Cost–Effective Prediction of Gender-Labeling Errors and Estimation of Gender-Labeling Error Rates in Candidate-Gene Association Studies

We describe a statistical approach to predict gender-labeling errors in candidate-gene association studies, when Y-chromosome markers have not been included in the genotyping set. The approach adds value to methods that consider only the heterozygosity of X-chromosome SNPs, by incorporating available information about the intensity of X-chromosome SNPs in candidate genes relative to autosomal SNPs from the same individual. To our knowledge, no published methods formalize a framework in which heterozygosity and relative intensity are simultaneously taken into account. Our method offers the advantage that, in the genotyping set, no additional space is required beyond that already assigned to X-chromosome SNPs in the candidate genes. We also show how the predictions can be used in a two-phase sampling design to estimate the gender-labeling error rates for an entire study, at a fraction of the cost of a conventional design

Risk of Late Mortality and Second Malignant Neoplasms among 5-Year Survivors of Young Adult Cancer: A Report of the Childhood, Adolescent, and Young Adult Cancer Survivors Research Program

We conducted a population-based retrospective study to assess the long-term risks of overall and cause-specific mortality and second malignant neoplasm (SMN) among survivors of young adult cancer compared to the risk in British Columbia (BC) population and to evaluate the effects of demographic and clinical factors on risk. 1248 5-year survivors of young adult cancer diagnosed 1970–1995 between 20 and 24 years of age were identified from the BC Cancer Registry and followed to the end of 2007. Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) were calculated. The Cox proportional hazards model was used to estimate the effects of different demographic and disease-related characteristics on the risk of death and SMN. A total of 138 deaths and 62 SMNs were observed during follow-up. The overall SMR was 5.9 (95% CI 4.9–6.9) and the absolute excess risk was 5.3 per 1,000 person-years. The overall SIR was 3.0 (95% CI 2.3–3.8). Treatment with radiation resulted in increased risks of death and SMN. These observed increased risks emphasize the importance of prevention, surveillance, and treatment of late effects in survivors of young adult cancers

Genetic Variation in Cell Death Genes and Risk of Non-Hodgkin Lymphoma

Background Non-Hodgkin lymphomas are a heterogeneous group of solid tumours that constitute the 5th highest cause of cancer mortality in the United States and Canada. Poor control of cell death in lymphocytes can lead to autoimmune disease or cancer, making genes involved in programmed cell death of lymphocytes logical candidate genes for lymphoma susceptibility. Materials and Methods We tested for genetic association with NHL and NHL subtypes, of SNPs in lymphocyte cell death genes using an established population-based study. 17 candidate genes were chosen based on biological function, with 123 SNPs tested. These included tagSNPs from HapMap and novel SNPs discovered by re-sequencing 47 cases in genes for which SNP representation was judged to be low. The main analysis, which estimated odds ratios by fitting data to an additive logistic regression model, used European ancestry samples that passed quality control measures (569 cases and 547 controls). A two-tiered approach for multiple testing correction was used: correction for number of tests within each gene by permutation-based methodology, followed by correction for the number of genes tested using the false discovery rate. Results Variant rs928883, near miR-155, showed an association (OR per A-allele: 2.80 [95% CI: 1.63–4.82]; pF = 0.027) with marginal zone lymphoma that is significant after correction for multiple testing. Conclusions This is the first reported association between a germline polymorphism at a miRNA locus and lymphoma

Quantitative Modeling of Cerenkov Light Production Efficiency from Medical Radionuclides

There has been recent and growing interest in applying Cerenkov radiation (CR) for biological applications. Knowledge of the production efficiency and other characteristics of the CR produced by various radionuclides would help in accessing the feasibility of proposed applications and guide the choice of radionuclides. To generate this information we developed models of CR production efficiency based on the Frank-Tamm equation and models of CR distribution based on Monte-Carlo simulations of photon and β particle transport. All models were validated against direct measurements using multiple radionuclides and then applied to a number of radionuclides commonly used in biomedical applications. We show that two radionuclides, Ac-225 and In-111, which have been reported to produce CR in water, do not in fact produce CR directly. We also propose a simple means of using this information to calibrate high sensitivity luminescence imaging systems and show evidence suggesting that this calibration may be more accurate than methods in routine current use

Smell and taste changes are early indicators of the COVID-19 pandemic and political decision effectiveness

In response to the COVID-19 pandemic, many governments have taken drastic measures to avoid an overflow of intensive care units. Accurate metrics of disease spread are critical for the reopening strategies. Here, we show that self-reports of smell/taste changes are more closely associated with hospital overload and are earlier markers of the spread of infection of SARS-CoV-2 than current governmental indicators. We also report a decrease in self-reports of new onset smell/taste changes as early as 5 days after lockdown enforcement. Cross-country comparisons demonstrate that countries that adopted the most stringent lockdown measures had faster declines in new reports of smell/taste changes following lockdown than a country that adopted less stringent lockdown measures. We propose that an increase in the incidence of sudden smell and taste change in the general population may be used as an indicator of COVID-19 spread in the population

Neutrino astronomy with the MACRO detector

High energy gamma ray astronomy is now a well established field and several sources have been discovered in the region from a few GeV up to several TeV. If sources involving hadronic processes exist, the production of photons would be accompanied by neutrinos too. Other possible neutrino sources could be related to the annihilation of WIMPs at the center of galaxies with black holes. We present the results of a search for point-like sources using 1100 upward-going muons produced by neutrino interactions in the rock below and inside the MACRO detector in the underground Gran Sasso Laboratory. These data show no evidence for a possible neutrino point-like source or for possible correlations between gamma ray bursts and neutrinos. They have been used to set flux upper limits for candidate point-like sources which are in the range 10^-14-10^-15 cm-2 s-1.Comment: 37 pages, 15 figures, replacement due to a typo in tab. 6, AASLaTex, submitted to Ap