Male Circumcision at Different Ages in Rwanda: A Cost-Effectiveness Study

Agnes Binagwaho and colleagues predict that circumcision of newborn boys would be effective and cost-saving as a long-term strategy to prevent HIV in Rwanda

Defective protein prenylation is a diagnostic biomarker of mevalonate kinase deficiency

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Genetic diversity and population structure of Ascochyta rabiei from the western Iranian Ilam and Kermanshah provinces using MAT and SSR markers

Knowledge of genetic diversity in A. rabiei provides different levels of information that are important in the management of crop germplasm resources. Gene flow on a regional level indicates a significant potential risk for the regional spread of novel alleles that might contribute to fungicide resistance or the breakdown of resistance genes. Simple sequence repeat (SSR) and mating type (MAT) markers were used to determine the genetic structure, and estimate genetic diversity and the prevalence of mating types in 103 Ascochyta rabiei isolates from seven counties in the Ilam and Kermanshah provinces of western Iran (Ilam, Aseman abad, Holaylan, Chardavol, Dareh shahr, Gilangharb, and Sarpul). A set of 3 microsatellite primer pairs revealed a total of 75 alleles; the number of alleles varied from 15 to 34 for each marker. A high level of genetic variability was observed among A. rabiei isolates in the region. Genetic diversity was high (He = 0.788) within populations with corresponding high average gene flow and low genetic distances between populations. The smallest genetic distance was observed between isolates from Ilam and Chardavol. Both mating types were present in all populations, with the majority of the isolates belonging to Mat1-1 (64%), but within populations the proportions of each mating type were not significantly different from 50%. Results from this study will be useful in breeding for Ascochyta blight-resistant cultivars and developing necessary control measures

Diagnosis, extent, impacts, and management of subsoil constraints in the northern grains cropping region of Australia

Productivity of grain crops grown under dryland conditions in north-eastern Australia depends on efficient use of rainfall and available soil moisture accumulated in the period preceding sowing. However, adverse subsoil conditions including high salinity, sodicity, nutrient imbalances, acidity, alkalinity, and high concentrations of chloride (Cl) and sodium (Na) in many soils of the region restrict ability of crop roots to access this stored water and nutrients. Planning for sustainable cropping systems requires identification of the most limiting constraint and understanding its interaction with other biophysical factors. We found that the primary effect of complex and variable combinations of subsoil constraints was to increase the crop lower limit (CLL), thereby reducing plant available water. Among chemical subsoil constraints, subsoil Cl concentration was a more effective indicator of reduced water extraction and reduced grain yields than either salinity or sodicity (ESP). Yield penalty due to high subsoil Cl was seasonally variable, with more in-crop rainfall (ICR) resulting in less negative impact. A conceptual model to determine realistic yield potential in the presence of subsoil Cl was developed from a significant positive linear relationship between CLL and subsoil Cl:Since grid sampling of soil to identify distribution of subsoil Cl, both spatially across landscape and within soil profile, is time-consuming and expensive, we found that electromagnetic induction, coupled with yield mapping and remote sensing of vegetation offers potential to rapidly identify possible subsoil Cl at paddock or farm scale.Plant species and cultivars were evaluated for their adaptations to subsoil Cl. Among winter crops, barley and triticale, followed by bread wheat, were more tolerant of high subsoil Cl concentrations than durum wheat. Chickpea and field pea showed a large decrease in yield with increasing subsoil Cl concentrations and were most sensitive of the crops tested. Cultivars of different winter crops showed minor differences in sensitivity to increasing subsoil Cl concentrations. Water extraction potential of oilseed crops was less affected than cereals with increasing levels of subsoil Cl concentrations. Among summer crops, water extraction potential of millet, mungbean, and sesame appears to be more sensitive to subsoil Cl than that of sorghum and maize; however, the differences were significant only to 0.7 m. Among pasture legumes, lucerne was more tolerant to high subsoil Cl concentrations than the others studied.Surface applied gypsum significantly improved wheat grain yield on soils with ESP >6 in surface soil (0–0.10 m). Subsurface applied gypsum at 0.20–0.30 m depth did not affect grain yield in the first year of application; however, there was a significant increase in grain yield in following years. Better subsoil P and Zn partially alleviated negative impact of high subsoil Cl. Potential savings from improved N fertilisation decisions for paddocks with high subsoil Cl are estimated at ~$AU10 million per annum

Immunosuppressive treatment for proliferative lupus nephritis

Background Cyclophosphamide, in combination with corticosteroids, has been first-line treatment for inducing disease remission for proliferative lupus nephritis, reducing death at five years from over 50% in the 1950s and 1960s to less than 10% in recent years. Several treatment strategies designed to improve remission rates and minimise toxicity have become available. Treatments, including mycophenolate mofetil (MMF) and calcineurin inhibitors, alone and in combination, may have equivalent or improved rates of remission, lower toxicity (less alopecia and ovarian failure) and uncertain effects on death, end-stage kidney disease (ESKD) and infection. This is an update of a Cochrane review first published in 2004 and updated in 2012. Objectives Our objective was to assess the evidence and evaluate the benefits and harms of different immunosuppressive treatments in people with biopsy-proven lupus nephritis. The following questions relating to management of proliferative lupus nephritis were addressed: 1) Are new immunosuppressive agents superior to or as effective as cyclophosphamide plus corticosteroids? 2) Which agents, dosages, routes of administration and duration of therapy should be used? 3) Which toxicities occur with the different treatment regimens? Search methods We searched the Cochrane Kidney and Transplant Specialised Register up to 2 March 2018 with support from the Cochrane Information Specialist using search terms relevant to this review. Studies in the Specialised Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov. Selection criteria Randomised controlled trials (RCTs) and quasi-RCTs comparing any immunosuppressive treatment for biopsy-proven class III, IV, V+III and V+VI lupus nephritis in adult or paediatric patients were included. Data collection and analysis Data were abstracted and the risks of bias were assessed independently by two authors. Dichotomous outcomes were calculated as risk ratio (RR) and measures on continuous scales calculated as mean differences (MD) with 95% confidence intervals (CI). The primary outcomes were death (all causes) and complete disease remission for induction therapy and disease relapse for maintenance therapy. Evidence certainty was determined using GRADE. Main results In this review update, 26 new studies were identified, to include 74 studies involving 5175 participants overall. Twenty-nine studies included children under the age of 18 years with lupus nephritis, however only two studies exclusively examined the treatment of lupus nephritis in patients less than 18 years of age. Induction therapy Sixty-seven studies (4791 participants; median 12 months duration (range 2.5 to 48 months)) reported induction therapy. The effects of all treatment strategies on death (all causes) and ESKD were uncertain (very low certainty evidence) as this outcome occurred very infrequently. Compared with intravenous (IV) cyclophosphamide, MMF may have increased complete disease remission (RR 1.17, 95% CI 0.97 to 1.42; low certainty evidence), although the range of effects includes the possibility of little or no difference. Compared to IV cyclophosphamide, MMF is probably associated with decreased alopecia (RR 0.29, 95% CI 0.19 to 0.46; 170 less (129 less to 194 less) per 1000 people) (moderate certainty evidence), increased diarrhoea (RR 2.42, 95% CI 1.64 to 3.58; 142 more (64 more to 257 more) per 1000 people) (moderate certainty evidence) and may have made little or no difference to major infection (RR 1.02, 95% CI 0.67 to 1.54; 2 less (38 less to 62 more) per 1000 people) (low certainty evidence). It is uncertain ifMMF decreased ovarian failure compared to IV cyclophosphamide because the certainty of the evidence was very low (RR 0.36, 95% CI 0.06 to 2.18; 26 less (39 less to 49 more) per 1000 people). Studies were not generally designed to measure ESKD. MMF combined with tacrolimus may have increased complete disease remission (RR 2.38, 95% CI 1.07 to 5.30; 336 more (17 to 1048 more) per 1000 people (low certainty evidence) compared with IV cyclophosphamide, however the effects on alopecia, diarrhoea, ovarian failure, and major infection remain uncertain. Compared to standard of care, the effects of biologics on most outcomes were uncertain because of low to very low certainty of evidence. Maintenance therapy Nine studies (767 participants; median 30 months duration (range 6 to 63 months)) reported maintenance therapy. In maintenance therapy, disease relapse is probably increased with azathioprine compared with MMF (RR 1.75, 95% CI 1.20 to 2.55; 114 more (30 to 236 more) per 1000 people (moderate certainty evidence).Multiple other interventions were compared as maintenance therapy, but patient-outcome data were sparse leading to imprecise estimates. Authors’ conclusions In this review update, studies assessing treatment for proliferative lupus nephritis were not designed to assess death (all causes) or ESKD. MMF may lead to increased complete disease remission compared with IV cyclophosphamide, with an acceptable adverse event profile, although evidence certainty was low and included the possibility of no difference. Calcineurin combined with lower dose MMF may improve induction of disease remission compared with IV cyclophosphamide, but the comparative safety profile of these therapies is uncertain. Azathioprine may increase disease relapse as maintenance therapy compared with MMF.Internal support - Cochrane Kidney and Transplant, Australia. External support - Cochrane Review Support Programme 2017, UK

Circumcision of Male Children for Reduction of Future Risk for HIV: Acceptability among HIV Serodiscordant Couples in Kampala, Uganda

The ultimate success of medical male circumcision for HIV prevention may depend on targeting male infants and children as well as adults, in order to maximally reduce new HIV infections into the future.We conducted a cross-sectional study among heterosexual HIV serodiscordant couples (a population at high risk for HIV transmission) attending a research clinic in Kampala, Uganda on perceptions and attitudes about medical circumcision for male children for HIV prevention. Correlates of willingness to circumcise male children were assessed using generalized estimating equations methods.318 HIV serodiscordant couples were interviewed, 51.3% in which the female partner was HIV uninfected. Most couples were married and cohabiting, and almost 50% had at least one uncircumcised male child of ≤18 years of age. Overall, 90.2% of male partners and 94.6% of female partners expressed interest in medical circumcision for their male children for reduction of future risk for HIV infection, including 79.9% of men and 87.6% of women who had an uncircumcised male child. Among both men and women, those who were knowledgeable that circumcision reduces men's risk for HIV (adjusted prevalence ratio [APR] 1.34 and 1.14) and those who had discussed the HIV prevention effects of medical circumcision with their partner (APR 1.08 and 1.07) were significantly (p≤0.05) more likely to be interested in male child circumcision for HIV prevention. Among men, those who were circumcised (APR 1.09, p = 0.004) and those who were HIV seropositive (APR 1.09, p = 0.03) were also more likely to be interested in child circumcision for HIV prevention.A high proportion of men and women in Ugandan heterosexual HIV serodiscordant partnerships were willing to have their male children circumcised for eventual HIV prevention benefits. Engaging both parents may increase interest in medical male circumcision for HIV prevention

Home-based subcutaneous immunoglobulin G replacement therapy under real-life conditions in children and adults with antibody deficiency

Background: Subcutaneous immunoglobulin (SCIG) therapy is an alternative to intravenous immunoglobulin (WIG) therapy.Methods: We evaluated the efficacy and safety of the SCIG Vivaglobin (R) (formerly known as Beriglobin (R) SC) under real-life conditions in a post-marketing observational study in 82 patients with primary or secondary antibody deficiencies. Health-related quality of life (HRQoL) was evaluated in a subset of 30 patients previously treated with WIG (including 11 children <14 years) using the Short Form 36 (SF-36) for patients >= 14 years of age (adults) and the Child Health Questionnaire - Parental Form 50 (CHQ-PF50) for children <14 years of age. Treatment preferences were assessed in adults.Results: The mean serum immunoglobulin G (IgG) trough level during SCIG treatment (7.5 g/L) was higher than during previous IVIG treatment (6.6 g/L; p<0.01). The investigators assessed the efficacy of SCIG therapy as "excellent" in 89% of patients. No systemic adverse drug reactions were observed. Improvements by >= 5 points were observed in 5 of 8 SF-36 subscales and in 6 of 12 CHQ-PF50 subscales. Statistically significant improvements (p <= 0.05) were observed for the SF-36 subscales of bodily pain, general health perceptions, and vitality (adults), and for the CHQ-PF50 subscales of general health perceptions, parental impact - time, parental impact - emotional, and family activities (children). Patients preferred SCIG over WIG therapy (92%) and home therapy over therapy at the clinic/physician (83%).Conclusion: This study confirms that therapy with Vivaglobin (R) at home is effective, safe, well tolerated, and improves quality of life in patients with antibody deficiency