Recovering from failure by asking for help

Robots inevitably fail, often without the ability to recover autonomously. We demonstrate an approach for enabling a robot to recover from failures by communicating its need for specific help to a human partner using natural language. Our approach automatically detects failures, then generates targeted spoken-language requests for help such as “Please give me the white table leg that is on the black table.” Once the human partner has repaired the failure condition, the system resumes full autonomy. We present a novel inverse semantics algorithm for generating effective help requests. In contrast to forward semantic models that interpret natural language in terms of robot actions and perception, our inverse semantics algorithm generates requests by emulating the human’s ability to interpret a request using the Generalized Grounding Graph (G[superscript 3]) framework. To assess the effectiveness of our approach, we present a corpus-based online evaluation, as well as an end-to-end user study, demonstrating that our approach increases the effectiveness of human interventions compared to static requests for help.Boeing CompanyU.S. Army Research Laboratory (Robotics Collaborative Technology Alliance

A Prospective Longitudinal Study of the Clinical Outcomes from Cryptococcal Meningitis following Treatment Induction with 800 mg Oral Fluconazole in Blantyre, Malawi

Introduction: Cryptococcal meningitis is the most common neurological infection in HIV infected patients in Sub Saharan Africa, where gold standard treatment with intravenous amphotericin B and 5 flucytosine is often unavailable or difficult to administer. Fluconazole monotherapy is frequently recommended in national guidelines but is a fungistatic drug compromised by uncertainty over optimal dosing and a paucity of clinical end-point outcome data. Methods: From July 2010 until March 2011, HIV infected adults with a first episode of cryptococcal meningitis were recruited at Queen Elizabeth Central Hospital, Blantyre, Malawi. Patients were treated with oral fluconazole monotherapy 800 mg daily, as per national guidelines. ART was started at 4 weeks. Outcomes and factors associated with treatment failure were assessed 4, 10 and 52 weeks after fluconazole initiation. Results: Sixty patients were recruited. 26/60 (43%) died by 4 weeks. 35/60 (58.0%) and 43/56 (77%) died or failed treatment by 10 or 52 weeks respectively. Reduced consciousness (Glasgow Coma Score ,14 of 15), moderate/severe neurological disability (modified Rankin Score .3 of 5) and confusion (Abbreviated Mental Test Score ,8 of 10) were all common at baseline and associated with death or treatment failure. ART prior to recruitment was not associated with better outcomes. Conclusions: Mortality and treatment failure from cryptococcal meningitis following initiation of treatment with 800 mg oral fluconazole is unacceptably high. To improve outcomes, there is an urgent need for better therapeutic strategies and point-of-care diagnostics, allowing earlier diagnosis before development of neurological deficit

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

Labrador retrievers under primary veterinary care in the UK: demography, mortality and disorders

Abstract Background Labrador retrievers are reportedly predisposed to many disorders but accurate prevalence information relating to the general population are lacking. This study aimed to describe demography, mortality and commonly recorded diseases in Labrador retrievers under UK veterinary care. Methods The VetCompass™ programme collects electronic patient record data on dogs attending UK primary-care veterinary practices. Demographic analysis covered all33,320 Labrador retrievers in the VetCompass™ database under veterinary care during 2013 while disorder and mortality data were extracted from a random sample of 2074 (6.2%) of these dogs. Results Of the Labrador retrievers with information available, 15,427 (46.4%) were female and 15,252 (53.6%) were male. Females were more likely to be neutered than males (59.7% versus 54.8%, P <  0.001). The overall mean adult bodyweight was 33.0 kg (SD 6.1). Adult males were heavier (35.2 kg, SD 5.9 kg) than adult females (30.4 kg, SD 5.2 kg) (P <  0.001). The median longevity of Labrador retrievers overall was 12.0 years (IQR 9.9–13.8, range 0.0–16.0). The most common recorded colours were black (44.6%), yellow (27.8%) and liver/chocolate (reported from hereon as chocolate) (23.8%). The median longevity of non-chocolate coloured dogs (n = 139, 12.1 years, IQR 10.2–13.9, range 0.0–16.0) was longer than for chocolate coloured animals (n = 34, 10.7 years, IQR 9.0–12.4, range 3.8–15.5) (P = 0.028). Of a random sample of 2074 (6.2%) Labrador retrievers under care in 2013 that had full disorder data extracted, 1277 (61.6%) had at least one disorder recorded. The total number of dogs who died at any date during the study was 176. The most prevalent disorders recorded were otitis externa (n = 215, prevalence 10.4%, 95% CI: 9.1–11.8), overweight/obesity (183, 8.8%, 95% CI: 7.6–10.1) and degenerative joint disease (115, 5.5%, 95% CI: 4.6–6.6). Overweight/obesity was not statistically significantly associated with neutering in females (8.3% of entire versus 12.5% of neutered, P = 0.065) but was associated with neutering in males (4.1% of entire versus 11.4% of neutered, P < 0.001). The prevalence of otitis externa in black dogs was 12.8%, in yellow dogs it was 17.0% but, in chocolate dogs, it rose to 23.4% (P < 0.001). Similarly, the prevalence of pyo-traumatic dermatitis in black dogs was 1.1%, in yellow dogs it was 1.6% but in chocolate dogs it rose to 4.0% (P = 0.011). Conclusions The current study assists prioritisation of health issues within Labrador retrievers. The most common disorders were overweight/obesity, otitis externa and degenerative joint disease. Males were significantly heavier females. These results can alert prospective owners to potential health issues and inform breed-specific wellness checks

Comparative genomics of isolates of a pseudomonas aeruginosa epidemic strain associated with chronic lung infections of cystic fibrosis patients

Pseudomonas aeruginosa is the main cause of fatal chronic lung infections among individuals suffering from cystic fibrosis (CF). During the past 15 years, particularly aggressive strains transmitted among CF patients have been identified, initially in Europe and more recently in Canada. The aim of this study was to generate high-quality genome sequences for 7 isolates of the Liverpool epidemic strain (LES) from the United Kingdom and Canada representing different virulence characteristics in order to: (1) associate comparative genomics results with virulence factor variability and (2) identify genomic and/or phenotypic divergence between the two geographical locations. We performed phenotypic characterization of pyoverdine, pyocyanin, motility, biofilm formation, and proteolytic activity. We also assessed the degree of virulence using the Dictyostelium discoideum amoeba model. Comparative genomics analysis revealed at least one large deletion (40-50 kb) in 6 out of the 7 isolates compared to the reference genome of LESB58. These deletions correspond to prophages, which are known to increase the competitiveness of LESB58 in chronic lung infection. We also identified 308 non-synonymous polymorphisms, of which 28 were associated with virulence determinants and 52 with regulatory proteins. At the phenotypic level, isolates showed extensive variability in production of pyocyanin, pyoverdine, proteases and biofilm as well as in swimming motility, while being predominantly avirulent in the amoeba model. Isolates from the two continents were phylogenetically and phenotypically undistinguishable. Most regulatory mutations were isolate-specific and 29% of them were predicted to have high functional impact. Therefore, polymorphism in regulatory genes is likely to be an important basis for phenotypic diversity among LES isolates, which in turn might contribute to this strain's adaptability to varying conditions in the CF lung

Party rules, party resources, and the politics of parliamentary democracies: how parties organize in the 21st Century

This article introduces the first findings of the Political Party Database (PPDB) project, a major survey of party organizations in parliamentary and semi-presidential democracies. The project’s first round of data covers 122 parties in 19 countries. In this paper we describe the scope of the database, then investigate what it tells us about contemporary party organization in these countries, focussing on parties’ resources, structures and internal decision-making. We examine organizational patterns by country and party family, and where possible we make temporal comparisons with older datasets. Our analyses suggest a remarkable coexistence of uniformity and diversity. In terms of the major organizational resources on which parties can draw, such as members, staff and finance, the new evidence largely confirms the continuation of trends identified in previous research: i.e., declining membership, but enhanced financial resources and more paid staff. We also find remarkable uniformity regarding the core architecture of party organizations. At the same time, however, we find substantial variation between countries and party families in terms of their internal processes, with particular regard to how internally democratic they are, and in the forms that this democratization takes

Mammalian microRNAs predominantly act to decrease target mRNA levels

MicroRNAs (miRNAs) are endogenous ~22-nucleotide RNAs that mediate important gene-regulatory events by pairing to the mRNAs of protein-coding genes to direct their repression. Repression of these regulatory targets leads to decreased translational efficiency and/or decreased mRNA levels, but the relative contributions of these two outcomes have been largely unknown, particularly for endogenous targets expressed at low-to-moderate levels. Here, we use ribosome profiling to measure the overall effects on protein production and compare these to simultaneously measured effects on mRNA levels. For both ectopic and endogenous miRNA regulatory interactions, lowered mRNA levels account for most (≥84%) of the decreased protein production. These results show that changes in mRNA levels closely reflect the impact of miRNAs on gene expression and indicate that destabilization of target mRNAs is the predominant reason for reduced protein output.National Institutes of Health (U.S.

A review of web-based support systems for students in higher education

Abstract Background Recent evidence suggests that there is an increasing need for accessible and anonymous services to support higher education (HE) students suffering from psychological and/or academic difficulties. Such difficulties can lead to several negative outcomes, including poor academic performance, sub-optimal mental health, reduced study satisfaction, and dropout from study. Currently, universities in the UK lack financial resources and the on-campus mental health services traditionally offered to students are increasingly economically unsustainable. Compounded by the perceived stigma of using such services, mental health providers have been driven to address the escalating needs of students through online services. Methods In this paper, we review online support systems identified through a literature search and a manual search of references in the identified papers. Further systems were identified through web searches, and systems still in development were identified by consultation with researchers in the field. We accessed systems online to extract relevant information, regarding the main difficulties addressed by the systems, the psychological techniques used and any relevant research evidence to support their effectiveness. Conclusion A large number of web-based support systems have been developed to support mental health and wellbeing, although few specifically target HE students. Further research is necessary to establish the effectiveness of such interventions in providing a cost-effective alternative to face-to-face therapy, particularly in certain settings such as HE institutions

Dimensionality of Carbon Nanomaterials Determines the Binding and Dynamics of Amyloidogenic Peptides: Multiscale Theoretical Simulations

Experimental studies have demonstrated that nanoparticles can affect the rate of protein self-assembly, possibly interfering with the development of protein misfolding diseases such as Alzheimer's, Parkinson's and prion disease caused by aggregation and fibril formation of amyloid-prone proteins. We employ classical molecular dynamics simulations and large-scale density functional theory calculations to investigate the effects of nanomaterials on the structure, dynamics and binding of an amyloidogenic peptide apoC-II(60-70). We show that the binding affinity of this peptide to carbonaceous nanomaterials such as C60, nanotubes and graphene decreases with increasing nanoparticle curvature. Strong binding is facilitated by the large contact area available for π-stacking between the aromatic residues of the peptide and the extended surfaces of graphene and the nanotube. The highly curved fullerene surface exhibits reduced efficiency for π-stacking but promotes increased peptide dynamics. We postulate that the increase in conformational dynamics of the amyloid peptide can be unfavorable for the formation of fibril competent structures. In contrast, extended fibril forming peptide conformations are promoted by the nanotube and graphene surfaces which can provide a template for fibril-growth

Experimental constraints on Li isotope fractionation during clay formation

Knowledge of the lithium (Li) isotope fractionation factor during clay mineral formation is a key parameter for Earth system models. This study refines our understanding of isotope fractionation during clay formation with essential implications for the interpretation of field data and the global geochemical cycle of Li. We synthesised Mg-rich layer silicates (stevensite and saponite) at temperatures relevant for Earth surface processes. The resultant solids were characterised by X-ray diffraction (XRD) and Fourier-transform infrared spectroscopy (FT-IR) to confirm the mineralogy and crystallinity of the product. Bulk solid samples were treated with ammonium chloride to remove exchangeable Li in order to distinguish the Li isotopic fractionation between these sites and structural (octahedral) sites. Bulk solids, residual solids and exchangeable solutions were all enriched in Li compared to the initial solution. On average, the exchangeable solutions had Li values 7‰ lower than the initial solution. The average difference between the residual solid and initial solution Li values () for the synthesised layer silicates was −16.6 ± 1.7‰ at 20  C, in agreement with modelling studies, extrapolations from high temperature experimental data and field observations. Three bonding environments were identified from Li-NMR spectra which were present in both bulk and residual solid Li-NMR spectra, implying that some exchangeable Li remains after treatment with ammonium chloride. The Li-NMR peaks were assigned to octahedral, outer-sphere (interlayer and adsorbed) and pseudo-hexagonal (ditrigonal cavity) Li. By combining the Li-NMR data with mass balance constraints we calculated a fractionation factor, based on a Monte Carlo minimum misfit method, for each bonding environment. The calculated values are −21.5 ± 1.1‰, −0.2 ± 1.9‰ and 15.0 ± 12.3‰ for octahedral, outer-sphere and pseudo-hexagonal sites respectively (errors 1). The bulk fractionation factor () is dependent on the chemistry of the initial solution. The higher the Na concentration in the initial solution the lower the bulk Li value. We suggest this is due to Na outcompeting Li for interlayer sites and as interlayer Li has a high Li value relative to octahedral Li, increased Na serves to lower the bulk Li value. Three experiments conducted at higher pH exhibited lower Li values in the residual solid. This could either be a kinetic effect, resulting from the higher reaction rate at high pH, or an equilibrium effect resulting from reduced Li incorporation in the residual solid and/or a change in Li speciation in solution. This study highlights the power of Li-NMR in experimental studies of clay synthesis to target site specific Li isotope fractionation factors which can then be used to provide much needed constraints on field processes