Faculty Bibliography

PURPOSE/OBJECTIVE:There is a need for research to facilitate the widespread implementation, dissemination and sustained utilization of evidence-based primary care screening, monitoring and care coordination guidelines, thereby increasing the impact of dental hygienists' actions on patients' oral and general health. The aims of this formative study are to explore dental hygienists' and dentists' perspectives regarding the integration of primary care activities into routine dental care, and assess the needs of dental hygienists and dentists regarding primary care coordination activities and use of information technology to obtain clinical information at chairside. METHODS:This qualitative study recruited 10 dental hygienists and 6 dentists from 10 New York City area dental offices with diverse patient mixes and volumes. A New York University faculty dental hygienist conducted semi-structured, in-depth interviews, which were digitally recorded and transcribed verbatim. Data analysis consisted of multilevel coding based on the Consolidated Framework for Implementation Research, resulting in emergent themes with accompanying categories. RESULTS:The dental hygienists and dentists interviewed as part of this study do not use evidence-based guidelines to screen their patients for primary care sensitive conditions. Overwhelmingly, dental providers believe that tobacco use and poor diet contribute to oral disease, and report using electronic devices at chairside to obtain web-based health information. CONCLUSION/CONCLUSIONS:Dental hygienists are well positioned to help facilitate greater integration of oral and general health care. Challenges include lack of evidence-based knowledge, coordination between dental hygienists and dentists, and systems-level support, with opportunities for improvement based upon a theory-driven framework.

Perchlorate is an endocrine-disrupting chemical that interferes with the normal functioning of the thyroid gland. Maternal thyroid dysfunction during gestation may alter fetal brain development. Perchlorate contamination is widespread: it is present in the body of all Americans tested and the majority of foods tested. The main sources of food contamination appear to be hypochlorite bleach, a disinfectant and sanitizer, that when poorly managed quickly degrades to perchlorate and perchlorate-laden plastic food packaging for dry food or localized contamination from manufacturing or processing of the chemical. Eliminating perchlorate from food packaging and improving bleach management, such as reducing concentration and storage time and temperature, would result in reduced perchlorate contamination of food and water.

OBJECTIVE:Metabolic syndrome is associated with insulin resistance and increased future risk of type 2 diabetes. This study investigates the relationship between insulin secretion, insulin resistance and individual metabolic syndrome components in subjects without a prior diagnosis of diabetes. RESEARCH DESIGN AND METHODS:We assessed insulin secretion during hyperglycemic clamps by infusing dextrose to maintain hyperglycemia (200mg/dL), followed by L-arginine administration. Studies in 98 individuals (mean age 45.3±1.2years, 56% female, 22% African-American, 49% with metabolic syndrome) were analyzed. We tested the association between the number of metabolic syndrome components and individual outcome variables using linear mixed-effects models to adjust for potential confounding effects of age, sex, and race. RESULTS:Insulin sensitivity index was reduced in the presence of 1 or more metabolic syndrome components. Insulin sensitivity was independently associated with age, waist circumference, male gender and decreased HDL cholesterol. The acute insulin response was greater with two or more metabolic syndrome components, and late glucose-stimulated and L-arginine-stimulated insulin responses exhibited a similar trend. In contrast, the disposition index, a measure of beta cell compensation for insulin resistance, was linearly lower with the number of metabolic syndrome components, and was negatively associated with age, Caucasian race, waist circumference, fasting glucose, and decreased HDL cholesterol. CONCLUSIONS:The insulin secretory response in metabolic syndrome is inadequate for the worsening insulin sensitivity, as demonstrated by a decline in disposition index. A dysfunctional insulin secretory response is evident in non-diabetic individuals and worsens with accumulation of metabolic syndrome components.

Previous research has highlighted the salience of spatial stigma on the lives of low-income residents, but has been theoretical in nature and/or has predominantly utilised qualitative methods with limited generalisability and ability to draw associations between spatial stigma and measured cardiovascular health outcomes. The primary objective of this study was to evaluate relationships between perceived spatial stigma, body mass index (BMI), and blood pressure among a sample of low-income housing residents in New York City (NYC). Data come from the community-based NYC Low-income Housing, Neighborhoods and Health Study. We completed a crosssectional analysis with survey data, which included the four items on spatial stigma, as well objectively measured BMI and blood pressure data (analytic n=116; 96.7% of the total sample). Global positioning systems (GPS) tracking of the sample was conducted for a week. In multivariable models (controlling for individual-level age, gender, race/ethnicity, education level, employment status, total household income, neighborhood percent non-Hispanic Black and neighborhood median household income) we found that participants who reported living in an area with a bad neighborhood reputation had higher BMI (B=4.2, 95%CI: -0.01, 8.3, P=0.051), as well as higher systolic blood pressure (B=13.2, 95%CI: 3.2, 23.1, P=0.01) and diastolic blood pressure (B=8.5, 95%CI: 2.8, 14.3, P=0.004). In addition, participants who reported living in an area with a bad neighborhood reputation had increased risk of obesity/overweight [relative risk (RR)=1.32, 95%CI: 1.1, 1.4, P=0.02) and hypertension/pre-hypertension (RR=1.66, 95%CI: 1.2, 2.4, P=0.007). However, we found no differences in spatial mobility (based GPS data) among participants who reported living in neighborhoods with and without spatial stigma (P>0.05). Further research is needed to investigate how placebased stigma may be associated with impaired cardiovascular health among individuals in stigmatised neighborhoods to inform effective cardiovascular risk reduction interventions.

In clinical trials with survival endpoint, it is common to observe an overlap between two Kaplan-Meier curves of treatment and control groups during the early stage of the trials, indicating a potential delayed treatment effect. Formulas have been derived for the asymptotic power of the log-rank test in the presence of delayed treatment effect and its accompanying sample size calculation. In this paper, we first reformulate the alternative hypothesis with the delayed treatment effect in a rescaled time domain, which can yield a simplified sample size formula for the log-rank test in this context. We further propose an intersection-union test to examine the efficacy of treatment with delayed effect and show it to be more powerful than the log-rank test. Simulation studies are conducted to demonstrate the proposed methods

PURPOSE: The application of pan-cancer next generation sequencing panels in the clinical setting has facilitated the identification of low frequency somatic mutations and the testing of new therapies in solid tumors using the 'basket trial' scheme. However, little consideration has been given to the relevance of non-synonymous germline variants which are likely to be uncovered in tumors and germline and which may be relevant to prognostication and prediction -of treatment response. EXPERIMENTAL DESIGN: We analyzed matched tumor and normal DNA from 34 melanoma patients using an Ion Torrent cancer-associated gene panel. We elected to study the germline variant Q472H in the kinase insert domain receptor (KDR), which was identified in 35% of melanoma patients in both a pilot and an independent 1,223 patient cohort. Using patient-derived melanoma cell lines and human samples, we assessed proliferation, invasion, VEGF levels and angiogenesis by analyzing tumor microvessel density using anti-CD34 antibody. RESULTS: Serum VEGF levels and tumor microvessel density were significantly higher in Q472H versus KDR wild-type patients. Primary cultures derived from melanomas harboring the KDR variant were more proliferative and invasive than KDR wild-type. Finally, using a VEGFR2 antibody, we showed that KDR Q472H cells were sensitive to targeted inhibition of VEGFR2, an effect that was not observed in KDR WT cells. CONCLUSION: Our data support the integration of germline analysis into personalized treatment decision-making and suggest that patients with germline KDR variant might benefit from anti-angiogenesis treatment.

BACKGROUND: The effectiveness of food retail interventions is largely undetermined, yet substantial investments have been made to improve access to healthy foods in food deserts and swamps via grocery and corner store interventions. This study evaluated the effects of corner store conversions in East Los Angeles and Boyle Heights, California on perceived accessibility of healthy foods, perceptions of corner stores, store patronage, food purchasing, and eating behaviors. METHODS: Household data (n = 1686) were collected at baseline and 12- to 24-months post-intervention among residents surrounding eight stores, three of which implemented a multi-faceted intervention and five of which were comparisons. Bivariate analyses and logistic and linear regressions were employed to assess differences in time, treatment, and the interaction between time and treatment to determine the effectiveness of this intervention. RESULTS: Improvements were found in perceived healthy food accessibility and perceptions of corner stores. No changes were found, however, in store patronage, purchasing, or consumption of fruits and vegetables. CONCLUSIONS: Results suggest limited effectiveness of food retail interventions on improving health behaviors. Future research should focus on other strategies to reduce community-level obesity.

BACKGROUND:The presence of population structure in a sample may confound the search for important genetic loci associated with disease. Our four samples in the Family Investigation of Nephropathy and Diabetes (FIND), European Americans, Mexican Americans, African Americans, and American Indians are part of a genome- wide association study in which population structure might be particularly important. We therefore decided to study in detail one component of this, individual genetic ancestry (IGA). From SNPs present on the Affymetrix 6.0 Human SNP array, we identified 3 sets of ancestry informative markers (AIMs), each maximized for the information in one the three contrasts among ancestral populations: Europeans (HAPMAP, CEU), Africans (HAPMAP, YRI and LWK), and Native Americans (full heritage Pima Indians). We estimate IGA and present an algorithm for their standard errors, compare IGA to principal components, emphasize the importance of balancing information in the ancestry informative markers (AIMs), and test the association of IGA with diabetic nephropathy in the combined sample. RESULTS:A fixed parental allele maximum likelihood algorithm was applied to the FIND to estimate IGA in four samples: 869 American Indians; 1385 African Americans; 1451 Mexican Americans; and 826 European Americans. When the information in the AIMs is unbalanced, the estimates are incorrect with large error. Individual genetic admixture is highly correlated with principle components for capturing population structure. It takes ~700 SNPs to reduce the average standard error of individual admixture below 0.01. When the samples are combined, the resulting population structure creates associations between IGA and diabetic nephropathy. CONCLUSIONS:The identified set of AIMs, which include American Indian parental allele frequencies, may be particularly useful for estimating genetic admixture in populations from the Americas. Failure to balance information in maximum likelihood, poly-ancestry models creates biased estimates of individual admixture with large error. This also occurs when estimating IGA using the Bayesian clustering method as implemented in the program STRUCTURE. Odds ratios for the associations of IGA with disease are consistent with what is known about the incidence and prevalence of diabetic nephropathy in these populations.

BACKGROUND:Despite interest in the importance of the home food environment and its potential influence on children's diets and social norms, there remain few self-report checklist methods that have been validated against the gold standard of researcher-conducted inventories. This study aimed to assess the criterion validity and reliability of the 'Home Food Availability Inventory Checklist' (HFAI-C), a 39-item checklist including categories of fruit, vegetables, snacks and drinks. METHODS:The HFAI-C was completed by 97 participants of White and Pakistani origin in the UK. Validity was determined by comparing participant-reported HFAI-C responses to data from researcher observations of home food availability using PABAK and weighted kappa statistics. The validity of measuring the amount of items (in addition to presence/absence) available was also determined. Test-retest reliability compared repeated administrations of the HFAI-C using intra-class correlation coefficients. RESULTS:Validity and reliability was fair to moderate overall. For validity, the average category-level PABAK ranged from 0.31 (95% CI: 0.25, 0.37) for vegetables to 0.44 (95% CI: 0.40, 0.49) for fruits. Assessment of the presence/absence of items demonstrated higher validity compared to quantity measurements. Reliability was increased when the HFAI-C was repeated close to the time of the first administration. For example, ICCs for reliability of the measurement of fruits were 0.52 (95%CI: 0.47, 0.56) if re-administered within 5 months, 0.58 (95% CI: 0.51, 0.64) within 30 days and 0.97 (95%CI: 0.94, 1.00) if re-administered on the same day. CONCLUSIONS:Overall, the HFAI-C demonstrated fair to moderate validity and reliability in a population of White and South Asian participants. This evaluation is consistent with previous work on other checklists in less diverse, more affluent populations. Our research supports the use of the HFAI-C as a useful, albeit imperfect, representation of researcher-conducted inventories. The feasibility of collecting information using the HFAI-C in large, multi-ethnic samples can facilitate examination of home food availability in relation to exposures such as ethnicity and outcomes including behavioural, social and health outcomes. Future work using the HFAI-C could provide important insights into a modifiable influence with potential to impact health.