Immunological and molecular features of the tumor microenvironment of long-term survivors of ovarian cancer.

BACKGROUND: Despite an overall poor prognosis, about 15% of patients with advanced-stage tubo-ovarian high-grade serous carcinoma (HGSC) survive ten or more years after standard treatment. METHODS: We evaluated the tumor microenvironment of this exceptional, understudied group using a large international cohort enriched for long-term survivors (LTS; 10+ years; n = 374) compared to medium-term (MTS; 5-7.99 years; n = 433) and short-term survivors (STS; 2-4.99 years; n = 416). Primary tumor samples were immunostained and scored for intra-epithelial and intra-stromal densities of 10 immune-cell subsets (including T cells, B cells, plasma cells, myeloid cells, PD-1+ cells, and PD-L1+ cells) and epithelial content. RESULTS: Positive associations with LTS compared to STS were seen for 9/10 immune-cell subsets. In particular, the combination of intra-epithelial CD8+ T cells and intra-stromal B cells showed near five-fold increased odds of LTS compared to STS. All of these associations were stronger in tumors with high epithelial content and/or the C4/Differentiated molecular subtype, despite immune-cell densities generally being higher in tumors with low epithelial content and/or the C2/Immunoreactive molecular subtype. CONCLUSIONS: The tumor microenvironment of HGSC long-term survivors is distinguished by the intersection of T and B cell co-infiltration, high epithelial content and C4/Differentiated molecular subtype, features which may inspire new approaches to immunotherapy. FUNDING: Ovarian Cancer Research Program (OCRP) of the Congressionally Directed Medical Research Program (CDMRP), U.S. Department of Defense (DOD); American Cancer Society; BC Cancer Foundation; Canada's Networks of Centres of Excellence; Canadian Cancer Society; Canadian Institutes of Health Research; Cancer Councils of New South Wales, Victoria, Queensland, South Australia and Tasmania, Cancer Foundation of Western Australia; Cancer Institute NSW; Cancer Research UK; Deutsche Forschungsgesellschaft; ELAN Funds of the University of Erlangen-Nuremberg; Fred C. and Katherine B. Andersen Foundation; Genome BC; German Cancer Research Center; German Federal Ministry of Education and Research, Programme of Clinical Biomedical Research; Instituto de Salud Carlos III; Mayo Foundation; Minnesota Ovarian Cancer Alliance; Ministerio de Economía y Competitividad; MRC; National Center for Advancing Translational Sciences; National Health and Medical Research Council of Australia (NHMRC); Ovarian Cancer Australia; Peter MacCallum Foundation; Sydney West Translational Cancer Research Centre; Terry Fox Research Institute; The Eve Appeal (The Oak Foundation); UK National Institute for Health Research Biomedical Research Centres at the University of Cambridge; University of Pittsburgh School of Medicine; U.S. National Cancer Institute of the National Institutes of Health; VGH & UBC Hospital Foundation; Victorian Cancer Agency.

Metformin use and survival in people with ovarian cancer: A population-based cohort study from British Columbia, Canada.

OBJECTIVES: There is an active debate regarding whether metformin use improves survival in people with ovarian cancer. We examined this issue using methods designed to avoid immortal time bias-as bias that occurs when participants in a study cannot experience the outcome for a certain portion of the study time. METHODS: We used time-dependent analyses to study the association between metformin use for all 4,951 patients diagnosed with ovarian cancer in 1997 through 2018 in the province of British Columbia, Canada. Cox proportional hazards models were run to estimate the association between metformin and survival in the full cohort of ovarian cancer patients and among a cohort restricted to patients with diabetes. RESULTS: Metformin use was associated with a 17 % better ovarian cancer survival in the full cohort (adjusted hazard ratio (aHR) = 0.83 (95 %CI 0.67, 1.02)), and a 16 % better ovarian cancer survival for serous cancers patient's cohort (aHR = 0.84 (95 %CI 0.66, 1.07)), although both were not significant. However, a statistically significant protective effect was observed when restricting to the diabetic cohort (aHR = 0.71 (95 %CI 0.54-0.91)), which was also seen among serous cancers (aHR = 0.73 (95 %CI 0.54-0.98)). CONCLUSION: Metformin use was associated with improved ovarian cancer survival. The lack of statistical significance in the full cohort may reflect that diabetes is associated with reduced cancer survival, and thus diabetes itself may offset the benefit of metformin when examining the full cohort. Future research should examine metformin use among non-diabetic ovarian cancer patients.

Pre-diagnosis tea and coffee consumption and survival after a diagnosis of ovarian cancer: results from the Ovarian Cancer Association Consortium.

BACKGROUND: Tea and coffee are the most frequently consumed beverages in the world. Green tea in particular contains compounds with potential anti-cancer effects, but its association with survival after ovarian cancer is uncertain. METHODS: We investigated the associations between tea and coffee consumption before diagnosis and survival using data from 10 studies in the Ovarian Cancer Association Consortium. Data on tea (green, black, herbal), coffee and caffeine intake were available for up to 5724 women. We used Cox proportional hazards regression to estimate adjusted hazard ratios (aHR) and 95% confidence intervals (CI). RESULTS: Compared with women who did not drink any green tea, consumption of one or more cups/day was associated with better overall survival (aHR = 0.84, 95% CI 0.71-1.00, p-trend = 0.04). A similar association was seen for ovarian cancer-specific survival in five studies with this information (aHR = 0.81, 0.66-0.99, p-trend = 0.045). There was no consistent variation between subgroups defined by clinical or lifestyle characteristics and adjustment for other aspects of lifestyle did not appreciably alter the estimates. We found no evidence of an association between coffee, black or herbal tea, or caffeine intake and survival. CONCLUSION: The observed association with green tea consumption before diagnosis raises the possibility that consumption after diagnosis might improve patient outcomes.

Variance components of sex determination in the copepod Tigriopus californicus estimated from a pedigree analysis.

Extensive theory exists regarding population sex ratio evolution that predicts equal sex ratio (when parental investment is equal). In most animals, sex chromosomes determine the sex of offspring, and this fixed genotype for sex has made theory difficult to test since genotypic variance for the trait (sex) is lacking. It has long been argued that the genotype has become fixed in most animals due to the strong selection for equal sex ratios. The marine copepod Tigriopus californicus has no sex chromosomes, multiple genes affecting female brood sex ratio, and a brood sex ratio that responds to selection. The species thus provides an opportune system in which to test established sex ratio theory. In this paper, we further our exploration of polygenic sex determination in T. californicus using an incomplete diallel crossing design for analysis of the variance components of sex determination in the species. Our data confirm the presence of extra-binomial variance for sex, further confirming that sex is not determined through simple Mendelian trait inheritance. In addition, our crosses and backcrosses of isofemale lines selected for biased brood sex ratios show intermediate phenotypic means, as expected if sex is a threshold trait determined by an underlying "liability" trait controlled by many genes of small effects. Furthermore, crosses between families from the same selection line had similar increases in phenotypic variance as crosses between families from different selection lines, suggesting families from artificial selection lines responded to selection pressure through different underlying genetic bases. Finally, we estimate heritability of an individual to be male or female on the observed binary scale as 0.09 (95% CI: 0.034-0.14). This work furthers our accumulating evidence for polygenic sex determination in T. californicus laying the foundation for this as a model species in future studies of sex ratio evolution theory.

Lifestyle and personal factors associated with having macroscopic residual disease after ovarian cancer primary cytoreductive surgery.

OBJECTIVE: The presence of macroscopic residual disease after primary cytoreductive surgery (PCS) is an important factor influencing survival for patients with high-grade serous ovarian cancer (HGSC). More research is needed to identify factors associated with having macroscopic residual disease. We analyzed 12 lifestyle and personal exposures known to be related to ovarian cancer risk or inflammation to identify those associated with having residual disease after surgery. METHODS: This analysis used data on 2054 patients with advanced stage HGSC from the Ovarian Cancer Association Consortium. The exposures were body mass index, breastfeeding, oral contraceptive use, depot-medroxyprogesterone acetate use, endometriosis, first-degree family history of ovarian cancer, incomplete pregnancy, menopausal hormone therapy use, menopausal status, parity, smoking, and tubal ligation. Logistic regression models were fit to assess the association between these exposures and having residual disease following PCS. RESULTS: Menopausal estrogen-only therapy (ET) use was associated with 33% lower odds of having macroscopic residual disease compared to never use (OR = 0.67, 95%CI 0.46-0.97, p = 0.033). Compared to nulliparous women, parous women who did not breastfeed had 36% lower odds of having residual disease (OR = 0.64, 95%CI 0.43-0.94, p = 0.022), while there was no association among parous women who breastfed (OR = 0.90, 95%CI 0.65-1.25, p = 0.53). CONCLUSIONS: The association between ET and having no macroscopic residual disease is plausible given a strong underlying biologic hypothesis between this exposure and diagnosis with HGSC. If this or the parity finding is replicated, these factors could be included in risk stratification models to determine whether HGSC patients should receive PCS or neoadjuvant chemotherapy.

Reproductive Factors Do Not Influence Survival with Ovarian Cancer.

BACKGROUND: Previous studies on the association between reproductive factors and ovarian cancer survival are equivocal, possibly due to small sample sizes. METHODS: Using data on 11,175 people diagnosed with primary invasive epithelial ovarian, fallopian tube, or primary peritoneal cancer (ovarian cancer) from 16 studies in the Ovarian Cancer Association Consortium (OCAC), we examined the associations between survival and age at menarche, combined oral contraceptive use, parity, breastfeeding, age at last pregnancy, and menopausal status using Cox proportional hazard models. The models were adjusted for age at diagnosis, race/ethnicity, education level, and OCAC study and stratified on stage and histotype. RESULTS: During the mean follow-up of 6.34 years (SD = 4.80), 6,418 patients passed away (57.4%). There was no evidence of associations between the reproductive factors and survival among patients with ovarian cancer overall or by histotype. CONCLUSIONS: This study found no association between reproductive factors and survival after an ovarian cancer diagnosis. IMPACT: Reproductive factors are well-established risk factors for ovarian cancer, but they are not associated with survival after a diagnosis of ovarian cancer.

High Prediagnosis Inflammation-Related Risk Score Associated with Decreased Ovarian Cancer Survival.

BACKGROUND: There is suggestive evidence that inflammation is related to ovarian cancer survival. However, more research is needed to identify inflammation-related factors that are associated with ovarian cancer survival and to determine their combined effects. METHODS: This analysis used pooled data on 8,147 women with invasive epithelial ovarian cancer from the Ovarian Cancer Association Consortium. The prediagnosis inflammation-related exposures of interest included alcohol use; aspirin use; other nonsteroidal anti-inflammatory drug use; body mass index; environmental tobacco smoke exposure; history of pelvic inflammatory disease, polycystic ovarian syndrome, and endometriosis; menopausal hormone therapy use; physical inactivity; smoking status; and talc use. Using Cox proportional hazards models, the relationship between each exposure and survival was assessed in 50% of the data. A weighted inflammation-related risk score (IRRS) was developed, and its association with survival was assessed using Cox proportional hazards models in the remaining 50% of the data. RESULTS: There was a statistically significant trend of increasing risk of death per quartile of the IRRS [HR = 1.09; 95% confidence interval (CI), 1.03-1.14]. Women in the upper quartile of the IRRS had a 31% higher death rate compared with the lowest quartile (95% CI, 1.11-1.54). CONCLUSIONS: A higher prediagnosis IRRS was associated with an increased mortality risk after an ovarian cancer diagnosis. Further investigation is warranted to evaluate whether postdiagnosis exposures are also associated with survival. IMPACT: Given that pre- and postdiagnosis exposures are often correlated and many are modifiable, our study results can ultimately motivate the development of behavioral recommendations to enhance survival among patients with ovarian cancer.

Cardiovascular medications and survival in people with ovarian cancer: A population-based cohort study from British Columbia, Canada.

OBJECTIVES: Research examining survival among people with ovarian cancer following use of statins or ß-blockers has been conflicting. Many studies to date have suffered from immortal time bias and/or had limited power. To address these limitations, we used time-dependent analyses to study the association between statin or ß-blocker use among all people diagnosed with an epithelial ovarian cancer in British Columbia, Canada between 1997 and 2015. METHODS: Population-based administrative data were linked for 4207 people with ovarian cancer. Statin or ß-blocker use was examined using time-dependent variables for any use, cumulative duration of use and by user-group according to whether use was initiated before or after their ovarian cancer diagnosis. Cox proportional hazards models were run to estimate the association between statin or ß-blocker use and survival. RESULTS: Any postdiagnosis use of statins was associated with better ovarian cancer survival in the full cohort (adjusted hazard ratio (aHR) = 0.76, 95% CI 0.64, 0.89) and among women with serous cancers (aHR = 0.80, 95%CI 0.67-0.96). This was primarily driven by new use post-diagnosis (aHR = 0.67, 95%CI, 0.51-0.89), but there was a trend towards better survival among those who continued use from before diagnosis (aHR 0.83, 95%CI, 0.68-1.00). There was no statistically significant association between ß-blocker use and survival. CONCLUSION: Postdiagnosis statin use was associated with improved survival among people with ovarian cancer. Given the consistency of this finding in the literature, we recommend a randomized clinical trial of statin use in people with ovarian cancer.

Sun protection changes among diverse elementary schoolchildren participating in a sun safety intervention: A latent transition analysis of a randomized controlled trial.

Children are a priority population for skin cancer prevention as excessive sun exposure in childhood increases the risk of melanoma in adulthood. The complexity of sun protective behaviors has posed measurement challenges for trials testing intervention efficacy. The current study evaluated a sun safety intervention for schoolchildren using latent transition analysis (LTA) to examine patterns of sun protection behaviors over time. A three-armed randomized controlled trial was conducted between 2012 and 2016 with two intervention groups (N = 3368) and an observation-only control group (N = 342) among 4th and 5th graders from 24 public schools in Los Angeles County. Both interventions conditions were grouped and compared to controls. Five self-reported sun protective behaviors were measured at baseline and three-month follow-up: use of sunscreen, long sleeves, long pants, hats, and shade seeking. Participants comprised 3710 schoolchildren, mean age 9 years, 47% female and 69% Latino. At baseline, four patterns of sun protection behaviors were found: children who engaged in 1) all sun protective behaviors; 2) few protective behaviors; 3) protective clothing and shade only; and 4) hats only. Children in the control group were likely to remain in their baseline status or transition to a less protective status at three-month follow-up. By contrast, 30% of children in the intervention group transitioned to a more protective status at follow-up. In this RCT of a sun safety intervention, children in the intervention transitioned to more protective behaviors compared to controls. Using LTA enriches understanding of intervention efficacy by modeling the complexity of sun protection behaviors over time. TRIAL REGISTRATION: School-based Randomized Trial of SunSmart Interventions, ClinicalTrials.gov Identifier: NCT04176237 https://clinicaltrials.gov/ct2/show/NCT04176237?cond=School-based+Randomized+Trial+of+SunSmart+Interventions&draw=2&rank=1.

Menopausal hormone therapy prior to the diagnosis of ovarian cancer is associated with improved survival.

PURPOSE: Prior studies of menopausal hormone therapy (MHT) and ovarian cancer survival have been limited by lack of hormone regimen detail and insufficient sample sizes. To address these limitations, a comprehensive analysis of 6419 post-menopausal women with pathologically confirmed ovarian carcinoma was conducted to examine the association between MHT use prior to diagnosis and survival. METHODS: Data from 15 studies in the Ovarian Cancer Association Consortium were included. MHT use was examined by type (estrogen-only (ET) or estrogen+progestin (EPT)), duration, and recency of use relative to diagnosis. Cox proportional hazards models were used to estimate the association between hormone therapy use and survival. Logistic regression and mediation analysis was used to explore the relationship between MHT use and residual disease following debulking surgery. RESULTS: Use of ET or EPT for at least five years prior to diagnosis was associated with better ovarian cancer survival (hazard ratio, 0.80; 95% CI, 0.74 to 0.87). Among women with advanced stage, high-grade serous carcinoma, those who used MHT were less likely to have any macroscopic residual disease at the time of primary debulking surgery (p for trend <0.01 for duration of MHT use). Residual disease mediated some (17%) of the relationship between MHT and survival. CONCLUSIONS: Pre-diagnosis MHT use for 5+ years was a favorable prognostic factor for women with ovarian cancer. This large study is consistent with prior smaller studies, and further work is needed to understand the underlying mechanism.

"I am not a statistic" ovarian cancer survivors' views of factors that influenced their long-term survival.

OBJECTIVE: Although a high proportion of women with advanced stage ovarian cancer die within five years, approximately 30% will survive longer than this. The factors contributing to exceptional survival are currently poorly understood. The viewpoints of ovarian cancer survivors were qualitatively explored to determine the factors they felt have influenced their exceptional ovarian cancer survival. METHODS: Four focus groups, one each in Los Angeles (California), Ann Arbor (Michigan), New York (New York) and Edmonton (Alberta, Canada), were conducted with women who had survived at least five years. Physical activity, diet, meditation, prayer, treatment, complementary medicine, and side effects were explored in semi-structured discussions. The audiotaped sessions were transcribed and coded and then analyzed using Dedoose Version 8.0.35, a qualitative analysis software. RESULTS: Of the 26 women who participated, 23 had advanced stage disease. Three overarching themes emerged: (a) survivors had improved their 'lifestyles', including but not limited to fitness and diet; (b) survivors were able to draw on strong support systems, which included family, friends, support groups, faith communities, and healthcare workers; and (c) survivors had a strong life purpose, which manifested as positivity, taking charge of their lives, and advocating for themselves. CONCLUSIONS: Long-term survivors have varying experiences with their cancer, but identified lifestyle modification, motivation and persistence, strong life purpose, and strong support systems as key elements in their better survival. These preliminary findings indicate the need for further prospective studies to determine whether meaningful differences exist between short term and long term survivors on these characteristics.

Adolescent Substance Use and Sensation-Seeking on Sexual Behaviors Among Young Adults from Continuation High Schools.

BACKGROUND: Youth from continuation high schools report greater substance use and sensation-seeking than youth from regular high schools, yet their long-term consequences on age at sexual onset and the number of sexual partners are unknown. OBJECTIVE: To examine substance use, sensation-seeking and sexual behaviors by gender and race/ethnicity and the effects of substance use and sensation-seeking in adolescence on age at sexual initiation and numbers of sexual partners by young adulthood. METHODS: Baseline and 4-year follow-up data on youth from 14 continuation high schools in Southern California who participated in a drug abuse prevention intervention were analyzed. Structural equation modeling assessed whether or not substance use or sensation-seeking in adolescence predicted age at sexual onset and numbers of sexual partners by young adulthood. RESULTS: Latinos had lower sensation-seeking and frequency of substance use and a later age at sexual onset than non-Latinos. Males were more likely than females to have multiple lifetime and recent sexual partners. The effects of adolescent substance use on the number of sexual partners by young adulthood were mediated fully by their age at sexual initiation. Sensation-seeking had no direct or indirect effects on sexual behaviors. Conclusions/Importance: Factors leading to and actual sexual risk behaviors among youth from continuation high schools vary by race/ethnicity and gender. Targeting these antecedent factors by race/ethnicity and gender may improve prevention efforts.

Correction: The Behavioral Response of Larval Amphibians (Ranidae) to Threats from Predators and Parasites.

[This corrects the article DOI: 10.1371/journal.pone.0049592.].

Prevalence of sun protection behaviors in Hispanic youth residing in a high ultraviolet light environment.

Although rates of late-stage melanoma are rising in Hispanics, particularly those living in high ultraviolet light environments, little is known about the prevalence of sun protective behaviors in Hispanic children. We analyzed baseline data including frequency of sunburn, sun protective behaviors, level of U.S. acculturation, and skin phototype from a cross-sectional survey of 2003 Hispanic elementary school children in Los Angeles, California, who participated in a skin cancer prevention intervention. Although the Hispanic children reported frequently engaging in some sun protective behaviors, they also had a high rate of sunburn (59%) that exceeded previous national estimates for non-Hispanic white children (43%). Fewer U.S.-acculturated children reported more frequent shade-seeking at home (P = .02), along with less shade-seeking at school (P = .001) and more sunscreen use at school (P = .02). The surprisingly high rate of sunburn in Hispanic children suggests that the way in which they are practicing sun protection is not preventing sunburns. Sun safety interventions should be targeted toward Hispanic youth to provide them with practical methods of effective sun protection, in addition to education on the risks of high sun exposure.

Local site differences in survival and parasitism of periwinkles (Littorina sitkana Philippi, 1846).

The periwinkle, Littorina sitkana, is found throughout the intertidal zone, often in isolated subpopulations. The majority of trematode parasites use snails as intermediate hosts, and decreased survivorship is often observed in snails infected with trematodes. Sampling L. sitkana from four sites in Barkley Sound, British Columbia, Canada, we test the effects of parasitic infection on snail survival using maximum likelihood and Bayesian approaches using the software MARK and WinBUGS. We found that survival of periwinkles and trematode community composition differed among sites, but survival and trematode prevalence were uncorrelated. WinBUGS performed better than MARK in two ways: (1) by allowing the use of information on known mortality, thus preventing survival overestimation; and (2) by giving more stable estimates while testing the effect of body size on snail survival. Our results suggest that snail survival depends heavily on local environmental factors that may vary greatly within a small geographical region. These findings are important because the majority of experimental studies on survival are done on snails from a single location.

Correlates of sun protection behaviors among Hispanic children residing in a high UVR environment.

BACKGROUND/PURPOSE: Rates of melanoma are rising in Hispanics in the United States. Excessive sun exposure in childhood increases the risk of melanoma in adulthood, and little is known about the factors motivating sun protection behaviors among Hispanic youth. METHODS: Correlates of sun protection were examined among Hispanic children residing in Los Angeles, California (N = 1891). Associations between multiple constructs (psychosocial, familial, and cultural) and sun protection outcomes (use of sunscreen, protective clothing, and shade seeking/sun avoidance) were examined. RESULTS: Family variables were associated with more frequent sun protection among Hispanic children across outcomes, as were perceived peer norms, perceived self-efficacy, and fewer sun protection barriers. Skin cancer risk factors such as lighter skin and sunburn experience, and level of acculturation were not associated with greater sun protection. CONCLUSION: Family sun protection habits are instrumental to Hispanic children's sun safe behaviors, and interventions that engage the family may be most effective. Increasing risk communication to high-risk subgroups of Hispanic children (those with lighter, more sun reactive skin) is important when developing intervention strategies. However, there is overlap between Hispanic children's sun protection correlates and those observed among non-Hispanic white children, suggesting that interventions to improve sun protection may generalize across cultural contexts.

Patterns of sun protective behaviors among Hispanic children in a skin cancer prevention intervention.

BACKGROUND: Invasive melanoma is becoming more common in U.S. Hispanics, yet little is known about the sun protection behaviors in this population, particularly children and adolescents who incur high ultraviolet (UV) exposures. METHODS: We used latent class analysis to examine patterns of sun protective behaviors in a cross-sectional survey of Hispanic elementary students participating in a sun safety intervention in Los Angeles from 2013- to 2014 (N=972). Five behavior indicators in two environments (school and home) representing multiple methods of sun protection were selected for the model. RESULTS: Results suggested a four-class model best fit the data. Classes were labeled in order of increasing risk as multiple protective behaviors (28%), clothing and shade (32%), pants only (15%), and low/inconsistent protective behaviors (25%). Children who reported high parental engagement with sun protection were significantly more likely to be classified in high overall protective categories (odds ratio (OR)=4.77). Girls were more likely than boys to be classified in the highest protecting class (OR=3.46), but were also more likely to be in the "pants only" class (OR=2.65). Sensitivity to sunburn was associated with less likelihood of being in the "clothing and shade" class (OR=0.53). CONCLUSION: The differences among these classes and their predictors reveal the heterogeneity and complexity of Hispanic children's sun protective behaviors. These findings have implications for the design and delivery of future sun protection interventions targeting Hispanic children, as strategies tailored to specific subgroups may be more effective in achieving meaningful behavioral changes.

Cognitive function in women with HIV: findings from the Women's Interagency HIV Study.

OBJECTIVE: In the largest cohort study of neuropsychological outcomes among HIV-infected women to date, we examined the association between HIV status and cognition in relation to other determinants of cognitive function (aim 1) and the pattern and magnitude of impairment across cognitive outcomes (aim 2). METHODS: From 2009 to 2011, 1,521 (1,019 HIV-infected) participants from the Women's Interagency HIV Study (WIHS) completed a comprehensive neuropsychological test battery. We used multivariable regression on raw test scores for the first aim and normative regression-based analyses (t scores) for the second aim. The design was cross-sectional. RESULTS: The effect sizes for HIV status on cognition were very small, accounting for only 0.05 to 0.09 SD units. The effect of HIV status was smaller than that of years of education, age, race, income, and reading level. In adjusted analyses, HIV-infected women performed worse than uninfected women on verbal learning, delayed recall and recognition, and psychomotor speed and attention. The largest deficit was observed in delayed memory. The association of low reading level with cognition was greater in HIV-infected compared to HIV-uninfected women. HIV biomarkers (CD4 count, history of AIDS-defining illness, viral load) were associated with cognitive dysfunction. CONCLUSIONS: The effect of HIV on cognition in women is very small except among women with low reading level or HIV-related comorbidities. Direct comparisons of rates of impairment in well-matched groups of HIV-infected men and women are needed to evaluate possible sex differences in cognition.

'What's in the NIDDK CDR?'--public query tools for the NIDDK central data repository.

The National Institute of Diabetes and Digestive Disease (NIDDK) Central Data Repository (CDR) is a web-enabled resource available to researchers and the general public. The CDR warehouses clinical data and study documentation from NIDDK funded research, including such landmark studies as The Diabetes Control and Complications Trial (DCCT, 1983-93) and the Epidemiology of Diabetes Interventions and Complications (EDIC, 1994-present) follow-up study which has been ongoing for more than 20 years. The CDR also houses data from over 7 million biospecimens representing 2 million subjects. To help users explore the vast amount of data stored in the NIDDK CDR, we developed a suite of search mechanisms called the public query tools (PQTs). Five individual tools are available to search data from multiple perspectives: study search, basic search, ontology search, variable summary and sample by condition. PQT enables users to search for information across studies. Users can search for data such as number of subjects, types of biospecimens and disease outcome variables without prior knowledge of the individual studies. This suite of tools will increase the use and maximize the value of the NIDDK data and biospecimen repositories as important resources for the research community. Database URL: https://www.niddkrepository.org/niddk/home.do.

Alcohol consumption trajectory patterns in adult women with HIV infection.

HIV-infected women with excessive alcohol consumption are at risk for adverse health outcomes, but little is known about their long-term drinking trajectories. This analysis included longitudinal data, obtained from 1996 to 2006, from 2,791 women with HIV from the Women's Interagency HIV Study. Among these women, the proportion in each of five distinct drinking trajectories was: continued heavy drinking (3 %), reduction from heavy to non-heavy drinking (4 %), increase from non-heavy to heavy drinking (8 %), continued non-heavy drinking (36 %), and continued non-drinking (49 %). Depressive symptoms, other substance use (crack/cocaine, marijuana, and tobacco), co-infection with hepatitis C virus (HCV), and heavy drinking prior to enrollment were associated with trajectories involving future heavy drinking. In conclusion, many women with HIV change their drinking patterns over time. Clinicians and those providing alcohol-related interventions might target those with depression, current use of tobacco or illicit drugs, HCV infection, or a previous history of drinking problems.