Piloting the Alcohol Feedback, Reflection, and Morning Evaluation (A-FRAME) Program : A Smartphone-delivered Alcohol Intervention

Many college students engage in heavy drinking and experience negative consequences, but typically show little motivation to change their drinking behavior. Although personalized feedback interventions (PFIs) show promise, improved effect sizes, engagement, and potential for reach are needed. We developed and pilot-tested a theory-based, smartphone-delivered PFI for heavy-drinking college students that incorporated innovations, including a choice of feedback delivered in multiple doses that occur close in time to drinking events. In an open trial, we delivered the 4-week intervention to 18 heavy-drinking students, followed by individual interviews of participants’ experience. Feasibility was demonstrated by high enrollment and response rates, and acceptability was demonstrated by positive participant ratings and interview responses. Results will inform efforts to continue to develop this novel and scalable mobile intervention for alcohol misuse among college students, with potential impact for the public health problem of high-risk drinking

Cancer incidence among capacitor manufacturing workers exposed to polychlorinated biphenyls

We evaluated cancer incidence in a cohort of polychlorinated biphenyl (PCB) exposed workers. Incident cancers, identified using state registries, were compared to those in a national population using standardized incidence ratios. Trends in prostate cancer incidence with cumulative PCB exposure were evaluated using standardized rate ratios and Cox regression models. For selected sites, cumulative PCB exposure was compared between aggressive (fatal/distant stage) and localized/regional cancers. We identified 3,371 invasive first primary cancer diagnoses among 21,317 eligible workers through 2007. Overall relative incidence was reduced. Elevations were only observed for respiratory cancers and among women, urinary organ cancers. Among men, prostate cancer incidence was reduced and not associated with cumulative PCB exposure although median exposures were significantly higher for aggressive compared to localized/regional prostate cancers. Previously observed associations between cumulative PCB exposure and prostate cancer mortality were not confirmed in this analysis; prostate cancer stage at diagnosis may explain the discrepancy. Am. J. Ind. Med. 60:198-207, 2017. Published 2016. This article is a U.S. Government work and is in the public domain in the USA

The Influence of Secondhand Smoke Exposure on Birth Outcomes in Jordan

This study investigates how secondhand smoke (SHS) exposure influences neonatal birth weight in Jordan, a country with high smoking prevalence. The findings revealed that as the average number of SHS exposure hours per week increased in the second trimester, the neonatal birth weight decreased while holding all covariates constant. Women who reported a higher average number of SHS exposure hours per week from work in the second trimester, home in the third trimester, and outside in the third trimester were at greater risk for having a low birth weight neonate than women who reported a lower average number of SHS exposure hours

Genome-Wide Discovery of Somatic Regulatory Variants in Diffuse Large B-Cell Lymphoma

Diffuse large B-cell lymphoma (DLBCL) is an aggressive cancer originating from mature B-cells. Prognosis is strongly associated with molecular subgroup, although the driver mutations that distinguish the two main subgroups remain poorly defined. Through an integrative analysis of whole genomes, exomes, and transcriptomes, we have uncovered genes and non-coding loci that are commonly mutated in DLBCL. Our analysis has identified novel cis-regulatory sites, and implicates recurrent mutations in the 3′ UTR of NFKBIZ as a novel mechanism of oncogene deregulation and NF-κB pathway activation in the activated B-cell (ABC) subgroup. Small amplifications associated with over-expression of FCGR2B (the Fcγ receptor protein IIB), primarily in the germinal centre B-cell (GCB) subgroup, correlate with poor patient outcomes suggestive of a novel oncogene. These results expand the list of subgroup driver mutations that may facilitate implementation of improved diagnostic assays and could offer new avenues for the development of targeted therapeutics.&nbsp

Metabolomics in Early Alzheimer's Disease: Identification of Altered Plasma Sphingolipidome Using Shotgun Lipidomics

The development of plasma biomarkers could facilitate early detection, risk assessment and therapeutic monitoring in Alzheimer's disease (AD). Alterations in ceramides and sphingomyelins have been postulated to play a role in amyloidogensis and inflammatory stress related neuronal apoptosis; however few studies have conducted a comprehensive analysis of the sphingolipidome in AD plasma using analytical platforms with accuracy, sensitivity and reproducibility.We prospectively analyzed plasma from 26 AD patients (mean MMSE 21) and 26 cognitively normal controls in a non-targeted approach using multi-dimensional mass spectrometry-based shotgun lipidomics to determine the levels of over 800 molecular species of lipids. These data were then correlated with diagnosis, apolipoprotein E4 genotype and cognitive performance. Plasma levels of species of sphingolipids were significantly altered in AD. Of the 33 sphingomyelin species tested, 8 molecular species, particularly those containing long aliphatic chains such as 22 and 24 carbon atoms, were significantly lower (p<0.05) in AD compared to controls. Levels of 2 ceramide species (N16:0 and N21:0) were significantly higher in AD (p<0.05) with a similar, but weaker, trend for 5 other species. Ratios of ceramide to sphingomyelin species containing identical fatty acyl chains differed significantly between AD patients and controls. MMSE scores were correlated with altered mass levels of both N20:2 SM and OH-N25:0 ceramides (p<0.004) though lipid abnormalities were observed in mild and moderate AD. Within AD subjects, there were also genotype specific differences.In this prospective study, we used a sensitive multimodality platform to identify and characterize an essentially uniform but opposite pattern of disruption in sphingomyelin and ceramide mass levels in AD plasma. Given the role of brain sphingolipids in neuronal function, our findings provide new insights into the AD sphingolipidome and the potential use of metabolomic signatures as peripheral biomarkers

Frequent mutation of histone-modifying genes in non-Hodgkin lymphoma

Follicular lymphoma (FL) and diffuse large B-cell lymphoma (DLBCL) are the two most common non-Hodgkin lymphomas (NHLs). Here we sequenced tumour and matched normal DNA from 13 DLBCL cases and one FL case to identify genes with mutations in B-cell NHL. We analysed RNA-seq data from these and another 113 NHLs to identify genes with candidate mutations, and then re-sequenced tumour and matched normal DNA from these cases to confirm 109 genes with multiple somatic mutations. Genes with roles in histone modification were frequent targets of somatic mutation. For example, 32% of DLBCL and 89% of FL cases had somatic mutations in MLL2, which encodes a histone methyltransferase, and 11.4% and 13.4% of DLBCL and FL cases, respectively, had mutations in MEF2B, a calcium-regulated gene that cooperates with CREBBP and EP300 in acetylating histones. Our analysis suggests a previously unappreciated disruption of chromatin biology in lymphomagenesis

Incidence trends and clinical-pathological characteristics of invasive cutaneous melanoma from 1980 to 2010 in the canton of Zurich, Switzerland

The aims of this paper are to describe the incidence trends of invasive cutaneous melanoma in the Canton of Zurich and to evaluate clinical and pathological factors such as cancer subtype, localization, age and Breslow thickness. A retrospective analysis was carried out with data from the population-based Cancer Registry of Zurich and Zug located in Zurich. A total of 8469 cases in 8034 different patients of invasive cutaneous melanoma were registered for the period 1980-2010 in the Canton of Zurich. Incidence trends were age standardized to the European standard population. Joinpoint regression was used to compute changes in incidence and mortality rates, measured as the annual percent change (APC). The most common subtypes of cutaneous melanoma were superficial spreading melanoma (SSM, 41.1%), followed by nodular melanoma (16.5%), lentigo maligna melanoma (13.5%), acral-lentiginous melanoma (5.0%) and other types of melanoma (2.8%); 21.1% were melanoma not otherwise specified. The trunk was the most frequent location (30.8%), followed by the lower limb and hip (26.4%) and the upper limb and shoulder (22.8%). Statistically significantly increasing incidence trends were observed for both men (APC=3.0%) and women (APC=2.1%). Incidences of SSM and melanoma not otherwise specified were the histological subtypes for which a significant increase in incidence was observed (APC for the period 1980-2010=3.2% for both). In terms of Breslow thickness, thin melanomas (0.01-1.00 mm) showed an increasing incidence. The incidence of melanoma increased in both men and women between 1980 and 2010. In terms of the different subtypes and Breslow thickness, increasing incidences of the SSM and of thin melanomas (0.01-1.00 mm) were observed. These observations are in agreement with other studies from Southern and Western Switzerland as well as other European countries and the USA