To examine the associations of antibiotic exposures during the first 2 years of life and the development of body mass over the first 7 years of life.
Longitudinal birth cohort study.
A total of 11 ...532 children born at 2500 g in the Avon Longitudinal Study of Parents and Children (ALSPAC), a population-based study of children born in Avon, UK in 1991-1992.
Exposures to antibiotics during three different early-life time windows (<6 months, 6-14 months, 15-23 months), and indices of body mass at five time points (6 weeks, 10 months, 20 months, 38 months and 7 years).
Antibiotic exposure during the earliest time window (<6 months) was consistently associated with increased body mass (+0.105 and +0.083 s.d. unit, increase in weight-for-length Z-scores at 10 and 20 months, P<0.001 and P=0.001, respectively; body mass index (BMI) Z-score at 38 months +0.067 s.d. units, P=0.009; overweight OR 1.22 at 38 months, P=0.029) in multivariable, mixed-effect models controlling for known social and behavioral obesity risk factors. Exposure from 6 to 14 months showed no association with body mass, while exposure from 15 to 23 months was significantly associated with increased BMI Z-score at 7 years (+0.049 s.d. units, P=0.050). Exposures to non-antibiotic medications were not associated with body mass.
Exposure to antibiotics during the first 6 months of life is associated with consistent increases in body mass from 10 to 38 months. Exposures later in infancy (6-14 months, 15-23 months) are not consistently associated with increased body mass. Although effects of early exposures are modest at the individual level, they could have substantial consequences for population health. Given the prevalence of antibiotic exposures in infants, and in light of the growing concerns about childhood obesity, further studies are needed to isolate effects and define life-course implications for body mass and cardiovascular risks.
Artificial Intelligence (AI) and robotics are likely to have a significant long-term impact on higher education (HE). The scope of this impact is hard to grasp partly because the literature is ...siloed, as well as the changing meaning of the concepts themselves. But developments are surrounded by controversies in terms of what is technically possible, what is practical to implement and what is desirable, pedagogically or for the good of society. Design fictions that vividly imagine future scenarios of AI or robotics in use offer a means both to explain and query the technological possibilities. The paper describes the use of a wide-ranging narrative literature review to develop eight such design fictions that capture the range of potential use of AI and robots in learning, administration and research. They prompt wider discussion by instantiating such issues as how they might enable teaching of high order skills or change staff roles, as well as exploring the impact on human agency and the nature of datafication.
Males and females share most of their genomes and express many of the same traits, yet the sexes often have markedly different selective optima for these shared traits. This sexually antagonistic ...(SA) selection generates intralocus sexual conflict that is thought to be resolved through the evolution of sexual dimorphism. However, we currently know little about the prevalence of SA selection, the components of fitness that generate sexual antagonism, or the relationship between sexual dimorphism and current SA selection. We reviewed published studies to address these questions, using 424 selection estimates representing 89 traits from 34 species. Males and females often differed substantially in the direction and magnitude of selection on shared traits, although statistically significant SA selection was relatively uncommon. Sexual selection generated stronger sexual antagonism than fecundity or viability selection, and these individual components of fitness tended to reinforce one another to generate even stronger sexual antagonism for net fitness. Traits exhibiting strong sexual dimorphism exhibited greater SA selection than did weakly dimorphic traits, although this pattern was not significant after we controlled for the inclusion of multiple traits nested within species. Our results suggest that intralocus sexual conflict often may persist despite the evolution of sexual dimorphism.
The functional interactions between the gut microbiota and the host are important for host physiology, homeostasis, and sustained health. We compared the skeletal muscle of germ-free mice that lacked ...a gut microbiota to the skeletal muscle of pathogen-free mice that had a gut microbiota. Compared to pathogen-free mouse skeletal muscle, germ-free mouse skeletal muscle showed atrophy, decreased expression of insulin-like growth factor 1, and reduced transcription of genes associated with skeletal muscle growth and mitochondrial function. Nuclear magnetic resonance spectrometry analysis of skeletal muscle, liver, and serum from germ-free mice revealed multiple changes in the amounts of amino acids, including glycine and alanine, compared to pathogen-free mice. Germ-free mice also showed reduced serum choline, the precursor of acetylcholine, the key neurotransmitter that signals between muscle and nerve at neuromuscular junctions. Reduced expression of genes encoding Rapsyn and Lrp4, two proteins important for neuromuscular junction assembly and function, was also observed in skeletal muscle from germ-free mice compared to pathogen-free mice. Transplanting the gut microbiota from pathogen-free mice into germ-free mice resulted in an increase in skeletal muscle mass, a reduction in muscle atrophy markers, improved oxidative metabolic capacity of the muscle, and elevated expression of the neuromuscular junction assembly genes
and
Treating germ-free mice with short-chain fatty acids (microbial metabolites) partly reversed skeletal muscle impairments. Our results suggest a role for the gut microbiota in regulating skeletal muscle mass and function in mice.
Acquisition of the intestinal microbiota begins at birth, and a stable microbial community develops from a succession of key organisms. Disruption of the microbiota during maturation by low-dose ...antibiotic exposure can alter host metabolism and adiposity. We now show that low-dose penicillin (LDP), delivered from birth, induces metabolic alterations and affects ileal expression of genes involved in immunity. LDP that is limited to early life transiently perturbs the microbiota, which is sufficient to induce sustained effects on body composition, indicating that microbiota interactions in infancy may be critical determinants of long-term host metabolic effects. In addition, LDP enhances the effect of high-fat diet induced obesity. The growth promotion phenotype is transferrable to germ-free hosts by LDP-selected microbiota, showing that the altered microbiota, not antibiotics per se, play a causal role. These studies characterize important variables in early-life microbe-host metabolic interaction and identify several taxa consistently linked with metabolic alterations.
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•Early life is a critical window of host-microbe metabolic interaction•Low-dose penicillin treatment amplifies diet-induced obesity•A transient early microbiota perturbation leads to long-term increased adiposity•The penicillin-altered microbiota has a causal role in inducing metabolic changes
Early-life transient perturbations of the intestinal microbiota drive changes in metabolism and body composition that persist in adult life.
Curcumin possesses many properties which may prevent or ameliorate pathological processes underlying age-related cognitive decline, dementia or mood disorders. These benefits in preclinical studies ...have not been established in humans. This randomized, double-blind, placebo-controlled trial examined the acute (1 and 3 h after a single dose), chronic (4 weeks) and acute-on-chronic (1 and 3 h after single dose following chronic treatment) effects of solid lipid curcumin formulation (400 mg as Longvida®) on cognitive function, mood and blood biomarkers in 60 healthy adults aged 60–85. One hour after administration curcumin significantly improved performance on sustained attention and working memory tasks, compared with placebo. Working memory and mood (general fatigue and change in state calmness, contentedness and fatigue induced by psychological stress) were significantly better following chronic treatment. A significant acute-on-chronic treatment effect on alertness and contentedness was also observed. Curcumin was associated with significantly reduced total and LDL cholesterol and had no effect on hematological safety measures. To our knowledge this is the first study to examine the effects of curcumin on cognition and mood in a healthy older population or to examine any acute behavioral effects in humans. Results highlight the need for further investigation of the potential psychological and cognitive benefits of curcumin in an older population.
Climate sensitivity to CO2 remains the key uncertainty in projections of future climate change. Transient climate response (TCR) is the metric of temperature sensitivity that is most relevant to ...warming in the next few decades and contributes the biggest uncertainty to estimates of the carbon budgets consistent with the Paris targets. Equilibrium climate sensitivity (ECS) is vital for understanding longer-term climate change and stabilisation targets. In the IPCC 5th Assessment Report (AR5), the stated “likely” ranges (16 %–84 % confidence) of TCR (1.0–2.5 K) and ECS (1.5–4.5 K) were broadly consistent with the ensemble of CMIP5 Earth system models (ESMs) available at the time. However, many of the latest CMIP6 ESMs have larger climate sensitivities, with 5 of 34 models having TCR values above 2.5 K and an ensemble mean TCR of 2.0±0.4 K. Even starker, 12 of 34 models have an ECS value above 4.5 K. On the face of it, these latest ESM results suggest that the IPCC likely ranges may need revising upwards, which would cast further doubt on the feasibility of the Paris targets. Here we show that rather than increasing the uncertainty in climate sensitivity, the CMIP6 models help to constrain the likely range of TCR to 1.3–2.1 K, with a central estimate of 1.68 K. We reach this conclusion through an emergent constraint approach which relates the value of TCR linearly to the global warming from 1975 onwards. This is a period when the signal-to-noise ratio of the net radiative forcing increases strongly, so that uncertainties in aerosol forcing become progressively less problematic. We find a consistent emergent constraint on TCR when we apply the same method to CMIP5 models. Our constraints on TCR are in good agreement with other recent studies which analysed CMIP ensembles. The relationship between ECS and the post-1975 warming trend is less direct and also non-linear. However, we are able to derive a likely range of ECS of 1.9–3.4 K from the CMIP6 models by assuming an underlying emergent relationship based on a two-box energy balance model. Despite some methodological differences; this is consistent with a previously published ECS constraint derived from warming trends in CMIP5 models to 2005. Our results seem to be part of a growing consensus amongst studies that have applied the emergent constraint approach to different model ensembles and to different aspects of the record of global warming.
The management of research data is now a major challenge for research organisations. Vast quantities of born-digital data are being produced in a wide variety of forms at a rapid rate in ...universities. This paper analyses the contribution of academic libraries to research data management (RDM) in the wider institutional context. In particular it: examines the roles and relationships involved in RDM, identifies the main components of an RDM programme, evaluates the major drivers for RDM activities, and analyses the key factors influencing the shape of RDM developments. The study is written from the perspective of library professionals, analysing data from 26 semi-structured interviews of library staff from different UK institutions. This is an early qualitative contribution to the topic complementing existing quantitative and case study approaches. Results show that although libraries are playing a significant role in RDM, there is uncertainty and variation in the relationship with other stakeholders such as IT services and research support offices. Current emphases in RDM programmes are on developments of policies and guidelines, with some early work on technology infrastructures and support services. Drivers for developments include storage, security, quality, compliance, preservation, and sharing with libraries associated most closely with the last three. The paper also highlights a 'jurisdictional' driver in which libraries are claiming a role in this space. A wide range of factors, including governance, resourcing and skills, are identified as influencing ongoing developments. From the analysis, a model is constructed designed to capture the main aspects of an institutional RDM programme. This model helps to clarify the different issues involved in RDM, identifying layers of activity, multiple stakeholders and drivers, and a large number of factors influencing the implementation of any initiative. Institutions may usefully benchmark their activities against the data and model in order to inform ongoing RDM activity.
Uncertainties in the response of vegetation to rising atmospheric CO2 concentrations1,2 contribute to the large spread in projections of future climate change3,4. Climate-carbon cycle models ...generally agree that elevated atmospheric CO2 concentrations will enhance terrestrial gross primary productivity (GPP). However, the magnitude of this CO2 fertilization effect varies from a 20 per cent to a 60 per cent increase in GPP for a doubling of atmospheric CO2 concentrations in model studies5-7. Here we demonstrate emergent constraints8-11 on large-scale CO2 fertilization using observed changes in the amplitude of the atmospheric CO2 seasonal cycle that are thought to be the result of increasing terrestrial GPP12-14. Our comparison of atmospheric CO2 measurements from Point Barrow in Alaska and Cape Kumukahi in Hawaii with historical simulations of the latest climate-carbon cycle models demonstrates that the increase in the amplitude of the CO2 seasonal cycle at both measurement sites is consistent with increasing annual mean GPP, driven in part by climate warming, but with differences in CO2 fertilization controlling the spread among the model trends. As a result, the relationship between the amplitude of the CO2 seasonal cycle and the magnitude of CO2 fertilization of GPP is almost linear across the entire ensemble of models. When combined with the observed trends in the seasonal CO2 amplitude, these relationships lead to consistent emergent constraints on the CO2 fertilization of GPP. Overall, we estimate a GPP increase of 37 ± 9 per cent for high-latitude ecosystems and 32 ± 9 per cent for extratropical ecosystems under a doubling of atmospheric CO2 concentrations on the basis of the Point Barrow and Cape Kumukahi records, respectively.
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