Towards rigorously faking bidirectional model transformations

Bidirectional model transformations (bx) are mechanisms for auto-matically restoring consistency between multiple concurrently modified models. They are, however, challenging to implement; many model transformation languages not supporting them at all. In this paper, we propose an approach for automatically obtaining the consistency guarantees of bx without the complexities of a bx language. First, we show how to “fake” true bidirectionality using pairs of unidirectional transformations and inter-model consistency constraints in Epsilon. Then, we propose to automatically verify that these transformations are consistency preserving — thus indistinguishable from true bx — by defining translations to graph rewrite rules and nested conditions, and leveraging recent proof calculi for graph transformation verification

Systematic reviews: guidance relevant for studies of older people

Systematic reviews and meta-analyses are increasingly common. This article aims to provide guidance for people conducting systematic reviews relevant to the healthcare of older people. An awareness of these issues will also help people reading systematic reviews to determine whether the results will influence their clinical practice. It is essential that systematic reviews are performed by a team which includes the required technical and clinical expertise. Those performing reviews for the first time should ensure they have appropriate training and support. They must be planned and performed in a transparent and methodologically robust way: guidelines are available. The protocol should be written—and if possible published—before starting the review. Geriatricians will be interested in a table of baseline characteristics, which will help to determine if the studied samples or populations are similar to their patients. Reviews of studies of older people should consider how they will manage issues such as different age cut-offs; non-specific presentations; multiple predictors and outcomes; potential biases and confounders. Systematic reviews and meta-analyses may provide evidence to improve older people's care, or determine where new evidence is required. Newer methodologies, such as meta-analyses of individual level data, network meta-analyses and umbrella reviews, and realist synthesis, may improve the reliability and clinical utility of systematic reviews

Linear and Non-linear associations between vitamin D and grip strength: a Mendelian Randomisation study in UK Biobank

BACKGROUND: Low vitamin D status is a widespread phenomenon. Similarly, muscle weakness, often indicated by low grip strength, is another public health concern; however, the vitamin D-grip strength relationship is equivocal. It is important to understand whether variation in vitamin D status causally influences muscle strength to elucidate whether supplementation may help prevent/treat muscle weakness. METHODS: UK Biobank participants, aged 37-73 years, with valid data on Vitamin D status (circulating 25-hydroxyvitamin D (25(OH)D) concentration) and maximum grip strength were included (N=368,890). We examined sex-specific cross-sectional associations between 25(OH)D and grip strength. Using Mendelian randomisation (MR), we estimated the strength of the 25(OH)D-grip strength associations using genetic instruments for 25(OH)D as our exposure. Crucially, because potential effects of vitamin D supplementation on strength could vary by underlying 25(OH)D status, we allowed for non-linear relationships between 25(OH)D and strength in all analyses. RESULTS: Mean(SD) of 25(OH)D was 50(21)nmol/L in males and females. In cross-sectional analyses there was evidence of non-linear associations between 25(OH)D and strength: e.g., compared to males with 50nmol/L circulating 25(OH)D, males with 75nmol/L had 0.36kg (0.31,0.40) stronger grip; males with 25nmol/L had 1.01kg (95% CI: 0.93,1.08) weaker grip. In MR analyses, linear and non-linear models fitted the data similarly well: e.g., 25nmol/L higher circulating 25(OH)D in males was associated with 0.25kg (-0.05,0.55) greater grip (regardless of initial 25(OH)D status). Results were similar, albeit weaker, for females. CONCLUSIONS: Using two different methods to triangulate evidence, our findings suggest moderate to small causal links between circulating 25(OH)D and grip strength

Correlations between in situ denitrification activity and nir-gene abundances in pristine and impacted prairie streams

Denitrification is a process that reduces nitrogen levels in headwaters and other streams. We compared nirS and nirK abundances with the absolute rate of denitrification, the longitudinal coefficient of denitrification (i.e., Kden, which represents optimal denitrification rates at given environmental conditions), and water quality in seven prairie streams to determine if nir-gene abundances explain denitrification activity. Previous work showed that absolute rates of denitrification correlate with nitrate levels; however, no correlation has been found for denitrification efficiency, which we hypothesise might be related to gene abundances. Water-column nitrate and soluble-reactive phosphorus levels significantly correlated with absolute rates of denitrification, but nir-gene abundances did not. However, nirS and nirK abundances significantly correlated with Kden, as well as phosphorus, although no correlation was found between Kden and nitrate. These data confirm that absolute denitrification rates are controlled by nitrate load, but intrinsic denitrification efficiency is linked to nirS and nirK gene abundances

Milk intake across adulthood and muscle strength decline from mid- to late life: the MRC National Survey of Health and Development

Milk is a source of several nutrients which may be beneficial for skeletal muscle. Evidence that links lower milk intake with declines in muscle strength from midlife to old age is lacking. We used data from the MRC NSHD to test sex-specific associations between milk consumption from age 36 to 60-64 years, low grip strength (GS) or probable sarcopenia, and GS decline from age 53 to 69 years. We included 1340 men and 1383 women with at least one measure of both milk intake and GS. Milk intake was recorded in 5-day food diaries (ages 36, 43, 53 and 60-64), and grand mean of total, reduced-fat and full-fat milk each categorised in thirds (T1 (lowest) to T3 (highest), g/day). GS was assessed at ages 53, 60-64, and 69, and probable sarcopenia classified at age 69. We employed logistic regression to examine the odds of probable sarcopenia, and multilevel models to investigate decline in GS in relation to milk intake thirds. Compared with T1, only T2 (58.7-145.2g/day) of reduced-fat milk was associated with lower odds of sex-specific low GS at age 69 (OR (95% CI): 0.59 (0.37, 0.94), p=0.03). In multilevel models, only T3 of total milk (≥237.5g/day) was associated with stronger GS in midlife in men (β (95% CI) = 1.82 (0.18, 3.45)kg, p=0.03) compared with T1 (≤152.0g/day), but not with GS decline over time. A higher milk intake across adulthood may promote muscle strength in midlife in men. Its role in muscle health in late life needs further examination

Discovery of quantitative trait loci for resistance to parasitic nematode infection in sheep: I. Analysis of outcross pedigrees

BACKGROUND: Currently most pastoral farmers rely on anthelmintic drenches to control gastrointestinal parasitic nematodes in sheep. Resistance to anthelmintics is rapidly increasing in nematode populations such that on some farms none of the drench families are now completely effective. It is well established that host resistance to nematode infection is a moderately heritable trait. This study was undertaken to identify regions of the genome, quantitative trait loci (QTL) that contain genes affecting resistance to parasitic nematodes. RESULTS: Rams obtained from crossing nematode parasite resistant and susceptible selection lines were used to derive five large half-sib families comprising between 348 and 101 offspring per sire. Total offspring comprised 940 lambs. Extensive measurements for a range of parasite burden and immune function traits in all offspring allowed each lamb in each pedigree to be ranked for relative resistance to nematode parasites. Initially the 22 most resistant and 22 most susceptible progeny from each pedigree were used in a genome scan that used 203 microsatellite markers spread across all sheep autosomes. This study identified 9 chromosomes with regions showing sufficient linkage to warrant the genotyping of all offspring. After genotyping all offspring with markers covering Chromosomes 1, 3, 4, 5, 8, 12, 13, 22 and 23, the telomeric end of chromosome 8 was identified as having a significant QTL for parasite resistance as measured by the number of Trichostrongylus spp. adults in the abomasum and small intestine at the end of the second parasite challenge. Two further QTL for associated immune function traits of total serum IgE and T. colubiformis specific serum IgG, at the end of the second parasite challenge, were identified on chromosome 23. CONCLUSION: Despite parasite resistance being a moderately heritable trait, this large study was able to identify only a single significant QTL associated with it. The QTL concerned adult parasite burdens at the end of the second parasite challenge when the lambs were approximately 6 months old. Our failure to discover more QTL suggests that most of the genes controlling this trait are of relatively small effect. The large number of suggestive QTL discovered (more than one per family per trait than would be expected by chance) also supports this conclusion

Droplet Size Impact on Efficacy of a Dicamba-plus-Glyphosate Mixture

Chemical weed control remains a widely used component of integrated weed management strategies because of its cost-effectiveness and rapid removal of crop pests. Additionally, dicamba-plus-glyphosate mixtures are a commonly recommended herbicide combination to combat herbicide resistance, specifically in recently commercially released dicamba-tolerant soybean and cotton. However, increased spray drift concerns and antagonistic interactions require that the application process be optimized to maximize biological efficacy while minimizing environmental contamination potential. Field research was conducted in 2016, 2017, and 2018 across three locations (Mississippi, Nebraska, and North Dakota) for a total of six site-years. The objectives were to characterize the efficacy of a range of droplet sizes [150 μm (Fine) to 900 μm (Ultra Coarse)] using a dicamba-plus-glyphosate mixture and to create novel weed management recommendations utilizing pulse-width modulation (PWM) sprayer technology. Results across pooled site-years indicated that a droplet size of 395 μm (Coarse) maximized weed mortality from a dicamba-plus-glyphosate mixture at 94 L ha–1. However, droplet size could be increased to 620 μm (Extremely Coarse) to maintain 90% of the maximum weed mortality while further mitigating particle drift potential. Although generalized droplet size recommendations could be created across site-years, optimum droplet sizes within each site-year varied considerably and may be dependent on weed species, geographic location, weather conditions, and herbicide resistance(s) present in the field. The precise, site-specific application of a dicamba-plus-glyphosate mixture using the results of this research will allow applicators to more effectively utilize PWM sprayers, reduce particle drift potential, maintain biological efficacy, and reduce the selection pressure for the evolution of herbicide-resistant weeds

Global variation in grip strength: a systematic review and meta-analysis of normative data.

Background: weak grip strength is a key component of sarcopenia and is associated with subsequent disability and mortality. We have recently established life course normative data for grip strength in Great Britain, but it is unclear whether the cut 209 Global variation in grip strength points we derived for weak grip strength are suitable for use in other settings. Our objective was to investigate differences in grip strength by world region using our data as a reference standard. Methods: we searched MEDLINE and EMBASE for reporting age- and gender-stratified normative data for grip strength. We extracted each item of normative data and converted it on to a Z-score scale relative to our British centiles. We performed meta-regression to pool the Z-scores and compare them by world region. Findings: our search returned 806 abstracts. Sixty papers met inclusion criteria and reported on 63 different samples. Seven UN regions were represented, although most samples (n = 44) were based in developed regions. We extracted 726 normative data items relating to 96,537 grip strength observations. Normative data from developed regions were broadly similar to our British centiles, with a pooled Z-score 0.12 SDs (95% CI: 0.07, 0.17) above the corresponding British centiles. By comparison, normative data from developing regions were clearly lower, with a pooled Z-score of −0.85 SDs (95% CI: −0.94, −0.76). Interpretation: our findings support the use of our British grip strength centiles and their associated cut points in consensus definitions for sarcopenia and frailty across developed regions, but highlight the need for different cut points in developing region