Simulations over South Asia using the Weather Research and Forecasting model with Chemistry (WRF-Chem): set-up and meteorological evaluation

The configuration and evaluation of the meteorology is presented for simulations over the South Asian region using the Weather Research and Forecasting model coupled with Chemistry (WRF-Chem). Temperature, water vapor, dew point temperature, zonal and meridional wind components, precipitation and tropopause pressure are evaluated against radiosonde and satellite-borne (AIRS and TRMM) observations along with NCEP/NCAR reanalysis fields for the year 2008. Chemical fields, with focus on tropospheric ozone, are evaluated in a companion paper. The spatial and temporal variability in meteorological variables is well simulated by the model with temperature, dew point temperature and precipitation showing higher values during summer/monsoon and lower during winter. The index of agreement for all the parameters is estimated to be greater than 0.6 indicating that WRF-Chem is capable of simulating the variations around the observed mean. The mean bias (MB) and root mean square error (RMSE) in modeled temperature, water vapor and wind components show an increasing tendency with altitude. MB and RMSE values are within ±2 K and 1–4 K for temperature, 30% and 20–65% for water vapor and 1.6 m s<sup>−1</sup> and 5.1 m s<sup>−1</sup> for wind components. The spatio-temporal variability of precipitation is also reproduced reasonably well by the model but the model overestimates precipitation in summer and underestimates precipitation during other seasons. Such a behavior of modeled precipitation is in agreement with previous studies on South Asian monsoon. The comparison with radiosonde observations indicates a relatively better model performance for inland sites as compared to coastal and island sites. The MB and RMSE in tropopause pressure are estimated to be less than 25 hPa. Sensitivity simulations show that biases in meteorological simulations can introduce errors of ±(10–25%) in simulations of tropospheric ozone, CO and NO<sub>x</sub>. Nevertheless, a comparison of statistical metrics with benchmarks indicates that the model simulated meteorology is of sufficient quality for use in chemistry simulations

Next Generation Sequencing Detects Premeiotic Errors in Human Oocytes

Autosomal aneuploidy is the leading cause of embryonic and foetal death in humans. This arises mainly from errors in meiosis I or II of oogenesis. A largely ignored source of error stems from germinal mosaicism, which leads to premeiotic aneuploidy. Molecular cytogenetic studies employing metaphase fluorescence in situ hybridization and comparative genomic hybridisation suggest that premeiotic aneuploidy may affect 10–20% of oocytes overall. Such studies have been criticised on technical grounds. We report here an independent study carried out on unmanipulated oocytes that have been analysed using next generation sequencing (NGS). This study confirms that the incidence of premeiotic aneuploidy in an unselected series of oocytes exceeds 10%. A total of 140 oocytes donated by 42 women gave conclusive results; of these, 124 (88.5%) were euploid. Sixteen out of 140 (11.4%) provided evidence of premeiotic aneuploidy. Of the 140, 112 oocytes were immature (germinal vesicle or metaphase I), of which 10 were aneuploid (8.93%); the remaining 28 were intact metaphase II-first polar body complexes, and six of these were aneuploid (21.4%). Of the 16 aneuploid cells, half contained simple errors (one or two abnormal chromosomes) and half contained complex errors. We conclude that germinal mosaicism leading to premeiotic aneuploidy is a consistent finding affecting at least 10% of unselected oocytes from women undergoing egg collection for a variety of reasons. The importance of premeiotic aneuploidy lies in the fact that, for individual oocytes, it greatly increases the risk of an aneuploid mature oocyte irrespective of maternal age. As such, this may account for some cases of aneuploid conceptions in very young women

Live birth rate is associated with oocyte yield and number of biopsied and suitable blastocysts to transfer in preimplantation genetic testing (PGT) cycles for monogenic disorders and chromosomal structural rearrangements

OBJECTIVES: To investigate whether live birth (LB) is associated with oocyte yield and number of biopsied and suitable blastocyst to transfer following preimplantation genetic testing (PGT) for monogenic disorders (PGT-M) and chromosomal structural rearrangements (PGT-SR). STUDY DESIGN: All couples underwent controlled ovarian stimulation, blastocyst biopsy, vitrification and transfer of suitable embryo(s) in a frozen embryo transfer (FET) cycle. RESULTS: Of 175 couples who underwent PGT treatment, 249 oocytes retrievals were carried out and 230 FET were subsequently undertaken. 122/230 (53%, 95% CI 47–59) FET resulted in a LB and 16/230 (7%, 95% CI 4–11) have resulted in ongoing pregnancies. 21/230 (9%, 95% CI 6–14) FET resulted in miscarriage and 69/230 (30%, 95% CI 24–36) concluded with failed implantation. Two (1%, 95% CI 0–3) transfers underwent termination for congenital malformation, with no evidence of misdiagnosis by prenatal testing. The relationship between number of oocytes retrieved and number of blastocysts biopsied and suitable embryos to transfer were significant (p = 0.00; Incidence rate ratio (IRR) 1.05; 95% 1.04–1.06; p = 0.00; IRR 1.04; 95%, 1.03–1.06), respectively. The number of oocytes collected (p = 0.007; OR 1.06; 95% CI 1.01–1.10), the number of blastocysts biopsied (p = 0.001; OR 1.14; 95% 95% CI 1.06–1.23) and the number of suitable embryos to transfer (p = 0.00; OR 1.38; 95% CI 1.17–1.64) were all significantly associated with the odds of achieving a LB. There is a 14% and 38% increased chance of a LB per additional blastocyst biopsied and suitable embryo to transfer, respectively. CONCLUSIONS: PGT-M and PGT-SR outcomes are significantly associated with egg yield, number of blastocysts to biopsy and suitable embryos to transfer

Effects of an adapted physical activity program on the physical condition of elderly women: an analysis of efficiency

Background: Specific research tools and designs can assist in identifying the efficiency of physical activity in elderly women. Objectives: To identify the effects of physical activity on the physical condition of older women. Method: A one-year-long physical activity program (123 sessions) was implemented for women aged 60 years or older. Four physical assessments were conducted, in which weight, height, BMI, blood pressure, heart rate, absences, grip strength, flexibility, VO2max, and static and dynamic balance were assessed. The statistical analyses included a repeated measures analysis, both inferential (analysis of variance - ANOVA) and effect size (Cohen's d coefficient), as well as identification of the participants' efficiency (Data Envelopment Analysis - DEA). Results: Despite the observation of differences that depended on the analysis used, the results were successful in the sense that they showed that physical activity adapted to older women can effectively change the decline in physical ability associated with aging, depending on the purpose of the study. The 60-65 yrs group was the most capable of converting physical activity into health benefits in both the short and long term. The >65 yrs group took less advantage of physical activity. Conclusions: Adherence to the program and actual time spent on each type of exercise are the factors that determine which population can benefit from physical activity programs. The DEA allows the assessment of the results related to time spent on physical activity in terms of health concerns. Article registered in Clinicaltrials.gov under number NCT01558401

Stratification of Patients With Sjögren’s Syndrome and Patients With Systemic Lupus Erythematosus According to Two Shared Immune Cell Signatures, With Potential Therapeutic Implications

OBJECTIVE: Similarities in the clinical and laboratory features of patients with primary Sjögren's syndrome (pSS) and systemic lupus erythematosus (SLE) have led to attempts to treat pSS and SLE patients with similar biologic therapeutics. However, the results of many clinical trials are disappointing, and no biologic treatments are licensed in pSS, while few are available for SLE patients with refractory disease. Identifying shared immunological features between pSS and SLE could lead to better treatment selection using a stratification approach. METHODS: Immune-phenotyping of 29 immune-cell subsets in peripheral blood from patients with pSS (n=45), SLE (n=29) and secondary SS associated with SLE (SLE/SS) (n=14) with low disease activity or in clinical remission, and sex-matched healthy controls (n=31), was performed using flow cytometry. Data were analysed using supervised machine learning (balanced random forest, sparse partial least squares discriminant analysis), logistic regression and multiple t-tests. Patients were stratified by k-means clustering, and clinical trajectory analysis. RESULTS: Patients with pSS and SLE had a similar immunological architecture despite having different clinical presentations and prognosis. K-means cluster analysis of the combined pSS, SLE and SLE/SS patient cohorts identified two endotypes characterized by distinct immune-cell profiles which spanned patient diagnoses. Logistic regression and machine learning models identified a signature of eight T-cell subsets that differentiated between the two endotypes with high accuracy (AUC=0.9979). Baseline and five-year clinical trajectory analysis identified differential damage scores and disease activity between the two endotypes. CONCLUSION: An immune-cell toolkit could differentiate patients across diseases with high accuracy for targeted therapeutic approaches

Effort-reward imbalance at work and risk of type 2 diabetes in a national sample of 50,552 workers in Denmark : A prospective study linking survey and register data

Objective: To examine the prospective relation between effort-reward imbalance at work and risk of type 2 diabetes. Methods: We included 50,552 individuals from a national survey of the working population in Denmark, aged 30-64 years and diabetes-free at baseline. Effort-reward imbalance was defined, in accordance with the literature, as a mismatch between high efforts at work (e.g. high work pace, time pressure), and low rewards received in return (e.g. low recognition, job insecurity) and assessed as a continuous and a categorical variable. Incident type 2 diabetes was identified in national health registers. Using Cox regression we calculated hazard ratios (HR) and 95% confidence intervals (95% CI) for estimating the association between effort-reward imbalance at baseline and risk of onset of type 2 diabetes during follow-up, adjusted for sex, age, socioeconomic status, cohabitation, children at home, migration background, survey year and sample method. Results: During 136,239 person-years of follow-up (mean = 2.7 years) we identified 347 type 2 diabetes cases (25.5 cases per 10,000 person-years). For each one standard deviation increase of the effort-reward imbalance score at baseline, the fully adjusted risk of type 2 diabetes during follow-up increased by 9% (HR: 1.09, 95% CI: 0.98-1.21). When we used effort-reward imbalance as a dichotomous variable, exposure to effort-reward imbalance was associated with an increased risk of type 2 diabetes with a HR of 1.27 (95% CI: 1.02-1.58). Conclusion The results of this nationwide study of the Danish workforce suggest that effort-reward imbalance at work may be a risk factor for type 2 diabetes.Peer reviewe

A need for the standardization of the pharmaceutical sector in Libya

Medicines are health technologies that can translate into tangible benefits for numerous acute as well as chronic health conditions. A nation's pharmaceutical sector needs to be appropriately structured and managed in order to ensure a safe, effective and quality supply of medicines to society. The process of medicines management involves the sequential management of five critical activity areas; namely; registration, selection, procurement, distribution and use. Formalized and standardized management of all five critical activity areas positively influences the availability, quality and affordability of medicines and ultimately increases the reliability and quality of the national healthcare system