Early-Life Exposures and Adult Cancer Risk: A Life Course Approach to Cancer Prevention

Background Despite emerging evidence indicating the potential importance of early-life exposures for adult cancer risk, there is limited research investigating cancer risk factors in early-life. The goals of this dissertation are to 1) elucidate whether maternal adiposity influences epigenetic processes in the offspring relevant to obesity and carcinogenesis and 2) inform primary cancer prevention strategies by addressing two modifiable, early-life risk factors: human papillomavirus (HPV) in males and unhealthy diet in postpartum teens. Methods Study 1: We evaluated the association of maternal pre-pregnancy body mass index (BMI) and gestational weight gain (GWG) with umbilical cord blood DNA methylation in a prospective study of 112 black and white mothers and infants, enrolled in Baltimore, MD, 2006-2007. Study 2: We identified predictors of HPV vaccination using electronic medical record data from 14,688 males aged 11-26 years in Maryland, 2012-2013. Study 3: We examined associations of perceived school and home food environments with dietary behaviors using baseline data from 853 postpartum teens enrolled in a weight-loss intervention study across 27 states, 2007-2009. Questionnaire items measuring perceived access to healthful items were used to categorize environments as “positive” or “negative”. Results Study 1: Maternal pre-pregnancy BMI and GWG were significantly associated with DNA methylation in several CpG sites within 17 candidate genes. A majority of these associations were sex-specific. Study 2: Approximately 15% of males initiated the HPV vaccine. Non-Hispanic black males (vs. non-Hispanic white) and publicly insured males (vs. private), were more likely to initiate the HPV vaccine, but less likely to receive subsequent doses. Frequent clinic visits (>3) were associated with increased uptake of all three doses. Study 3: A positive school environment was related to healthful eating behaviors such as fruit consumption. In contrast, a positive home environment was associated with frequent consumption of a wider variety of healthful items as well as infrequent consumption of unhealthful food and beverages. Conclusion Early-life is an important, yet understudied period with respect to cancer risk. A better understanding of early-life factors from both an etiologic and primary prevention perspective will help to inform interventions that may substantially impact current cancer prevention strategies

Bowhead and Beluga Whale Distributions, Sighting Rates, and Habitat Associations in the Western Beaufort Sea in Summer and Fall 2009–16, with Comparison to 1982–91

We analyzed data from line-transect aerial surveys for marine mammals conducted in the western Beaufort Sea (shore to 72˚ N, 140˚–157˚ W) from July to October of 2009–16 to investigate the distribution, behaviors, sighting rates, and habitat use preferences of bowhead and beluga whales. The habitat use data allowed for direct comparison with data collected in the same area from 1982 to 1991. Both species are ice-adapted, migrating through leads in sea ice in spring, and are seasonal inhabitants of the western Beaufort Sea during summer and fall. From 2009 to 2016, bowheads were seen in all survey months, with the highest overall sighting rate (whales per km) in August. Bowhead sighting rates were highest in the whales’ preferred habitats: outer shelf habitat (51–200 m depth) in July and inner shelf-shallow habitat (≤ 20 m depth) in August, September, and October. Beluga whales were also seen in all survey months, with highest overall sighting rate in July. Beluga whales were overwhelmingly associated with continental slope habitat (201–2000 m depth) in all months. Bowhead distribution and depth preferences in summer months of 2009–16 differed from those observed in 1982–91, when bowheads were not seen during limited survey effort in July and preferred outer continental shelf habitat in August. These differences indicate that bowhead whale preference for shallow shelf habitat now occurs earlier in summer than it used to. Beluga distribution and depth preference remained similar between 1982–91 and 2009–16, with strong preference for continental slope during both periods. Differences in sea ice cover habitat association for both species are likely due more to the relative lack of sea ice in recent years compared to the earlier period than to shifts in habitat preference. Habitat partitioning between bowhead and beluga whales in the western Beaufort Sea remained evident except in July, when both species used continental slope habitat. In July – October 2009–16, the distribution, sighting rates, and behavior of both bowheads and belugas in the western Beaufort showed considerable interannual variation, which underscores the importance of annual sampling to accurate records of the complex western Beaufort Sea ecosystem.Nous avons analysé les données découlant de levés aériens de transects linéaires pour mammifères marins, levés effectués dans l’ouest de la mer de Beaufort (de la rive jusqu’à 72˚ N, et de 140˚ jusqu’à 157˚ O) de juillet à octobre 2009 à 2016. Ces levés avaient pour but d’étudier la distribution, les comportements, les taux d’observation ainsi que les préférences d’utilisation de l’habitat des baleines boréales et des bélugas. Les données relatives à l’utilisation de l’habitat ont permis d’établir des comparaisons directes avec les données recueillies dans le même secteur de 1982 à 1991. Ces deux espèces sont adaptées à la glace, migrent par des chenaux formés dans la glace de mer au printemps et sont des habitants saisonniers de l’ouest de la mer de Beaufort pendant l’été et l’automne. Entre 2009 et 2016, des baleines boréales ont été aperçues pendant tous les mois visés par les levés, le taux d’observation général le plus élevé (nombre de baleines par km) ayant été enregistré au mois d’août. Les taux d’observation des baleines boréales étaient les plus élevés dans les habitats préférés de ces baleines, soit l’habitat de la plateforme externe (de 51 m à 200 m de profondeur) en juillet et l’habitat de la plateforme interne peu profonde (≤ 20 m de profondeur) en août, en septembre et en octobre. Des bélugas ont également été aperçus pendant tous les mois visés par les levés, le taux d’observation général le plus élevé ayant été enregistré en juillet. Les bélugas étaient massivement associés à l’habitat de la pente continentale (de 201 m à 2 000 m de profondeur) pendant tous les mois. La distribution et les préférences de profondeur des baleines boréales pendant les mois d’été 2009 à 2016 différaient de celles observées de 1982 à 1991, lorsque les baleines boréales n’ont pas été aperçues dans le cadre des quelques levés qui ont été effectués en juillet et préféraient leur habitat de la plateforme continentale externe en août. Ces différences indiquent que la préférence des baleines boréales pour l’habitat de la plateforme peu profonde se manifeste maintenant plus tôt l’été qu’auparavant. De 1982 à 1991 et de 2009 à 2016, la distribution des bélugas et leur préférence de profondeur sont restées semblables, avec une préférence marquée pour la pente continentale pendant les deux périodes. Pour les deux espèces, les différences sur le plan de l’association de la couverture de glace marine sont vraisemblablement davantage attribuables au manque relatif de glace de mer ces dernières années comparativement à la période précédente plutôt qu’à une variation de la préférence de l’habitat. Dans l’ouest de la mer de Beaufort, la séparation de l’habitat entre les baleines boréales et les bélugas demeurait évidente, sauf en juillet, quand les deux espèces utilisaient l’habitat de la pente continentale. De juillet à octobre 2009 à 2016, la distribution, les taux d’observation et le comportement des baleines boréales et des bélugas dans l’ouest de la mer de Beaufort ont affiché une variation considérable d’une année à l’autre, ce qui fait ressortir l’importance de faire des échantillonnages annuels afin d’obtenir des données précises au sujet de l’écosystème complexe de l’ouest de la mer de Beaufort

Reporting and Assessing the Quality of Diagnostic Accuracy Studies for Cervical Cancer Screening and Management.

ObjectiveWe adapted the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool for studies of cervical cancer screening and management and used the adapted tool to evaluate the quality of studies included in a systematic review supporting the 2019 Risk-Based Management Consensus Guidelines.MethodsWe evaluated the quality of all studies included in our systematic review for postcolposcopy (n = 5) and posttreatment (n = 23) surveillance using QUADAS-2 criteria. Subsequently, we adapted signaling questions to indications of cervical cancer screening and management. An iterative process was carried out to evaluate interrater agreement between 2 study authors (M.A.C. and N.W.). Discrepant ratings were discussed, and criteria were adapted accordingly. We also evaluated the influence of study quality on risk estimates and between study variation using stratified subgroup meta-analyses.ResultsTwelve signaling questions for bias assessment that were adapted to or newly developed for cervical cancer screening and management are described here. Interrater agreement on bias assessment increased from 70% to 83% during the adaptation process. Detailed assessment of bias and applicability showed that all studies on postcolposcopy management and 90% of studies on posttreatment management had high risk of bias in at least 1 domain. Most commonly, high risk of bias was observed for the patient selection domain, indicating the heterogeneity of study designs and clinical practice in reported studies.ConclusionsThe adapted QUADAS-2 will have broad application for researchers, evidence evaluators, and journals who are interested in designing, conducting, evaluating, and publishing studies for cervical cancer screening and management

Influence of home and school environments on specific dietary behaviors among postpartum, high-risk teens, 27 states, 2007-2009

INTRODUCTION: The objective of this study was to determine whether perceptions of the home and school food environments are related to food and beverage intakes of postpartum teens. METHODS: Our study was a baseline, cross-sectional analysis of 853 postpartum teens enrolled in a weight-loss intervention study across 27 states from 2007 through 2009. Eight-item scales assessed perceived accessibility and availability of foods and beverages in school and home environments. Associations between environments and intakes were assessed by using χ(2) and using logistic regression with generalized estimating equations (GEE), respectively. RESULTS: Overall, 52% of teens perceived their school food environment as positive, and 68% of teens perceived their home food environment as positive. A positive school environment was independently associated with fruit consumption and 100% fruit juice consumption. A positive home environment was independently associated with fruit, vegetable, and water consumption and infrequent consumption of soda and chips (χ(2) P < .05). Having only a positive school environment was associated with fruit consumption (GEE odds ratio [OR], 3.1; 95% confidence interval [CI], 1.5–6.5), and having only a positive home environment was associated with fruit (GEE OR, 2.9; 95% CI, 1.6–5.6), vegetable (GEE OR, 3.1; 95% CI, 1.5–6.2), and water (GEE OR, 2.6; 95% CI, 1.7–4.0) consumption and infrequent consumption of soda (GEE OR, 0.5; 95% CI, 0.3–0.7). Results for positive home and school environments were similar to those for positive home only. CONCLUSION: Home and school environments are related to dietary behaviors among postpartum teens, with a positive home environment more strongly associated with healthful behaviors

Is Content Really King? An Objective Analysis of the Public's Response to Medical Videos on YouTube

Medical educators and patients are turning to YouTube to teach and learn about medical conditions. These videos are from authors whose credibility cannot be verified & are not peer reviewed. As a result, studies that have analyzed the educational content of YouTube have reported dismal results. These studies have been unable to exclude videos created by questionable sources and for non-educational purposes. We hypothesize that medical education YouTube videos, authored by credible sources, are of high educational value and appropriately suited to educate the public. Credible videos about cardiovascular diseases were identified using the Mayo Clinic's Center for Social Media Health network. Content in each video was assessed by the presence/absence of 7 factors. Each video was also evaluated for understandability using the Suitability Assessment of Materials (SAM). User engagement measurements were obtained for each video. A total of 607 videos (35 hours) were analyzed. Half of all videos contained 3 educational factors: treatment, screening, or prevention. There was no difference between the number of educational factors present & any user engagement measurement (p NS). SAM scores were higher in videos whose content discussed more educational factors (p<0.0001). However, none of the user engagement measurements correlated with higher SAM scores. Videos with greater educational content are more suitable for patient education but unable to engage users more than lower quality videos. It is unclear if the notion “content is king� applies to medical videos authored by credible organizations for the purposes of patient education on YouTube

Planetary Candidates Observed by Kepler. VIII. A Fully Automated Catalog With Measured Completeness and Reliability Based on Data Release 25

We present the Kepler Object of Interest (KOI) catalog of transiting exoplanets based on searching four years of Kepler time series photometry (Data Release 25, Q1-Q17). The catalog contains 8054 KOIs of which 4034 are planet candidates with periods between 0.25 and 632 days. Of these candidates, 219 are new and include two in multi-planet systems (KOI-82.06 and KOI-2926.05), and ten high-reliability, terrestrial-size, habitable zone candidates. This catalog was created using a tool called the Robovetter which automatically vets the DR25 Threshold Crossing Events (TCEs, Twicken et al. 2016). The Robovetter also vetted simulated data sets and measured how well it was able to separate TCEs caused by noise from those caused by low signal-to-noise transits. We discusses the Robovetter and the metrics it uses to sort TCEs. For orbital periods less than 100 days the Robovetter completeness (the fraction of simulated transits that are determined to be planet candidates) across all observed stars is greater than 85%. For the same period range, the catalog reliability (the fraction of candidates that are not due to instrumental or stellar noise) is greater than 98%. However, for low signal-to-noise candidates between 200 and 500 days around FGK dwarf stars, the Robovetter is 76.7% complete and the catalog is 50.5% reliable. The KOI catalog, the transit fits and all of the simulated data used to characterize this catalog are available at the NASA Exoplanet Archive.Comment: 61 pages, 23 Figures, 9 Tables, Accepted to The Astrophysical Journal Supplement Serie

A population-based cross-sectional study of age-specific risk factors for high risk human papillomavirus prevalence in rural Nigeria

<p>Abstract</p> <p>Background</p> <p>Cervical cancer, caused by persistent infection with carcinogenic human papillomavirus (HR-HPV), is particularly prevalent in Sub-Saharan Africa and is associated with a high mortality rate. Some studies in West Africa, including our own, have found unusually high HR-HPV across all ages with a slight peak in older women. This increased prevalence at older ages may complicate screen-and-treat programs, which are implemented in regions where HPV prevalence declines with age and typically target women between 30-49 years. A better understanding of the determinants of high HR-HPV prevalence at older ages is needed. The goal of this study is to explore risk factors for HR-HPV prevalence by age among women in our population-based study in Irun, a rural town in southwestern Nigeria.</p> <p>Methods</p> <p>1,420 women were administered a clinic-based questionnaire regarding sexual and reproductive behavior, marital status (including co-wives), and malaria exposure. Logistic regression compared questionnaire responses and PCR positivity for a set of 13 carcinogenic HR-HPV types. Results were stratified by age (15-29, 30-45, 46-55, and 56+ years).</p> <p>Results</p> <p>Birth control use and age at first pregnancy were associated with HR-HPV (<it>p-value </it>= 0.03 and 0.05, respectively). Early age at sexual debut and multiple sex partners were risks for HR-HPV, but did not reach significance (<it>p-value </it>= 0.1 and 0.07, respectively). Neither self-reported malaria nor presence of co-wives in the household was associated with HR-HPV (<it>p-value </it>= 0.85 and 0.24, respectively). In age sub-categories, early age at sexual debut was a significant risk factor for HR-HPV among women 35-45 years (<it>p-value = 0.02</it>). Early age at first pregnancy remained a significant risk factor for women aged 56+ years (<it>p-value </it>= 0.04). Greater than 2 sex partners and use of birth control were associated (though not significantly) with HR-HPV in women aged 30-45 (<it>p-value </it>= 0.08, respectively).</p> <p>Conclusions</p> <p>In this high-risk region with elevated HR-HPV prevalence at older ages, we confirmed previously described, behavioral determinants of HR-HPV. There was no association with self-reported malaria or co-wives, which we had hypothesized might correlate with HR-HPV at older ages.</p

Money, Love, and Fragile Reciprocity in Contemporary Havana, Cuba

Among low-income Havana residents, men frequently give money and other forms of material support to women in whom they have a romantic interest. For women, men's material contributions are expressions of responsibility and care. While men share this view to a degree, they sometimes have more ambiguous emotions regarding such practices. These tensions in different views of gendered reciprocity are influenced by large-scale changes that have taken place in Cuban society since the 1990s. Although, traditionally, state socialism has embraced ideas of gender egalitarianism and women's independent income, the post-Soviet period has seen the emergence of new inequalities, dependencies, and marginalizations that threaten earlier, socialist understandings of intimacy. The importance that women currently place on material wealth in terms of their views of a desirable partner highlights the gendered consequences of Cuba's contemporary economic transformations and their complex interplay with individuals' aspirations for love.Peer reviewe

Transcriptome dynamics of CD4⁺ T cells during malaria maps gradual transit from effector to memory

The dynamics of CD4⁺ T cell memory development remain to be examined at genome scale. In malaria-endemic regions, antimalarial chemoprevention protects long after its cessation and associates with effects on CD4⁺ T cells. We applied single-cell RNA sequencing and computational modelling to track memory development during Plasmodium infection and treatment. In the absence of central memory precursors, two trajectories developed as T helper 1 (T_H1) and follicular helper T (T_(FH)) transcriptomes contracted and partially coalesced over three weeks. Progeny of single clones populated T_H1 and T_(FH) trajectories, and fate-mapping suggested that there was minimal lineage plasticity. Relationships between T_(FH) and central memory were revealed, with antimalarials modulating these responses and boosting T_H1 recall. Finally, single-cell epigenomics confirmed that heterogeneity among effectors was partially reset in memory. Thus, the effector-to-memory transition in CD4⁺ T cells is gradual during malaria and is modulated by antiparasitic drugs. Graphical user interfaces are presented for examining gene-expression dynamics and gene–gene correlations (http://haquelab.mdhs.unimelb.edu.au/cd4_memory/)