370 research outputs found
The 25 November 1988 Saguenay, Quebec, Earthquake: Source Parameters and the Attenuation of Strong Ground Motion
The Saguenay earthquake of 25 November 1988 occurred close to the southern margin of the Saguenay Graben in southern Quebec. It was caused by almost purely dip-slip faulting centered at a depth of 26 km with a P axis oriented northeast-southwest. This faulting mechanism is similar to those of the larger historical earthquakes in eastern North America, but the focal depth is substantially greater than all but one of these events. The seismic moment estimated from regional PnI waves and teleseismic long-period body waves is 5 × 10^(24) dyne-cm., corresponding to a moment magnitude of 5.8. The source duration of the earthquake is estimated to be 1.8 sec, corresponding to a stress drop of 160 bars, which is not significantly higher than the average stress drop of 120 bars estimated from previous large earthquakes in eastern North America. In order to simultaneously match the recorded ground motion amplitudes of strong-motion acceleration, strong-motion velocity, and teleseismic short-period and long-period body waves, it is necessary to use a source function having a complex shape that implies the presence of asperities and larger local stress drops. The large set of strong-motion recordings of the Saguenay earthquake has been used to validate a procedure for estimating strong ground motion attenuation based on a simple wave propagation model. The most important feature of the recorded strong motions is that their peak amplitudes do not decay significantly with distance inside 120 km, but then decay abruptly beyond 120 km. Profiles of recorded accelerograms with absolute times indicate that at distances beyond 64 km the peak ground motions are due to strong postcritical reflections from velocity gradients in the lower crust. The principal shear-wave arrivals and the variation of their peak amplitudes with distance were reproduced in synthetic seismograms generated using a regional crustal structure model. The critical distances for the postcritical reflections were short because of the deep focal depth of the event, causing the elevation of ground motion amplitudes out to 120 km. Similar studies of earthquakes in other regions of eastern North America indicate that the strength of the postcritical reflections, and the distance ranges over which they are dominant, are controlled by the focal depth and crustal structure. Regional variations in crustal structure thus give rise to predictable regional variations in strong ground motion attenuation
Associations between diabetes and both cardiovascular disease and all-cause mortality are modified by grip strength: evidence from UK Biobank, a prospective population-based cohort study
OBJECTIVE Grip strength and diabetes are predictors of mortality and cardiovascular disease (CVD), but whether these risk factors interact to predispose to adverse health outcomes is unknown. This study determined the interactions between diabetes and grip strength and their association with health outcomes.
RESEARCH DESIGN AND METHODS We undertook a prospective, general population cohort study by using UK Biobank. Cox proportional hazards models were used to explore the associations between both grip strength and diabetes and the outcomes of all-cause mortality and CVD incidence/mortality as well as to test for interactions between diabetes and grip strength.
RESULTS 347,130 UK Biobank participants with full data available (mean age 55.9 years, BMI 27.2 kg/m2, 54.2% women) were included in the analysis, of which 13,373 (4.0%) had diabetes. Over a median follow-up of 4.9 years (range 3.3–7.8 years), 6,209 died (594 as a result of CVD), and 4,301 developed CVD. Participants with diabetes were at higher risk of all-cause and CVD mortality and CVD incidence. Significant interactions (P < 0.05) existed whereby the risk of CVD mortality was higher in participants with diabetes with low (hazard ratio [HR] 4.05 [95% CI 2.72, 5.80]) versus high (HR 1.46 [0.87, 2.46]) grip strength. Similar results were observed for all-cause mortality and CVD incidence.
CONCLUSIONS Risk of adverse health outcomes among people with diabetes is lower in those with high grip strength. Low grip strength may be useful to identify a higher-risk subgroup of patients with diabetes. Intervention studies are required to determine whether resistance exercise can reduce risk
An assessment of the strength of knots and splices used as eye terminations in a sailing environment
Research into knots, splices and other methods of forming an eye termination has been limited, despite the fact that they are essential and strongly affect the performance of a rope. The aim of this study was to carry out a comprehensive initial assessment of the breaking strength of eye terminations commonly used in a sailing environment, thereby providing direction for further work in the field. Supports for use in a regular tensile testing machine were specially developed to allow individual testing of each sample and a realistic spread of statistical data to be obtained. Over 180 break tests were carried out on four knots (the bowline, double bowline, figure-of-eight loop and perfection loop) and two splices (three-strand eye splice and braid-on-braid splice). The factors affecting their strength were investigated. A statistical approach to the analysis of the results was adopted. The type of knot was found to have a significant effect on the strength. This same effect was seen in both types of rope construction (three-strand and braid-on-braid). Conclusions were also drawn as to the effect of splice length, eye size, manufacturer and rope diameter on the breaking strength of splices. Areas of development and further investigation were identified
Hurst's Rescaled Range Statistical Analysis for Pseudorandom Number Generators used in Physical Simulations
The rescaled range statistical analysis (R/S) is proposed as a new method to
detect correlations in pseudorandom number generators used in Monte Carlo
simulations. In an extensive test it is demonstrated that the RS analysis
provides a very sensitive method to reveal hidden long run and short run
correlations. Several widely used and also some recently proposed pseudorandom
number generators are subjected to this test. In many generators correlations
are detected and quantified.Comment: 12 pages, 12 figures, 6 tables. Replaces previous version to correct
citation [19
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CCR5AS lncRNA variation differentially regulates CCR5, influencing HIV disease outcome.
Multiple genome-wide studies have identified associations between outcome of human immunodeficiency virus (HIV) infection and polymorphisms in and around the gene encoding the HIV co-receptor CCR5, but the functional basis for the strongest of these associations, rs1015164A/G, is unknown. We found that rs1015164 marks variation in an activating transcription factor 1 binding site that controls expression of the antisense long noncoding RNA (lncRNA) CCR5AS. Knockdown or enhancement of CCR5AS expression resulted in a corresponding change in CCR5 expression on CD4+ T cells. CCR5AS interfered with interactions between the RNA-binding protein Raly and the CCR5 3' untranslated region, protecting CCR5 messenger RNA from Raly-mediated degradation. Reduction in CCR5 expression through inhibition of CCR5AS diminished infection of CD4+ T cells with CCR5-tropic HIV in vitro. These data represent a rare determination of the functional importance of a genome-wide disease association where expression of a lncRNA affects HIV infection and disease progression
Genome-Wide Association Study Identifies Genetic Loci Associated with Iron Deficiency
The existence of multiple inherited disorders of iron metabolism in man, rodents and other vertebrates suggests genetic contributions to iron deficiency. To identify new genomic locations associated with iron deficiency, a genome-wide association study (GWAS) was performed using DNA collected from white men aged ≥25 y and women ≥50 y in the Hemochromatosis and Iron Overload Screening (HEIRS) Study with serum ferritin (SF) ≤ 12 µg/L (cases) and iron replete controls (SF>100 µg/L in men, SF>50 µg/L in women). Regression analysis was used to examine the association between case-control status (336 cases, 343 controls) and quantitative serum iron measures and 331,060 single nucleotide polymorphism (SNP) genotypes, with replication analyses performed in a sample of 71 cases and 161 controls from a population of white male and female veterans screened at a US Veterans Affairs (VA) medical center. Five SNPs identified in the GWAS met genome-wide statistical significance for association with at least one iron measure, rs2698530 on chr. 2p14; rs3811647 on chr. 3q22, a known SNP in the transferrin (TF) gene region; rs1800562 on chr. 6p22, the C282Y mutation in the HFE gene; rs7787204 on chr. 7p21; and rs987710 on chr. 22q11 (GWAS observed P<1.51×10−7 for all). An association between total iron binding capacity and SNP rs3811647 in the TF gene (GWAS observed P = 7.0×10−9, corrected P = 0.012) was replicated within the VA samples (observed P = 0.012). Associations with the C282Y mutation in the HFE gene also were replicated. The joint analysis of the HEIRS and VA samples revealed strong associations between rs2698530 on chr. 2p14 and iron status outcomes. These results confirm a previously-described TF polymorphism and implicate one potential new locus as a target for gene identification
Targeted suppression of autoreactive CD8+ T-cell activation using blocking anti-CD8 antibodies
CD8+ T-cells play a role in the pathogenesis of autoimmune diseases such as multiple sclerosis and type 1 diabetes. However, drugs that target the entire CD8+ T-cell population are not desirable because the associated lack of speci city can lead to unwanted consequences, most notably an enhanced susceptibility to infection. Here, we show that autoreactive CD8+ T-cells are highly dependent on CD8 for ligand-induced activation via the T-cell receptor (TCR). In contrast, pathogen-speci c CD8+ T-cells are relatively CD8-independent. These generic di erences relate to an intrinsic dichotomy that segregates self-derived and exogenous antigen-speci c TCRs according to the monomeric interaction a nity with cognate peptide-major histocompatibility complex class I (pMHCI). As a consequence, “blocking” anti-CD8 antibodies can suppress autoreactive CD8+ T-cell activation in a relatively selective manner. These ndings provide a rational basis for the development and in vivo assessment of novel therapeutic strategies that preferentially target disease-relevant autoimmune responses within the CD8+ T-cell compartment
Clinical Outcomes and Survival Following Treatment of Metastatic Castrate-Refractory Prostate Cancer With Docetaxel Alone or With Strontium-89, Zoledronic Acid, or Both
Importance Bony metastatic castrate-refractory prostate cancer (CRPC) has a poor prognosis and high morbidity. Zoledronic acid (ZA) is commonly combined with docetaxel in practice but lacks evidence that combining is effective, and strontium-89 (Sr89) is generally used palliatively in patients unfit for chemotherapy. Phase 2 analysis of the TRAPEZE trial confirmed combining the agents was safe and feasible, and the objectives of phase 3 include assessment of the treatments on survival.
Objective To determine clinical effectiveness and cost-effectiveness of combining docetaxel, ZA, and Sr89, all having palliative benefits and used in bony metastatic CRPC to control bone symptoms and, for docetaxel, to prolong survival.
Design, Setting, and Participants The TRAPEZE trial is a 2 × 2 factorial trial comparing docetaxel alone or with ZA, Sr89, or both. A cohort of 757 participants were recruited between February 2005 and February 2012 from hospitals in the United Kingdom. Overall, 169 participants (45%) had received palliative radiotherapy, and the median (IQR) prostate-specific antigen level was 146 (51-354). Follow-ups were performed for at least 12 months.
Interventions Up to 10 cycles of docetaxel alone; docetaxel with ZA; docetaxel with a single Sr89 dose after 6 cycles; or docetaxel with both ZA and Sr89.
Main Outcomes and Measures Primary outcomes included clinical progression-free survival (CPFS) (pain progression, skeletal-related events [SREs], or death) and cost-effectiveness. Secondary outcomes included SRE-free interval, pain progression–free interval, total SREs, and overall survival (OS).
Results Overall, of 757 participants, 349 (46%) completed docetaxel treatment. Median (IQR) age was 68 (63-73) years. Clinical progression-free survival did not reach statistical significance for either Sr89 or ZA. Cox regression analysis adjusted for all stratification variables showed benefit of Sr89 on CPFS (hazard ratio [HR], 0.85; 95% CI, 0.73-0.99; P = .03) and confirmed no effect of ZA (HR, 0.98; 95% CI, 0.85-1.14; P = .81); ZA had a significant effect on SRE-free interval (HR, 0.78; 95% CI, 0.65-0.95; P = .01). For OS, there was no effect of either Sr89 (HR, 0.92; 95% CI, 0.79-1.08; P = 0.34) or ZA (HR, 0.99; 95% CI, 0.84-1.16; P = 0.91).
Conclusions and Relevance Strontium-89 combined with docetaxel improved CPFS but did not improve OS, SRE-free interval, or total SREs; ZA did not improve CPFS or OS but did significantly improve median SRE-free interval and reduced total SREs by around one-third, suggesting a role as postchemotherapy maintenance therapy
Ghana's evolving protein economy
This paper provides an initial analysis of Ghana's protein economy in the light on current debates about nutritional transition and livestock revolution. Ghana's strong economic growth and reducing levels of poverty make it a particularly interesting case. Protein-rich foods, including fish and livestock products, supply 20-40 percent of protein consumed. Overall fish is becoming less important and poultry more important; but there also are large difference in household expenditure on protein-rich foods across wealth categories, regions and areas. Specifically, the protein element of the nutritional transition and the consumption side of the livestock revolution would appear to be unfolding at different speeds and in different ways, along an axis that is urban-south-non-poor at one end, and rural-north-poor at the other. We explore the policy and political economy dimensions of these change
Access and utilisation of primary health care services comparing urban and rural areas of Riyadh Providence, Kingdom of Saudi Arabia
The Kingdom of Saudi Arabia (KSA) has seen an increase in chronic diseases. International evidence suggests that early intervention is the best approach to reduce the burden of chronic disease. However, the limited research available suggests that health care access remains unequal, with rural populations having the poorest access to and utilisation of primary health care centres and, consequently, the poorest health outcomes. This study aimed to examine the factors influencing the access to and utilisation of primary health care centres in urban and rural areas of Riyadh province of the KSA
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