A 3-year multicentre randomized controlled trial of etonogestrel- and levonorgestrel-releasing contraceptive implants, with non-randomized matched copper-intrauterine device controls

STUDY QUESTION Is there any difference in the clinical performance of the 3-year one-rod etonogestrel (ENG)- and the 5-year two-rod levonorgestrel (LNG)-releasing contraceptive implants during 3 years of insertion, and between implant and intrauterine device (IUD) contraception, in particular complaints possibly related to hormonal contraceptives? SUMMARY ANSWER The cumulative contraceptive effectiveness after 3 years and method continuation through 2.5 years were not significantly different between ENG and LNG implants, but both outcomes were significantly worse in the non-randomized age-matched group of IUD users than in the combined implant group. WHAT IS KNOWN ALREADY ENG- and LNG-releasing implants are safe and highly efficacious contraceptives with pregnancy rates reported to be 0.0-0.5 per 100 women-years (W-Y). No head-to-head comparative study of the two implants has been undertaken, and little information is available on comparisons of complaints of side effects of implant and copper IUD users. STUDY DESIGN, SIZE, DURATION This was an open parallel group RCT with 1:1 allocation ratio of the ENG and the LNG implants with non-randomized control group of women choosing TCu380A IUD to address lack of reliable data on common side effects typically attributed to the use of progestogen-only contraceptives. After device(s) placement, follow-ups were at 2 weeks, 3 and 6 months, and semi-annually thereafter for 3 years or until pregnancy, removal or expulsion of the implant/IUD occurred. PARTICIPANTS, SETTING, METHODS The study took place in family planning clinics in Brazil, Chile, Dominican Republic, Hungary, Thailand, Turkey and Zimbabwe. Women seeking long-term contraception were enlisted after an eligibility check and informed consent, and 2982 women were enrolled: 1003, 1005 and 974 in the ENG-implant, LNG-implant and IUD groups, respectively; 995, 997 and 971, respectively, were included in the per protocol analysis reported here. MAIN RESULTS AND THE ROLE OF CHANCE ENG and LNG implants each had the same 3-year cumulative pregnancy rate of 0.4 per 100 W-Y [95% confidence interval (CI) 0.1-1.4]. A weight of ≥70 kg at admission was unrelated to pregnancy. Method continuation rates for ENG and LNG implants at 2.5 years were 69.8 (95% CI 66.8-72.6) and 71.8 per 100 W-Y (68.8-74.5), and at 3 years 12.1 (95% CI 5.2-22.0) and 52.0 per 100 W-Y (95% CI 41.8-61.2), respectively. Bleeding disturbances, the most frequent reason for method discontinuation, were significantly more common in the ENG group [16.7 (95% CI 14.4-19.3)] than in the LNG group [12.5 (95% CI 10.5-14.9)] (P 0.019). The 3-year cumulative loss to follow-up was lower in the ENG- than in the LNG-implant group, 8.1 (95% CI 6.4-10.2) and 14.4 per 100 W-Y (95% CI 12.1-17.1), respectively. The median duration of implant removal was 50 s shorter among women with ENG than among women with LNG implant (P < 0.0001). In the observational comparison between IUD and implant users, the 3-year relative risk for pregnancy in IUD group compared with the combined implant group was 5.7 per 100 W-Y (95% CI 4.4-7.3) (P = 0.0003). The 3-year expulsion rate of the IUD was 17.8 per 100 W-Y (95% CI 14.5-21.9), while the discontinuation rate for bleeding disturbances was 8.5 (95% CI 6.7-10.9). Frequency of complaints of headache and dizziness was not significantly different between implant and IUD users (P = 0.16 and 0.77, respectively), acne and bleeding irregularities were more frequent among implant users (P < 0.0001), while heavy bleeding and lower abdominal pain occurred more often among IUD than implant users (P < 0.0001). LIMITATIONS, REASONS FOR CAUTION Few women were ≤19 years old or nulligravida, the proportion of implant users ≥70 kg was <20% and <8% were obese. WIDER IMPLICATIONS OF THE FINDINGS Findings of the study can inform policy makers and clinicians about choice of implant, but also about TCu380A IUD in relation to implants. STUDY FUNDING/COMPETING INTEREST(S) UNDP/UNFPA/WHO/UNICEF/World Bank Special Programme of Research, Development and Research Training in Human Reproduction (HRP), Department of Reproductive Health and Research (RHR), World Health Organization (WHO). This report contains the views of an international expert group and does not necessarily represent the decisions or the stated policy of the WHO. TRIAL REGISTRATION ISRCTN33378571 registered on 22 March 2004. The first participant was enrolled on 12 May 200

Does weight loss improve semen quality and reproductive hormones? results from a cohort of severely obese men

<p>Abstract</p> <p>Background</p> <p>A high body mass index (BMI) has been associated with reduced semen quality and male subfecundity, but no studies following obese men losing weight have yet been published. We examined semen quality and reproductive hormones among morbidly obese men and studied if weight loss improved the reproductive indicators.</p> <p>Methods</p> <p>In this pilot cohort study, 43 men with BMI > 33 kg/m²were followed through a 14 week residential weight loss program. The participants provided semen samples and had blood samples drawn, filled in questionnaires, and had clinical examinations before and after the intervention. Conventional semen characteristics as well as sperm DNA integrity, analysed by the sperm chromatin structure assay (SCSA) were obtained. Serum levels of testosterone, estradiol, sex hormone-binding globulin (SHBG), luteinizing hormone (LH), follicle-stimulating hormone (FSH), anti-Müllerian hormone (AMH) and inhibin B (Inh-B) were measured.</p> <p>Results</p> <p>Participants were from 20 to 59 years of age (median = 32) with BMI ranging from 33 to 61 kg/m². At baseline, after adjustment for potential confounders, BMI was inversely associated with sperm concentration (p = 0.02), total sperm count (p = 0.02), sperm morphology (p = 0.04), and motile sperm (p = 0.005) as well as testosterone (p = 0.04) and Inh-B (p = 0.04) and positively associated to estradiol (p < 0.005). The median (range) percentage weight loss after the intervention was 15% (3.5 - 25.4). Weight loss was associated with an increase in total sperm count (p = 0.02), semen volume (p = 0.04), testosterone (p = 0.02), SHBG (p = 0.03) and AMH (p = 0.02). The group with the largest weight loss had a statistically significant increase in total sperm count [193 millions (95% CI: 45; 341)] and normal sperm morphology [4% (95% CI: 1; 7)].</p> <p>Conclusion</p> <p>This study found obesity to be associated with poor semen quality and altered reproductive hormonal profile. Weight loss may potentially lead to improvement in semen quality. Whether the improvement is a result of the reduction in body weight per se or improved lifestyles remains unknown.</p

Potential Impact of Digital Finance on Small Business Lending: the ‘Fx12’ Case Study

Digital innovation technologies are part of the so-called Digital Transformation (DT); also in the financial sector, DT has become an imperative for companies. A branch of DT is the Digital Finance (DF) and in the last decade, DF (also known as FinTech) has become more and more popular. In a nutshell, DF is the Internet-based generation of traditional finance, and it represents a revolution currently taking place in the financial system; at the same time, FinTech has had an impact on both incumbents, with a change of the business models, and on new competitors, i.e., DF Start-ups. In this exploratory research, a case study has been longitudinally investigated, in which the unit of analysis is a finance firm and not a finance project (i.e., adopting an institutional, and not occasional, point of view). More specifically, the top management of FX12 (Naples, Italy) has been contacted, with several interviews over three months; this start-up was founded in 2019, for assisting the financing of Small and Medium Enterprises (SMEs). The FX12 case study demonstrates that FinTech companies could also support Small Business Lending (SBL), implicating that FinTech can also play a fundamental role in funding local economic growth. Limits of the research and potential developments are then discussed

Adjoint shape optimization coupled with LES-adapted RANS of a U-bend duct for pressure loss reduction

Nowadays, as industrial designs are close to their optimal configurations, the challenge lies in the extraction of the last percentages of improvement. This necessitates accurate evaluations of the performance and represents a significant higher computational cost. The present work aims at integrating Large Eddy Simulations in the optimization framework for an accurate evaluation of the flow field. The number of expensive evaluations is kept to a minimum by using the adjoint method for the evaluation of the gradient of the objective function. Divergence of the gradients due to the chaotic flow motion is avoided by an additional step which decouples the Large Eddy Simulations from the gradient calculations. An adaptation process based on a Reynolds Averaged Navier-Stokes simulation is therefore sought to mimic the more accurate Large Eddy Simulation results. The obtained field is then used in combination with an adjoint shape optimization routine. The method is tested on the design of a U-bend for internal cooling channels by minimizing its pressure loss. Starting from an optimized geometry obtained through a classical approach based on RANS evaluations, further improvements of the design are achieved with the application of the proposed strategy when performances are evaluated by means of LES

A simple fluorescent labeling technique to study virus adsorption in Newcastle disease virus infected cells

The present study demonstrates that the fluorescent general membrane dyes PKH67 and PKH26 are suitable to label Newcastle disease virus, an enveloped virus belonging to the family of paramyxoviridae. Adsorption of the labeled virus particles was tracked, visualized and quantitated using confocal laser scanning microscopy. The specificity of PKH-labeling was determined by colocalization analysis of the PKH signal with NDV-specific immunolabeling, and by using mock-infected controls and infection with detergent-pretreated labeled virus particles. The infectivity of the NDV particles was not affected by the labeling procedure as indicated by the results of a cytotoxicity ATP assay, an apoptosis assay and detection of virus-specific RNA and protein by qPCR and Western blotting, respectively, in cells infected with PKH-labeled and unlabeled virus particles. This technique can be used as an inexpensive, sensitive and rapid alternative method in the analysis of adsorption and internalization of enveloped viruses by the infected cells

LES investigation of Prandtl number effects over a backward facing step and consequences in terms of best practice guidelines for RANS

Liquid metal cooled reactors have been relying on Computational Fluid Dynamics (CFD) analyzes for their design and safety evaluation. However, for industrial simulations using the RANS framework, the major challenge is the modeling of the turbulent heat transfer in the low Prandtl number coolant (Pr ≃ 0.001 − 0.01). More advanced models require to be tested, calibrated and validated on a wide variety of flows to make them applicable to Liquid Metal Reactors (LMR). In this work, Prandtl number effects on the turbulent heat transfer are investigated by carrying out Large-Eddy Simulations (LES) in abruptly separated flows. To simply represent the detached areas and wall interactions that dominate the upper plenum of a LMF, an unconfined Backward-Facing Step (BFS) is chosen as benchmark test-case. To evaluate the accuracy of the LES, wind tunnel tests were performed in air (Pr ≃ 0.71) and in a He-Xe gas mixture (Pr ≃ 0.2), before extending the database to Lead Bismuth-Eutectic (LBE). At such low Prandtl number (Pr = 0.025), large differences in scale are observed between the momentum and the thermal field. The molecular effects previously negligible become significant, to the extent where conduction becomes a major heat transport mechanism. Regarding RANS modeling, a critical review of the widely used Reynolds analogy is proposed by extracting the turbulent Prandtl number from the LES; this parameter varies significantly across the domain. Finally, the performance of several RANS model is assessed by comparison to this reference data and a Best practice guideline is proposed for this type of flows. © 2019 American Nuclear Society. All rights reserved