Are we doing enough? Improved breastfeeding practices at 14 weeks but challenges of non-initiation and early cessation of breastfeeding remain: Findings of two consecutive cross-sectional surveys in KwaZulu-Natal, South Africa

Background KwaZulu-Natal (KZN) Initiative for breastfeeding support (KIBS) was a multipronged intervention to support the initiation and sustaining of breastfeeding, implemented between 2014 and 2017. We present results of two surveys conducted before and after KIBS implementation to assess changes in infant feeding practices in KZN over this time period. Methods Two cross-sectional surveys were conducted in primary health care clinics. Multistage stratified random sampling was used to select clinics and participants. Sample size was calculated to provide district estimates of 14-week exclusive breastfeeding (EBF) rates at baseline (KIBS1), and provincial estimates at endpoint (KIBS2). At KIBS1 the sample required was nine participating clinics in each of 11 districts (99 clinics) with 369 participants per district (N = 4059), and at KIBS2 was 30 clinics in KZN with 30 participants per clinic (N = 900). All caregivers aged ≥15 years attending the clinic with infants aged 13- < 16 weeks were eligible to participate. Data was collected using structured interviews on android devices. Multi-variable logistic regression was used to adjust odds ratios for differences between time points. Results At KIBS1 (May2014- March2015), 4172 interviews were conducted with carers, of whom 3659 (87.6%) were mothers. At KIBS2 (January–August 2017), 929 interviews were conducted which included 788 (84.8%) mothers. Among all carers the proportion exclusively breastfeeding was 44.6 and 50.5% (p = 0.1) at KIBS1 and KIBS2 respectively, but greater improvements in EBF were shown among mothers (49.9 vs 59.1: p = 0.02). There were reductions in mixed breastfeeding among all infants (23.2% vs 16.3%; p = 0.016). Although there was no change in the proportion of carers who reported not breastfeeding (31.9% vs 32.8%; p = 0.2), the duration of breastfeeding among mothers who had stopped breastfeeding was longer at KIBS2 compared to KIBS1 (p = 0.0015). Mothers who had returned to work or school were less likely to be breastfeeding (adjusted odds ratio [AOR] 3.76; 95% CI 3.1–4.6), as were HIV positive mothers (AOR 2.1; 95% CI 1.7–2.6). Conclusion Despite improvements to exclusive breastfeeding, failure to initiate and sustain breastfeeding is a challenge to achieving optimal breastfeeding practices. Interventions are required to address these challenges and support breastfeeding particularly among working mothers and HIV positive mothers.publishedVersio

Moving Beyond the 2018 Minimum International Care Considerations for Osteoporosis Management in Duchenne Muscular Dystrophy (DMD)

Individuals living with Duchenne muscular dystrophy (DMD) are at significant risk of bone fragility due to osteoporosis, with the most potent drivers of fragility fractures in this context stemming from the aggressive myopathy and long term oral glucocorticoid therapy. Young people with DMD have a high fracture burden, with reported total and vertebral fracture rates that are four [1, 2] and 535 times [1] higher than those of healthy growing boys, respectively. Vertebral fractures can occur as early as six months following daily glucocorticoid initiation [3]. Up to 75% of young people with DMD sustain at least one fracture after eight years of glucocorticoid therapy [4]. Fractures in DMD can lead to devastating outcomes, including steeper rates of functional decline, premature and permanent loss of ambulation, chronic pain, and even death from fat embolism syndrome or adrenal crisis following long bone fractures [2, 5–8]. The potential for serious consequences and medical complications linked to fractures has driven efforts to develop effective guidelines for timely bone health surveillance and treatment with more recent efforts to develop fracture prevention strategies.To guide clinicians in the management of DMD and its related co-morbidities (including skeletal health), the first internationally-endorsed, minimum standards of care were published in 2010 under the moniker “Clinical Care Considerations” [9, 10]. This document recommends that osteoporosis monitoring include spine x-rays if back pain or kyphosis is present, followed by initiation of intravenous bisphosphonate therapy if vertebral fractures are identified [10]. In the years following the inaugural 2010 Clinical Care Considerations, studies were published showing that vertebral fractures, a key manifestation of bone fragility among children and adults living with glucorticoid-treated chronic conditions, were frequently asymptomatic, necessitating routine surveillance for early detection [3, 11]. It was also better appreciated that even a single long bone fracture can signal osteoporosis in a persistently high-risk setting such as DMD, and prompt initiation of bone protection therapy is important.With this new knowledge, the latest international, minimum standards of clinical care for DMD published in 2018, known as Care Considerations [12–14], recommended routine, standardized spine imaging for early detection of vertebral fractures, combined with more timely bone-targeted (bisphosphonate) intervention in the presence of vertebral or low trauma long bone fractures [12]. At the same time, the ever-changing therapeutic landscape for the treatment of the underlying condition calls for ongoing examination of the intimate relationship between muscle and bone development in DMD, including the effect of different DMD treatment approaches on the skeletal and endocrine systems. The overall goal of such focus is to harvest discussions about optimal management that will foster bone strength and prevent fractures in this high-risk setting across all underlying disease-targeted treatment paradigms for people with DMD

Moving beyond the 2018 minimum international care considerations for osteoporosis management in duchenne muscular dystrophy (DMD): Meeting report from the 3rd International Muscle-Bone Interactions Meeting 7th and 14th November 2022

This current manuscript summarizes the proceedings of the “Third Muscle-bone interactions in Duchenne Muscular Dystrophy Symposium: Moving Beyond the 2018 Minimum International Standards of Care for Osteoporosis Management”, an event co-organized by the World Duchenne Organization (www.worldduchenne.org) and the International Conference on Children’s Bone Health (www.theiscbh.org). This virtual symposium, held on November 7th and 14th 2022, brought together a total of 385 delegates representing 55 countries registered for the symposium, which included 239 clinicians, 70 researchers, 40 patient representatives and others from pharmaceutical companies and regulators. This symposium aimed to review the evidence base that informed the 2018 international minimum Care Considerations, best practices for implementation of these Care Considerations, and emerging knowledge that has arisen from research since the 2018 Care Considerations that shines light on the path forward. The online symposium and this report cover the following areas: 1. Current understanding of the bone morbidity in DMD, especially in relation to conventional glucocorticoid therapy. 2. The published, 2018 minimum international Care Considerations for osteoporosis monitoring and management in DMD. 3. Real world initiatives and challenges in the implementation of the 2018 minimum international Care Considerations for osteoporosis monitoring and management in DMD. 4. The need to consider strategies to move beyond the 2018 minimum international Care Considerations to prevent first fractures in DMD. 5. New therapies in DMD with potential impact on skeletal outcomes

The Eighth Data Release of the Sloan Digital Sky Survey: First Data from SDSS-III

The Sloan Digital Sky Survey (SDSS) started a new phase in August 2008, with new instrumentation and new surveys focused on Galactic structure and chemical evolution, measurements of the baryon oscillation feature in the clustering of galaxies and the quasar Ly alpha forest, and a radial velocity search for planets around ~8000 stars. This paper describes the first data release of SDSS-III (and the eighth counting from the beginning of the SDSS). The release includes five-band imaging of roughly 5200 deg^2 in the Southern Galactic Cap, bringing the total footprint of the SDSS imaging to 14,555 deg^2, or over a third of the Celestial Sphere. All the imaging data have been reprocessed with an improved sky-subtraction algorithm and a final, self-consistent photometric recalibration and flat-field determination. This release also includes all data from the second phase of the Sloan Extension for Galactic Understanding and Evolution (SEGUE-2), consisting of spectroscopy of approximately 118,000 stars at both high and low Galactic latitudes. All the more than half a million stellar spectra obtained with the SDSS spectrograph have been reprocessed through an improved stellar parameters pipeline, which has better determination of metallicity for high metallicity stars.Comment: Astrophysical Journal Supplements, in press (minor updates from submitted version

Erratum: “The eighth data release of the Sloan Digital Sky Survey: first data from SDSS-III” (2011, ApJS, 193, 29)

Section 3.5 of Aihara et al. (2011) described various sources of systematic error in the astrometry of the imaging data of the Sloan Digital Sky Survey (SDSS). In addition to these sources of error, there is an additional and more serious error, which introduces a large systematic shift in the astrometry over a large area around the north celestial pole. The region has irregular boundaries but in places extends as far south as declination δ ≈ 41◦. The sense of the shift is that the positions of all sources in the affected area are offset by roughly 250 mas in a northwest direction. We have updated the SDSS online documentation to reflect these errors, and to provide detailed quality information for each SDSS field

SDSS-III: Massive Spectroscopic Surveys of the Distant Universe, the Milky Way Galaxy, and Extra-Solar Planetary Systems

Building on the legacy of the Sloan Digital Sky Survey (SDSS-I and II), SDSS-III is a program of four spectroscopic surveys on three scientific themes: dark energy and cosmological parameters, the history and structure of the Milky Way, and the population of giant planets around other stars. In keeping with SDSS tradition, SDSS-III will provide regular public releases of all its data, beginning with SDSS DR8 (which occurred in Jan 2011). This paper presents an overview of the four SDSS-III surveys. BOSS will measure redshifts of 1.5 million massive galaxies and Lya forest spectra of 150,000 quasars, using the BAO feature of large scale structure to obtain percent-level determinations of the distance scale and Hubble expansion rate at z<0.7 and at z~2.5. SEGUE-2, which is now completed, measured medium-resolution (R=1800) optical spectra of 118,000 stars in a variety of target categories, probing chemical evolution, stellar kinematics and substructure, and the mass profile of the dark matter halo from the solar neighborhood to distances of 100 kpc. APOGEE will obtain high-resolution (R~30,000), high signal-to-noise (S/N>100 per resolution element), H-band (1.51-1.70 micron) spectra of 10^5 evolved, late-type stars, measuring separate abundances for ~15 elements per star and creating the first high-precision spectroscopic survey of all Galactic stellar populations (bulge, bar, disks, halo) with a uniform set of stellar tracers and spectral diagnostics. MARVELS will monitor radial velocities of more than 8000 FGK stars with the sensitivity and cadence (10-40 m/s, ~24 visits per star) needed to detect giant planets with periods up to two years, providing an unprecedented data set for understanding the formation and dynamical evolution of giant planet systems. (Abridged)Comment: Revised to version published in The Astronomical Journa

Reflections on the 'History and Historians' of the black woman's role in the community of slaves: enslaved women and intimate partner sexual violence

Taking as points of inspiration Peter Parish’s 1989 book, Slavery: History and Historians, and Angela Davis’s seminal 1971 article, “Reflections on the black woman’s role in the community of slaves,” this probes both historiographically and methodologically some of the challenges faced by historians writing about the lives of enslaved women through a case study of intimate partner violence among enslaved people in the antebellum South. Because rape and sexual assault have been defined in the past as non-consensual sexual acts supported by surviving legal evidence (generally testimony from court trials), it is hard for historians to research rape and sexual violence under slavery (especially marital rape) as there was no legal standing for the rape of enslaved women or the rape of any woman within marriage. This article suggests enslaved women recognized that black men could both be perpetrators of sexual violence and simultaneously be victims of the system of slavery. It also argues women stoically tolerated being forced into intimate relationships, sometimes even staying with “husbands” imposed upon them after emancipation

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

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

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