Forensic Excavation of Rock Masses: A Technique to Investigate Discontinuity Persistence

True persistence of rock discontinuities (areas with insignificant tensile strength) is an important factor controlling the engineering behaviour of fractured rock masses, but is extremely difficult to quantify using current geological survey methodologies, even where there is good rock exposure. Trace length as measured in the field or using remote measurement devices is actually only broadly indicative of persistence for rock engineering practice and numerical modelling. Visible traces of discontinuities are treated as if they were open fractures within rock mass classifications, despite many such traces being non-persistent and actually retaining considerable strength. The common assumption of 100% persistence, based on trace length, is generally extremely conservative in terms of strength and stiffness, but not always so and may lead to a wrong prediction of failure mechanism or of excavatability. Assuming full persistence would give hopelessly incorrect predictions of hydraulic conductivity. A new technique termed forensic excavation of rock masses is introduced, as a procedure for directly investigating discontinuity persistence. This technique involves non-explosive excavation of rock masses by injecting an expansive chemical splitter along incipient discontinuities. On expansion, the splitter causes the incipient traces to open as true joints. Experiments are described in which near-planar rock discontinuities, through siltstone and sandstone, were opened up by injecting the splitter into holes drilled along the lines of visible traces of the discontinuities in the laboratory and in the field. Once exposed the surfaces were examined to investigate the pre-existing persistence characteristics of the incipient discontinuities. One conclusion from this study is that visible trace length of a discontinuity can be a poor indicator of true persistence (defined for a fracture area with negligible tensile strength). An observation from this series of experiments was that freshly failed surfaces through pre-existing rock bridges were relatively rough compared to sections of pre-existing weaker areas of geologically developed (though still incipient) discontinuities. Fractographic features such as hackle and rib marks were typical of the freshly broken rock bridges, whereas opened-up areas of incipient discontinuity were smoother. Schmidt hammer rebound values were generally higher for the rock bridge areas, probably reflecting their lower degree of chemical and physical weathering

The logic-bias effect: The role of effortful processing in the resolution of belief-logic conflict.

According to the default interventionist dual-process account of reasoning, belief-based responses to reasoning tasks are based on Type 1 processes generated by default, which must be inhibited in order to produce an effortful, Type 2 output based on the validity of an argument. However, recent research has indicated that reasoning on the basis of beliefs may not be as fast and automatic as this account claims. In three experiments, we presented participants with a reasoning task that was to be completed while they were generating random numbers (RNG). We used the novel methodology introduced by Handley, Newstead & Trippas (Journal of Experimental Psychology: Learning, Memory, and Cognition, 37, 28-43, 2011), which required participants to make judgments based upon either the validity of a conditional argument or the believability of its conclusion. The results showed that belief-based judgments produced lower rates of accuracy overall and were influenced to a greater extent than validity judgments by the presence of a conflict between belief and logic for both simple and complex arguments. These findings were replicated in Experiment 3, in which we controlled for switching demands in a blocked design. Across all three experiments, we found a main effect of RNG, implying that both instructional sets require some effortful processing. However, in the blocked design RNG had its greatest impact on logic judgments, suggesting that distinct executive resources may be required for each type of judgment. We discuss the implications of our findings for the default interventionist account and offer a parallel competitive model as an alternative interpretation for our findings

Accelerated in vivo proliferation of memory phenotype CD4+ T-cells in human HIV-1 infection irrespective of viral chemokine co-receptor tropism.

CD4(+) T-cell loss is the hallmark of HIV-1 infection. CD4 counts fall more rapidly in advanced disease when CCR5-tropic viral strains tend to be replaced by X4-tropic viruses. We hypothesized: (i) that the early dominance of CCR5-tropic viruses results from faster turnover rates of CCR5(+) cells, and (ii) that X4-tropic strains exert greater pathogenicity by preferentially increasing turnover rates within the CXCR4(+) compartment. To test these hypotheses we measured in vivo turnover rates of CD4(+) T-cell subpopulations sorted by chemokine receptor expression, using in vivo deuterium-glucose labeling. Deuterium enrichment was modeled to derive in vivo proliferation (p) and disappearance (d*) rates which were related to viral tropism data. 13 healthy controls and 13 treatment-naive HIV-1-infected subjects (CD4 143-569 cells/ul) participated. CCR5-expression defined a CD4(+) subpopulation of predominantly CD45R0(+) memory cells with accelerated in vivo proliferation (p = 2.50 vs 1.60%/d, CCR5(+) vs CCR5(-); healthy controls; P<0.01). Conversely, CXCR4 expression defined CD4(+) T-cells (predominantly CD45RA(+) naive cells) with low turnover rates. The dominant effect of HIV infection was accelerated turnover of CCR5(+)CD45R0(+)CD4(+) memory T-cells (p = 5.16 vs 2.50%/d, HIV vs controls; P<0.05), naïve cells being relatively unaffected. Similar patterns were observed whether the dominant circulating HIV-1 strain was R5-tropic (n = 9) or X4-tropic (n = 4). Although numbers were small, X4-tropic viruses did not appear to specifically drive turnover of CXCR4-expressing cells (p = 0.54 vs 0.72 vs 0.44%/d in control, R5-tropic, and X4-tropic groups respectively). Our data are most consistent with models in which CD4(+) T-cell loss is primarily driven by non-specific immune activation

Collaborative planning approach to inform the implementation of a healthcare manager intervention for hispanics with serious mental illness: a study protocol

Background: This study describes a collaborative planning approach that blends principles of community-based participatory research (CBPR) and intervention mapping to modify a healthcare manager intervention to a new patient population and provider group and to assess the feasibility and acceptability of this modified intervention to improve the physical health of Hispanics with serious mental illness (SMI) and at risk for cardiovascular disease (CVD). Methods: The proposed study uses a multiphase approach that applies CBPR principles and intervention-mapping steps--an intervention-planning approach--to move from intervention planning to pilot testing. In phase I, a community advisory board composed of researchers and stakeholders will be assembled to learn and review the intervention and make initial modifications. Phase II uses a combination of qualitative methods--patient focus groups and stakeholder interviews--to ensure that the modifications are acceptable to all stakeholders. Phase III uses results from phase II to further modify the intervention, develop an implementation plan, and train two care managers on the modified intervention. Phase IV consists of a 12-month open pilot study (N = 30) to assess the feasibility and acceptability of the modified intervention and explore its initial effects. Lastly, phase V consists of analysis of pilot study data and preparation for future funding to develop a more rigorous evaluation of the modified intervention. Discussion: The proposed study is one of the few projects to date to focus on improving the physical health of Hispanics with SMI and at risk for CVD by using a collaborative planning approach to enhance the transportability and use of a promising healthcare manager intervention. This study illustrates how blending health-disparities research and implementation science can help reduce the disproportionate burden of medical illness in a vulnerable population

Avian W and mammalian Y chromosomes convergently retained dosage-sensitive regulators

After birds diverged from mammals, different ancestral autosomes evolved into sex chromosomes in each lineage. In birds, females are ZW and males are ZZ, but in mammals females are XX and males are XY. We sequenced the chicken W chromosome, compared its gene content with our reconstruction of the ancestral autosomes, and followed the evolutionary trajectory of ancestral W-linked genes across birds. Avian W chromosomes evolved in parallel with mammalian Y chromosomes, preserving ancestral genes through selection to maintain the dosage of broadly expressed regulators of key cellular processes. We propose that, like the human Y chromosome, the chicken W chromosome is essential for embryonic viability of the heterogametic sex. Unlike other sequenced sex chromosomes, the chicken W chromosome did not acquire and amplify genes specifically expressed in reproductive tissues. We speculate that the pressures that drive the acquisition of reproduction-related genes on sex chromosomes may be specific to the male germ line

Geographic differences in allele frequencies of susceptibility SNPs for cardiovascular disease

<p>Abstract</p> <p>Background</p> <p>We hypothesized that the frequencies of risk alleles of SNPs mediating susceptibility to cardiovascular diseases differ among populations of varying geographic origin and that population-specific selection has operated on some of these variants.</p> <p>Methods</p> <p>From the database of genome-wide association studies (GWAS), we selected 36 cardiovascular phenotypes including coronary heart disease, hypertension, and stroke, as well as related quantitative traits (eg, body mass index and plasma lipid levels). We identified 292 SNPs in 270 genes associated with a disease or trait at <it>P </it>< 5 × 10^-8. As part of the Human Genome-Diversity Project (HGDP), 158 (54.1%) of these SNPs have been genotyped in 938 individuals belonging to 52 populations from seven geographic areas. A measure of population differentiation, <it>F</it>_ST, was calculated to quantify differences in risk allele frequencies (RAFs) among populations and geographic areas.</p> <p>Results</p> <p>Large differences in RAFs were noted in populations of Africa, East Asia, America and Oceania, when compared with other geographic regions. The mean global <it>F</it>_ST(0.1042) for 158 SNPs among the populations was not significantly higher than the mean global <it>F</it>_STof 158 autosomal SNPs randomly sampled from the HGDP database. Significantly higher global <it>F</it>_ST(<it>P </it>< 0.05) was noted in eight SNPs, based on an empirical distribution of global <it>F</it>_STof 2036 putatively neutral SNPs. For four of these SNPs, additional evidence of selection was noted based on the integrated Haplotype Score.</p> <p>Conclusion</p> <p>Large differences in RAFs for a set of common SNPs that influence risk of cardiovascular disease were noted between the major world populations. Pairwise comparisons revealed RAF differences for at least eight SNPs that might be due to population-specific selection or demographic factors. These findings are relevant to a better understanding of geographic variation in the prevalence of cardiovascular disease.</p

Barriers and enablers to the implementation of the 6-PACK falls prevention program: A preimplementation study in hospitals participating in a cluster randomised controlled trial

Evidence for effective falls prevention interventions in acute wards is limited. One reason for this may be suboptimal program implementation. This study aimed to identify perceived barriers and enablers of the implementation of the 6-PACK falls prevention program to inform the implementation in a randomised controlled trial. Strategies to optimise successful implementation of 6-PACK were also sought. A mixed-methods approach was applied in 24 acute wards from 6 Australian hospitals. Participants were nurses working on participating wards and senior hospital staff including Nurse Unit Managers; senior physicians; Directors of Nursing; and senior personnel involved in quality and safety or falls prevention. Information on barriers and enablers of 6-PACK implementation was obtained through surveys, focus groups and interviews. Questions reflected the COM-B framework that includes three behaviour change constructs of: capability, opportunity and motivation. Focus group and interview data were analysed thematically, and survey data descriptively. The survey response rate was 60% (420/702), and 12 focus groups (n = 96 nurses) and 24 interviews with senior staff were conducted. Capability barriers included beliefs that falls could not be prevented; and limited knowledge on falls prevention in patients with complex care needs (e.g. cognitive impairment). Capability enablers included education and training, particularly face to face case study based approaches. Lack of resources was identified as an opportunity barrier. Leadership, champions and using data to drive practice change were recognised as opportunity enablers. Motivation barriers included complacency and lack of ownership in falls prevention efforts. Motivation enablers included senior staff articulating clear goals and a commitment to falls prevention; and use of reminders, audits and feedback. The information gained from this study suggests that regular practical face-to-face education and training for nurses; provision of equipment; audit, reminders and feedback; leadership and champions; and the provision of falls data is key to successful falls prevention program implementation in acute hospitals

Microarray-Based Maps of Copy-Number Variant Regions in European and Sub-Saharan Populations

The genetic basis of phenotypic variation can be partially explained by the presence of copy-number variations (CNVs). Currently available methods for CNV assessment include high-density single-nucleotide polymorphism (SNP) microarrays that have become an indispensable tool in genome-wide association studies (GWAS). However, insufficient concordance rates between different CNV assessment methods call for cautious interpretation of results from CNV-based genetic association studies. Here we provide a cross-population, microarray-based map of copy-number variant regions (CNVRs) to enable reliable interpretation of CNV association findings. We used the Affymetrix Genome-Wide Human SNP Array 6.0 to scan the genomes of 1167 individuals from two ethnically distinct populations (Europe, N = 717; Rwanda, N = 450). Three different CNV-finding algorithms were tested and compared for sensitivity, specificity, and feasibility. Two algorithms were subsequently used to construct CNVR maps, which were also validated by processing subsamples with additional microarray platforms (Illumina 1M-Duo BeadChip, Nimblegen 385K aCGH array) and by comparing our data with publicly available information. Both algorithms detected a total of 42669 CNVs, 74% of which clustered in 385 CNVRs of a cross-population map. These CNVRs overlap with 862 annotated genes and account for approximately 3.3% of the haploid human genome

Assessing population genetic structure via the maximisation of genetic distance

<p>Abstract</p> <p>Background</p> <p>The inference of the hidden structure of a population is an essential issue in population genetics. Recently, several methods have been proposed to infer population structure in population genetics.</p> <p>Methods</p> <p>In this study, a new method to infer the number of clusters and to assign individuals to the inferred populations is proposed. This approach does not make any assumption on Hardy-Weinberg and linkage equilibrium. The implemented criterion is the maximisation (via a <it>simulated annealing </it>algorithm) of the averaged genetic distance between a predefined number of clusters. The performance of this method is compared with two Bayesian approaches: STRUCTURE and BAPS, using simulated data and also a real human data set.</p> <p>Results</p> <p>The simulations show that with a reduced number of markers, BAPS overestimates the number of clusters and presents a reduced proportion of correct groupings. The accuracy of the new method is approximately the same as for STRUCTURE. Also, in Hardy-Weinberg and linkage disequilibrium cases, BAPS performs incorrectly. In these situations, STRUCTURE and the new method show an equivalent behaviour with respect to the number of inferred clusters, although the proportion of correct groupings is slightly better with the new method. Re-establishing equilibrium with the randomisation procedures improves the precision of the Bayesian approaches. All methods have a good precision for <it>F</it>_{<it>ST </it>}≥ 0.03, but only STRUCTURE estimates the correct number of clusters for <it>F</it>_{<it>ST </it>}as low as 0.01. In situations with a high number of clusters or a more complex population structure, MGD performs better than STRUCTURE and BAPS. The results for a human data set analysed with the new method are congruent with the geographical regions previously found.</p> <p>Conclusion</p> <p>This new method used to infer the hidden structure in a population, based on the maximisation of the genetic distance and not taking into consideration any assumption about Hardy-Weinberg and linkage equilibrium, performs well under different simulated scenarios and with real data. Therefore, it could be a useful tool to determine genetically homogeneous groups, especially in those situations where the number of clusters is high, with complex population structure and where Hardy-Weinberg and/or linkage equilibrium are present.</p

Genotype, haplotype and copy-number variation in worldwide human populations

Genome-wide patterns of variation across individuals provide a powerful source of data for uncovering the history of migration, range expansion, and adaptation of the human species. However, high-resolution surveys of variation in genotype, haplotype and copy number have generally focused on a small number of population groups(1-3). Here we report the analysis of high-quality genotypes at 525,910 single-nucleotide polymorphisms ( SNPs) and 396 copy-number-variable loci in a worldwide sample of 29 populations. Analysis of SNP genotypes yields strongly supported fine-scale inferences about population structure. Increasing linkage disequilibrium is observed with increasing geographic distance from Africa, as expected under a serial founder effect for the out-of-Africa spread of human populations. New approaches for haplotype analysis produce inferences about population structure that complement results based on unphased SNPs. Despite a difference from SNPs in the frequency spectrum of the copy-number variants (CNVs) detected-including a comparatively large number of CNVs in previously unexamined populations from Oceania and the Americas-the global distribution of CNVs largely accords with population structure analyses for SNP data sets of similar size. Our results produce new inferences about inter-population variation, support the utility of CNVs in human population-genetic research, and serve as a genomic resource for human-genetic studies in diverse worldwide populations.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62552/1/nature06742.pd