The relationship of women's status and empowerment with skilled birth attendant use in Senegal and Tanzania.

BackgroundMaternal mortality remains unacceptably high in sub-Saharan Africa with 179,000 deaths occurring each year, accounting for 2-thirds of maternal deaths worldwide. Progress in reducing maternal deaths and increasing Skilled Birth Attendant (SBA) use at childbirth has stagnated in Africa. Although several studies demonstrate the important influences of women's status and empowerment on SBA use, this evidence is limited, particularly in Africa. Furthermore, few studies empirically test the operationalization of women's empowerment and incorporate multidimensional measures to represent the potentially disparate influence of women's status and empowerment on SBA use across settings.MethodsThis study examined the relationship of women's status and empowerment with SBA use in two African countries--Senegal and Tanzania--using the 2010 Demographic and Health Surveys (weighted births n = 10,688 in SN; 6748 in TZ). Factor analysis was first conducted to identify the structure and multiple dimensions of empowerment. Then, a multivariate regression analysis was conducted to examine associations between these empowerment dimensions and SBA use.ResultsOverall, women's status and empowerment were positively related to SBA use. Some sociodemographic characteristics showed similar effects across countries (e.g., age, wealth, residence, marital relationship, parity); however, women's status and empowerment influence SBA use differently by setting. Namely, women's education directly and positively influenced SBA use in Tanzania, but not in Senegal. Further, each of the dimensions of empowerment influenced SBA use in disparate ways. In Tanzania women's higher household decision-making power and employment were related to SBA use, while in Senegal more progressive perceptions of gender norms and older age at first marriage were related to SBA use.ConclusionsThis study provides evidence of the disparate influences of women's status and empowerment on SBA use across settings. Results indicate that efforts to increase SBA use and to reduce maternal mortality through the improvement of women's status and empowerment should focus both on improving girls' education and delaying marriage, as well as transforming gender norms and decision-making power. However, given the multi-dimensional and contextual nature of women's status and empowerment, it is critical to identify key drivers to increase SBA use in a given setting for contextually tailored policy and programming

Reconsidering (in)equality in the use of IUDs in the United States: A closer look across the reproductive life course

Background: Long-acting reversible contraceptives (LARCs), such as the intrauterine device (IUD), have received increased attention for their contraceptive effectiveness and reversibility. Although demographers have long acknowledged the importance of parity and childbearing intentions for contraceptive choice, we know little about how contraceptive use varies across the reproductive life course. Objective: Guided by the expectation that contraceptive method characteristics (e.g., reversibility, effectiveness) contribute to method choice ‒ and that the salience of method characteristics vary by reproductive life stage and education ‒ we investigate variability in IUD use patterns. Methods: We use 2008-2010 and 2011-2013 National Survey of Family Growth data to compare women's IUD-use patterns across educational groups and at three reproductive life stages: before a first birth occurs ("starters"), between births ("spacers"), and after planned childbearing ends altogether ("limiters"). Results: IUD use is more common among spacers than among starters or limiters. Moreover, IUD use is associated with educational advantage among starters and limiters, but not among spacers. Educational differences in IUD use among starters and limiters persist when demographic background characteristics are controlled. Conclusions: Our understanding of variability in IUD use changes considerably when viewing educational gradients through the lens of the reproductive life course. Contribution: We shed new light on variability in IUD use across the reproductive life course. To best support women's contraceptive preferences, it is important to consider the ways in which structural determinants (e.g., education, reproductive health policies and programs) shape women's contraceptive choices at various stages of the reproductive life course

Measurement of and Trends in Unintended Birth in Bangladesh, 1983-2000

Bangladesh has experienced a rapid decline in fertility in the past several decades, facilitated by proactive population policies, provision of contraceptives, and broader societal shifts, encouraging smaller families and use of contraceptive to achieve revised childbearing norms. This paper presents 18 years of data from the Sample Registration System, a demographic surveillance system operated by the Maternal and Child Health-Family Planning Extension Project in six study areas in Bangladesh. Prospective measurements of women\u2019s fertility preferences were used for classifying nearly 25,000 birth outcomes from 1983 to 2000 as intended, unintended, or \u2018up to God/Allah\u2019. Over the 18-year period, the level of unintended births varied from 22% to 38%, with the lowest levels in the mid-1990s. Fatalistic responses declined significantly from 25% in the mid-1980s to 1% by the late 1990s. Results of the comparison of two geographic areas of Bangladesh indicate differential declines in the levels of unintended pregnancies over the study period. Prospective measurements of unintended pregnancies were 2-3 times the magnitude indicated by retrospective estimates of unwanted births from the demographic and health surveys conducted during the study period. This unique dataset provides a rare opportunity to visualize the vast changes in fertility preferences and unintended births in Bangladesh from 1983 to 2000. Significant declines in fatalistic responses reflect broader social changes that occurred in Bangladesh to facilitate the fertility decline and contraceptive uptake. The drastic differences between prospective and retrospective measurements of fertility preferences highlight the importance of considering the strengths and limitations of each method when attempting to estimate the true level of unintended pregnancies and births in a population

Maternal health care seeking by rural Tibetan women: characteristics of women delivering at a newly-constructed birth center in western China

Background: Increasing skilled birth attendance at delivery is key to reducing maternal mortality, particularly among marginalized populations. Despite China’s successful rollout of a national policy to promote facility deliveries, challenges remain among rural and ethnic minority populations. In response, a Tibetan Birth and Training Center (TBTC) was constructed in 2010 to provide high-quality obstetric care in a home-like environment to a predominantly Tibetan population in Tso-ngon (Qinghai) province in western China to improve maternal care in the region. This study examines if and how first users of the TBTC differ from women in the broader community, and how this information may inform subsequent maternal health care interventions in this area. Methods: Trained, Tibetan interviewers administered a face-to-face, quantitative questionnaire to two groups of married, Tibetan women: women who had delivered at the TBTC between June 2011-June 2012 (n = 114) and a non-equivalent comparison group of women from the same communities who had delivered in the last two years, but not at the TBTC (n = 108). Chi-squared and ANOVA tests were conducted to detect differences between the samples. Results: There were no significant differences between the samples in education or income; however, women from the TBTC sample were significantly younger (25.55 vs. 28.16 years; p < 0.001) and had fewer children (1.54 vs. 1.70; p = 0.05). Items measuring maternity health care-seeking and perceived importance of health facility amenities indicated minimal differences between the samples. However, as compared to the community sample, the TBTC sample had a greater proportion of women who reported having the final say regarding where to deliver (26 % vs. 14 %; p = 0.02) and having a friend or family member who delivered at home (50 % vs. 28 %; p < 0.001). Conclusions: Findings did not support the hypothesis that the TBTC attracts lower-income, less-educated women. Minimal differences in women's characteristics and perceptions regarding delivery care between the two samples suggest that the TBTC is serving a broad cross-section of women. Differences between the samples with respect to delivery care decision-making and desire for skilled birth care underscore areas that may be further explored and supported in subsequent efforts to promote facility delivery in this population, and similar populations, of women

Cross-site comparison of ribosomal depletion kits for Illumina RNAseq library construction

Background Ribosomal RNA (rRNA) comprises at least 90% of total RNA extracted from mammalian tissue or cell line samples. Informative transcriptional profiling using massively parallel sequencing technologies requires either enrichment of mature poly-adenylated transcripts or targeted depletion of the rRNA fraction. The latter method is of particular interest because it is compatible with degraded samples such as those extracted from FFPE and also captures transcripts that are not poly-adenylated such as some non-coding RNAs. Here we provide a cross-site study that evaluates the performance of ribosomal RNA removal kits from Illumina, Takara/Clontech, Kapa Biosystems, Lexogen, New England Biolabs and Qiagen on intact and degraded RNA samples. Results We find that all of the kits are capable of performing significant ribosomal depletion, though there are differences in their ease of use. All kits were able to remove ribosomal RNA to below 20% with intact RNA and identify ~ 14,000 protein coding genes from the Universal Human Reference RNA sample at >1FPKM. Analysis of differentially detected genes between kits suggests that transcript length may be a key factor in library production efficiency. Conclusions These results provide a roadmap for labs on the strengths of each of these methods and how best to utilize them. Keywords: RNAseqr; RNA depletion; Illumina; NGS; ABRF; TranscriptomicsNational Cancer Institute (U.S.) (Grant P30-CA14051)National Institute of Environmental Health Sciences (Grant P30-ES002109

Mutations in KEOPS-Complex Genes Cause Nephrotic Syndrome with Primary Microcephaly

Galloway-Mowat syndrome (GAMOS) is an autosomal-recessive disease characterized by the combination of early-onset nephrotic syndrome (SRNS) and microcephaly with brain anomalies. Here we identified recessive mutations in OSGEP, TP53RK, TPRKB, and LAGE3, genes encoding the four subunits of the KEOPS complex, in 37 individuals from 32 families with GAMOS. CRISPR-Cas9 knockout in zebrafish and mice recapitulated the human phenotype of primary microcephaly and resulted in early lethality. Knockdown of OSGEP, TP53RK, or TPRKB inhibited cell proliferation, which human mutations did not rescue. Furthermore, knockdown of these genes impaired protein translation, caused endoplasmic reticulum stress, activated DNA-damage-response signaling, and ultimately induced apoptosis. Knockdown of OSGEP or TP53RK induced defects in the actin cytoskeleton and decreased the migration rate of human podocytes, an established intermediate phenotype of SRNS. We thus identified four new monogenic causes of GAMOS, describe a link between KEOPS function and human disease, and delineate potential pathogenic mechanisms

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population