Coupling models of cattle and farms with models of badgers for predicting the dynamics of bovine tuberculosis (TB)

Bovine TB is a major problem for the agricultural industry in several countries. TB can be contracted and spread by species other than cattle and this can cause a problem for disease control. In the UK and Ireland, badgers are a recognised reservoir of infection and there has been substantial discussion about potential control strategies. We present a coupling of individual based models of bovine TB in badgers and cattle, which aims to capture the key details of the natural history of the disease and of both species at approximately county scale. The model is spatially explicit it follows a very large number of cattle and badgers on a different grid size for each species and includes also winter housing. We show that the model can replicate the reported dynamics of both cattle and badger populations as well as the increasing prevalence of the disease in cattle. Parameter space used as input in simulations was swept out using Latin hypercube sampling and sensitivity analysis to model outputs was conducted using mixed effect models. By exploring a large and computationally intensive parameter space we show that of the available control strategies it is the frequency of TB testing and whether or not winter housing is practised that have the most significant effects on the number of infected cattle, with the effect of winter housing becoming stronger as farm size increases. Whether badgers were culled or not explained about 5%, while the accuracy of the test employed to detect infected cattle explained less than 3% of the variance in the number of infected cattle

Resection of thoracic malignancies infiltrating cardiac structures with use of cardiopulmonary bypass

Background: Only few reports exist on malignant thoracic neoplasms that require cardiopulmonary bypass during resection. We aimed to investigate the early and late clinical outcome of these patients. Methods: Patients with thoracic malignancies that underwent surgery between 2002 and 2014 were analyzed. All patients had cardiopulomonary bypass support during resection. Clinical and perioperative data was retrospectively reviewed for outcome and overall survival. Results: Fifteen patients (12 female, mean age of 55 ± 15 years, range 24 to 80 years) were identified. Eleven (8 female) were diagnosed with primary thoracic malignomas and four with metastases. Three patients died early postoperatively. Patients diagnosed with sarcoma had a significantly worse outcome than non-sarcoma patients (83.3 ± 15.2 % after 1 year, 31.3 ± 24.5 % after 5 years vs. 83.3 ± 15.2 % after 1 year, 0 ± 0 % after 5 years, p = 0.005). Conclusions: Malignancies with extension into cardiac structures or infiltration of great vessels can be resected with cardiopulmonary bypass support and tolerable risk. Carefully selected patients can undergo advanced operative procedures with an acceptable 1-year-survival, but only few patients achieved good long-term outcome

Editorial Peer Reviewers' Recommendations at a General Medical Journal: Are They Reliable and Do Editors Care?

BACKGROUND: Editorial peer review is universally used but little studied. We examined the relationship between external reviewers' recommendations and the editorial outcome of manuscripts undergoing external peer-review at the Journal of General Internal Medicine (JGIM). METHODOLOGY/PRINCIPAL FINDINGS: We examined reviewer recommendations and editors' decisions at JGIM between 2004 and 2008. For manuscripts undergoing peer review, we calculated chance-corrected agreement among reviewers on recommendations to reject versus accept or revise. Using mixed effects logistic regression models, we estimated intra-class correlation coefficients (ICC) at the reviewer and manuscript level. Finally, we examined the probability of rejection in relation to reviewer agreement and disagreement. The 2264 manuscripts sent for external review during the study period received 5881 reviews provided by 2916 reviewers; 28% of reviews recommended rejection. Chance corrected agreement (kappa statistic) on rejection among reviewers was 0.11 (p<.01). In mixed effects models adjusting for study year and manuscript type, the reviewer-level ICC was 0.23 (95% confidence interval [CI], 0.19-0.29) and the manuscript-level ICC was 0.17 (95% CI, 0.12-0.22). The editors' overall rejection rate was 48%: 88% when all reviewers for a manuscript agreed on rejection (7% of manuscripts) and 20% when all reviewers agreed that the manuscript should not be rejected (48% of manuscripts) (p<0.01). CONCLUSIONS/SIGNIFICANCE: Reviewers at JGIM agreed on recommendations to reject vs. accept/revise at levels barely beyond chance, yet editors placed considerable weight on reviewers' recommendations. Efforts are needed to improve the reliability of the peer-review process while helping editors understand the limitations of reviewers' recommendations

Measuring the positive psychological well-being of people with rheumatoid arthritis: a cross-sectional validation of the subjective vitality scale

Introduction: People with rheumatoid arthritis (RA) frequently suffer from compromised physical and psychological health, however, little is known about positive indicators of health, due to a lack of validated outcome measures. This study aims to validate a clinically relevant outcome measure of positive psychological well-being for people with RA. The first study examined the reliability and factorial validity of the Subjective Vitality Scale (SVS), whilst study 2 tested the instruments convergent validity. Methods: In study 1, National Rheumatoid Arthritis Society members (N = 333; M age = 59.82 years SD = 11.00) completed a postal questionnaire. For study 2, participants (N = 106; M age = 56 years, SD = 12 years) were those recruited to a randomized control trial comparing two physical activity interventions who completed a range of health-related questionnaires. Results: The SVS had a high level of internal consistency (α = .93, Rho = .92). Confirmatory factor analysis supported the uni-dimensional factor structure of the questionnaire among RA patients [χ = 1327 (10), CFI = 1.0, SRMSR = .01 and RMSEA = .00 (.00 - .08)]. Support for the scales convergent validity was revealed by significant (p < .05) relationships, in expected directions, with health related quality of life (r = .59), physical function (r = .58), feelings of fatigue (r = −.70), anxiety (r = −.57) and depression (r = −.73). Conclusions: Results from two studies have provided support for the internal consistency, factorial structure and convergent validity of the Subjective Vitality Scale. Researchers and healthcare providers may employ this clinically relevant, freely available and brief assessment with the confidence that it is a valid and reliable measure of positive psychological well-being for RA patients

Utilisation of an operative difficulty grading scale for laparoscopic cholecystectomy

Background A reliable system for grading operative difficulty of laparoscopic cholecystectomy would standardise description of findings and reporting of outcomes. The aim of this study was to validate a difficulty grading system (Nassar scale), testing its applicability and consistency in two large prospective datasets. Methods Patient and disease-related variables and 30-day outcomes were identified in two prospective cholecystectomy databases: the multi-centre prospective cohort of 8820 patients from the recent CholeS Study and the single-surgeon series containing 4089 patients. Operative data and patient outcomes were correlated with Nassar operative difficultly scale, using Kendall’s tau for dichotomous variables, or Jonckheere–Terpstra tests for continuous variables. A ROC curve analysis was performed, to quantify the predictive accuracy of the scale for each outcome, with continuous outcomes dichotomised, prior to analysis. Results A higher operative difficulty grade was consistently associated with worse outcomes for the patients in both the reference and CholeS cohorts. The median length of stay increased from 0 to 4 days, and the 30-day complication rate from 7.6 to 24.4% as the difficulty grade increased from 1 to 4/5 (both p < 0.001). In the CholeS cohort, a higher difficulty grade was found to be most strongly associated with conversion to open and 30-day mortality (AUROC = 0.903, 0.822, respectively). On multivariable analysis, the Nassar operative difficultly scale was found to be a significant independent predictor of operative duration, conversion to open surgery, 30-day complications and 30-day reintervention (all p < 0.001). Conclusion We have shown that an operative difficulty scale can standardise the description of operative findings by multiple grades of surgeons to facilitate audit, training assessment and research. It provides a tool for reporting operative findings, disease severity and technical difficulty and can be utilised in future research to reliably compare outcomes according to case mix and intra-operative difficulty

Ubiquitous molecular substrates for associative learning and activity-dependent neuronal facilitation.

Recent evidence suggests that many of the molecular cascades and substrates that contribute to learning-related forms of neuronal plasticity may be conserved across ostensibly disparate model systems. Notably, the facilitation of neuronal excitability and synaptic transmission that contribute to associative learning in Aplysia and Hermissenda, as well as associative LTP in hippocampal CA1 cells, all require (or are enhanced by) the convergence of a transient elevation in intracellular Ca2+ with transmitter binding to metabotropic cell-surface receptors. This temporal convergence of Ca2+ and G-protein-stimulated second-messenger cascades synergistically stimulates several classes of serine/threonine protein kinases, which in turn modulate receptor function or cell excitability through the phosphorylation of ion channels. We present a summary of the biophysical and molecular constituents of neuronal and synaptic facilitation in each of these three model systems. Although specific components of the underlying molecular cascades differ across these three systems, fundamental aspects of these cascades are widely conserved, leading to the conclusion that the conceptual semblance of these superficially disparate systems is far greater than is generally acknowledged. We suggest that the elucidation of mechanistic similarities between different systems will ultimately fulfill the goal of the model systems approach, that is, the description of critical and ubiquitous features of neuronal and synaptic events that contribute to memory induction

Common marmoset (Callithrix jacchus) personality, subjective well-being, hair cortisol level and AVPR1a, OPRM1, and DAT genotypes

We studied personality, subjective well-being, and hair cortisol level, in common marmosets Callithrix jacchus, a small, cooperatively breeding New World monkey, by examining their associations with one another and genotypes. Subjects were 68 males and 9 females that lived in the RIKEN Center for Life Science Technologies. Personality and subjective well-being were assessed by keeper ratings on two questionnaires, hair samples were obtained to assay cortisol level and buccal swabs were used to assess AVPR1a, OPRM1 and DAT genotypes. Three personality domains—Dominance, Sociability, and Neuroticism—were identified. Consistent with findings in other species, Sociability and Neuroticism were related to higher and lower subjective well-being, respectively. Sociability was also associated with higher hair cortisol levels. The personality domains and hair cortisol levels were heritable and associated with genotypes: the short form of AVPR1a was associated with lower Neuroticism and the AA genotype of the A111T SNP of OPRM1 was related to lower Dominance, lower Neuroticism, and higher hair cortisol level. Some genetic associations were not in directions that one would expect given findings in other species. These findings provide insights into the proximate and ultimate bases of personality in common marmosets, other primates and humans

NADPH oxidases in cardiovascular disease: insights from in vivo models and clinical studies

NADPH oxidase family enzymes (or NOXs) are the major sources of reactive oxygen species (ROS) that are implicated in the pathophysiology of many cardiovascular diseases. These enzymes appear to be especially important in the modulation of redox-sensitive signalling pathways that underlie key cellular functions such as growth, differentiation, migration and proliferation. Seven distinct members of the family have been identified of which four (namely NOX1, 2, 4 and 5) may have cardiovascular functions. In this article, we review our current understanding of the roles of NOX enzymes in several common cardiovascular disease states, with a focus on data from genetic studies and clinical data where available