To analyse preterm birth rates worldwide to assess the incidence of this public health problem, map the regional distribution of preterm births and gain insight into existing assessment strategies.
...Data on preterm birth rates worldwide were extracted during a previous systematic review of published and unpublished data on maternal mortality and morbidity reported between 1997 and 2002. Those data were supplemented through a complementary search covering the period 2003-2007. Region-specific multiple regression models were used to estimate the preterm birth rates for countries with no data.
We estimated that in 2005, 12.9 million births, or 9.6% of all births worldwide, were preterm. Approximately 11 million (85%) of these preterm births were concentrated in Africa and Asia, while about 0.5 million occurred in each of Europe and North America (excluding Mexico) and 0.9 million in Latin America and the Caribbean. The highest rates of preterm birth were in Africa and North America (11.9% and 10.6% of all births, respectively), and the lowest were in Europe (6.2%).
Preterm birth is an important perinatal health problem across the globe. Developing countries, especially those in Africa and southern Asia, incur the highest burden in terms of absolute numbers, although a high rate is also observed in North America. A better understanding of the causes of preterm birth and improved estimates of the incidence of preterm birth at the country level are needed to improve access to effective obstetric and neonatal care.
Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor.
To determine the efficacy and safety of ...abaloparatide, 80 μg, vs placebo for prevention of new vertebral fracture in postmenopausal women at risk of osteoporotic fracture.
The Abaloparatide Comparator Trial In Vertebral Endpoints (ACTIVE) was a phase 3, double-blind, RCT (March 2011-October 2014) at 28 sites in 10 countries. Postmenopausal women with bone mineral density (BMD) T score ≤-2.5 and >-5.0 at the lumbar spine or femoral neck and radiological evidence ≥2 mild or ≥1 moderate lumbar or thoracic vertebral fracture or history of low-trauma nonvertebral fracture within the past 5 years were eligible. Postmenopausal women (>65 y) with fracture criteria and a T score ≤-2.0 and >-5.0 or without fracture criteria and a T score ≤-3.0 and >-5.0 could enroll.
Blinded, daily subcutaneous injections of placebo (n = 821); abaloparatide, 80 μg (n = 824); or open-label teriparatide, 20 μg (n = 818) for 18 months.
Primary end point was percentage of participants with new vertebral fracture in the abaloparatide vs placebo groups. Sample size was set to detect a 4% difference (57% risk reduction) between treatment groups. Secondary end points included change in BMD at total hip, femoral neck, and lumbar spine in abaloparatide-treated vs placebo participants and time to first incident nonvertebral fracture. Hypercalcemia was a prespecified safety end point in abaloparatide-treated vs teriparatide participants.
Among 2463 women (mean age, 69 years range, 49-86), 1901 completed the study. New morphometric vertebral fractures occurred less frequently in the active treatment groups vs placebo. The Kaplan-Meier estimated event rate for nonvertebral fracture was lower with abaloparatide vs placebo. BMD increases were greater with abaloparatide than placebo (all P < .001). Incidence of hypercalcemia was lower with abaloparatide (3.4%) vs teriparatide (6.4%) (risk difference RD, −2.96 95%CI, −5.12 to −0.87; P = .006). table: see text.
Among postmenopausal women with osteoporosis, the use of subcutaneous abaloparatide, compared with placebo, reduced the risk of new vertebral and nonvertebral fractures over 18 months. Further research is needed to understand the clinical importance of RD, the risks and benefits of abaloparatide treatment, and the efficacy of abaloparatide vs other osteoporosis treatments.
clinicaltrials.gov Identifier: NCT01343004.
Herein, the mechanism of catalytic allylic C–H amination reactions promoted by Cp*Rh complexes is reported. Reaction kinetics experiments, stoichiometric studies, and DFT calculations demonstrate ...that the allylic C–H activation to generate a Cp*Rh(π–allyl) complex is viable under mild reaction conditions. The role of external oxidants in the catalytic cycle is elucidated. Quantum mechanical calculations, stoichiometric reactions, and cyclic voltammetry experiments concomitantly support an oxidatively induced reductive elimination process of the allyl fragment with an acetate ligand proceeding through a Rh(IV) intermediate. Stoichiometric oxidation and bulk electrolysis of the proposed π–allyl intermediate are also reported to support these analyses. Lastly, evidence supporting the amination of an allylic acetate intermediate is presented. We show that Cp*Rh(III)2+ behaves as a Lewis acid catalyst to complete the allylic amination reaction.
The quality of life (QOL) of children with developmental coordination disorder (DCD) is largely unknown, but evidence suggests that multiple QOL domains are affected by the disorder. While DCD is ...primarily considered a motor disorder, multiple studies have reported psychological and social concerns in children with this condition. Our primary aim was to present the current state of the evidence regarding the physical, psychological, and social QOL domains that can be affected in children with DCD. Systematic review of articles from seven databases through November 2010 (MEDLINE, EMBASE, CINAHL, PsycINFO, ERIC, CDSR, DARE) was conducted. Search terms included developmental coordination disorder, dyspraxia, quality of life, life satisfaction, well‐being, activities of daily living, and participation. Two independent reviewers screened titles, s, and full‐text articles. Studies meeting the following criteria were selected: (1) sample comprised solely of individuals with coordination difficulties consistent with DCD; (2) outcome measures related to physical, psychological, or socials domains of QOL; and (3) articles published in English. Data were extracted by one author and verified by a second. Outcomes were categorized according to physical, psychological and social domains of QOL and study quality was rated by case definitions of DCD based on diagnostic criteria as per the Diagnostic and Statistical Manual – 4th edition. Forty‐one articles were included. Most studies reported significantly poorer results in physical, psychological and social functioning in children with DCD compared with peers. Despite the impact of DCD on multiple domains, only one study used a QOL measure as an outcome. Although DCD impacts several QOL domains, the QOL of children with this disorder remains largely unknown. The next critical step is for clinicians and researchers to use QOL measures to gather information on how DCD may affect the QOL of children with this disorder.
Geophysical observations indicate that patches of localized fracturing occur within otherwise viscous regions of subduction plate boundaries. These observations place uncertainty on the possible ...down‐dip extent of the seismogenic zone, and as a result the maximum magnitude of subduction thrust earthquakes. However, the processes controlling where and how localized fracturing occurs within otherwise viscous shear zones are unclear. We examined three exposures of exhumed plate boundary on Kyushu, Japan, which contain subducted sediments and hydrated oceanic crust deformed at ∼300 to ∼500°C. These exposures preserve subduction‐related viscous deformation, which in two of the studied exposures has a mutually overprinting relationship with quartz veins, indicating localized cyclical embrittlement. Where observed, fractures are commonly near lithological contacts that form viscosity contrasts. Mineral equilibrium calculations for a metabasalt composition indicate that exposures showing cyclical embrittlement deformed at pressure‐temperature conditions near dehydration reactions that consume prehnite and chlorite. In contrast, dominantly viscous deformation occurred at intervening pressure‐temperature conditions. We infer that at conditions close to metamorphic dehydration reactions, only small stress perturbations are required for transient embrittlement, driven by localized dehydration reactions reducing effective stress, and/or locally increased shear stresses along rheological contrasts. Our results show that the protolith composition of the subducting oceanic lithosphere controls the locations and magnitudes of dehydration reactions, and the viscosity of metamorphosed oceanic crust. Therefore, compositional variations might drive substantial variations in slip style.
Plain Language Summary
Along tectonic plate boundaries, with increasing depth, pressure and temperature, plate movement by brittle fracturing is suppressed, and mechanisms allowing steady slip become more efficient. Along subduction plate boundaries, where one plate sinks beneath another, observations indicate that a proportion of slip sometimes occurs by fracturing at pressure‐temperature conditions where steady slip typically dominates. We use outcrops of an ancient, inactive plate boundary exposed on Kyushu, Japan to investigate the reason for this behavior. We found that chemical reactions, triggered by increasing temperature in sinking oceanic crust, produce water, with the effect of locally raising the fluid pressure within the plate boundary. We suggest that locally raised fluid pressures assist fracturing at pressure‐temperature conditions where steady slip typically dominates. In some outcrops, fractures are especially common along contacts between different rock types, suggesting that mixing of different materials along the plate boundary might also favor fracturing.
Key Points
Brittle fracturing occurred locally within viscously deforming hydrated oceanic crust and subducted sediments
Fracturing is localized at viscosity contrasts and P‐T conditions of metamorphic dehydration reactions
Rocks that deformed at P‐T conditions away from dehydration reactions record dominantly viscous behavior
Tobacco smoke exposure increases the risk and severity of lower respiratory tract infections in children, yet the mechanisms remain unclear. We hypothesized that tobacco smoke exposure would modify ...the lower airway microbiome.
Secondary analysis of a multicenter cohort of 362 children between ages 31 days and 18 years mechanically ventilated for >72 h. Tracheal aspirates from 298 patients, collected within 24 h of intubation, were evaluated via 16 S ribosomal RNA sequencing. Smoke exposure was determined by creatinine corrected urine cotinine levels ≥30 µg/g.
Patients had a median age of 16 (IQR 568) months. The most common admission diagnosis was lower respiratory tract infection (53%). Seventy-four (20%) patients were smoke exposed and exhibited decreased richness and Shannon diversity. Smoke exposed children had higher relative abundances of Serratia spp., Moraxella spp., Haemophilus spp., and Staphylococcus aureus. Differences were most notable in patients with bacterial and viral respiratory infections. There were no differences in development of acute respiratory distress syndrome, days of mechanical ventilation, ventilator free days at 28 days, length of stay, or mortality.
Among critically ill children requiring prolonged mechanical ventilation, tobacco smoke exposure is associated with decreased richness and Shannon diversity and change in microbial communities.
Tobacco smoke exposure is associated with changes in the lower airways microbiome but is not associated with clinical outcomes among critically ill pediatric patients requiring prolonged mechanical ventilation. This study is among the first to evaluate the impact of tobacco smoke exposure on the lower airway microbiome in children. This research helps elucidate the relationship between tobacco smoke exposure and the lower airway microbiome and may provide a possible mechanism by which tobacco smoke exposure increases the risk for poor outcomes in children.
•LBBD for resource allocation problems with monotonic performance measures.•Subproblems that are neither optimization nor verification problems.•The use of simulation modelling to derive strong ...Logic-Based Benders Cuts.•An application to Nursing Home Shift Scheduling problem.•An application to an Airport Check-in Counter Allocation problem.
Operations Research practitioners often want to model complicated functions that are difficult to encode in their underlying optimisation framework. A common approach is to solve an approximate model, and then use a simulation to evaluate the true objective value of one or more solutions. We propose a new approach to integrating simulation into the optimisation model itself. The idea is to run the simulation at each incumbent solution to a master problem. The simulation results are then used to guide the trajectory of the optimisation model itself using logic-based Benders cuts. We test the approach on a class of stochastic resource allocation problems with monotonic performance measures. We derive strong novel Benders cuts that are provably valid for all problems of the given form. We consider two concrete examples: a nursing home shift scheduling problem, and an airport check in counter allocation problem. While previous papers on these applications could only approximately solve realistic instances, we are able to solve them exactly within a reasonable amount of time. Moreover, while those papers account for the inherent variance of the problem by including estimates of the underlying random variables as model parameters, we are able to compute sample-average approximations to optimality with up to 100 scenarios.
There are limited data on the efficacy of vaccination against confirmed influenza in pregnant women with and those without human immunodeficiency virus (HIV) infection and protection of their ...infants.
We conducted two double-blind, randomized, placebo-controlled trials of trivalent inactivated influenza vaccine (IIV3) in South Africa during 2011 in pregnant women infected with HIV and during 2011 and 2012 in pregnant women who were not infected. The immunogenicity, safety, and efficacy of IIV3 in pregnant women and their infants were evaluated until 24 weeks after birth. Immune responses were measured with a hemagglutination inhibition (HAI) assay, and influenza was diagnosed by means of reverse-transcriptase-polymerase-chain-reaction (RT-PCR) assays of respiratory samples.
The study cohorts included 2116 pregnant women who were not infected with HIV and 194 pregnant women who were infected with HIV. At 1 month after vaccination, seroconversion rates and the proportion of participants with HAI titers of 1:40 or more were higher among IIV3 recipients than among placebo recipients in both cohorts. Newborns of IIV3 recipients also had higher HAI titers than newborns of placebo recipients. The attack rate for RT-PCR-confirmed influenza among both HIV-uninfected placebo recipients and their infants was 3.6%. The attack rates among HIV-uninfected IIV3 recipients and their infants were 1.8% and 1.9%, respectively, and the respective vaccine-efficacy rates were 50.4% (95% confidence interval CI, 14.5 to 71.2) and 48.8% (95% CI, 11.6 to 70.4). Among HIV-infected women, the attack rate for placebo recipients was 17.0% and the rate for IIV3 recipients was 7.0%; the vaccine-efficacy rate for these IIV3 recipients was 57.7% (95% CI, 0.2 to 82.1).
Influenza vaccine was immunogenic in HIV-uninfected and HIV-infected pregnant women and provided partial protection against confirmed influenza in both groups of women and in infants who were not exposed to HIV. (Funded by the Bill and Melinda Gates Foundation and others; ClinicalTrials.gov numbers, NCT01306669 and NCT01306682.).
Periodontal Ehlers-Danlos Syndrome (pEDS) is a rare autosomal dominant type of EDS characterised by severe early-onset periodontitis, lack of attached gingiva, pretibial plaques, joint hypermobility ...and skin hyperextensibility as per the 2017 International EDS Classification. In 2016, deleterious pathogenic heterozygous variants were identified in
and
, which encode components of the complement system.
Individuals with a clinical suspicion of pEDS were clinically and molecularly assessed through the National EDS Service in London and Sheffield and in genetic services in Austria, Sweden and Australia. Transmission electron microscopy and fibroblast studies were performed in a small subset of patients.
A total of 21 adults from 12 families were clinically and molecularly diagnosed with pEDS, with
variants in all families. The age at molecular diagnosis ranged from 21-73 years (mean 45 years), male: female ratio 5:16. Features of easy bruising (90%), pretibial plaques (81%), skin fragility (71%), joint hypermobility (24%) and vocal changes (38%) were identified as well as leukodystrophy in 89% of those imaged.
This cohort highlights the clinical features of pEDS in adults and contributes several important additional clinical features as well as novel deleterious variants to current knowledge. Hypothetical pathogenic mechanisms which may help to progress understanding and management of pEDS are also discussed.
We present a full high resolution SPIRE FTS spectrum of the nearby ultraluminous infrared galaxy Mrk 231. In total 25 lines are detected, including CO J = 5–4 through J = 13–12, 7 rotational lines of ...H2O, 3 of OH+ and one line each of H2O+, CH+, and HF. We find that the excitation of the CO rotational levels up to J = 8 can be accounted for by UV radiation from star formation. However, the approximately flat luminosity distribution of the CO lines over the rotational ladder above J = 8 requires the presence of a separate source of excitation for the highest CO lines. We explore X-ray heating by the accreting supermassive black hole in Mrk 231 as a source of excitation for these lines, and find that it can reproduce the observed luminosities. We also consider a model with dense gas in a strong UV radiation field to produce the highest CO lines, but find that this model strongly overpredicts the hot dust mass in Mrk 231. Our favoured model consists of a star forming disk of radius 560 pc, containing clumps of dense gas exposed to strong UV radiation, dominating the emission of CO lines up to J = 8. X-rays from the accreting supermassive black hole in Mrk 231 dominate the excitation and chemistry of the inner disk out to a radius of 160 pc, consistent with the X-ray power of the AGN in Mrk 231. The extraordinary luminosity of the OH+ and H2O+ lines reveals the signature of X-ray driven excitation and chemistry in this region.
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