Circulating resistin levels and risk of multiple myeloma in three prospective cohorts

BACKGROUND: Resistin is a polypeptide hormone secreted by adipose tissue. A prior hospital-based case-control study reported serum resistin levels to be inversely associated with risk of multiple myeloma (MM). To date, this association has not been investigated prospectively. METHODS: We measured resistin concentrations for pre-diagnosis peripheral blood samples from 178 MM cases and 358 individually matched controls from three cohorts participating in the MM cohort consortium. RESULTS: In overall analyses, higher resistin levels were weakly associated with reduced MM risk. For men, we observed a statistically significant inverse association between resistin levels and MM (odds ratio, 0.44; 95% confidence interval (CI) 0.24-0.83 and 0.54; 95% CI 0.29-0.99, for the third and fourth quartiles, respectively, vs the lowest quartile; Ptrend=0.03). No association was observed for women. CONCLUSIONS: This study provides the first prospective evidence that low circulating resistin levels may be associated with an increased risk of MM, particularly for men

Cost-effectiveness of left ventricular assist devices (LVADs) for patients with advanced heart failure : analysis of the British NHS Bridge to Transplant (BTT) program

Background: A previous cost-effectiveness analysis showed that bridge to transplant (BTT) with early design left ventricular assist devices (LVADs) for advanced heart failure was more expensive than medical management while appearing less beneficial. Older LVADs were pulsatile, but current second and third generation LVADs are continuous flow pumps. This study aimed to estimate comparative cost-effectiveness of BTT with durable implantable continuous flow LVADs compared to medical management in the British NHS. Methods and results: A semi-Markov multi-state economic model was built using NHS costs data and patient data in the British NHS Blood and Transplant Database (BTDB). Quality-adjusted life years (QALYs) and incremental costs per QALY were calculated for patients receiving LVADs compared to those receiving inotrope supported medical management. LVADs cost £80,569 ($127,887) at 2011 prices and delivered greater benefit than medical management. The estimated probabilistic incremental cost-effectiveness ratio (ICER) was £53,527 ($84,963)/QALY (95%CI: £31,802–£94,853; $50,479–$150,560) (over a lifetime horizon). Estimates were sensitive to choice of comparator population, relative likelihood of receiving a heart transplant, time to transplant, and LVAD costs. Reducing the device cost by 15% decreased the ICER to £50,106 ($79,533)/QALY. Conclusions: Durable implantable continuous flow LVADs deliver greater benefits at higher costs than medical management in Britain. At the current UK threshold of £20,000 to £30,000/QALY LVADs are not cost effective but the ICER now begins to approach that of an intervention for end of life care recently recommended by the British NHS. Cost-effectiveness estimates are hampered by the lack of randomized trials

Getting It on Record: Issues and Strategies for Ethnographic Practice in Recording Studios

The recording studio has been somewhat neglected as a site for ethnographic fieldwork in the field of ethno-musicology and, moreover, the majority of published studies tend to overlook the specific concerns faced by the researcher within these contexts. Music recording studios can be places of creativity, artistry, and collaboration, but they often also involve challenging, intimidating, and fractious relations. Given that recording studios are, first and foremost, concerned with documenting musicians’ performances, we discuss the concerns of getting studio interactions “on record” in terms of access, social relations, and methods of data collection. This article reflects on some of the issues we faced when conducting our fieldwork within British music recording facilities and makes suggestions based on strategies that we employed to address these issues

Should patients with abnormal liver function tests in primary care be tested for chronic viral hepatitis: cost minimisation analysis based on a comprehensively tested cohort

Background Liver function tests (LFTs) are ordered in large numbers in primary care, and the Birmingham and Lambeth Liver Evaluation Testing Strategies (BALLETS) study was set up to assess their usefulness in patients with no pre-existing or self-evident liver disease. All patients were tested for chronic viral hepatitis thereby providing an opportunity to compare various strategies for detection of this serious treatable disease. Methods This study uses data from the BALLETS cohort to compare various testing strategies for viral hepatitis in patients who had received an abnormal LFT result. The aim was to inform a strategy for identification of patients with chronic viral hepatitis. We used a cost-minimisation analysis to define a base case and then calculated the incremental cost per case detected to inform a strategy that could guide testing for chronic viral hepatitis. Results Of the 1,236 study patients with an abnormal LFT, 13 had chronic viral hepatitis (nine hepatitis B and four hepatitis C). The strategy advocated by the current guidelines (repeating the LFT with a view to testing for specific disease if it remained abnormal) was less efficient (more expensive per case detected) than a simple policy of testing all patients for viral hepatitis without repeating LFTs. A more selective strategy of viral testing all patients for viral hepatitis if they were born in countries where viral hepatitis was prevalent provided high efficiency with little loss of sensitivity. A notably high alanine aminotransferase (ALT) level (greater than twice the upper limit of normal) on the initial ALT test had high predictive value, but was insensitive, missing half the cases of viral infection. Conclusions Based on this analysis and on widely accepted clinical principles, a "fast and frugal" heuristic was produced to guide general practitioners with respect to diagnosing cases of viral hepatitis in asymptomatic patients with abnormal LFTs. It recommends testing all patients where a clear clinical indication of infection is present (e.g. evidence of intravenous drug use), followed by testing all patients who originated from countries where viral hepatitis is prevalent, and finally testing those who have a notably raised ALT level (more than twice the upper limit of normal). Patients not picked up by this efficient algorithm had a risk of chronic viral hepatitis that is lower than the general population

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 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

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

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

Attitudes towards Human Papillomavirus vaccination among African parents in a city in the north of England: A qualitative study.

Background: Human papillomavirus (HPV) is sexually transmitted and has been conclusively linked to cervical cancer and genital warts. Cervical cancer is attributed to approximately 1100 deaths annually in UK, and is the second most common female cancer globally. It has been suggested that black African women are more predisposed to HPV infection and cervical cancer. A vaccine has been developed to reduce HPV infection, and in the UK, has been offered to 12-13 year old adolescent girls through schools as part of their childhood immunization programme since 2008. Upon programme initiation, it was noted that vaccine uptake was lower in schools where girls from ethnic minority groups were proportionately higher. Objectives: The study’s objectives were to explore factors influencing UK based African parents’ acceptance or decline of the HPV vaccine, whether fathers and mothers share similar views pertaining to vaccination and any interfamily tensions resulting from differing views. Methodology: A qualitative study was conducted with five African couples residing in north England. Face to face semi-structured interviews were carried out. Participants were parents to at least one daughter aged between 8 and 14 years. Recruitment was done through purposive sampling using snowballing. Results: HPV and cervical cancer awareness was generally low, with awareness lower in fathers. HPV vaccination was generally unacceptable among the participants, with fear of promiscuity, infertility and concerns that it’s still a new vaccine with yet unknown side effects cited as reasons for vaccine decline. There was HPV risk denial 3 as religion and good cultural upbringing seemed to result in low risk perceptions, with HPV and cervical cancer generally perceived as a white person’s disease. Religious values and cultural norms influenced vaccine decision-making, with fathers acting as the ultimate decision makers. Current information about why the vaccine is necessary was generally misunderstood. Conclusion: Tailored information addressing religious and cultural concerns may improve vaccine acceptability in African parents