Spirituality and Religiosity in Adolescents Living with Sickle Cell Disease

This study purports to address paucity in the literature regarding how adolescents with sickle cell disease (SCD) describe and experience spirituality and religiosity (S/R). This was a qualitative descriptive study. Two semi-structured interviews were conducted with nine adolescents (Mage = 16.2 years). Data were analyzed using a template analysis style and a concurrent analysis process of data reduction. Three major themes encompassed the participants’ descriptions of the relationships between S/R, health and illness in their lives including S/R as sources for coping, influence of S/R beliefs on health and illness, and sharing S/R with Health Care Providers (HCPs). S/R as coping mechanisms included six threads: interconnecting with God, interconnecting with others, interconnecting with creative arts, scriptural metanarratives, transcendent experiences, and acceptance and finding meaning. Expectations of health providers included two threads: Religiosity is private/personal and sharing spiritual and religious beliefs is risky. S/R are particularly salient for adolescents with SCD

Forced Rayleigh Scattering Studies of Tracer Diffusion in a Nematic Liquid Crystal: The Relevance of Complementary Gratings

We have employed forced Rayleigh scattering (FRS) to study the diffusion of an azo tracer molecule (methyl red) through a nematic liquid crystal (5CB). This system was first investigated in an important study by Hara et al. (Japan. J. Appl. Phys. 23, 1420 [1984]). Since that time, it has become clear that the presence of complementary ground-state and photoproduct FRS gratings can result in nonexponential profiles, and that complementary-grating effects are significant even when "minor" deviations from exponential decay are observed. We have investigated the methyl red/5CB system in order to evaluate the possible effects of complementary gratings. In the isotropic phase, we find that the presence of complementary gratings results in a nonmonotonic FRS signal, which significantly changes the values inferred for the isotropic diffusion coefficients. As a result, the previously reported discontinuity at the nematic/isotropic transition temperature (TNI) is not present in the new data. On the other hand, in the nematic phase, the new experiments largely confirm the previous observations of single-exponential FRS decay and the non-Arrhenius temperature dependence of the nematic diffusion coefficients close to TNI. Finally, we have also observed that the decrease in the diffusion anisotropy with increasing temperature can be correlated with the 5CB nematic order parameter S(T) over the full nematic temperature range.Comment: Accepted in the Journal of Chemical Physics; to appear February 200

Extension of corporate services brands: the effect of perceived similarity extension and perceived quality brand

O principal objetivo deste estudo é avaliar o efeito da qualidade percebida da marca-mãe e da similaridade percebida sobre as avaliações de extensões de marcas corporativas de serviços. Adicionalmente, também se deseja verificar se a elaboração das características da extensão contribuem para a sua avaliação. As hipóteses foram testadas por meio de três experimentos que envolveram no total 1.131 respondentes. No Estudo 1 foram utilizadas marcas fictícias como estímulo e verificou-se que a qualidade da marca-mãe teve efeito mais importante que a similaridade percebida sobre as avaliações de uma extensão de marca de serviços. No Estudo 2, utilizando como estímulos marcas reais, os mesmos resultados do Estudo 1 foram obtidos. No Estudo 3 verificou-se que a elaboração das características da extensão contribuiu positivamente apenas para uma das extensões propostas para a marca-mãe de alta qualidade, mas não teve nenhum efeito para as extensões propostas para a marca-mãe de baixa qualidade. Tomados em conjunto, os resultados sugerem que a qualidade percebida da marca-mãe tem papel fundamental na avaliação de extensões de marcas corporativas de serviços. O estudo contribui ainda com diversas hipóteses para estudos futuros e implicações gerenciais para gerentes de marcas corporativas de serviços.The main objective of this study is to assess the effect of parent brand perceived quality and perceived similarity on the evaluation of corporate service brand extensions. It is also the intention of this study to verify whether providing information cues about the characteristics of the extension contributes to the brand extension evaluation. The hypotheses were tested by means of three experiments involving 1,131 subjects. The results of Study 1, conducted with fictitious brands as stimuli, demonstrated that the perceived quality of the parent brand played a more significant role than perceived similarity on the evaluations of brand extensions. In Study 2, where real brands were used as stimuli, the results were the same as in Study 1. Study 3 found that providing information cues about the characteristics of the extensions had a positive effect for one of the extensions of the high quality parent brand but not for the two proposed extensions of the low quality parent brand. Taken as a whole, the results suggest that the perceived quality of the parent-brand plays a fundamental role in the evaluation of corporate service brand extensions. The study also contributes several hypotheses for future studies and managerial implications for managers of corporate service brands

lentiglobin gene therapy for transfusion dependent β thalassemia outcomes from the phase 1 2 northstar and phase 3 northstar 2 studies

Introduction Transfusion-dependent β-thalassemia (TDT) is a severe genetic disease characterized by anemia, iron overload and serious comorbidities for which gene therapy may be an effective treatment option. LentiGlobin gene therapy contains autologous CD34+ hematopoietic stem cells (HSCs) transduced ex vivo with the BB305 lentiviral vector (LVV) encoding β-globin with a T87Q substitution. Objective Evaluate the efficacy and safety of LentiGlobin in patients with TDT in the phase 1/2 Northstar (HGB-204; NCT01745120) and phase 3 Northstar-2 (HGB-207; NCT02906202) studies. Methods Patients with TDT (≥100 mL/kg/yr of red blood cells [RBCs] or ≥8 RBC transfusions/yr) received G-CSF and plerixafor for mobilization and HSCs were transduced with the BB305 LVV. Patients underwent single agent busulfan myeloablative conditioning, were infused with transduced cells, and were followed for engraftment, safety, and efficacy. Statistics are presented as median (min – max). Results As of March 7, 2018, 18 patients (12 – 35 yrs) were treated in Northstar (follow-up 32.1 [23.1 – 41.9] months) and as of May 15, 2018, 11 patients (12 – 24 yrs) were treated in Northstar-2 (follow-up 8.5 [0.3 – 16.2] months). Patients received a median cell dose of 8.0 (5.0 – 19.4) CD34+ cells × 106/kg in both studies. The median time to neutrophil and platelet engraftment in both studies was 19 (14 – 30) days and 44 (19 – 191) days, respectively; 1 patient in Northstar-2 (0.3 months follow-up) had not engrafted at time of analysis. Of 6 patients with platelet engraftment ≥ Day 60, 4 had non-serious bleeding events prior to engraftment. All 6 had intact spleens and 3/6 received G-CSF between Days 0 – 21. Both factors appeared associated with time to platelet engraftment. In Northstar, 8/10 patients with non-β0/β0 genotypes and 2/8 patients with β0/β0 genotypes achieved transfusion independence (TI; weighted average hemoglobin [Hb] ≥ 9 g/dL without RBC transfusions for ≥ 12 months). Median Hb during TI was 10.0 (9.3 – 13.1) g/dL. In Northstar-2, 7/8 patients with non-β0/β0 genotypes and ≥ 6 months follow-up stopped RBC transfusions with Hb of 11.1 – 13.3 g/dL at last visit; the first patient treated achieved TI. Non-hematologic grade ≥ 3 adverse events post-infusion in ≥ 5/29 (15%) patients were stomatitis, febrile neutropenia, and pharyngeal inflammation. Veno-occlusive liver disease attributed to busulfan occurred in 4/29 patients (Table 1). There was no transplant-related mortality, vector-mediated replication competent lentivirus, or clonal dominance. Conclusion In Northstar, 80% of patients with non-β0/β0 genotypes achieved TI and early Northstar-2 data suggest that patients can achieve near-normal Hb without transfusions. The safety profile of LentiGlobin is consistent with myeloablative busulfan conditioning. Longer time to platelet engraftment was observed in few patients, but no graft failure or deaths were reported

Employment in the Ecuadorian cut-flower industry and the risk of spontaneous abortion

<p>Abstract</p> <p>Background</p> <p>Research on the potentially adverse effects of occupational pesticide exposure on risk of spontaneous abortion (SAB) is limited, particularly among female agricultural workers residing in developing countries.</p> <p>Methods</p> <p>Reproductive histories were obtained from 217 Ecuadorian mothers participating in a study focusing on occupational pesticide exposure and children's neurobehavioral development. Only women with 2+ pregnancies were included in this study (n = 153). Gravidity, parity and frequency of SAB were compared between women with and without a history of working in the cut-flower industry in the previous 6 years. Logistic regression analysis was conducted to assess the relation between SAB and employment in the flower industry adjusting for maternal age.</p> <p>Results</p> <p>In comparison to women not working in the flower industry, women working in the flower industry were significantly younger (27 versus 32 years) and of lower gravidity (3.3 versus 4.5) and reported more pregnancy losses. A 2.6 (95% CI: 1.03-6.7) fold increase in the odds of pregnancy loss among exposed women was observed after adjusting for age. Odds of reporting an SAB increased with duration of flower employment, increasing to 3.4 (95% CI: 1.3, 8.8) among women working 4 to 6 years in the flower industry compared to women who did not work in the flower industry.</p> <p>Conclusion</p> <p>This exploratory analysis suggests a potential adverse association between employment in the cut-flower industry and SAB. Study limitations include the absence of a temporal relation between exposure and SAB, no quantification of specific pesticides, and residual confounding such as physical stressors (i.e., standing). Considering that approximately half of the Ecuadorian flower laborers are women, our results emphasize the need for an evaluating the reproductive health effects of employment in the flower industry on reproductive health in this population.</p

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment