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Antenatal exogenous glucocorticoids (ANG) are standard management for women at risk of preterm birth but are reputed to impair glucose tolerance in preterm offspring. We compared lambs born preterm (137 days gestation) following labour induced with exogenous glucocorticoids (G-Prem, glucocorticoid-induced preterm group), or with a progesterone synthesis inhibitor (NG-Prem, non-glucocorticoid-induced preterm group), with term-born lambs (Term; 149 days). We assessed glucose tolerance, insulin secretion and sensitivity at 4 and 10 months n = 11–14/group) and pancreatic and hepatic gene and protein expression at 4 weeks post-term (4 weeks; n = 6/group) and 12 months (12 months; n = 12–13/group). NG-Prem had higher plasma glucose concentrations than G-Prem, but not Term, at 4 months (Mean[SEM] mM: NG-Prem = 4.1[0.1]; G-Prem = 3.4[0.1]; Term = 3.7[0.1]; p = 0.003) and 10 months (NG-Prem = 3.9[0.1]; G-Prem = 3.5[0.1]; Term = 3.7[0.1]; p = 0.01). Insulin sensitivity decreased from 4 to 10 months, in NG-Prem but not in Term (Mean[SEM] µmol·ml−1·kg−1·min−1·ng−1, 4 vs. 10 months: NG-Prem = 18.7[2.5] vs. 9.5[1.5], p < 0.01; Term: 12.1[2.8] vs. 10.4[1.5], p = 0.44). At 12 months, β-cell mass in NG-Prem was reduced by 30% vs. G-Prem (p < 0.01) and 75% vs. Term (p < 0.01) and was accompanied by an increased β-cell apoptosis: proliferation ratio at 12 months. At 12 months, pancreatic glucokinase, igf2 and insulin mRNA levels were reduced 21%–71% in NG-Prem vs. G-Prem and 42%–80% vs. Term. Hepatic glut2 mRNA levels in NG-Prem were 250% of those in G-Prem and Term. Thus, induction of preterm birth without exogenous glucocorticoids more adversely affected pancreas and liver than induction with exogenous glucocorticoids. These findings do not support that ANG lead to long-term adverse metabolic effects, but support an effect of preterm birth itself.
Recent comparisons between classical Wagner theory for the impact of two liquid droplets and direct numerical simulations in Cimpeanu & Moore (J. Fluid Mech., vol. 856, 2018, pp. 764–796) show that, in some regimes, the inviscid theory over-predicts the thickness of the root of the splash jet that forms in the impact, while also struggling to predict the angle at which the jet is emitted. The effect of capillary and viscous perturbations to Helmholtz flows was investigated in a previous study, see Moore et al. (J. Fluid Mech., vol. 742, 2014, R1). However, the paper in question ignored a term in the second-order perturbation analysis, which needs to be included in order to predict the displacement of the inviscid free boundary to lowest order. In this paper, we derive a singular integro-differential equation for the free-surface perturbations caused by viscosity in Helmholtz flows and discuss its application both in the context of Wagner theory and more generally. In particular, viscosity can induce non-monotonic behaviour in the free boundary profiles near points of maximum curvature.
With the recent discovery of a dozen dusty star-forming galaxies and around 30 quasars at z > 5 that are hyper-luminous in the infrared (μ LIR > 1013 L⊙, where μ is a lensing magnification factor), the possibility has opened up for SPICA, the proposed ESA M5 mid-/far-infrared mission, to extend its spectroscopic studies toward the epoch of reionisation and beyond. In this paper, we examine the feasibility and scientific potential of such observations with SPICA’s far-infrared spectrometer SAFARI, which will probe a spectral range (35–230 μm) that will be unexplored by ALMA and JWST. Our simulations show that SAFARI is capable of delivering good-quality spectra for hyper-luminous infrared galaxies at z = 5 − 10, allowing us to sample spectral features in the rest-frame mid-infrared and to investigate a host of key scientific issues, such as the relative importance of star formation versus AGN, the hardness of the radiation field, the level of chemical enrichment, and the properties of the molecular gas. From a broader perspective, SAFARI offers the potential to open up a new frontier in the study of the early Universe, providing access to uniquely powerful spectral features for probing first-generation objects, such as the key cooling lines of low-metallicity or metal-free forming galaxies (fine-structure and H2 lines) and emission features of solid compounds freshly synthesised by Population III supernovae. Ultimately, SAFARI’s ability to explore the high-redshift Universe will be determined by the availability of sufficiently bright targets (whether intrinsically luminous or gravitationally lensed). With its launch expected around 2030, SPICA is ideally positioned to take full advantage of upcoming wide-field surveys such as LSST, SKA, Euclid, and WFIRST, which are likely to provide extraordinary targets for SAFARI.
Background: Continuous video-EEG (cvEEG) monitoring is the standard of care for diagnosis and management of neonatal seizures. However, it is labour-intensive. We aimed to establish consistency in monitoring of newborns utilising NICU nurses. Methods: Neonatal nurses were trained to apply scalp electrodes, troubleshoot technical issues. Guidelines, checklists and visual training modules were developed. A central network system allowed remote access to the cvEEGs by the epileptologist for timely interpretation and feedback. We compared 100 infants with moderate to severe HIE before and after the training program. Results: 192 cvEEGs were performed. Of the 100 infants compared; time to initiate brain monitoring decreased by average of 31.5 hours, in electrographic seizure detection increased(20% compared to 34% a), seizure clinical misdiagnosis decreased (65% compared to 36% ), and Anti-Seizure burden decreased. Conclusions: Training experienced NICU nurses to set-up, start and monitor cvEEG can decrease the time to initiate cvEEG which may lead to better seizure diagnosis and management.
Background: Despite advances in neonatal care, neonates with moderate to severe HIE are at high risk of mortality and morbidity. we report the impact of a dedicated NNCC team on short term mortality and morbidities. Methods: A retrospective cohort study on neonates with moderate to serve HIE between July 1st 2008 and December 31st 2017. primary outcome : a composite of death and/or brain injury on MRI. Secondary outcomes: rate of cooling, length of hospital stay, anti-seizure medication burden, and use of inotropes. A regression analysis was done adjusting for gestational age, birth weight, gender, out-born status, Apgar score at 10 minutes, cord blood pH, and HIE clinical staging Results: 216 neonates were included, 109 before NNCC implementation, and 107 thereafter. NNCC program resulted in reduction in the primary outcome (AOR: 0.28, CI: 0.14-0.54, p<0.001) and brain injury (AOR: 0.28, CI: 0.14-0.55, p<0.001). It decreased average length of stay/infants by 5 days (p=0.03), improved cooling rate (73% compared to 93% , p <0.001), reduced: seizure misdiagnosis (71% compared to 23%, P <0.001), anti-seizure medication burden (P = 0.001), and inotrope use (34% compared to 53%, p=0.004) Conclusions: NNCC program decreased mortality and brain injury , shortened the length of hospital stay and improved care of neonates with significant HIE.
Nighttime eating is often associated with a negative impact on weight management and cardiometabolic health. However, data from recent acute metabolic studies have implicated a benefit of ingesting a bedtime snack for weight management. The present study compared the impact of ingesting a milk snack containing either 10 (BS10) or 30 g (BS30) protein with a non-energetic placebo (BS0) 30 min before bedtime on next morning metabolism, appetite and energy intake in mildly overweight males (age: 24·3 (sem 0·8) years; BMI: 27·4 (sem 1·1) kg/m2). Next morning measurements of RMR, appetite and energy intake were measured using indirect calorimetry, visual analogue scales and an ad libitum breakfast, respectively. Bedtime milk ingestion did not alter next morning RMR (BS0: 7822 (sem 276) kJ/d, BS10: 7482 (sem 262) kJ/d, BS30: 7851 (sem 261) kJ/d, P=0·19) or substrate utilisation as measured by RER (P=0·64). Bedtime milk ingestion reduced hunger (P=0·01) and increased fullness (P=0·04) during the evening immediately after snack ingestion, but elicited no effect the next morning. Next morning breakfast (BS0: 2187 (sem 365) kJ, BS10: 2070 (sem 336) kJ, BS30: 2582 (sem 384) kJ, P=0·21) and 24 h post-trial (P=0·95) energy intake was similar between conditions. To conclude, in mildly overweight adults, compared with a non-energetic placebo, a bedtime milk snack containing 10 or 30 g of protein does not confer changes in next morning whole-body metabolism and appetite that may favour weight management.
Our current global food system – from food production to consumption, including manufacture, packaging, transport, retail and associated businesses – is responsible for extensive negative social and environmental impacts which threaten the long-term well-being of society. This has led to increasing calls from science–policy organizations for major reform and transformation of the global food system. However, our knowledge regarding food system transformations is fragmented and this is hindering the development of co-ordinated solutions. Here, we collate recent research across several academic disciplines and sectors in order to better understand the mechanisms that ‘lock-in’ food systems in unsustainable states.
The age-related loss of skeletal muscle mass and function is caused, at least in part, by a reduced muscle protein synthetic response to protein ingestion. The magnitude and duration of the postprandial muscle protein synthetic response to ingested protein is dependent on the quantity and quality of the protein consumed. This review characterises the anabolic properties of animal-derived and plant-based dietary protein sources in older adults. While approximately 60 % of dietary protein consumed worldwide is derived from plant sources, plant-based proteins generally exhibit lower digestibility, lower leucine content and deficiencies in certain essential amino acids such as lysine and methionine, which compromise the availability of a complete amino acid profile required for muscle protein synthesis. Based on currently available scientific evidence, animal-derived proteins may be considered more anabolic than plant-based protein sources. However, the production and consumption of animal-derived protein sources is associated with higher greenhouse gas emissions, while plant-based protein sources may be considered more environmentally sustainable. Theoretically, the lower anabolic capacity of plant-based proteins can be compensated for by ingesting a greater dose of protein or by combining various plant-based proteins to provide a more favourable amino acid profile. In addition, leucine co-ingestion can further augment the postprandial muscle protein synthetic response. Finally, prior exercise or n-3 fatty acid supplementation have been shown to sensitise skeletal muscle to the anabolic properties of dietary protein. Applying one or more of these strategies may support the maintenance of muscle mass with ageing when diets rich in plant-based protein are consumed.
The Grotte Cosquer (southeastern France) is a Paleolithic painted cave only accessible by a deep-water dive. The cave has yielded numerous Paleolithic engravings and drawings, which were produced from wood charcoal. This article presents new radiocarbon dates obtained on samples collected in 2012 directly on 17 parietal representations and at the soil surface, and discusses the 14C results obtained since the discovery of the cave in 1992. A total of 41 samples were dated with ages ranging from 33,000 to 20,000 cal BP. They show that the cave was intermittently decorated over about 10,000 yr.
Behavioral traits generally show moderate to strong genetic influence, with heritability estimates of around 50%. Some recent research has suggested that trust may be an exception because it is more strongly influenced by social interactions. In a sample of over 7,000 adolescent twins from the United Kingdom's Twins Early Development Study, we found broad sense heritability estimates of 57% for generalized trust and 51% for trust in friends. Genomic-relatedness-matrix restricted maximum likelihood (GREML) estimates in the same sample indicate that 21% of the narrow sense genetic variance can be explained by common single nucleotide polymorphisms for generalized trust and 43% for trust in friends. As expected, this implies a large amount of unexplained heritability, although power is low for estimating DNA-based heritability. The missing heritability may be accounted for by interactions between DNA and the social environment during development or via gene–environment correlations with rare variants. How these genes and environments correlate seem especially important for the development of trust.
Africa is experiencing a rapid increase in adult obesity and associated cardiometabolic diseases (CMDs). The H3Africa AWI-Gen Collaborative Centre was established to examine genomic and environmental factors that influence body composition, body fat distribution and CMD risk, with the aim to provide insights towards effective treatment and intervention strategies. It provides a research platform of over 10 500 participants, 40–60 years old, from Burkina Faso, Ghana, Kenya and South Africa. Following a process that involved community engagement, training of project staff and participant informed consent, participants were administered detailed questionnaires, anthropometric measurements were taken and biospecimens collected. This generated a wealth of demographic, health history, environmental, behavioural and biomarker data. The H3Africa SNP array will be used for genome-wide association studies. AWI-Gen is building capacity to perform large epidemiological, genomic and epigenomic studies across several African counties and strives to become a valuable resource for research collaborations in Africa.
To describe treatment and referral patterns and National Health Service resource use in patients with chronic pain associated with low back pain or osteoarthritis, from a Primary Care perspective.
Osteoarthritis and low back pain are the two commonest debilitating causes of chronic pain, with high health and social costs, and particularly important in primary care. Understanding current practice and resource use in their management will inform health service and educational requirements and the design and optimisation of future care.
Multi-centre, retrospective, descriptive study of adults (⩾18 years) with chronic pain arising from low back pain or osteoarthritis, identified through primary care records. Five general practices in Scotland, England (two), Northern Ireland and Wales. All patients with a diagnosis of low back pain or osteoarthritis made on or before 01/09/2006 who had received three or more prescriptions for pain medication were identified and a sub-sample randomly selected then consented to an in-depth review of their medical records (n=264). Data on management of chronic pain were collected retrospectively from patients’ records for three years from diagnosis (‘newly diagnosed’ patients) or for the most recent three years (‘established’ patients).
Patients received a wide variety of pain medications with no overall common prescribing pattern. GP visits represented the majority of the resource use and ‘newly diagnosed’ patients were significantly more likely to visit their GP for pain management than ‘established’ patients. Although ‘newly diagnosed’ patients had more referrals outside the GP practice, the number of visits to secondary care for pain management was similar for both groups.
This retrospective study confirmed the complexity of managing these causes of chronic pain and the associated high resource use. It provides an in-depth picture of prescribing and referral patterns and of resource use.
Inspired by recent calculations by Thoraval et al. (Phys. Rev. Lett., vol. 108, 2012, p. 264506) relating to droplet impact, this paper presents an analysis of the perturbations to the free surface caused by small surface tension and viscosity in steady Helmholtz flows. In particular, we identify the regimes in which appreciable vorticity can be shed from the boundary layer to the bulk flow.
Maternal undernutrition during pregnancy increases offspring obesity and metabolic disease risk. We hypothesized that periconceptional undernutrition in sheep from 60 days before conception through to day 30 of gestation (UN) would decrease voluntary locomotor activity in adult offspring. Distance travelled was measured at 18 months of age for ∼48 h in the paddock. Data were analysed using multiple regression analysis, with explanatory variables including sex, nutrition group, birth weight, average time between GPS measurements and percentage of time during the measurement period spent in daylight. Mean (±s.e.) distance walked (m/h) was greater for control (CON) than UN animals, and greater for females than males [110.2 (6.5), CON females; 110.7 (6.3), CON males; 105.1 (5.3), UN females and 95.5 (5.8), UN males; P = 0.02 for nutrition group effect and for sex effect]. Periconceptional undernutrition may lead to a significant decrease in voluntary physical activity in adult offspring.