Faculty Bibliography

Microarray studies generate a large number of p-values from many gene expression comparisons. The estimate of the proportion of the p-values sampled from the null hypothesis draws broad interest. The two-component mixture model is often used to estimate this proportion. If the data are generated under the null hypothesis, the p-values follow the uniform distribution. What is the distribution of p-values when data are sampled from the alternative hypothesis? The distribution is derived for the chi-squared test. Then this distribution is used to estimate the proportion of p-values sampled from the null hypothesis in a parametric framework. Simulation studies are conducted to evaluate its performance in comparison with five recent methods. Even in scenarios with clusters of correlated p-values and a multicomponent mixture or a continuous mixture in the alternative, the new method performs robustly. The methods are demonstrated through an analysis of a real microarray dataset.

As more young women survive breast cancer, fertility preservation (FP) is an important component of care. This review highlights the importance of early pretreatment referral, reviews the risks of infertility associated with breast cancer treatment, and defines existing and emerging techniques for FP. The techniques reviewed include ovarian suppression, embryo cryopreservation, oocyte cryopreservation, and ovarian tissue cryopreservation and transplantation. The barriers women face, such as not being appropriately referred and the costs of treatment, also are addressed. Multidisciplinary, patient-centered care is essential to discussing FP with patients with breast cancer and ensuring appropriate care that includes quality of life in survivorship.

The health of people ever incarcerated in New York City (NYC) jails during 2001 to 2005 was characterized by matching jail, shelter, mortality, sexually transmitted infection, HIV, and tuberculosis (TB) data from the NYC Departments of Health and Mental Hygiene, Correction, and Homeless Services. Compared with nonincarcerated people and those living in the lowest income NYC neighborhoods, those ever incarcerated had higher HIV prevalence and HIV case rates. Ever-incarcerated females also had higher rates of gonorrhea and syphilis than nonincarcerated females. Ever-incarcerated people who used the single adult homeless shelter system had higher HIV, gonorrhea, and TB case rates and all-cause mortality rates than ever-incarcerated people without shelter use, when adjusting for other variables. People ever incarcerated in NYC jails are at risk for conditions of public health importance. Sex-specific jail- and community-based interventions are needed.

Research Findings: Recent research has explored relations between classroom quality and child executive function (EF), but little is known about how teachers' well-being, including stress, relates to child EF-a crucial component of self-regulation. We hypothesized that teacher stress is negatively or curvilinearly related to child EF and classroom quality may be one mechanism explaining this relation. Furthermore, as working with young, low-income children may be particularly stressful, we tested the extent to which the relation between teacher stress and child EF varies by school-level poverty. Two-level hierarchical linear models using a sample of 171 kindergarten children and 33 teachers revealed a marginally significant linear relation between teacher stress and child EF (spring) controlling for baseline child EF (fall); there was no evidence for mediation by classroom quality. School-level poverty moderated the relation between teacher stress and child EF: Children attending low-poverty schools demonstrated smaller gains in EF when their teachers reported higher stress levels. However, in high-poverty schools high levels of teacher stress were not a risk factor for child EF. Practice or Policy: These novel findings are a first step to understanding how teachers' well-being relates to child EF across schools and have implications for supporting teachers.

BACKGROUND: The Primary Care Information Project (PCIP) is a program administered by the New York City Department of Health and Mental Hygiene to help primary care providers adopt a fully functional electronic health record (EHR) and focus on population health. PCIP also offers practices assistance with the National Committee for Quality Assurance (NCQA) patient-centered medical home (PCMH) recognition application. The objectives of this study were to assess the presence of key dimensions of PCMH among PCIP practices with 5 or fewer providers and to determine whether and to what extent NCQA recognition was related to the presence of these dimensions. METHODS: Analyses relied on data collected from a comprehensive practice assessment survey of PCIP practices administered in summer 2012. The survey was developed to assess discrete dimensions of the PCMH model and other practice characteristics. The study population includes practices for which survey results were available among PCIP practices with 5 or fewer providers (63% response rate; n = 83). RESULTS: At the time of survey, 57% of practices had received some level of NCQA recognition (n = 47). Practices with recognition scored significantly higher on several dimensions, including whole person orientation, team-based care, care coordination and integration, and quality and safety. CONCLUSIONS: Results indicate that very small urban practices in New York City are implementing many key features of PCMH. In general, practices with NCQA recognition scored higher on PCMH constructs and domains relative to practices without recognition; however, there is room for improvement on construct and domain scores in both groups.

Background: The United Arab Emirates (UAE) is experiencing increasing rates of obesity, type 2 diabetes (T2D) and its complications. We tested if soluble levels of cell surface-cleaved RAGE (sRAGE) or endogenous secretory RAGE (esRAGE), the product of alternative mRNA splicing of AGER, are associated with T2D and obesity in the UAE.
Method(s): A case-control study was performed in the Diabetes, Endocrinology and General Medical Clinics of the Sheikh Khalifa Medical City in Abu Dhabi. 216 T2D subjects and 215 controls (mean age 57.4+/-12.1 vs. 50.7+/-15.4 years, respectively) were enrolled. Plasma sRAGE and esRAGE levels, anthropomorphic characteristics and routine chemistries were measured. The relationship between sRAGE and esRAGE with obesity and T2D status was tested using a linear regression model.
Result(s): Univariate analyses comparing T2D case and control subjects revealed differences in sRAGE (1,033+/-545.3 vs. 1,169+/-664.1 pg/ml, respectively; p=0.02) but not esRAGE. Covariate adjustment revealed that differences in sRAGE were significant after correction for age and sex and additionally for waist-hip ratio (WHR); total cholesterol (TC), HDL; hsCRP; Vit D; or triglyceride (TG) levels separately. In cases or controls, we tested associations of body mass index (BMI) or WHR with sRAGE and esRAGE. In controls but not T2D cases, sRAGE and esRAGE were significantly associated with BMI, after correction for age and sex and additionally for eGFR; blood pressure; TC, HDL; hsCRP; Vit D; creatinine; TG and HbA1c in a combined model. In the case of WHR, in controls and T2D cases, there were no associations with sRAGE, but only in T2D cases, WHR was associated with esRAGE after correction for age and sex and blood pressure; TC, HDL; hsCRP, HbA1c, creatinine; TG, eGFR, Vit D and TG in a combined model.
Conclusion(s): Levels of sRAGE but not esRAGE distinguish T2D case vs. controls in the UAE population. Genetic and unique obesity-dependent factors may underlie lack of association between esRAGE in cases vs. controls, which may affect vulnerability to T2D and its complications in the UAE

Little is known about how neighborhood noise influences cardiovascular disease (CVD) risk among low-income populations. The aim of this study was to investigate associations between neighborhood noise complaints and body mass index (BMI) and blood pressure (BP) among low-income housing residents in New York City (NYC), including the use of global positioning system (GPS) data. Data came from the NYC Low-Income Housing, Neighborhoods and Health Study in 2014, including objectively measured BMI and BP data (N = 102, Black = 69%), and 1 week of GPS data. Noise reports from "NYC 311" were used to create a noise complaints density (unit: 1000 reports/km2) around participants' home and GPS-defined activity space neighborhoods. In fully-adjusted models, we examined associations of noise complaints density with BMI (kg/m2), and systolic and diastolic BP (mmHg), controlling for individual- and neighborhood-level socio-demographics. We found inverse relationships between home noise density and BMI (B = -2.7 [kg/m2], p = 0.009), and systolic BP (B = -5.3 mmHg, p = 0.008) in the fully-adjusted models, and diastolic BP (B = -3.9 mmHg, p = 0.013) in age-adjusted models. Using GPS-defined activity space neighborhoods, we observed inverse associations between noise density and systolic BP (B = -10.3 mmHg, p = 0.019) in fully-adjusted models and diastolic BP (B = -7.5 mmHg, p = 0.016) in age-adjusted model, but not with BMI. The inverse associations between neighborhood noise and CVD risk factors were unexpected. Further investigation is needed to determine if these results are affected by unobserved confounding (e.g., variations in walkability). Examining how noise could be related to CVD risk could inform effective neighborhood intervention programs for CVD risk reduction.

Hydroxy-4-methoxybenzophenone, also known as benzophenone-3 (BP-3), is a commonly used ultraviolet filter in skincare and as a food additive. Large concentrations of similar phenolic compounds have been detected in urine, amniotic fluid, and placental tissue, thereby raising questions about its impact on reproduction. The objective of this paper was to investigate the reproductive toxicity of BP-3 in humans and animals. In humans, studies showed that high levels of BP-3 exposure could be linked to an increase in male birth weight but a decline in female birth weight and male gestational age. In fish, BP-3 exposure resulted in a decline in egg production, hatching, and testosterone, along with a down-regulation of steroidogenic genes. In rats, a decrease in epididymal sperm density and a prolonged estrous cycle for females was observed. These positive associations may be attributed to an altered estrogen and testosterone balance as a result of endocrine disrupting effects of BP-3. However, the current body of literature is limited by non-uniform exposure and outcome measurements in studies both across and within species and future studies will need to be conducted in a standardized fashion to allow for a more significant contribution to the literature that allows for better comparison across studies.

Background: Retinal imaging by optical coherence tomography (OCT) has gained increasing attention in multiple sclerosis and other neuroinflammatory and neurodegenerative disorders. Ambiguous and incomplete reporting of methodology and OCT-derived data have limited the ability to compare data and to apply and generalize findings in the past. To improve this situation, the Advised Protocol for Optical coherence tomography Study Terminology and Elements (APOSTEL) recommendations have been developed to outline core information to be provided when reporting quantitative OCT studies with help of a 9-point checklist (Cruz-Herranz and Balk et al., Neurology 2016). The APOSTEL recommendations currently have the evidence level of an expert opinion (Class IV). Objective: To advance the APOSTEL recommendations for OCT reporting in a formalized procedure towards evidence-based guidelines. Methods: Studies reporting quantitative OCT results published within the last 24 months have been identified by a Pubmed search. The corresponding authors of these 1472 articles will be contacted and asked to participate in an online survey to evaluate and give feedback on the initial APOSTEL recommendations. The feedback obtained will be anonymized and distributed to a panel of international experts for evaluation and revision of the recommendations. After the initial round the corresponding authors who gave feedback will be informed about the intermediate results and asked to participate in the survey for a second time. This procedure will be repeated if necessary following the consensus-building procedure of a DELPHI process. To this end, for each round the feedback obtained as well as any revisions made to the APOSTEL recommendations will be summarized and questionnaires will be used for evaluation in order to reach consensus and to develop evidencebased guidelines for prospective OCT studies. Results: The degree of consensus of the survey's participants will be reported for the initial and the revised versions of the recommendations as well as the revisions made to the initial version. Conclusion: Formal guidelines for the reporting of quantitative OCT studies will be presented as well as the process of how they were developed

Background: The association of peripapillary retinal nerve fibre layer (pRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness, with neurodegeneration in multiple sclerosis (MS) is well established. The potential relationship of the adjoining inner nuclear layer (INL) with inflammatory disease activity is less well understood. Objective: To investigate the longitudinal relationship of INL volume changes with inflammatory disease activity. Methods: In this longitudinal multi-center study, spectral-domain optical coherence tomography (OCT) and clinical data were collected in 821 patients with MS, from eleven MS centres between 2010 and 2017. All patients had at least two visits (minimum follow- up of 6 months). Clinical data included EDSS score, occurring of relapses, including MS-associated optic neuritis (MSON). At each centre, automated segmentation of OCT scans was performed to obtain data on the pRNFL, GCIPL and INL. Annualized changes were calculated and generalized estimation equations were used to analyze longitudinal changes and associations with clinical measures. Results: In total, 1596 eyes from 798 patients (68.2% female), with a disease duration of 9.4 (+/-8.9) years, were included. Mean follow up duration was 2.3 years (range 0.5 to 5.2 years). Microcystic macular oedema (MMO) was present in 1.3% of eyes (20/1299 eyes). Clinical relapses other than MSON were present in 24.9% of patients, and disease progression was observed in 30.1%. In eyes with an episode of MSON during follow-up (N=61/1584), INL volume showed a significant increase over time (DELTAINL=0.01 mm3, p< 0.001), whereas in eyes without MSON during followup, no significant change in INL was observed (DELTAINL=0.00, p=0.308). Increase in INL volume in MSON eyes was related to a decrease in GCIPL volume (beta=-2.6, p=0.006). In eyes with MMO, the INL volume at the last visit was 0.06 mm3 higher compared to eyes without (p=0.003). There was no significant association between clinical relapses other than MSON, and INL volume changes (DELTAINL=0.00 mm3, p=0.773). Likewise, an in-or decrease in INL volume was independent of change of the EDSS score (OR=1.16, p=0.293, 95% CI 0.88-1.52). Conclusion: Our data demonstrate that an increase of the INL volume is associated with adjacent inflammation of the optic nerve and retina, but not with global physical disability. Therefore INL volume changes may be considered as a secondary outcome measure for anti-inflammatory treatment in MSON trials