Ion cyclotron wall conditioning experiments on Tore Supra in presence of the toroidal magnetic field

Wall conditioning techniques applicable in the presence of the high toroidal magnetic field will be required for the operation of ITER for tritium removal, isotopic ratio control and recovery to normal operation after disruptions. Recently ion cyclotron wall conditioning (ICWC) experiments have been carried out on Tore Supra in order to assess the efficiency of this technique in ITER relevant conditions. The ICRF discharges were operated in He/H-2 Mixtures at the Tore Supra nominal field (3.8 T) and a RF frequency of 48 MHz, i.e. within the ITER operational space. RF pulses of 60 s (max.) were applied using a standard Tore Supra two-strap resonant double loop antenna in ICWC mode, operated either in pi or 0-phasing with a noticeable improvement of the RF coupling in the latter case. In order to assess the efficiency of the technique for the control of isotopic ratio the wall was first preloaded using a D-2 glow discharge. After 15 minutes of ICWC in He/H-2 gas mixtures the isotopic ratio was altered from 4% to 50% at the price of an important H implantation into the walls. An overall analysis comparing plasma production and the conditioning efficiency as a function of discharge parameters is given

I'll stand next to them until they don't need me anymore'. :Voluntary work in debt counseling in Rotterdam

De schuldenproblematiek in Nederland neemt toe. Gemeenten en welzijnsorganisaties ontwikkelen daarom verschillende interventies gericht op vroegsignalering en het toeleiden van burgers met schulden naar professionele schuldhulpverlening. Vrijwilligers spelen een belangrijke rol in deze interventies. Dit artikel biedt inzicht in de waarde en worstelingen van vrijwilligerswerk in deschuldhulpverlening, door de bevindingen te presenteren van een casusonderzoek naar de ervaren effectiviteit van vrijwillige inzet bij een lokaal schuldhulpverleningsproject in Rotterdam. Uit het onderzoek blijkt dat de ervaren effectiviteit van vrijwillige inzet in het project bepaald wordt door zeven factoren: (1) tijd, (2) taal en cultuur, (3) positie als vrijwilliger, (4) warme overdracht, (5) sociale steun, (6) praktische hulp, (7) belangenbehartiging en bemiddeling. De aandachtspunten in het project zijn: (1) onduidelijke taak- en rolverdeling tussen vrijwilligers en beroepskrachten, (2) grensbewaking, (3) begeleidingsduur, (4) verantwoording werkzaamheden en aansturing vrijwilligers, (5) professionele ontwikkeling. De studie laat zien dat vrijwilligers mensen met schuldenproblemen in een vroeger stadium naar professionele schuldhulpverlening kunnen begeleiden en hen sociale en praktische steun bieden. Het begeleiden en ondersteunen van mensen met (ernstige) schuldenproblemen vraagt echter veel van de kennis, vaardigheden en houding van vrijwilligers. Vrijwillige inzet bij schuldhulpverlening is belangrijk, maar kan professionele schuldhulpverlening niet vervangen. TREFWOORDENSchuldhulpverlening, schulden, sociaal werk, vrijwilligers, vrijwilligerswerk, samenwerking beroepskrachten en vrijwilligersABSTRACTHousehold debt problems in the Netherlands are rising. Municipalities and social welfare organisations are developing interventions aimed at guiding people with debt problems to professional debt counselling at an early stage. Volunteers play an important role in these interventions. This article provides insight into the value and struggles of voluntary work in debt counselling, through presenting the findings of a case study into the perceived effectiveness of voluntary work in a debt counselling programme in Rotterdam. The findings show that the perceived effectiveness of voluntary work in the programme depends on seven factors: (1) time, (2) language and culture, (3) position as volunteer, (4) ‘warm transfer’, (5) social support, (6) practical help, (7) advocating and mediating. Bottlenecks in the programme are: (1) unclear task- and role divisions, (2) guarding boundaries, (3) duration of support, (4) accountability and managing volunteers, (5) professional development. The article shows that volunteers can guide people with debt problems to professional debt counselling at an earlier stage and can offer them much needed social and practical support. However, guiding and supporting people with (severe) debt problems requires a specific set of knowledge, skills and attitudes. Voluntary work is important, but should not replace professional debt counselling

Regulation of Intestinal UDP-Glucuronosyltransferase 1A1 by the Farnesoid X Receptor Agonist Obeticholic Acid Is Controlled by Constitutive Androstane Receptor through Intestinal Maturation

UDP-glucuronosyltransferase (UGT) 1A1 is the only transferase capable of conjugating serum bilirubin. However, temporal delay in the development of the UGT1A1 gene leads to an accumulation of serum bilirubin in newborn children. Neonatal humanized UGT1 (hUGT1) mice, which accumulate severe levels of total serum bilirubin (TSB), were treated by oral gavage with obeticholic acid (OCA), a potent FXR agonist. OCA treatment led to dramatic reduction in TSB levels. Analysis of UGT1A1 expression confirmed that OCA induced intestinal and not hepatic UGT1A1. Interestingly, Cyp2b10, a target gene of the nuclear receptor CAR, was also induced by OCA in intestinal tissue. In neonatal hUGT1/Car(-/-) mice, OCA was unable to induce CYP2B10 and UGT1A1, confirming that CAR and not FXR is involved in the induction of intestinal UGT1A1. However, OCA did induce FXR target genes, such as Shp, in both intestines and liver with induction of Fgf15 in intestinal tissue. Circulating FGF15 activates hepatic FXR and, together with hepatic Shp, blocks Cyp7a1 and Cyp7b1 gene expression, key enzymes in bile acid metabolism. Importantly, the administration of OCA in neonatal hUGT1 mice accelerates intestinal epithelial cell maturation, which directly impacts on induction of the UGT1A1 gene and the reduction in TSB levels. Accelerated intestinal maturation is directly controlled by CAR, since induction of enterocyte marker genes sucrase-isomaitase, alkaline phosphatase 3, and keratin 20 by OCA does not occur in hUGT1/Car(-/-) mice. Thus, new findings link an important role for CAR in intestinal UGT1A1 induction and its role in the intestinal maturation pathway. SIGNIFICANCE STATEMENT Obeticholic acid (OCA) activates FXR target genes in both liver and intestinal tissues while inducing intestinal UGT1A1, which leads to the elimination of serum bilirubin in humanized UGT1 mice. However, the induction of intestinal UGT1A1 and the elimination of bilirubin by OCA is driven entirely by activation of intestinal CAR and not FXR. The elimination of serum bilirubin is based on a CARdependent mechanism that facilitates the acceleration of intestinal epithelium cell differentiation, an event that underlies the induction of intestinal UGT1A1

Residual confounding after adjustment for age: a minor issue in breast cancer screening effectiveness

Residual confounding, after adjustment for age, is the major criticism of observational studies on breast cancer screening effectiveness. We developed realistic scenarios for the prevalence and strength of risk factors on screened and not screened groups, and explored the impact of residual confounding bias. Our results demonstrate that residual confounding bias is a minor issue in screening programme evaluations

Clinical osteoarthritis of the hip and knee and fall risk: The role of low physical functioning and pain medication

Objective: Several studies have found an increased fall risk in persons with osteoarthritis (OA). However, most prospective studies did not use a clinical definition of OA. In addition, it is not clear which factors explain this risk. Our objectives were: (1) to confirm the prospective association between clinical OA of the hip and knee and falls; (2) to examine the modifying effect of sex; and (3) to examine whether low physical performance, low physical activity and use of pain medication are mediating these relationships. Methods: Baseline and 1-year follow-up data from the European Project on OSteoArthritis (EPOSA) were used involving pre-harmonized data from five European population-based cohort studies (ages 65 85, n = 2535). Clinical OA was defined according to American College of Rheumatology (ACR) criteria. Falls were assessed using self-report. Results: Over the follow-up period, 27.7% of the participants fell once or more (defined as faller), and 9.8% fell twice or more (recurrent faller). After adjustment for confounding, clinical knee OA was associated with the risk of becoming a recurrent faller (relative risk=1.55; 95% confidence interval: 1.10 2.18), but not with the risk of becoming a faller. No associations between clinical hip OA and (recurrent) falls were observed after adjustment for confounding. Use of opioids and analgesics mediated the associations between clinical OA and (recurrent) falls, while physical performance and physical activity did not. Conclusion: Individuals with clinical knee OA were at increased risk for recurrent falls. This relationship was mediated by pain medication, particularly opioids. The fall risk needs to be considered when discussing the risk benefit ratio of prescribing these medicationsSources of support: The Longitudinal Aging Study Amsterdam (LASA) is financially supported by the Dutch Ministry of Health, Welfare and Sports (grant no 311669, grant recipient D.J.H. Deeg). The Pe~nagrande study was partially supported by the National Fund for Health Research (Fondo de Investigaciones en Salud) of Spain (grant no FIS PI 05/1898; FIS RETICEF RD06/0013/1013 and FIS PS09/02143, grant recipients A. Otero, M.V. Castell). The Hertfordshire Cohort Study is supported by the Medical Research Council of Great Britain, Versus Arthritis, the British Heart Foundation and the International Osteoporosis Foundation (grant no MRC_MC_UP_A620_1014, grant recipients C. Cooper, E. Dennison). The Italian cohort was supported by the National Research Council of Italy (CNR), Research Project “Aging: molecular and technological innovations for improving the health of the elderly population" (Prot. MIUR 2867, grant recipient: S. Maggi). The Swedish Twin Registry is managed by Karolinska Institutet and receives funding through the Swedish Research Council (grant no 2017-00641, grant recipient Karolinska Institutet

The role of plasma concentrations and drug characteristics of beta-blockers in fall risk of older persons

Beta-blocker usage is inconsistently associated with increased fall risk in the literature. However, due to age-related changes and interindividual heterogeneity in pharmacokinetics and dynamics, it is difficult to predict which older adults are more at risk for falls. Therefore, we wanted to explore whether elevated plasma concentrations of selective and nonselective beta-blockers are associated with an increased risk of falls in older beta-blocker users. To answer our research question, we analyzed samples of selective (metoprolol, n = 316) and nonselective beta-blockers (sotalol, timolol, propranolol, and carvedilol, n = 179) users from the B-PROOF cohort. The associations between the beta-blocker concentration and time to first fall were assessed using Cox proportional hazard models. Change of concentration over time in relation to fall risk was assessed with logistic regression models. Models were adjusted for potential confounders. Our results showed that above the median concentration of metoprolol was associated with an increased fall risk (HR 1.55 [1.11–2.16], p =.01). No association was found for nonselective beta-blocker concentrations. Also, changes in concentration over time were not associated with increased fall risk. To conclude, metoprolol plasma concentrations were associated with an increased risk of falls in metoprolol users while no associations were found for nonselective beta-blockers users. This might be caused by a decreased β1-selectivity in high plasma concentrations. In the future, beta-blocker concentrations could potentially help clinicians estimate fall risk in older beta-blockers users and personalize treatment.</p

Non-skeletal health effects of vitamin D supplementation: a systematic review on findings from meta-analyses summarizing trial data

Background A large number of observational studies have reported harmful effects of low 25-hydroxyvitamin D (25OHD) levels on non-skeletal outcomes. We performed a systematic quantitative review on characteristics of randomized clinical trials (RCTs) included in meta-analyses (MAs) on non-skeletal effects of vitamin D supplementation. Methods and findings We identified systematic reviews (SR) reporting summary data in terms of MAs of RCTs on selected non-skeletal outcomes. For each outcome, we summarized the results from available SRs and scrutinized included RCTs for a number of predefined characteristics. We identified 54 SRs including data from 210 RCTs. Most MAs as well as the individual RCTs reported null-findings on risk of cardiovascular diseases, type 2 diabetes, weight-loss, and malignant diseases. Beneficial effects of vitamin D supplementation was reported in 1 of 4 MAs on depression, 2 of 9 MAs on blood pressure, 3 of 7 MAs on respiratory tract infections, and 8 of 12 MAs on mortality. Most RCTs have primarily been performed to determine skeletal outcomes, whereas non-skeletal effects have been assessed as secondary outcomes. Only one-third of the RCTs had low level of 25OHD as a criterion for inclusion and a mean baseline 25OHD level below 50 nmol/L was only present in less than half of the analyses. Conclusions Published RCTs have mostly been performed in populations without low 25OHD levels. The fact that most MAs on results from RCTs did not show a beneficial effect does not disprove the hypothesis suggested by observational findings on adverse health outcomes of low 25OHD levels

A Randomized Controlled Trial to Examine the Effect of 2-Year Vitamin B12 and Folic Acid Supplementation on Physical Performance, Strength, and Falling: Additional Findings from the B-PROOF Study

Elevated homocysteine concentrations are associated with a decline in physical function in elderly persons. Homocysteine-lowering therapy may slow down this decline. This study aimed to examine the effect of a 2-year intervention of vitamin B12 and folic acid supplementation on physical performance, handgrip strength, and risk of falling in elderly subjects in a double-blind, randomized placebo-controlled trial. Participants aged ≥65 years with elevated plasma homocysteine concentrations [12–50 µmol/L (n = 2919)] were randomly assigned to daily supplementation of 500 µg vitamin B12, 400 µg folic acid, and 600 I

Impact of prevalent and incident vertebral fractures on utility: results from a patient-based and a population-based sample

Data are scarce on the impact of vertebral fractures (VFX) on utility. The objective of this study was to assess the impact of prevalent and incident VFX on utility in both a patient-based and population-based sample. Data from the Multiple Outcomes of Raloxifene Evaluation (MORE) study (n = 550 for prevalent VFX and n = 174 for incident VFX) and the European Prospective Osteoporosis Study (EPOS) (n = 236) were used. Utility was assessed by the index score of the EQ-5D. In the MORE study, highly statistically significant associations were found between utility and the presence of prevalent VFX (p < 0.001), number of prevalent VFX (p < 0.001), severity of prevalent VFX (p < 0.001), the combination of number and severity of prevalent VFX (p = 0.001) and location of prevalent VFX (p = 0.019). The mean utility was significantly lower among women who suffered an incident VFX (utility = 0.67) than among women who did not (utility = 0.77) (p = 0.005), although utility loss was not significantly different between the two groups (p = 0.142). In EPOS, the combination of number and severity of incident VFX was significantly related to utility (p = 0.030). In conclusion, utility is lower among persons with prevalent and incident VFX, especially in a patient-based sample. Utility loss was not significantly different between women without and with incident VFX