The self-reported Montgomery-Åsberg depression rating scale is a useful evaluative tool in major depressive disorder

Abstract Background The use of Patient-reported Outcomes (PROs) as secondary endpoints in the development of new antidepressants has grown in recent years. The objective of this study was to assess the psychometric properties of the 9-item, patient-administered version of the Montgomery-Åsberg Depression Rating Scale (MADRS-S). Methods Data from a multicentre, double-blind, 8-week, randomised controlled trial of 278 outpatients diagnosed with Major Depressive Disorder were used to evaluate the validity, reliability and sensitivity to change of the MADRS-S using psychometric methods. A Receiver Operating Characteristic (ROC) curve was plotted to identify the most appropriate threshold to define perceived remission. Results No missing values were found at the item level, indicating good acceptability of the scale. The construct validity was satisfactory: all items contributed to a common underlying concept, as expected. The correlation between MADRS-S and physicians' MADRS was moderate (r = 0.54, p Conclusion Taking account of patient's perceptions of the severity of their own symptoms along with the psychometric properties of the MADRS-S enable its use for evaluative purposes in the development of new antidepressant drugs.</p

NHS health checks: a cross- sectional observational study on equity of uptake and outcomes

Background The National Health Checks programme aims to reduce the incidence of cardiovascular diseases and health inequalities in England. We assessed equity of uptake and outcomes from NHS Health Checks in general practices in Bristol, UK. Methods A cross-sectional study using patient-level data, from 38 general practices. We descriptively analysed the socioeconomic status (SES) of patients invited and the SES and ethnicity of those attending. Logistic regression was used to test associations between invitation and attendance, with population characteristics. Results Between June 2010 to October 2014, 31,881 patients were invited, and 13,733 NHS Health Checks completed. 47% of patients invited from the three least and 39% from the two most-deprived index of multiple deprivation quintiles, completed a Check. Proportions of invited patients, by ethnicity were 64% non-black and Asian and 31% black and Asian. Men were less likely to attend than women (OR 0.73, 95% confidence interval 0.67 to 0.80), as were patients ≤ 49 compared to ≥ 70 years (OR 0.40, 95% confidence interval 0.65 to 0.83). After controlling for SES and population characteristics, compared to patients with low CVD risk, high risk patients were more likely to be prescribed cardiovascular drugs (OR 6.2, 95% confidence interval 4.51 to 8.40). Compared to men, women (OR 01.18, 95% confidence interval 1.03 to 1.35) were more likely to be prescribed cardiovascular drugs, as were those ≤ 49 years (50–59 years, OR 1.42, 95% confidence intervals 1.13–1.79, 60–69 years, OR 1.60, 95% confidence intervals, 1.22–2.10, ≥ 70 years, OR 1.64, 95% confidence intervals, 1.14 to 2.35). Controlling for population characteristics, the following groups were most likely to be referred to lifestyle services: younger women (OR 2.22, 95% CI 1.69 to 2.94), those in the most deprived IMD quintile (OR 3.22, 95% CI 1.63 to 6.36) and those at highest risk of CVD (OR, 2.77, 95% CI 1.91 to 4.02). Conclusions We found no statistically significant evidence of inequity in attendance for an NHS Health Check by SES. Being older or a woman were associated with better attendance. Targeting men, younger patients and ethnic minority groups may improve equity in uptake for NHS Health Checks

Genome wide analysis of gene expression changes in skin from patients with type 2 diabetes

Non-healing chronic ulcers are a serious complication of diabetes and are a major healthcare problem. While a host of treatments have been explored to heal or prevent these ulcers from forming, these treatments have not been found to be consistently effective in clinical trials. An understanding of the changes in gene expression in the skin of diabetic patients may provide insight into the processes and mechanisms that precede the formation of non-healing ulcers. In this study, we investigated genome wide changes in gene expression in skin between patients with type 2 diabetes and non-diabetic patients using next generation sequencing. We compared the gene expression in skin samples taken from 27 patients (13 with type 2 diabetes and 14 non-diabetic). This information may be useful in identifying the causal factors and potential therapeutic targets for the prevention and treatment of diabetic related diseases

Raman spectroscopy: elucidation of biochemical changes in carcinogenesis of oesophagus

Several techniques are under development to diagnose oesophageal adenocarcinoma at an earlier stage. We have demonstrated the potential of Raman spectroscopy, an optical diagnostic technique, for the identification and classification of malignant changes. However, there is no clear recognition of the biochemical changes that distinguish between the different stages of disease. Our aim is to understand these changes through Raman mapping studies. Raman spectral mapping was used to analyse 20-μm sections of tissue from 29 snap-frozen oesophageal biopsies. Contiguous haematoxylin and eosin sections were reviewed by a consultant pathologist. Principal component analysis was used to identify the major differences between the spectra across each map. Pseudocolour score maps were generated and the peaks of corresponding loads identified enabling visualisation of the biochemical changes associated with malignancy. Changes were noted in the distribution of DNA, glycogen, lipids and proteins. The mean spectra obtained from selected regions demonstrate increased levels of glycogen in the squamous area compared with increased DNA levels in the abnormal region. Raman spectroscopy is a highly sensitive and specific technique for demonstration of biochemical changes in the carcinogenesis of Barrett's oesophagus. There is potential for in vivo application for real-time endoscopic optical diagnosis

Changing pattern in the basal ganglia: motor switching under reduced dopaminergic drive

Action selection in the basal ganglia is often described within the framework of a standard model, associating low dopaminergic drive with motor suppression. Whilst powerful, this model does not explain several clinical and experimental data, including varying therapeutic efficacy across movement disorders. We tested the predictions of this model in patients with Parkinson’s disease, on and off subthalamic deep brain stimulation (DBS), focussing on adaptive sensory-motor responses to a changing environment and maintenance of an action until it is no longer suitable. Surprisingly, we observed prolonged perseverance under on-stimulation, and high inter-individual variability in terms of the motor selections performed when comparing the two conditions. To account for these data, we revised the standard model exploring its space of parameters and associated motor functions and found that, depending on effective connectivity between external and internal parts of the globus pallidus and saliency of the sensory input, a low dopaminergic drive can result in increased, dysfunctional, motor switching, besides motor suppression. This new framework provides insight into the biophysical mechanisms underlying DBS, allowing a description in terms of alteration of the signal-to-baseline ratio in the indirect pathway, which better account of known electrophysiological data in comparison with the standard model

Description and validation of a Markov model of survival for individuals free of cardiovascular disease that uses Framingham risk factors

BACKGROUND: Estimation of cardiovascular disease risk is increasingly used to inform decisions on interventions, such as the use of antihypertensives and statins, or to communicate the risks of smoking. Crude 10-year cardiovascular disease risk risks may not give a realistic view of the likely impact of an intervention over a lifetime and will underestimate of the risks of smoking. A validated model of survival to act as a decision aid in the consultation may help to address these problems. This study aims to describe the development of such a model for use with people free of cardiovascular disease and evaluates its accuracy against data from a United Kingdom cohort. METHODS: A Markov cycle tree evaluated using cohort simulation was developed utilizing Framingham estimates of cardiovascular risk, 1998 United Kingdom mortality data, the relative risk for smoking related non-cardiovascular disease risk and changes in systolic blood pressure and serum total cholesterol total cholesterol with age. The model's estimates of survival at 20 years for 1391 members of the Whickham survey cohort between the ages of 35 and 65 were compared with the observed survival at 20-year follow-up. RESULTS: The model estimate for survival was 75% and the observed survival was 75.4%. The correlation between estimated and observed survival was 0.933 over 39 subgroups of the cohort stratified by estimated survival, 0.992 for the seven 5-year age bands from 35 to 64, 0.936 for the ten 10 mmHg systolic blood pressure bands between 100 mmHg and 200 mmHg, and 0.693 for the fifteen 0.5 mmol/l total cholesterol bands between 3.0 and 10.0 mmol/l. The model significantly underestimated mortality in those people with a systolic blood pressure greater than or equal to 180 mmHg (p = 0.006). The average gain in life expectancy from the elimination of cardiovascular disease risk as a cause of death was 4.0 years for all the 35 year-old men in the sample (n = 24), and 1.8 years for all the 35 year-old women in the sample (n = 32). CONCLUSIONS: This model accurately estimates 20-year survival in subjects from the Whickham cohort with a systolic blood pressure below 180 mmHg

Evolutionary and pulsational properties of white dwarf stars

Abridged. White dwarf stars are the final evolutionary stage of the vast majority of stars, including our Sun. The study of white dwarfs has potential applications to different fields of astrophysics. In particular, they can be used as independent reliable cosmic clocks, and can also provide valuable information about the fundamental parameters of a wide variety of stellar populations, like our Galaxy and open and globular clusters. In addition, the high densities and temperatures characterizing white dwarfs allow to use these stars as cosmic laboratories for studying physical processes under extreme conditions that cannot be achieved in terrestrial laboratories. They can be used to constrain fundamental properties of elementary particles such as axions and neutrinos, and to study problems related to the variation of fundamental constants. In this work, we review the essentials of the physics of white dwarf stars. Special emphasis is placed on the physical processes that lead to the formation of white dwarfs as well as on the different energy sources and processes responsible for chemical abundance changes that occur along their evolution. Moreover, in the course of their lives, white dwarfs cross different pulsational instability strips. The existence of these instability strips provides astronomers with an unique opportunity to peer into their internal structure that would otherwise remain hidden from observers. We will show that this allows to measure with unprecedented precision the stellar masses and to infer their envelope thicknesses, to probe the core chemical stratification, and to detect rotation rates and magnetic fields. Consequently, in this work, we also review the pulsational properties of white dwarfs and the most recent applications of white dwarf asteroseismology.Comment: 85 pages, 28 figures. To be published in The Astronomy and Astrophysics Revie

Chromosomes of Theridiidae spiders (Entelegynae): Interspecific karyotype diversity in Argyrodes and diploid number intraspecific variability in Nesticodes rufipes

Theridiidae is a derived family within the Araneoidea clade. In contrast to closely related groups, the 2n(male) = 20+X1 X 2 with acro/telocentric chromosomes is the most widespread karyotype among the theridiid spiders. In this work, the cytogenetic analysis of Argyrodes elevatus revealed original chromosome features different from those previously registered for Theridiidae, including the presence of 2n(male) = 20+X with meta/submetacentric chromosomes. Most individuals of Nesticodes rufipes showed family conserved karyotype characteristics. However, one individual had a 2n(male) = 24 due to the presence of an extra chromosome pair, which exhibited regular behavior and reductional segregation during meiosis. After silver staining, mitotic cells exhibited NORs localized on the terminal regions of the short arms of pairs 2, 3, and 4 of A. elevatus and on the terminal regions of long arms of pair 4 of N. rufipes. The comparative analysis with data from phylogenetically related species allowed the clarification of the origin of the interspecific and intraspecific chromosome variability observed in Argyrodes and in N. rufipes, respectively

Impact of transient groundwater storage on the discharge of Himalayan rivers

International audienceIn the course of the transfer of precipitation into rivers, water is temporarily stored in reservoirs with different residence times such as soils, groundwater, snow and glaciers. In the central Himalaya, the water budget is thought to be primarily controlled by monsoon rainfall, snow and glacier melt, and secondarily by evapotranspiration. An additional contribution from deep groundwater has been deduced from the chemistry of Himalayan rivers, but its importance in the annual water budget remains to be evaluated. Here we analyse records of daily precipitation and discharge within twelve catchments in Nepal over about 30 years. We observe annual hysteresis loops--that is, a time lag between precipitation and discharge--in both glaciated and unglaciated catchments and independent of the geological setting. We infer that water is stored temporarily in a reservoir with characteristic response time of about 45 days, suggesting a diffusivity typical of fractured basement aquifers. We estimate this transient storage capacity at about 28km3 for the three main Nepal catchments; snow and glacier melt contribute around 14km3yr-1, about 10% of the annual river discharge. We conclude that groundwater storage in a fractured basement influences significantly the Himalayan river discharge cycle