Robots that can adapt like animals

As robots leave the controlled environments of factories to autonomously function in more complex, natural environments, they will have to respond to the inevitable fact that they will become damaged. However, while animals can quickly adapt to a wide variety of injuries, current robots cannot "think outside the box" to find a compensatory behavior when damaged: they are limited to their pre-specified self-sensing abilities, can diagnose only anticipated failure modes, and require a pre-programmed contingency plan for every type of potential damage, an impracticality for complex robots. Here we introduce an intelligent trial and error algorithm that allows robots to adapt to damage in less than two minutes, without requiring self-diagnosis or pre-specified contingency plans. Before deployment, a robot exploits a novel algorithm to create a detailed map of the space of high-performing behaviors: This map represents the robot's intuitions about what behaviors it can perform and their value. If the robot is damaged, it uses these intuitions to guide a trial-and-error learning algorithm that conducts intelligent experiments to rapidly discover a compensatory behavior that works in spite of the damage. Experiments reveal successful adaptations for a legged robot injured in five different ways, including damaged, broken, and missing legs, and for a robotic arm with joints broken in 14 different ways. This new technique will enable more robust, effective, autonomous robots, and suggests principles that animals may use to adapt to injury

An investigation of movement dynamics and muscle activity during traditional and accentuated-eccentric squatting.

Introduction: Accentuated-eccentric loading (AEL) takes advantage of the high force producing potential of eccentric muscle contractions, potentially maximising mechanical tension within the muscle. However, evidence is lacking on how AEL squatting may load the involved musculature, limiting scientifically justified programming recommendations. The purpose of this study was to investigate the effects of concentric and eccentric loads on joint loading and muscle activity of the lower limbs. Methods: Resistance trained males performed traditional squatting (20–100% of concentric one-repetition maximum [1RM]) and AEL squatting with eccentric loads (110–150% of 1RM) provided by a novel motorised isotonic resistance machine (Kineo). Kinetics and kinematics of the hip, knee, and ankle joints were collected, with electromyography from the gluteus maximus, vastus lateralis, biceps femoris, and gastrocnemius medialis. A secondary cohort underwent a kinematic and electromyography analysis of squatting technique to compare Kineo and back and front barbell squatting. Results: Knee joint peak eccentric moments occurred at 120% 1RM (P = 0.045), with no further increase thereafter. As eccentric load increased, the time course of moment development occurred earlier in the eccentric phase. This resulted in a 37% increase in eccentric knee extensor work from the 80% 1RM trial to the 120% 1RM trial (P<0.001). Neither hip nor ankle joints displayed further change in kinetics as eccentric load increased above 100% 1RM. Electromyographic activity during traditional squatting was ~15–30% lower in all eccentric trials than in concentric trials for all muscles. EMG plateaued between a load of 80–100% 1RM during the eccentric trials and did not increase with AEL. No significant differences in kinematics were found between Kineo and barbell squatting. Conclusions: The knee extensors appear to be preferentially loaded during AEL squatting. The greater work performed during the eccentric phase of the squat as eccentric load increased suggests greater total mechanical tension could be the cause of adaptations from AEL. Our data suggest that AEL should be programmed with a load of 120% of 1RM. Further studies are needed to confirm the longer-term training effects of AEL

Mechanical loading of bioengineered skeletal muscle in vitro recapitulates gene expression signatures of resistance exercise in vivo.

Understanding the role of mechanical loading and exercise in skeletal muscle (SkM) is paramount for delineating the molecular mechanisms that govern changes in muscle mass. However, it is unknown whether loading of bioengineered SkM in vitro adequately recapitulates the molecular responses observed after resistance exercise (RE) in vivo. To address this, the transcriptional and epigenetic (DNA methylation) responses were compared after mechanical loading in bioengineered SkM in vitro and after RE in vivo. Specifically, genes known to be upregulated/hypomethylated after RE in humans were analyzed. Ninety-three percent of these genes demonstrated similar changes in gene expression post-loading in the bioengineered muscle when compared to acute RE in humans. Furthermore, similar differences in gene expression were observed between loaded bioengineered SkM and after programmed RT in rat SkM tissue. Hypomethylation occurred for only one of the genes analysed (GRIK2) post-loading in bioengineered SkM. To further validate these findings, DNA methylation and mRNA expression of known hypomethylated and upregulated genes post-acute RE in humans were also analyzed at 0.5, 3, and 24 h post-loading in bioengineered muscle. The largest changes in gene expression occurred at 3 h, whereby 82% and 91% of genes responded similarly when compared to human and rodent SkM respectively. DNA methylation of only a small proportion of genes analyzed (TRAF1, MSN, and CTTN) significantly increased post-loading in bioengineered SkM alone. Overall, mechanical loading of bioengineered SkM in vitro recapitulates the gene expression profile of human and rodent SkM after RE in vivo. Although some genes demonstrated differential DNA methylation post-loading in bioengineered SkM, such changes across the majority of genes analyzed did not closely mimic the epigenetic response to acute-RE in humans

Smoke-free legislation and the incidence of paediatric respiratory infections and wheezing/asthma: interrupted time series analyses in the four UK nations

We investigated the association between introduction of smoke-free legislation in the UK (March 2006 for Scotland, April 2007 for Wales and Northern Ireland, and July 2007 for England) and the incidence of respiratory diseases among children. We extracted monthly counts of new diagnoses of wheezing/asthma and RTIs among children aged 0–12 years from all general practices in the Clinical Practice Research Datalink during 1997–2012. Interrupted time series analyses were performed using generalised additive mixed models, adjusting for underlying incidence trends, population size changes, seasonal factors, and pandemic influenza, as appropriate. 366,642 new wheezing/asthma diagnoses and 4,324,789 RTIs were observed over 9,536,003 patient-years. There was no statistically significant change in the incidence of wheezing/asthma after introduction of smoke-free legislation in England (incidence rate ratio (IRR) 0.94, 95% CI 0.81–1.09) or any other UK country (Scotland: IRR 0.99, 95% CI 0.83–1.19; Wales: IRR 1.09, 95% CI 0.89–1.35; Northern Ireland: IRR 0.96, 95% CI 0.76–1.22). Similarly no statistically significant changes in RTI incidence were demonstrated (England: IRR 0.95, 95% CI 0.86–1.06; Scotland: IRR 0.96, 95% CI 0.83–1.11; Wales: IRR 0.97, 95% CI 0.86–1.09; Northern Ireland: IRR 0.90, 95% CI 0.79–1.03). There were no demonstrable reductions in the incidence of paediatric wheezing/asthma or RTIs following introduction of smoke-free legislation in the UK

Extraordinary lifespans in ants: a test of evolutionary theories of ageing

Senescence presents not only a medical problem, but also an evolutionary paradox because it should be opposed by natural selection. Evolutionary hypotheses propose that ageing evolves as the necessary cost of processes increasing early reproductive success(1,2), or because of weaker selection against late-acting mutations(3). A prediction of these hypotheses is that the rate of ageing should increase and the average lifespan decrease as the rate of extrinsic mortality increases(1-7). Alternatively, non-adaptive, purely mechanistic hypotheses invoke damage to DNA, cells, tissues and organs as being the unique cause of senescence and ineluctable death of organisms(8). Here we show that the evolution of eusociality is associated with a 100-fold increase in insect lifespan. Such an increase is predicted by evolutionary theories because termite, bee and ant queens live in colonies that are sheltered and heavily defended against predators. Moreover, a comparison of ants with contrasting life histories also reveals an association between lifespan and extrinsic rate of mortality. These results provide strong support for evolutionary theories of ageing, as purely mechanistic hypotheses of senescence do not propose any association between the rate of extrinsic mortality and lifespans

Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis

Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis

Predictors of children's secondhand smoke exposure at home: a systematic review and narrative synthesis of the evidence

BACKGROUND: Children's exposure to secondhand smoke (SHS) has been causally linked to a number of childhood morbidities and mortalities. Over 50% of UK children whose parents are smokers are regularly exposed to SHS at home. No previous review has identified the factors associated with children's SHS exposure in the home. AIM: To identify by systematic review, the factors which are associated with children's SHS exposure in the home, determined by parent or child reports and/or biochemically validated measures including cotinine, carbon monoxide or home air particulate matter. METHODS: Electronic searches of MEDLINE, EMBASE, PsychINFO, CINAHL and Web of Knowledge to July 2014, and hand searches of reference lists from publications included in the review were conducted. FINDINGS: Forty one studies were included in the review. Parental smoking, low socioeconomic status and being less educated were all frequently and consistently found to be independently associated with children's SHS exposure in the home. Children whose parents held more negative attitudes towards SHS were less likely to be exposed. Associations were strongest for parental cigarette smoking status; compared to children of non-smokers, those whose mothers or both parents smoked were between two and 13 times more likely to be exposed to SHS. CONCLUSION: Multiple factors are associated with child SHS exposure in the home; the best way to reduce child SHS exposure in the home is for smoking parents to quit. If parents are unable or unwilling to stop smoking, they should instigate smoke-free homes. Interventions targeted towards the socially disadvantaged parents aiming to change attitudes to smoking in the presence of children and providing practical support to help parents smoke outside the home may be beneficial

AMBIsome Therapy Induction OptimisatioN (AMBITION): High dose AmBisome for cryptococcal meningitis induction therapy in sub-Saharan Africa: economic evaluation protocol for a randomised controlled trial-based equivalence study.

INTRODUCTION: Cryptococcal meningitis is responsible for around 15% of all HIV-related deaths globally. Conventional treatment courses with amphotericin B require prolonged hospitalisation and are associated with multiple toxicities and poor outcomes. A phase II study has shown that a single high dose of liposomal amphotericin may be comparable to standard treatment. We propose a phase III clinical endpoint trial comparing single, high-dose liposomal amphotericin with the WHO recommended first-line treatment at six sites across five counties. An economic analysis is essential to support wide-scale implementation. METHODS AND ANALYSIS: Country-specific economic evaluation tools will be developed across the five country settings. Details of patient and household out-of-pocket expenses and any catastrophic healthcare expenditure incurred will be collected via interviews from trial patients. Health service patient costs and related household expenditure in both arms will be compared over the trial period in a probabilistic approach, using Monte Carlo bootstrapping methods. Costing information and number of life-years survived will be used as the input to a decision-analytic model to assess the cost-effectiveness of a single, high-dose liposomal amphotericin to the standard treatment. In addition, these results will be compared with a historical cohort from another clinical trial. ETHICS AND DISSEMINATION: The AMBIsome Therapy Induction OptimisatioN (AMBITION) trial has been evaluated and approved by the London School of Hygiene and Tropical Medicine, University of Botswana, Malawi National Health Sciences, University of Cape Town, Mulago Hospital and Zimbabwe Medical Research Council research ethics committees. All participants will provide written informed consent or if lacking capacity will have consent provided by a proxy. The findings of this economic analysis, part of the AMBITION trial, will be disseminated through peer-reviewed publications and at international and country-level policy meetings. TRIAL REGISTRATION: ISRCTN 7250 9687; Pre-results

Smoking, respiratory symptoms and likely asthma in young people: evidence from postal questionnaire surveys in the Wythenshawe Community Asthma Project (WYCAP)

BACKGROUND: Although it is recognised that smoking is a major risk factor for subjects with chronic obstructive pulmonary disease and is associated with respiratory symptoms, there is less agreement concerning the relationship between asthma and smoking. This study aims to examine the relationship between cigarette smoking and asthma prevalence. METHOD: Data were used from two postal questionnaire surveys (1999 and 2001) in two general practice populations, using a respiratory questionnaire based on the ECRHQ and a generic quality of life questionnaire (EQ-5D). Only subjects less than 45 years old were included in the survey. An empirical definition of likely asthma was used based on respiratory questionnaire responses. Smoking was examined according to three categories, current smoker, ex smoker and never smoker. RESULTS: Almost 3500 subjects were included in the analyses. Current smokers had a higher prevalence of likely asthma compared to never smokers, odds ratio (OR) 1.59 (95% confidence interval (CI) 1.24 to 2.04). and also compared to ex smokers OR 1.79 (CI 1.25 to 2.56), but there was no difference between ex smokers and never smokers (OR 1.00 (0.75–1.35)). Current smoking was also positively associated with all symptoms but not with a history of hayfever/eczema. CONCLUSION: Although the positive association found between current smoking and obstructive airways disease is likely to be due to the effect of cigarettes on asthma, it could reflect an association with early COPD (GOLD stages 0 or 1). Smoking cessation has a beneficial effect on the prevalence of respiratory symptoms and is therefore of paramount importance among these young adults

Probabilistic downscaling of remote sensing data with applications for multi-scale biogeochemical flux modeling

Upscaling ecological information to larger scales in space and downscaling remote sensing observations or model simulations to finer scales remain grand challenges in Earth system science. Downscaling often involves inferring subgrid information from coarse-scale data, and such ill-posed problems are classically addressed using regularization. Here, we apply two-dimensional Tikhonov Regularization (2DTR) to simulate subgrid surface patterns for ecological applications. Specifically, we test the ability of 2DTR to simulate the spatial statistics of high-resolution (4 m) remote sensing observations of the normalized difference vegetation index (NDVI) in a tundra landscape. We find that the 2DTR approach as applied here can capture the major mode of spatial variability of the high-resolution information, but not multiple modes of spatial variability, and that the Lagrange multiplier (γ) used to impose the condition of smoothness across space is related to the range of the experimental semivariogram. We used observed and 2DTR-simulated maps of NDVI to estimate landscape-level leaf area index (LAI) and gross primary productivity (GPP). NDVI maps simulated using a γ value that approximates the range of observed NDVI result in a landscape-level GPP estimate that differs by ca 2% from those created using observed NDVI. Following findings that GPP per unit LAI is lower near vegetation patch edges, we simulated vegetation patch edges using multiple approaches and found that simulated GPP declined by up to 12% as a result. 2DTR can generate random landscapes rapidly and can be applied to disaggregate ecological information and compare of spatial observations against simulated landscapes