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Rinaldi I.,German Cancer Research Center | Rinaldi I.,Heidelberg Ion Therapy Center | Ferrari A.,CERN | Mairani A.,Heidelberg Ion Therapy Center | And 4 more authors.
Physics in Medicine and Biology | Year: 2011

Monte Carlo (MC) codes are useful tools to simulate the complex processes of proton beam interactions with matter. In proton therapy, nuclear reactions influence the dose distribution. Therefore, the validation of nuclear models adopted in MC codes is a critical requisite for their use in this field. A simple integral test can be performed using a multi-layer Faraday cup (MLFC). This method allows separation of the nuclear and atomic interaction processes, which are responsible for secondary particle emission and the finite primary proton range, respectively. In this work, the propagation of 160 MeV protons stopping in two MLFCs made of polyethylene and copper has been simulated by the FLUKA MC code. The calculations have been performed with and without secondary electron emission and transport, as well as charge sharing in the dielectric layers. Previous results with other codes neglected those two effects. The impact of this approximation has been investigated and found to be relevant only in the proximity of the Bragg peak. Longitudinal charge distributions computed with FLUKA with both approaches have been compared with experimental data from the literature. Moreover, the contribution of different processes to the measurable signal has been addressed. A thorough analysis of the results has demonstrated that the nuclear and electromagnetic models of FLUKA reproduce the two sets of experimental data reasonably well. © 2011 Institute of Physics and Engineering in Medicine.


Bachireddy C.,Yale University | Soule M.C.,Massachussetts General Hospital | Izenberg J.M.,Yale University | Dvoryak S.,Ukrainian Institute on Public Health Policy | And 2 more authors.
Drug and Alcohol Dependence | Year: 2014

Background: People who inject drugs (PWID) experience poor outcomes and fuel HIV epidemics in middle-income countries in Eastern Europe and Central Asia. We assess integrated/co-located (ICL) healthcare for HIV-infected PWID, which despite international recommendations, is neither widely available nor empirically examined. Methods: A 2010 cross-sectional study randomly sampled 296 HIV-infected opioid-dependent PWID from two representative HIV-endemic regions in Ukraine where ICL, non-co-located (NCL) and harm reduction/outreach (HRO) settings are available. ICL settings provide onsite HIV, addiction, and tuberculosis services, NCLs only treat addiction, and HROs provide counseling, needles/syringes, and referrals, but no opioid substitution therapy (OST). The primary outcome was receipt of quality healthcare, measured using a quality healthcare indicator (QHI) composite score representing percentage of eight guidelines-based recommended indicators met for HIV, addiction and tuberculosis treatment. The secondary outcomes were individual QHIs and health-related quality-of-life (HRQoL). Results: On average, ICL-participants had significantly higher QHI composite scores compared to NCL- and HRO-participants (71.9% versus 54.8% versus 37.0%, p<. 0.001) even after controlling for potential confounders. Compared to NCL-participants, ICL-participants were significantly more likely to receive antiretroviral therapy (49.5% versus 19.2%, p<. 0.001), especially if CD4. ≤. 200 (93.8% versus 62.5% p<. 0.05); guideline-recommended OST dosage (57.3% versus 41.4%, p<. 0.05); and isoniazid preventive therapy (42.3% versus 11.2%, p<. 0.001). Subjects receiving OST had significantly higher HRQoL than those not receiving it (p<. 0.001); however, HRQoL did not differ significantly between ICL- and NCL-participants. Conclusions: These findings suggest that OST alone improves quality-of-life, while receiving care in integrated settings collectively and individually improves healthcare quality indicators for PWID. © 2013 Elsevier Ireland Ltd.


Ezell J.,Vanderbilt University | Shui A.,Massachussetts General Hospital | Sanders K.,Vanderbilt University | Veenstra-VanderWeele J.,Columbia University
Pediatrics | Year: 2016

OBJECTIVES: To determine whether adopted children with Autism spectrum disorder (ASD) differ from the general ASD population in terms of diagnosis, internalizing and externalizing behaviors, sleep problems, and medications. METHODS: We studied 163 adoptees in the Autism Speaks Autism Treatment Network (ATN) in comparison with 5624 nonadopted ATN participants (aged 1.5-17.6 years; mean [SD] = 6.2 [3.4] years). Gender, age, race, ethnicity, IQ, and categorical Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, ASD diagnosis were tested for differences by group (adopted versus nonadopted) by using independent-samples t tests for continuous variables and Fisher's exact tests for categorical variables. Logistic or linear regression models were used to examine the association between adoption status and several outcome variables, after controlling for covariates. RESULTS: After controlling for demographics and diagnosis, there were significant differences in group characteristics, including greater propensity for externalizing behavior (P < .001), internalizing behavior (P = .001), and sleep problems (P < .001) in the adopted population. Adoptees were also prescribed psychotropic medications (P < .001) more often than the nonadoptees. Adoptees received a diagnosis of pervasive developmental disorder-not otherwise specified significantly more frequently than controls (odds ratio = 1.8; CI = 1.3- 2.5; P < .001), despite no significant difference in symptoms on standardized measures. CONCLUSIONS: These results suggest that the population of adopted children with ASD differs from the general ASD population both with regard to diagnostic subtype and co-occurring behavioral problems. Future research should evaluate the contributions of specific factors associated with adoption such as biological family history, pregnancy history, early childhood experience, and age at adoption. © 2016 by the American Academy of Pediatrics.


Evan Pollack C.,Johns Hopkins University | Wang H.,Johns Hopkins University | Bekelman J.E.,University of Pennsylvania | Weissman G.,University of Pennsylvania | And 4 more authors.
Value in Health | Year: 2014

Objectives Variation in care within and across geographic areas remains poorly understood. The goal of this article was to examine whether physician social networks - as defined by shared patients - are associated with rates of complications after radical prostatectomy. Methods In five cities, we constructed networks of physicians on the basis of their shared patients in 2004-2005 Surveillance, Epidemiology and End Results-Medicare data. From these networks, we identified subgroups of urologists who most frequently shared patients with one another. Among men with localized prostate cancer who underwent radical prostatectomy, we used multilevel analysis with generalized linear mixed-effect models to examine whether physician network structure - along with specific characteristics of the network subgroups - was associated with rates of 30-day and late urinary complications, and long-term incontinence after accounting for patient-level sociodemographic, clinical factors, and urologist patient volume. Results Networks included 2677 men in five cities who underwent radical prostatectomy. The unadjusted rate of 30-day surgical complications varied across network subgroups from an 18.8 percentage-point difference in the rate of complications across network subgroups in city 1 to a 26.9 percentage-point difference in city 5. Large differences in unadjusted rates of late urinary complications and long-term incontinence across subgroups were similarly found. Network subgroup characteristics - average urologist centrality and patient racial composition - were significantly associated with rates of surgical complications. Conclusions Analysis of physician networks using Surveillance, Epidemiology and End Results-Medicare data provides insight into observed variation in rates of complications for localized prostate cancer. If validated, such approaches may be used to target future quality improvement interventions. © 2014 International Society for Pharmacoeconomics and Outcomes Research (ISPOR).


Leduc M.S.,The Jackson Laboratory | Lyons M.,The Jackson Laboratory | Darvishi K.,The Jackson Laboratory | Walsh K.,The Jackson Laboratory | And 7 more authors.
Journal of Lipid Research | Year: 2011

Genome-wide association (GWA) studies represent a powerful strategy for identifying susceptibility genes for complex diseases in human populations but results must be confirmed and replicated. Because of the close homology between mouse and human genomes, the mouse can be used to add evidence to genes suggested by human studies. We used the mouse quantitative trait loci (QTL) map to interpret results from a GWA study for genes associated with plasma HDL cholesterol levels. We first positioned single nucleotide polymorphisms (SNPs) from a human GWA study on the genomic map for mouse HDL QTL. We then used mouse bioinformatics, sequencing, and expression studies to add evidence for one well-known HDL gene (Abca1) and three newly identified genes (Galnt2, Wwox, and Cdh13), thus supporting the results of the human study. For GWA peaks that occur in human haplotype blocks with multiple genes, we examined the homologous regions in the mouse to prioritize the genes using expression, sequencing, and bioinformatics from the mouse model, showing that some genes were unlikely candidates and adding evidence for candidate genes Mvk and Mmab in one haplotype block and Fads1 and Fads2 in the second haplotype block. Our study highlights the value of mouse genetics for evaluating genes found in human GWA studies. Copyright © 2011 by the American Society for Biochemistry and Molecular Biology, Inc.

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