254 research outputs found
Public Administration and Policy Degree Programs in Legal Education: The McGeorge School of Law Case Study
Population-based outreach versus care as usual to prevent suicide attempt: study protocol for a randomized controlled trial
Genetic risk prediction and neurobiological understanding of alcoholism
We have used a translational Convergent Functional Genomics (CFG) approach to discover genes involved in alcoholism, by gene-level integration of genome-wide association study (GWAS) data from a German alcohol dependence cohort with other genetic and gene expression data, from human and animal model studies, similar to our previous work in bipolar disorder and schizophrenia. A panel of all the nominally significant P-value single-nucleotide length polymorphisms (SNPs) in the top candidate genes discovered by CFG (n = 135 genes, 713 SNPs) was used to generate a genetic risk prediction score (GRPS), which showed a trend towards significance (P = 0.053) in separating alcohol dependent individuals from controls in an independent German test cohort. We then validated and prioritized our top findings from this discovery work, and subsequently tested them in three independent cohorts, from two continents. In order to validate and prioritize the key genes that drive behavior without some of the pleiotropic environmental confounds present in humans, we used a stress-reactive animal model of alcoholism developed by our group, the D-box binding protein (DBP) knockout mouse, consistent with the surfeit of stress theory of addiction proposed by Koob and colleagues. A much smaller panel (n = 11 genes, 66 SNPs) of the top CFG-discovered genes for alcoholism, cross-validated and prioritized by this stress-reactive animal model showed better predictive ability in the independent German test cohort (P = 0.041). The top CFG scoring gene for alcoholism from the initial discovery step, synuclein alpha (SNCA) remained the top gene after the stress-reactive animal model cross-validation. We also tested this small panel of genes in two other independent test cohorts from the United States, one with alcohol dependence (P = 0.00012) and one with alcohol abuse (a less severe form of alcoholism; P = 0.0094). SNCA by itself was able to separate alcoholics from controls in the alcohol-dependent cohort (P = 0.000013) and the alcohol abuse cohort (P = 0.023). So did eight other genes from the panel of 11 genes taken individually, albeit to a lesser extent and/or less broadly across cohorts. SNCA, GRM3 and MBP survived strict Bonferroni correction for multiple comparisons. Taken together, these results suggest that our stress-reactive DBP animal model helped to validate and prioritize from the CFG-discovered genes some of the key behaviorally relevant genes for alcoholism. These genes fall into a series of biological pathways involved in signal transduction, transmission of nerve impulse (including myelination) and cocaine addiction. Overall, our work provides leads towards a better understanding of illness, diagnostics and therapeutics, including treatment with omega-3 fatty acids. We also examined the overlap between the top candidate genes for alcoholism from this work and the top candidate genes for bipolar disorder, schizophrenia, anxiety from previous CFG analyses conducted by us, as well as cross-tested genetic risk predictions. This revealed the significant genetic overlap with other major psychiatric disorder domains, providing a basis for comorbidity and dual diagnosis, and placing alcohol use in the broader context of modulating the mental landscape
Genetic polymorphisms of N-acetyltransferase 1 and 2 and risk of cigarette smoking-related bladder cancer
Aromatic amines from cigarette smoking or occupational exposure, recognized risk factors for bladder cancer, are metabolized by N-acetyltransferases (NAT). This study examined the association of (NAT) 1 and 2 genotypes with the risk of smoking-related bladder cancer. A total of 74 pathologically confirmed bladder cancer patients and 184 controls were serially recruited from the National Taiwan University Hospital. History of cigarette smoking and other risk factors for bladder cancer was obtained through standardized questionnaire interview. Peripheral blood lymphocytes were collected from each subject and genotyped for NAT1 and NAT2 by DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism methods. Allele frequency distributions of NAT1 and NAT2 were similar between cases and controls. There was a significant dose–response relationship between the risk of bladder cancer and the quantity and duration of cigarette smoking. The biological gradients were significant among subjects carrying NAT1*10 allele or NAT2 slow acetylators, but not among NAT2 rapid acetylators without NAT1*10 allele. The results are consistent with the hypothesis that NAT1 and NAT2 might modulate the susceptibility to bladder cancer associated with cigarette smoking. © 1999 Cancer Research Campaig
Poboljšana elektromagnetska kompatibilnost (EMC) sklopnog energetskog pretvarača sa slučajnom modulacijom
This paper surveys some analytical and experimental results concerning different randomized modulation strategies in switched-mode power converters (SMPCs). After a short review of practical experiences within the literature it presents the benefits of several randomized schemes for power converters (i.e. reduced electromagnetic interference - EMI, and lower acoustic noise). It also introduces the mathematical background for dealing with randomized modulation within the medium-frequency range: power spectrum density (PSD). Finally, the EMI measurements confirm the improved EMC performances of the randomized boost rectifier, as also in the DC-DC buck converter.Ovaj članak istražuje analitičke i eksperimentalne rezultate različitih slučajnih strategija modulacije u sklopnim energetskim pretvaračima (SMPCs). Nakon kratkog pregleda praktičnih iskustava iz literature, predstavljene su prednosti nekoliko slučajnih shema za energetske pretvarače (smanjena elektromagnetska interferencija - EMI, i niži akustični šum). Također, uvedena je matematička podloga za rad sa slučajnom modulacijom u području srednjih frekvencija: spektralna gustoća snage (PSD). Konačno, EMI mjerenja potvrđuju poboljšanja EMC performansi slučajnih uzlaznih ispravljača, kao i DC-DC silaznih pretvarača
Usefulness and limitations of transthoracic echocardiography in heart transplantation recipients
Transthoracic echocardiography is a primary non-invasive modality for investigation of heart transplant recipients. It is a versatile tool which provides comprehensive information about cardiac structure and function. Echocardiographic examinations can be easily performed at the bedside and serially repeated without any patient's discomfort. This review highlights the usefulness of Doppler echocardiography in the assessment of left ventricular and right ventricular systolic and diastolic function, of left ventricular mass, valvular heart disease, pulmonary arterial hypertension and pericardial effusion in heart transplant recipients. The main experiences performed by either standard Doppler echocardiography and new high-tech ultrasound technologies are summarised, pointing out advantages and limitations of the described techniques in diagnosing acute allograft rejection and cardiac graft vasculopathy. Despite the sustained efforts of echocardiographic technique in predicting the biopsy state, endocardial myocardial biopsies are still regarded as the gold standard for detection of acute allograft rejection. Conversely, stress echocardiography is able to identify accurately cardiac graft vasculopathy and has a recognised prognostic in this clinical setting. A normal stress-echo justifies postponement of invasive studies. Another use of transthoracic echocardiography is the monitorisation and the visualisation of the catheter during the performance of endomyocardial biopsy. Bedside stress echocardiography is even useful to select appropriately heart donors with brain death. The ultrasound monitoring is simple and effective for monitoring a safe performance of biopsy procedures
Absence of evidence for the conservation outcomes of systematic conservation planning around the globe : A systematic map
Background Systematic conservation planning is a discipline concerned with the prioritisation of resources for biodiversity conservation and is often used in the design or assessment of terrestrial and marine protected area networks. Despite being an evidence-based discipline, to date there has been no comprehensive review of the outcomes of systematic conservation plans and assessments of the relative effectiveness of applications in different contexts. To address this fundamental gap in knowledge, our primary research question was: what is the extent, distribution and robustness of evidence on conservation outcomes of systematic conservation planning around the globe? Methods A systematic mapping exercise was undertaken using standardised search terms across 29 sources, including publication databases, online repositories and a wide range of grey literature sources. The review team screened articles recursively, first by title only, then abstract and finally by full-text, using inclusion criteria related to systematic conservation plans conducted at sub-global scales and reported on since 1983. We sought studies that reported outcomes relating to natural, human, social, financial or institutional outcomes and which employed robust evaluation study designs. The following information was extracted from included studies: bibliographic details, background information including location of study and broad objectives of the plan, study design, reported outcomes and context. Results Of the approximately 10,000 unique articles returned through our searches, 1209 were included for full-text screening and 43 studies reported outcomes of conservation planning interventions. However, only three studies involved the use of evaluation study designs which are suitably rigorous for inclusion, according to best-practice guidelines. The three included studies were undertaken in the Gulf of California (Mexico), Réunion Island, and The Nature Conservancy’s landholdings across the USA. The studies varied widely in context, purpose and outcomes. Study designs were non-experimental or qualitative, and involved use of spatial landholdings over time, stakeholder surveys and modelling of alternative planning scenarios. Conclusion Rigorous evaluations of systematic conservation plans are currently not published in academic journals or made publicly available elsewhere. Despite frequent claims relating to positive implications and outcomes of these planning activities, we show that evaluations are probably rarely conducted. This finding does not imply systematic conservation planning is not effective but highlights a significant gap in our understanding of how, when and why it may or may not be effective. Our results also corroborate claims that the literature on systematic conservation planning is dominated by methodological studies, rather than those that focus on implementation and outcomes, and support the case that this is a problematic imbalance in the literature. We emphasise the need for academics and practitioners to publish the outcomes of systematic conservation planning exercises and to consider employing robust evaluation methodologies when reporting project outcomes. Adequate reporting of outcomes will in turn enable transparency and accountability between institutions and funding bodies as well as improving the science and practice of conservation planning
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