Spin glass overlap barriers in three and four dimensions

For the Edwards-Anderson Ising spin-glass model in three and four dimensions (3d and 4d) we have performed high statistics Monte Carlo calculations of those free-energy barriers $F^q_B$ which are visible in the probability density $P_J(q)$ of the Parisi overlap parameter $q$. The calculations rely on the recently introduced multi-overlap algorithm. In both dimensions, within the limits of lattice sizes investigated, these barriers are found to be non-self-averaging and the same is true for the autocorrelation times of our algorithm. Further, we present evidence that barriers hidden in $q$ dominate the canonical autocorrelation times.Comment: 20 pages, Latex, 12 Postscript figures, revised version to appear in Phys. Rev.

Praktijktoets Waterwijzer Landbouw in pilotgebieden de Raam en Vecht

In het kader van het kennisprogramma Lumbricus is voor twee gebieden op de zandgronden een praktijktoets uitgevoerd voor de Waterwijzer Landbouw. Geconcludeerd is dat het mogelijk is met de Waterwijzer Landbouw om uitgesplist droogte en natschade voor gras en mais te berekenen. De studie heeft laten zien dat Waterwijzer Landbouw – zeker na uitbreiding voor andere gewassen en de bedrijfsvoering – een goed instrument is en onmisbaar is bij het doorrekenen van klimaatscenario’s, het bepalen van effecten op gewasopbrengsten en voor het klimaatrobuust inrichten van gebieden. Zo kan straks met behulp van de Waterwijzer Landbouw ook de meest geschikte gewassen voor specieke gebieden bepaald worden

A placebo-controlled proof-of-concept study of alirocumab on postprandial lipids and vascular elasticity in insulin-treated patients with type 2 diabetes mellitus

Aim: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular disease (CVD) linked to atherogenic dyslipidaemia and postprandial hyperlipidaemia. Alirocumab, a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor, improves CVD risk by reducing the concentration of low-density lipoprotein-cholesterol (LDL-C). However, effects of PCK9 inhibitors on other aspects of diabetic dyslipidaemia, particularly in the postprandial situation, are less clear. Material and Methods: Twelve male patients with T2DM on an intensive insulin regimen completed a 6-week randomized, double-blind, placebo-controlled, proof-of-concept study. Participants received three biweekly dosages of subcutaneous alirocumab (150 mg) or placebo. Before and after the intervention, fasting and postprandial triglyceride (TG) plasma levels, apolipoprotein (apo) B48, lipoprotein composition isolated by ultracentrifugation, vascular function and markers of inflammation were evaluated. Results: Alirocumab treatment reduced fasting plasma TG levels (between group median change −24.7%; P = 0.018) and fasting apoB48 serum levels (−35.9%; P = 0.039) compared with placebo. Alirocumab reduced the plasma TG area under the curve (AUC) (−26.4%; P = 0.006) and apoB48 AUC (−55.7%; P = 0.046), as well as plasma TG incremental AUC (−21.4%; P = 0.04) and apoB48 incremental AUC (−26.8%; P = 0.02). In addition, alirocumab reduced fasting and postprandial TG levels in very low-density lipoprotein (VLDL) and LDL. Alirocumab improved fasting pulse wave velocity, but no changes in postprandial markers of inflammation were observed. Conclusions: In addition to the well-known LDL-C-reducing effects, 6 weeks of alirocumab treatment lowered both fasting and postprandial plasma TG levels by reducing the TG levels in VLDL and LDL and the concentration of intestinal remnants

Reducing unnecessary vitamin testing in general practice: barriers and facilitators according to general practitioners and patients

OBJECTIVE: There has been an increase in testing of vitamins in patients in general practice, often based on irrational indications or for non-specific symptoms, causing increasing healthcare expenditures and medicalisation of patients. So far, there is little evidence of effective strategies to reduce this overtesting in general practice. Therefore, the aim of this qualitative study was to explore the barriers and facilitators for reducing the number of (unnecessary) vitamin D and B12 laboratory tests ordered. DESIGN AND SETTING: This qualitative study, based on a grounded theory design, used semistructured interviews among general practitioners (GPs) and patients from two primary care networks (147 GPs, 195 000 patients). These networks participated in the Reducing Vitamin Testing in Primary Care Practice (REVERT) study, a clustered randomized trial comparing two de-implementation strategies to reduce test ordering in primary care in the Netherlands. PARTICIPANTS: Twenty-one GPs, with a maximum of 1 GP per practice who took part in the REVERT study, and 22 patients (who were invited by their GP during vitamin-related consultations) were recruited, from which 20 GPs and 19 patients agreed to participate in this study. RESULTS: The most important factor hampering vitamin-test reduction programmes is the mismatch between patients and medical professionals regarding the presumed appropriate indications for testing for vitamin D and B12. In contrast, the most important facilitator for vitamin-test reduction may be updating GPs' knowledge about test indications and their awareness of their own testing behaviour. CONCLUSION: To achieve a sustainable reduction in vitamin testing, guidelines with clear and uniform recommendations on evidence-based indications for vitamin testing, combined with regular (individual) feedback on test-ordering behaviour, are needed. Moreover, the general public needs access to clear and reliable information on vitamin testing. Further research is required to measure the effect of these strategies on the number of vitamin test requests. TRIAL REGISTRATION NUMBER: WAG/mb/16/039555

Everolimus Exposure and Early Metabolic Response as Predictors of Treatment Outcomes in Breast Cancer Patients Treated with Everolimus and Exemestane

Imaging- and therapeutic targets in neoplastic and musculoskeletal inflammatory diseas

Women’s beliefs about medicines and adherence to pharmacotherapy in pregnancy: Opportunities for community pharmacists?

Background During pregnancy women might weigh benefits of treatment against potential risks to the unborn child. However, non-adherence to necessary treatment can adversely affect both mother and child. To optimize pregnant women’s beliefs and medication adherence, community pharmacists are ideally positioned to play an important role in primary care. Objective This narrative review aimed to summarize the evidence on 1) pregnant women’s beliefs, 2) medication adherence in pregnancy, and 3) community pharmacists’ counselling during pregnancy. Method Three search strategies were used in Medline and Embase to find original studies evaluating women’s beliefs, medication adherence and community pharmacists’ counselling during pregnancy. All original descriptive and analytic epidemiological studies performed in Europe, North America and Australia, written in English and published from 2000 onwards were included. Results We included 14 studies reporting on women’s beliefs, 11 studies on medication adherence and 9 on community pharmacists’ counselling during pregnancy. Women are more reluctant to use medicines during pregnancy and tend to overestimate the teratogenic risk of medicines. Risk perception varies with type of medicine, level of health literacy, education level and occupation. Furthermore, low medication adherence during pregnancy is common. Finally, limited evidence showed current community pharmacists’ counselling is insufficient. Barriers hindering pharmacists are insufficient knowledge and limited access to reliable information. Conclusion Concerns about medication use and non-adherence are widespread among pregnant women. Community pharmacists’ counselling during pregnancy is insufficient. Further education, training and research are required to support community pharmacists in fulfilling all the opportunities they have when counselling pregnant women

Diagnostic yield of colonoscopy surveillance in testicular cancer survivors treated with platinum-based chemotherapy: study protocol of a prospective cross-sectional cohort study

Background: Testicular cancer (TC) survivors have an increased risk of various second primary malignancies. A recent cohort study detected an increased risk of colorectal cancer (CRC) in TC survivors treated with platinum-based chemotherapy with a hazard ratio of 3.9. CRC risk increased with higher cisplatin-dose. We know that colonoscopy surveillance in high-risk populations results in reduced incidence and mortality of CRC. TC survivors treated with platinum-based chemotherapy can potentially benefit from colonoscopy surveillance; however, to which extent is unknown. Furthermore, the pathogenesis of these secondary CRCs is unknown, and better insights into the carcinogenesis may affect surveillance decisions. Methods: This prospective multicenter study will be performed in four Dutch hospitals. TC survivors are eligible if treated with ≥ 3 cycles of cisplatin before age 50. Colonoscopy will be performed ≥ 8 years after initial treatment (minimum and maximum ages at colonoscopy, 35 and 75 years, respectively). The primary aim of the study is the diagnostic yield of advanced neoplasia detected during colonoscopy. As secondary aim, we will evaluate the molecular profile of advanced colorectal neoplasia and will assess current platinum levels in blood and urine and correlate blood-platinum levels with prevalence of colorectal lesions. Furthermore, we will investigate effectiveness of fecal immunochemical testing (FIT) and burden of colonoscopy by two questionnaires. Demographic data, previous history, results of colonoscopy, hemoglobin level of FIT and results of molecular and platinum levels will be obtained. Yield of colonoscopy will be determined by detection rate of adenoma and serrated lesions, advanced adenoma detection rate and CRC detection rate. The MISCAN model will be used for cost-effectiveness analyses of CRC surveillance. With 234 participants undergoing colonoscopy, we can detect an absolute difference of 6% of advanced neoplasia with 80% power. Discussion: TC survivors treated with cisplatin-based chemotherapy can benefit from CRC surveillance. Evaluation of the diagnostic performance and patient acceptance of CRC surveillance is of importance to develop surveillance recommendations. Insight into the carcinogenesis of cisplatin-related advanced colorectal lesions will contribute to CRC prevention in the increasing number of TC survivors. The results may also be important for the many other cancer survivors treated with platinum-based chemotherapy. Trial registration: Clinical Trials: NCT04180033, November 27, 2019, https://clinicaltrials.gov/ct2/sh

Measurement of CP observables in B± → D(⁎)K± and B± → D(⁎)π± decays

Measurements of CP observables in B ± →D (⁎) K ± and B ± →D (⁎) π ± decays are presented, where D (⁎) indicates a neutral D or D ⁎ meson that is an admixture of D (⁎)0 and D¯ (⁎)0 states. Decays of the D ⁎ meson to the Dπ 0 and Dγ final states are partially reconstructed without inclusion of the neutral pion or photon, resulting in distinctive shapes in the B candidate invariant mass distribution. Decays of the D meson are fully reconstructed in the K ± π ∓ , K + K − and π + π − final states. The analysis uses a sample of charged B mesons produced in pp collisions collected by the LHCb experiment, corresponding to an integrated luminosity of 2.0, 1.0 and 2.0 fb −1 taken at centre-of-mass energies of s=7, 8 and 13 TeV, respectively. The study of B ± →D ⁎ K ± and B ± →D ⁎ π ± decays using a partial reconstruction method is the first of its kind, while the measurement of B ± →DK ± and B ± →Dπ ± decays is an update of previous LHCb measurements. The B ± →DK ± results are the most precise to date