Sign language experience has little effect on face and biomotion perception in bimodal bilinguals.

Sensory and language experience can affect brain organization and domain-general abilities. For example, D/deaf individuals show superior visual perception compared to hearing controls in several domains, including the perception of faces and peripheral motion. While these enhancements may result from sensory loss and subsequent neural plasticity, they may also reflect experience using a visual-manual language, like American Sign Language (ASL), where signers must process moving hand signs and facial cues simultaneously. In an effort to disentangle these concurrent sensory experiences, we examined how learning sign language influences visual abilities by comparing bimodal bilinguals (i.e., sign language users with typical hearing) and hearing non-signers. Bimodal bilinguals and hearing non-signers completed online psychophysical measures of face matching and biological motion discrimination. No significant group differences were observed across these two tasks, suggesting that sign language experience is insufficient to induce perceptual advantages in typical-hearing adults. However, ASL proficiency (but not years of experience or age of acquisition) was found to predict performance on the motion perception task among bimodal bilinguals. Overall, the results presented here highlight a need for more nuanced study of how linguistic environments, sensory experience, and cognitive functions impact broad perceptual processes and underlying neural correlates.

Hybrid feature engineering of medical data via variational autoencoders with triplet loss: a COVID-19 prognosis study.

Medical machine learning frameworks have received much attention in recent years. The recent COVID-19 pandemic was also accompanied by a surge in proposed machine learning algorithms for tasks such as diagnosis and mortality prognosis. Machine learning frameworks can be helpful medical assistants by extracting data patterns that are otherwise hard to detect by humans. Efficient feature engineering and dimensionality reduction are major challenges in most medical machine learning frameworks. Autoencoders are novel unsupervised tools that can perform data-driven dimensionality reduction with minimum prior assumptions. This study, in a novel approach, investigated the predictive power of latent representations obtained from a hybrid autoencoder (HAE) framework combining variational autoencoder (VAE) characteristics with mean squared error (MSE) and triplet loss for forecasting COVID-19 patients with high mortality risk in a retrospective framework. Electronic laboratory and clinical data of 1474 patients were used in the study. Logistic regression with elastic net regularization (EN) and random forest (RF) models were used as final classifiers. Moreover, we also investigated the contribution of utilized features towards latent representations via mutual information analysis. HAE Latent representations model achieved decent performance with an area under ROC curve of 0.921 (±0.027) and 0.910 (±0.036) with EN and RF predictors, respectively, over the hold-out data in comparison with the raw (AUC EN: 0.913 (±0.022); RF: 0.903 (±0.020)) models. The study aims to provide an interpretable feature engineering framework for the medical environment with the potential to integrate imaging data for efficient feature engineering in rapid triage and other clinical predictive models.

Assessment of anesthesia on physiological stability and BOLD signal reliability during visual or acoustic stimulation in the cat.

BACKGROUND: Neuroimaging methods including fMRI provide powerful tools to observe whole-brain functional networks. This is particularly powerful in animal models, allowing these networks to be probed using complementary methods. However, most animals must be anesthetized for neuroimaging, giving rise to complications resulting from anesthetic effects on the animal's physiological and neurological functions. For example, an established protocol for feline neuroimaging involves co-administration of ketamine and isoflurane - the latter of which is known to suppress cortical function. NEW METHOD: Here, we compare this established protocol to alfaxalone, a single-agent anesthetic for functional neuroimaging. We first compare the two in a controlled environment to assess relative safety and to measure physiological stability over an extended time window. We then compare patterns of auditory and visually-evoked activity measured at 7  T to assess mean signal strength and between-subjects signal variability. RESULTS IN COMPARISON WITH EXISTING METHODS: We show that alfaxalone results in more stable respiratory rates over the 120 min testing period, with evidence of smaller between-measurements variability within this time window, when compared to ketamine plus isoflurane. Moreover, we demonstrate that both agents evoke similar mean BOLD signals across animals, but that alfaxalone elicits more consistent BOLD activity in response to sound stimuli across all ROIs observed. CONCLUSIONS: Alfaxalone is observed to be more physiologically stable, evoking a more consistent BOLD signal across animals than the co-administration of ketamine and isoflurane. Thus, an alfaxalone-based protocol may represent a better approach for neuroimaging in animal models requiring anesthesia.

Impact of Type 2 Myocardial Infarction (MI) on Hospital-Level MI Outcomes: Implications for Quality and Public Reporting.

BACKGROUND: The International Classification of Diseases (ICD) coding system does not recognize type 2 myocardial infarction (MI) as a separate entity; therefore, patients with type 2 MI continue to be categorized under the general umbrella of non-ST-segment-elevation myocardial infarction (NSTEMI). We aim to evaluate the impact of type 2 MI on hospital-level NSTEMI metrics and discuss the implications for quality and public reporting. METHODS AND RESULTS: We conducted a single-center retrospective analysis of 1318 patients discharged with a diagnosis of NSTEMI between July 2013 and October 2014. The Third Universal Definition was used to define type 1 and type 2 MI. Weighted Kaplan-Meier curves were used to analyze risk of mortality and readmission. Overall, 1039 patients met NSTEMI criteria per the Third Universal Definition; of those, 264 (25.4%) had type 2 MI. Patients with type 2 MI were older, were more likely to have chronic kidney disease, and had lower peak troponin levels. Compared with type 1 MI patients, those with type 2 MI had higher inpatient mortality (17.4% versus 4.7%, P<0.0001) and were more likely to die from noncardiovascular causes (71.7% versus 25.0%, P<0.0001). Despite weighting for patient characteristics and discharge medications, patients with type 2 MI had higher mortality at both 30 days (risk ratio: 3.63; 95% confidence interval, 1.67-7.88) and 1 year (risk ratio: 1.98; 95% confidence interval, 1.44-2.73) after discharge. Type 2 MI was also associated with a lower 30-day cardiovascular-related readmission (risk ratio: 0.49; 95% confidence interval, 0.12-2.06). CONCLUSIONS: NSTEMI metrics are significantly affected by type 2 MI patients. Type 2 MI patients have distinct etiologies, are managed differently, and have higher mortality compared with patients with type 1 MI. Moving forward, it may be appropriate to exclude type 2 MI data from NSTEMI quality metrics.

An open resource for transdiagnostic research in pediatric mental health and learning disorders.

Technological and methodological innovations are equipping researchers with unprecedented capabilities for detecting and characterizing pathologic processes in the developing human brain. As a result, ambitions to achieve clinically useful tools to assist in the diagnosis and management of mental health and learning disorders are gaining momentum. To this end, it is critical to accrue large-scale multimodal datasets that capture a broad range of commonly encountered clinical psychopathology. The Child Mind Institute has launched the Healthy Brain Network (HBN), an ongoing initiative focused on creating and sharing a biobank of data from 10,000 New York area participants (ages 5-21). The HBN Biobank houses data about psychiatric, behavioral, cognitive, and lifestyle phenotypes, as well as multimodal brain imaging (resting and naturalistic viewing fMRI, diffusion MRI, morphometric MRI), electroencephalography, eye-tracking, voice and video recordings, genetics and actigraphy. Here, we present the rationale, design and implementation of HBN protocols. We describe the first data release (n=664) and the potential of the biobank to advance related areas (e.g., biophysical modeling, voice analysis).

Peripheral Visual Reaction Time Is Faster in Deaf Adults and British Sign Language Interpreters than in Hearing Adults.

Following auditory deprivation, the remaining sense of vision has shown selective enhancement in visual cognition, especially in the area of near peripheral vision. Visual acuity is poor in the far periphery and may be an area where sound confers the greatest advantage in hearing persons. Experience with a visuospatial language such as British Sign Language (BSL) makes additional demands on the visual system. To test the different and separable effects of deafness and use of a visuo-spatial language on far peripheral visual processing, we investigated visual reaction times (RTs) and response accuracy to visual stimuli, between 30° and 85° along the four cardinal and four inter-cardinal meridians. We used three luminances of static, briefly illuminated stimuli in visually normal adults. The cohort tested included profoundly congenitally deaf adults (N = 17), hearing fluent BSL users (N = 8) and hearing non-signing adults (N = 18). All participants were tested using a peripheral forced choice paradigm designed previously to test deaf and hearing children (Codina et al., 2011a). Deaf adults demonstrated significantly faster RTs to all far peripheral stimuli and exceeded the abilities of both signing and non-signing hearing adults. Deaf adults were significantly faster than BSL interpreters, who in turn were significantly faster than hearing non-signing adults. The differences in RT demonstrated between groups were consistent across all visual field meridians and were not localized to any one region of the visual field. There were no differences found between any groups in accuracy of detecting these static stimuli at any retinal location. Early onset auditory deprivation appears to lead to a response time visual advantage in far peripheral responses to briefly presented, static LED stimuli, especially in the right visual field. Fluency in BSL facilitates faster visuo-motor responses in the peripheral visual field, but to a lesser extent than congenital, profound deafness.

"The Pleasure Is Better as I've Gotten Older": Sexual Health, Sexuality, and Sexual Risk Behaviors Among Older Women Living With HIV.

There is limited research examining the sexual health and well-being of older women living with HIV (OWLH). Most studies focus on sexual dysfunction, leaving aside the richer context of sexuality and sexual health, including the effect of age-related psychosocial and interpersonal changes on sexual health behaviors. Guided by the integrative biopsychosocial model and the sexual health model, this study explored the importance of sex and sexuality among OWLH to identify their sexual health and HIV prevention needs for program planning. A purposive sample (n = 50) of OWLH was selected from a parent study (n = 2052). We conducted 8 focus groups and 41 in-depth interviews with 50 African American and Latina OWLH aged 50-69 years old in three U.S. cities. The triangulation approach was used to synthesize the data. Six salient themes emerged: sexual pleasure changes due to age, sexual freedom as women age, the role of relationships in sexual pleasure, changes in sexual ability and sexual health needs, sexual risk behaviors, and ageist assumptions about older women's sexuality. We found that sexual pleasure and the need for intimacy continue to be important for OWLH, but that changing sexual abilities and sexual health needs, such as the reduction of sexual desire, as well as increased painful intercourse due to menopause-associated vaginal drying, were persistent barriers to sexual fulfillment and satisfaction. Particular interpersonal dynamics, including low perceptions of the risk of HIV transmission as related to gender, viral suppression, and habitual condomless sex with long-term partners without HIV transmission have resulted in abandoning safer sex practices with serodiscordant partners. These findings suggest that HIV prevention for OWLH should focus on how sexual function and satisfaction intersect with sexual risk. HIV prevention for OWLH should promote ways to maintain satisfying and safe sex lives among aging women.

Prevalence and Predictors of Hospitalizations Among HIV-Infected and At-Risk HIV-Uninfected Women.

OBJECTIVES: We evaluated the Veterans Aging Cohort Study (VACS) Index score, an index composed of age, CD4 count, viral load, hemoglobin, Hepatitis C coinfection, Fibrosis Index-4, and estimated glomerular filtration rate, and psychosocial and clinical risk factors for all-cause hospitalization among HIV-infected women on highly active antiretroviral therapy and HIV-uninfected women. METHODS: Data were collected from 2008 to 2014 from 1585 highly active antiretroviral therapy-experienced HIV infected and 692 uninfected women. Cox proportional hazards regression evaluated predictors of first hospitalization over 2 years. RESULTS: Among HIV-infected women, VACS Index score (per 5 points) [adjusted hazard ratio (aHR) 1.08; 95% confidence interval (CI): 1.06 to 1.11], Centers for Epidemiologic Studies-Depression (CESD) scores ≥16 (aHR 1.61; 95% CI: 1.30 to 1.99), smoking (aHR 1.26; 95% CI: 1.02 to 1.55), abuse history (aHR 1.52; 95% CI: 1.20 to 1.93), diabetes (aHR 1.63; 95% CI: 1.31 to 2.04), and black race (aHR 1.28; 95% CI: 1.03 to 1.59) increased risk of hospitalization. Among HIV-uninfected women, VACS Index score (aHR 1.08; 95% CI: 1.03 to 1.13), CESD scores ≥16 (aHR 1.38; 95% CI: 1.02 to 1.86), diabetes (aHR 2.15; 95% CI: 1.57 to 2.95), and black race (aHR 1.61; 95% CI: 1.15 to 2.24) predicted subsequent hospitalization. CONCLUSIONS: Psychosocial and clinical factors were associated with risk of hospitalization independently of the VACS Index score. Additional research on contextual and psychosocial influences on health outcomes among women is needed.

Trends in Nonlipid Cardiovascular Disease Risk Factor Management in the Women's Interagency HIV Study and Association with Adherence to Antiretroviral Therapy.

Cardiovascular disease (CVD) is increasingly common among women with HIV, but literature on nonlipid CVD risk factor management is lacking. We examined semiannual trends from 2006 to 2014 in hypertension treatment and control (blood pressure <140/90 mmHg), diabetes treatment and control (fasting glucose <130 mg/dL), and smoking quit rates in the Women's Interagency HIV Study. Unadjusted and adjusted Poisson regression models tested time trends and differences between HIV+ and HIV- women. Among antiretroviral therapy (ART) users, we examined the association of ART adherence and virologic suppression with each outcome. We evaluated 1636 HIV+ and 683 HIV- women, with a hypertension prevalence of 40% and 38%, respectively; diabetes prevalence of 21% and 22%; and smoking prevalence of 37% and 48%. Hypertension treatment was higher among HIV+ than HIV- women (77% vs. 67%, p < 0.001) and increased over time with no difference in trend by HIV status. Hypertension control was greater among HIV+ women (56% vs. 43%, p < 0.001) and increased over time among HIV+ but not HIV- women. Diabetes treatment was similar among HIV+ and HIV- women (48% vs. 49%) and increased over time in both groups. Diabetes control was greater among HIV+ women (73% vs. 64%, p = 0.03) and did not change over time. The percent of recent smokers who reported no longer smoking was similar between HIV+ and HIV- women (10% vs. 9%), with no differences over time. Virologic suppression was significantly associated with increased hypertension treatment and greater control. HIV+ women have better control of hypertension and diabetes than HIV- women, but many are still not at target levels.

Autologous hematopoietic cell transplantation for HIV-related lymphoma: results of the BMT CTN 0803/AMC 071 trial.

Autologous hematopoietic cell transplant (AHCT) for HIV-infected patients is largely limited to centers with HIV-specific expertise. The Blood and Marrow Transplant Clinical Trials Network 0803/AIDS Malignancy Consortium 071 trial is a multicenter phase 2 study of AHCT for patients with HIV-related lymphoma (HRL). Eligible patients had chemotherapy-sensitive relapsed/persistent HRL, were >15 years of age, and had treatable HIV infection. Patients were prepared using carmustine, etoposide, cytarabine, and melphalan and received consistent management of peritransplant antiretroviral treatment. The primary endpoint was 1-year overall survival. Forty-three patients were enrolled; 40 underwent AHCT. Pretransplant HIV viral load was undetectable (<50 copies/mL) in 32 patients (80%); the median CD4 count was 249/µL (range, 39-797). At a median follow-up of 24.8 months, 1-year and 2-year overall survival probabilities were 87.3% (95% confidence interval [CI], 72.1-94.5) and 82% (95% CI, 65.9-91), respectively. The probability of 2-year progression-free survival was 79.8% (95% CI, 63.7-89.4). One-year transplant-related mortality was 5.2%. Median time to neutrophil and platelet recovery was 11 days and 18 days, respectively. Nine patients experienced a total of 13 unexpected grade 3-5 adverse events posttransplant (10 grade 3 and 3 grade 4 events). Twenty-two patients had at least 1 infectious episode posttransplant. At 1 year post-AHCT, median CD4(+) T-cell count was 280.3 (range, 28.8-1148.0); 82.6% had an undetectable HIV viral load. Trial patients were compared with 151 matched Center for International Bone Marrow Transplant Research controls. Outcomes between HIV-infected patients and controls were not statistically significantly different. HRL patients should be considered candidates for AHCT if they meet standard transplant criteria. The trial was registered at www.clinicaltrials.gov as #NCT01141712.

Listeria monocytogenes wall teichoic acid decoration in virulence and cell-to-cell spread.

Wall teichoic acid (WTA) comprises a class of glycopolymers covalently attached to the peptidoglycan of gram positive bacteria. In Listeria monocytogenes, mutations that prevent addition of certain WTA decorating sugars are attenuating. However, the steps required for decoration and the pathogenic process interrupted are not well described. We systematically examined the requirement for WTA galactosylation in a mouse oral-virulent strain by first creating mutations in four genes whose products conferred resistance to a WTA-binding bacteriophage. WTA biochemical and structural studies indicated that galactosylated WTA was directly required for bacteriophage adsorption and that mutant WTA lacked appreciable galactose in all except one mutant - which retained a level ca. 7% of the parent. All mutants were profoundly attenuated in orally infected mice and were impaired in cell-to-cell spread in vitro. Confocal microscopy of cytosolic mutants revealed that all expressed ActA on their cell surface and formed actin tails with a frequency similar to the parent. However, the mutant tails were significantly shorter - suggesting a defect in actin based motility. Roles for the gene products in WTA galactosylation are proposed. Identification and interruption of WTA decoration pathways may provide a general strategy to discover non-antibiotic therapeutics for gram positive infections. © 2016 John Wiley & Sons Ltd.

Dysregulated B-cell TLR2 expression and elevated regulatory B-cell frequency precede the diagnosis of AIDS-related non-Hodgkin lymphoma.

OBJECTIVES: In antiretroviral therapy (ART)-treated patients, to determine if AIDS-related non-Hodgkin lymphoma (AIDS-NHL) is preceded by: elevated frequency of potentially malignant abnormal activated/germinal center-like B cells, elevated serum prevalence of B-cell stimulatory Toll-like receptor (TLR) ligands resulting from HIV infection-associated microbial translocation, dysregulated B-cell TLR expression/signaling, and perturbations in the frequency of immunoregulatory cells. DESIGN: A case-control study nested with a cohort study of HIV-infected women. METHODS: Prediagnostic AIDS-NHL cases (n = 12, collected 1-12 months before diagnosis) and controls (n = 42) from the Women's Interagency HIV Study cohort, were matched for HIV and ART status, age, race, and CD4 lymphocyte count. Serum levels of TLR ligands, the prevalence of malignancy-associated abnormal activated/germinal center-like (CD19CD10CD71CD86AID) B cells, TLR2 expression on B cells, expression of TLR2-modulating micro-RNA, and the frequency of regulatory T and B cells were assessed. RESULTS: Diagnosis of AIDS-NHL was preceded by a significantly elevated frequency of activated/germinal center-like CD19CD10CD71CD86AID B cells (P = 0.0072), elevated serum prevalence of the TLR2 ligand, and significantly elevated B-cell TLR2 expression (P = 0.0015), positively correlating with the frequency of activated/germinal center-like B cells (rho = 0.7273, P = 0.0144). In cases, a purified subset of activated/germinal center-like B cells exhibited decreased expression of microRNAs that modulate TLR2 signaling, including miR-21, 146a, 146b, and 155. Finally, cases also exhibited significantly elevated frequencies of antitumor immunity inhibitory regulatory B cells (P = 0.0024), but not regulatory T cells. CONCLUSIONS: Our findings suggest that increased microbial translocation and dysregulated TLR expression/signaling, coupled with an elevated frequency of regulatory B cells, precede the diagnosis of AIDS-NHL in HIV-infected ART-treated patients.

The New Face of Head and Neck Cancer: The HPV Epidemic.

There has been a significant increase in the incidence of human papillomavirus (HPV)-mediated oropharyngeal cancer in the United States. This entity is most commonly diagnosed in nonsmoking middle-aged white males. The majority of the patients present with asymptomatic, persistent neck masses despite antibiotic therapy. An awareness of this condition and a high degree of suspicion is necessary for timely diagnosis. HPV-mediated oropharyngeal squamous cell carcinomas (HPV-OPSCCs) are unique biologically and clinically, and affected patients enjoy better outcomes with existing standard therapies than do patients with OPSCC mediated by tobacco exposure. The p16 protein is usually overexpressed in HPV-OPSCC, and its detection on immunohistochemistry is a reliable surrogate marker for this disease. In this review, we discuss current paradigms in the diagnosis and management of HPV-OPSCC, and we emphasize pertinent research questions to investigate going forward, including whether to deintensify treatment in these patients.

Gender-Related Risk Factors Improve Mortality Predictive Ability of VACS Index Among HIV-Infected Women.

BACKGROUND: Adding gender-related modifiable characteristics or behaviors to the Veterans Aging Cohort Study (VACS) index might improve the accuracy of predicting mortality among HIV-infected women on treatment. We evaluated the VACS index in women with HIV, determined whether additional variables would improve mortality prediction, and quantified the potential for improved survival associated with reduction in these additional risk factors. METHODS: The VACS index (based on age, CD4 count, HIV-1 RNA, hemoglobin, aspartate aminotransferase, alanine aminotransferase, platelets, creatinine, and Hepatitis C status) was validated in HIV-infected women in the Women's Interagency HIV Study (WIHS) who initiated antiretroviral therapy between January 1996 and December 2007. Models were constructed adding race, depression, abuse, smoking, substance use, transactional sex, and comorbidities to determine whether predictability improved. Population attributable fractions were calculated. RESULTS: The VACS index accurately predicted 5-year mortality in 1057 WIHS women with 1 year on highly active antiretroviral therapy with c-index 0.83 [95% confidence interval (CI): 0.79 to 0.87]. In multivariate analysis, the VACS index score [adjusted hazard ratio (aHR) for a 5-point increment 1.30; 95% CI: 1.25 to 1.35], depressive symptoms (aHR 1.73; 95% CI: 1.17 to 2.56), and history of transactional sex (aHR 1.93; 95% CI: 1.33 to 1.82) were independent statistically significant predictors of mortality. CONCLUSIONS: Both depression and transactional sex significantly improved the performance of the VACS index in predicting mortality among HIV-infected women. Providing treatment for depression and addressing economic and psychosocial instability in HIV-infected women would improve health and perhaps point to a broader public health approach to reducing HIV mortality.

Cervical Precancer Risk in HIV-Infected Women Who Test Positive for Oncogenic Human Papillomavirus Despite a Normal Pap Test.

BACKGROUND: Determining cervical precancer risk among human immunodeficiency virus (HIV)-infected women who despite a normal Pap test are positive for oncogenic human papillomavirus (oncHPV) types is important for setting screening practices. METHODS: A total of 2791 HIV-infected and 975 HIV-uninfected women in the Women's Interagency HIV Study were followed semiannually with Pap tests and colposcopy. Cumulative risks of cervical intraepithelial neoplasia grade 2 or greater (CIN-2+; threshold used for CIN treatment) and grade 3 or greater (CIN-3+; threshold to set screening practices) were measured in HIV-infected and HIV-uninfected women with normal Pap tests, stratified by baseline HPV results, and also in HIV-infected women with a low-grade squamous intraepithelial lesion (LSIL; benchmark indication for colposcopy). RESULTS: At baseline, 1021 HIV-infected and 518 HIV-uninfected women had normal Pap tests, of whom 154 (15%) and 27 (5%), respectively, tested oncHPV positive. The 5-year CIN-2+ cumulative risk in the HIV-infected oncHPV-positive women was 22% (95% confidence interval [CI], 9%-34%), 12% (95% CI, 0%-22%), and 14% (95% CI, 2%-25%) among those with CD4 counts <350, 350-499, and ≥500 cells/µL, respectively, whereas it was 10% (95% CI, 0%-21%) in those without HIV. For CIN-3+, the cumulative risk averaged 4% (95% CI, 1%-8%) in HIV-infected oncHPV-positive women, and 10% (95% CI, 0%-23%) among those positive for HPV type 16. In HIV-infected women with LSIL, CIN-3+ risk was 7% (95% CI, 3%-11%). In multivariate analysis, HIV-infected HPV16-positive women had 13-fold (P = .001) greater CIN-3+ risk than oncHPV-negative women (referent), and HIV-infected women with LSIL had 9-fold (P < .0001) greater risk. CONCLUSIONS: HIV-infected women with a normal Pap result who test HPV16 positive have high precancer risk (similar to those with LSIL), possibly warranting immediate colposcopy. Repeat screening in 1 year may be appropriate if non-16 oncHPV is detected.

Lung cancer incidence and survival among HIV-infected and uninfected women and men.

OBJECTIVES: To determine the lung cancer incidence and survival time among HIV-infected and uninfected women and men. DESIGN: Two longitudinal studies of HIV infection in the United States. METHODS: Data from 2549 women in the Women's Interagency HIV Study (WIHS) and 4274 men in the Multicenter AIDS Cohort Study (MACS), all with a history of cigarette smoking, were analyzed. Lung cancer incidence rates and incidence rate ratios were calculated using Poisson regression analyses. Survival time was assessed using Kaplan-Meier and Cox proportional-hazard analyses. RESULTS: Thirty-seven women and 23 men developed lung cancer (46 HIV-infected and 14 HIV-uninfected) during study follow-up. In multivariable analyses, the factors that were found to be independently associated with a higher lung cancer incidence rate ratios were older age, less education, 10 or more pack-years of smoking, and a prior diagnosis of AIDS pneumonia (vs. HIV-uninfected women). In an adjusted Cox model that allowed different hazard functions for each cohort, a history of injection drug use was associated with shorter survival, and a lung cancer diagnosis after 2001 was associated with longer survival. In an adjusted Cox model restricted to HIV-infected participants, nadir CD4 lymphocyte cell count less than 200 was associated with shorter survival time. CONCLUSIONS: Our data suggest that pulmonary damage and inflammation associated with HIV infection may be causative for the increased risk of lung cancer. Encouraging and assisting younger HIV-infected smokers to quit and to sustain cessation of smoking is imperative to reduce the lung cancer burden in this population.

Longitudinal Trends in Sexual Behaviors with Advancing Age and Menopause Among Women With and Without HIV-1 Infection.

We assessed changes in self-reported sexual activity (SA) over 13 years among HIV-infected and uninfected women. The impact of aging and menopause on SA and unprotected anal or vaginal intercourse (UAVI) was examined among women in the Women's Interagency HIV Study (WIHS), stratifying by HIV status and detectable viral load among HIV-infected women. Generalized mixed linear models were fitted for each outcome, adjusted for relevant covariates. HIV-uninfected women evidenced higher levels of SA and UAVI than HIV-infected. The odds of SA declined by 62-64 % per decade of age. The odds of SA in a 6-month interval for women aged 40-57 declined by 18-22 % post-menopause (controlling for age). Among HIV+/detectable women only, the odds of any UAVI decreased by 17 % per decade of age; the odds of UAVI were unchanged pre-menopause, and then decreased by 28 % post-menopause. Elucidating the factors accounting for ongoing unprotected sex among older women should inform interventions.

Risk of breast cancer with CXCR4-using HIV defined by V3 loop sequencing.

OBJECTIVE: Evaluate the risk of female breast cancer associated with HIV-CXCR4 (X4) tropism as determined by various genotypic measures. METHODS: A breast cancer case-control study, with pairwise comparisons of tropism determination methods, was conducted. From the Women's Interagency HIV Study repository, one stored plasma specimen was selected from 25 HIV-infected cases near the breast cancer diagnosis date and 75 HIV-infected control women matched for age and calendar date. HIV-gp120 V3 sequences were derived by Sanger population sequencing (PS) and 454-pyro deep sequencing (DS). Sequencing-based HIV-X4 tropism was defined using the geno2pheno algorithm, with both high-stringency DS [false-positive rate (3.5) and 2% X4 cutoff], and lower stringency DS (false-positive rate, 5.75 and 15% X4 cutoff). Concordance of tropism results by PS, DS, and previously performed phenotyping was assessed with kappa (κ) statistics. Case-control comparisons used exact P values and conditional logistic regression. RESULTS: In 74 women (19 cases, 55 controls) with complete results, prevalence of HIV-X4 by PS was 5% in cases vs 29% in controls (P = 0.06; odds ratio, 0.14; confidence interval: 0.003 to 1.03). Smaller case-control prevalence differences were found with high-stringency DS (21% vs 36%, P = 0.32), lower stringency DS (16% vs 35%, P = 0.18), and phenotyping (11% vs 31%, P = 0.10). HIV-X4 tropism concordance was best between PS and lower stringency DS (93%, κ = 0.83). Other pairwise concordances were 82%-92% (κ = 0.56-0.81). Concordance was similar among cases and controls. CONCLUSIONS: HIV-X4 defined by population sequencing (PS) had good agreement with lower stringency DS and was significantly associated with lower odds of breast cancer.