Neuroactive steroids in depression and anxiety disorders: Clinical studies

Certain neuroactive steroids modulate ligand-gated ion channels via non-genomic mechanisms. Especially 3 alpha-reduced pregnane steroids are potent positive allosteric modulators of the gamma-aminobutyric acid type A (GABA(A)) receptor. During major depression, there is a disequilibrium of 3 alpha-reduced neuroactive steroids, which is corrected by clinically effective pharmacological treatment. To investigate whether these alterations are a general principle of successful antidepressant treatment, we studied the impact of nonpharmacological treatment options on neuroactive steroid concentrations during major depression. Neither partial sleep deprivation, transcranial magnetic stimulation, nor electroconvulsive therapy affected neuroactive steroid levels irrespectively of the response to these treatments. These studies suggest that the changes in neuroactive steroid concentrations observed after antidepressant pharmacotherapy more likely reflect distinct pharmacological properties of antidepressants rather than the clinical response. In patients with panic disorder, changes in neuroactive steroid composition have been observed opposite to those seen in depression. However, during experimentally induced panic induction either with cholecystokinine-tetrapeptide or sodium lactate, there was a pronounced decline in the concentrations of 3 alpha-reduced neuroactive steroids in patients with panic disorder, which might result in a decreased GABAergic tone. In contrast, no changes in neuroactive steroid concentrations could be observed in healthy controls with the exception of 3 alpha,5 alpha-tetrahydrodeoxycorticosterone. The modulation of GABA(A) receptors by neuroactive steroids might contribute to the pathophysiology of depression and anxiety disorders and might offer new targets for the development of novel anxiolytic compounds. Copyright (c) 2006 S. Karger AG, Basel

Integration of decision support systems to improve decision support performance

Decision support system (DSS) is a well-established research and development area. Traditional isolated, stand-alone DSS has been recently facing new challenges. In order to improve the performance of DSS to meet the challenges, research has been actively carried out to develop integrated decision support systems (IDSS). This paper reviews the current research efforts with regard to the development of IDSS. The focus of the paper is on the integration aspect for IDSS through multiple perspectives, and the technologies that support this integration. More than 100 papers and software systems are discussed. Current research efforts and the development status of IDSS are explained, compared and classified. In addition, future trends and challenges in integration are outlined. The paper concludes that by addressing integration, better support will be provided to decision makers, with the expectation of both better decisions and improved decision making processes

Sex-specific relevance of diabetes to occlusive vascular and other mortality : a collaborative meta-analysis of individual data from 980 793 adults from 68 prospective studies

Background: Several studies have shown that diabetes confers a higher relative risk of vascular mortality among women than among men, but whether this increased relative risk in women exists across age groups and within defined levels of other risk factors is uncertain. We aimed to determine whether differences in established risk factors, such as blood pressure, BMI, smoking, and cholesterol, explain the higher relative risks of vascular mortality among women than among men. Methods: In our meta-analysis, we obtained individual participant-level data from studies included in the Prospective Studies Collaboration and the Asia Pacific Cohort Studies Collaboration that had obtained baseline information on age, sex, diabetes, total cholesterol, blood pressure, tobacco use, height, and weight. Data on causes of death were obtained from medical death certificates. We used Cox regression models to assess the relevance of diabetes (any type) to occlusive vascular mortality (ischaemic heart disease, ischaemic stroke, or other atherosclerotic deaths) by age, sex, and other major vascular risk factors, and to assess whether the associations of blood pressure, total cholesterol, and body-mass index (BMI) to occlusive vascular mortality are modified by diabetes. Findings: Individual participant-level data were analysed from 980793 adults. During 9 center dot 8 million person-years of follow-up, among participants aged between 35 and 89 years, 19686 (25 center dot 6%) of 76965 deaths were attributed to occlusive vascular disease. After controlling for major vascular risk factors, diabetes roughly doubled occlusive vascular mortality risk among men (death rate ratio [RR] 2 center dot 10, 95% CI 1 center dot 97-2 center dot 24) and tripled risk among women (3 center dot 00, 2 center dot 71-3 center dot 33; x(2) test for heterogeneity p<0 center dot 0001). For both sexes combined, the occlusive vascular death RRs were higher in younger individuals (aged 35-59 years: 2 center dot 60, 2 center dot 30-2 center dot 94) than in older individuals (aged 70-89 years: 2 center dot 01, 1 center dot 85-2 center dot 19; p=0 center dot 0001 for trend across age groups), and, across age groups, the death RRs were higher among women than among men. Therefore, women aged 35-59 years had the highest death RR across all age and sex groups (5 center dot 55, 4 center dot 15-7 center dot 44). However, since underlying confounder-adjusted occlusive vascular mortality rates at any age were higher in men than in women, the adjusted absolute excess occlusive vascular mortality associated with diabetes was similar for men and women. At ages 35-59 years, the excess absolute risk was 0 center dot 05% (95% CI 0 center dot 03-0 center dot 07) per year in women compared with 0 center dot 08% (0 center dot 05-0 center dot 10) per year in men; the corresponding excess at ages 70-89 years was 1 center dot 08% (0 center dot 84-1 center dot 3 2) per year in women and 0 center dot 91% (0 center dot 77-1 center dot 05) per year in men. Total cholesterol, blood pressure, and BMI each showed continuous log-linear associations with occlusive vascular mortality that were similar among individuals with and without diabetes across both sexes. Interpretation: Independent of other major vascular risk factors, diabetes substantially increased vascular risk in both men and women. Lifestyle changes to reduce smoking and obesity and use of cost-effective drugs that target major vascular risks (eg, statins and antihypertensive drugs) are important in both men and women with diabetes, but might not reduce the relative excess risk of occlusive vascular disease in women with diabetes, which remains unexplained

Towards accurate and precise T1 and extracellular volume mapping in the myocardium: a guide to current pitfalls and their solutions

Mapping of the longitudinal relaxation time (T1) and extracellular volume (ECV) offers a means of identifying pathological changes in myocardial tissue, including diffuse changes that may be invisible to existing T1-weighted methods. This technique has recently shown strong clinical utility for pathologies such as Anderson- Fabry disease and amyloidosis and has generated clinical interest as a possible means of detecting small changes in diffuse fibrosis; however, scatter in T1 and ECV estimates offers challenges for detecting these changes, and bias limits comparisons between sites and vendors. There are several technical and physiological pitfalls that influence the accuracy (bias) and precision (repeatability) of T1 and ECV mapping methods. The goal of this review is to describe the most significant of these, and detail current solutions, in order to aid scientists and clinicians to maximise the utility of T1 mapping in their clinical or research setting. A detailed summary of technical and physiological factors, issues relating to contrast agents, and specific disease-related issues is provided, along with some considerations on the future directions of the field. Towards accurate and precise T1 and extracellular volume mapping in the myocardium: a guide to current pitfalls and their solutions. Available from: https://www.researchgate.net/publication/317548806_Towards_accurate_and_precise_T1_and_extracellular_volume_mapping_in_the_myocardium_a_guide_to_current_pitfalls_and_their_solutions [accessed Jun 13, 2017]

Rotating biological contactors : a review on main factors affecting performance

Rotating biological contactors (RBCs) constitute a very unique and superior alternative for biodegradable matter and nitrogen removal on account of their feasibility, simplicity of design and operation, short start-up, low land area requirement, low energy consumption, low operating and maintenance cost and treatment efficiency. The present review of RBCs focus on parameters that affect performance like rotational speed, organic and hydraulic loading rates, retention time, biofilm support media, staging, temperature, influent wastewater characteristics, biofilm characteristics, dissolved oxygen levels, effluent and solids recirculation, stepfeeding and medium submergence. Some RBCs scale-up and design considerations, operational problems and comparison with other wastewater treatment systems are also reported.Fundação para a Ciência e a Tecnologia (FCT

A new scheme to calculate isotope effects

We present a new scheme to calculate isotope effects. Only selected frequencies at the target level of theory are calculated. The frequencies are selected by an analysis of the Hessian from a lower level of theory. We obtain accurate isotope effects without calculating the full Hessian at the target level of theory. The calculated frequencies are very accurate. The scheme converges to the correct isotope effect

Exploring the role of organizational policies and procedures in promoting research utilization in registered nurses

<p>Abstract</p> <p>Background</p> <p>Policies and procedures (P&Ps) have been suggested as one possible strategy for moving research evidence into practice among nursing staff in hospitals. Research in the area of P&Ps is limited, however. This paper explores: 1) nurses' use of eight specific research-based practices (RBPs) and RBP overall, 2) nurses' use and understanding of P&Ps, and 3) the role of P&Ps in promoting research utilization.</p> <p>Methods</p> <p>Staff nurses from the eight health regions governing acute care services across the Canadian province of Newfoundland and Labrador completed an anonymous questionnaire regarding their use of eight RBPs and associated P&Ps. Data were also obtained from authorities in six of the eight regions about existing relevant P&Ps. We used descriptive statistics and multivariate regression analysis to assess the relationship between key independent variables and self-reported use of RBP.</p> <p>Results</p> <p>Use of the eight RBPs ranged from 7.8% to 88.6%, depending on the practice. Nurses ranked P&P manuals as their number one source of practice knowledge. Most respondents (84.8%) reported that the main reason they consult the P&P manual is to confirm they are practicing according to agency rules. Multivariate regression analysis identified three significant predictors of being a user versus non-user of RBP overall: awareness, awareness by regular use, and persuasion. Six significant predictors of being a consistent versus less consistent user of RBP overall were also identified: perception of P&P existence, unit, nursing experience, personal experience as a source of practice knowledge, number of existing research-based P&Ps, and lack of time as a barrier to consulting P&P manuals.</p> <p>Conclusion</p> <p>Findings suggest that nurses use P&Ps to guide their practice. However, the mere existence of P&Ps is not sufficient to translate research into nursing practice. Individual and organizational factors related to nurses' understanding and use of P&Ps also play key roles. Thus, moving research evidence into practice will require careful interplay between the organization and the individual. P&Ps may be the interface through which this occurs.</p

A 10 year case study on the changing determinants of University student satisfaction in the UK

Higher Education (HE), once the prerogative of a tiny elite, is now accessible to larger numbers of people around the world than ever before yet despite the fact that an understanding of student satisfaction has never been more important for today’s universities, the concept remains poorly understood. Here we use published data from the UK’s National Student Survey (NSS), representing data from 2.3 million full-time students collected from 2007 to 2016, as a case study of the benefits and limitations of measuring student satisfaction that might have applicability for other countries, particularly those that, like the UK, have experienced significant growth in student numbers. The analyses showed that the factor structure of the NSS remained generally stable and that the ability of the NSS to discriminate between different subjects at different universities actually improved over the ten-year sample period. The best predictors of overall satisfaction were 'Teaching Quality' and 'Organisation & Management', with 'Assessment & Feedback' having relatively weak predictive ability, despite the sector's tangible efforts to improve on this metric. The tripling of student fees in 2012 for English students (but not the rest of the UK) was used as a ‘natural experiment’ to investigate the sensitivity of student satisfaction ratings to the real economic costs of HE. The tuition fee increase had no identifiable negative effect, with student satisfaction steadily improving throughout the decade. Although the NSS was never designed to measure perceived value-for money, its insensitivity to major changes in the economic costs of HE to the individual suggest that the conventional concept of student satisfaction is incomplete. As such we propose that the concept of student satisfaction: (i) needs to be widened to take into account the broader economic benefits to the individual student by including measures of perceived value-for-money and (ii) should measure students’ level of satisfaction in the years post-graduation, by which time they may have a greater appreciation of the value of their degree in the workplace

Gender, Obesity and Repeated Elevation of C-Reactive Protein: Data from the CARDIA Cohort

C-reactive Protein (CRP) measurements above 10 mg/L have been conventionally treated as acute inflammation and excluded from epidemiologic studies of chronic inflammation. However, recent evidence suggest that such CRP elevations can be seen even with chronic inflammation. The authors assessed 3,300 participants in The Coronary Artery Risk Development in Young Adults study, who had two or more CRP measurements between 1992/3 and 2005/6 to a) investigate characteristics associated with repeated CRP elevation above 10 mg/L; b) identify subgroups at high risk of repeated elevation; and c) investigate the effect of different CRP thresholds on the probability of an elevation being one-time rather than repeated. 225 participants (6.8%) had one-time and 103 (3.1%) had repeated CRP elevation above 10 mg/L. Repeated elevation was associated with obesity, female gender, low income, and sex hormone use. The probability of an elevation above 10 mg/L being one-time rather than repeated was lowest (51%) in women with body mass index above 31 kg/m2, compared to 82% in others. These findings suggest that CRP elevations above 10 mg/L in obese women are likely to be from chronic rather than acute inflammation, and that CRP thresholds above 10 mg/L may be warranted to distinguish acute from chronic inflammation in obese women