Objective
To determine the risk of spontaneous and medically indicated preterm birth associated with mode of birth in previous term‐born pregnancy.
Design
Retrospective cohort study.
Setting
Two UK ...maternity units.
Population or sample
A total of 16 340 women with first two consecutive singleton births and the first birth at term.
Methods
Retrospective cohort study using routinely collected clinical data.
Main outcome measures
Incidence of spontaneous preterm birth and medically indicated preterm birth at less than 37 weeks of gestation after term birth, in relation to mode of birth in first pregnancy. Subgroup analysis on cervical dilatation at the time of first caesarean birth.
Results
Compared with vaginal birth, emergency caesarean birth at full dilatation was associated with an increase in spontaneous preterm birth (2.3% vaginal birth versus 4.5% full dilatation caesarean; adjusted odds ratio aOR 3.29, 95% CI 2.02–5.13, P < 0.001). Elective caesarean, emergency caesarean at <4 cm dilatation, and emergency caesarean at 4–9 cm dilatation were associated with increased medically indicated preterm birth (0.8% vaginal births versus 1.9% elective caesarean, 3.3% <4 cm caesarean, 1.3% 4–9 cm caesarean; aOR 2.30, 95% CI 1.19–4.15, P = 0.009; aOR 4.68, 95% CI 2.98–7.24, P < 0.001; and aOR 2.43, 95% CI 1.43–4.00, P = 0.001, respectively).
Conclusions
Term caesarean in the first stage of labour or performed prelabour is associated with medically indicated preterm birth. Term caesarean in the second stage of labour is associated with spontaneous preterm birth.
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Caesarean in the second stage of labour is associated with spontaneous preterm birth.
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Caesarean in the second stage of labour is associated with spontaneous preterm birth.
Alterations involving the RET kinase are implicated in the pathogenesis of lung, thyroid and other cancers. However, the clinical activity of multikinase inhibitors (MKIs) with anti-RET activity in ...RET-altered patients appears limited, calling into question the therapeutic potential of targeting RET. LOXO-292 is a selective RET inhibitor designed to inhibit diverse RET fusions, activating mutations and acquired resistance mutations.
Potent anti-RET activity, high selectivity, and central nervous system coverage were confirmed preclinically using a variety of in vitro and in vivo RET-dependent tumor models. Due to clinical urgency, two patients with RET-altered, MKI-resistant cancers were treated with LOXO-292, utilizing rapid dose-titration guided by real-time pharmacokinetic assessments to achieve meaningful clinical exposures safely and rapidly.
LOXO-292 demonstrated potent and selective anti-RET activity preclinically against human cancer cell lines harboring endogenous RET gene alterations; cells engineered to express a KIF5B-RET fusion protein −/+ the RET V804M gatekeeper resistance mutation or the common RET activating mutation M918T; and RET-altered human cancer cell line and patient-derived xenografts, including a patient-derived RET fusion-positive xenograft injected orthotopically into the brain. A patient with RET M918T-mutant medullary thyroid cancer metastatic to the liver and an acquired RET V804M gatekeeper resistance mutation, previously treated with six MKI regimens, experienced rapid reductions in tumor calcitonin, CEA and cell-free DNA, resolution of painful hepatomegaly and tumor-related diarrhea and a confirmed tumor response. A second patient with KIF5B-RET fusion-positive lung cancer, acquired resistance to alectinib and symptomatic brain metastases experienced a dramatic response in the brain, and her symptoms resolved.
These results provide proof-of-concept of the clinical actionability of RET alterations, and identify selective RET inhibition by LOXO-292 as a promising treatment in heavily pretreated, multikinase inhibitor-experienced patients with diverse RET-altered tumors.
Gram-negative
bacteria have a dual lifestyle: they are mutualists of
nematodes and are pathogens of insects. Together, this nematode–bacterium partnership has been used to successfully control a wide ...range of agricultural insect pests.
produce a diverse array of small molecules that play key biological roles in regulating their dual roles. In particular, several secondary metabolites (SM) produced by this bacterium are known to play a critical role in the maintenance of a monoxenic infection in the insect host and are also known to prevent contamination of the cadaver from soil microbes and/or predation by arthropods. A few of the SM this bacteria produce have been isolated and identified, and their biological activities have also been tested in laboratory assays. Over the past two decades, analyses of the genomes of several
spp. have revealed the presence of SM numerous gene clusters that comprise more than 6% of these bacteria genomes. Furthermore, genome mining and characterization of biosynthetic pathways, have uncovered the richness of these compounds, which are predicted to vary across different
spp. and strains. Although progress has been made in the identification and function of SM genes and gene clusters, the targeted testing for the bioactivity of molecules has been scarce or mostly focused on medical applications. In this review, we summarize the current knowledge of
SM, emphasizing on their activity against plant pathogens and parasites. We further discuss their potential in the management of agricultural pests and the steps that need to be taken for the implementation of
SM in pest management.
A relationship between low back pain (LBP) and prolonged standing or prolonged sitting at work has not been clearly shown, despite its biological plausibility. Because sitting and standing postures ...vary as to duration and freedom to alternate postures, and standing postures vary as to mobility, associations between specific working postures and LBP were explored using multiple logistic regression. Associations between work factors and self-reported LBP during the previous 12 months that interfered with usual activities were examined among 4493 standing workers and 3237 sitting workers interviewed in the 1998 Quebec Health and Social Survey; 24.5% reported significant LBP. Since the same conditions can correspond to different physiological demands for sitting compared with standing workers, analyses were performed separately for the two groups. Standing without freedom to sit was associated with LBP. Different occupational physical and psychosocial factors were associated with LBP in sitting compared with standing populations.
Background A nationwide survey of family members of people with intellectual and developmental disabilities ranging in age from birth through adulthood was conducted to replicate a similar effort by ...Wehmeyer and update the knowledge base concerning technology use by people with intellectual and developmental disabilities.
Method Survey responses provided information about use of technology for mobility, hearing and vision, communication, independent living, and in the area of computer use. In addition, survey items queried the use of electronic and information technology devices such as use of email, mobile telephones and digital cameras.
Results Survey results showed that although the use of computers for individuals with intellectual and developmental disabilities is more prevalent, other technology use frequency is much the same as in the late 1990s. However, technology needs did vary among school‐age individuals over time.
Conclusion Implications of results for technology use of people with disabilities are discussed through the lens of frequency of use and needs for individuals with disabilities.
Induction of labour (IOL) is one of the most commonly performed interventions in maternity care, with outpatient cervical ripening increasingly offered as an option for women undergoing IOL. The ...COVID-19 pandemic has changed the context of practice and the option of returning home for cervical ripening may now assume greater significance. This work aimed to examine whether and how the COVID-19 pandemic has changed practice around IOL in the UK.
We used an online questionnaire to survey senior obstetricians and midwives at all 156 UK NHS Trusts and Boards that currently offer maternity services. Responses were analysed to produce descriptive statistics, with free text responses analysed using a conventional content analysis approach.
Responses were received from 92 of 156 UK Trusts and Boards, a 59% response rate. Many Trusts and Boards reported no change to their IOL practice, however 23% reported change in methods used for cervical ripening; 28% a change in criteria for home cervical ripening; 28% stated that more women were returning home during cervical ripening; and 24% noted changes to women's response to recommendations for IOL. Much of the change was reported as happening in response to attempts to minimise hospital attendance and restrictions on birth partners accompanying women.
The pandemic has changed practice around induction of labour, although this varied significantly between NHS Trusts and Boards. There is a lack of formal evidence to support decision-making around outpatient cervical ripening: the basis on which changes were implemented and what evidence was used to inform decisions is not clear.
Severe Acute Respiratory Syndrome coronavirus-2 (SARS-CoV-2) has challenged public health agencies globally. In order to effectively target government responses, it is critical to identify the ...individuals most at risk of coronavirus disease-19 (COVID-19), developing severe clinical signs, and mortality. We undertook a systematic review of the literature to present the current status of scientific knowledge in these areas and describe the need for unified global approaches, moving forwards, as well as lessons learnt for future pandemics.
Medline, Embase and Global Health were searched to the end of April 2020, as well as the Web of Science. Search terms were specific to the SARS-CoV-2 virus and COVID-19. Comparative studies of risk factors from any setting, population group and in any language were included. Titles, abstracts and full texts were screened by two reviewers and extracted in duplicate into a standardised form. Data were extracted on risk factors for COVID-19 disease, severe disease, or death and were narratively and descriptively synthesised.
One thousand two hundred and thirty-eight papers were identified post-deduplication. Thirty-three met our inclusion criteria, of which 26 were from China. Six assessed the risk of contracting the disease, 20 the risk of having severe disease and ten the risk of dying. Age, gender and co-morbidities were commonly assessed as risk factors. The weight of evidence showed increasing age to be associated with severe disease and mortality, and general comorbidities with mortality. Only seven studies presented multivariable analyses and power was generally limited. A wide range of definitions were used for disease severity.
The volume of literature generated in the short time since the appearance of SARS-CoV-2 has been considerable. Many studies have sought to document the risk factors for COVID-19 disease, disease severity and mortality; age was the only risk factor based on robust studies and with a consistent body of evidence. Mechanistic studies are required to understand why age is such an important risk factor. At the start of pandemics, large, standardised, studies that use multivariable analyses are urgently needed so that the populations most at risk can be rapidly protected.
This review was registered on PROSPERO as CRD42020177714 .
Hawara Portrait Mummy 4, a Roman-era Egyptian portrait mummy, was studied with computed tomography (CT) and with CT-guided synchrotron X-ray diffraction mapping. These are the first X-ray diffraction ...results obtained non-invasively from objects within a mummy. The CT data showed human remains of a 5-year-old child, consistent with the female (but not the age) depicted on the portrait. Physical trauma was not evident in the skeleton. Diffraction at two different mummy-to-detector separations allowed volumetric mapping of features including wires and inclusions within the wrappings and the skull and femora. The largest uncertainty in origin determination was approximately 1.5 mm along the X-ray beam direction, and diffraction- and CT-determined positions matched. Diffraction showed that the wires were a modern dual-phase steel and showed that the 7 × 5 × 3 mm inclusion ventral of the abdomen was calcite. Tracing the 00.2 and 00.4 carbonated apatite (bone's crystalline phase) reflections back to their origins produced cross-sectional maps of the skull and of femora; these maps agreed with transverse CT slices within approximately 1 mm. Coupling CT and position-resolved X-ray diffraction, therefore, offers considerable promise for non-invasive studies of mummies.
We report the detection of a transiting Earth-size planet around GJ 357, a nearby M2.5 V star, using data from the Transiting Exoplanet Survey Satellite (TESS). GJ 357 b (TOI-562.01) is a transiting, ...hot, Earth-sized planet (Teq = 525 ± 11 K) with a radius of Rb = 1.217 ± 0.084 R⊕ and an orbital period of Pb = 3.93 d. Precise stellar radial velocities from CARMENES and PFS, as well as archival data from HIRES, UVES, and HARPS also display a 3.93-day periodicity, confirming the planetary nature and leading to a planetary mass of Mb = 1.84 ± 0.31 M⊕. In addition to the radial velocity signal for GJ 357 b, more periodicities are present in the data indicating the presence of two further planets in the system: GJ 357 c, with a minimum mass of Mc = 3.40 ± 0.46 M⊕ in a 9.12 d orbit, and GJ 357 d, with a minimum mass of Md = 6.1 ± 1.0 M⊕ in a 55.7 d orbit inside the habitable zone. The host is relatively inactive and exhibits a photometric rotation period of Prot = 78 ± 2 d. GJ 357 b isto date the second closest transiting planet to the Sun, making it a prime target for further investigations such as transmission spectroscopy. Therefore, GJ 357 b represents one of the best terrestrial planets suitable for atmospheric characterization with the upcoming JWST and ground-based ELTs.
Entomopathogenic nematodes of the genus
have a mutualistic relationship with bacteria of the genus
and together they form an antagonist partnership against their insect hosts. The nematodes ...(third-stage infective juveniles, or IJs) protect the bacteria from the external environmental stressors and vector them from one insect host to another.
produce secondary metabolites and antimicrobial compounds inside the insect that protect the cadaver from soil saprobes and scavengers. The bacteria also become the nematodes' food, allowing them to grow and reproduce. Despite these benefits, it is yet unclear what the potential metabolic costs for
IJs are relative to the maintenance and vectoring of
. In this study, we performed a comparative dual RNA-seq analysis of IJs of two nematode-bacteria partnerships:
-
and
-
. For each association, three conditions were studied: (1) IJs reared in the insect (
colonized), (2) colonized IJs reared on liver-kidney agar (
colonized), and (3) IJs depleted by the bacteria reared on liver-kidney agar (
aposymbiotic). Our study revealed the downregulation of numerous genes involved in metabolism pathways, such as carbohydrate, amino acid, and lipid metabolism when IJs were reared
, both colonized and without the symbiont. This downregulation appears to impact the longevity pathway, with the involvement of glycogen and trehalose metabolism, as well as arginine metabolism. Additionally, a differential expression of the venom protein known to be secreted by the nematodes was observed when both
species were depleted of their symbiotic partners. These results suggest
IJs may have a mechanism to adapt their virulence in absence of their symbionts.
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