Univariate Analysis Of Association Research Articles

Prevalence of Maternal Measles Antibody and Its Associated Factors among Infants in Coastal Karnataka, India.

Background:The current recommendation in India to commence first dose of measles immunization is at 9 months of age. The effectiveness of measles vaccination is greatly impacted by the level of maternal measles antibody (MMA) during infancy.Objectives:To find the prevalence of MMA and to study the maternal and infant factors associated with persistence of MMA among the infants in a Indian rural community.Methodology:Dried blood spot sample was collected before vaccination among infants aged 9 months and above when they came for first dose of measles vaccine to assess measles-specific maternal IgG antibody titers by enzyme immunoassay. Maternal and child factors influencing persistence of MMA were collected by interviewing the mothers. Association between various factors affecting seropositivity was tested using univariate logistic regression analysis and strength of association is reported as risk ratio with 95% confidence interval.Results:Based on the qualitative estimation among all the recruited children (250) in the study, 4 (1.6%) infants showed the presence of MMA whereas 25 (10%) of children had MMA on quantitative estimation. The effect of maternal factors, child nutrition, and sociodemographic factors on the presence of MMA was not found to be statistically significant.Conclusion:The prevalence of persistent MMA (IgG titer ≥200 mIU/ml) among the infants aged 9–12 months was 10%. The choice of vaccinating infants at the end of 9 months for the first dose of measles vaccine is justified as the remaining (90%) of infants were susceptible for measles infection at this age.

Generalized Structured Component Analysis in candidate gene association studies: applications and limitations

Background: Generalized Structured Component Analysis (GSCA) is a component-based alternative to traditional covariance-based structural equation modelling. This method has previously been applied to test for association between candidate genes and clinical phenotypes, contrasting with traditional genetic association analyses that adopt univariate testing of many individual single nucleotide polymorphisms (SNPs) with correction for multiple testing. Methods: We first evaluate the ability of the GSCA method to replicate two previous findings from a genetics association study of developmental language disorders. We then present the results of a simulation study to test the validity of the GSCA method under more restrictive data conditions, using smaller sample sizes and larger numbers of SNPs than have previously been investigated. Finally, we compare GSCA performance against univariate association analysis conducted using PLINK v1.9. Results: Results from simulations show that power to detect effects depends not just on sample size, but also on the ratio of SNPs with effect to number of SNPs tested within a gene. Inclusion of many SNPs in a model dilutes true effects. Conclusions: We propose that GSCA is a useful method for replication studies, when candidate SNPs have been identified, but should not be used for exploratory analysis.

Multivariate Analyses Reveal Biological Components Related to Neuronal Signaling and Immunity Mediating Electroencephalograms Abnormalities in Alcohol-Dependent Individuals from the Collaborative Study on the Genetics of Alcoholism Cohort.

The underlying molecular mechanisms associated with alcohol use disorder (AUD) risk have only been partially revealed using traditional approaches such as univariate genomewide association and linkage-based analyses. We therefore aimed to identify gene clusters related to Electroencephalograms (EEG) neurobiological phenotypes distinctive to individuals with AUD using a multivariate approach. The current project adopted a bimultivariate data-driven approach, parallel independent component analysis (para-ICA), to derive and explore significant genotype-phenotype associations in a case-control subset of the Collaborative Study on the Genetics of Alcoholism (COGA) dataset. Para-ICA subjects comprised N=799 self-reported European Americans (367 controls and 432 AUD cases), recruited from COGA, who had undergone resting EEG and genotyping. Both EEG and genomewide single nucleotide polymorphism (SNP) data were preprocessed prior to being subjected to para-ICA in order to derive genotype-phenotype relationships. From the data, 4 EEG frequency and 4 SNP components were estimated, with 2 significantly correlated EEG-genetic relationship pairs. The first such pair primarily represented theta activity, negatively correlated with a genetic cluster enriched for (but not limited to) ontologies/disease processes representing cell signaling, neurogenesis, transmembrane drug transportation, alcoholism, and lipid/cholesterol metabolism. The second component pair represented mainly alpha activity, positively correlated with a genetic cluster with ontologies similarly enriched as the first component. Disease-related enrichments for this component revealed heart and autoimmune disorders as top hits. Loading coefficients for both the alpha and theta components were significantly reduced in cases compared to controls. Our data suggest plausible multifactorial genetic components, primarily enriched for neuronal/synaptic signaling/transmission, immunity, and neurogenesis, mediating low-frequency alpha and theta abnormalities in alcohol addiction.

Blood lipids and angina pectoris (by epidemiological cardiological Rose questionnaire) in the population of 25-45 years of Novosibirsk

Cross-sectional survey of the population aged 25-45 in Novosibirsk was carried out. The study included 1439 people (656 men and 783 women). Within the framework of the complex survey program, thestandardized epidemiological questionnaire of Rose (WHO, 1984) was used. Blood levels of total cholesterol (total C), triglycerides (TG), low and high density lipoprotein cholesterol (LDL-C, HDL-C) were determinate by biochemical methods. For all lipid indicators, significant differences were found between men and women. The levels of total C, TG and LDL-C were significantly higher, and the level of HDL-C was lower in men, than in women. According to the Rose questionnaire, out of 1439 people included in the study, 12 patients (0.8%) had AP (75% women). In persons with AP, blood levels of TG were 1.8 times higher, and the levels ofHDL-C in blood was 1.2 times lower compared to persons without AP. Univariate analysis of associations of AP with CHD risk factors showed that the chance of developing angina pectoris in the population of 25-45 years was significantly increased in individuals with high blood TG levels (OR 3,515, DI 1,106-11,168, p = 0.039) and low HDL-C (OR 1,203, DI 1,054-1,372, p = 0.006). A natural, although statistically not significant (OR 3,165, p=0,055, due to the small number of groups with AP) increasing in thechance ofdeveloping AP in hypertension was detected. In the young population of 25-45 years in Novosibirsk, elevated blood levels of TG, reduced levels of HDL-C, and hypertension were associated with AP, according to Rosecardiological questionnaire, which underlines the importance of conducting screening surveys of the young population to improve effective prevention and treatment of diseases.

Sleep Quality and Fatigue Are Associated with Pain Exacerbations of Hip Osteoarthritis: An Internet-based Case-crossover Study.

To evaluate the association of sleep quality, sleep duration, and fatigue with hip pain exacerbations in persons with symptomatic hip osteoarthritis (OA). Participants (n = 252) were followed for 90 days and asked to complete online questionnaires at 10-day intervals (control periods). A hip pain exacerbation (case periods) was defined as an increase of 2 points in pain intensity compared with baseline on a numeric rating scale (0-10). Subjective sleep quality and sleep duration were assessed using the Pittsburgh Sleep Quality Index, and fatigue was measured by Multidimensional Assessment of Fatigue in both periods. Univariable and multivariable conditional logistic regressions were used to assess the association. Of the 252 participants, 130 (52%) were included in the final analysis. Univariate association analysis showed that both poor sleep quality and greater fatigue were associated with increased odds of pain exacerbations (OR 1.72, 95% CI 1.04-2.86; OR 1.92, 95% CI 1.21-3.05, respectively). Short sleep duration was not associated with pain exacerbations. Poor sleep quality and greater fatigue remained associated with pain exacerbations after adjustment for physical activity and night pain levels in multivariable analysis. There was no significant interaction between sleep quality and fatigue (p = 0.21). Poor sleep quality and greater fatigue were related to pain exacerbation in persons with symptomatic hip OA. Sleep disorders and fatigue should be considered when dealing with pain exacerbations.

Body mass index (BMI) and toxicities and association with clinical outcomes (CO) in metastatic renal cell carcinoma (mRCC) patients (pts) treated with cabozantinib (cabo).

613 Background: BMI has been explored as a prognostic factor in cancer pts and treatment-related toxicities have been associated with responses to VEGF-targeted therapy in mRCC pts. We investigated the association of BMI and adverse events (AEs) and CO in mRCC pts treated with cabo. Methods: A retrospective analysis of 65 pts with mRCC treated with cabo at Winship Cancer Institute from 2016 to 2018 was performed. Overall survival (OS), progression-free survival (PFS), and objective response (OR) were used to measure CO. OS and PFS were calculated from first cabo dose to death and radiographic or clinical progression, respectively. An OR was defined as a partial response (PR) or a complete response (CR) using RECISTv1.1. BMI was collected at baseline (BL) and 6 (±2) weeks after cabo initiation. AEs were obtained from clinic notes. Univariate analysis (UVA) of association between BMI and CO was carried out using logistic regression model for OR and proportional hazard model for OS and PFS. Results: The median age was 63 years and 26% were African American. The majority were either IMDC intermediate or poor-risk (59% and 34%, respectively). Most pts (67%) had a BMI ≥ 25 and the median BMI at BL was 26.6. There was no difference in incidence of AEs between pts with BMI < 25 and pts with BMI ≥ 25. Gastrointestinal (GI) AEs incidence was also comparable among pts with a BMI ≥ 25 (62%) and pts with BMI < 25 (57%, p = 0.666). Increased BMI at 6W was significantly associated with prolonged OS and increased baseline BMI at BL showed a trend towards longer OS (Table). Conclusions: Increased BMI may be associated with improved CO in mRCC pts treated with cabo, but there may not be a difference in AEs based on BMI. Larger analyses are needed to validate these findings. [Table: see text]

Analysis of toxicity and clinical outcomes (CO) in full versus reduced dose cabozantinib (cabo) in metastatic renal cell carcinoma (mRCC) patients (pts).

671 Background: The full dose of cabo is 60 mg, but some pts are treated with a reduced dose with the clinical anticipation of adverse events (AEs). We compared AEs and CO in mRCC pts treated with full versus reduced dose cabo. Methods: We performed a retrospective analysis of 65 mRCC pts treated with cabo at Winship Cancer Institute from 2016-2018. CO were measured by overall survival (OS), progression-free survival (PFS), and objective response (OR). OS and PFS were measured from first dose of cabo to date of death and clinical or radiographic progression, respectively. OR was defined as partial response (PR) or complete response (CR) per RECISTv1.1. AEs were collected from clinic notes. Univariate analysis (UVA) of association between AEs and CO was performed using logistic regression model. Results: Most pts were males (68%) and the median age was 63 years. Most (79%) had clear cell RCC (ccRCC) and the majority were IMDC intermediate (59%) or poor (39%) risk. Most pts (68%) received 60 mg and 48% of these pts underwent a dose reduction for AEs. Nearly all pts (95%) who started on a reduced dose experienced AEs, compared to 66% for pts treated with 60 mg. OR rate was similar for pts on 60 mg (18%) and pts on a reduced dose (19%). The median survival was comparable in pts treated with 60 mg and pts treated with a reduced dose (10.9 vs. 8.8 months, p=0.92 for OS and 5.6 vs. 5.1 months, p=0.23 for PFS) per Kaplan Meier estimation. AEs, particularly gastrointestinal (GI) AEs, were associated with significantly lower chance of OR (Table). Conclusions: CO may be comparable in mRCC pts treated with full versus reduced dose of cabo, but a reduced dose of cabo may not be associated with decreased AEs. GI side effects may be a poor prognostic factor in mRCC pts treated with cabo. Larger studies are warranted to validate these findings. [Table: see text]

CT Radiogenomic Characterization of the Alternative Lengthening of Telomeres Phenotype in Pancreatic Neuroendocrine Tumors.

The objective of this study was to identify imaging characteristics in patients with known pancreatic neuroendocrine tumors (PanNETs) that predict the alternative lengthening of telomeres (ALT) phenotype by blinded retrospective review of preoperative multiphasic CT scans. For this retrospective study of 121 preoperative CT examinations of patients with resected PanNETs, two radiologists independently reviewed the CT examinations for tumor characteristics including size, shape, cystic or necrotic elements, calcifications, invasion of adjacent organs and vessels, biliary duct dilatation, pancreatic duct dilatation, and hepatic metastases. Univariate analysis of association of CT characteristics with ALT phenotype was performed with Fisher exact tests or t tests, and multivariate analysis was assessed by multiple logistic regression. Univariate analysis showed that the following CT features were significantly associated with the ALT phenotype: lobulated or irregular tumor shape (p = 0.001), tumor necrosis (p = 0.002), vascular invasion (p < 0.001), pancreatic duct dilatation (p < 0.001), and hepatic metastasis (p < 0.001). Multivariate analysis found that the combination of pancreatic duct dilatation, hepatic metastasis, and size of tumor ≥ 3 cm was a strong predictor of ALT phenotype (odds ratio = 20.3; 95% CI = 2.3-176.3; AUC = 0.58; p = 0.006). This study showed that several preoperative CT features of PanNETs are associated with the ALT phenotype, which is known to predict poor prognosis. Additionally, CT findings of intratumoral calcifications and metastases predicted poor survival independent of the ALT status.

A pilot Indian family-based association study between dyslexia and Reelin pathway genes, DCDC2 and ROBO1, identifies modest association with a triallelic unit TAT in the gene RELN.

Dyslexia is a neurodevelopmental disorder that manifests as a reading disability despite normal intelligence and adequate educational opportunity. Twin and family studies have indicated a genetic component, while genome-wide studies have implicated a number of susceptibility genes, most of which have direct or indirect roles in neuronal migration. Reelin (RELN) has important biological functions facilitating migration of neurons. Polymorphisms in RELN have been implicated in related disorders like autism and schizophrenia but have not been examined in dyslexia. We hypothesized that not only RELN, but its interactors in the neuronal migration pathway may play roles in the etiology of dyslexia. Twenty two functional variants across six RELN signalling genes (RELN, VLDLR, APOER2, DAB1, LIS1 and NDEL1) and two dyslexia candidate genes (DCDC2 and ROBO1) were analyzed for association in twenty six nuclear and three extended families with individuals affected with dyslexia. Univariate association analysis was suggestive of association (puncorrected = 0.01) with rs362746 in RELN which however did not withstand Bonferroni corrections (pcorrected = 0.21). Multimarker tests indicated significant association (p = 0.037), based on which we tested for haplotype associations. Although there were no significant haplotypic associations, we found that a three marker unit with rs3808039 and rs2072403 flanking and independently in linkage disequilibrium with rs362746 was significantly overtransmitted (risk allelic combination - TAT) to dyslexia affected individuals in the sample (p = 0.002). Our results suggest preliminary evidence for a new potential risk variant in the RELN locus for dyslexia.

Abstract 2607: Blood based biomarkers and association with clinical outcome (CO) in advanced stage patients (pts) treated with immunotherapy (IO)

Abstract Background: Optimal biomarkers for cancer pts treated with IO are currently lacking. Markers of inflammation, such as neutrophil-to-lymphocyte ratio (NLR), monocyte-to-lymphocyte ratio (MLR), and platelet-to-lymphocyte ratio (PLR) are readily available and associated with poor outcomes. We investigated the association between these markers and CO in pts treated with IO. Methods: We conducted a retrospective review of 90 pts with advanced cancer treated on IO-based phase I trials at the Winship Cancer Institute of Emory University between 2009-2017. Baseline NLR, MLR, and PLR were treated as continuous variables and rescaled by their own standard deviation. Overall survival (OS) was measured from the first dose of IO to date of death or hospice referral. Progression-free survival (PFS) was determined from first dose of IO to clinical or radiographic progression or death. We defined clinical benefit (CB) as complete response, partial response, or stable disease. Univariate association (UVA) and multivariable analysis (MVA) were carried out using Cox proportional hazard model or logistic regression model. Baseline covariates included race, gender, ECOG PS, # of prior therapies, Royal Marsden Hospital (RMH) risk group, IO indication, and # of metastatic sites. Results: The median pt age was 63 years and most (59%) were men. The most common histologies were melanoma (33%) and GI cancers (22%). The majority (81%) were RMH good risk. 46% of pts had CB on IO. The median NLR, MLR, and PLR was 3.63, 0.48, and 182.65, respectively. Increased NLR, MLR, and PLR were all associated with worse OS, PFS, and chance of CB (Table 1). NLR, MLR and PLR are highly correlated to each other (Pearson correlation coefficients ≥ 0.8, all p &amp;lt; 0.0001). Conclusion: NLR, MLR, and PLR are strongly associated with CO in pts treated with IO. Prospective validation of these findings are warranted. Table 1: UVA and MVA of NLR, MRL, and PLR with CO OS PFSCBUVAMVAUVAMVAUVAMVAHR (CI)p-valueHR (CI)p-valueHR (CI)p-valueHR (CI)p-valueOR (CI)p-valueOR (CI)p-valueNLR1.37 (1.11-1.70)0.003*1.30 (1.02-1.66)0.031*1.42 (1.18-1.70)&amp;lt;0.001*1.32 (1.06-1.63)0.011*0.47 (0.23-0.94)0.033*0.57 (0.26-1.27)0.169MLR1.38 (1.14-1.67)&amp;lt;0.001*1.22 (0.98-1.52)0.071.39 (1.18-1.63)&amp;lt;0.001*1.26 (1.03-1.55)0.026*0.45 (0.23-0.89)0.021*0.71 (0.32-1.57)0.398PLR1.40 (1.15-1.69)&amp;lt;0.001*1.27 (1.03-1.56)0.027*1.40 (1.19-1.63)&amp;lt;0.001*1.27 (1.06-1.53)0.01*0.35 (0.17-0.74)0.006*0.28 (0.11-0.67)0.005* *statistically significant Citation Format: Dylan J. Martini, Yuan Liu, Colleen Lewis, Hannah Collins, Mehmet Akce, Haydn Kissick, Bradley C. Carthon, Walid L. Shaib, Olatunji B. Alese, Rathi Pillai, Conor E. Steuer, Christina Wu, David H. Lawson, Ragini Kudchadkar, Bassel El-Rayes, Viraj A. Master, Suresh Ramalingam, Taofeek K. Owonikoko, R Donald Harvey, Mehmet Asim Bilen. Blood based biomarkers and association with clinical outcome (CO) in advanced stage patients (pts) treated with immunotherapy (IO) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 2607.

Necrotizing soft tissue infections - a multicentre, prospective observational study (INFECT): protocol and statistical analysis plan.

The INFECT project aims to advance our understanding of the pathophysiological mechanisms in necrotizing soft tissue infections (NSTIs). The INFECT observational study is part of the INFECT project with the aim of studying the clinical profile of patients with NSTIs and correlating these to patient-important outcomes. With this protocol and statistical analysis plan we describe the methods used to obtain data and the details of the planned analyses. The INFECT study is a multicentre, prospective observational cohort study. Patients with NSTIs are enrolled in five Scandinavian hospitals, which are all referral centres for NSTIs. The primary outcomes are the descriptive variables of the patients. Secondary outcomes include identification of factors associated with 90-day mortality and amputation; associations between affected body part, maximum skin defect and Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score and 90-day mortality; 90-day mortality in patients with and without acute kidney injury (AKI) and LRINEC score of six and above or below six; and association between affected body part at arrival and microbiological findings. Exploratory outcomes include univariate analyses of baseline characteristics associations with 90-day mortality. The statistical analyses will be conducted in accordance with the predefined statistical analysis plan. Necrotizing soft tissue infections result in severe morbidity and mortality. The INFECT study will be the largest prospective study in patients with NSTIs to date and will provide important data for clinicians, researchers and policy makers on the characteristics and outcomes of these patients.

PROGNOSTIC FACTORS IN PATIENTS WITH RELAPSED OR REFRACTORY SYSTEMIC ANAPLASTIC LARGE T‐CELL LYMPHOMA (ALCL) RECEIVING BRENTUXIMAB VEDOTIN AND OUTCOME AFTER TREATMENT FAILURE.

Background: Brentuximab vedotin (BV) has shown significant clinical activity in anaplastic large T-cell lymphoma (ALCL). However, the management of those who relapse or have disease progression on BV is challenging. We sought to evaluate the features that may be associated with the response to BV and to assess the outcome after the disease progression. Method: This is a multicenter retrospective study analyzing the outcome of patients who received BV for relapsed or refractory systemic ALCL. A total of 55 patients that had been treated with BV for relapsed or refractory disease were identified. Characteristics at the start of BV were analyzed for their association with failure free survival (FFS) and overall survival (OS). Failure of BV was defined by disease progression, relapse or change of therapy. Patients who received a stem cell transplant (SCT) were censored at the time of transplant for the FFS analysis. Results: The median age of patients at the time of the first cycle of BV was 55 years (range 13–88); most patients were male (82%), and the majority had refractory disease (53%). ALK positive in 14 cases (25%). BV therapy was started within 1 year of the initial diagnosis in 52% of patients. A total of 11 patients (20%) had undergone SCT prior to BV. Overall response rate was 71%, including CR in 45%. With a median follow-up of 30 months, the median FFS was 15 months, and the median OS was not reached. The 2-year FFS and OS was 31% and 59%, respectively. In patients who received BV following failure of primary CHOP (like) therapy, the ORR and CR were 69% and 54%, respectively. Outcomes were similar in patients who had received a prior SCT (2-y FFS 30%, 2-y OS 57%) or had received BV either pre-SCT or were transplant ineligible (2-y FFS 30%, 2-y OS 64%). Twenty-one patients went on to SCT (auto n = 13; allo n = 8) following response to BV. By univariate analyses, PS (0–1 vs >2), sIPI (0–1 vs 2–3 vs 4–5), and interval from diagnosis (≤1 year vs >1) were associated with a shorter FFS. Multivariate analysis showed only sIPI to be independently associated with FFS (Hazard ratio [HR] 2.6, p = 0.004). Univariate analysis for association with OS determined PS, extranodal involvement (≤1 vs >1), high LDH, sIPI, refractory disease (vs relapse) to be associated with shorter OS. Multivariate analysis identified sIPI (HR 3.7, p = 0.001) and refractory disease (HR 2.6, p = 0.036) to be independently associated with OS. Twenty-two patients had PD on BV, and two had treatment tolerance requiring a change in therapy. In this group (n = 24), the median OS after BV failure was only 3 months, and 2-year OS was 30%. Of 6 long-term (>1 year) survivors, five underwent subsequent SCT (allo n = 3, auto n = 2). One had good response to investigational clinical trial treatment, and one had localized indolent disease. Conclusions: Refractory disease to last therapy and higher sIPI at start of BV were associated with inferior outcomes in ALCL following BV. Further, patients with disease progression after use of BV have a dismal outcome. Keywords: anaplastic large cell lymphoma (ALCL); brentuximab vedotin; prognostic indices.

Outcomes of Twin Pregnancies in Women Age 45 or Older [30R

INTRODUCTION: Singleton pregnancies in well-selected women 45 and older undergoing assisted reproduction have a high likelihood of successful pregnancies with an increased risk of hypertensive disorders of pregnancy. Our objective was to investigate outcomes of twin gestations in women age 45 or older. METHODS: Historical cohort of 97 women age 45 or older with twin gestations cared for by 2 referral centers between 2005-2016. Analysis included baseline demographic and clinical characteristics. Pregnancy outcomes included gestational age at delivery, hypertensive disease in pregnancy, gestational diabetes, and IUGR. Univariate analysis of association between patient characteristics and outcomes were performed using student t-test and chi square. RESULTS: Mean maternal age at delivery was 47.7 +/- 2.0 with 99% undergoing IVF and 95.9% using donor egg. Patients have low baseline rates of hypertension (6.2%), obesity (8.0%) and pre-gestational diabetes (1%). 40.2% of women developed preeclampsia, 45.8% developed IUGR, 14.5% developed gestational diabetes, and 13.4% had an indicated preterm birth prior to 34 weeks. On univariate analysis, No baseline risk factors were associated with the development of preeclampsia or IUGR. Women of white race had a decreased risk of indicated preterm birth &lt; 34 weeks (8.2% vs. 29.2%, p=0.009) and a decreased risk of gestational diabetes (9.6% vs. 30.4%, p=0.014). CONCLUSION: Twin pregnancy in women age 45 or older is associated with high rates of hypertensive disease in pregnancy and IUGR but overall outcomes are reassuring. Twin pregnancy should not be discouraged in well-selected, healthy women age 45 or older simply due to age alone.

Initial Performance of NI-RADS to Predict Residual or Recurrent Head and Neck Squamous Cell Carcinoma.

The Head and Neck Imaging Reporting and Data System (NI-RADS) surveillance template for head and neck cancer includes a numeric assessment of suspicion for recurrence (1-4) for the primary site and neck. Category 1 indicates no evidence of recurrence; category 2, low suspicion of recurrence; category 3, high suspicion of recurrence; and category 4, known recurrence. Our purpose was to evaluate the performance of the NI-RADS scoring system to predict local and regional disease recurrence or persistence. This study was classified as a quality-improvement project by the institutional review board. A retrospective database search yielded 500 consecutive cases interpreted using the NI-RADS template. Cases without a numeric score, non-squamous cell carcinoma primary tumors, and primary squamous cell carcinoma outside the head and neck were excluded. The electronic medical record was reviewed to determine the subsequent management, pathology results, and outcome of clinical and radiologic follow-up. A total of 318 scans and 618 targets (314 primary targets and 304 nodal targets) met the inclusion criteria. Among the 618 targets, 85.4% were scored NI-RADS 1; 9.4% were scored NI-RADS 2; and 5.2% were scored NI-RADS 3. The rates of positive disease were 3.79%, 17.2%, and 59.4% for each NI-RADS category, respectively. Univariate association analysis demonstrated a strong association between the NI-RADS score and ultimate disease recurrence, with P < .001 for primary and regional sites. The baseline performance of NI-RADS was good, demonstrating significant discrimination among the categories 1-3 for predicting disease.

Coronary Heart Disease risk profile among women attending Tertiary Care Hospital in Southern Karnataka, India

Background: Present study was conducted to assess the risk factors of CHD in women who had undergone Coronary Angiography for CHD evaluation. Objectives of the study were to assess the CHD Risk profile among women attending Tertiary Care Hospital at Mysore city and to enlist the clinical presentation of women admitted to tertiary care Hospital. Settings and Design: Hospital based cross sectional study. Methods: All the women who were admitted to the Department of Cardiology from April 2015 to January 2016 were interviewed using pre structured proforma. Details of the female patients who had undergone Angiography from September 2013 to March 2015 were also collected from Medical Record Section of the Hospital. Statistical Analysis: Proportion and mean were used for relevant univariate analysis and significance of association was tested using appropriate tests of significance. Results: 17% of women were known cases of CHD. 87.4% of women were admitted with the symptom of chest pain. 44% of women who presented with IHD belonged to normal and underweight BMI category. Among the clinically suspected or diagnosed to be cases of CHD, 75% had blocks in their coronaries. Single artery block (29.7%) and triple artery block (22.5%) were predominant. Left anterior descending artery had significant block (&gt;70%) in 36% of women. Left circumflex artery and right coronary arteries showed significant blocks in 26% and 22.5% participants. Conclusions: Earlier age of presentation, higher proportion of coronary blocks in majority of study women belonging to normal or underweight BMI category are alarms of changing pattern of CHD in Indian women.

Pharmacogenetic analysis of high-dose methotrexate treatment in children with osteosarcoma.

Inter-individual differences in toxic symptoms and pharmacokinetics of high-dose methotrexate (MTX) treatment may be caused by genetic variants in the MTX pathway. Correlations between polymorphisms and pharmacokinetic parameters and the occurrence of hepato- and myelotoxicity were studied. Single nucleotide polymorphisms (SNPs) of the ABCB1, ABCC1, ABCC2, ABCC3, ABCC10, ABCG2, GGH, SLC19A1 and NR1I2 genes were analyzed in 59 patients with osteosarcoma. Univariate association analysis and Bayesian network-based Bayesian univariate and multilevel analysis of relevance (BN-BMLA) were applied. Rare alleles of 10 SNPs of ABCB1, ABCC2, ABCC3, ABCG2 and NR1I2 genes showed a correlation with the pharmacokinetic values and univariate association analysis. The risk of toxicity was associated with five SNPs in the ABCC2 and NR1I2 genes. Pharmacokinetic parameters were associated with four SNPs of the ABCB1, ABCC3, NR1I2, and GGH genes, and toxicity was shown to be associated with ABCC1 rs246219 and ABCC2 rs717620 using the univariate and BN-BMLA method. BN-BMLA analysis detected relevant effects on the AUC0-48 in the following SNPs: ABCB1 rs928256, ABCC3 rs4793665, and GGH rs3758149. In both univariate and multivariate analyses the SNPs ABCB1 rs928256, ABCC3 rs4793665, GGH rs3758149, and NR1I2 rs3814058 SNPs were relevant. These SNPs should be considered in future dose individualization during treatment.

Bacterial Urinary Tract Infection after Transrectal Placement of Fiducial Markers prior to Proton Radiotherapy for Prostate Cancer.

To determine the incidence of a bacterial urinary tract infection (UTI) necessitating hospitalization after transrectal placement of fiducial markers prior to proton radiotherapy (RT) for prostate cancer. Six hundred sixty six patients returning for follow up after proton RT consented to participate in this institutional review board (IRB) approved study. Patients were queried whether they required hospitalization within 1 month of transrectal placement of fiducial markers. Patients were treated with proton RT between August 2006 and December 2014. Median International Prostate Symptom Score (IPSS) was 7. Sixty four patients (9.6%) had diabetes, 9 patients (1.4%) had chronic obstructive pulmonary disease, 6 patients (0.9%) had prior bladder surgery, 7 patients (1.1%) had a transurethral prostatectomy within 3 months, and 549 patients (82.4%) had a course of antibiotics within 6 months. Fifty five patients (8.3%) were taking tamsulosin, 16 patients (2.4%) were taking finasteride, and 62 patients (9.3%) were taking saw palmetto. The interval between the most recent prostate biopsy prior to fiducial placement and fiducial marker placement was less than 6 months in 609 patients (91.4%). No patient had a prior recent rectal culture. Ten patients (1.5%) developed a bacterial UTI necessitating hospitalization after transrectal placement of fiducial markers. A bacterial UTI occurred in 3 (0.7%) of 440 patients treated from 2006 to 2012 and in 7 (3.1%) of 226 patients treated from 2013 to 2014. Univariate analysis of potential association of a bacterial UTI with the following parameters revealed: IPSS less than or greater than the median (p=0.3400), diabetes (p=0.6099), tamsulosin (p=0.9999), saw palmetto (p=0.0093), interval between prostate biopsy and placement of fiducials (p=0.9999), year of treatment (p=0.0363), and antibiotics within 6 months (p=0.2233). A bacterial UTI was observed in 4 (6.5%) of 62 patients who were taking saw palmetto versus 6 (1.0%) of 604 patients who were not taking this medication. The incidence of a bacterial UTI between 2006 and 2012 was 3 (0.7%) of 440 patients and from 2013 to 2014 was 7 (3.1%) of 226 patients. Multivariate analysis revealed that the likelihood of a bacterial UTI was increased in patients taking saw palmetto (p=0.0044) and those treated in 2013-2014 (p=0.0303). The incidence of a bacterial UTI requiring hospitalization after transrectal placement of fiducial markers prior to proton RT was 1.5% and was impacted by taking saw palmetto and year of treatment. Patients treated during 2013 and 2014 had a significantly higher risk of a bacterial UTI requiring hospitalization.

Mouse and Human Genetic Analyses Associate Kalirin with Ventral Striatal Activation during Impulsivity and with Alcohol Misuse.

Impulsivity is associated with a spectrum of psychiatric disorders including drug addiction. To investigate genetic associations with impulsivity and initiation of drug taking, we took a two-step approach. First, we identified genes whose expression level in prefrontal cortex, striatum and accumbens were associated with impulsive behavior in the 5-choice serial reaction time task across 10 BXD recombinant inbred (BXD RI) mouse strains and their progenitor C57BL/6J and DBA2/J strains. Behavioral data were correlated with regional gene expression using GeneNetwork (www.genenetwork.org), to identify 44 genes whose probability of association with impulsivity exceeded a false discovery rate of < 0.05. We then interrogated the IMAGEN database of 1423 adolescents for potential associations of SNPs in human homologs of those genes identified in the mouse study, with brain activation during impulsive performance in the Monetary Incentive Delay task, and with novelty seeking scores from the Temperament and Character Inventory, as well as alcohol experience. There was a significant overall association between the human homologs of impulsivity-related genes and percentage of premature responses in the MID task and with fMRI BOLD-response in ventral striatum (VS) during reward anticipation. In contrast, no significant association was found between the polygenic scores and anterior cingulate cortex activation. Univariate association analyses revealed that the G allele (major) of the intronic SNP rs6438839 in the KALRN gene was significantly associated with increased VS activation. Additionally, the A-allele (minor) of KALRN intronic SNP rs4634050, belonging to the same haplotype block, was associated with increased frequency of binge drinking.

Factors associated with cardiovascular diseases in adults

Study design: cross-sectional study, population-based household survey. Objective: To identify the factors associated with cardiovascular disease in the adult population in the metropolitan region of Maringá Methodology: Participants were 1232 individuals of both sexes and aged between 20 and 59 years living in the metropolitan region of Maringa, Parana. For the identification of associated factors was used multiple logistic regression unconditioned after univariate association analysis. Results: Most subjects were female (72.2%), aged between 40 and 59 years (54.1%), white (72.3%), with a partner (66.1%) and belongs to economy class C (56%). The prevalence of cardiovascular disease was 27.9%, the most prevalent Arterial Hypertension (25.8%) and angina (5%). The factors associated with cardiovascular disease in general, and isolated cardiovascular disease, were waist circumference (p=0.004), body mass index (p=0.023), dyslipidemia (p=0.002) and alcohol consumption (p=0.024). Smoking was associated specifically to Acute Myocardial Infarction and Heart Failure. Conclusion: The results indicate that it is imperative concern and the union of efforts by health professionals on the need for establishment of preventive measures related to the risk factors responsible for the occurrence of cardiovascular diseases

Smooth-Threshold Multivariate Genetic Prediction with Unbiased Model Selection.

We develop a new genetic prediction method, smooth-threshold multivariate genetic prediction, using single nucleotide polymorphisms (SNPs) data in genome-wide association studies (GWASs). Our method consists of two stages. At the first stage, unlike the usual discontinuous SNP screening as used in the gene score method, our method continuously screens SNPs based on the output from standard univariate analysis for marginal association of each SNP. At the second stage, the predictive model is built by a generalized ridge regression simultaneously using the screened SNPs with SNP weight determined by the strength of marginal association. Continuous SNP screening by the smooth thresholding not only makes prediction stable but also leads to a closed form expression of generalized degrees of freedom (GDF). The GDF leads to the Stein's unbiased risk estimation (SURE), which enables data-dependent choice of optimal SNP screening cutoff without using cross-validation. Our method is very rapid because computationally expensive genome-wide scan is required only once in contrast to the penalized regression methods including lasso and elastic net. Simulation studies that mimic real GWAS data with quantitative and binary traits demonstrate that the proposed method outperforms the gene score method and genomic best linear unbiased prediction (GBLUP), and also shows comparable or sometimes improved performance with the lasso and elastic net being known to have good predictive ability but with heavy computational cost. Application to whole-genome sequencing (WGS) data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) exhibits that the proposed method shows higher predictive power than the gene score and GBLUP methods.