The association of criminal justice supervision setting with overdose mortality: a longitudinal cohort study.

Background and aimsDespite the high prevalence of substance use among people in the US criminal justice system, little is known about the incidence of overdose mortality by use patterns, drug convictions and supervision setting. We examined the associations between these characteristics and overdose mortality.DesignRetrospective cohort study.Setting and participantsIndividuals sentenced to prison, jail, probation or jail plus probation for a felony conviction in Michigan, USA from 2003 to 2006.MeasurementsUsing the National Death Index, we assessed overdose mortality to December 2012. We calculated overdose mortality rates by pre-sentence opioid use, drug convictions and supervision setting. Multivariable analyses were conducted using competing risks regression with time-varying covariates.FindingsAmong 140 266 individuals followed over a mean of 7.84 years [standard deviation (SD) = 1.52], 14.9% of the 1131 deaths were due to overdose (102.8 per 100 000 person-years). Over the follow-up, more than half of overdose deaths occurred in the community (57.7%), nearly a third (28.8%) on probation and 12.8% on parole. The adjusted risk of overdose death was lower on probation [hazard ratio (HR) = 0.71, 95% confidence interval (CI) = 0.60, 0.85] than in the community without probation or parole (HR = 1.00) but not significantly different on parole (HR = 1.13, 95% CI = 0.87, 1.47). Pre-sentence daily opioid use (HR = 3.54, 95% CI = 3.24, 3.87) was associated with an increased risk. Drug possession (HR = 1.11, 95% CI = 0.93, 1.31) and delivery convictions (HR = 0.92, 95% CI = 0.77, 1.09) were not significantly associated with overdose mortality.ConclusionsBased on the absolute or relative risk, parole, probation and community settings are appropriate settings for enhanced overdose prevention interventions. Ensuring that individuals with pre-sentence opioid use have access to harm reduction and drug treatment services may help to prevent overdose among people involved with the criminal justice system

Multibody aircraft study, volume 2

The potential benefits of a multibody aircraft when compared to a single body aircraft are presented. The analyses consist principally of a detailed point design analysis of three multibody and one single body aircraft, based on a selected payload of 350,000 kg (771,618 lb), for final aircraft definitions; sensitivity studies to evaluate the effects of variations in payload, wing semispan body locations, and fuel price; recommendations as to the research and technology requirements needed to validate the multibody concept. Two, two body, one, three body, and one single body aircraft were finalized for the selected payload, with DOC being the prime figure of merit. When compared to the single body, the multibody aircraft showed a reduction in DOC by as much as 11.3 percent. Operating weight was reduced up to 14 percent, and fly away cost reductions ranged from 8.6 to 13.4 percent. Weight reduction, hence cost, of the multibody aircraft resulted primarily from the wing bending relief afforded by the bodies being located outboard on the wing

Genotype Directed Therapy in Murine Mismatch Repair Deficient Tumors

The PI3K/AKT/mTOR pathway has frequently been found activated in human tumors. We show that in addition to Wnt signaling dysfunction, the PI3K/AKT/mTOR pathway is often upregulated in mouse Msh2−/− initiated intestinal tumors. NVP-BEZ235 is a dual PI3K/mTOR inhibitor toxic to many cancer cell lines and currently involved in clinical trials. We have treated two mouse models involving Msh2 that develop small intestinal and/or colonic tumors with NVP-BEZ235, and a subset of animals with NVP-BEZ235 and MEK inhibitor ADZ4266. The disease phenotype has been followed with pathology, 18F FDG PET imaging, and endoscopy. Intestinal adenocarcinomas are significantly decreased in multiplicity by both drug regimens. The majority of tumors treated with combined therapy regress significantly, while a small number of highly progressed tumors persist. We have examined PTEN, AKT, MEK 1&2, MAPK, S6K, mTOR, PDPK1, and Cyclin D1 and find variable alterations that include downregulation of PTEN, upregulation of AKT and changes in its phosphorylated forms, upregulation of pMEK 1&2, p42p44MAPK, pS6K, and Cyclin D1. Apoptosis has been found intact in some tumors and not in others. Our data indicate that NVP-BEZ235 alone and in combination with ADZ4266 are effective in treating a proportion of colorectal cancers, but that highly progressed resistant tumors grow in the presence of the drugs. Pathways upregulated in some resistant tumors also include PDPK1, suggesting that metabolic inhibitors may also be useful in treating these tumors

Immunohistochemical detection of macrophage migration inhibitory factor in fetal and adult bovine epididymis: Release by the apocrine secretion mode?

Originally defined as a lymphokine inhibiting the random migration of macrophages, the macrophage migration inhibitory factor (MIF) is an important mediator of the host response to infection. Beyond its function as a classical cytokine, MIF is currently portrayed as a multifunctional protein with growth-regulating properties present in organ systems beyond immune cells. In previous studies, we detected substantial amounts of MIF in the rat epididymis and epididymal spermatozoa, where it appears to play a role during post-testicular sperm maturation and the acquisition of fertilization ability. To explore its presence in other species not yet examined in this respect, we extended the range of studies to the bull. Using a polyclonal antibody raised against MIF purified from bovine eye lenses, we detected MIF in the epithelium of the adult bovine epididymis with the basal cells representing a prominently stained cell type. A distinct accumulation of MIF at the apical cell pole of the epithelial cells and in membranous vesicles localized in the lumen of the epididynnal duct was obvious. In the fetal bovine epididymis, we also detected MIF in the epithelium, whereas MIF accumulation was evident at the apical cell surface and in apical protrusions. By immuno-electron microscopy of the adult bovine epididymis, we localized MIF in apical protrusions of the epithelial cells and in luminal membrane-bound vesicles that were found in close proximity to sperm cells. Although the precise origin of the MIF-containing vesicles remains to be delineated, our morphological observations support the hypothesis that they become detached from the apical surface of the epididymal epithelial cells. Additionally, an association of MIF with the outer dense fibers of luminal spermatozoa was demonstrated. Data obtained in this study suggest MIF release by an apocrine secretion mode in the bovine epididymis. Furthermore, MIF localized in the basal cells of the epithelium and in the connective tissue could be responsible for regulating the migration of macrophages in order to avoid contact of immune cells with spermatozoa that carry a wide range of potent antigens. Copyright (c) 2006 S. Karger AG, Basel

Doctor of Philosophy

dissertationOne of the fundamental building blocks of many computational sciences is the construction and use of a discretized, geometric representation of a problem domain, often referred to as a mesh. Such a discretization enables an otherwise complex domain to be represented simply, and computation to be performed over that domain with a finite number of basis elements. As mesh generation techniques have become more sophisticated over the years, focus has largely shifted to quality mesh generation techniques that guarantee or empirically generate numerically well-behaved elements. In this dissertation, the two complementary meshing subproblems of vertex placement and element creation are analyzed, both separately and together. First, a dynamic particle system achieves adaptivity over domains by inferring feature size through a new information passing algorithm. Second, a new tetrahedral algorithm is constructed that carefully combines lattice-based stenciling and mesh warping to produce guaranteed quality meshes on multimaterial volumetric domains. Finally, the ideas of lattice cleaving and dynamic particle systems are merged into a unified framework for producing guaranteed quality, unstructured and adaptive meshing of multimaterial volumetric domains

Storage of ascocarps and ascospore progeny of Cochliobolus heterostrophus.

Cochliobolus heterostrophus is a filamentous ascomycete that causes southern leaf blight of maize

Natural climate solutions

Our thanks for inputs by L. Almond, A. Baccini, A. Bowman, S. CookPatton, J. Evans, K. Holl, R. Lalasz, A. Nassikas, M. Spalding, M. Wolosin, and expert elicitation respondents. Our thanks for datasets developed by the Hansen lab and the NESCent grasslands working group (C. Lehmann, D. Griffith, T. M. Anderson, D. J. Beerling, W. Bond, E. Denton, E. Edwards, E. Forrestel, D. Fox, W. Hoffmann, R. Hyde, T. Kluyver, L. Mucina, B. Passey, S. Pau, J. Ratnam, N. Salamin, B. Santini, K. Simpson, M. Smith, B. Spriggs, C. Still, C. Strömberg, and C. P. Osborne). This study was made possible by funding from the Doris Duke Charitable Foundation. Woodbury was supported in part by USDA-NIFA Project 2011-67003-30205 Data deposition: A global spatial dataset of reforestation opportunities has been deposited on Zenodo (https://zenodo.org/record/883444). This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1710465114/-/DCSupplemental.Peer reviewedPublisher PD

Estimating above ground net biomass change in tropical and subtropical forests: refinement of IPCC default values using forest plot data

As countries advance in greenhouse gas (GHG) accounting for climate change mitigation, consistent estimates of above ground biomass (AGB) net change are needed for the tropics and subtropics. Countries with limited forest monitoring capabilities rely on 2006 IPCC default AGB net change values, which are averages per ecological zone, per continent. These previous defaults come from single studies, provide no uncertainty indications, and aggregate old secondary forests and old-growth forests. In this study, we update these default values using forest plot data. In comparison with previous estimates, new values include data published from 2006 onwards, are derived from multiple sites per global ecological zone, provide measures of variation, and divide forests >20 years old into older secondary forests and old-growth forests. We compiled 176 AGB chronosequences in secondary forests and AGB net change rates from 536 permanent plots in old-growth and managed or logged forests. In this dataset, across all continents and ecozones, AGB net change rates in younger secondary forests (go years) are higher than rates in older secondary (>20 years and ≤100 years) forests and managed or logged forests, which in turn are higher than rates in old-growth forests (> 100 years). Data availability is highest for North and South America, followed by Asia then Africa. We provide a rigorous and traceable refinement of the IPCC 2006 AGB net change default rates, identify which areas in the tropics and subtropics require more research on AGB change, and reflect on possibilities for improvement as more data becomes available