Dynamical approach to spectator fragmentation in Au+Au reactions at 35 MeV/A

The characteristics of fragment emission in peripheral $^{197}$Au+$^{197}$Au collisions 35 MeV/A are studied using the two clusterization approaches within framework of \emph{quantum molecular dynamics} model. Our model calculations using \emph{minimum spanning tree} (MST) algorithm and advanced clusterization method namely \emph{simulated annealing clusterization algorithm} (SACA) showed that fragment structure can be realized at an earlier time when spectators contribute significantly toward the fragment production even at such a low incident energy. Comparison of model predictions with experimental data reveals that SACA method can nicely reproduce the fragment charge yields and mean charge of the heaviest fragment. This reflects suitability of SACA method over conventional clusterization techniques to investigate spectator matter fragmentation in low energy domain.Comment: 6 pages, 5 figures, accepte

Natalizumab affects T-cell phenotype in multiple sclerosis: implications for JCV reactivation

The anti-CD49d monoclonal antibody natalizumab is currently an effective therapy against the relapsing-remitting form of multiple sclerosis (RRMS). Natalizumab therapeutic efficacy is limited by the reactivation of the John Cunningham polyomavirus (JCV) and development of progressive multifocal leukoencephalopathy (PML). To correlate natalizumab-induced phenotypic modifications of peripheral blood T-lymphocytes with JCV reactivation, JCV-specific antibodies (serum), JCV-DNA (blood and urine), CD49d expression and relative abundance of peripheral blood T-lymphocyte subsets were longitudinally assessed in 26 natalizumab-treated RRMS patients. Statistical analyses were performed using GraphPad Prism and R. Natalizumab treatment reduced CD49d expression on memory and effector subsets of peripheral blood T-lymphocytes. Moreover, accumulation of peripheral blood CD8+ memory and effector cells was observed after 12 and 24 months of treatment. CD4+ and CD8+ T-lymphocyte immune-activation was increased after 24 months of treatment. Higher percentages of CD8+ effectors were observed in subjects with detectable JCV-DNA. Natalizumab reduces CD49d expression on CD8+ T-lymphocyte memory and effector subsets, limiting their migration to the central nervous system and determining their accumulation in peripheral blood. Impairment of central nervous system immune surveillance and reactivation of latent JCV, can explain the increased risk of PML development in natalizumab-treated RRMS subjects

Persistent organic pollutant levels in human visceral and subcutaneous adipose tissue in obese individuals - Depot differences and dysmetabolism implications

Background: The role of persistent organic pollutants (POPs) with endocrine disrupting activity in the aetiology of obesity and other metabolic dysfunctions has been recently highlighted. Adipose tissue (AT) is a common site of POPs accumulation where they can induce adverse effects on human health. Objectives: To evaluate the presence of POPs in human visceral (vAT) and subcutaneous (scAT) adipose tissue in a sample of Portuguese obese patients that underwent bariatric surgery, and assess their putative association with metabolic disruption preoperatively, as well as with subsequent body mass index (BMI) reduction. Methods: AT samples (n=189) from obese patients (BMI ≥35) were collected and the levels of 13 POPs were determined by gas chromatography with electron-capture detection (GC-ECD). Anthropometric and biochemical data were collected at the time of surgery. BMI variation was evaluated after 12 months and adipocyte size was measured in AT samples. Results: Our data confirm that POPs are pervasive in this obese population (96.3% of detection on both tissues), their abundance increasing with age (RS=0.310, p<0.01) and duration of obesity (RS=0.170, p<0.05). We observed a difference in AT depot POPs storage capability, with higher levels of ΣPOPs in vAT (213.9±204.2 compared to 155.1±147.4 ng/g of fat, p<0.001), extremely relevant when evaluating their metabolic impact. Furthermore, there was a positive correlation between POP levels and the presence of metabolic syndrome components, namely dysglycaemia and hypertension, and more importantly with cardiovascular risk (RS=0.277, p<0.01), with relevance for vAT (RS=0.315, p<0.01). Finally, we observed an interesting relation of higher POP levels with lower weight loss in older patients. Conclusion: Our sample of obese subjects allowed us to highlight the importance of POPs stored in AT on the development of metabolic dysfunction in a context of obesity, shifting the focus to their metabolic effects and not only for their recognition as environmental obesogens

Association between global leukocyte DNA methylation and cardiovascular risk in postmenopausal women

BACKGROUND: Genetic studies to date have not provided satisfactory evidence regarding risk polymorphisms for cardiovascular disease (CVD). Conversely, epigenetic mechanisms, including DNA methylation, seem to influence the risk of CVD and related conditions. Because postmenopausal women experience an increase in CVD, we set out to determine whether global DNA methylation was associated with cardiovascular risk in this population. METHODS: In this cross sectional study carried out in a university hospital, 90 postmenopausal women without prior CVD diagnosis (55.5 ± 4.9 years, 5.8 [3.0–10.0] years since menopause) were enrolled. DNA was extracted from peripheral leukocytes and global DNA methylation levels were obtained with an ELISA kit. Cardiovascular risk was estimated by the Framingham General Cardiovascular Risk Score (10-year risk) (FRS). Clinical and laboratory variables were assessed. Patients were stratified into two CVD risk groups: low (FRS: <10 %, n = 69) and intermediate/high risk (FRS ≥10 %, n = 21). RESULTS: Age, time since menopause, blood pressure, total cholesterol, and LDL-c levels were higher in FRS ≥10 % group vs. FRS <10 % group. BMI, triglycerides, HDL-c, HOMA-IR, glucose and hsC-reactive protein levels were similar in the two groups. Global DNA methylation (% 5mC) in the overall sample was 26.5 % (23.6–36.9). The FRS ≥10 % group presented lower global methylation levels compared with the FRS <10 % group: 23.9 % (20.6–29.1) vs. 28.8 % (24.3–39.6), p = 0.02. This analysis remained significant even after adjustment for time since menopause (p = 0.02). CONCLUSIONS: Our results indicate that lower global DNA methylation is associated with higher cardiovascular risk in postmenopausal women

A genetic programming approach to development of clinical prediction models: A case study in symptomatic cardiovascular disease

BACKGROUND:Genetic programming (GP) is an evolutionary computing methodology capable of identifying complex, non-linear patterns in large data sets. Despite the potential advantages of GP over more typical, frequentist statistical approach methods, its applications to survival analyses are rare, at best. The aim of this study was to determine the utility of GP for the automatic development of clinical prediction models. METHODS:We compared GP against the commonly used Cox regression technique in terms of the development and performance of a cardiovascular risk score using data from the SMART study, a prospective cohort study of patients with symptomatic cardiovascular disease. The composite endpoint was cardiovascular death, non-fatal stroke, and myocardial infarction. A total of 3,873 patients aged 19-82 years were enrolled in the study 1996-2006. The cohort was split 70:30 into derivation and validation sets. The derivation set was used for development of both GP and Cox regression models. These models were then used to predict the discrete hazards at t = 1, 3, and 5 years. The predictive ability of both models was evaluated in terms of their risk discrimination and calibration using the validation set. RESULTS:The discrimination of both models was comparable. At time points t = 1, 3, and 5 years the C-index was 0.59, 0.69, 0.64 and 0.66, 0.70, 0.70 for the GP and Cox regression models respectively. At the same time points, the calibration of both models, which was assessed using calibration plots and the generalization of the Hosmer-Lemeshow test statistic, was also comparable, but with the Cox model being better calibrated to the validation data. CONCLUSION:Using empirical data, we demonstrated that a prediction model developed automatically by GP has predictive ability comparable to that of manually tuned Cox regression. The GP model was more complex, but it was developed in a fully automated way and comprised fewer covariates. Furthermore, it did not require the expertise normally needed for its derivation, thereby alleviating the knowledge elicitation bottleneck. Overall, GP demonstrated considerable potential as a method for the automated development of clinical prediction models for diagnostic and prognostic purposes

Online information and support needs of women with advanced breast cancer: A qualitative analysis

Purpose: Women with advanced breast cancer (ABC) face significant adjustment challenges, yet few resources provide them with information and support, and attendance barriers can preclude access to face to face psychosocial support. This paper reports on two qualitative studies examining (i) whether information and support-seeking preferences of women with ABC could be addressed in an online intervention, and (ii) how an existing intervention for patients with early stage cancer could be adapted for women with ABC. Methods: Women with ABC participated in telephone interviews about their information and support- seeking preferences (N = 21) and evaluated an online intervention focused on early-stage cancer (N = 15). Interviews were transcribed and underwent thematic analysis using the framework method to identify salient themes. Results: Participants most commonly sought medical, lifestyle-related, and practical information/support; however, when presented with an online intervention, participants most commonly gave positive feedback on content on coping with emotional distress. Difficulty finding information and barriers to using common sources of information/support including health professionals, family and friends, and peers were reported; however, some women also reported not wanting information or support. All participants evaluating the existing intervention gave positive feedback on various components, with results suggesting an online intervention could be an effective means of providing information/support to women with ABC, given improved specificity/relevance to ABC and increased tailoring to individuals circumstances and preferences. Conclusions: Adaptation of an existing online intervention for early stage cancer appears a promising avenue to address the information and support needs of women with ABC