Prevalence of substance use in high school students from the United States

Substance use and abuse have become a rising epidemic all around the United States. Using the data of the 2013 Youth Risk Behavior Survey (YRBS), this study examined the prevalence of substance use in high school students in the United States. This study hoped to find answers to three questions: 1) Are there gender differences in substance use among high school students in the United States? 2) Are there grade level differences in the substance use? And 3) Are there race differences in substance use? Data for the study included responses from 13,583 students on the 2013 YRBS that were publicly available at the Centers for Disease and Control website. In general, results of chi-Square (chi^2) tests indicated significant grade level and race differences in smoking, alcohol drinking, and drug use. Gender differences in substance use were generally not apparent

Cluster analysis of multiplex ligation-dependent probe amplification data in choroidal melanoma.

PurposeTo determine underlying correlations in multiplex ligation-dependent probe amplification (MLPA) data and their significance regarding survival following treatment of choroidal melanoma (CM).MethodsMLPA data were available for 31 loci across four chromosomes (1p, 3, 6, and 8) in tumor material obtained from 602 patients with CM treated at the Liverpool Ocular Oncology Center (LOOC) between 1993 and 2012. Data representing chromosomes 3 and 8q were analyzed in depth since their association with CM patient survival is well-known. Unsupervised k-means cluster analysis was performed to detect latent structure in the data set. Principal component analysis (PCA) was also performed to determine the intrinsic dimensionality of the data. Survival analyses of the identified clusters were performed using Kaplan-Meier (KM) and log-rank statistical tests. Correlation with largest basal tumor diameter (LTD) was investigated.ResultsChromosome 3: A two-cluster (bimodal) solution was found in chromosome 3, characterized by centroids at unilaterally normal probe values and unilateral deletion. There was a large, significant difference in the survival characteristics of the two clusters (log-rank, p<0.001; 5-year survival: 80% versus 40%). Both clusters had a broad distribution in LTD, although larger tumors were characteristically in the poorer outcome group (Mann-Whitney, p<0.001). Threshold values of 0.85 for deletion and 1.15 for gain optimized the classification of the clusters. PCA showed that the first principal component (PC1) contained more than 80% of the data set variance and all of the bimodality, with uniform coefficients (0.28±0.03). Chromosome 8q: No clusters were found in chromosome 8q. Using a conventional threshold-based definition of 8q gain, and in conjunction with the chromosome 3 clusters, three prognostic groups were identified: chromosomes 3 and 8q both normal, either chromosome 3 or 8q abnormal, and both chromosomes 3 and 8q abnormal. KM analysis showed 5-year survival figures of approximately 97%, 80%, and 30% for these prognostic groups, respectively (log-rank, p<0.001). All MLPA probes within both chromosomes were significantly correlated with each other (Spearman, p<0.001).ConclusionsWithin chromosome 3, the strong correlation between the MLPA variables and the uniform coefficients from the PCA indicates a lack of evidence for a signature gene that might account for the bimodality we observed. We hypothesize that the two clusters we found correspond to binary underlying states of complete monosomy or disomy 3 and that these states are sampled by the complete ensemble of probes. Consequently, we would expect a similar pattern to emerge in higher-resolution MLPA data sets. LTD may be a significant confounding factor. Considering chromosome 8q, we found that chromosome 3 cluster membership and 8q gain as traditionally defined have an indistinguishable impact on patient outcome

Monoclonal antibodies to uveal melanoma

This thesis concerns the immunology of uveal melanoma It is introduced by a critical review of the literature on this neoplasm, and on tumour immunology with special reference to melanoma Two main conclusions could be drawn from this review Firstly, further progress in the immunology of uveal melanoma is dependent on a better understanding of the antigenicity of this tumour and on the availability of suitable antigens for testing the anti-tumour immune response Secondly, the best chance of achieving these objectives, at present, is by the application of monoclonal antibody technology Accordingly, the main aims of this study were to determine the feasibility and scope of producing monoclonal antibodies to uveal melanoma Monoclonal antibodies were prepared using the rat hybridoma system Tissue specimens from over 80 uveal melanomas were used to immunise rats and for the necessary immuno-assays Hybridomas were screened by ELISA Eleven monoclonal antibodies were produced Most of these were of the IgM isotype and all reacted with intracellular antigens The most specific was mAb 4A3 Nevertheless, immunohistochemistry on frozen and fixed sections and immunofluorescence microscopy using cell suspensions showed that this antibody reacted with several types of normal and malignant cells Western blotting demonstrated that the 4A3 antigen had a molecular weight of 55-62 kD The 4A3 antigen was detected in the subretinal fluid of five patients with uveal melanoma with the use of this technique, and in one of two patients with rhegmatogenous retinal detachment ELISA reactivity of the rat monoclonal antibodies with uveal melanoma cells was inhibited by serum from 10 out of 12 patients with uveal melanoma and from two out of eight healthy individuals B Lymphocytes of patients with uveal melanoma were EBV transformed in vitro and tested by ELISA for reactivity with autologous tumour The results were similar to those obtained with lymphocytes from healthy individuals This suggested that such techniques were inadequate for analysing humoral immunity to melanoma and unsuitable for the production of human monoclonal antibodies to this tumour In conclusion, specific monoclonal antibodies to uveal melanoma could be very useful, but such antibodies are unlikely to be produced using conventional methods Better results will probably be achieved if uncultured tissue from a single tumour were used for all immunisation and assay procedures required for one fusion, and if more efficient techniques for selecting hybridomas were available

Differences in uveal melanomas between men and women from the British Isles

and showed more circumferential spread in ciliary body (Po0.001) and iris (P ¼ 0.003). Tumours in men were more likely to extend to within 3 mm of optic disc or fovea (46.3 vs 39.0%, Po0.001), showing more extensive optic-disc involvement (Po0.001). The median largest basal tumour diameter was 12.2 mm in men and 11.9 mm in women (P ¼ 0.001). The tumour thickness had a median of 4.4 mm and 3.8 mm in men and women, respectively (P ¼ 0.015). The 180 ciliary body tumours occurred in 112 women and 68 men. In these, the prevalence of extraocular spread was higher in women (19.6 vs 8.8%; P ¼ 0.052). The 175 iris melanomas were more common in women than men (103 vs 72, respectively). Conclusions In men, UMs tend to be larger and more posterior than in women

Does ocular treatment of uveal melanoma influence survival?

Treatment of uveal (intraocular) melanoma is aimed at prolonging life, if possible conserving the eye and useful vision. About 50% of patients develop fatal metastatic disease despite successful eradication of the primary intraocular tumour. The effect of ocular treatment on survival is unknown, because the same survival data from case series can be interpreted in different ways. Treatment is therefore based on intuition and varies greatly between centres. Randomised trials of treatment vs non-treatment of asymptomatic tumours are desirable but would be controversial, difficult, expensive and possibly inconclusive. Strategies for coping with uncertainty are needed to avoid unethical care

A Case of Metastatic Atypical Neuroendocrine Tumor with ALK Translocation and Diffuse Brain Metastases.

A challenge in precision medicine requires identification of actionable driver mutations. Critical to such effort is the deployment of sensitive and well-validated assays for mutation detection. Although identification of such alterations within the tumor tissue remains the gold standard, many advanced non-small cell lung cancer cases have only limited tissue samples, derived from small biopsies or fine-needle aspirates, available for testing. More recently, noninvasive methods using either circulating tumor cells or tumor DNA (ctDNA) have become an alternative method for identifying molecular biomarkers and screening patients eligible for targeted therapies. In this article, we present a case of a 52-year-old never-smoking male who presented with widely metastatic atypical neuroendocrine tumor to the bones and the brain. Molecular genotyping using DNA harvested from a bone metastasis was unsuccessful due to limited material. Subsequent ctDNA analysis revealed an ALK translocation. The clinical significance of the mutation in this particular cancer type and therapeutic strategies are discussed.Key pointsTo our knowledge, this index case represents the first reported ALK translocation identified in an atypical carcinoid tumor.Liquid biopsy such as circulating tumor DNA is a feasible alternative platform for identifying sensitizing genomic alterations.Second-generation ALK inhibitors represent a new paradigm for treating ALK-positive patients with brain metastases

Microarray comparative genomic hybridisation analysis of intraocular uveal melanomas identifies distinctive imbalances associated with loss of chromosome 3

Defining regions of genomic imbalance can identify genes involved in tumour development. Conventional cytogenetics has identified several nonrandom copy number alterations (CNA) in uveal melanomas (UVM), which include monosomy 3, chromosome 6 abnormalities and gain of 8q. To gain further insight into the CNAs and define the regions involved more precisely we analysed 18 primary UVMs using 1 Mb BAC microarray comparative genomic hybridisation (CGH). Our analysis showed that the most common genomic imbalances were 8q gain (78%), 6p gain (67%) and monosomy 3 (56%). Two distinct CGH profiles could be delineated on the basis of the chromosome 3 status. The most common genetic changes in monosomy 3 tumours, in our study, were gain of 8q11.21–q24.3, 6p25.1–p21.2, 21q21.2–q21.3 and 21q22.13–q22.3 and loss of 1p36.33–p34.3, 1p31.1–p21.2, 6q16.2–q25.3 and 8p23.3–p11.23. In contrast, disomy 3 tumours showed recurrent gains of only 6p25.3–p22.3 and 8q23.2–q24.3. Our approach allowed definition of the smallest overlapping regions of imbalance, which may be important in the development of UVM

Alternative proteins are functional regulators in cell reprogramming by PKA activation

It has been recently shown that many proteins are lacking from reference databases used in mass spectrometry analysis, due to their translation templated on alternative open reading frames. This questions our current understanding of gene annotation and drastically expands the theoretical proteome complexity. The functions of these alternative proteins (AltProts) still remain largely unknown. We have developed a large-scale and unsupervised approach based on cross-linking mass spectrometry (XL-MS) followed by shotgun proteomics to gather information on the functional role of AltProts by mapping them back into known signalling pathways through the identification of their reference protein (RefProt) interactors. We have identified and profiled AltProts in a cancer cell reprogramming system: NCH82 human glioma cells after 0, 16, 24 and 48 h Forskolin stimulation. Forskolin is a protein kinase A activator inducing cell differentiation and epithelial-mesenchymal transition. Our data show that AltMAP2, AltTRNAU1AP and AltEPHA5 interactions with tropomyosin 4 are downregulated under Forskolin treatment. In a wider perspective, Gene Ontology and pathway enrichment analysis (STRING) revealed that RefProts associated with AltProts are enriched in cellular mobility and transfer RNA regulation. This study strongly suggests novel roles of AltProts in multiple essential cellular functions and supports the importance of considering them in future biological studies