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In recent years there has been an increased interest in using protein mass spectroscopy to discriminate diseased from healthy individuals with the aim of discovering molecular markers for disease. A crucial step before any statistical analysis is the pre-processing of the mass spectrometry data. Statistical results are typically strongly affected by the specific pre-processing techniques used. One important pre-processing step is the removal of chemical and instrumental noise from the mass spectra. Wavelet denoising techniques are a standard method for denoising. Existing techniques, however, do not accommodate errors that vary across the mass spectrum, but instead assume a homogeneous error structure. In this paper we propose a novel wavelet denoising approach that deals with heterogeneous errors by incorporating a variance change point detection method in the thresholding procedure. We study our method on real and simulated mass spectrometry data and show that it improves on performances of peak detection methods.

Cardiac catheterization procedures using fluoroscopy reduce patient morbidity and mortality compared to operative procedures. These diagnostic and therapeutic procedures require radiation exposure to patients and physicians. The objectives of the present investigation were to provide a systematic comprehensive summary of the reported radiation doses received by operators due to diagnostic or interventional fluoroscopically-guided procedures, to identify the primary factors influencing operator radiation dose, and to evaluate whether there have been temporal changes in the radiation doses received by operators performing these procedures. Using PubMed, we identified all English-language journal articles and other published data reporting radiation exposures to operators from diagnostic or interventional fluoroscopically-guided cardiovascular procedures from the early 1970's through the present. We abstracted the reported radiation doses, dose measurement methods, fluoroscopy system used, operational features, radiation protection features, and other relevant data. We calculated effective doses to operators in each study to facilitate comparisons. The effective doses ranged from 0.02-38.0 microSv for DC (diagnostic catheterizations), 0.17-31.2 microSv for PCI (percutaneous coronary interventions), 0.24-9.6 microSv for ablations, and 0.29-17.4 microSv for pacemaker or intracardiac defibrillator implantations. The ratios of doses between various anatomic sites and the thyroid, measured over protective shields, were 0.9 +/- 1.0 for the eye, 1.0 +/- 1.5 for the trunk, and 1.3 +/- 2.0 for the hand. Generally, radiation dose is higher on the left side of an operator's body, because the operator's left side is closer to the primary beam when standing at the patient's right side. Modest operator dose reductions over time were observed for DC and ablation, primarily due to reduction in patient doses due to decreased fluoroscopy/cineradiography time and dose rate by technology improvement. Doses were not reduced over time for PCI. The increased complexity of medical procedures appears to have offset dose reductions due to improvements in technology. The large variation in operator doses observed for the same type of procedure suggests that optimizing procedure protocols and implementing general use of the most effective types of protective devices and shields may reduce occupational radiation doses to operators. We had considerable difficulty in comparing reported dosimetry results because of significant differences in dosimetric methods used in each study and multiple factors influencing the actual doses received. Better standardization of dosimetric methods will facilitate future analyses aimed at determining how well medical radiation workers are being protected.

Classification problems have received considerable attention in biological and medical applications. In particular, classification methods combining to microarray technology play an important role in diagnosing and predicting disease, such as cancer, in medical research. Primary objective in classification is to build an optimal classifier based on the training sample in order to predict unknown class in the test sample. In this paper, we propose a unified approach for optimal gene classification with conjunction with functional principal component analysis (FPCA) in functional data analysis (FNDA) framework to classify time-course gene expression profiles based on information from the patterns. To derive an optimal classifier in FNDA, we also propose to find optimal number of bases in the smoothing step and functional principal components in FPCA using a cross-validation technique, and compare the performance of some popular classification techniques in the proposed setting. We illustrate the propose method with a simulation study and a real world data analysis.

The inflammatory response initiated upon burn injury is also associated with extensive metabolic adjustments. While there is a significant body of literature on the characterization of these changes at the metabolite level, little is known on the mechanisms of induction, especially with respect to the role of gene expression. We have comprehensively analyzed changes in gene expression in rat livers during the first 7 d after 20% total body surface area burn injury using Affymetrix microarrays. A total of 740 genes were significantly altered in expression at 1, 2, 4, and 7 d after burn injury compared to sham-burn controls. Functional classification based on gene ontology terms indicated that metabolism, transport, signaling, and defense/inflammation response accounted for more than 70% of the significantly altered genes. Fisher least-significant difference post-hoc testing of the 740 differentially expressed genes indicated that over 60% of the genes demonstrated significant changes in expression either on d 1 or on d 7 postburn. The gene expression trends were corroborated by biochemical measurements of triglycerides and fatty acids 24 h postburn but not at later time points. This suggests that fatty acids are used, at least in part, in the liver as energy substrates for the first 4 d after injury. Our data also suggest that long-term regulation of energy substrate utilization in the liver following burn injury is primarily at the posttranscriptional level. Last, relevance networks of significantly expressed genes indicate the involvement of key small molecules in the hepatic response to 20% total body surface area burn injury.

BackgroundThe excess incidence of thyroid cancer in Ukraine and Belarus observed a few years after the Chernobyl accident is considered to be largely the result of 131I released from the reactor. Although the Belarus thyroid cancer prevalence data has been previously analyzed, no account was taken of dose measurement error.MethodsWe examined dose-response patterns in a thyroid screening prevalence cohort of 11,732 persons aged under 18 at the time of the accident, diagnosed during 1996-2004, who had direct thyroid 131I activity measurement, and were resident in the most radio-actively contaminated regions of Belarus. Three methods of dose-error correction (regression calibration, Monte Carlo maximum likelihood, Bayesian Markov Chain Monte Carlo) were applied.ResultsThere was a statistically significant (p0.2).ConclusionsIn summary, the relatively small contribution of unshared classical dose error in the current study results in comparatively modest effects on the regression parameters.

39 Background: Health-related quality of life (HRQoL) outcomes are important in treatment selection for prostate cancer. The Expanded Prostate Cancer Index Composite (EPIC) is a validated and widely-utilized HRQoL survey which accounts for newer radiotherapeutic, surgical, and hormonal treatment methods. We present a meta-analysis of patient reported HRQoL outcomes collected with EPIC and compare HRQoL trends with radiation therapy, surgery, or active surveillance as primary treatment. Methods: The PubMed database was systematically searched for all studies which presented data directly derived from the use of EPIC on patients with prostate cancer prior to 07/09/2014. All eligible studies were selected for either inclusion and analysis or exclusion based on pre-determined criteria. The data from included studies was compiled and a simulation-based estimation method using Approximate Bayesian Computation was performed to obtain missing standard deviation estimate. A longitudinal meta-analysis was conducted to estimate EPIC-profiles for each component using Bayesian p-spline method. Results: Over 4,000 studies were searched, 152 were deemed eligible, and 39 were included. The calculated mean summary score estimates are shown in the attached table. Conclusions: In the urinary domain, radical prostatectomy (RP) has lower acute scores than active surveillance (AS) or radiation therapy (RT) without long-term difference. In the bowel domain, RT has lower scores than AS or RP acutely and long-term. In the sexual domain, RT and RP have lower acute scores than AS. RP has lower scores than RT without long-term difference. In the hormonal domain, little difference was noted between modalities. [Table: see text]

e16001 Background: Cetuximab (Cx) + radiation therapy (RT) is well tolerated and has improved survival in patients (pts) with LA-HNSCC. However, its efficacy when compared to HD-DDP + RT has been questioned. At our institution, low-dose weekly carboplatin (Carbo) is added to Cx + RT for pts unsuitable for HD-DDP. Methods: We reviewed records of 16 pts with LA-HNSCC treated with definitive Cx + Carbo + RT at the University of Miami from 2007-2011. Median follow-up was 9.4 months (range: 1-50 months). Results: Median age: 71.5 years (range: 57-90 years); 15 male, 1 female.ECOG PS 0=15, 1=1. TNM staging was: T1= 1, T2= 5, T3=8, T4=2; N stage: N0=8, N1=5, N2a=2, N2b=1. All pts received weekly Carbo (AUC 1.5-2), Cx given conventionally and daily conventionally-fractionated RT. Median total weeks of concurrent systemic therapy= 7 (range: 3-8 weeks). RT was delivered to a median total dose of 70 Gy (range 30-74 Gy). Of the 15 evaluable pts, there were: 12 CR, 2 PR, and 1 PD. There were 2 local in-field failures, 1 regional failure, and 3 distant failures. At last follow-up, 11/16 pts remained with NED. 3-year locoregional recurrence was 29.5% (95% CI: 5.3%-45.9%). Toxicity (NCI-CTCAE v4.0): Mean percentage of weight loss was 14% (range: 6-26%). Two pts required systemic therapy dose-reduction. Three pts experienced a treatment delay and 3 did not finish RT as planned including one pt who received only 30Gy due to death secondary to MI during treatment. Conclusions: In this small retrospective series, Carbo/Cx/RT was well-tolerated and efficacious in pts unsuitable for HD-DDP having LA-HNSCC. Acute toxicities were similar to Cx + RT, likely due to the non-overlapping toxicity profiles of the two systemic agents. We hypothesize that the addition of a well-tolerated cytotoxic chemotherapy agent may improve the therapeutic ratio of Cx + RT in pts who are poor candidates for more aggressive therapies and warrants evaluation in a prospective manner. [Table: see text]

The detection of gene-gene interaction is an important approach to understand the etiology of rheumatoid arthritis (RA). The goal of this study is to identify gene-gene interaction of SNPs at the allelic level contributing to RA using real data sets (Problem 1) of North American Rheumatoid Arthritis Consortium (NARAC) provided by Genetic Analysis Workshop 16 (GAW16). We applied our novel method that can detect the interaction by a definition of nonrandom association of alleles that occurs when the contribution to RA of a particular allele inherited in one gene depends on a particular allele inherited at other unlinked genes. Starting with 639 single-nucleotide polymorphisms (SNPs) from 26 candidate genes, we identified ten two-way interacting genes and one case of three-way interacting genes. SNP rs2476601 on PTPN22 interacts with rs2306772 on SLC22A4, which interacts with rs881372 on TRAF1 and rs2900180 on C5, respectively. SNP rs2900180 on C5 interacts with rs2242720 on RUNX1, which interacts with rs881375 on TRAF1. Furthermore, rs2476601 on PTPN22 also interacts with three SNPs (rs2905325, rs1476482, and rs2106549) in linkage disequilibrium (LD) on IL6. The other three SNPs (rs2961280, rs2961283, and rs2905308) in LD on IL6 interact with two SNPs (rs477515 and rs2516049) on HLA-DRB1. SNPs rs660895 and rs532098 on HLA-DRB1 interact with rs2834779 and four SNPs in LD on RUNX1. Three-way interacting genes of rs10229203 on IL6, rs4816502 on RUNX1, and rs10818500 on C5 were also detected.