Properties of small molecular drug loading and diffusion in a fluorinated PEG hydrogel studied by ^1H molecular diffusion NMR and ^(19)F spin diffusion NMR

R_f-PEG (fluoroalkyl double-ended poly(ethylene glycol)) hydrogel is potentially useful as a drug delivery depot due to its advanced properties of sol–gel two-phase coexistence and low surface erosion. In this study, ^1H molecular diffusion nuclear magnetic resonance (NMR) and ^(19)F spin diffusion NMR were used to probe the drug loading and diffusion properties of the R_f-PEG hydrogel for small anticancer drugs, 5-fluorouracil (FU) and its hydrophobic analog, 1,3-dimethyl-5-fluorouracil (DMFU). It was found that FU has a larger apparent diffusion coefficient than that of DMFU, and the diffusion of the latter was more hindered. The result of ^(19)F spin diffusion NMR for the corresponding freeze-dried samples indicates that a larger portion of DMFU resided in the R_f core/IPDU intermediate-layer region (where IPDU refers to isophorone diurethane, as a linker to interconnect the R_f group and the PEG chain) than that of FU while the opposite is true in the PEG–water phase. To understand the experimental data, a diffusion model was proposed to include: (1) hindered diffusion of the drug molecules in the R_f core/IPDU-intermediate-layer region; (2) relatively free diffusion of the drug molecules in the PEG-water phase (or region); and (3) diffusive exchange of the probe molecules between the above two regions. This study also shows that molecular diffusion NMR combined with spin diffusion NMR is useful in studying the drug loading and diffusion properties in hydrogels for the purpose of drug delivery applications

Do regional brain volumes and major depressive disorder share genetic architecture?:A study of Generation Scotland (<i>n</i>=19,762), UK Biobank (<i>n</i>=24,048) and the English Longitudinal Study of Ageing (<i>n</i>=5,766)

Major depressive disorder (MDD) is a heritable and highly debilitating condition. It is commonly associated with subcortical volumetric abnormalities, the most replicated of these being reduced hippocampal volume. Using the most recent published data from Enhancing Neuroimaging Genetics through Meta-analysis (ENIGMA) consortium's genome-wide association study of regional brain volume, we sought to test whether there is shared genetic architecture between seven subcortical brain volumes and intracranial volume (ICV) and MDD. We explored this using linkage disequilibrium score regression, polygenic risk scoring (PRS) techniques, Mendelian randomisation (MR) analysis and BUHMBOX. Utilising summary statistics from ENIGMA and Psychiatric Genomics Consortium, we demonstrated that hippocampal volume was positively genetically correlated with MDD (rG=0.46, P=0.02), although this did not survive multiple comparison testing. None of the other six brain regions studied were genetically correlated and amygdala volume heritability was too low for analysis. Using PRS analysis, no regional volumetric PRS demonstrated a significant association with MDD or recurrent MDD. MR analysis in hippocampal volume and MDD identified no causal association, however, BUHMBOX analysis identified genetic subgrouping in GS:SFHS MDD cases only (P=0.00281). In this study, we provide some evidence that hippocampal volume and MDD may share genetic architecture in a subgroup of individuals, albeit the genetic correlation did not survive multiple testing correction and genetic subgroup heterogeneity was not replicated. In contrast, we found no evidence to support a shared genetic architecture between MDD and other regional subcortical volumes or ICV

Study of hadronic event-shape variables in multijet final states in pp collisions at √s=7 TeV

Peer reviewe

Constraints on parton distribution functions and extraction of the strong coupling constant from the inclusive jet cross section in pp collisions at √s=7 TeV

Peer reviewe

Internações por condições sensíveis à atenção primária em Campo Grande, Mato Grosso do Sul, Brasil, 2000 a 2009

Este estudo analisou a correlação entre a evolução da cobertura do Estratégia Saúde da Família (ESF) e a taxa das internações por condições sensíveis à atenção primária (ICSAP), em Campo Grande, Mato Grosso do Sul, Brasil, no período de 2000 a 2009. O estudo de caráter ecológico foi conduzido utilizando-se os dados do Sistema de Informações Hospitalares (SIH), disponíveis no site do Departamento de Informática do SUS (DATASUS) e do Instituto Brasileiro de Geografia e Estatística (IBGE). Na análise estatística foram utilizados o coeficiente de correlação linear de Pearson e sua significância. Campo Grande apresentou correlação inversa seguindo a tendência do país de redução das referidas internações. Na apreciação por categorias de internações observou-se uma correlação direta com a tuberculose pulmonar, a angina pectoris e as doenças relacionadas ao pré-natal e parto. Os resultados sugerem que o aumento da cobertura do ESF tem contribuído para a queda nas taxas de internações por ICSAP.This study analyzed the correlation between evolution in coverage of the Family Health Strategy (FHS) and the hospital admissions rate for primary care-sensitive conditions (PCSC) in Campo Grande, Mato Grosso do Sul State, Brazil, from 2000 to 2009. This was an ecological study using data from the Hospital Information System (SIH), available from the Information System of the Brazilian Unified National Health System (DATASUS) and the Brazilian Institute of Geography and Statistics (IBGE). Statistical analysis used Pearson's linear correlation coefficient and its significance. Campo Grande showed an inverse correlation, following the trend for the country as a whole, with a reduction in such admissions. The analysis of categories of hospital admissions showed a direct correlation with pulmonary tuberculosis, angina pectoris, and conditions related to prenatal care and childbirth. The results suggest that increased coverage of the FHS has contributed to a reduction in hospitalization rates for PCSC

Measurement of prompt J/ψ pair production in pp collisions at√s = 7 Tev

Abstract: Production of prompt J/ψ meson pairs in proton-proton collisions at (formula presented.) = 7 TeV is measured with the CMS experiment at the LHC in a data sample corresponding to an integrated luminosity of about 4.7 fb−1. The two J/ψ mesons are fully reconstructed via their decays into μ+μ− pairs. This observation provides for the first time access to the high-transverse-momentum region of J/ψ pair production where model predictions are not yet established. The total and differential cross sections are measured in a phase space defined by the individual J/ψ transverse momentum (pTJ/ψ) and rapidity (|yJ/ψ|): |yJ/ψ | 6.5 GeV/c; 1.2 4.5 GeV/c. The total cross section, assuming unpolarized prompt J/ψ pair production is 1.49 ± 0.07 (stat) ±0.13 (syst) nb. Different assumptions about the J/ψ polarization imply modifications to the cross section ranging from −31% to +27%

Study of Vector Boson Scattering and Search for New Physics in Events with Two Same-Sign Leptons and Two Jets

A study of vector boson scattering in pp collisions at a center-of-mass energy of 8 TeV is presented. The data sample corresponds to an integrated luminosity of 19.4 fb(-1) collected with the CMS detector. Candidate events are selected with exactly two leptons of the same charge, two jets with large rapidity separation and high dijet mass, and moderate missing transverse energy. The signal region is expected to be dominated by electroweak same-sign W-boson pair production. The observation agrees with the standard model prediction. The observed significance is 2.0 standard deviations, where a significance of 3.1 standard deviations is expected based on the standard model. Cross section measurements for (WW +/-)-W-+/- and WZ processes in the fiducial region are reported. Bounds on the structure of quartic vector-boson interactions are given in the framework of dimension-eight effective field theory operators, as well as limits on the production of doubly charged Higgs bosons