Consistency, Proportionality, and Substantive Judicial Review in Capital Sentencing

Symposium: Toward A Model Death Penalty Code: The Massachusetts Governor\u27s Council Report

Of Prosecutors and Special Prosecutors: An Organizational Perspective

The Independent Counsel (IC) statute, designed to restore public trust in the impartial administration of criminal justice after Watergate, ultimately fueled rather than quieted the perception that partisan politics drives the investigation of high-ranking government officials. Congress, in an inspiring display of bipartisanship, bid it a muted farewell. The statute\u27s fate was sealed by the enormous controversy surrounding the investigation conducted by Independent Counsel Kenneth Starr. Although Start did not bring criminal charges against President Clinton, his office went pretty far in that direction, committing considerable enforcement resources to that end, bringing criminal charges against people believed to have information that would implicate Clinton, and deploying arguments of prosecutorial prerogative that have significantly changed the legal landscape. Like many others, we have found this exercise of prosecutorial power terribly troubling. Also troubling, however, is the difficulty we (and others) have had in identifying neutral principles of prosecutorial discretion that Starr violated. The standard criticisms of Starr\u27s investigation do not meet that measure. The standard criticisms of the IC mechanism generally, though possessing greater force, are similarly unsatisfying. This essay, written from the perspective of two former federal prosecutors, springs from our effort to identify the fundamental shortcomings of the IC concept, particularly as manifested in the Starr investigation, and to decide whether efforts to cure those shortcomings with a new and improved version of the IC approach are warranted

Adolescent idiopathic scoliosis (AIS), environment, exposome and epigenetics: a molecular perspective of postnatal normal spinal growth and the etiopathogenesis of AIS with consideration of a network approach and possible implications for medical therapy

Genetic factors are believed to play an important role in the etiology of adolescent idiopathic scoliosis (AIS). Discordant findings for monozygotic (MZ) twins with AIS show that environmental factors including different intrauterine environments are important in etiology, but what these environmental factors may be is unknown. Recent evidence for common chronic non-communicable diseases suggests epigenetic differences may underlie MZ twin discordance, and be the link between environmental factors and phenotypic differences. DNA methylation is one important epigenetic mechanism operating at the interface between genome and environment to regulate phenotypic plasticity with a complex regulation across the genome during the first decade of life. The word exposome refers to the totality of environmental exposures from conception onwards, comprising factors in external and internal environments. The word exposome is used here also in relation to physiologic and etiopathogenetic factors that affect normal spinal growth and may induce the deformity of AIS. In normal postnatal spinal growth we propose a new term and concept, physiologic growth-plate exposome for the normal processes particularly of the internal environments that may have epigenetic effects on growth plates of vertebrae. In AIS, we propose a new term and concept pathophysiologic scoliogenic exposome for the abnormal processes in molecular pathways particularly of the internal environment currently expressed as etiopathogenetic hypotheses; these are suggested to have deforming effects on the growth plates of vertebrae at cell, tissue, structure and/or organ levels that are considered to be epigenetic. New research is required for chromatin modifications including DNA methylation in AIS subjects and vertebral growth plates excised at surgery. In addition, consideration is needed for a possible network approach to etiopathogenesis by constructing AIS diseasomes. These approaches may lead through screening, genetic, epigenetic, biochemical, metabolic phenotypes and pharmacogenomic research to identify susceptible individuals at risk and modulate abnormal molecular pathways of AIS. The potential of epigenetic-based medical therapy for AIS cannot be assessed at present, and must await new research derived from the evaluation of epigenetic concepts of spinal growth in health and deformity. The tenets outlined here for AIS are applicable to other musculoskeletal growth disorders including infantile and juvenile idiopathic scoliosis

Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer

Pathogenesis of adolescent idiopathic scoliosis in girls - a double neuro-osseous theory involving disharmony between two nervous systems, somatic and autonomic expressed in the spine and trunk: possible dependency on sympathetic nervous system and hormones with implications for medical therapy

Anthropometric data from three groups of adolescent girls - preoperative adolescent idiopathic scoliosis (AIS), screened for scoliosis and normals were analysed by comparing skeletal data between higher and lower body mass index subsets. Unexpected findings for each of skeletal maturation, asymmetries and overgrowth are not explained by prevailing theories of AIS pathogenesis. A speculative pathogenetic theory for girls is formulated after surveying evidence including: (1) the thoracospinal concept for right thoracic AIS in girls; (2) the new neuroskeletal biology relating the sympathetic nervous system to bone formation/resorption and bone growth; (3) white adipose tissue storing triglycerides and the adiposity hormone leptin which functions as satiety hormone and sentinel of energy balance to the hypothalamus for long-term adiposity; and (4) central leptin resistance in obesity and possibly in healthy females. The new theory states that AIS in girls results from developmental disharmony expressed in spine and trunk between autonomic and somatic nervous systems. The autonomic component of this double neuro-osseous theory for AIS pathogenesis in girls involves selectively increased sensitivity of the hypothalamus to circulating leptin (genetically-determined up-regulation possibly involving inhibitory or sensitizing intracellular molecules, such as SOC3, PTP-1B and SH2B1 respectively), with asymmetry as an adverse response (hormesis); this asymmetry is routed bilaterally via the sympathetic nervous system to the growing axial skeleton where it may initiate the scoliosis deformity (leptin-hypothalamic-sympathetic nervous system concept = LHS concept). In some younger preoperative AIS girls, the hypothalamic up-regulation to circulating leptin also involves the somatotropic (growth hormone/IGF) axis which exaggerates the sympathetically-induced asymmetric skeletal effects and contributes to curve progression, a concept with therapeutic implications. In the somatic nervous system, dysfunction of a postural mechanism involving the CNS body schema fails to control, or may induce, the spinal deformity of AIS in girls (escalator concept). Biomechanical factors affecting ribs and/or vertebrae and spinal cord during growth may localize AIS to the thoracic spine and contribute to sagittal spinal shape alterations. The developmental disharmony in spine and trunk is compounded by any osteopenia, biomechanical spinal growth modulation, disc degeneration and platelet calmodulin dysfunction. Methods for testing the theory are outlined. Implications are discussed for neuroendocrine dysfunctions, osteopontin, sympathoactivation, medical therapy, Rett and Prader-Willi syndromes, infantile idiopathic scoliosis, and human evolution. AIS pathogenesis in girls is predicated on two putative normal mechanisms involved in trunk growth, each acquired in evolution and unique to humans

Of Prosecutors and Special Prosecutors: An Organizational Perspective

The Independent Counsel (IC) statute, designed to restore public trust in the impartial administration of criminal justice after Watergate, ultimately fueled rather than quieted the perception that partisan politics drives the investigation of high-ranking government officials. Congress, in an inspiring display of bipartisanship, bid it a muted farewell. The statute\u27s fate was sealed by the enormous controversy surrounding the investigation conducted by Independent Counsel Kenneth Starr. Although Start did not bring criminal charges against President Clinton, his office went pretty far in that direction, committing considerable enforcement resources to that end, bringing criminal charges against people believed to have information that would implicate Clinton, and deploying arguments of prosecutorial prerogative that have significantly changed the legal landscape. Like many others, we have found this exercise of prosecutorial power terribly troubling. Also troubling, however, is the difficulty we (and others) have had in identifying neutral principles of prosecutorial discretion that Starr violated. The standard criticisms of Starr\u27s investigation do not meet that measure. The standard criticisms of the IC mechanism generally, though possessing greater force, are similarly unsatisfying. This essay, written from the perspective of two former federal prosecutors, springs from our effort to identify the fundamental shortcomings of the IC concept, particularly as manifested in the Starr investigation, and to decide whether efforts to cure those shortcomings with a new and improved version of the IC approach are warranted