Comorbid Medical Conditions as Predictors of Overall Survival in Glioblastoma Patients

Glioblastoma (GBM) is an aggressive central nervous system tumor with a poor prognosis. This study was conducted to determine any comorbid medical conditions that are associated with survival in GBM. Data were collected from medical records of all patients who presented to VCU Medical Center with GBM between January 2005 and February 2015. Patients who underwent surgery/biopsy were considered for inclusion. Cox proportional hazards regression modeling was performed to assess the relationship between survival and sex, race, and comorbid medical conditions. 163 patients met inclusion criteria. Comorbidities associated with survival on individual-characteristic analysis included: history of asthma (Hazard Ratio [HR]: 2.63; 95% Confidence Interval [CI]: 1.24–5.58; p = 0.01), hypercholesterolemia (HR: 1.95; 95% CI: 1.09–3.50; p = 0.02), and incontinence (HR: 2.29; 95% CI: 0.95–5.57; p = 0.07). History of asthma (HR: 2.22; 95% CI: 1.02–4.83; p = 0.04) and hypercholesterolemia (HR: 1.99; 95% CI: 1.11–3.56; p = 0.02) were associated with shorter survival on multivariable analysis. Surgical patients with GBM who had a prior history of asthma or hypercholesterolemia had significantly higher relative risk for mortality on individual-characteristic and multivariable analyses

Structure-based design and synthesis of antiparasitic pyrrolopyrimidines targeting pteridine reductase 1

The treatment of Human African Trypanosomiasis remains a major unmet health need in sub-Saharan Africa. Approaches involving new molecular targets are important and pteridine reductase 1 (PTR1), an enzyme that reduces dihydrobiopterin in Trypanosoma spp. has been identified as a candidate target and it has been shown previously that substituted pyrrolo[2,3-d]pyrimidines are inhibitors of PTR1 from T. brucei (J. Med. Chem. 2010, 53, 221-229). In this study, 61 new pyrrolo[2,3-d]pyrimidines have been prepared, designed with input from new crystal structures of 23 of these compounds complexed with PTR1, and evaluated in screens for enzyme inhibitory activity against PTR1 and in vitro antitrypanosomal activity. 8 compounds were sufficiently active in both screens to take forward to in vivo evaluation. Thus although evidence for trypanocidal activity in a stage I disease model in mice was obtained, the compounds were too toxic to mice for further development

Lepton polarization asymmetry in radiative dileptonic B-meson decays in MSSM

In this paper we study the polarization asymmetries of the final state lepton in the radiative dileptonic decay of B meson (\bsllg) in the framework of Minimal Supersymmetric Standard Model (MSSM) and various other unified models within the framework of MSSM e.g. mSUGRA, SUGRA (where condition of universality of scalar masses is relaxed) etc. Lepton polarization, in addition of having a longitudinal component (\pl), can have two other components, \pt and \pn, lying in and perpendicular to the decay plane, which are proportional to \ml and hence are significant for final state being $\mu^+ ~ \mu^-$ or $\tau^+ \~\tau^-$. We analyse the dependence of these polarization asymmetries on the parameters of the various models.Comment: typos corrected to match with published versio

A novel form of recessive limb girdle muscular dystrophy with mental retardation and abnormal expression of alpha-dystroglycan

Cataloged from PDF version of article.The limb girdle muscular dystrophies are a heterogeneous group of conditions characterized by proximal muscle weakness and disease onset ranging from infancy to adulthood. We report here eight patients from seven unrelated families affected by a novel and relatively mild form of autosomal recessive limb girdle muscular dystrophy (LGMD2) with onset in the first decade of life and characterized by severe mental retardation but normal brain imaging. Immunocytochemical studies revealed a significant selective reduction of α-dystroglycan expression in the muscle biopsies. Linkage analysis excluded known loci for both limb girdle muscular dystrophy and congenital muscular dystrophies in the consanguineous families. We consider that this represents a novel form of muscular dystrophy with associated brain involvement. The biochemical studies suggest that it may belong to the growing number of muscular dystrophies with abnormal expression of α-dystroglycan. © 2003 Published by Elsevier B.V

Intracranial internal carotid artery calcification is not predictive of future cognitive decline

BACKGROUND: Intracranial internal carotid artery (ICA) calcification is a common incidental finding in non-contrast head CT. We evaluated the predictive value of ICAC (ICAC) for future risk of cognitive decline and compared the results with conventional imaging biomarkers of dementia. METHODS: In a retrospective observational cohort, we included 230 participants with a PET-CT scan within 18 months of a baseline clinical assessment and longitudinal imaging assessments. Intracranial ICAC was quantified on baseline CT scans using the Agatson calcium score, and the association between baseline ICA calcium scores and the risk of conversion from a CDR of zero in baseline to a persistent CDR \u3e 0 at any follow-up visit, as well as longitudinal changes in cognitive scores, were evaluated through linear and mixed regression models. We also evaluated the association of conventional imaging biomarkers of dementia with longitudinal changes in cognitive scores and a potential indirect effect of ICAC on cognition through these biomarkers. RESULTS: Baseline ICA calcium score could not distinguish participants who converted to CDR \u3e 0. ICA calcium score was also unable to predict longitudinal changes in cognitive scores, imaging biomarkers of small vessel disease such as white matter hyperintensities (WMH) volume, or AD such as hippocampal volume, AD cortical signature thickness, and amyloid burden. Severity of intracranial ICAC increased with age and in men. Higher WMH volume and amyloid burden as well as lower hippocampal volume and AD cortical signature thickness at baseline predicted lower Mini-Mental State Exam scores at longitudinal follow-up. Baseline ICAC was indirectly associated with longitudinal cognitive decline, fully mediated through WMH volume. CONCLUSIONS: In elderly and preclinical AD populations, atherosclerosis of large intracranial vessels as demonstrated through ICAC is not directly associated with a future risk of cognitive impairment, or progression of imaging biomarkers of AD or small vessel disease

Chromatin profiling of cortical neurons identifies individual epigenetic signatures in schizophrenia

Both heritability and environment contribute to risk for schizophrenia. However, the molecular mechanisms of interactions between genetic and non-genetic factors remain unclear. Epigenetic regulation of neuronal genome may be a presumable mechanism in pathogenesis of schizophrenia. Here, we performed analysis of open chromatin landscape of gene promoters in prefrontal cortical (PFC) neurons from schizophrenic patients. We cataloged cell-type-based epigenetic signals of transcriptional start sites (TSS) marked by histone H3-K4 trimethylation (H3K4me3) across the genome in PFC from multiple schizophrenia subjects and age-matched control individuals. One of the top-ranked chromatin alterations was found in the major histocompatibility (MHC) locus on chromosome 6 highlighting the overlap between genetic and epigenetic risk factors in schizophrenia. The chromosome conformation capture (3C) analysis in human brain cells revealed the architecture of multipoint chromatin interactions between the schizophrenia-associated genetic and epigenetic polymorphic sites and distantly located HLA-DRB5 and BTNL2 genes. In addition, schizophrenia-specific chromatin modifications in neurons were particularly prominent for non-coding RNA genes, including an uncharacterized LINC01115 gene and recently identified BNRNA_052780. Notably, protein-coding genes with altered epigenetic state in schizophrenia are enriched for oxidative stress and cell motility pathways. Our results imply the rare individual epigenetic alterations in brain neurons are involved in the pathogenesis of schizophrenia

New Physics in b -> s mu+ mu-: CP-Conserving Observables

We perform a comprehensive study of the impact of new-physics operators with different Lorentz structures on decays involving the b -> s mu+ mu- transition. We examine the effects of new vector-axial vector (VA), scalar-pseudoscalar (SP) and tensor (T) interactions on the differential branching ratios and forward-backward asymmetries (A_{FB}'s) of Bsbar -> mu+ mu-, Bdbar -> Xs mu+ mu-, Bsbar -> mu+ mu- gamma, Bdbar -> Kbar mu+ mu-, and Bdbar -> K* mu+ mu-, taking the new-physics couplings to be real. In Bdbar -> K* mu+ mu-, we further explore the polarization fraction f_L, the angular asymmetry A_T^{(2)}, and the longitudinal-transverse asymmetry A_{LT}. We identify the Lorentz structures that would significantly impact these observables, providing analytical arguments in terms of the contributions from the individual operators and their interference terms. In particular, we show that while the new VA operators can significantly enhance most of the asymmetries beyond the Standard Model predictions, the SP and T operators can do this only for A_{FB} in Bdbar -> Kbar mu+ mu-.Comment: 54 pages, JHEP format, 45 figures (included). 5/6/2013: typos in K* mu mu angular coefficients corrected, typos in Eq. (D.12) corrected, added a missing term in I3LT in Eq. (D.16). Numerical analysis unchange

Comparative assessment of gasification based coal power plants with various CO2 capture technologies producing electricity and hydrogen

Seven different types of gasification-based coal conversion processes for producing mainly electricity and in some cases hydrogen (H2), with and without carbon dioxide (CO2) capture, were compared on a consistent basis through simulation studies. The flowsheet for each process was developed in a chemical process simulation tool “Aspen Plus”. The pressure swing adsorption (PSA), physical absorption (Selexol), and chemical looping combustion (CLC) technologies were separately analyzed for processes with CO2 capture. The performances of the above three capture technologies were compared with respect to energetic and exergetic efficiencies, and the level of CO2 emission. The effect of air separation unit (ASU) and gas turbine (GT) integration on the power output of all the CO2 capture cases is assessed. Sensitivity analysis was carried out for the CLC process (electricity-only case) to examine the effect of temperature and water-cooling of the air reactor on the overall efficiency of the process. The results show that, when only electricity production in considered, the case using CLC technology has an electrical efficiency 1.3% and 2.3% higher than the PSA and Selexol based cases, respectively. The CLC based process achieves an overall CO2 capture efficiency of 99.9% in contrast to 89.9% for PSA and 93.5% for Selexol based processes. The overall efficiency of the CLC case for combined electricity and H2 production is marginally higher (by 0.3%) than Selexol and lower (by 0.6%) than PSA cases. The integration between the ASU and GT units benefits all three technologies in terms of electrical efficiency. Furthermore, our results suggest that it is favorable to operate the air reactor of the CLC process at higher temperatures with excess air supply in order to achieve higher power efficiency

The integration of social concerns into electricity power planning : a combined delphi and AHP approach

The increasing acceptance of the principle of sustainable development has been a major driving force towards new approaches to energy planning. This is a complex process involving multiple and conflicting objectives, in which many agents were able to influence decisions. The integration of environmental, social and economic issues in decision making, although fundamental, is not an easy task, and tradeoffsmust be made. The increasing importance of social aspects adds additional complexity to the traditional models that must now deal with variables recognizably difficult to measure in a quantitative scale. This study explores the issue of the social impact, as a fundamental aspect of the electricity planning process, aiming to give a measurable interpretation of the expected social impact of future electricity scenarios. A structured methodology, based on a combination of the Analytic Hierarchy Process and Delphi process, is proposed. The methodology is applied for the social evaluation of future electricity scenarios in Portugal, resulting in the elicitation and assignment of average social impact values for these scenarios. The proposed tool offers guidance to decision makers and presents a clear path to explicitl