Preterm-labour-associated preterm birth is a common cause of perinatal mortality and morbidity in twin pregnancy. We aimed to test the hypothesis that the Arabin pessary would reduce ...preterm-labour-associated preterm birth by 40% or greater in women with a twin pregnancy and a short cervix.
We conducted an open-label randomised controlled trial in 57 hospital antenatal clinics in the UK and Europe. From 1 April 2015 to 14 February 2019, 2,228 women with a twin pregnancy underwent cervical length screening between 18 weeks 0 days and 20 weeks 6 days of gestation. In total, 503 women with cervical length ≤ 35 mm were randomly assigned to pessary in addition to standard care (n = 250, mean age 32.4 years, mean cervical length 29 mm, with pessary inserted in 230 women 92.0%) or standard care alone (n = 253, mean age 32.7 years, mean cervical length 30 mm). The pessary was inserted before 21 completed weeks of gestation and removed at between 35 and 36 weeks or before birth if earlier. The primary obstetric outcome, spontaneous onset of labour and birth before 34 weeks 0 days of gestation, was present in 46/250 (18.4%) in the pessary group compared to 52/253 (20.6%) following standard care alone (adjusted odds ratio aOR 0.87 95% CI 0.55-1.38, p = 0.54). The primary neonatal outcome-a composite of any of stillbirth, neonatal death, periventricular leukomalacia, early respiratory morbidity, intraventricular haemorrhage, necrotising enterocolitis, or proven sepsis, from birth to 28 days after the expected date of delivery-was present in 67/500 infants (13.4%) in the pessary group compared to 76/506 (15.0%) following standard care alone (aOR 0.86 95% CI 0.54-1.36, p = 0.50). The positive and negative likelihood ratios of a short cervix (≤35 mm) to predict preterm birth before 34 weeks were 2.14 and 0.83, respectively. A meta-analysis of data from existing publications (4 studies, 313 women) and from STOPPIT-2 indicated that a cervical pessary does not reduce preterm birth before 34 weeks in women with a short cervix (risk ratio 0.74 95% CI 0.50-1.11, p = 0.15). No women died in either arm of the study; 4.4% of babies in the Arabin pessary group and 5.5% of babies in the standard treatment group died in utero or in the neonatal period (p = 0.53). Study limitations include lack of power to exclude a smaller than 40% reduction in preterm labour associated preterm birth, and to be conclusive about subgroup analyses.
These results led us to reject our hypothesis that the Arabin pessary would reduce the risk of the primary outcome by 40%. Smaller treatment effects cannot be ruled out.
ISRCTN Registry ISRCTN 02235181. ClinicalTrials.gov NCT02235181.
Background
In twin pregnancies, the rates of adverse perinatal outcome and subsequent long‐term morbidity are substantial, and mainly result from preterm birth (PTB).
Objectives
To assess the ...effectiveness of progestogen treatment in the prevention of neonatal morbidity or PTB in twin pregnancies using individual participant data meta‐analysis (IPDMA).
Search strategy
We searched international scientific databases, trial registration websites, and references of identified articles.
Selection criteria
Randomised clinical trials (RCTs) of 17–hydroxyprogesterone caproate (17Pc) or vaginally administered natural progesterone, compared with placebo or no treatment.
Data collection and analysis
Investigators of identified RCTs were asked to share their IPD. The primary outcome was a composite of perinatal mortality and severe neonatal morbidity. Prespecified subgroup analyses were performed for chorionicity, cervical length, and prior spontaneous PTB.
Main results
Thirteen trials included 3768 women and their 7536 babies. Neither 17Pc nor vaginal progesterone reduced the incidence of adverse perinatal outcome (17Pc relative risk, RR 1.1; 95% confidence interval, 95% CI 0.97–1.4, vaginal progesterone RR 0.97; 95% CI 0.77–1.2). In a subgroup of women with a cervical length of ≤25 mm, vaginal progesterone reduced adverse perinatal outcome when cervical length was measured at randomisation (15/56 versus 22/60; RR 0.57; 95% CI 0.47–0.70) or before 24 weeks of gestation (14/52 versus 21/56; RR 0.56; 95% CI 0.42–0.75).
Author's conclusions
In unselected women with an uncomplicated twin gestation, treatment with progestogens (intramuscular 17Pc or vaginal natural progesterone) does not improve perinatal outcome. Vaginal progesterone may be effective in the reduction of adverse perinatal outcome in women with a cervical length of ≤25 mm; however, further research is warranted to confirm this finding.
This Letter details a measurement of the ionization yield (Q(y)) of 6.7 keV(40)Ar atoms stopping in a liquid argon detector. The Q(y) of 3.6-6.3 detected e(-)/keV, for applied electric fields in the ...range 240-2130 V/cm, is encouraging for the use of this detector medium to search for the signals from hypothetical dark matter particle interactions and from coherent elastic neutrino-nucleus scattering. A significant dependence of Q(y) on the applied electric field is observed and explained in the context of ion recombination.
Huntington disease (HD) is the most common monogenic neurodegenerative disorder in populations of European ancestry, but occurs at lower prevalence in populations of East Asian or black African ...descent. New mutations for HD result from CAG repeat expansions of intermediate alleles (IAs), usually of paternal origin. The differing prevalence of HD may be related to the rate of new mutations in a population, but no comparative estimates of IA frequency or the HD new mutation rate are available. In this study, we characterize IA frequency and the CAG repeat distribution in fifteen populations of diverse ethnic origin. We estimate the HD new mutation rate in a series of populations using molecular IA expansion rates. The frequency of IAs was highest in Hispanic Americans and Northern Europeans, and lowest in black Africans and East Asians. The prevalence of HD correlated with the frequency of IAs by population and with the proportion of IAs found on the HD‐associated A1 haplotype. The HD new mutation rate was estimated to be highest in populations with the highest frequency of IAs. In European ancestry populations, one in 5,372 individuals from the general population and 7.1% of individuals with an expanded CAG repeat in the HD range are estimated to have a molecular new mutation. Our data suggest that the new mutation rate for HD varies substantially between populations, and that IA frequency and haplotype are closely linked to observed epidemiological differences in the prevalence of HD across major ancestry groups in different countries.
CUORE: a cryogenic underground observatory for rare events Arnaboldi, C; Avignone III, F.T; Beeman, J ...
Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment,
02/2004, Letnik:
518, Številka:
3
Journal Article
Recenzirano
Odprti dostop
CUORE is a proposed tightly packed array of 1000 TeO
2 bolometers, each being a cube
5
cm
on a side with a mass of
760
g
. The array consists of 25 vertical towers, arranged in a square of 5 towers×5 ...towers, each containing 10 layers of four crystals. The design of the detector is optimized for ultralow-background searches: for neutrinoless double-beta decay of
130
Te
(33.8% abundance), cold dark matter, solar axions, and rare nuclear decays. A preliminary experiment involving 20 crystals
3×3×6
cm
3
of
340
g
has been completed, and a single CUORE tower is being constructed as a smaller-scale experiment called CUORICINO. The expected performance and sensitivity, based on Monte Carlo simulations and extrapolations of present results, are reported.
Neighborhood environment attributes of walkability and access to recreation facilities have been related to physical activity and weight status, but most self-report environment measures are lengthy. ...The 17-item PANES (Physical Activity Neighborhood Environment Scale) was developed to be comprehensive but brief enough for use in multipurpose surveys. The current study evaluated test-retest and alternate-form reliability of PANES items compared with multi-item subscales from the longer NEWS-A (Neighborhood Environment Walkability Scale--Abbreviated).
Participants were 291 adults recruited from neighborhoods that varied in walkability in 3 US cities. Surveys were completed twice with a 27-day interval.
Test-retest ICCs for PANES items ranged from .52 to .88. Spearman correlations for the PANES single item vs NEWS-A subscale comparisons ranged from .27 to .81 (all P < .01).
PANES items related to land use mix, residential density, pedestrian infrastructure, aesthetic qualities, and safety from traffic and crime were supported by correlations with NEWS-A subscales. Access to recreation facilities and street connectivity items were not supported. The brevity of PANES allows items to be included in studies or surveillance systems to expand knowledge about neighborhood environments.
Nuclear explosions expose ubiquitous materials to large numbers of neutrons, producing a variety of radioactive isotopes. To simulate such phenomena from both fission and thermonuclear explosions, we ...irradiated 29 different targets with approximately 3 and 14 MeV neutrons and measured the beta-delayed gamma rays using germanium detectors. For each neutron energy, the expected radioisotopes, half-lives, and gamma ray energies were deduced. From measurements of the ratios of activities of the radionuclides produced by neutron irradiations, we were able to identify several materials that are particularly sensitive to the neutron energy spectra.
•Distinguishing nuclear weapons types using radioactive signatures.•Fast neutron activation of ubiquitous materials.•29 different targets irradiated.•8 targets identified that provide unique signature of thermonuclear devices.
Interleukin-17A is considered to be central to the pathogenesis of psoriasis. We evaluated secukinumab, a fully human anti-interleukin-17A monoclonal antibody, in patients with moderate-to-severe ...plaque psoriasis.
In two phase 3, double-blind, 52-week trials, ERASURE (Efficacy of Response and Safety of Two Fixed Secukinumab Regimens in Psoriasis) and FIXTURE (Full Year Investigative Examination of Secukinumab vs. Etanercept Using Two Dosing Regimens to Determine Efficacy in Psoriasis), we randomly assigned 738 patients (in the ERASURE study) and 1306 patients (in the FIXTURE study) to subcutaneous secukinumab at a dose of 300 mg or 150 mg (administered once weekly for 5 weeks, then every 4 weeks), placebo, or (in the FIXTURE study only) etanercept at a dose of 50 mg (administered twice weekly for 12 weeks, then once weekly). The objective of each study was to show the superiority of secukinumab over placebo at week 12 with respect to the proportion of patients who had a reduction of 75% or more from baseline in the psoriasis area-and-severity index score (PASI 75) and a score of 0 (clear) or 1 (almost clear) on a 5-point modified investigator's global assessment (coprimary end points).
The proportion of patients who met the criterion for PASI 75 at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 81.6% with 300 mg of secukinumab, 71.6% with 150 mg of secukinumab, and 4.5% with placebo; in the FIXTURE study, the rates were 77.1% with 300 mg of secukinumab, 67.0% with 150 mg of secukinumab, 44.0% with etanercept, and 4.9% with placebo (P<0.001 for each secukinumab dose vs. comparators). The proportion of patients with a response of 0 or 1 on the modified investigator's global assessment at week 12 was higher with each secukinumab dose than with placebo or etanercept: in the ERASURE study, the rates were 65.3% with 300 mg of secukinumab, 51.2% with 150 mg of secukinumab, and 2.4% with placebo; in the FIXTURE study, the rates were 62.5% with 300 mg of secukinumab, 51.1% with 150 mg of secukinumab, 27.2% with etanercept, and 2.8% with placebo (P<0.001 for each secukinumab dose vs. comparators). The rates of infection were higher with secukinumab than with placebo in both studies and were similar to those with etanercept.
Secukinumab was effective for psoriasis in two randomized trials, validating interleukin-17A as a therapeutic target. (Funded by Novartis Pharmaceuticals; ERASURE and FIXTURE ClinicalTrials.gov numbers, NCT01365455 and NCT01358578, respectively.).
We report the development and testing of an accurate mass–time tag library for plant natural product profiling. Display omitted
► The development of an accurate mass–time tag approach for the ...identification of plant natural products is reported. ► LC/MS and MS/MS data sets were integrated into online spectral search tools and repositories. ► The utility was demonstrated by the detection of active principles in 27 medicinal plant species.
We report the development and testing of an accurate mass–time (AMT) tag approach for the LC/MS-based identification of plant natural products (PNPs) in complex extracts. An AMT tag library was developed for approximately 500 PNPs with diverse chemical structures, detected in electrospray and atmospheric pressure chemical ionization modes (both positive and negative polarities). In addition, to enable peak annotations with high confidence, MS/MS spectra were acquired with three different fragmentation energies. The LC/MS and MS/MS data sets were integrated into online spectral search tools and repositories (Spektraris and MassBank), thus allowing users to interrogate their own data sets for the potential presence of PNPs. The utility of the AMT tag library approach is demonstrated by the detection and annotation of active principles in 27 different medicinal plant species with diverse chemical constituents.
Healing mechanisms are disrupted in complex wounds. Proteases may persist longer in nonhealing wounds. We sought to investigate whether protease activity, protease inhibitor activity, or their ...combinations are independent prognostic factors for healing of complex wounds. We searched MEDLINE, EMBASE, CINAHL, and The Cochrane Library to March 2019. Study selection comprised longitudinal studies assessing the independent effect of proteases, their inhibitors or ratios of the two, on healing of complex wounds, while controlling for confounding factors. Two reviewers independently extracted data and assessed risk of bias. We conducted meta‐analyses separately for proteases, inhibitors, and ratios. We graded the evidence certainty (quality). We identified eight eligible studies in 10 cohorts involving 343 participants. Risk of bias was moderate or high. Elevated protease activity may be associated with less wound healing (standardized mean difference SMD: −0.41, 95% CI −0.72 to −0.11; nine cohorts); and elevated protease inhibitor activity with more healing (SMD: 0.37, 95% CI 0.06‐0.68; five cohorts), this is low certainty evidence. Increased protease: inhibitor ratios may be associated with less healing (SMD −0.47, 95% CI −0.94 to −0.01; four cohorts), but this evidence is of very low certainty. Heterogeneity in protease activity was unexplained by prespecified subgroup analyses for wound type or protease activity status, but partially explained by protease class. Posthoc analysis suggested elevated levels of a particular protease, MMP‐1, may be associated with more healing and other proteases with less healing. This is low/very low certainty evidence. Limitations were small included studies at moderate or high risk of bias, and the use of posthoc analyses. Elevated protease activity and protease: inhibitor ratios may be associated with less healing, and elevated inhibitor levels with more healing. There may be important differences between MMP‐1 and other proteases. High quality research is needed to explore these new findings further.
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