Muscle cell-derived Ccl8 is a negative regulator of skeletal muscle regeneration.

Skeletal muscles undergo robust regeneration upon injury, and infiltrating immune cells play a major role in not only clearing damaged tissues but also regulating the myogenic process through secreted cytokines. Chemokine C-C motif ligand 8 (Ccl8), along with Ccl2 and Ccl7, has been reported to mediate inflammatory responses to suppress muscle regeneration. Ccl8 is also expressed by muscle cells, but a role of the muscle cell-derived Ccl8 in myogenesis has not been reported. In this study, we found that knockdown of Ccl8, but not Ccl2 or Ccl7, led to increased differentiation of C2C12 myoblasts. Analysis of existing single-cell transcriptomic datasets revealed that both immune cells and muscle stem cells (MuSCs) in regenerating muscles express Ccl8, with the expression by MuSCs at a much lower level, and that the temporal patterns of Ccl8 expression were different in MuSCs and macrophages. To probe a function of muscle cell-derived Ccl8 in vivo, we utilized a mouse system in which Cas9 was expressed in Pax7+ myogenic progenitor cells (MPCs) and Ccl8 gene editing was induced by AAV9-delivered sgRNA. Depletion of Ccl8 in Pax7+ MPCs resulted in accelerated muscle regeneration after barium chloride-induced injury in both young and middle-aged mice, and intramuscular administration of a recombinant Ccl8 reversed the phenotype. Accelerated regeneration was also observed when Ccl8 was depleted in Myf5+ or MyoD+ MPCs by similar approaches. Our results suggest that muscle cell-derived Ccl8 plays a unique role in regulating the initiation of myogenic differentiation during injury-induced muscle regeneration.

Neuromodulatory effects of parietal high-definition transcranial direct-current stimulation on network-level activity serving fluid intelligence.

Fluid intelligence (Gf) involves rational thinking skills and requires the integration of information from different cortical regions to resolve novel complex problems. The effects of non-invasive brain stimulation on Gf have been studied in attempts to improve Gf, but such studies are rare and the few existing have reached conflicting conclusions. The parieto-frontal integration theory of intelligence (P-FIT) postulates that the parietal and frontal lobes play a critical role in Gf. To investigate the suggested role of parietal cortices, we applied high-definition transcranial direct current stimulation (HD-tDCS) to the left and right parietal cortices of 39 healthy adults (age 19-33 years) for 20 min in three separate sessions (left active, right active and sham). After completing the stimulation session, the participants completed a logical reasoning task based on Raven's Progressive Matrices during magnetoencephalography. Significant neural responses at the sensor level across all stimulation conditions were imaged using a beamformer. Whole-brain, spectrally constrained functional connectivity was then computed to examine the network-level activity. Behaviourally, we found that participants were significantly more accurate following left compared to right parietal stimulation. Regarding neural findings, we found significant HD-tDCS montage-related effects in brain networks thought to be critical for P-FIT, including parieto-occipital, fronto-occipital, fronto-parietal and occipito-cerebellar connectivity during task performance. In conclusion, our findings showed that left parietal stimulation improved abstract reasoning abilities relative to right parietal stimulation and support both P-FIT and the neural efficiency hypothesis. KEY POINTS: Abstract reasoning is a critical component of fluid intelligence and is known to be served by multispectral oscillatory activity in the fronto-parietal cortices. Recent studies have aimed to improve abstract reasoning abilities and fluid intelligence overall through behavioural training, but the results have been mixed. High-definition transcranial direct-current stimulation (HD-tDCS) applied to the parietal cortices modulated task performance and neural oscillations during abstract reasoning. Left parietal stimulation resulted in increased accuracy and decreased functional connectivity between occipital regions and frontal, parietal, and cerebellar regions. Future studies should investigate whether HD-tDCS alters abstract reasoning abilities in those who exhibit declines in performance, such as healthy ageing populations.

Surface Enrichment and Depletion of Components in a Ternary Drug-Surfactant-Polymer Amorphous Solid Dispersion.

Amorphous solid dispersions (ASDs) can be used to enhance the solubility and bioavailability of poorly soluble drugs. An ASD is often a ternary system containing a drug, a surfactant, and a polymer. Recent work on binary ASDs has observed significant differences between surface and bulk compositions, with impacts on wettability and stability. Here we investigate a ternary ASD composed of the antifungal posaconazole, the surfactant Span 80, and a dispersion polymer (PVP or PVP/VA). The surfactant loading was fixed at the typical level of 5 wt %, and the drug/polymer ratio was varied. We observed strong surface enrichment of the surfactant and simultaneous depletion of the drug. This effect is already pronounced in the binary drug-surfactant system and is enhanced by the addition of the polymers. Between the two polymers, the more hydrophilic PVP causes a stronger enhancement of the surface enrichment effect. These results demonstrate the impact of component interactions on the surface composition of ASDs and the performance.

Microplastic in Dredged Sediments: From Databases to Strategic Responses.

Microplastics (MPs) accumulate in sediments, yet guidelines for evaluating MP risks in dredged sediments are lacking. The objective of this study was to review existing literature on MPs in sediments to improve fundamental knowledge of MP exposures and develop a publicly available database of MPs in sediments. Twelve percent of the reviewed papers (nine studies) included sediment core samples with MP concentrations generally decreasing with depth, peaking in the top 15 cm. The remaining papers evaluated surficial grab samples (0 to 15 cm depth) from various water bodies with MPs detected in almost every sample. Median MP concentrations (items/kg dry sediment) increased in this order: lakes and reservoirs (184), estuarine (263), Great Lakes nearshore areas and tributaries (290), riverine (410), nearshore marine areas (487), dredge activities (817), and harbors (948). Dredging of recurrent shoaling sediments could be expected to contain MPs at various depths with concentrations influenced by the time elapsed since the last dredging event. These results offer key insights into the presence and variability of MPs in dredged sediments, informing environmental monitoring and risk assessment strategies.

Tet1 Isoforms Differentially Regulate Gene Expression, Synaptic Transmission, and Memory in the Mammalian Brain.

The dynamic regulation of DNA methylation in postmitotic neurons is necessary for memory formation and other adaptive behaviors. Ten-eleven translocation 1 (TET1) plays a part in these processes by oxidizing 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), thereby initiating active DNA demethylation. However, attempts to pinpoint its exact role in the nervous system have been hindered by contradictory findings, perhaps due in part, to a recent discovery that two isoforms of the Tet1 gene are differentially expressed from early development into adulthood. Here, we demonstrate that both the shorter transcript (Tet1S ) encoding an N-terminally truncated TET1 protein and a full-length Tet1 (Tet1FL ) transcript encoding canonical TET1 are co-expressed in the adult mouse brain. We show that Tet1S is the predominantly expressed isoform and is highly enriched in neurons, whereas Tet1FL is generally expressed at lower levels and more abundant in glia, suggesting their roles are at least partially cell type-specific. Using viral-mediated, isoform and neuron-specific molecular tools, we find that the individual repression of each transcript leads to the dysregulation of unique gene ensembles and contrasting changes in basal synaptic transmission. In addition, Tet1S repression enhances, while Tet1FL impairs, hippocampal-dependent memory in male mice. Together, our findings demonstrate that each Tet1 isoform serves a distinct role in the mammalian brain.SIGNIFICANCE STATEMENT In the brain, activity-dependent changes in gene expression are required for the formation of long-term memories. DNA methylation plays an essential role in orchestrating these learning-induced transcriptional programs by influencing chromatin accessibility and transcription factor binding. Once thought of as a stable epigenetic mark, DNA methylation is now known to be impermanent and dynamically regulated, driving neuroplasticity in the brain. We found that Tet1, a member of the ten-eleven translocation (TET) family of enzymes that mediates removal of DNA methyl marks, is expressed as two separate isoforms in the adult mouse brain and that each differentially regulates gene expression, synaptic transmission and memory formation. Together, our findings demonstrate that each Tet1 isoform serves a distinct role in the CNS.

Correlates of Disclosure of Virginity Status Among U.S. College Students.

Disclosure of virginity status (DVS) refers to the extent to which an individual reveals that they identify as a virgin or not to different individuals in their lives. The purpose of this study was to investigate how generalized self-disclosure, virginity beliefs, and religiosity, as well as interactions with gender and virginity status, relate to DVS to family, peers, and religious communities. Southern U.S. college students (N = 690) took an online sexuality questionnaire. Generalized self-disclosure did not relate to DVS, suggesting that DVS represents a unique form of self-disclosure. Gender by virginity status interactions suggested that societal double standards of gender and virginity status (i.e., non-virgin women and virgin men being stigmatized for their virginity identifications) may be most relevant to one's decision to disclose to family, and somewhat relevant to one's decision to disclose to religious communities. Individuals high in religiosity overall tended to disclose their virginity status when they identified as a virgin, but not as a non-virgin. Virgins concealed their virginity status from religious communities when they stigmatized their own virginity but disclosed to family and peers when they viewed virginity as a gift. Overall, the results suggest that, although religiosity and virginity beliefs indeed play a role in DVS toward certain targets, one's gender and virginity status appear to be most important. Increased education on the double standard regarding gender and virginity status may help reduce stigma and improve sexual well-being.

Surface-enhanced crystal nucleation and polymorph selection in amorphous posaconazole.

Molecules at a liquid/vapor interface have different organizations and mobilities from those in the bulk. These differences potentially influence the rate of crystal nucleation, but the effect remains imperfectly understood. We have measured the crystal nucleation rates at the surface and in the bulk of amorphous poscaconazole, a rod-like molecule known to have a preferred interfacial orientation. We find that surface nucleation is vastly enhanced over bulk nucleation, by ∼9 orders of magnitude, and selects a different polymorph (II) from bulk nucleation (I). This phenomenon mirrors the recently reported case of D-arabitol and stems from the similarity of anisotropic surface molecular packing to the structure of the surface-nucleating polymorph. In contrast to these two systems, the surface enhancement of nucleation is weaker (though still significant) in acetaminophen and in water and does not select a different polymorph. Together, the systems investigated to date all feature surface enhancement, not suppression, of crystal nucleation, and those showing a polymorphic change feature (1) structural reconstruction at the surface relative to the bulk and (2) existence of a different polymorph that can take advantage of the surface environment to nucleate. These results help predict the effect of a liquid/vapor interface on crystal nucleation and polymorph selection, especially in systems with a large surface/volume ratio, such as atmospheric water and amorphous particles.

Enablers and inhibitors of community participation in Ghana's Community-based Health Planning and Services programme: a qualitative study in the Builsa North Municipality.

BACKGROUND: Community participation is essential for the successful implementation of primary health care programmes across the globe, including sub-Saharan Africa. The Community-based Health Planning and Services (CHPS) programme is one of the primary health care interventions in Ghana which by design and implementation heavily relies on community participation. However, there is little evidence to establish the factors enabling or inhibiting community participation in the Ghanaian CHPS programme. This study, therefore, explored the enabling and inhibiting factors influencing community participation in the design and implementation of the CHPS programme in the Builsa North Municipality in the Upper East Region of Ghana. METHODS: A qualitative approach, using a cross-sectional design, was employed to allow for a detailed in-depth exploration of the enabling and inhibiting factors influencing community participation in the design and implementation of the CHPS programme. The data were collected in January 2020, through key informant interviews with a stratified purposive sample of 106 respondents, selected from the 15 functional CHPS facilities in the Municipality. The data were audio-recorded, transcribed and manually analysed using thematic analysis. RESULTS: The results showed that, public education on the CHPS concept, capacity of the community to contribute material resources towards the construction of CHPS facilities, strong and effective community leadership provided by community chiefs and assembly persons, the spirit of volunteerism and trust in the benefits of the CHPS programme were the enablers of community participation in the programme. However, volunteer attrition, competing economic activities, lack of sense of ownership by distant beneficiaries, external contracting of the construction of CHPS facilities and illiteracy constituted the inhibiting factors of community participation in the programme. CONCLUSION: Extensive public education, volunteer incentivization and motivation, and the empowerment of communities to construct their own CHPS compounds are issues that require immediate policy attention to enhance effective community participation in the programme.

Society for Acute Medicine Benchmarking Audit 2021 (SAMBA21): assessing national performance of acute medicine services.

INTRODUCTION: The Society for Acute Medicine Benchmarking Audit 2021 (SAMBA21) took place on 17th June 2021, providing the first assessment of performance against the Society for Acute Medicine's Clinical Quality Indicators (CQIs) within acute medical units since the start of the COVID-19 pandemic. METHODS: All acute hospitals in the UK were invited to participate. Data were collected on unit structure, and for patients admitted to acute medicine services over a 24-hour period, with follow-up at 7 days. RESULTS: 158 units participated in SAMBA21, from 156 hospitals. 8973 patients were included. The number of admissions per unit had increased compared to SAMBA19 (Sign test p<0.005). An early warning score was recorded within 30 minutes of hospital arrival in 77.4% of patients. 87.4% of unplanned admissions were seen by a tier 1 clinician within 4 hours of arrival. Overall, the medical team performed the initial clinician assessment for 36.4% of unplanned medical admissions. More than a third of medical admissions had their initial assessment in Same Day Emergency Care (SDEC) in 25.4% of hospitals. 62.1% of unplanned admissions were seen by two other clinical decision makers prior to consultant review. Of those unplanned admissions requiring consultant review, 67.8% were seen within the target time. More than a third of unplanned admissions were discharged the same day in 41.8% of units. CONCLUSION: Performance against the CQIs for acute medicine was maintained in comparison to previous rounds of SAMBA, despite increased admissions. There remains considerable variation in unit structure and performance within acute medical services.

Length of stay in Acute Medical Admissions: Analysis from the Society for Acute Medicine Benchmarking Audit.

INTRODUCTION: Medical admissions to hospital represent a diverse range of patients, from those managed on ambulatory pathways through Same Day Emergency Care (SDEC) services, to those requiring prolonged inpatient admission. An understanding of current patterns of admission through acute medicine services and patient factors associated with longer hospital admission is needed to guide service planning and improvement. METHODS: Data from the Society for Acute Medicine Benchmarking Audit (SAMBA) 2021 were analysed. Patients admitted to acute medicine services during a 24-hour period on 17th June 2021 were included, with data recording patient demographics, frailty score, acuity and follow-up of outcomes after seven days. RESULTS: 8101 unplanned medical admissions were included, from 156 hospitals. 31.6% were discharged without overnight admission; the median hospital performance was 30.1% (IQR 19.3-39.3%). 22.1% of patients remained in hospital for more than 7 days. Those remaining in hospital for more than 48 hours and for more than seven days were more likely to be aged over 70, to be frail, or to have a NEWS2 of 3 or more on arrival to hospital. CONCLUSION: The proportion of acute medical attendances receiving overnight admission varies between hospitals. Length of stay is impacted by patient factors and illness acuity. Strategies to reduce inpatient service pressures must ensure effective care for older patients and those with frailty.

Developing priorities for quality improvement in acute medicine using a modified Delphi method A consensus process hosted by the Society for Acute Medicine Quality Improvement Committee (SAM-QI).

INTRODUCTION: The SAM Quality Improvement Committee (SAM-QI), set up in 2016, has worked over the last year to determine the priority Acute Medicine QI topics. They have also discussed and put forward proposals to improve QI training for Acute Medicine professionals. METHODS: A modified Delphi process was completed over four rounds to determine priority QI topics. Online meetings were also used to develop proposals for QI training. RESULTS: Same Day Emergency Care (SDEC) was chosen as the priority topic for QI work within Acute Medicine. CONCLUSION: The SAM-QI group settled on SDEC being the priority topic for Acute Medicine QI development. Throughout the Delphi process SAM-QI has also developed proposals for QI training that will help Acute Medicine professionals deliver coordinated meaningful improvements in care.

Plasma Plasmodium falciparum Histidine-rich Protein 2 Concentrations in Children With Malaria Infections of Differing Severity in Kilifi, Kenya.

BACKGROUND: Most previous studies support a direct link between total parasite load and the clinical severity of Plasmodium falciparum malaria infections. METHODS: We estimated P. falciparum parasite loads in 3 groups of children with malaria infections of differing severity: (1) children with World Health Organization-defined severe malaria (n = 1544), (2) children admitted with malaria but without features of severity (n = 200), and (3) children in the community with asymptomatic parasitemia (n = 33). RESULTS: Peripheral parasitemias were highest in those with uncomplicated malaria (geometric mean [GM] parasite count, 111 064/µL; 95% confidence interval, CI, 86 798-141 819/µL), almost 3 times higher than in those with severe malaria (39 588/µL; 34 990-44 791/µL) and >100 times higher than in those with asymptomatic malaria (1092/µL; 523-2280/µL). However, the GM P. falciparum histidine-rich protein 2 (PfHRP2) values (95% CI) increased with severity, being 7 (4-12) ng/mL in asymptomatic malaria, 843 (655-1084) ng/mL in uncomplicated malaria, and 1369 (1244-1506) ng/mL in severe malaria. PfHRP2 concentrations were markedly lower in the subgroup of patients with severe malaria and concomitant invasive bacterial infections of blood or cerebrospinal fluid (GM concentration, 312 ng/mL; 95% CI, 175-557 ng/mL; P < .001) than in those without such infections (1439 ng/mL; 1307-1584; P < .001). CONCLUSIONS: The clinical severity of malaria infections related strongly to the total burden of P. falciparum parasites. A quantitative test for plasma concentrations of PfHRP2 could be useful in identifying children at the greatest clinical risk and identifying critically ill children in whom malaria is not the primary cause.

Bypassing primary healthcare facilities for maternal healthcare in North West Ghana: socio-economic correlates and financial implications.

BACKGROUND: Bypassing primary health care (PHC) facilities for maternal health care is an increasing phenomenon. In Ghana, however, there is a dearth of systematic evidence on bypassing PHC facilities for maternal healthcare. This study investigated the prevalence of bypassing PHC facilities for maternal healthcare, and the socio-economic factors and financial costs associated with bypassing PHC facilities within two municipalities in Northwestern Ghana. METHODS: A quantitative cross-sectional design was implemented between December 2019 and March 2020. Multistage stratified sampling was used to select 385 mothers receiving postnatal care in health facilities for a survey. Using STATA 12 software, bivariate analysis with chi-square test and binary logistic regression models were run to determine the socio-economic and demographic factors associated with bypassing PHC facilities. The two-sample independent group t-test was used to estimate the mean differences in healthcare costs of those who bypassed their PHC facilities and those who did not. RESULTS: The results revealed the prevalence of bypassing PHC facilities as 19.35 % for antenatal care, 33.33 % for delivery, and 38.44 % for postnatal care. The municipality of residence, ethnicity, tertiary education, pregnancy complications, means of transport, nature of the residential location, days after childbirth, age, and income were statistically significantly (p < 0.05) associated with bypassing PHC facilities for various maternal care services. Compared to the non-bypassers, the bypassers incurred a statistically significantly (P < 0.001) higher mean extra financial cost of GH₵112.09 (US$19.73) for delivery, GH₵44.61 (US$7.85) for postnatal care and ₵43.34 (US$7.65) for antenatal care. This average extra expenditure was incurred on transportation, feeding, accommodation, medicine, and other non-receipted expenses. CONCLUSIONS: The study found evidence of bypassing PHC facilities for maternal healthcare. Addressing this phenomenon of bypassing and its associated cost, will require effective policy reforms aimed at strengthening the service delivery capacities of PHC facilities. We recommend that the Ministry of Health and Ghana Health Service should embark on stakeholder engagement and sensitization campaigns on the financial consequences of bypassing PHC facilities for maternal health care. Future research, outside healthcare facility settings, is also required to understand the specific supply-side factors influencing bypassing of PHC facilities for maternal healthcare within the study area.

A perspective on the role of uncertainty in sustainability science and engineering.

The Trans-Atlantic Research and Development Interchange on Sustainability Workshop (TARDIS) is a meeting on scientific topics related to sustainability. The 2019 workshop theme was "On the Role of Uncertainty in Managing the Earth for Global Sustainability." This paper presents the perspectives on this topic derived from talks and discussions at the 2019 TARDIS workshop. There are four kinds of uncertainties encountered in sustainability ranging from clear enough futures to true surprises. The current state-of-the-art in assessing and mitigating these uncertainties is discussed.

Detection of MCM5 as a novel non-invasive aid for the diagnosis of endometrial and ovarian tumours.

BACKGROUND: MCM5 is a protein involved in DNA replication, facilitating cell proliferation. In normal epithelium MCM5 expression is restricted to the cells in the basal proliferative compartments, however in the presence of a tumour MCM5 positive cells are present at the surface epithelium and are shed into bodily fluids. The aim of this study was to determine the sensitivity of MCM5 as a biomarker for the detection of endometrial and ovarian cancer. METHODS: Patients with known ovarian or endometrial cancers, or known benign gynaecological conditions, were enrolled. Informed consent was obtained prior to the collection of full void urine, and either a vaginal tampon (worn for 6-8 h), or a vaginal swab. Vaginal secretions were extracted from the tampon or swab, centrifuged and lysed. Urine samples were centrifuged and lysed. MCM5 levels were determined by MCM5-ELISA (Arquer Diagnostics Ltd). RESULTS: 125 patients completed the study protocol, 41 patients had endometrial cancer, 26 ovarian cancer, and 58 benign controls. All patients provided a urine sample and either a tampon or vaginal swab sample. Urine MCM5 levels were higher in cancer patients than controls (p < 0.0001), there was no significant difference in levels between tampon samples or vaginal swab samples in cancer patients when compared to controls. Performance of MCM5 to discriminate cancer from benign disease was high with an area under the ROC curve of 0.83 for endometrial cancer and 0.68 for ovarian cancer. Using a cut off of 12 pg/mL, overall sensitivity for endometrial cancer was 87.8, and 61.5% for ovarian cancer with a specificity of 75.9%. CONCLUSIONS: MCM5 is a novel sensitive and specific biomarker for the detection of ovarian and endometrial tumours in urine samples, which is likely to have clinical utility as a diagnostic aid.

Integration of the Duke Activity Status Index into preoperative risk evaluation: a multicentre prospective cohort study.

BACKGROUND: The Duke Activity Status Index (DASI) questionnaire might help incorporate self-reported functional capacity into preoperative risk assessment. Nonetheless, prognostically important thresholds in DASI scores remain unclear. We conducted a nested cohort analysis of the Measurement of Exercise Tolerance before Surgery (METS) study to characterise the association of preoperative DASI scores with postoperative death or complications. METHODS: The analysis included 1546 participants (≥40 yr of age) at an elevated cardiac risk who had inpatient noncardiac surgery. The primary outcome was 30-day death or myocardial injury. The secondary outcomes were 30-day death or myocardial infarction, in-hospital moderate-to-severe complications, and 1 yr death or new disability. Multivariable logistic regression modelling was used to characterise the adjusted association of preoperative DASI scores with outcomes. RESULTS: The DASI score had non-linear associations with outcomes. Self-reported functional capacity better than a DASI score of 34 was associated with reduced odds of 30-day death or myocardial injury (odds ratio: 0.97 per 1 point increase above 34; 95% confidence interval [CI]: 0.96-0.99) and 1 yr death or new disability (odds ratio: 0.96 per 1 point increase above 34; 95% CI: 0.92-0.99). Self-reported functional capacity worse than a DASI score of 34 was associated with increased odds of 30-day death or myocardial infarction (odds ratio: 1.05 per 1 point decrease below 34; 95% CI: 1.00-1.09), and moderate-to-severe complications (odds ratio: 1.03 per 1 point decrease below 34; 95% CI: 1.01-1.05). CONCLUSIONS: A DASI score of 34 represents a threshold for identifying patients at risk for myocardial injury, myocardial infarction, moderate-to-severe complications, and new disability.

Erratum: First Dark Matter Constraints from a SuperCDMS Single-Charge Sensitive Detector [Phys. Rev. Lett. 121, 051301 (2018)].

This corrects the article DOI: 10.1103/PhysRevLett.121.051301.

Associations between maternal physical activity in early and late pregnancy and offspring birth size: remote federated individual level meta-analysis from eight cohort studies.

OBJECTIVE: Evidence on the impact of leisure time physical activity (LTPA) in pregnancy on birth size is inconsistent. We aimed to examine the association between LTPA during early and late pregnancy and newborn anthropometric outcomes. DESIGN: Individual level meta-analysis, which reduces heterogeneity across studies. SETTING: A consortium of eight population-based studies (seven European and one US) comprising 72 694 participants. METHODS: Generalised linear models with consistent inclusion of confounders (gestational age, sex, parity, maternal age, education, ethnicity, BMI, smoking, and alcohol intake) were used to test associations between self-reported LTPA at either early (8-18 weeks gestation) or late pregnancy (30+ weeks) and the outcomes. Results were pooled using random effects meta-analyses. MAIN OUTCOME MEASURES: Birth weight, large-for-gestational age (LGA), macrosomia, small-for-gestational age (SGA), % body fat, and ponderal index at birth. RESULTS: Late, but not early, gestation maternal moderate to vigorous physical activity (MVPA), vigorous activity, and LTPA energy expenditure were modestly inversely associated with BW, LGA, macrosomia, and ponderal index, without heterogeneity (all: I2  = 0%). For each extra hour/week of MVPA, RR for LGA and macrosomia were 0.97 (95% CI: 0.96, 0.98) and 0.96 (95% CI: 0.94, 0.98), respectively. Associations were only modestly reduced after additional adjustments for maternal BMI and gestational diabetes. No measure of LTPA was associated with risk for SGA. CONCLUSIONS: Physical activity in late, but not early, pregnancy is consistently associated with modestly lower risk of LGA and macrosomia, but not SGA. TWEETABLE ABSTRACT: In an individual participant meta-analysis, late pregnancy moderate to vigorous physical activity modestly reduced birth size outcomes.

Origin and age of the earliest Martian crust from meteorite NWA 7533.

The ancient cratered terrain of the southern highlands of Mars is thought to hold clues to the planet's early differentiation, but until now no meteoritic regolith breccias have been recovered from Mars. Here we show that the meteorite Northwest Africa (NWA) 7533 (paired with meteorite NWA 7034) is a polymict breccia consisting of a fine-grained interclast matrix containing clasts of igneous-textured rocks and fine-grained clast-laden impact melt rocks. High abundances of meteoritic siderophiles (for example nickel and iridium) found throughout the rock reach a level in the fine-grained portions equivalent to 5 per cent CI chondritic input, which is comparable to the highest levels found in lunar breccias. Furthermore, analyses of three leucocratic monzonite clasts show a correlation between nickel, iridium and magnesium consistent with differentiation from impact melts. Compositionally, all the fine-grained material is alkalic basalt, chemically identical (except for sulphur, chlorine and zinc) to soils from Gusev crater. Thus, we propose that NWA 7533 is a Martian regolith breccia. It contains zircons for which we measured an age of 4,428 ± 25 million years, which were later disturbed 1,712 ± 85 million years ago. This evidence for early crustal differentiation implies that the Martian crust, and its volatile inventory, formed in about the first 100 million years of Martian history, coeval with earliest crust formation on the Moon and the Earth. In addition, incompatible element abundances in clast-laden impact melt rocks and interclast matrix provide a geochemical estimate of the average thickness of the Martian crust (50 kilometres) comparable to that estimated geophysically.

Help seeking for antibiotics; is the influence of a personal social network relevant?

BACKGROUND: Health policy focuses on reducing antibiotic prescribing that in order to succeed requires the public to hold similar attitudes towards judicious use. Social network influences on health behaviour and attitudes are well established and yet these influences are not sufficiently acknowledged in the UK's antibiotic stewardship programmes. Therefore, the aim of this study was to evaluate individuals' attitudes and behaviours towards antibiotics and also identify the social network influences on these in the process of help seeking for self-limiting illnesses. METHODS: From a social network approach the methods used were a personal community mapping exercise which was carried out ahead of a semi-structured interview. A purposive sample was drawn from across the Wessex region and participants were recruited via GP practices and pharmacists. In total 14 adults, and 10 parents of children, who had received a prescription for antibiotics for a self-limiting illness within the 3 months preceding the interview were recruited and interviewed. RESULTS: Three network types were identified; diverse, family and friend and restricted. The type of network an individual has appears to have an influence on antibiotic attitudes and behaviours. Most notably, the more diverse a network the more likely the individual will delay in help seeking from healthcare professionals as they draw upon self-care strategies advised by network members. The role of the GP varies according to network type too. Individuals' with diverse networks draw upon GP network members to provide clarity and certainty following a period of self-care. People with restricted networks are more reliant upon the GP, seek help quicker and also more likely to prioritise the GPs advice over other sources of information. CONCLUSION: The understanding a social network approach brings to help seeking behaviour for antibiotics could help practitioners modify their consultation approach to mitigate some uncertainties and perceptions around prescribing behaviour.