the Mytilus species complex, encompassing at least three putative species: M. edulis, Mytilus galloprovincialis, and Mytilus trossulus. These three species occur on both sides of the Atlantic and hybridize in nature, and both M. edulis and M. galloprovincialis are important aquaculture species. They are also invasive species in many parts of the world. Here, we present a chromosome-level assembly of M. edulis. We used a combination of PacBio sequencing and Dovetail's Omni-C technology to generate an assembly with 14 long scaffolds containing 94% of the predicted length of the M. edulis genome (1.6 out of 1.7 Gb). Assembly statistics were as follows: total length = 1.65 Gb, N50 = 116 Mb, L50 = 7, and L90 = 13. BUSCO analysis showed 92.55% eukaryote BUSCOs identified. AB-Initio annotation using RNA-seq from mantle, gills, muscle, and foot predicted 47,128 genes. These gene models were combined with IsoSeq validation resulting in 45,379 full CDS protein sequences and 129,708 isoforms. Using GBS and shotgun sequencing, we also sequenced several eastern Canadian populations of Mytilus to characterize single-nucleotide as well as structural variance. This high-quality genome for M. edulis provides a platform to develop tools that can be used in breeding, molecular ecology and evolution to address questions of both commercial and environmental perspectives.