Prevalence, awareness, treatment and control of hypertension in Malaysia: a national study of 16,440 subjects,”

Summary Study design: A cross-sectional study was conducted in all states of Malaysia to determine the prevalence, awareness, treatment and control of hypertension. A stratified two-stage cluster sampling design with proportional allocation was used. Methods: Trained nurses obtained two blood pressure measurements from each subject. Hypertension was defined as mean systolic blood pressure 4140 mmHg, diastolic blood pressure 490 mmHg, or a self-reported diagnosis of hypertension and taking antihypertensive medication. All data were analysed using Stata 9.2 software and took the complex survey design into account. A two-sided P-value of o0.05 was considered to be statistically significant. Results: The overall prevalence of hypertension for subjects aged X15 years was 27.8% (95% confidence interval (CI) 26.9-28.8). The prevalence of hypertension was significantly higher in males (29.6%, 95% CI 28.3-31.0) compared with females (26.0%, 95% CI 25.0-27.1). Multivariate logistic regression showed that the odds of having hypertension increased with increasing age, in males, in subjects with a family history of hypertension, with increasing body mass index, in non-smokers and with decreasing levels of education. Only 34.6% of the subjects with hypertension were aware of their hypertensive status, and 32.4 were taking antihypertensive medication. Amongst the latter group, only 26.8% had their blood pressure under control. The prevalence of hypertension amongst those aged X30 years has increased from 32.9% in 1996 to 40.5% in 2004. Conclusion: In Malaysia, the prevalence of hypertension is high, but levels of awareness, treatment and control are low. There is an urgent need for a ARTICLE IN PRES

Arctic sea ice data assimilation combining an ensemble Kalman filter with a novel Lagrangian sea ice model for the winter 2019–2020

Advanced data assimilation (DA) methods, widely used in geophysical and climate studies to merge observations with numerical models, can improve state estimates and consequent forecasts. We interface the deterministic ensemble Kalman filter (DEnKF) to the Lagrangian neXt generation Sea Ice Model, neXtSIM. The ensemble is generated by perturbing the atmospheric and oceanic forcing throughout the simulations and randomly initialized ice cohesion. Our ensemble–DA system assimilates sea ice concentration (SIC) from the Ocean and Sea Ice Satellite Application Facility (OSI-SAF) and sea ice thickness (SIT) from the merged CryoSat-2 and SMOS datasets (CS2SMOS). Because neXtSIM is computationally solved on a time-dependent evolving mesh, it is a challenging application for ensemble–DA. As a solution, we perform the DEnKF analysis on a fixed and regular reference mesh, on which model variables are interpolated before the DA and then back to each member's mesh after the DA. We evaluate the impact of assimilating different types of sea ice observations on the model's forecast skills of the Arctic sea ice by comparing satellite observations and a free-run ensemble in an Arctic winter period, 2019–2020. Significant improvements in modeled SIT indicate the importance of assimilating weekly CS2SMOS SIT, while the improvements of SIC and ice extent are moderate but benefit from daily ingestion of the OSI-SAF SIC. For most of the winter, the correlation between SIT and SIC is weaker, which results in little cross-inference between the two variables in the assimilation step. Overall, the ensemble–DA system based on the stand-alone sea ice model demonstrates the feasibility of winter Arctic sea ice prediction with good computational efficiency. These results open the path toward operational implementation and the extension to multi-year assimilation.</p

Prognostic Role of Gene Mutations in Chronic Myelomonocytic Leukemia Patients Treated With Hypomethylating Agents

Somatic mutations contribute to the heterogeneous prognosis of chronic myelomonocytic leukemia (CMML). Hypomethylating agents (HMAs) are active in CMML, but analyses of small series failed to identify mutations predicting response or survival. We analyzed a retrospective multi-center cohort of 174 CMML patients treated with a median of 7 cycles of azacitidine (n = 68) or decitabine (n = 106). Sequencing data before treatment initiation were available for all patients, from Sanger (n = 68) or next generation (n = 106) sequencing. Overall response rate (ORR) was 52%, including complete response (CR) in 28 patients (17%). In multivariate analysis, ASXL1 mutations predicted a lower ORR (Odds Ratio [OR] = 0.85, p = 0.037), whereas TET2mut/ASXL1wt genotype predicted a higher CR rate (OR = 1.18, p = 0.011) independently of clinical parameters. With a median follow-up of 36.7 months, overall survival (OS) was 23.0 months. In multivariate analysis, RUNX1mut (Hazard Ratio [HR] = 2.00, p = .011), CBLmut (HR = 1.90, p = 0.03) genotypes and higher WBC (log10(WBC) HR = 2.30, p = .005) independently predicted worse OS while the TET2mut/ASXL1wt predicted better OS (HR = 0.60, p = 0.05). CMML-specific scores CPSS and GFM had limited predictive power. Our results stress the need for robust biomarkers of HMA activity in CMML and for novel treatment strategies in patients with myeloproliferative features and RUNX1 mutations. Keywords: Chronic myelomonocytic leukemia, Hypomethylating agents, Somatic mutations, Prognosi

Retrospective analysis of pacritinib in patients with myelofibrosis and severe thrombocytopenia

Thrombocytopenia is common in patients with myelofibrosis (MF) and is a well-established adverse prognostic factor. Both of the approved Janus kinase (JAK) inhibitors, ruxolitinib and fedratinib, can worsen thrombocytopenia and have not been evaluated in patients with severe thrombocytopenia (platelet counts \u3c50×109/L). Pacritinib, a novel JAK2/interleukin-1 receptor-associated kinase 1 inhibitor, has been studied in two phase III trials (PERSIST-1 and PERSIST- 2), both of which enrolled patients with MF and severe thrombocytopenia. In order to better characterize treatment outcomes for this population with advanced disease, we present a retrospective analysis of efficacy and safety data in the 189 patients with severe thrombocytopenia treated in the PERSIST studies. The proportion of patients in the pacritinib group meeting efficacy endpoints was greater than in the BAT group for ≥35% spleen volume reduction (23% vs. 2%, P=0.0007), ≥50% modified Total Symptom Score reduction (25% vs. 8%, P=0.044), and self-reported symptom benefit ( much or very much improved; 25% vs. 8%, P=0.016) at the primary analysis time point (week 24). The adverse event profile of pacritinib was manageable, and dose modification was rarely required. There was no excess in bleeding or death in pacritinib-treated patients. These results indicate that pacritinib is a promising treatment for patients with MF who lack safe and effective therapeutic options due to severe thrombocytopenia

CeLAND: search for a 4th light neutrino state with a 3 PBq 144Ce-144Pr electron antineutrino generator in KamLAND

The reactor neutrino and gallium anomalies can be tested with a 3-4 PBq (75-100 kCi scale) 144Ce-144Pr antineutrino beta-source deployed at the center or next to a large low-background liquid scintillator detector. The antineutrino generator will be produced by the Russian reprocessing plant PA Mayak as early as 2014, transported to Japan, and deployed in the Kamioka Liquid Scintillator Anti-Neutrino Detector (KamLAND) as early as 2015. KamLAND's 13 m diameter target volume provides a suitable environment to measure the energy and position dependence of the detected neutrino flux. A characteristic oscillation pattern would be visible for a baseline of about 10 m or less, providing a very clean signal of neutrino disappearance into a yet-unknown, sterile neutrino state. This will provide a comprehensive test of the electron dissaperance neutrino anomalies and could lead to the discovery of a 4th neutrino state for Delta_m^2 > 0.1 eV^2 and sin^2(2theta) > 0.05.Comment: 67 pages, 50 figures. Th. Lasserre thanks the European Research Council for support under the Starting Grant StG-30718

Lower-limb lengths and angles in children older than six years: Reliability and reference values by EOS® stereoradiography

Lower-limb alignment in children is classically assessed clinically or based on conventional radiography, which is associated with projection bias. Low-dose biplanar radiography was described recently as an alternative to conventional imaging. The primary objective of this study was to assess the reliability of length and angle values inferred from 3D reconstructions in children seen in everyday practice. The secondary objective was to obtain reference values for goniometry parameters in children. The paediatric reliability study was done in 18 volunteers who were divided into three groups based on whether they were typically developing (TD) children, had skeletal development abnormalities, or had cerebral palsy. The reference data were obtained in 129 TD children. Each study participant underwent biplanar radiography with 3D reconstruction performed by experts and radiology technicians. Goniometry parameters were computed automatically. Reproducibility was assessed based on the intra-class coefficient (ICC) and the ISO 5725 standard (standard deviation of reproducibility, SDR). For length parameters, the ICCs ranged from 0.94 to 1.00 and the SDR from 2.1 to 3.5 mm. For angle parameters, the ICC and SDR ranges were 0.60–0.95 and 0.9°–4.6°, respectively. No significant differences were found across experts or radiology technicians. Age-specific reference data are reported. These findings confirm the reliability of low-dose biplanar radiography for assessing lower-limb parameters in children seen in clinical practice. In addition, the study provides reference data for commonly measured parameters

JAK2/IDH-mutant–driven myeloproliferative neoplasm is sensitive to combined targeted inhibition

Patients with myeloproliferative neoplasms (MPNs) frequently progress to bone marrow failure or acute myeloid leukemia (AML), and mutations in epigenetic regulators such as the metabolic enzyme isocitrate dehydrogenase (IDH) are associated with poor outcomes. Here, we showed that combined expression of Jak2V617Fand mutant IDH1R132Hor Idh2R140Q induces MPN progression, alters stem/progenitor cell function, and impairs differentiation in mice. Jak2V617FIdh2R140Q–mutant MPNs were sensitive to small-molecule inhibition of IDH. Combined inhibition of JAK2 and IDH2 normalized the stem and progenitor cell compartments in the murine model and reduced disease burden to a greater extent than was seen with JAK inhibition alone. In addition, combined JAK2 and IDH2 inhibitor treatment also reversed aberrant gene expression in MPN stem cells and reversed the metabolite perturbations induced by concurrent JAK2 and IDH2 mutations. Combined JAK2 and IDH2 inhibitor therapy also showed cooperative efficacy in cells from MPN patients with both JAK2mutand IDH2mutmutations. Taken together, these data suggest that combined JAK and IDH inhibition May offer a therapeutic advantage in this high-risk MPN subtype.Damon Runyon Cancer Research Foundation (DRG-2241-15)Howard Hughes Medical Institute (Faculty Scholars Award)Stand Up To CancerNational Cancer Institute (U.S.) (P50CA165962)National Cancer Institute (U.S.) (P30CA14051)Koch Institute for Integrative Cancer Research ( Dana-Farber Harvard Cancer Center Bridge Project)Leukemia & Lymphoma Society of America. Specialized Center of Research (SCOR) ProgramNational Institutes of Health (U.S.) (grant U54OD020355-01)National Institutes of Health (U.S.) (grant NCI R01CA172636)National Institutes of Health (U.S.) (grant R35CA197594)National Cancer Institute (U.S.) (Cancer Center Support Grant (P30 CA008747)

Pegylated interferon alfa-2a for polycythemia vera or essential thrombocythemia resistant or intolerant to hydroxyurea

Prior studies have reported high response rates with recombinant interferon-a (rIFN-a) therapy in patients with essential thrombocythemia (ET) and polycythemia vera (PV). To further define the role of rIFN-a,we investigated the outcomes of pegylated-rIFN-a2a (PEG) therapy in ET and PV patients previously treated with hydroxyurea (HU). The Myeloproliferative Disorders Research Consortium (MPD-RC)-111 study was an investigator-initiated, international, multicenter, phase 2 trial evaluating the ability of PEG therapy to induce complete (CR) and partial (PR) hematologic responses in patients with high-risk ET or PVwho were either refractory or intolerant to HU. The study included 65 patients with ET and 50 patients with PV. The overall response rates (ORRs; CR/PR) at 12 monthswere 69.2%(43.1% and 26.2%) in ET patients and 60% (22% and 38%) in PV patients. CR rates were higher in CALR-mutated ET patients (56.5% vs 28.0%; P 5 .01), compared with those in subjects lacking a CALR mutation. The median absolute reduction in JAK2V617F variant allele fraction was 26% (range, 284%to 47%) in patients achieving a CR vs 14%(range, 218% to 56%) in patients with PR or nonresponse (NR). Therapy was associated with a significant rate of adverse events (AEs); most were manageable, and PEG discontinuation related to AEs occurred in only 13.9% of subjects. We conclude that PEG is an effective therapy for patients with ET or PV who were previously refractory and/or intolerant of HU