n-spin correlation functions for the two-dimensional Ising model

It is noted that expressions for the T=Tc n-spin correlation functions of a two-dimensional Ising system obtained by continuum methods do agree with exact results for restricted geometries. This leads to the conjecture that the continuum result is true for all n and all geometries. Speculation regarding the behavior of these functions away from T=Tc are made. © 1978 The American Physical Society

Toward High Fidelity Materials Property Prediction from Multiscale Modeling and Simulation

The current approach to materials discovery and design remains dominated by experimental testing, frequently based on little more than trial and error. With the advent of ever more powerful computers, rapid, reliable, and reproducible computer simulations are beginning to represent a feasible alternative. As high performance computing reaches the exascale, exploiting the resources efficiently presents interesting challenges and opportunities. Multiscale modeling and simulation of materials are extremely promising candidates for exploiting these resources based on the assumption of a separation of scales in the architectures of nanomaterials. Examples of hierarchical and concurrent multiscale approaches are presented which benefit from the weak scaling of monolithic applications, thereby efficiently exploiting large scale computational resources. Several multiscale techniques, incorporating the electronic to the continuum scale, which can be applied to the efficient design of a range of nanocomposites, are discussed. Then the work on the development of a software toolkit designed to provide verification, validation, and uncertainty quantification to support actionable prediction from such calculations is discussed

An International Study of the Ability and Cost-Effectiveness of Advertising Methods to Facilitate Study Participant Self-Enrolment Into a Pilot Pharmacovigilance Study During Early Pregnancy

Knowledge of the fetal effects of maternal medication use in pregnancy is often inadequate and current pregnancy pharmacovigilance (PV) surveillance methods have important limitations. Patient self-reporting may be able to mitigate some of these limitations, providing an adequately sized study sample can be recruited.To compare the ability and cost-effectiveness of several direct-to-participant advertising methods for the recruitment of pregnant participants into a study of self-reported gestational exposures and pregnancy outcomes.The Pharmacoepidemiological Research on Outcomes of Therapeutics by a European Consortium (PROTECT) pregnancy study is a non-interventional, prospective pilot study of self-reported medication use and obstetric outcomes provided by a cohort of pregnant women that was conducted in Denmark, the Netherlands, Poland, and the United Kingdom. Direct-to-participant advertisements were provided via websites, emails, leaflets, television, and social media platforms.Over a 70-week recruitment period direct-to-participant advertisements engaged 43,234 individuals with the study website or telephone system; 4.78% (2065/43,234) of which were successfully enrolled and provided study data. Of these 90.4% (1867/2065) were recruited via paid advertising methods, 23.0% (475/2065) of whom were in the first trimester of pregnancy. The overall costs per active recruited participant were lowest for email (€23.24) and website (€24.41) advertisements and highest for leaflet (€83.14) and television (€100.89). Website adverts were substantially superior in their ability to recruit participants during their first trimester of pregnancy (317/668, 47.5%) in comparison with other advertising methods (P<.001). However, we identified international variations in both the cost-effectiveness of the various advertisement methods used and in their ability to recruit participants in early pregnancy.Recruitment of a pregnant cohort using direct-to-participant advertisement methods is feasible, but the total costs incurred are not insubstantial. Future research is needed to identify advertising strategies capable of recruiting large numbers of demographically representative pregnant women, preferentially in early pregnancy

Triangulating molecular evidence to prioritize candidate causal genes at established atopic dermatitis loci

Genome-wide association studies for atopic dermatitis (AD) have identified 25 reproducible loci. We attempt to prioritize candidate causal genes at these loci using extensive molecular resources compiled into a bioinformatics pipeline. We identified a list of 103 molecular resources for AD aetiology, including expression, protein and DNA methylation QTL datasets in skin or immune-relevant tissues which were tested for overlap with GWAS signals. This was combined with functional annotation using regulatory variant prediction, and features such as promoter-enhancer interactions, expression studies and variant fine-mapping. For each gene at each locus, we condensed the evidence into a prioritization score. Across the investigated loci, we detected significant enrichment of genes with adaptive immune regulatory function and epidermal barrier formation among the top prioritized genes. At 8 loci, we were able to prioritize a single candidate gene (IL6R, ADO, PRR5L, IL7R, ETS1, INPP5D, MDM1, TRAF3). In addition, at 6 of the 25 loci, our analysis prioritizes less familiar candidates (SLC22A5, IL2RA, MDM1, DEXI, ADO, STMN3). Our analysis provides support for previously implicated genes at several AD GWAS loci, as well as evidence for plausible additional candidates at others, which may represent potential targets for drug discovery

The effect of sea temperature and food availability on the spawning success of Cape Anchovy engraulis capensis in the Southern Benguela

Data on the thermal structure, copepod biomass and production, and total number of eggs of the Cape anchovy Engraulis capensis were obtained from monthly surveys during the periods August 1993 – March1994 and September 1994 – March 1995 on the western Agulhas Bank and off the South-Western Cape, South Africa. Previous work suggested that anchovy spawn on the western Agulhas Bank in temperaturesbetween 16 and 19°C, where they feed predominantly on copepods. This study shows that the western Bank is a more suitable spawning area for anchovy, having greater thermal stability, a larger area of 16–19°Cwater and a more consistent food environment than off the South-Western Cape. Also, copepod production on the western Bank was highest in 16–19°C water. To identify factors controlling the area of this watermass, a cluster analysis was used on a suite of hydrographic variables. Three periods were identified: winter (August-September), spring (October-December) and summer (January-March), reflecting changes in theextent of the 16–19°C water and anchovy spawning, both of which peaked during spring. Spring was further characterized by infrequent surface upwelling. During summer, upwelling frequently reached the surface andthe upwelling front migrated offshore, constricting the area of 16–19°C water. It is hypothesized that spawning success in anchovy is dependent upon the extent of suitable spawning habitat, both spatially (16–19°Cwater) and temporally (spring). To put this concept into a predictive framework, the number of anchovy eggs was regressed against the area of 16–19°C water; a significant, positive relationship (p < 0.001, r2 = 0.56, n = 17) was found. An implication of the hypothesis is that the duration of spawning may be important to recruitment

QALY and health care costs-based damage cost toolkit for evaluating air quality measures

This toolkit is targeted at local authorities in the UK. It aims to generate estimates of QALY losses and health care costs (NHS and PSS) per tonne of emission of PM2.5 and NOx (or NO2) emitted, in order to support the economic evaluation of air quality measures. As a number of inputs were derived from the Leeds-Bradford Low Emission Zone (LEZ) feasibility study, the toolkit is especially appropriate for the economic evaluation of air quality measures in this region, using information on the targeted population size and the expected annual reduction in pollutant load (spread-sheet “using emission data only”). Alternatively, in order to evaluate air quality measures outside of West Yorkshire or in areas with a substantial different population density than Leeds/Bradford, it is possible to enter area-specific estimates of avoided cases of adverse health endpoints as input data of the toolkit (via spread-sheet “Using emissions and HIA results”)

Changes in midbrain pain receptor expression, gait and behavioral sensitivity in a rat model of radiculopathy.

Intervertebral disc herniation may contribute to inflammatory processes that associate with radicular pain and motor deficits. Molecular changes at the affected dorsal root ganglion (DRG), spinal cord, and even midbrain, have been documented in rat models of radiculopathy or nerve injury. The objective of this study was to evaluate gait and the expression of key pain receptors in the midbrain in a rodent model of radiculopathy. Radiculopathy was induced by harvesting tail nucleus pulposus (NP) and placing upon the right L5 DRG in rats (NP-treated, n=12). Tail NP was discarded in sham-operated animals (n=12). Mechanical allodynia, weight-bearing, and gait were evaluated in all animals over time. At 1 and 4 weeks after surgery, astrocyte and microglial activation was tested in DRG sections. Midbrain sections were similarly evaluated for immunoreactivity to serotonin (5HT(2B)), mu-opioid (µ-OR), and metabotropic glutamate (mGluR4 and 5) receptor antibodies. NP-treated animals placed less weight on the affected limb 1 week after surgery and experienced mechanical hypersensitivity over the duration of the study. Astroctye activation was observed at DRGs only at 4 weeks after surgery. Findings for pain receptors in the midbrain of NP-treated rats included an increased expression of 5HT(2B) at 1, but not 4 weeks; increased expression of µ-OR and mGluR5 at 1 and 4 weeks (periaqueductal gray region only); and no changes in expression of mGluR4 at any point in this study. These observations provide support for the hypothesis that the midbrain responds to DRG injury with a transient change in receptors regulating pain responses

The Role of Graphene in Enhancing the Material Properties of Thermosetting Polymers

Graphene continues to attract considerable attention from the materials science community through its potential for improving the mechanical properties of polymer thermosets, yet there remains considerable uncertainty over the underlying mechanisms. The effect of introducing graphene sheets to a typical thermosetting polymer network on mechanical behaviour is explored here through concurrently coupling molecular dynamics with a finite element solver. In this multiscale approach, Graphene is observed to act in two ways: as passive microscopic defects, dispersing crack propagation (high deformation); and as active geometric constraints, impeding polymer conformational changes (low deformation). By contrast, single‐scale atomistic simulations alone predict little measurable difference in the properties of the graphene‐enhanced epoxy resins as compared with the pure polymer case. The multiscale model predicts that epoxy resins reinforced with graphene nanoparticles exhibit enhanced overall elastoplastic properties, reducing strain energy dissipation by up to 70%. Importantly, this is only observed when taking into account the complex boundary conditions, mainly involving shear, arising from coupling physics on length scales separated by five orders of magnitude. The approach herein clearly highlights a novel role of graphene nanoparticles in actively constraining the surrounding polymer matrix, impeding local dissipative mechanisms, and resisting shear deformation