Recent Cases

Antitrust Law--Clayton Act--Statistics of Market Concentration and Increased Market Share are Insufficient to Show Violation of Section 7 When Other Factors Mandate a Conclusion that Competition will not be Substantially Lessened by the Contested Acquisition -- Preservation of a large number of marginal competitors does not necessarily result in the optimum level of competition, and size per se is not illegal\u27 and should not be equated with anticompetitive effect. Seemingly, the competitive objectives of antimerger law have been infused with a theory characterized by socio-political feelings of hostility towards large, integrated corporations contrasted with friendliness toward small, independent business units . The Court has in the recent past attempted to preserve these social and political values by applying the simplest available criteria in antimerger cases-statistics demonstrating a decreasing number of competitors and an increasing market share in the hands of a few. In the instant opinion, however, the Court has returned its emphasis to a method of analysis characterized by an examination of the relevant economic factors and a consideration of statistical data of market structure, a seemingly desirable result since it represents a realization that only through a wide-ranging economic inquiry can the Court realistically assess and regulate economic and market behavior for the benefit of the public. ========================= Criminal Procedure--Federal Habeas Corpus -- A Writ of Habeas Corpus May Be Issued in Advance of Trial to Prevent Double Jeopardy When a Juvenile Has Been Previously Adjudicated a Delinquent Petitioner was adjudicated a delinquent and committed to a juvenile institution by a state juvenile court after his arrest on a charge of rape and subsequently was indicted by a grand jury for the same offense. The state criminal court dismissed the indictment on the ground that it subjected petitioner to double jeopardy, but the appellate level reversed, holding that the juvenile court judge should have waived jurisdiction and certified the case to criminal court pursuant to state statutes. The State Supreme Court affirmed the appellate decision and ordered the indictment reinstated. Alleging that his prosecution under the indictment would violate the double jeopardy clause of the fifth amendment and transgress fundamental fairness concepts of the fourteenth amendment, petitioner sought a writ of habeas corpus to terminate his physical custody, which had been prolonged because of the indictment. Rejecting the State\u27s arguments that petitioner had not exhausted state remedies and that jeopardy did not attach in juvenile adjudications, the United States District Court for the Middle District of Florida declared further prosecution unconstitutional and granted a writ of habeas corpus compelling petitioner\u27s release., On appeal to the United States Court of Appeals for the Fifth Circuit, held, affirmed

Toxic Stress and Quality of Life in Early School‐Aged Ugandan Children With and Without Perinatal Human Immunodeficiency Virus Infection

Caregiver’s and child’s self‐reported quality of life (QOL) was defined using standardized questionnaires in a sample (N = 277) of 6–10 years old HIV‐infected, HIV‐exposed uninfected, and HIV‐unexposed uninfected children from Uganda. Psychosocial stress (acute stress and cumulative lifetime adversity) and physiologic stress (dysregulations across 13 biomarkers), perinatal HIV status, and their interaction were related to child QOL via general linear models. Lower child‐ and caregiver‐reported psychosocial stress were dose‐dependently associated with higher QOL (acute stress: mean difference coefficient b = 8.1–14.8, effect size [ES] = 0.46–0.83). Lower allostasis was dose‐dependently associated with higher QOL (b = 6.1–9.7, ES = 0.34–0.54). Given low caregiver acute stress, QOL for HIV‐infected was similar to HIV‐uninfected children; however, given high caregiver acute stress, a QOL disadvantage (b = −7.8, 95% CI: −12.8, −2.8; ES = −0.73) was evident for HIV‐infected versus uninfected children. Testing of caregiver stress reduction interventions is warranted to increase wellbeing in dependent children.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/156459/2/cad20355.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/156459/1/cad20355_am.pd

Genetic Evidence for a Link Between Favorable Adiposity and Lower Risk of Type 2 Diabetes, Hypertension, and Heart Disease.

Recent genetic studies have identified some alleles that are associated with higher BMI but lower risk of type 2 diabetes, hypertension, and heart disease. These "favorable adiposity" alleles are collectively associated with lower insulin levels and higher subcutaneous-to-visceral adipose tissue ratio and may protect from disease through higher adipose storage capacity. We aimed to use data from 164,609 individuals from the UK Biobank and five other studies to replicate associations between a genetic score of 11 favorable adiposity variants and adiposity and risk of disease, to test for interactions between BMI and favorable adiposity genetics, and to test effects separately in men and women. In the UK Biobank, the 50% of individuals carrying the most favorable adiposity alleles had higher BMIs (0.120 kg/m(2) [95% CI 0.066, 0.174]; P = 1E-5) and higher body fat percentage (0.301% [0.230, 0.372]; P = 1E-16) compared with the 50% of individuals carrying the fewest alleles. For a given BMI, the 50% of individuals carrying the most favorable adiposity alleles were at lower risk of type 2 diabetes (odds ratio [OR] 0.837 [0.784, 0.894]; P = 1E-7), hypertension (OR 0.935 [0.911, 0.958]; P = 1E-7), and heart disease (OR 0.921 [0.872, 0.973]; P = 0.003) and had lower blood pressure (systolic -0.859 mmHg [-1.099, -0.618]; P = 3E-12 and diastolic -0.394 mmHg [-0.534, -0.254]; P = 4E-8). In women, these associations could be explained by the observation that the alleles associated with higher BMI but lower risk of disease were also associated with a favorable body fat distribution, with a lower waist-to-hip ratio (-0.004 cm [95% CI -0.005, -0.003] 50% vs. 50%; P = 3E-14), but in men, the favorable adiposity alleles were associated with higher waist circumference (0.454 cm [0.267, 0.641] 50% vs. 50%; P = 2E-6) and higher waist-to-hip ratio (0.0013 [0.0003, 0.0024] 50% vs. 50%; P = 0.01). Results were strengthened when a meta-analysis with five additional studies was conducted. There was no evidence of interaction between a genetic score consisting of known BMI variants and the favorable adiposity genetic score. In conclusion, different molecular mechanisms that lead to higher body fat percentage (with greater subcutaneous storage capacity) can have different impacts on cardiometabolic disease risk. Although higher BMI is associated with higher risk of diseases, better fat storage capacity could reduce the risk.This is the author accepted manuscript. The final version is available from the American Diabetes Association via http://dx.doi.org/10.2337/db15-167

Absence of XMRV and Closely Related Viruses in Primary Prostate Cancer Tissues Used to Derive the XMRV-Infected Cell Line 22Rv1

The 22Rv1 cell line is widely used for prostate cancer research and other studies throughout the world. These cells were established from a human prostate tumor, CWR22, that was serially passaged in nude mice and selected for androgen independence. The 22Rv1 cells are known to produce high titers of xenotropic murine leukemia virus-related virus (XMRV). Recent studies suggested that XMRV was inadvertently created in the 1990's when two murine leukemia virus (MLV) genomes (pre-XMRV1 and pre-XMRV-2) recombined during passaging of the CWR22 tumor in mice. The conclusion that XMRV originated from mice and not the patient was based partly on the failure to detect XMRV in early CWR22 xenografts. While that deduction is certainly justified, we examined the possibility that a closely related virus could have been present in primary tumor tissue. Here we report that we have located the original prostate tumor tissue excised from patient CWR22 and have assayed the corresponding DNA by PCR and the tissue sections by fluorescence in situ hybridization for the presence of XMRV or a similar virus. The primary tumor tissues lacked mouse DNA as determined by PCR for intracisternal A type particle DNA, thus avoiding one of the limitations of studying xenografts. We show that neither XMRV nor a closely related virus was present in primary prostate tissue of patient CWR22. Our findings confirm and reinforce the conclusion that XMRV is a recombinant laboratory-generated mouse virus that is highly adapted for human prostate cancer cells

Can a "pre-worn" bearing surface geometry reduce the wear of metal-on-metal hip replacements? – A numerical wear simulation study

Total Hip Replacement (THR) is generally a highly successful treatment for late stage hip joint diseases and wear, however, wear continues to be one of the major causes of metal-on-metal THR's failure. Hip replacements typically experience a two-stage wear; a higher initial wear rate in the beginning followed by a lower steady-state one with the surface profile changed. This alludes to the potential use of a cup with a non-spherical interior cavity with an initial geometry similar to a worn surface which may benefit from lower wear rate. In this paper wear is numerically simulated with a cup having a non-spherical geometry inspired by the initial stage of wear. A wear model was recently developed by the authors for the THR, which considered the lubricated contact in both elastohydrodynamic lubrication (EHL) and mixed lubrication regime, rather than a dry contact used in most of other studies of wear modelling in the academic literature. In this study the wear model has been updated by introducing the 'λ ratio' (the ratio of film thickness to surface roughness) and addressing the non-Newtonian shear-thinning properties of the synovial fluid. This wear model was able to describe the non-linear wear evolution process due to the change of worn profiles. Firstly the wear of a spherical hip joint was simulated until a steady-state wear rate is achieved. Then a non-spherical joint was proposed in which the cup bearing geometry was generated by the previously predicted worn profile from the spherical joint. At last the wear of this "pre-worn" hip bearing was simulated and compared to the spherical one. Approximately 40% reduction in the steady-state wear rate and 50% in the total accumulated wear has been observed in the non-spherical hip joint. This study presented a full numerical analysis of the relationship between lubrication, wear reduction and the geometry change, and quantitatively suggested the optimal geometry to reduce running-in wear

Corridor Gothic

This article investigates the role of the corridor in Gothic fiction and horror film from the late eighteenth century to the present day. It seeks to establish this transitional space as a crucial locus, by tracing the rise of the corridor as a distinct mode of architectural distribution in domestic and public buildings since the eighteenth century. The article tracks pivotal appearances of the corridor in fiction and film, and in the final phase argues that it has become associated with a specific emotional tenor, less to do with amplified fear and horror and more with emotions of Angst or dread

Genome-wide associations for birth weight and correlations with adult disease

Birth weight (BW) is influenced by both foetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease1. These lifecourse associations have often been attributed to the impact of an adverse early life environment. We performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where foetal genotype was associated with BW (P <5x10-8). Overall, ˜15% of variance in BW could be captured by assays of foetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure (rg-0.22, P =5.5x10-13), T2D (rg-0.27, P =1.1x10-6) and coronary artery disease (rg-0.30, P =6.5x10-9) and, in large cohort data sets, demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions (P =1.9x10-4). We have demonstrated that lifecourse associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and have highlighted some of the pathways through which these causal genetic effects are mediated

Genome-wide associations for birth weight and correlations with adult disease

Birth weight (BW) has been shown to be influenced by both fetal and maternal factors and in observational studies is reproducibly associated with future risk of adult metabolic diseases including type 2 diabetes (T2D) and cardiovascular disease. These life-course associations have often been attributed to the impact of an adverse early life environment. Here, we performed a multi-ancestry genome-wide association study (GWAS) meta-analysis of BW in 153,781 individuals, identifying 60 loci where fetal genotype was associated with BW ($\textit{P}$  < 5 × 10$^{-8}$). Overall, approximately 15% of variance in BW was captured by assays of fetal genetic variation. Using genetic association alone, we found strong inverse genetic correlations between BW and systolic blood pressure ($\textit{R}$ $_{g}$ = -0.22, $\textit{P}$  = 5.5 × 10$^{-13}$), T2D ($\textit{R}$ $_{g}$ = -0.27, $\textit{P}$  = 1.1 × 10$^{-6}$) and coronary artery disease ($\textit{R}$ $_{g}$ = -0.30, $\textit{P}$  = 6.5 × 10$^{-9}$). In addition, using large -cohort datasets, we demonstrated that genetic factors were the major contributor to the negative covariance between BW and future cardiometabolic risk. Pathway analyses indicated that the protein products of genes within BW-associated regions were enriched for diverse processes including insulin signalling, glucose homeostasis, glycogen biosynthesis and chromatin remodelling. There was also enrichment of associations with BW in known imprinted regions ($\textit{P}$ = 1.9 × 10$^{-4}$). We demonstrate that life-course associations between early growth phenotypes and adult cardiometabolic disease are in part the result of shared genetic effects and identify some of the pathways through which these causal genetic effects are mediated.For a full list of the funders pelase visit the publisher's website and look at the supplemetary material provided. Some of the funders are: British Heart Foundation, Cancer Research UK, Medical Research Council, National Institutes of Health, Royal Society and Wellcome Trust

Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors.

Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.The Fenland Study is funded by the Medical Research Council (MC_U106179471) and Wellcome Trust

Disclosure by Issuers of Municipal Securities: An Analysis of Recent Proposals and a Suggested Approach

The following considerations impacting on the disclosure issue have been developed in this Note: the uniqueness of the municipal securities industry, owing to the diverse natures of the securities, the wide variety of issuers, and the particular means of marketing the securities; the special circumstances created for underwriters by the competitive bidding process; the varied roles of other participants in the distribution process--fiscal agents, bond counsel, governmental accountants; the existing state machinery for regulation and control; the practical limitations on the SEC--both in staff capacity and expertise; the need for uniformity in disclosure to prevent weakened marketability of municipal securities and restrictive bidding by underwriters; and the constraints of sovereign immunity on issuer amenability to suit for violations of disclosure duties. Each of the above affects what course should be taken on the question of disclosure by issuers of municipal securities. The salient considerations are uniqueness, the need for uniformity, notions of federalism,and sovereign immunity