Faculty Bibliography

Restaurants are understudied yet increasingly important food environment institutions for tackling diet-related diseases. This scoping review analyzes research and gray literature (n = 171 records) to assess which healthy eating promotion strategies have been implemented in restaurants and the associated motivations, barriers, and outcomes, compared by restaurant type (corporate/chain vs. independently owned restaurants) and initiator (restaurant-initiated vs. investigator-initiated). We found that the most commonly reported strategy was the increase of generally healthy offerings and the promotion of such offerings. Changes in food availability were more common among corporate restaurants and initiated by restaurants, while environmental facilitators were more commonly initiated by investigators and associated with independently owned restaurants. Aside from those associated with revenue, motivations and barriers for healthy eating promoting strategies varied by restaurant type. While corporate restaurants were also motivated by public health criticism, independently owned restaurants were motivated by interests to improve community health. Revenue concerns were followed by food sourcing issues in corporate restaurants and lack of interest among independently owned restaurants. Among reporting sources, most outcomes were revenue positive. This study shows the need for practice-based evidence and accounting for restaurant business models to tailor interventions and policies for sustained positive changes in these establishments.

Prostate cancer is a complex disease that affects millions of men globally, predominantly in high human development index regions. Patients with localized disease at a low to intermediate risk of recurrence generally have a favourable outcome of 99% overall survival for 10 years if the disease is detected and treated at an early stage. Key genetic alterations include fusions of TMPRSS2 with ETS family genes, amplification of the MYC oncogene, deletion and/or mutation of PTEN and TP53 and, in advanced disease, amplification and/or mutation of the androgen receptor (AR). Prostate cancer is usually diagnosed by prostate biopsy prompted by a blood test to measure prostate-specific antigen levels and/or digital rectal examination. Treatment for localized disease includes active surveillance, radical prostatectomy or ablative radiotherapy as curative approaches. Men whose disease relapses after prostatectomy are treated with salvage radiotherapy and/or androgen deprivation therapy (ADT) for local relapse, or with ADT combined with chemotherapy or novel androgen signalling-targeted agents for systemic relapse. Advanced prostate cancer often progresses despite androgen ablation and is then considered castration-resistant and incurable. Current treatment options include AR-targeted agents, chemotherapy, radionuclides and the poly(ADP-ribose) inhibitor olaparib. Current research aims to improve prostate cancer detection, management and outcomes, including understanding the fundamental biology at all stages of the disease.

BACKGROUND/UNASSIGNED:ADAPTABLE (Aspirin Dosing: A Patient-centric Trial Assessing Benefits and Long-Term Effectiveness) is a pragmatic clinical trial examining high-dose versus low-dose aspirin among patients with cardiovascular disease. ADAPTABLE is leveraging novel approaches for clinical trial conduct to expedite study completion and reduce costs. One pivotal aspect of the trial conduct is maximizing clinician engagement. METHODS/RESULTS/UNASSIGNED:Clinician engagement can be diminished by barriers including time limitations, insufficient research infrastructure, lack of research training, inadequate compensation for research activities, and clinician beliefs. We used several key approaches to boost clinician engagement such as empowering clinician champions, including a variety of clinicians, nurses and advanced practice providers, periodic newsletters and coordinated team celebrations, and deploying novel technological solutions. Specifically, some centers generated electronic health records-based best practice advisories and research dashboards. Future large pragmatic trials will benefit from standardization of the various clinician engagement strategies especially studies leveraging electronic health records-based approaches like research dashboards. Financial or academic "credit" for clinician engagement in clinical research may boost participation rates in clinical studies. CONCLUSION/UNASSIGNED:Maximizing clinician engagement is important for the success of clinical trials; the strategies employed in the ADAPTABLE trial may serve as a template for future pragmatic studies.

Background: Sideline diagnostic tests for concussion are vulnerable to volitional poor performance ("sandbagging") on baseline assessments, motivated by desire to subvert concussion detection and potential removal from play. We investigated eye movements during sandbagging versus best effort on the King-Devick (KD) test, a rapid automatized naming (RAN) task. Methods: Participants performed KD testing during oculography following instructions to sandbag or give best effort. Results: Twenty healthy participants without concussion history were included (mean age 27 ± 8 years). Sandbagging resulted in longer test times (89.6 ± 39.2 s vs 48.2 ± 8.5 s, p < .001), longer inter-saccadic intervals (459.5 ± 125.4 ms vs 311.2 ± 79.1 ms, p < .001) and greater numbers of saccades (171.4 ± 47 vs 138 ± 24.2, p < .001) and reverse saccades (wrong direction for reading) (21.2% vs 11.3%, p < .001). Sandbagging was detectable using a logistic model with KD times as the only predictor, though more robustly detectable using eye movement metrics. Conclusions: KD sandbagging results in eye movement differences that are detectable by eye movement recordings and suggest an invalid test score. Objective eye movement recording during the KD test shows promise for distinguishing between best effort and post-injury performance, as well as for identifying sandbagging red flags.

Although policies to remove lead from gasoline have resulted in a substantial reduction in airborne lead, multiple industries are known to generate lead that is released in the air. The present study examines the extent to which residential proximity to a documented source of airborne lead is associated with intellectual and executive function in children. Data were available for n = 849 children from the Family Life Project. Geolocation for children's residences between birth and 36 months were referenced against the Environmental Protection Agency's Risk Screening Environmental Indicators (RSEI) database, which estimates exposure for each ½ mile grid in the contiguous United States. Instrumental variable models were employed to estimate causal associations between exposure and cognitive outcomes measured at 36, 48, and 60 months, using census-documented density of manufacturing employment as the instrument. Models of continuous lead dosage indicated small negative effects for both child IQ and executive function (EF). These results indicate that RSEI estimates of airborne lead exposure are meaningfully associated with decrements in cognitive development.

PURPOSE/OBJECTIVE:Tobacco-use is a causative or exacerbating risk factor for benign and malignant urologic disease. However, it is not well known how often urologists screen for tobacco use and provide tobacco cessation treatment at the population level. Therefore, we sought to evaluate how often urologists see patients for tobacco-related diagnoses in the outpatient setting and how often these visits include tobacco-use screening and treatment. MATERIALS AND METHODS/METHODS:We used the National Ambulatory Medical Care Survey (NAMCS) public use files for the years 2014-2016 to identify all outpatient urology visits with adults 18 years and older. Clinic visit reasons were categorized according to diagnoses associated with the encounter: all urologic diagnoses, a tobacco-related urologic condition, or a urologic cancer. Our primary outcome was the percentage of visits during which tobacco screening was reported. Secondary outcomes included reported delivery of cessation counseling and provision of cessation pharmacotherapy. RESULTS:We identified 4,625 unique urologic outpatient encounters, representing a population-weighted estimate of 63.9 million visits over three years. Approximately a third of all urology visits were for a tobacco-related urologic diagnoses and 15% were for urologic cancers. An estimated 1.1 million visits over three years were with patients who identified as current tobacco users. Of all visits, 70% included tobacco screening. However, only 7% of visits with current smokers included counseling and only 3% were prescribed medications. No differences in screening and treatment were observed between visit types. CONCLUSIONS:Urologists regularly see patients for tobacco-related conditions and frequently, though not universally, screen patients for tobacco. However, urologists rarely offer counseling or cessation treatment. These findings may represent missed opportunities to decrease the morbidity associated with tobacco use.

BACKGROUND:Pancreatic cancer (PC) is a complex disease in which both non-genetic and genetic factors interplay. To date, 40 GWAS hits have been associated with PC risk in individuals of European descent, explaining 4.1% of the phenotypic variance. METHODS:We complemented a new conventional PC GWAS (1D) with genome spatial autocorrelation analysis (2D) permitting to prioritize low frequency variants not detected by GWAS. These were further expanded via Hi-C map (3D) interactions to gain additional insight into the inherited basis of PC. In silico functional analysis of public genomic information allowed prioritization of potentially relevant candidate variants. RESULTS:We identified several new variants located in genes for which there is experimental evidence of their implication in the biology and function of pancreatic acinar cells. Among them is a novel independent variant in NR5A2 (rs3790840) with a meta-analysis p value = 5.91E-06 in 1D approach and a Local Moran's Index (LMI) = 7.76 in 2D approach. We also identified a multi-hit region in CASC8-a lncRNA associated with pancreatic carcinogenesis-with a lowest p value = 6.91E-05. Importantly, two new PC loci were identified both by 2D and 3D approaches: SIAH3 (LMI = 18.24), CTRB2/BCAR1 (LMI = 6.03), in addition to a chromatin interacting region in XBP1-a major regulator of the ER stress and unfolded protein responses in acinar cells-identified by 3D; all of them with a strong in silico functional support. CONCLUSIONS:This multi-step strategy, combined with an in-depth in silico functional analysis, offers a comprehensive approach to advance the study of PC genetic susceptibility and could be applied to other diseases.

BACKGROUND:Altered postinjury platelet behavior is recognized in the pathophysiology of trauma-induced coagulopathy (TIC), but the mechanisms remain largely undefined. Studies suggest that soluble factors released by injury may inhibit signaling pathways and induce structural changes in circulating platelets. Given this, we sought to examine the impact of treating healthy platelets with plasma from injured patients. We hypothesized that healthy platelets treated ex-vivo with plasma from injured patients with shock would impair platelet aggregation, while treatment with plasma from injured patients with significant injury burden, but without shock, would enhance platelet aggregation. METHODS:Plasma samples were isolated from injured patients (pretransfusion) and healthy donors at a Level I trauma center and stored at -80°C. Plasma samples from four separate patients in each of the following stratified clinical groups were used: mild injury/no shock (injury severity score [ISS] 2-15, base excess [BE]>-6), mild injury/with shock (ISS 2-15, BE≤-6), severe injury/no shock (ISS>25, BE>-6), severe injury/with shock (ISS>25, BE≤-6), minimal injury (ISS 0/1, BE>-6), and healthy. Platelets were isolated from three healthy adult males and were treated with plasma for 30 min. Aggregation was stimulated with a thrombin receptor agonist and measured via multiple-electrode platelet aggregometry. Data were normalized to HEPES Tyrode's (HT) buffer-only treated platelets. Associations of plasma treatment groups with platelet aggregation measures were tested with Mann-Whitney U tests. RESULTS:Platelets treated with plasma from patients with shock (regardless of degree of injury) had significantly impaired thrombin-stimulated aggregation compared with platelets treated with plasma from patients without shock (P = 0.002). Conversely, platelets treated with plasma from patients with severe injury, but without shock, had amplified thrombin-stimulated aggregation (P = 0.030). CONCLUSION:Shock-mediated soluble factors impair platelet aggregation, and tissue injury-mediated soluble factors amplify platelet aggregation. Future characterization of these soluble factors will support development of novel treatments of TIC.