317 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
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
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
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
Developmental coordination disorder, psychopathology and IQ in 22q11.2 deletion syndrome
Background 22q11.2 Deletion Syndrome (22q11.2DS) is associated with high rates of neurodevelopmental disorder, however the links between developmental coordination disorder, intellectual function and psychiatric disorder remain unexplored. Aims Establish the prevalence of indicative Developmental Coordination Disorder (DCD) in children with 22q11.2DS, and examine associations with IQ, neuro-cognition and psychopathology. In-home neuro-cognitive assessments and psychiatric interviews of 70 children with 22q11.2DS (mean age=11.24, s.d=2.2) and 32 control siblings (mean age=11.5, s.d=2.1). Nine children with 22q11.2DS and indicative DCD were subsequently assessed in an occupational therapy clinic. Results Indicative DCD was found in 81.4% of children with 22q11.2DS, compared to 6.3% in control siblings (OR=36.7, p<0.001). Eight of nine (89%) children with indicative DCD met DSM-5 criteria for DCD. Poorer coordination was associated with increased numbers of anxiety, (p<0.001), Attention Deficit Hyperactivity Disorder (ADHD) (p<0.001) and Autism Spectrum Disorder (ASD) symptoms (p<0.001) in children with 22q11.2DS. Furthermore, 100% of children with 22q11.2DS and ADHD had indicative DCD, as did 90% of children with anxiety disorder and 96% of children who screened positive for ASD. DCDQ score was related to sustained attention (p=0.006), even after history of epileptic fits (p=0.006) and heart problems (p=0.009) was taken into account
Correction: The psychiatric phenotypes of 1q21 distal deletion and duplication.
Copy number variants are amongst the most highly penetrant risk factors for psychopathology and neurodevelopmental deficits, but little information about the detailed clinical phenotype associated with particular variants is available. We present the largest study of the microdeletion and -duplication at the distal 1q21 locus, which has been associated with schizophrenia and intellectual disability, in order to investigate the range of psychiatric phenotypes. Clinical and cognitive data from 68 deletion and 55 duplication carriers were analysed with logistic regression analysis to compare frequencies of mental disorders between carrier groups and controls, and linear mixed models to compare quantitative phenotypes. Both children and adults with copy number variants at 1q21 had high frequencies of psychopathology. In the children, neurodevelopmental disorders were most prominent (56% for deletion, 68% for duplication carriers). Adults had increased prevalence of mood (35% for deletion [OR = 6.6 (95% CI: 1.4–40.1)], 55% for duplication carriers [8.3 (1.4–55.5)]) and anxiety disorders (24% [1.8 (0.4–8.4)] and 55% [10.0 (1.9–71.2)]). The adult group, which included mainly genetically affected parents of probands, had an IQ in the normal range. These results confirm high prevalence of neurodevelopmental disorders associated with CNVs at 1q21 but also reveal high prevalence of mood and anxiety disorders in a high-functioning adult group with these CNVs. Because carriers of neurodevelopmental CNVs who show relevant psychopathology but no major cognitive impairment are not currently routinely receiving clinical genetic services widening of genetic testing in psychiatry may be considered
Psychiatric disorders in children with 16p11.2 deletion and duplication
Deletion and duplication of 16p11.2 (BP4–BP5) have been associated with an increased risk of intellectual disability and psychiatric disorder. This is the first study to compare the frequency of a broad spectrum of psychiatric disorders in children with 16p11.2 deletion and duplication. We aimed to evaluate (1) the nature and prevalence of psychopathology associated with copy number variation (CNV) in children with 16p11.2 by comparing deletion and duplication carriers with family controls; (2) whether deletion and duplication carriers differ in frequency of psychopathology. 217 deletion carriers, 77 deletion family controls, 114 duplication carriers, and 32 duplication family controls participated in the study. Measures included standardized research diagnostic instruments. Deletion carriers had a higher frequency of any psychiatric disorder (OR = 8.9, p < 0.001), attention deficit hyperactivity disorder (ADHD) (OR = 4.0, p = 0.01), and autism spectrum disorder (ASD) (OR = 39.9, p = 0.01) than controls. Duplication carriers had a higher frequency of any psychiatric diagnosis (OR = 5.3, p = 0.01) and ADHD (OR = 7.0, p = 0.02) than controls. The prevalence of ASD in child carriers of deletions and duplications was similar (22% versus 26%). Comparison of the two CNV groups indicated a higher frequency of ADHD in children with the duplication than deletion (OR = 2.7, p = 0.04) as well as a higher frequency of overall psychiatric disorders (OR = 2.8, p = 0.02) and psychotic symptoms (OR = 4.7, p = 0.02). However, no differences between deletion and duplications carriers in the prevalence of ASD were found. Both deletion and duplication are associated with an increased risk of psychiatric disorder, supporting the importance of early recognition, diagnosis, and intervention in these groups
MicroRNA-135b promotes cancer progression by acting as a downstream effector of oncogenic pathways in colon cancer
MicroRNA deregulation is frequent in human colorectal cancers (CRCs), but little is known as to whether it represents a bystander event or actually drives tumor progression in vivo. We show that miR-135b overexpression is triggered in mice and humans by APC loss, PTEN/PI3K pathway deregulation, and SRC overexpression and promotes tumor transformation and progression. We show that miR-135b upregulation is common in sporadic and inflammatory bowel disease-associated human CRCs and correlates with tumor stage and poor clinical outcome. Inhibition of miR-135b in CRC mouse models reduces tumor growth by controlling genes involved in proliferation, invasion, and apoptosis. We identify miR-135b as a key downsteam effector of oncogenic pathways and a potential target for CRC treatment
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