Supplementary Figure and Table from Genetic Variability of Smoking Persistence in African Americans
Immune cell–based therapies are promising strategies to facilitate immunosuppression withdrawal after organ transplantation. Regulatory dendritic cells (DCreg) are innate immune cells that down-regulate alloimmune responses in preclinical models. Here, we performed clinical monitoring and comprehensive assessment of peripheral and allograft tissue immune cell populations in DCreg-infused live-donor liver transplant (LDLT) recipients up to 12 months (M) after transplant. Thirteen patients were given a single infusion of donor-derived DCreg 1 week before transplant (STUDY) and were compared with 40 propensity-matched standard-of-care (SOC) patients. Donor-derived DCreg infusion was well tolerated in all STUDY patients. There were no differences in postoperative complications or biopsy-confirmed acute rejection compared with SOC patients up to 12M. DCreg administration was associated with lower frequencies of effector T-bet + Eomes + CD8 + T cells and CD16 bright natural killer (NK) cells and an increase in putative tolerogenic CD141 + CD163 + DCs compared with SOC at 12M. Antidonor proliferative capacity of interferon-γ + (IFN-γ + ) CD4 + and CD8 + T cells was lower compared with antithird party responses in STUDY participants, but not in SOC patients, at 12M. In addition, lower circulating concentrations of interleukin-12p40 (IL-12p40), IFN-γ, and CXCL10 were detected in STUDY participants compared with SOC patients at 12M. Analysis of 12M allograft biopsies revealed lower frequencies of graft-infiltrating CD8 + T cells, as well as attenuation of cytolytic T H 1 effector genes and pathways among intragraft CD8 + T cells and NK cells, in DCreg-infused patients. These reductions may be conducive to reduced dependence on immunosuppressive drug therapy or immunosuppression withdrawal.
AbstractTo date, most genetic association analyses of smoking behaviors have been conducted in populations of European ancestry and many of these studies focused on the phenotype that measures smoking quantity, that is, cigarettes per day. Additional association studies in diverse populations with different linkage disequilibrium patterns and an alternate phenotype, such as total tobacco exposure which accounts for intermittent periods of smoking cessation within a larger smoking period as measured in large cardiovascular risk studies, can aid the search for variants relevant to smoking behavior. For these reasons, we undertook an association analysis by using a genotyping array that includes 2,100 genes to analyze smoking persistence in unrelated African American participants from the Atherosclerosis Risk in Communities study. A locus located approximately 4 kb downstream from the 3′-UTR of the brain-derived neurotrophic factor (BDNF) significantly influenced smoking persistence. In addition, independent variants rs12915366 and rs12914385 in the cluster of genes encoding nicotinic acetylcholine receptor subunits (CHRNA5–CHRNA3–CHRNB4) on 15q25.1 were also associated with the phenotype in this sample of African American subjects. To our knowledge, this is the first study to more extensively evaluate the genome in the African American population, as a limited number of previous studies of smoking behavior in this population included evaluations of only single genomic regions. Cancer Prev Res; 4(5); 729–34. ©2011 AACR.
Tran, Lillian M. MD; Macedo, Camila MD; Zahorchak, Alan F. MS; Tabib, Tracy MS; Styn, Mindi A. PhD; Metes, Diana M. MD; Lakkis, Fadi G. MD; Humar, Abhinav MD; Thomson, Angus W. PhD Author Information
Regulatory dendritic cells (DCreg) promote transplant tolerance following their adoptive transfer in experimental animals. We investigated the feasibility, safety, fate, and impact on host T cells of donor monocyte-derived DCreg infused into prospective, living donor liver transplant patients, 7 days before transplantation. The DCreg expressed a tolerogenic gene transcriptional profile, high cell surface programed death ligand-1 (PD-L1):CD86 ratios, high IL-10/no IL-12 productivity and poor ability to stimulate allogeneic T cell proliferation. Target DCreg doses (range 2.5–10 × 106 cells/kg) were achieved in all but 1 of 15 recipients, with no infusion reactions. Following DCreg infusion, transiently elevated levels of donor HLA and immunoregulatory PD-L1, CD39, and CD73 were detected in circulating small extracellular vesicles. At the same time, flow and advanced image stream analysis revealed intact DCreg and “cross-dressing” of host DCs in blood and lymph nodes. PD-L1 co-localization with donor HLA was observed at higher levels than with recipient HLA. Between DCreg infusion and transplantation, T-bethiEomeshi memory CD8+ T cells decreased, whereas regulatory (CD25hiCD127–Foxp3+): T-bethiEomeshi CD8+ T cell ratios increased. Thus, donor-derived DCreg infusion may induce systemic changes in host antigen-presenting cells and T cells potentially conducive to modulated anti-donor immune reactivity at the time of transplant.
Background Based on strong preclinical data showing that regulatory dendritic cells (DCreg) of donor origin can promote long-term graft survival in rodents and suppress allograft rejection in non-human primates, we have embarked on a first-in-human phase I/II safety and preliminary efficacy trial of donor-derived DCreg in living donor liver transplantation (LTx). Methods In the study protocol, DCreg are generated from elutriated monocytes isolated from the leukapheresed donor,14-28 days (d) before transplant. The donor-derived DCreg are infused iv (target range 2.5-10.106/kg) 7 d before transplant (d −7), while a half dose of MPA is administered from d −7 to d 0. Standard-of-care immunosuppression (steroid, MPA, tacrolimus) is administered post-LTx, and in those patients that meet eligibility criteria for weaning, immunosuppressive therapy is gradually withdrawn, starting with MPA reduction 6 mths post-LTx. Sequential immunological analyses are conducted on recipient blood and tissue samples to track the donor-derived DCreg, evaluate anti-donor reactivity and examine potential mechanisms of immune hyporesponsiveness. In the first LTx recipient (HLA-B12+) to receive donor-derived (HLA-A3+) DCreg, peripheral blood samples were obtained before and after cell infusion; native liver tissue was obtained at the time of graft implantation. Results Donor-derived DCreg generated for infusion were HLA-DR+, CD1c−, CD11c+, CD83−, IRF4lo and expressed a high programed death ligand-1 (PD-L1):CD86 ratio. In parallel small scale in vitro functional analyses, the DCreg failed to respond to LPS, and induced donor-specific hyporesponsiveness of recipient CD4 and CD8 T cells. The donor-derived DCreg (HLA-A3+) displaying a similar phenotype to that exhibited pre-infusion, were detected in whole blood immediately after completion of the cell infusion that comprised 5.106 DCreg/kg (450.106 total DCreg). No infusion reaction or cytokine release response was observed. Three days post-infusion (d −4), HLA-A3+ donor-derived DC could no longer be detected in blood, although a small population of DC co-expressing both recipient (HLA-B12) and donor MHC (HLA-A3), ie cross-dressed DC, were evident in the circulation. At the time of transplant, before graft implantation, cross-dressed (HLA-A3+B12+) DC could also be detected in non-parenchymal cell populations isolated from the diseased native liver. Using a 14-color panel of mAbs, these tissue-resident cross-dressed DC were PD-L1hi, IRF4lo and Foxp3hi Conclusions After safe infusion of donor-derived DCreg into a prospective living donor LTx recipient, cross-dressed DC were detected in the peripheral blood within a few days and in the native diseased liver at the time of graft implantation. These cross-dressed DC, that appear to have acquired donor MHC from the infused DCreg, exhibit low levels of the DC transcription/maturation factor IRF4 and high levels of PD-L1 and Foxp3, suggesting possible in vivo regulatory function.
Self-monitoring (SM) of food intake is central to weight loss treatment. Technology makes it possible to reinforce this behavior change strategy by providing real-time feedback (FB) tailored to the diary entry. To test the feasibility of providing 1–4 daily FB messages tailored to dietary recordings via a smartphone, we conducted a 12-week pilot randomized clinical trial in Pittsburgh, PA in US in 2015. We compared 3 groups: SM using the Lose It! smartphone app (Group 1); SM+FB (Group 2); and SM+FB+attending three in-person group sessions (Group 3). The sample (N=39) was mostly white and female with a mean body mass index of 33.76kg/m2. Adherence to dietary SM was recorded daily, weight was assessed at baseline and 12weeks. The mean percentage of days adherent to dietary SM was similar among Groups 1, 2, and 3 (p=0.66) at 53.50% vs. 55.86% vs. 65.33%, respectively. At 12weeks, all groups had a significant percent weight loss (p<0.05), with no differences among groups (−2.85% vs. −3.14% vs. −3.37%) (p=0.95); 26% of the participants lost≥5% of their baseline weight. Mean retention was 74% with no differences among groups (p=0.37). All groups adhered to SM at levels comparable to or better than other weight loss studies and lost acceptable amounts of weight, with minimal intervention contact over 12weeks. These preliminary findings suggest this 3-group approach testing SM alone vs. SM with real-time FB messages alone or supplemented with limited in-person group sessions warrants further testing in a larger, more diverse sample and for a longer intervention period.
Background Ecological momentary assessment (EMA) assesses individuals’ current experiences, behaviors, and moods as they occur in real time and in their natural environment. EMA studies, particularly those of longer duration, are complex and require an infrastructure to support the data flow and monitoring of EMA completion. Objective Our objective is to provide a practical guide to developing and implementing an EMA study, with a focus on the methods and logistics of conducting such a study. Methods The EMPOWER study was a 12-month study that used EMA to examine the triggers of lapses and relapse following intentional weight loss. We report on several studies that informed the implementation of the EMPOWER study: (1) a series of pilot studies, (2) the EMPOWER study’s infrastructure, (3) training of study participants in use of smartphones and the EMA protocol and, (4) strategies used to enhance adherence to completing EMA surveys. Results The study enrolled 151 adults and had 87.4% (132/151) retention rate at 12 months. Our learning experiences in the development of the infrastructure to support EMA assessments for the 12-month study spanned several topic areas. Included were the optimal frequency of EMA prompts to maximize data collection without overburdening participants; the timing and scheduling of EMA prompts; technological lessons to support a longitudinal study, such as proper communication between the Android smartphone, the Web server, and the database server; and use of a phone that provided access to the system’s functionality for EMA data collection to avoid loss of data and minimize the impact of loss of network connectivity. These were especially important in a 1-year study with participants who might travel. It also protected the data collection from any server-side failure. Regular monitoring of participants’ response to EMA prompts was critical, so we built in incentives to enhance completion of EMA surveys. During the first 6 months of the 12-month study interval, adherence to completing EMA surveys was high, with 88.3% (66,978/75,888) completion of random assessments and around 90% (23,411/25,929 and 23,343/26,010) completion of time-contingent assessments, despite the duration of EMA data collection and challenges with implementation. Conclusions This work informed us of the necessary preliminary steps to plan and prepare a longitudinal study using smartphone technology and the critical elements to ensure participant engagement in the potentially burdensome protocol, which spanned 12 months. While this was a technology-supported and -programmed study, it required close oversight to ensure all elements were functioning correctly, particularly once human participants became involved.
African Americans (AAs) bear a disproportionate burden of the obesity epidemic, yet have historically been underrepresented in weight loss research. We conducted a narrative review of large ( N > 75) randomized prospective clinical trials of standard behavioral treatment for weight loss that reported results in the past 15 years (2001-2015) to (a) determine the rates of inclusion and reported results for AAs and (b) further identify strategies that may result in improved outcomes. Of the 23 trials reviewed, 69.6% of the studies met or exceeded population estimates for AAs in the United States. However, only 10 reported outcomes and/or considered race in the analytic approach. At 6 months, AA participants consistently lost less weight than White participants. The use of culturally tailored intervention materials and monthly personal telephone calls were reported as factors that may have enhanced treatment response. Future behavioral weight loss trials should also increase reporting of outcomes by race.
Background: The surveillance of patients with nondysplastic Barrett's esophagus (NDBE) has a high cost and is of limited effectiveness in preventing esophageal adenocarcinoma (EAC). Ablation for NDBE remains expensive and controversial. Biomarkers of genomic instability have shown promise in identifying patients with NDBE at high risk for progression to EAC. Here, we evaluate the cost-effectiveness of using such biomarkers to stratify patients with NDBE by risk for EAC and, subsequently, the cost-effectiveness of ablative therapy.Methods: A Markov decision tree was used to evaluate four strategies in a hypothetical cohort of 50-year old patients with NDBE over their lifetime: strategy I, natural history without surveillance; strategy II, surveillance per current guidelines; strategy III, ablation for all patients; strategy IV, risk stratification with use of a biomarker panel to assess genomic instability (i.e., mutational load [ML]). Patients with no ML underwent minimal surveillance, patients with low ML underwent standard surveillance, and patients with high ML underwent ablation. The incremental cost-effectiveness ratio (ICER) and incremental net health benefit (INHB) were assessed.Results: Strategy IV provided the best values for quality-adjusted life years (QALYs), ICER, and INHB in comparison with strategies II and III. Results were robust in sensitivity analysis. In a Monte Carlo analysis, the relative risk for the development of cancer in the patients managed with strategy IV was decreased. Critical determinants of strategy IV cost-effectiveness were the complete response rate, cost of ablation, and surveillance interval in patients with no ML.Conclusion: The use of ML to stratify patients with NDBE by risk was the most cost-effective strategy for preventive EAC treatment. Targeting ablation toward patients with high ML presents an opportunity for a paradigm shift in the management of NDBE.
Cigarette smoking is the leading preventable cause of death worldwide. The aim of this study is to conduct a prospective and retrospective analysis of smoking behavior changes in the Lovelace Smokers Cohort (LSC) and the Pittsburgh Lung Screening Study cohort (PLuSS). Area under the curve (AUC) for risk models predicting relapse based on demographic, smoking, and relevant clinical variables was 0.93 and 0.79 in LSC and PLuSS, respectively. The models for making a quit attempt had limited prediction ability in both cohorts (AUC≤0.62). We identified an ethnic disparity in adverse smoking behavior change that Hispanic smokers were less likely to make a quit attempt and were more likely to relapse after a quit attempt compared to non-Hispanic Whites. SNPs at 15q25 and 11p14 loci were associated with risk for smoking relapse in the LSC. Rs6495308 at 15q25 has a large difference in minor allele frequency between non-Hispanic Whites and Hispanics (0.46 versus 0.23, P<0.0001) and was associated with risk for ever relapse at same magnitude between the two ethnic groups (OR=1.36, 95% CI=1.10 to 1.67 versus 1.59, 95% CI=1.00 to 2.53, P=0.81). In summary, the risk prediction model established in LSC and PLuSS provided an excellent to outstanding distinguishing for abstainers who will or will not relapse. The ethnic disparity in adverse smoking behavior between Hispanics and non-Hispanic Whites may be at least partially explained by the sequence variants at 15q25 locus that contains multiple nicotine acetylcholine receptors.
Objective The SELF Trial examined the effect of adding individual self-efficacy (SE) enhancement sessions to standard behavioral weight loss treatment (SBT). Methods Participants were randomly assigned to SBT or SBT plus SE sessions (SBT+SE). Outcome measures were weight loss maintenance, quality of life, intervention adherence, and self-efficacy at 12 and 18 months. Results The sample (N = 130) was female (83.08%) with a mean (SD) body mass index of 33.15 (4.11) kg m2. There was a significant time effect for percent weight change (P = 0.002) yet no significant group or group-by-time effects. The weight loss for the SBT+SE group was 8.38% (7.48) at 12 months and 8.00% (7.87) at 18 months, with no significant difference between the two time points (P = 0.06). However, weight loss for the SBT group was 6.95% (6.67) at 12 months and 5.96% (7.35) at 18 months, which was significantly different between the two time points (P = 0.005), indicating that the SBT group had significant weight regain. Conclusions Both groups achieved clinically significant weight loss. The group receiving an intervention targeting enhanced self-efficacy had greater weight loss maintenance whereas the SBT group demonstrated significant weight regain possibly related to the greater attention provided to the SBT+SE group.
G A A b st ra ct s patterns between normal colonic tissue (N), tubular adenoma (ADT), tubulovillous adenoma (ADTV) and colorectal cancer (CRC) biopsy tissue samples. Furthermore, our aim was to analyze and confirm the expression level of adenoma and CRC related miRNAs in matched plasma samples. METHODS: Sixty fresh frozen colorectal biopsy (n=20 N, n=11 ADT, n= 9 ADTV, n=20 CRC) and 16 matched plasma samples (n=4 N, n=4 ADT, n=4 ADTV, n=4 CRC) were collected and total RNA including miRNA was isolated (High Pure miRNA Isolation Kit, Roche,Germany). MiRNA expression analysis was performed on GeneChip® miRNA 3.0 Arrays (Affymetrix,USA). Then, the results of microarray analysis were confirmed on RT-qPCR arrays (microRNAReady-to-use PCRHuman Panel I+II V2.R; Exiqon, Denmark). The matched plasma samples were also evaluated by the same miRNA expression and RTqPCR arrays. The obtained results were analyzed by Expression Console (Affymetrix,USA). RESULTS: Out of the 1733 detectable number of miRNAs on the array, in normal biopsies 442, in adenomas 460, and in CRC 441 miRNA could be identified. In plasma these were 306, 334, and 321 miRNA, respectively. Interestingly, 12 miRNAs were upregulated (e.g. miR-31 logFC=3, p<0,001) and 11 miRNA were downregulated only (e.g. miR-10b, logFC=1.7 p<0.001) in neoplastic lesions (AD+CRC) compared to N tissue samples. 11 miRNAs showed altered expression between ADT and ADTV (e.g. miR-183 LogFC=1.5 p<0.007). Expression levels of 9 miRNAs were found to be changed between ADT,TV and CRC groups based on tissue biopsy microarray data (e.g. miR-196a logFC=-1.8 p<0.001). Only three miRNA(-31;-4506;-452*) have been found to be differentially expressed in adenoma compared to normal. Significant positive overexpression was observed in tissue (logFC=5 p= 0.003) and in plasma (logFC=0.3 p=0.02) in case of miR-31 in the adenoma cases. Moreover, increased expressions were detected in CRC compared to healthy controls in tissue and plasma levels of miR-187;-675;-3591-3p (p<0.05). The observed miRNA expression changes could be confirmed by RT-qPCR arrays in both plasma and tissue samples. CONCLUSION: A small number (n=23) of miRNA showed characteristic alterations during neoplastic development in biopsy tissue. Our observations suggest that miRNA are also present in the plasma fraction and their expression is positively correlated with matched tissue expression levels. The identified miRNA expression changes are consistent by different methods through the adenoma-dysplasia-carcinoma sequence.
OBJECTIVES:Risk stratification in Barrett's esophagus (BE) is challenging. We evaluated the ability of a panel of genetic markers to predict progression to high-grade dysplasia (HGD) or esophageal adenocarcinoma (EAC). METHODS:In this case-control study, we assessed a measure of genetic instability, the mutational load (ML), in predicting progression to HGD or EAC. Cases had nondysplastic BE or low-grade dysplasia (LGD) at baseline and developed HGD/EAC ≥1 year later. Controls were matched 2:1, had nondysplastic BE or LGD, and no progression at follow-up. Formalin-fixed, paraffin-embedded tissue was microdissected for the epithelium. Loss of heterozygosity (LOH) and microsatellite instability (MSI) were assessed. ML was calculated from derangements in 10 genomic loci. High-clonality LOH mutations were assigned a value of 1, low-clonality mutations were assigned a value of 0.5, and MSI 0.75 at the first loci, and 0.5 for additional loci. These values were summed to the ML. Receiver operator characteristic (ROC) curves were created. RESULTS:There were 69 patients (46 controls and 23 cases). Groups were similar in age, follow-up time, baseline histology, and the number of microdissected targets. Mean ML in pre-progression biopsies was higher in cases (2.21) than in controls (0.42; P<0.0001). Sensitivity was 100% at ML ≥0.5 and specificity was 96% at ML ≥1.5. Accuracy was highest at 89.9% for ML ≥1. ROC curves for ML ≥1 demonstrated an area under the curve (AUC) of 0.95. CONCLUSIONS:ML in pre-progression BE tissue predicts progression to HGD or EAC. Although further validation is necessary, ML may have utility as a biomarker in endoscopic surveillance of BE.
Health-related technology, its relevance, and its availability are rapidly evolving. Technology offers great potential to minimize and/or mitigate barriers associated with achieving optimal health, performance, and readiness. In support of the U.S. Army Surgeon General's vision for a "System for Health" and its Performance Triad initiative, the U.S. Army Telemedicine and Advanced Technology Research Center hosted a workshop in April 2013 titled "Incentives to Create and Sustain Change for Health." Members of government and academia participated to identify and define the opportunities, gain clarity in leading practices and research gaps, and articulate the characteristics of future technology solutions to create and sustain real change in the health of individuals, the Army, and the nation. The key factors discussed included (1) public health messaging, (2) changing health habits and the environmental influence on health, (3) goal setting and tracking, (4) the role of incentives in behavior change intervention, and (5) the role of peer and social networks in change. This report summarizes the recommendations on how technology solutions could be employed to leverage evidence-based best practices and identifies gaps in research where further investigation is needed.
OBJECTIVE:Obesity has been linked to a wide spectrum of malignancies, with the strongest association demonstrated for endometrial cancer. Although the mechanisms are not yet entirely clear, a number of risk biomarkers have been proposed, including altered adipokines. Systemic levels of these adipose derived molecules have also been linked in prior research to self-reported quality of life (QOL). The study objective was to examine the hypothesis that adipokine changes during intentional weight loss may be associated with changes in QOL.METHODS:Fifty-two female participants were selected from two behavioral weight loss trials (SMART and PREFER) on the basis of achieving successful weight loss at 6month assessment, availability of blood samples and completion of standard SF-36 QOL questionnaires. Levels of adiponectin, leptin, and resistin were measured using xMAP immunoassays. Changes in QOL were examined using linear regression models in relation to pre- and post-intervention changes in biomarker levels and BMI.RESULTS:Significant changes between pre- and post-intervention were observed for leptin. Controlling for baseline BMI, leptin was the only biomarker that predicted change in QOL (Physical Component Scale, PCS). Linear regression models demonstrated that leptin continued to be a significant predictor of change in PCS when other possible predictor variables were included in the model.CONCLUSIONS:This study is among the first to demonstrate that changes in PCS may be regulated by levels of both metabolic variables and adipokines. An improved understanding of biological mechanisms associated with weight loss and the role of QOL may help guide preventive strategies for obesity-associated cancers.
BACKGROUND:This study aimed to better understand the supporting role that mutational profiling (MP) of DNA from microdissected cytology slides and supernatant specimens may play in the diagnosis of malignancy in fine-needle aspirates (FNA) and biliary brushing specimens from patients with pancreaticobiliary masses.METHODS:Cytology results were examined in a total of 30 patients with associated surgical (10) or clinical (20) outcomes. MP of DNA from microdissected cytology slides and from discarded supernatant fluid was analyzed in 26 patients with atypical, negative or indeterminate cytology.RESULTS:Cytology correctly diagnosed aggressive disease in 4 patients. Cytological diagnoses for the remaining 26 were as follows: 16 negative (9 false negative), 9 atypical, 1 indeterminate. MP correctly determined aggressive disease in 1 false negative cytology case and confirmed a negative cytology diagnosis in 7 of 7 cases of non-aggressive disease. Of the 9 atypical cytology cases, MP correctly diagnosed 7 as positive and 1 as negative for aggressive disease. One specimen that was indeterminate by cytology was correctly diagnosed as non-aggressive by MP. When first line malignant (positive) cytology results were combined with positive second line MP results, 12/21 cases of aggressive disease were identified, compared to 4/21 cases identified by positive cytology alone.CONCLUSIONS:When first line cytology results were uncertain (atypical), questionable (negative), or not possible (non-diagnostic/indeterminate), MP provided additional information regarding the presence of aggressive disease. When used in conjunction with first line cytology, MP increased detection of aggressive disease without compromising specificity in patients that were difficult to diagnose by cytology alone.
Background:Evidence supports the role of feedback in reinforcing motivation for behavior change. Feedback that provides reinforcement has the potential to increase dietary self-monitoring and enhance attainment of recommended dietary intake. Objective:The aim of this study was to examine the impact of daily feedback (DFB) messages, delivered remotely, on changes in dietary intake. Methods:This was a secondary analysis of the Self- Monitoring And Recording using Technology (SMART) Trial, a single-center, 24-month randomized clinical trial of behavioral treatment for weight loss. Participants included 210 obese adults (mean body mass index, 34.0 kg/m2) who were randomized to either a paper diary (PD), personal digital assistant (PDA), or PDA plus daily tailored feedback messages (PDA + FB). To determine the role of daily tailored feedback in dietary intake, we compared the self-monitoring with DFB group (DFB group; n = 70) with the self-monitoring without DFB group (no-DFB group, n = 140). All participants received a standard behavioral intervention for weight loss. Self-reported changes in dietary intake were compared between the DFB and no-DFB groups and were measured at baseline and at 6, 12, 18, and 24 months. Linear mixed modeling was used to examine percentage changes in dietary intake from baseline. Results:Compared with the no-DFB group, the DFB group achieved a larger reduction in energy (−22.8% vs −14.0%; P = .02) and saturated fat (−11.3% vs −0.5%; P = .03) intake and a trend toward a greater decrease in total fat intake (−10.4% vs −4.7%; P = .09). There were significant improvements over time in carbohydrate intake and total fat intake for both groups (P values < .05). Conclusion:Daily tailored feedback messages designed to target energy and fat intake and delivered remotely in real time using mobile devices may play an important role in the reduction of energy and fat intake.
Barrett's Esophagus (BE) is a known precursor to esophageal adenocarcinoma (EAC); however, the risk of progression is low. Risk stratification before histologically evident progression could allow for more targeted surveillance/treatment strategies. Genomic instability has been associated with progression. DNA from lower risk BE histological classifications can, in some cases, share a similar level of genomic instability as higher risk histological classifications (high grade dysplasia [HGD] and EAC). This longitudinal study aimed to determine if mutational load (ML), a measure of genomic instability, could identify and distinguish patients at high and low risk of progression.