2·6 million pregnancies were estimated to have ended in stillbirth in 2015. The aim of the AFFIRM study was to test the hypothesis that introduction of a reduced fetal movement (RFM), care package ...for pregnant women and clinicians that increased women's awareness of the need for prompt reporting of RFM and that standardised management, including timely delivery, would alter the incidence of stillbirth.
This stepped wedge, cluster-randomised trial was done in the UK and Ireland. Participating maternity hospitals were grouped and randomised, using a computer-generated allocation scheme, to one of nine intervention implementation dates (at 3 month intervals). This date was concealed from clusters and the trial team until 3 months before the implementation date. Each participating hospital had three observation periods: a control period from Jan 1, 2014, until randomised date of intervention initiation; a washout period from the implementation date and for 2 months; and the intervention period from the end of the washout period until Dec 31, 2016. Treatment allocation was not concealed from participating women and caregivers. Data were derived from observational maternity data. The primary outcome was incidence of stillbirth. The primary analysis was done according to the intention-to-treat principle, with births analysed according to whether they took place during the control or intervention periods, irrespective of whether the intervention had been implemented as planned. This study is registered with www.ClinicalTrials.gov, number NCT01777022.
37 hospitals were enrolled in the study. Four hospitals declined participation, and 33 hospitals were randomly assigned to an intervention implementation date. Between Jan 1, 2014, and Dec, 31, 2016, data were collected from 409 175 pregnancies (157 692 deliveries during the control period, 23 623 deliveries in the washout period, and 227 860 deliveries in the intervention period). The incidence of stillbirth was 4·40 per 1000 births during the control period and 4·06 per 1000 births in the intervention period (adjusted odds ratio aOR 0·90, 95% CI 0·75–1·07; p=0·23).
The RFM care package did not reduce the risk of stillbirths. The benefits of a policy that promotes awareness of RFM remains unproven.
Chief Scientist Office, Scottish Government (CZH/4/882), Tommy's Centre for Maternal and Fetal Health, Sands.
ABSTRACT
Classical novae are shock-powered multiwavelength transients triggered by a thermonuclear runaway on an accreting white dwarf. V1674 Her is the fastest nova ever recorded (time to declined ...by two magnitudes is t2 = 1.1 d) that challenges our understanding of shock formation in novae. We investigate the physical mechanisms behind nova emission from GeV γ-rays to cm-band radio using coordinated Fermi-LAT, NuSTAR, Swift, and VLA observations supported by optical photometry. Fermi-LAT detected short-lived (18 h) 0.1–100 GeV emission from V1674 Her that appeared 6 h after the eruption began; this was at a level of (1.6 ± 0.4) × 10−6 photons cm−2 s−1. Eleven days later, simultaneous NuSTAR and Swift X-ray observations revealed optically thin thermal plasma shock-heated to kTshock = 4 keV. The lack of a detectable 6.7 keV Fe Kα emission suggests super-solar CNO abundances. The radio emission from V1674 Her was consistent with thermal emission at early times and synchrotron at late times. The radio spectrum steeply rising with frequency may be a result of either free-free absorption of synchrotron and thermal emission by unshocked outer regions of the nova shell or the Razin–Tsytovich effect attenuating synchrotron emission in dense plasma. The development of the shock inside the ejecta is unaffected by the extraordinarily rapid evolution and the intermediate polar host of this nova.
Cassini observations of Titan's weather patterns over >13 years, almost half a Saturnian year, provide insight into seasonal circulation patterns and the methane cycle. The Imaging Science Subsystem ...and the Visual and Infrared Mapping Spectrometer documented cloud locations, characteristics, morphologies, and behavior. Clouds were generally more prevalent in the summer hemisphere, but there were surprises in locations and timing of activity: Southern clouds were common at midlatitudes, northern clouds initially appeared much sooner than model predictions, and north polar summer convective systems did not appear before the mission ended. Differences from expectations constrain atmospheric circulation models, revealing factors that best match observations, including the roles of surface and subsurface reservoirs. The preference for clouds at mid‐northern latitudes rather than near the pole is consistent with models that include widespread polar near‐surface methane reservoirs in addition to the lakes and seas, suggesting a broader subsurface methane table is accessible to the atmosphere.
Plain Language Summary
We monitored methane clouds in the atmosphere of Saturn's moon Titan for over 13 years, using images from the Cassini spacecraft. The observations cover almost half of Titan's year, showing how weather patterns changed from late southern summer to northern summer (approximately mid‐January through late June on Earth). During southern summer, extensive clouds and, on one occasion, rainfall were observed near Titan's south pole. But surprisingly, this weather pattern did not repeat at the north pole in northern summer. By comparing weather observations to atmospheric models, we can determine sources for the moisture in the atmosphere. Our analysis shows that, in addition to Titan's lakes and seas, there may also be liquid beneath the surface near both poles. This result is consistent with other evidence that suggests there may be underground connections between some of the lakes and seas. Knowing there may be more liquid below Titan's surface helps explain how methane is supplied to the atmosphere and how Titan's methane cycle works (similar to Earth's water cycle: evaporation, cloud formation, rain, and surface collection into rivers, lakes, and oceans). With the end of the Cassini mission, Earth‐based telescopes will continue to watch for large clouds on Titan.
Key Points
Cassini's Imaging Science Subsystem and Visual and Infrared Mapping Spectrometer documented tropospheric clouds on Titan for over 13 years
Meteorological activity generally followed Titan's seasons but showed key differences from model predictions in timing and cloud locations
Comparison to models suggests broad polar subsurface methane reservoirs are accessible to the atmosphere in addition to the lakes and seas
The aim of these guidelines is to provide recommendations for decolonizing regimens targeting multidrug-resistant Gram-negative bacteria (MDR-GNB) carriers in all settings.
These evidence-based ...guidelines were produced after a systematic review of published studies on decolonization interventions targeting the following MDR-GNB: third-generation cephalosporin-resistant Enterobacteriaceae (3GCephRE), carbapenem-resistant Enterobacteriaceae (CRE), aminoglycoside-resistant Enterobacteriaceae (AGRE), fluoroquinolone-resistant Enterobacteriaceae (FQRE), extremely drug-resistant Pseudomonas aeruginosa (XDRPA), carbapenem-resistant Acinetobacter baumannii (CRAB), cotrimoxazole-resistant Stenotrophomonas maltophilia (CRSM), colistin-resistant Gram-negative organisms (CoRGNB), and pan-drug-resistant Gram-negative organisms (PDRGNB). The recommendations are grouped by MDR-GNB species. Faecal microbiota transplantation has been discussed separately. Four types of outcomes were evaluated for each target MDR-GNB:(a) microbiological outcomes (carriage and eradication rates) at treatment end and at specific post-treatment time-points; (b) clinical outcomes (attributable and all-cause mortality and infection incidence) at the same time-points and length of hospital stay; (c) epidemiological outcomes (acquisition incidence, transmission and outbreaks); and (d) adverse events of decolonization (including resistance development). The level of evidence for and strength of each recommendation were defined according to the GRADE approach. Consensus of a multidisciplinary expert panel was reached through a nominal-group technique for the final list of recommendations.
The panel does not recommend routine decolonization of 3GCephRE and CRE carriers. Evidence is currently insufficient to provide recommendations for or against any intervention in patients colonized with AGRE, CoRGNB, CRAB, CRSM, FQRE, PDRGNB and XDRPA. On the basis of the limited evidence of increased risk of CRE infections in immunocompromised carriers, the panel suggests designing high-quality prospective clinical studies to assess the risk of CRE infections in immunocompromised patients. These trials should include monitoring of development of resistance to decolonizing agents during treatment using stool cultures and antimicrobial susceptibility results according to the EUCAST clinical breakpoints.
Patients with advanced salivary gland mucoepidermoid carcinoma (MEC) are treated with surgery and radiotherapy, as current systemic therapies are largely ineffective. As such, current treatment ...frequently leads to poor long-term survival due to locoregional recurrence or metastases. We have shown that salivary gland cancer stem cells (CSCs) are resistant to platinum-based chemotherapy and drive tumor progression. The purpose of this study was to investigate the effect of therapeutic inhibition of mTOR (mechanistic target of rapamycin) on resistance of CSCs to cisplatin, a prototypic platinum-based chemotherapeutic agent. Viability assays determined the effect of several inhibitors of PI3k/mTOR signaling (e.g., temsirolimus, BKM120, AZD8055, PF4708671) and/or cisplatin on survival of human MEC cells. The impact of mTOR inhibitors and/or cisplatin on MEC stemness was examined with salisphere assays, flow cytometry for ALDH/CD44 (CSC markers for MEC), and Western blots for Bmi-1 expression (marker of stem cell self-renewal). Salivary gland MEC patient-derived xenografts were used to examine the effect of cisplatin and/or temsirolimus on CSCs in vivo. We observed that cisplatin induced mTOR and S6K1 phosphorylation, increased the number and size of MEC salispheres, and induced Bmi-1 expression and the fraction of CSCs in MEC models in vitro. Cisplatin also increased the fraction of CSCs in vivo. In contrast, mTOR inhibition (e.g., temsirolimus) blocked cisplatin-induced Bmi-1 expression and salisphere formation in vitro. Remarkably, temsirolimus slowed down tumor growth and decreased the fraction of CSCs (P < 0.05) even in presence of cisplatin in a short-term in vivo experiment. Collectively, these results demonstrate that therapeutic inhibition of mTOR ablates cytotoxic-resistant CSCs, and they suggest that a combination of an mTOR inhibitor and platinum-based chemotherapy might be beneficial to patients with salivary gland mucoepidermoid carcinoma.
Background Epidemiologic evidence indicates that aspirin use is associated with reduced risks of colon cancer and possibly several other cancers, including prostate and breast cancers. Recent results ...from the Women's Health Study randomized trial indicate that long-term use of low-dose aspirin (100 mg every other day) does not substantially reduce cancer risk. However, the potential effect of long-term daily use of higher doses of aspirin on cancer incidence remains uncertain. Methods We examined associations between long-term daily use of adult-strength aspirin (≥325 mg/day) and both overall cancer incidence and incidence of 10 types of cancer among 69810 men and 76303 women participating in the Cancer Prevention Study II Nutrition Cohort, a relatively elderly population. Aspirin use was reported at enrollment in 1992–1993 and updated in 1997, 1999, and 2001. Multivariable Cox proportional hazards regression was used to calculate rate ratios (RRs). Results During follow-up through June 2003, 10931 men and 7196 women were diagnosed with cancer. Long-term (≥5 years) daily use of adult-strength aspirin, compared with no use, was associated with lower overall cancer incidence in men (multivariable-adjusted RR = 0.84, 95% confidence interval CI = 0.76 to 0.93) and non–statistically significantly lower overall cancer incidence in women (multivariable-adjusted RR = 0.86, 95% CI = 0.73 to 1.03). Overall cancer incidence per 100000 person-years (standardized to the age distributions of men and women in the study) with long-term daily aspirin use and no aspirin use was 1858 and 2163, respectively, among men and 1083 and 1169, respectively, among women. Long-term daily aspirin use was associated with lower incidence of colorectal cancer (RR = 0.68, 95% CI = 0.52 to 0.90 among men and women combined) and prostate cancer (RR = 0.81, 95% CI = 0.70 to 0.94) and a non–statistically significant lower risk of female breast cancer (RR = 0.83, 95% CI = 0.63 to 1.10). Conclusions Long-term daily use of adult-strength aspirin may be associated with modestly reduced overall cancer incidence in populations among whom colorectal, prostate, and breast cancers are common.
This is a study on the tribological behaviour of ZnO nanoparticles as an additive to a polyalphaolefin (PAO6) and on the influence of dispersing agents (OL100 and OL300). Anti-wear tests were run on ...a Falex Roxana four-ball machine and EP properties were obtained using a Stanhope Seta Shell Four-Ball EP Lubricant Tester. Ensuing SEM and EDS analysis of the worn surface highlighted a number of conclusions: OL300 has better dispersant properties than OL100; OL100 and OL300 are potentially useful as wear reducer additives in PAO6; formation of aggregates was found for 1 and 1.5% of ZnO in PAO6
+
3% OL300 suspension, and these non-coated ZnO nanoparticles had an abrasive behaviour in the AW region, despite their lower hardness compared to steel surfaces; ZnO nanoparticles do not act as anti-wear agent under certain conditions but in EP conditions, from the initial seizure load, they decrease wear; the EP behaviour improvement of PAO6
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1% OL300
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ZnO mixtures was related to the increase of ZnO nanoparticle concentration and their surface deposition on the wear scar surface; PAO6
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3% OL300
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0.3% ZnO displayed the best EP behaviour in PAO6
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3% OL300
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ZnO mixtures, while PAO6
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3% OL300
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1% ZnO and PAO6
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3% OL300
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3% ZnO were worse, despite Zn deposition on the wear scar surface.
The relationship of magnetic clouds (MCs) to interplanetary coronal mass ejections (ICMEs) is still an open issue in space research. The view that all ICMEs would originate as magnetic flux ropes has ...received increasing attention, although near the orbit of the Earth only about one-third of ICMEs show clear MC signatures and often the MC occupies only a portion of the more extended region showing ICME signatures. In this work we analyze 79 events between 1996 and 2009 reported in existing ICME/MC catalogs (Wind magnetic cloud list and the Richardson and Cane ICME list) using near-Earth observations by ACE (Advanced Composition Explorer) and Wind. We perform a systematic comparison of cases where ICME and MC signatures coincided and where ICME signatures extended significantly beyond the MC boundaries. We find clear differences in the characteristics of these two event types. In particular, the events where ICME signatures continued more than 6 h past the MC rear boundary had 2.7 times larger speed difference between the ICME's leading edge and the preceding solar wind, 1.4 times higher magnetic fields, 2.1 times larger widths and they experienced three times more often strong expansion than the events for which the rear boundaries coincided. The events with significant mismatch in MC and ICME boundary times were also embedded in a faster solar wind and the majority of them were observed close to the solar maximum. Our analysis shows that the sheath, the MC and the regions of ICME-related plasma in front and behind the MC have different magnetic field, plasma and charge state characteristics, thus suggesting that these regions separate already close to the Sun. Our study shows that the geometrical effect (the encounter through the CME leg and/or far from the flux rope center) does not contribute much to the observed mismatch in the MC and ICME boundary times.
We identify stellar structures in the PHANGS sample of 74 nearby galaxies and construct morphological masks of sub-galactic environments based on
Spitzer
3.6
μ
m images. At the simplest level, we ...distinguish five environments: centres, bars, spiral arms, interarm regions, and discs without strong spirals. Slightly more sophisticated masks include rings and lenses, which are publicly released but not explicitly used in this paper. We examine trends with environment in the molecular gas content, star formation rate, and depletion time using PHANGS–ALMA CO(2–1) intensity maps and tracers of star formation. The interarm regions and discs without strong spirals clearly dominate in area, whereas molecular gas and star formation are quite evenly distributed among the five basic environments. We reproduce the molecular Kennicutt–Schmidt relation with a slope compatible with unity within the uncertainties and without significant slope differences among environments. In contrast to what has been suggested by early studies, we find that bars are not always deserts devoid of gas and star formation, but instead they show large diversity. Similarly, spiral arms do not account for most of the gas and star formation in disc galaxies, and they do not have shorter depletion times than the interarm regions. Spiral arms accumulate gas and star formation, without systematically boosting the star formation efficiency. Centres harbour remarkably high surface densities and on average shorter depletion times than other environments. Centres of barred galaxies show higher surface densities and wider distributions compared to the outer disc; yet, depletion times are similar to unbarred galaxies, suggesting highly intermittent periods of star formation when bars episodically drive gas inflow, without enhancing the central star formation efficiency permanently. In conclusion, we provide quantitative evidence that stellar structures in galaxies strongly affect the organisation of molecular gas and star formation, but their impact on star formation efficiency is more subtle.
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