203 research outputs found

    Manual of Criminal Law and Procedure

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    Intended to aid to Alaska law enforcement officers in the performance of their duties in the field, this manual was designed to provide brief, quick access to major points of substantive and procedural criminal law. The manual contained discussion and procedural guidelines for investigatory stops, identification procedures including line-ups, arrest, search and seizure, interrogation, as well as discussion of justification for the use of nondeadly and deadly force whether by peace officers or civilians, culpability, entrapment, trial preparation, and media relations. The section on substantive criminal law deals with a selection of crimes most likely to be encountered by "street" officers as defined with the recently enacted Revised Alaska Criminal Code (effective January 1, 1980), desribing elements of each crime, investigative hints, and differences with previous provisions of the criminal code, where relevant.Alaska Department of Law Grant No. 78-A-014Introduction / Criminal Procedures / Substantive Criminal Law / Justification / Culpability / Entrapment / Trial Preparation / Media Relations / Appendice

    Policy Feedback and the Politics of the Affordable Care Act

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    There is a large body of literature devoted to how “policies create politics” and how feedback effects from existing policy legacies shape potential reforms in a particular area. Although much of this literature focuses on self‐reinforcing feedback effects that increase support for existing policies over time, Kent Weaver and his colleagues have recently drawn our attention to self‐undermining effects that can gradually weaken support for such policies. The following contribution explores both self‐reinforcing and self‐undermining policy feedback in relationship to the Affordable Care Act, the most important health‐care reform enacted in the United States since the mid‐1960s. More specifically, the paper draws on the concept of policy feedback to reflect on the political fate of the ACA since its adoption in 2010. We argue that, due in part to its sheer complexity and fragmentation, the ACA generates both self‐reinforcing and self‐undermining feedback effects that, depending of the aspect of the legislation at hand, can either facilitate or impede conservative retrenchment and restructuring. Simultaneously, through a discussion of partisan effects that shape Republican behavior in Congress, we acknowledge the limits of policy feedback in the explanation of policy stability and change

    A Unifying Model of Genome Evolution Under Parsimony

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    We present a data structure called a history graph that offers a practical basis for the analysis of genome evolution. It conceptually simplifies the study of parsimonious evolutionary histories by representing both substitutions and double cut and join (DCJ) rearrangements in the presence of duplications. The problem of constructing parsimonious history graphs thus subsumes related maximum parsimony problems in the fields of phylogenetic reconstruction and genome rearrangement. We show that tractable functions can be used to define upper and lower bounds on the minimum number of substitutions and DCJ rearrangements needed to explain any history graph. These bounds become tight for a special type of unambiguous history graph called an ancestral variation graph (AVG), which constrains in its combinatorial structure the number of operations required. We finally demonstrate that for a given history graph GG, a finite set of AVGs describe all parsimonious interpretations of GG, and this set can be explored with a few sampling moves.Comment: 52 pages, 24 figure

    Comparative Antibiotic Resistance of Diarrheal Pathogens from Vietnam and Thailand, 1996-1999

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    Antimicrobial resistance rates for shigella, campylobacter, nontyphoidal salmonella, and enterotoxigenic Escherichia coli were compared for Vietnam and Thailand from 1996 to 1999. Resistance to trimethoprim-sulfamethoxazole, ampicillin, chloramphenicol, and tetracycline was common. Quinolone resistance remains low in both countries, except among campylobacter and salmonella organisms in Thailand. Nalidixic acid resistance among salmonellae has more than doubled since 1995 (to 21%) in Thailand but is not yet documented in Vietnam. Resistance to quinolones correlated with resistance to azithromycin in both campylobacter and salmonella in Thailand. This report describes the first identification of this correlation and its epidemiologic importance among clinical isolates. These data illustrate the growing magnitude of antibiotic resistance and important differences between countries in Southeast Asia

    MED27 Variants Cause Developmental Delay, Dystonia, and Cerebellar Hypoplasia

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    The Mediator multiprotein complex functions as a regulator of RNA polymerase II-catalyzed gene transcription. In this study, exome sequencing detected biallelic putative disease-causing variants in MED27, encoding Mediator complex subunit 27, in 16 patients from 11 families with a novel neurodevelopmental syndrome. Patient phenotypes are highly homogeneous, including global developmental delay, intellectual disability, axial hypotonia with distal spasticity, dystonic movements, and cerebellar hypoplasia. Seizures and cataracts were noted in severely affected individuals. Identification of multiple patients with biallelic MED27 variants supports the critical role of MED27 in normal human neural development, particularly for the cerebellum. ANN NEUROL 2021Peer reviewe

    Effect of Deutetrabenazine on Chorea Among Patients With Huntington Disease A Randomized Clinical Trial

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    Importance Deutetrabenazine is a novel molecule containing deuterium, which attenuates CYP2D6 metabolism and increases active metabolite half-lives and may therefore lead to stable systemic exposure while preserving key pharmacological activity. Objective To evaluate efficacy and safety of deutetrabenazine treatment to control chorea associated with Huntington disease. Design, Setting, and Participants Ninety ambulatory adults diagnosed with manifest Huntington disease and a baseline total maximal chorea score of 8 or higher (range, 0-28; lower score indicates less chorea) were enrolled from August 2013 to August 2014 and randomized to receive deutetrabenazine (n = 45) or placebo (n = 45) in a double-blind fashion at 34 Huntington Study Group sites. Interventions Deutetrabenazine or placebo was titrated to optimal dose level over 8 weeks and maintained for 4 weeks, followed by a 1-week washout. Main Outcomes and Measures Primary end point was the total maximal chorea score change from baseline (the average of values from the screening and day-0 visits) to maintenance therapy (the average of values from the week 9 and 12 visits) obtained by in-person visits. This study was designed to detect a 2.7-unit treatment difference in scores. The secondary end points, assessed hierarchically, were the proportion of patients who achieved treatment success on the Patient Global Impression of Change (PGIC) and on the Clinical Global Impression of Change (CGIC), the change in 36-Item Short Form– physical functioning subscale score (SF-36), and the change in the Berg Balance Test. Results Ninety patients with Huntington disease (mean age, 53.7 years; 40 women [44.4%]) were enrolled. In the deutetrabenazine group, the mean total maximal chorea scores improved from 12.1 (95% CI, 11.2-12.9) to 7.7 (95% CI, 6.5-8.9), whereas in the placebo group, scores improved from 13.2 (95% CI, 12.2-14.3) to 11.3 (95% CI, 10.0-12.5); the mean between-group difference was –2.5 units (95% CI, –3.7 to –1.3) (P < .001). Treatment success, as measured by the PGIC, occurred in 23 patients (51%) in the deutetrabenazine group vs 9 (20%) in the placebo group (P = .002). As measured by the CGIC, treatment success occurred in 19 patients (42%) in the deutetrabenazine group vs 6 (13%) in the placebo group (P = .002). In the deutetrabenazine group, the mean SF-36 physical functioning subscale scores decreased from 47.5 (95% CI, 44.3-50.8) to 47.4 (44.3-50.5), whereas in the placebo group, scores decreased from 43.2 (95% CI, 40.2-46.3) to 39.9 (95% CI, 36.2-43.6), for a treatment benefit of 4.3 (95% CI, 0.4 to 8.3) (P = .03). There was no difference between groups (mean difference of 1.0 unit; 95% CI, –0.3 to 2.3; P = .14), for improvement in the Berg Balance Test, which improved by 2.2 units (95% CI, 1.3-3.1) in the deutetrabenazine group and by 1.3 units (95% CI, 0.4-2.2) in the placebo group. Adverse event rates were similar for deutetrabenazine and placebo, including depression, anxiety, and akathisia. Conclusions and Relevance Among patients with chorea associated with Huntington disease, the use of deutetrabenazine compared with placebo resulted in improved motor signs at 12 weeks. Further research is needed to assess the clinical importance of the effect size and to determine longer-term efficacy and safety

    Genetic effects on gene expression across human tissues

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    Characterization of the molecular function of the human genome and its variation across individuals is essential for identifying the cellular mechanisms that underlie human genetic traits and diseases. The Genotype-Tissue Expression (GTEx) project aims to characterize variation in gene expression levels across individuals and diverse tissues of the human body, many of which are not easily accessible. Here we describe genetic effects on gene expression levels across 44 human tissues. We find that local genetic variation affects gene expression levels for the majority of genes, and we further identify inter-chromosomal genetic effects for 93 genes and 112 loci. On the basis of the identified genetic effects, we characterize patterns of tissue specificity, compare local and distal effects, and evaluate the functional properties of the genetic effects. We also demonstrate that multi-tissue, multi-individual data can be used to identify genes and pathways affected by human disease-associated variation, enabling a mechanistic interpretation of gene regulation and the genetic basis of diseas
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