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Genetic research on nicotine dependence has utilized multiple assessments that are in weak agreement.
Methods
We conducted a genome-wide association study (GWAS) of nicotine dependence defined using the Diagnostic and Statistical Manual of Mental Disorders (DSM-NicDep) in 61,861 individuals (47,884 of European ancestry [EUR], 10,231 of African ancestry, and 3,746 of East Asian ancestry) and compared the results to other nicotine-related phenotypes.
Results
We replicated the well-known association at the CHRNA5 locus (lead single-nucleotide polymorphism [SNP]: rs147144681, p = 1.27E−11 in EUR; lead SNP = rs2036527, p = 6.49e−13 in cross-ancestry analysis). DSM-NicDep showed strong positive genetic correlations with cannabis use disorder, opioid use disorder, problematic alcohol use, lung cancer, material deprivation, and several psychiatric disorders, and negative correlations with respiratory function and educational attainment. A polygenic score of DSM-NicDep predicted DSM-5 tobacco use disorder criterion count and all 11 individual diagnostic criteria in the independent National Epidemiologic Survey on Alcohol and Related Conditions-III sample. In genomic structural equation models, DSM-NicDep loaded more strongly on a previously identified factor of general addiction liability than a “problematic tobacco use” factor (a combination of cigarettes per day and nicotine dependence defined by the Fagerström Test for Nicotine Dependence). Finally, DSM-NicDep showed a strong genetic correlation with a GWAS of tobacco use disorder as defined in electronic health records (EHRs).
Conclusions
Our results suggest that combining the wide availability of diagnostic EHR data with nuanced criterion-level analyses of DSM tobacco use disorder may produce new insights into the genetics of this disorder.
Edited by
Marietta Auer, Max Planck Institute for Legal History and Legal Theory,Paul B. Miller, University of Notre Dame, Indiana,Henry E. Smith, Harvard Law School, Massachusetts,James Toomey, University of Iowa
Edited by
Marietta Auer, Max Planck Institute for Legal History and Legal Theory,Paul B. Miller, University of Notre Dame, Indiana,Henry E. Smith, Harvard Law School, Massachusetts,James Toomey, University of Iowa
Edited by
Marietta Auer, Max Planck Institute for Legal History and Legal Theory,Paul B. Miller, University of Notre Dame, Indiana,Henry E. Smith, Harvard Law School, Massachusetts,James Toomey, University of Iowa
Edited by
Marietta Auer, Max Planck Institute for Legal History and Legal Theory,Paul B. Miller, University of Notre Dame, Indiana,Henry E. Smith, Harvard Law School, Massachusetts,James Toomey, University of Iowa
Edited by
Marietta Auer, Max Planck Institute for Legal History and Legal Theory,Paul B. Miller, University of Notre Dame, Indiana,Henry E. Smith, Harvard Law School, Massachusetts,James Toomey, University of Iowa
Edited by
Marietta Auer, Max Planck Institute for Legal History and Legal Theory,Paul B. Miller, University of Notre Dame, Indiana,Henry E. Smith, Harvard Law School, Massachusetts,James Toomey, University of Iowa
This chapter critically examines the treatment of concepts of legal personality and representation provided by the great (if lamentably now mostly forgotten) German realist phenomenologist Adolf Reinach. In The A Priori Foundations of the Civil Law (1913), Reinach offers what is meant to be a phenomenological elucidation of the a priori nature (essential formal characteristics) of a wide variety of foundational legal concepts, the latter understood as denoting distinctive modalities of speech act. The primary interest of the chapter lies in the analysis that Reinach provides of concepts of personality and representation. However, one cannot understand what is distinctive in – and distinctively compelling or puzzling about – Reinach’s analysis of these concepts without appreciating what is distinctive about his general methodology of conceptual analysis (i.e., his phenomenological, speech act theoretical understanding of social behavior denoted by legal concepts). Thus, in addition to examining Reinach’s views on persons, legal personhood, and legal representation, the chapter provides a critical introduction to Reinachian conceptual analysis and explains its enduring interest for contemporary private law theory.
Edited by
Marietta Auer, Max Planck Institute for Legal History and Legal Theory,Paul B. Miller, University of Notre Dame, Indiana,Henry E. Smith, Harvard Law School, Massachusetts,James Toomey, University of Iowa
Edited by
Marietta Auer, Max Planck Institute for Legal History and Legal Theory,Paul B. Miller, University of Notre Dame, Indiana,Henry E. Smith, Harvard Law School, Massachusetts,James Toomey, University of Iowa
Edited by
Marietta Auer, Max Planck Institute for Legal History and Legal Theory,Paul B. Miller, University of Notre Dame, Indiana,Henry E. Smith, Harvard Law School, Massachusetts,James Toomey, University of Iowa
Edited by
Marietta Auer, Max Planck Institute for Legal History and Legal Theory,Paul B. Miller, University of Notre Dame, Indiana,Henry E. Smith, Harvard Law School, Massachusetts,James Toomey, University of Iowa
This volume introduces the legal philosopher Adolf Reinach and his contributions to speech act theory, as well as his analysis of basic legal concepts and their relationship to positive law. Reinach's thorough analysis has recently garnered growing interest in private law theory, yet his 'phenomenological realist' philosophical approach is not in line with contemporary mainstream approaches. The essays in this volume resuscitate and interrogate Reinach's unique account of the foundations of private law, situating him in contemporary private law theory and broader philosophical currents. The work also makes Reinach's methods more accessible to those unfamiliar with early phenomenology. Together these contributions prove that while Reinach's perspective on private law shares similarities and points of departure with trends in today's legal theory, many of his insights remain singular and illuminating in their own right. This title is also available as Open Access on Cambridge Core.
Although the link between alcohol involvement and behavioral phenotypes (e.g. impulsivity, negative affect, executive function [EF]) is well-established, the directionality of these associations, specificity to stages of alcohol involvement, and extent of shared genetic liability remain unclear. We estimate longitudinal associations between transitions among alcohol milestones, behavioral phenotypes, and indices of genetic risk.
Methods
Data came from the Collaborative Study on the Genetics of Alcoholism (n = 3681; ages 11–36). Alcohol transitions (first: drink, intoxication, alcohol use disorder [AUD] symptom, AUD diagnosis), internalizing, and externalizing phenotypes came from the Semi-Structured Assessment for the Genetics of Alcoholism. EF was measured with the Tower of London and Visual Span Tasks. Polygenic scores (PGS) were computed for alcohol-related and behavioral phenotypes. Cox models estimated associations among PGS, behavior, and alcohol milestones.
Results
Externalizing phenotypes (e.g. conduct disorder symptoms) were associated with future initiation and drinking problems (hazard ratio (HR)⩾1.16). Internalizing (e.g. social anxiety) was associated with hazards for progression from first drink to severe AUD (HR⩾1.55). Initiation and AUD were associated with increased hazards for later depressive symptoms and suicidal ideation (HR⩾1.38), and initiation was associated with increased hazards for future conduct symptoms (HR = 1.60). EF was not associated with alcohol transitions. Drinks per week PGS was linked with increased hazards for alcohol transitions (HR⩾1.06). Problematic alcohol use PGS increased hazards for suicidal ideation (HR = 1.20).
Conclusions
Behavioral markers of addiction vulnerability precede and follow alcohol transitions, highlighting dynamic, bidirectional relationships between behavior and emerging addiction.
Several hypotheses may explain the association between substance use, posttraumatic stress disorder (PTSD), and depression. However, few studies have utilized a large multisite dataset to understand this complex relationship. Our study assessed the relationship between alcohol and cannabis use trajectories and PTSD and depression symptoms across 3 months in recently trauma-exposed civilians.
Methods
In total, 1618 (1037 female) participants provided self-report data on past 30-day alcohol and cannabis use and PTSD and depression symptoms during their emergency department (baseline) visit. We reassessed participant's substance use and clinical symptoms 2, 8, and 12 weeks posttrauma. Latent class mixture modeling determined alcohol and cannabis use trajectories in the sample. Changes in PTSD and depression symptoms were assessed across alcohol and cannabis use trajectories via a mixed-model repeated-measures analysis of variance.
Results
Three trajectory classes (low, high, increasing use) provided the best model fit for alcohol and cannabis use. The low alcohol use class exhibited lower PTSD symptoms at baseline than the high use class; the low cannabis use class exhibited lower PTSD and depression symptoms at baseline than the high and increasing use classes; these symptoms greatly increased at week 8 and declined at week 12. Participants who already use alcohol and cannabis exhibited greater PTSD and depression symptoms at baseline that increased at week 8 with a decrease in symptoms at week 12.
Conclusions
Our findings suggest that alcohol and cannabis use trajectories are associated with the intensity of posttrauma psychopathology. These findings could potentially inform the timing of therapeutic strategies.
The objective of this study is to determine the physical evaluations and assessment tools used by a group of Canadian healthcare professionals treating adults with spasticity.
Methods:
A cross-sectional web-based 19-question survey was developed to determine the types of physical evaluations, tone-related impairment measurements, and assessment tools used in the management of adults with spasticity. The survey was distributed to healthcare professionals from the Canadian Advances in Neuro-Orthopedics for Spasticity Congress database.
Results:
Eighty study participants (61 physiatrists and 19 other healthcare professionals) completed the survey and were included. Nearly half (46.3%, 37/80) of the participants reported having an inter- or trans-disciplinary team managing individuals with spasticity. Visual observation of movement, available range of motion determination, tone during velocity-dependent passive range of motion looking for a spastic catch, spasticity, and clonus, and evaluation of gait were the most frequently used physical evaluations. The most frequently used spasticity tools were the Modified Ashworth Scale, goniometer, and Goal Attainment Scale. Results were similar in brain- and spinal cord-predominant etiologies. To evaluate goals, qualitative description was used most (37.5%).
Conclusion:
Our findings provide a better understanding of the spasticity management landscape in Canada with respect to staffing, physical evaluations, and outcome measurements used in clinical practice. For all etiologies of spasticity, visual observation of patient movement, Modified Ashworth Scale, and qualitative goal outcomes descriptions were most commonly used to guide treatment and optimize outcomes. Understanding the current practice of spasticity assessment will help provide guidance for clinical evaluation and management of spasticity.
This chapter examines two modalities of equitable intervention in corporate governance in cases of shareholder conflict. The first involves the extension of fiduciary duties to controlling shareholders, and the second judicial review on the grounds of oppression. Both forms of intervention are intended to be responsive to pathologies inherent in majoritarian governance in organizations featuring enfranchised members. Notwithstanding long-settled authority in Delaware and other American states for the proposition that controlling shareholders are fiduciaries of minority shareholders, I argue that fiduciary regulation is an inapt modality of equitable intervention given the nature of the problems generated by majority rule in corporations. By comparison, the oppression remedy—favored in commonwealth jurisdictions—enables more apt and effective tailored responses to these problems. The choice between these modalities of intervention implicates a choice between equity’s supplemental contributions to first-order law and its corrective, second-order intervention in first-order law. The chapter concludes with some general reflections on the place of equity in contemporary law.
This article provides an overview of selected ongoing international efforts that have been inspired by Edward Zigler's vision to improve programs and policies for young children and families in the United States. The efforts presented are in close alignment with three strategies articulated by Edward Zigler: (a) conduct research that will inform policy advocacy; (b) design, implement, and revise quality early childhood development (ECD) programs; and (c) invest in building the next generation of scholars and advocates in child development. The intergenerational legacy left by Edward Zigler has had an impact on young children not only in the United States, but also across the globe. More needs to be done. We need to work together with a full commitment to ensure the optimal development of each child.