Discreet element modeling of under sleeper pads using a box test

It has recently been reported that under sleeper pads (USPs) could improve ballasted rail track by decreasing the sleeper settlement and reducing particle breakage. In order to find out what happens at the particle-pad interface, discrete element modelling (DEM) is used to provide micro mechanical insight. The same positive effects of USP are found in the DEM simulations. The evidence provided by DEM shows that application of a USP allows more particles to be in contact with the pad, and causes these particles to transfer a larger lateral load to the adjacent ballast but a smaller vertical load beneath the sleeper. This could be used to explain why the USP helps to reduce the track settlement. In terms of particle breakage, it is found that most breakage occurs at the particle-sleeper interface and along the main contact force chains between particles under the sleeper. The use of USPs could effectively reduce particle abrasion that occurs in both of these regions

Discrete element modelling and cavity expansion analysis of cone penetration testing

This paper uses the discrete element method (DEM) in three dimensions to simulate cone penetration testing (CPT) of granular materials in a calibration chamber. Several researchers have used different numerical techniques such as strain path methods and finite element methods to study CPT problems. The DEM is a useful alternative tool for studying cone penetration problems because of its ability to provide micro mechanical insight into the behaviour of granular materials and cone penetration resistance. A 30° chamber segment and a particle refinement method were used for the simulations. Giving constant mass to each particle in the sample was found to reduce computational time significantly, without significantly affecting tip resistance. The effects of initial sample conditions and particle friction coefficient on tip resistance are investigated and found to have an important effect on the tip resistance. Biaxial test simulations using DEM are conducted to obtain the basic granular material properties for obtaining CPT analytical solutions based on continuum mechanics. Macro properties of the samples for different input micro parameters are presented and used to obtain the analytical CPT results. Comparison between the numerical simulations and analytical solutions show good agreement

Protocol of the COSMIN study: COnsensus-based Standards for the selection of health Measurement INstruments

BACKGROUND: Choosing an adequate measurement instrument depends on the proposed use of the instrument, the concept to be measured, the measurement properties (e.g. internal consistency, reproducibility, content and construct validity, responsiveness, and interpretability), the requirements, the burden for subjects, and costs of the available instruments. As far as measurement properties are concerned, there are no sufficiently specific standards for the evaluation of measurement properties of instruments to measure health status, and also no explicit criteria for what constitutes good measurement properties. In this paper we describe the protocol for the COSMIN study, the objective of which is to develop a checklist that contains COnsensus-based Standards for the selection of health Measurement INstruments, including explicit criteria for satisfying these standards. We will focus on evaluative health related patient-reported outcomes (HR-PROs), i.e. patient-reported health measurement instruments used in a longitudinal design as an outcome measure, excluding health care related PROs, such as satisfaction with care or adherence. The COSMIN standards will be made available in the form of an easily applicable checklist. METHOD: An international Delphi study will be performed to reach consensus on which and how measurement properties should be assessed, and on criteria for good measurement properties. Two sources of input will be used for the Delphi study: (1) a systematic review of properties, standards and criteria of measurement properties found in systematic reviews of measurement instruments, and (2) an additional literature search of methodological articles presenting a comprehensive checklist of standards and criteria. The Delphi study will consist of four (written) Delphi rounds, with approximately 30 expert panel members with different backgrounds in clinical medicine, biostatistics, psychology, and epidemiology. The final checklist will subsequently be field-tested by assessing the inter-rater reproducibility of the checklist. DISCUSSION: Since the study will mainly be anonymous, problems that are commonly encountered in face-to-face group meetings, such as the dominance of certain persons in the communication process, will be avoided. By performing a Delphi study and involving many experts, the likelihood that the checklist will have sufficient credibility to be accepted and implemented will increase

Unity through truth

Renewed worries about the unity of the proposition have been taken as a crucial stumbling block for any traditional conception of propositions. These worries are often framed in terms of how entities independent of mind and language can have truth conditions: why is the proposition that Desdemona loves Cassio true if and only if she loves him? I argue that the best understanding of these worries shows that they should be solved by our theory of truth and not our theory of content. Specifically, I propose a version of the redundancy theory according to which ‘it is true that Desdemona loves Cassio’ expresses the same proposition as ‘Desdemona loves Cassio’. Surprisingly, this variant of the redundancy theory treats ‘is true’ as an ordinary predicate of the language, thereby defusing many standard criticisms of the redundancy theory

The Back 2 Activity Trial: education and advice versus education and advice plus a structured walking programme for chronic low back pain

<p>Abstract</p> <p>Background</p> <p>Current evidence supports the use of exercise-based treatment for chronic low back pain that encourages the patient to assume an active role in their recovery. Walking has been shown it to be an acceptable type of exercise with a low risk of injury. However, it is not known whether structured physical activity programmes are any more effective than giving advice to remain active.</p> <p>Methods/Design</p> <p>The proposed study will test the feasibility of using a pedometer-driven walking programme, as an adjunct to a standard education and advice session in participants with chronic low back pain. Fifty adult participants will be recruited via a number of different sources. Baseline outcome measures including self reported function; objective physical activity levels; fear-avoidance beliefs and health-related quality of life will be recorded. Eligible participants will be randomly allocated under strict, double blind conditions to one of two treatments groups. Participants in group A will receive a single education and advice session with a physiotherapist based on the content of the 'Back Book'. Participants in group B will receive the same education and advice session. In addition, they will also receive a graded pedometer-driven walking programme prescribed by the physiotherapist. Follow up outcomes will be recorded by the same researcher, who will remain blinded to group allocation, at eight weeks and six months post randomisation. A qualitative exploration of participants' perception of walking will also be examined by use of focus groups at the end of the intervention. As a feasibility study, treatment effects will be represented by point estimates and confidence intervals. The assessment of participant satisfaction will be tabulated, as will adherence levels and any recorded difficulties or adverse events experienced by the participants or therapists. This information will be used to modify the planned interventions to be used in a larger randomised controlled trial.</p> <p>Discussion</p> <p>This paper describes the rationale and design of a study which will test the feasibility of using a structured, pedometer-driven walking programme in participants with chronic low back pain.</p> <p>Trial Registration</p> <p>[ISRCTN67030896]</p

Plant Responses to Extreme Climatic Events: A Field Test of Resilience Capacity at the Southern Range Edge

The expected and already observed increment in frequency of extreme climatic events may result in severe vegetation shifts. However, stabilizing mechanisms promoting community resilience can buffer the lasting impact of extreme events. The present work analyzes the resilience of a Mediterranean mountain ecosystem after an extreme drought in 2005, examining shoot-growth and needle-length resistance and resilience of dominant tree and shrub species (Pinus sylvestris vs Juniperus communis, and P. nigra vs J. oxycedrus) in two contrasting altitudinal ranges. Recorded high vegetative-resilience values indicate great tolerance to extreme droughts for the dominant species of pine-juniper woodlands. Observed tolerance could act as a stabilizing mechanism in rear range edges, such as the Mediterranean basin, where extreme events are predicted to be more detrimental and recurrent. However, resistance and resilience components vary across species, sites, and ontogenetic states: adult Pinus showed higher growth resistance than did adult Juniperus; saplings displayed higher recovery rates than did conspecific adults; and P. nigra saplings displayed higher resilience than did P. sylvestris saplings where the two species coexist. P. nigra and J. oxycedrus saplings at high and low elevations, respectively, were the most resilient at all the locations studied. Under recurrent extreme droughts, these species-specific differences in resistance and resilience could promote changes in vegetation structure and composition, even in areas with high tolerance to dry conditions.This study was supported by Ministerio de Ciencia e Innovación (Spanish Government) Projects CGL2008-04794 and CGL2011-29910 to R.Z., and by grant FPU-MEC (AP2005-1561) to A. H

Genome-Wide Identification of Calcium-Response Factor (CaRF) Binding Sites Predicts a Role in Regulation of Neuronal Signaling Pathways

Calcium-Response Factor (CaRF) was first identified as a transcription factor based on its affinity for a neuronal-selective calcium-response element (CaRE1) in the gene encoding Brain-Derived Neurotrophic Factor (BDNF). However, because CaRF shares no homology with other transcription factors, its properties and gene targets have remained unknown. Here we show that the DNA binding domain of CaRF has been highly conserved across evolution and that CaRF binds DNA directly in a sequence-specific manner in the absence of other eukaryotic cofactors. Using a binding site selection screen we identify a high-affinity consensus CaRF response element (cCaRE) that shares significant homology with the CaRE1 element of Bdnf. In a genome-wide chromatin immunoprecipitation analysis (ChIP-Seq), we identified 176 sites of CaRF-specific binding (peaks) in neuronal genomic DNA. 128 of these peaks are within 10kB of an annotated gene, and 60 are within 1kB of an annotated transcriptional start site. At least 138 of the CaRF peaks contain a common 10-bp motif with strong statistical similarity to the cCaRE, and we provide evidence predicting that CaRF can bind independently to at least 64.5% of these motifs in vitro. Analysis of this set of putative CaRF targets suggests the enrichment of genes that regulate intracellular signaling cascades. Finally we demonstrate that expression of a subset of these target genes is altered in the cortex of Carf knockout (KO) mice. Together these data strongly support the characterization of CaRF as a unique transcription factor and provide the first insight into the program of CaRF-regulated transcription in neurons

Restriction associated DNA-genotyping at multiple spatial scales in Arabidopsis lyrata reveals signatures of pathogen-mediated selection

Background: Genome scans based on outlier analyses have revolutionized detection of genes involved in adaptive processes, but reports of some forms of selection, such as balancing selection, are still limited. It is unclear whether high throughput genotyping approaches for identification of single nucleotide polymorphisms have sufficient power to detect modes of selection expected to result in reduced genetic differentiation among populations. In this study, we used Arabidopsis lyrata to investigate whether signatures of balancing selection can be detected based on genomic smoothing of Restriction Associated DNA sequencing (RAD-seq) data. We compared how different sampling approaches (both within and between subspecies) and different background levels of polymorphism (inbreeding or outcrossing populations) affected the ability to detect genomic regions showing key signatures of balancing selection, specifically elevated polymorphism, reduced differentiation and shifts towards intermediate allele frequencies. We then tested whether candidate genes associated with disease resistance (R-gene analogs) were detected more frequently in these regions compared to other regions of the genome. Results: We found that genomic regions showing elevated polymorphism contained a significantly higher density of R-gene analogs predicted to be under pathogen-mediated selection than regions of non-elevated polymorphism, and that many of these also showed evidence for an intermediate site-frequency spectrum based on Tajima’s D. However, we found few genomic regions that showed both elevated polymorphism and reduced FST among populations, despite strong background levels of genetic differentiation among populations. This suggests either insufficient power to detect the reduced population structure predicted for genes under balancing selection using sparsely distributed RAD markers, or that other forms of diversifying selection are more common for the R-gene analogs tested. Conclusions: Genome scans based on a small number of individuals sampled from a wide range of populations were sufficient to confirm the relative scarcity of signatures of balancing selection across the genome, but also identified new potential disease resistance candidates within genomic regions showing signatures of balancing selection that would be strong candidates for further sequencing efforts

Genome-Wide Identification, Characterization and Phylogenetic Analysis of the Rice LRR-Kinases

LRR-kinases constitute the largest subfamily of receptor-like kinases in plants and regulate a wide variety of processes related to development and defense. Through a reiterative process of sequence analysis and re-annotation, we identified 309 LRR-kinase genes in the rice genome (Nipponbare). Among them, 127 genes in the Rice Annotation Project Database and 85 in Refseq of NCBI were amended (in addition, 62 LRR-kinase genes were not annotated in Refseq). The complete set of LRR-kinases was characterized. These LRR-kinases were classified into five groups according to phylogenetic analysis, and the genes in groups 1, 2, 3 and 4 usually have fewer introns than those in group 5. The introns in the LRR domain, which are highly conserved in regards to their positions and configurations, split the first Leu or other amino residues at this position of the ‘xxLxLxx’ motif with phase 2 and usually separate one or more LRR repeats exactly. Tandemly repeated LRR motifs have evolved from exon duplication, mutation and exon shuffling. The extensive distribution and diversity of the LRR-kinase genes have been mainly generated by tandem duplication and mutation after whole genome duplication. Positive selection has made a limited contribution to the sequence diversity after duplication, but positively selected sites located in the LRR domain are thought to involve in the protein-protein interaction

Validation of two generic patient-reported outcome measures in patients with type 2 diabetes

<p>Abstract</p> <p>Background</p> <p>Prior to using a generic patient-reported outcome measure (PRO), the measure should be validated within the target population. The purpose of the current study was to validate two generic measures in patients with type 2 diabetes.</p> <p>Methods</p> <p>Patients with type 2 diabetes in Scotland and England completed two generic measures: EQ-5D and Psychological General Well-Being Index (PGWB). Two diabetes-specific measures were administered: ADS and DSC-R. Analyses assessed reliability and validity.</p> <p>Results</p> <p>There were 130 participants (53 Scotland; 77 England; 64% male; mean age = 55.7 years). Responses on the EQ-5D and PGWB reflected moderate impairment consistent with previous diabetes samples: mean EQ-5D Index score, 0.75; EQ-5D VAS, 68.8; PGWB global score, 67.9. All scales of the PGWB demonstrated good internal consistency reliability (Cronbach's alpha = 0.77 to 0.97). The EQ-5D and PGWB demonstrated convergent validity through significant correlations with the ADS (r = 0.48 to 0.61), DSC-R scales (r = 0.33 to 0.81 except ophthalmology subscale), and Body Mass Index (r = 0.15 to 0.38). The EQ-5D and PGWB discriminated between groups of patients known to differ in diabetes-related characteristics (e.g., history of hypoglycemia).</p> <p>Conclusion</p> <p>Results support the use of the EQ-5D and PGWB among patients with type 2 diabetes, possibly in combination with condition-specific measures.</p