Missing Features Reconstruction Using a Wasserstein Generative Adversarial Imputation Network

Missing data is one of the most common preprocessing problems. In this paper, we experimentally research the use of generative and non-generative models for feature reconstruction. Variational Autoencoder with Arbitrary Conditioning (VAEAC) and Generative Adversarial Imputation Network (GAIN) were researched as representatives of generative models, while the denoising autoencoder (DAE) represented non-generative models. Performance of the models is compared to traditional methods k-nearest neighbors (k-NN) and Multiple Imputation by Chained Equations (MICE). Moreover, we introduce WGAIN as the Wasserstein modification of GAIN, which turns out to be the best imputation model when the degree of missingness is less than or equal to 30%. Experiments were performed on real-world and artificial datasets with continuous features where different percentages of features, varying from 10% to 50%, were missing. Evaluation of algorithms was done by measuring the accuracy of the classification model previously trained on the uncorrupted dataset. The results show that GAIN and especially WGAIN are the best imputers regardless of the conditions. In general, they outperform or are comparative to MICE, k-NN, DAE, and VAEAC.Comment: Preprint of the conference paper (ICCS 2020), part of the Lecture Notes in Computer Scienc

Evaluation of a validated methylation triage signature for human papillomavirus positive women in the HPV FOCAL cervical cancer screening trial.

Human papillomavirus (HPV)-based cervical cancer screening requires triage of HPV positive women to identify those at risk of cervical intraepithelial neoplasia grade 2 (CIN2) or worse. We conducted a blinded case-control study within the HPV FOCAL randomized cervical cancer screening trial of women aged 25-65 to examine whether baseline methylation testing using the S5 classifier provided triage performance similar to an algorithm relying on cytology and HPV genotyping. Groups were randomly selected from women with known HPV/cytology results and pathology outcomes. Group 1: 104 HPV positive (HPV+), abnormal cytology (54 CIN2/3; 50 <CIN2); Group 2: 103 HPV+, normal cytology with HPV persistence at 12 mo. (53 CIN2/3; 50 <CIN2); Group 3: 50 HPV+, normal cytology with HPV clearance at 12 mo. (assumed <CIN2), total n=257. For the combined groups, S5 risk score CIN2/3 relative sensitivity, specificity and positive predictive value (PPV) were compared with other triage approaches. Methylation showed a highly significant increasing trend with disease severity. For CIN3, S5 relative sensitivity and specificity were: 93.2% (95%CI: 81.4-98.0) and 41.8% (35.2-48.8), compared to 86.4% (75.0-95.7) and 49.8% (43.1-56.6) respectively for combined abnormal cytology/HPV16/18 positivity (differences not statistically significant at 5% level); adjusted PPVs were 18.2% (16.2-20.4) and 19.3% (16.6-22.2) respectively. S5 was also positive in baseline specimens from eight cancers detected during or after trial participation. The S5 methylation score had high sensitivity and PPV for CIN3, compatible with US and European thresholds for colposcopy referral. Methylation signatures can identify most HPV positive women at increased risk of cervical cancer from their baseline screening specimens.The HPV FOCAL Trial was funded by the Canadian Institutes for Health Research (grant no. MCT82072). The methylation case-control study was funded by Cancer Research UK (grant no. C569/A10404)

Sex Differences and Eating Disorder Risk Among Psychiatric Conditions, Compulsive Behaviors and Substance Use in a Screened Canadian National Sample

OBJECTIVE: This study examined sex differences and eating disorder risk among psychiatric conditions, compulsive behaviors (i.e., gambling, suicide thoughts and attempts) and substance use in a nationally representative sample. METHOD: Data from participants of the Canadian Community Health Survey Cycle 1.2 who completed the Eating Attitudes Test (n=5116) were analyzed. Sex differences were compared among psychiatric comorbidities according to eating disorder risk, binging, vomiting and dieting behavior. Poisson regression analysis provided prevalence ratios (PRs) of disordered eating adjusting for age, marital status, income, body mass index and recent distress. RESULTS: Pronounced sex differences were associated with eating disorder risk (PRs 4.89-11.04; all P values \u3c.0001). Findings of particular interest included significantly higher PRs for eating disorder risk in males associated with gambling (PR 5.07, P\u3c.0001) and for females associated with steroid and inhalant use as well as suicide thoughts and attempts (PRs 5.40-5.48, all P values \u3c.0001). DISCUSSION: The findings from this detailed exploration of sex differences and eating disorder risk among psychiatric conditions, compulsive behaviors and substance use suggest that problem gambling, the use of inhalants and steroids and suicidal ideation in relationship to eating disorder risk warrant further investigation

Cardiac death after breast radiotherapy and the QUANTEC cardiac guidelines

Background: Breast/chest wall irradiation (RT) increases risk of cardiovascular death. International Quantitative Analysis of Normal Tissue Effects in the Clinic (QUANTEC) guidelines state for partial heart irradiation a “V25Gy <10% will be associated with a <1% probability of cardiac mortality” in long-term follow-up after RT. We assessed whether women treated with breast/chest wall RT 10-years ago who died of cardiovascular disease (CVD) violated QUANTEC guidelines. / Materials/methods: A population-based database identified all cardiovascular deaths in women with early-stage breast cancer <80 years, treated with adjuvant breast/chest wall RT from 2002 to 2006. Ten-year rate of cardiovascular death was calculated using a Kaplan-Meier method. Patients were matched on a 2:1 basis with controls that did not die of CVD. For left-sided cases, the heart and left anterior descending (LAD) artery were retrospectively delineated. Dose-volume histograms were calculated, and heart V25Gy compared to QUANTEC guidelines. / Results: 5249 eligible patients received breast/chest wall RT from 2002 to 2006: 76 (1.4% at 10-years) died of CVD by June 2015. Forty-two patients received left-sided RT (1.7% CVD death at 10-years), 34 right-sided RT (1.3% at 10-years). Heart V25Gy did not exceed 10% in any left-sided cases. No cardiac dosimetry parameter distinguished left-sided cases from controls. / Conclusions: QUANTEC guidelines were not violated in any patient that died of CVD after left-sided RT. The risk of radiation induced cardiac death at 10-years appears to be very low if MHD is <3.3 Gy and maximum LAD dose (EQD23 Gy) is <45.4 Gy. Further studies are needed to evaluate heart and LAD constraints in the CT-planning era

Willingness to Self-Collect a Sample for HPV-Based Cervical Cancer Screening in a Well-Screened Cohort: HPV FOCAL Survey Results

Self-collection may provide an opportunity for innovation within population-based human papillomavirus (HPV) cervical cancer screening programs by providing an alternative form of engagement for all individuals. The primary objective was to determine willingness to self-collect a vaginal sample for primary HPV screening and factors that impact willingness in individuals who participated in the Human Papillomavirus For Cervical Cancer (HPV FOCAL) screening trial, a large randomized controlled cervical screening trial. A cross-sectional online survey was distributed between 2017 and 2018 to 13,176 eligible participants exiting the FOCAL trial. Bivariate and multivariable logistic regression assessed factors that influence willingness to self-collect on 4945 respondents. Overall, 52.1% of respondents indicated willingness to self-collect an HPV sample. In multivariable analysis, the odds of willingness to self-collect were significantly higher in participants who agreed that screening with an HPV test instead of a Pap test was acceptable to them (odds ratio (OR): 1.45 (95% confidence interval (CI): 1.15, 1.82), those who indicated that collecting their own HPV sample was acceptable to them (p < 0.001), and those with higher educational ascertainment (OR: 1.31, 95% CI: 1.12, 1.54). The findings offer insight into the intentions to self-collect in those already engaged in screening, and can inform cervical cancer screening programs interested in offering alternative approaches to HPV-based screening.Medicine, Faculty ofNon UBCReviewedFacultyResearche

Colposcopy referral rates post-introduction of primary screening with human papillomavirus testing: evidence from a large British Columbia cohort studyResearch in context

Summary: Background: Shifting from cytology to human papillomavirus (HPV)-based cervical cancer screening will initially increase colposcopy referrals. The anticipated impact on health systems has been raised as a concern for implementation. It is unclear if the higher rate of colposcopy referrals is sustained after initial HPV-based screens or reverts to new lower baselines due to earlier detection and treatment of precancer. This study aimed to investigate long-term rates of colposcopy referrals after participation in HPV-based screening. Methods: Participants of HPV for Cervical Cancer Screening trial (HPV FOCAL) received one (HPV1, N = 6204) or two (HPV2, N = 9540) HPV-based screens. After exit, they returned to British Columbia's (BC) cytology screening program. A comparison cohort from the BC screening population (BCS, N = 1,140,745) was identified, mirroring trial inclusion criteria. All participants were followed for 10–14 years through the provincial screening registry. Colposcopy referral rates per 1000 screens were calculated for each group. Trial colposcopy referrals for HPV1 and HPV2 were calculated under two referral scenarios: (1) all HPV positive referred to colposcopy; (2) cytology triage with ASCUS or greater referred to colposcopy. Colposcopy referrals from post-trial screens in HPV1 an HPV2 and all screens in BCS were based on actual recommendations from the screening program. A multivariable flexible survival regression model compared hazard ratios (HR) throughout follow-up. Findings: Scenario 2 referral rates were higher during initial HPV screen(s) vs cytology screen (HPV1: 28 per 1000 screens (95% CI: 24, 33), HPV2: 32 per 1000 screens (95% CI: 29, 36), BCS: 8 per 1000 screens (95% CI: 8.9)). However, post-trial rates in HPV1 and HPV2 were significantly lower than in BCS. Cumulative rates in HPV1 and HPV2 approached the cumulative rate in BCS 11–12 years after HPV-based screening (HPV1: 11 per 1000 screens (95% CI: 10, 12), HPV2: 16 per 1000 screens (95% CI: 15–17), BCS: 11 per 1000 screens (95% CI: 10, 11)). Adjusted models demonstrated reductions in referral rates in HPV1 (HR = 0.6, 95% CI: 0.5, 0.7) and HPV2 (HR = 0.7, 95% CI: 0.6, 0.8) relative to BCS by 54 and 72 months post-final HPV screen respectively. Interpretation: Reduced colposcopy referral rates were observed after initial rounds of HPV-based screening. After initial HPV screening, referral rates to colposcopy after cytology triage were below the current rates seen in a centralized cytology program after approximately four years. Any expected increase in referrals at initiation of HPV-based screening could be countered by staged program implementation. Funding: This work was supported by the National Institutes of Health (R01 CA221918), Michael Smith Health Research BC (RT-2021-1595), and the Canadian Institutes of Health Research (MCT82072)