440 research outputs found
A Note on the Nineteenth Century Law of Seduction
The authors examine Prince Edward Island\u27s Seduction Act of 1876, which departed from the model of seduction legislation of other Canadian provinces. Based on study of the limited surviving court records they note a number of ways in which the tort of seduction operated differently in nineteenth century Prince Edward Island than it did elsewher
Differential effect of CLK SR Kinases on HIV-1 gene expression: potential novel targets for therapy
<p>Abstract</p> <p>Background</p> <p>RNA processing plays a critical role in the replication of HIV-1, regulated in part through the action of host SR proteins. To explore the impact of modulating SR protein activity on virus replication, the effect of increasing or inhibiting the activity of the Cdc2-like kinase (CLK) family of SR protein kinases on HIV-1 expression and RNA processing was examined.</p> <p>Results</p> <p>Despite their high homology, increasing individual CLK expression had distinct effects on HIV-1, CLK1 enhancing Gag production while CLK2 inhibited the virus. Parallel studies on the anti-HIV-1 activity of CLK inhibitors revealed a similar discrepant effect on HIV-1 expression. TG003, an inhibitor of CLK1, 2 and 4, had no effect on viral Gag synthesis while chlorhexidine, a CLK2, 3 and 4 inhibitor, blocked virus production. Chlorhexidine treatment altered viral RNA processing, decreasing levels of unspliced and single spliced viral RNAs, and reduced Rev accumulation. Subsequent experiments in the context of HIV-1 replication in PBMCs confirmed the capacity of chlorhexidine to suppress virus replication.</p> <p>Conclusions</p> <p>Together, these findings establish that HIV-1 RNA processing can be targeted to suppress virus replication as demonstrated by manipulating individual CLK function and identified chlorhexidine as a lead compound in the development of novel anti-viral therapies.</p
Survey of Handlers of 158 Police Dogs in New Zealand: Functional Assessment and Canine Orthopedic Index
Objectives: To determine the functional assessment (FA) of fitness and Canine Orthopedic Index (COI) scores of 158 police dogs. The hypothesis was the dogs would have excellent fitness and no evidence of orthopedic disease regardless of age as reported by the handlers.Study Design:Observational, prospective study.Sample Population: Handlers of dogs >1 year of age in active duty or breeding/active duty.Methods: COI and FA questionnaires were completed via e-mail. Fisher's Exact test for count data assessed scores by age group (<2 years, 2–5 years, >5 years); Wilcoxon Signed-rank test correlated COI parameters (stiffness, function, gait, quality of life) to FA.Results: The dogs were 3.2 ± 2.4 (mean ± standard deviation) years-old, 96% were German Shepherds and 111 were male. 32% of dogs could hold the “Hup” position for no longer than 4 s and 8% frequently had difficulty with this task. Difficulty jumping into vehicles occurred in 1/3 of the dogs. Overall FA was impaired in 20% (score >8), abnormal in 15% (score = 5–7), and reduced (score = 1–4) in 36% of dogs. Only 29% had normal function (FA score = 0) and these were significantly younger (2.8 ± 1.7 years, p < 0.05) than impaired dogs (6.6 ± 2.2 years). COI stiffness score was abnormal in 37% (3.3 ± 2.2) and gait was abnormal in 41% (5.4 ± 4.0). Quality of life (QOL) was excellent in 69% of dogs. Stiffness for the <2 year-old group was 0.2 ± 0.8, for the 2–5 year-old group was 1.1 ± 2.0 and for the >5 year-old group was 3.2 ± 2.4. Gait score for the <2 year group was 0.8 ± 2.2, and for the 2–5 year group was 1.9 ± 3.2 and for the >5 year group was 6.0 ± 4.3. Quality of life was close to excellent for the <2 year-olds (0.3 ± 1.1) and 2–5 year-olds (0.8 ± 2.0) but the >5 year-olds scored higher (3.0 ± 2.5). Only the COI gait score correlated with the FA score (p = 0.30).Conclusions and Clinical Relevance: Police dogs were reported by handlers to have good to excellent QOL, however, increasing age was associated with declining FA and COI scores
Inflammatory bowel disease: the role of inflammatory cytokine gene polymorphisms.
The mechanisms responsible for development of inflammatory bowel disease (IBD) have not been fully elucidated, although the main cause of disease pathology is attributed to up-regulated inflammatory processes. The aim of this study was to investigate frequencies of polymorphisms in genes encoding pro-inflammatory and anti-inflammatory markers in IBD patients and controls. We determined genotypes of patients with IBD (n= 172) and healthy controls (n= 389) for polymorphisms in genes encoding various cytokines (interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF), IL-10, IL-1 receptor antagonist). Association of these genotypes to disease incidence and pathophysiology was investigated. No strong association was found with occurrence of IBD. Variation was observed between the ulcerative colitis study group and the control population for the TNF-alpha-308 polymorphism (p= 0.0135). There was also variation in the frequency of IL-6-174 and TNF-alpha-308 genotypes in the ulcerative colitis group compared with the Crohn's disease group (p= 0.01). We concluded that polymorphisms in inflammatory genes are associated with variations in IBD phenotype and disease susceptibility. Whether the polymorphisms are directly involved in regulating cytokine production, and consequently pathophysiology of IBD, or serve merely as markers in linkage disequilibrium with susceptibility genes remains unclear
Sedentary time in older men and women: an international consensus statement and research priorities
Sedentary time is a modifiable determinant of poor health, and in older adults, reducing sedentary time may be an important first step in adopting and maintaining a more active lifestyle. The primary purpose of this consensus statement is to provide an integrated perspective on current knowledge and expert opinion pertaining to sedentary behaviour in older adults on the topics of measurement, associations with health outcomes, and interventions. A secondary yet equally important purpose is to suggest priorities for future research and knowledge translation based on gaps identified. A five-step Delphi consensus process was used. Experts in the area of sedentary behaviour and older adults (n=15) participated in three surveys, an in-person consensus meeting, and a validation process. The surveys specifically probed measurement, health outcomes, interventions, and research priorities. The meeting was informed by a literature review and conference symposium, and it was used to create statements on each of the areas addressed in this document. Knowledge users (n=3) also participated in the consensus meeting. Statements were then sent to the experts for validation. It was agreed that self-report tools need to be developed for understanding the context in which sedentary time is accumulated. For health outcomes, it was agreed that the focus of sedentary time research in older adults needs to include geriatric-relevant health outcomes, that there is insufficient evidence to quantify the dose-response relationship, that there is a lack of evidence on sedentary time from older adults in assisted facilities, and that evidence on the association between sedentary time and sleep is lacking. For interventions, research is needed to assess the impact that reducing sedentary time, or breaking up prolonged bouts of sedentary time has on geriatric-relevant health outcomes. Research priorities listed for each of these areas should be considered by researchers and funding agencies
Accelerating slip rates on the Puente Hills blind thrust fault system beneath metropolitan Los Angeles, California, USA
Slip rates represent the average displacement across a fault over time and are essential to estimating earthquake recurrence for probabilistic seismic hazard assessments. We demonstrate that the slip rate on the western segment of the Puente Hills blind thrust fault system, which is beneath downtown Los Angeles, California (USA), has accelerated from ∼0.22 mm/yr in the late Pleistocene to ∼1.33 mm/yr in the Holocene. Our analysis is based on syntectonic strata derived from the Los Angeles River, which has continuously buried a fold scarp above the blind thrust. Slip on the fault beneath our field site began during the late-middle Pleistocene and progressively increased into the Holocene. This increase in rate implies that the magnitudes and/or the frequency of earthquakes on this fault segment have increased over time. This challenges the characteristic earthquake model and presents an evolving and potentially increasing seismic hazard to metropolitan Los Angeles
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