Finding polynomial loop invariants for probabilistic programs

Quantitative loop invariants are an essential element in the verification of probabilistic programs. Recently, multivariate Lagrange interpolation has been applied to synthesizing polynomial invariants. In this paper, we propose an alternative approach. First, we fix a polynomial template as a candidate of a loop invariant. Using Stengle's Positivstellensatz and a transformation to a sum-of-squares problem, we find sufficient conditions on the coefficients. Then, we solve a semidefinite programming feasibility problem to synthesize the loop invariants. If the semidefinite program is unfeasible, we backtrack after increasing the degree of the template. Our approach is semi-complete in the sense that it will always lead us to a feasible solution if one exists and numerical errors are small. Experimental results show the efficiency of our approach.Comment: accompanies an ATVA 2017 submissio

Counterexample-Guided Polynomial Loop Invariant Generation by Lagrange Interpolation

We apply multivariate Lagrange interpolation to synthesize polynomial quantitative loop invariants for probabilistic programs. We reduce the computation of an quantitative loop invariant to solving constraints over program variables and unknown coefficients. Lagrange interpolation allows us to find constraints with less unknown coefficients. Counterexample-guided refinement furthermore generates linear constraints that pinpoint the desired quantitative invariants. We evaluate our technique by several case studies with polynomial quantitative loop invariants in the experiments

Measures for assessing practice change in medical practitioners

BACKGROUND: There are increasing numbers of randomised trials and systematic reviews examining the efficacy of interventions designed to bring about a change in clinical practice. The findings of this research are being used to guide strategies to increase the uptake of evidence into clinical practice. Knowledge of the outcomes measured by these trials is vital not only for the interpretation and application of the work done to date, but also to inform future research in this expanding area of endeavour and to assist in collation of results in systematic reviews and meta-analyses. METHODS: The objective of this review was to identify methods used to measure change in the clinical practices of health professionals following an intervention aimed at increasing the uptake of evidence into practice. All published trials included in a recent, comprehensive Health Technology Assessment of interventions to implement clinical practice guidelines and change clinical practice (n = 228) formed the sample for this study. Using a standardised data extraction form, one reviewer (SH), extracted the relevant information from the methods and/or results sections of the trials. RESULTS: Measures of a change of health practitioner behaviour were the most common, with 88.8% of trials using these as outcome measures. Measures that assessed change at a patient level, either actual measures of change or surrogate measures of change, were used in 28.8% and 36.7% of studies (respectively). Health practitioners' knowledge and attitudes were assessed in 22.8% of the studies and changes at an organisational level were assessed in 17.6%. CONCLUSION: Most trials of interventions aimed at changing clinical practice measured the effect of the intervention at the level of the practitioner, i.e. did the practitioner change what they do, or has their knowledge of and/or attitude toward that practice changed? Less than one-third of the trials measured, whether or not any change in practice, resulted in a change in the ultimate end-point of patient health status

Alterations in the gut microbiome implicate key taxa and metabolic pathways across inflammatory arthritis phenotypes

Musculoskeletal diseases affect up to 20% of adults worldwide. The gut microbiome has been implicated in inflammatory conditions, but large-scale metagenomic evaluations have not yet traced the routes by which immunity in the gut affects inflammatory arthritis. To characterize the community structure and associated functional processes driving gut microbial involvement in arthritis, the Inflammatory Arthritis Microbiome Consortium investigated 440 stool shotgun metagenomes comprising 221 adults diagnosed with rheumatoid arthritis, ankylosing spondylitis, or psoriatic arthritis and 219 healthy controls and individuals with joint pain without an underlying inflammatory cause. Diagnosis explained about 2% of gut taxonomic variability, which is comparable in magnitude to inflammatory bowel disease. We identified several candidate microbes with differential carriage patterns in patients with elevated blood markers for inflammation. Our results confirm and extend previous findings of increased carriage of typically oral and inflammatory taxa and decreased abundance and prevalence of typical gut clades, indicating that distal inflammatory conditions, as well as local conditions, correspond to alterations to the gut microbial composition. We identified several differentially encoded pathways in the gut microbiome of patients with inflammatory arthritis, including changes in vitamin B salvage and biosynthesis and enrichment of iron sequestration. Although several of these changes characteristic of inflammation could have causal roles, we hypothesize that they are mainly positive feedback responses to changes in host physiology and immune homeostasis. By connecting taxonomic alternations to functional alterations, this work expands our understanding of the shifts in the gut ecosystem that occur in response to systemic inflammation during arthritis

Multivariable association discovery in population-scale meta-omics studies.

It is challenging to associate features such as human health outcomes, diet, environmental conditions, or other metadata to microbial community measurements, due in part to their quantitative properties. Microbiome multi-omics are typically noisy, sparse (zero-inflated), high-dimensional, extremely non-normal, and often in the form of count or compositional measurements. Here we introduce an optimized combination of novel and established methodology to assess multivariable association of microbial community features with complex metadata in population-scale observational studies. Our approach, MaAsLin 2 (Microbiome Multivariable Associations with Linear Models), uses generalized linear and mixed models to accommodate a wide variety of modern epidemiological studies, including cross-sectional and longitudinal designs, as well as a variety of data types (e.g., counts and relative abundances) with or without covariates and repeated measurements. To construct this method, we conducted a large-scale evaluation of a broad range of scenarios under which straightforward identification of meta-omics associations can be challenging. These simulation studies reveal that MaAsLin 2\u27s linear model preserves statistical power in the presence of repeated measures and multiple covariates, while accounting for the nuances of meta-omics features and controlling false discovery. We also applied MaAsLin 2 to a microbial multi-omics dataset from the Integrative Human Microbiome (HMP2) project which, in addition to reproducing established results, revealed a unique, integrated landscape of inflammatory bowel diseases (IBD) across multiple time points and omics profiles

A case study evaluation of competitors undertaking an antarctic ultra-endurance event: nutrition, hydration and body composition variables

Background: The nutritional demands of ultra-endurance racing are well documented. However, the relationship between nutritional consumption and performance measures are less obvious for athletes competing in Polar conditions. Therefore, the aim of this study was to evaluate dietary intake, hydration status, body composition and performance times throughout an 800-km Antarctic race. Methods: The event organisers declared that 17 competitors would participate in the South Pole race. Of the 17 competitors, pre-race data were collected from 13 participants (12 males and 1 female (M±SD): age: 40.1±8.9 years; weight 83.9±10.3kg; and body fat percentage: 21.9±3.8%). Dietary recall, body composition and urinary osmolarity were assessed pre-race, midway checkpoint and end race. Data were compared on the basis of fast finishers (the Norwegian team (n=3) who won in a record of 14 day) and slower finishers (the remaining teams (n=10) reaching the South Pole between 22 and 28 days). Results: The percentage contribution of macronutrients to daily energy intake for all participants was as follows: carbohydrate (CHO) - 23.7% (221±82 g.day-1), fat = 60.6% (251±127g.day-1) and protein = 15.7% (117±52g.day-1). Energy demands were closer met by faster finishers compared to slower finishers (5,332±469 vs. 3,048±1,140kcal.day-1, p=0.02). Average reduction in body mass throughout the race was 8.3±5.5kg, with an average loss of lean mass of 2.0±4.1kg. There as a significant negative correlation between changes in lean mass and protein intake (p=0.03), and lean mass and energy intake (p=0.03). End-race urinary osmolarity was significantly elevated for faster finishers compared to slower finishers and control volunteers (faster finishers: 933±157mOsmol.L-1; slower finishers: 543±92mOsmol.L-1; control: 515±165mOsmol.L-1, p+0.04). Conclusions: Throughout the race, both groups were subjected to a negative change in energy balance which partly explained reduced body mass. Carbohydrate availability was limited inferring a greater reliance on fat and protein metabolism. Consequently, loss in fat-free mass was more prevalent with insufficient protein and caloric intake, which may relate to performance

First narrow-band search for continuous gravitational waves from known pulsars in advanced detector data

Spinning neutron stars asymmetric with respect to their rotation axis are potential sources of continuous gravitational waves for ground-based interferometric detectors. In the case of known pulsars a fully coherent search, based on matched filtering, which uses the position and rotational parameters obtained from electromagnetic observations, can be carried out. Matched filtering maximizes the signalto- noise (SNR) ratio, but a large sensitivity loss is expected in case of even a very small mismatch between the assumed and the true signal parameters. For this reason, narrow-band analysis methods have been developed, allowing a fully coherent search for gravitational waves from known pulsars over a fraction of a hertz and several spin-down values. In this paper we describe a narrow-band search of 11 pulsars using data from Advanced LIGO’s first observing run. Although we have found several initial outliers, further studies show no significant evidence for the presence of a gravitational wave signal. Finally, we have placed upper limits on the signal strain amplitude lower than the spin-down limit for 5 of the 11 targets over the bands searched; in the case of J1813-1749 the spin-down limit has been beaten for the first time. For an additional 3 targets, the median upper limit across the search bands is below the spin-down limit. This is the most sensitive narrow-band search for continuous gravitational waves carried out so far

A Unique Combination of Male Germ Cell miRNAs Coordinates Gonocyte Differentiation

The last 100 years have seen a concerning decline in male reproductive health associated with decreased sperm production, sperm function and male fertility. Concomitantly, the incidence of defects in reproductive development, such as undescended testes, hypospadias and testicular cancer has increased. Indeed testicular cancer is now recognised as the most common malignancy in young men. Such cancers develop from the pre-invasive lesion Carcinoma in Situ (CIS), a dysfunctional precursor germ cell or gonocyte which has failed to successfully differentiate into a spermatogonium. It is therefore essential to understand the cellular transition from gonocytes to spermatogonia, in order to gain a better understanding of the aetiology of testicular germ cell tumours. MicroRNA (miRNA) are important regulators of gene expression in differentiation and development and thus highly likely to play a role in the differentiation of gonocytes. In this study we have examined the miRNA profiles of highly enriched populations of gonocytes and spermatogonia, using microarray technology. We identified seven differentially expressed miRNAs between gonocytes and spermatogonia (down-regulated: miR-293, 291a-5p, 290-5p and 294*, up-regulated: miR-136, 743a and 463*). Target prediction software identified many potential targets of several differentially expressed miRNA implicated in germ cell development, including members of the PTEN, and Wnt signalling pathways. These targets converge on the key downstream cell cycle regulator Cyclin D1, indicating that a unique combination of male germ cell miRNAs coordinate the differentiation and maintenance of pluripotency in germ cells

Stridulations Reveal Cryptic Speciation in Neotropical Sympatric Ants

The taxonomic challenge posed by cryptic species underlines the importance of using multiple criteria in species delimitation. In the current paper we tested the use of acoustic analysis as a tool to assess the real diversity in a cryptic species complex of Neotropical ants. In order to understand the potential of acoustics and to improve consistency in the conclusions by comparing different approaches, phylogenetic relationships of all the morphs considered were assessed by the analysis of a fragment of the mitochondrial DNA cytochrome b. We observed that each of the cryptic morph studied presents a morphologically distinct stridulatory organ and that all sympatric morphs produce distinctive stridulations. This is the first evidence of such a degree of specialization in the acoustic organ and signals in ants, which suggests that stridulations may be among the cues used by these ants during inter-specific interactions. Mitochondrial DNA variation corroborated the acoustic differences observed, confirming acoustics as a helpful tool to determine cryptic species in this group of ants, and possibly in stridulating ants in general. Congruent morphological, acoustic and genetic results constitute sufficient evidence to propose each morph studied here as a valid new species, suggesting that P. apicalis is a complex of at least 6 to 9 species, even if they present different levels of divergence. Finally, our results highlight that ant stridulations may be much more informative than hitherto thought, as much for ant communication as for integrative taxonomists