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"Sullivan, Patrick"
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Belonging together : dealing with the politics of disenchantment in Australian Indigenous policy
Comprehensive and optimistic, this examination describes current Indigenous affairs policy in Australia, concentrating on the period following the end of the Aboriginal and Torres Strait Islander Commission in 2004. It provides a unique overview of the trajectory of current policy, advancing a new consolidated approach to Indigenous policy that moves beyond the debate over self-determination and assimilation. Arguing that the interests of Indigenous peoples, settlers, and immigrants are fundamentally shared, it proposes adaptation on both sides, but particularly for the descendants of settlers and immigrants. Advancing the body of knowledge in the field of the anthropology of policy and public administration, this empirical study is a must-read for policy-makers, academics, and indigenous peoples alike.
Book
Progress in the HIV epidemic: Identifying goals and measuring success
Substantial progress has been made towards the goal of ending the HIV/AIDS epidemic due to advancements in both prevention and treatment of HIV. However, major challenges still remain. We describe basic principles of epidemic control in the context of HIV and identify a number of attainable goals in terms of control and elimination of HIV in specific populations and risk groups, given currently available HIV prevention and treatment methods. Currently available HIV prevention methods make it a feasible goal to eliminate HIV transmission attributable to mother-to-child transmission and blood transfusions. Reductions in transmission attributable to sexual behavior and injection drug use are feasible, but elimination of these modes of transmission will require further advancements in behavioral and biomedical HIV prevention. With regard to HIV-related mortality, we argue that elimination of death due to HIV-related causes is a feasible goal. HIV-related deaths should be treated as sentinel events triggering epidemiological investigation into the breakdowns in the HIV care continuum that led to them. We briefly discuss additional considerations that will affect the success of HIV prevention programs.
Journal Article
Environmental pollution is associated with increased risk of psychiatric disorders in the US and Denmark
The search for the genetic factors underlying complex neuropsychiatric disorders has proceeded apace in the past decade. Despite some advances in identifying genetic variants associated with psychiatric disorders, most variants have small individual contributions to risk. By contrast, disease risk increase appears to be less subtle for disease-predisposing environmental insults. In this study, we sought to identify associations between environmental pollution and risk of neuropsychiatric disorders. We present exploratory analyses of 2 independent, very large datasets: 151 million unique individuals, represented in a United States insurance claims dataset, and 1.4 million unique individuals documented in Danish national treatment registers. Environmental Protection Agency (EPA) county-level environmental quality indices (EQIs) in the US and individual-level exposure to air pollution in Denmark were used to assess the association between pollution exposure and the risk of neuropsychiatric disorders. These results show that air pollution is significantly associated with increased risk of psychiatric disorders. We hypothesize that pollutants affect the human brain via neuroinflammatory pathways that have also been shown to cause depression-like phenotypes in animal studies.
Journal Article
A Pilot Randomized Trial of Intervention Components Addressing Drug Use in Couples HIV Testing and Counseling (CHTC) with Male Couples
Men who have sex with men (MSM) experience high rates of substance use and HIV infection. Main partners are the source of many (35–68%) of these new HIV infections. This study developed and examined the efficacy of two adjunct components to couples HIV testing and counseling (CHTC)—communication training (CT) videos and a substance use module (SUM)—to reduce drug use and sexual HIV transmission risk in MSM couples. Participants included 70 male couples randomized into one of four conditions: CHTC, CHTC + CT videos, CHTC + SUM, and CHTC + CT videos + SUM. Participants completed a survey pre-intervention and 1-, 3-, and 6-months later. Completion of the SUM in the absence of CT videos was associated with significant immediate decreases in drug use and related problems; however, at 3- and 6-month follow ups, the SUM was only associated with reductions in drug use and related problems among men who also viewed the CT videos. There were no between-condition differences in sexual behavior. CHTC may serve as a vehicle for the delivery of brief substance use intervention for MSM couples.ClinicalTrails.gov NCT # 03125915
Journal Article
Genetic architectures of psychiatric disorders: the emerging picture and its implications
Key Points
Psychiatric disorders cause enormous morbidity, mortality and personal and societal costs.
Despite considerable investigation, little is known for certain about aetiologies. Genetic approaches are a major avenue of investigation.
In the past 5 years, a considerable number of new findings have been discovered that meet community standards for robustness and replication.
Where sample sizes are sufficiently large, genome-wide association has yielded several dozen findings that suggest novel biological mechanisms.
Studies of rare variation (generally using genome-wide association study chips) have yielded over ten copy number variants that confer markedly increased risk. However, these tend to be nonspecific and increase risk for multiple different neuropsychiatric conditions.
Studies of exonic variation have yielded new findings for autism. However, for autism and schizophrenia, these findings are not abundant, and their genetic architectures do not appear to consist of a series of Mendelian traits, making the 'many Mendelian model' very unlikely.
Looking at the psychiatric disorders for which there are sufficient genetics data, it seems that these disorders are fairly typical complex traits with genetic variation scattered across the allelic spectrum.
For the first time, a fairly complete enumeration of the 'parts list' for these disorders is attainable using established methods. Further study using a balanced portfolio of methods to assess multiple forms of genetic variation is likely to yield many additional new findings.
This Review considers recent findings — from genome-wide association studies, structural variant studies and exome sequencing — about the genetics of nine psychiatric disorders. The authors evaluate the implications of our current picture of the genetic architectures of these conditions for future research strategies.
Psychiatric disorders are among the most intractable enigmas in medicine. In the past 5 years, there has been unprecedented progress on the genetics of many of these conditions. In this Review, we discuss the genetics of nine cardinal psychiatric disorders (namely, Alzheimer's disease, attention-deficit hyperactivity disorder, alcohol dependence, anorexia nervosa, autism spectrum disorder, bipolar disorder, major depressive disorder, nicotine dependence and schizophrenia). Empirical approaches have yielded new hypotheses about aetiology and now provide data on the often debated genetic architectures of these conditions, which have implications for future research strategies. Further study using a balanced portfolio of methods to assess multiple forms of genetic variation is likely to yield many additional new findings.
Journal Article
27-Hydroxycholesterol Links Hypercholesterolemia and Breast Cancer Pathophysiology
Hypercholesterolemia is a risk factor for estrogen receptor (ER)-positive breast cancers and is associated with a decreased response of tumors to endocrine therapies. Here, we show that 27-hydroxycholesterol (27HC), a primary metabolite of cholesterol and an ER and liver X receptor (LXR) ligand, increases ER-dependent growth and LXR-dependent metastasis in mouse models of breast cancer. The effects of cholesterol on tumor pathology required its conversion to 27HC by the cytochrome P450 oxidase CYP27A1 and were attenuated by treatment with CYP27A1 inhibitors. In human breast cancer specimens, CYP27A1 expression levels correlated with tumor grade. In high-grade tumors, both tumor cells and tumor-associated macrophages exhibited high expression levels of the enzyme. Thus, lowering circulating cholesterol levels or interfering with its conversion to 27HC may be a useful strategy to prevent and/or treat breast cancer.
Journal Article
Schizophrenia genomics: genetic complexity and functional insights
Determining the causes of schizophrenia has been a notoriously intractable problem, resistant to a multitude of investigative approaches over centuries. In recent decades, genomic studies have delivered hundreds of robust findings that implicate nearly 300 common genetic variants (via genome-wide association studies) and more than 20 rare variants (via whole-exome sequencing and copy number variant studies) as risk factors for schizophrenia. In parallel, functional genomic and neurobiological studies have provided exceptionally detailed information about the cellular composition of the brain and its interconnections in neurotypical individuals and, increasingly, in those with schizophrenia. Taken together, these results suggest unexpected complexity in the mechanisms that drive schizophrenia, pointing to the involvement of ensembles of genes (polygenicity) rather than single-gene causation. In this Review, we describe what we now know about the genetics of schizophrenia and consider the neurobiological implications of this information.In recent years, genomic studies have identified numerous genetic variants as risk factors for schizophrenia. Sullivan et al. describe our current understanding of the complex genetic architecture of schizophrenia and consider how the genomic findings can be interrogated to boost our understanding of the neurobiology of the disorder.
Journal Article