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Background: Continuous energy restriction (CER) is purported to be problematic because of reductions in fat-free mass (FFM), compensatory motivation to overeat, and weakened satiety. Intermittent energy restriction (IER) is an alternative behavioral weight loss (WL) strategy that may mitigate some of these limitations., Objective: The objective of the DIVA study was to compare the effects of CER and IER on appetite when the degree of WL (≥5%) is matched., Methods: Women with overweight/obesity (BMI 25.0-34.9 kg/m2; age 18-55 y) were recruited for this controlled-feeding RCT via CER (25% daily energy restriction) or IER (alternating ad libitum and 75% energy restriction days). Probe days were conducted at baseline and post-intervention to assess body composition, ad libitum energy intake and subjective appetite in response to a fixed-energy breakfast, and eating behavior traits. After baseline measurements, participants were allocated to CER (n = 22) or IER (n = 24). Per protocol analyses (≥5% WL within 12 wk) were conducted with use of repeated measures ANOVA., Results: Thirty of 37 completers reached ≥5% WL [CER (n = 18): 6.3 ± 0.8% in 57 ± 16 d, IER (n = 12): 6.6 ± 1.1% in 67 ± 13 d; % WL P = 0.43 and days P = 0.10]. Fat mass [-3.9 (95% CI: -4.3, -3.4) kg] and FFM [-1.3 (95% CI: -1.6, -1.0) kg] were reduced post-WL (P < 0.001), with no group differences. Self-selected meal size decreased post-WL in CER (P = 0.03) but not in IER (P = 0.19). Hunger AUC decreased post-WL (P < 0.05), with no group differences. Satiety quotient remained unchanged and was similar in both groups. Both interventions improved dietary restraint, craving control, susceptibility to hunger, and binge eating (P < 0.001)., Conclusions: Controlled ≥5% WL via CER or IER did not differentially affect changes in body composition, reductions in hunger, and improvements in eating behavior traits. This suggests that neither CER nor IER lead to compensatory adaptations in appetite in women with overweight/obesity. This trial was registered at clinicaltrials.gov as NCT03447600., (Copyright © The Author(s) 2019.)

Background: Several studies have explored the role of human brown adipose tissue (BAT) in energy expenditure. However, the link between BAT and appetite regulation needs to be more rigorously examined., Objectives: We aimed to investigate the associations of BAT volume and 18F-fluordeoxyglucose (18F-FDG) uptake after a personalized cold exposure with energy intake and appetite-related sensations in young healthy humans., Methods: A total of 102 young adults (65 women; age: 22.08 ± 2.17 y; BMI: 25.05 ± 4.93 kg/m 2) took part in this cross-sectional study. BAT volume, BAT 18F-FDG uptake, and skeletal muscle 18F-FDG uptake were assessed by means of static 18F-FDG positron-emission tomography and computed tomography scans after a 2-h personalized exposure to cold. Energy intake was estimated via an objectively measured ad libitum meal and three nonconsecutive 24-h dietary recalls. Appetite-related sensations (i.e., hunger and fullness) were recorded by visual analog scales before and after a standardized breakfast (energy content = 50% of basal metabolic rate) and the ad libitum meal. Body composition was assessed by a whole-body DXA scan., Results: BAT volume and 18F-FDG uptake were not associated with quantified ad libitum energy intake (all P > 0.088), nor with habitual energy intake estimated from the 24-h dietary recalls (all P  > 0.683). Lean mass was positively associated with both the energy intake from the ad libitum meal (β: 17.612, R2 = 0.213; P < 0.001) and the habitual energy intake (β: 16.052, R2 = 0.123; P = 0.001). Neither the interaction BAT volume × time elapsed after meal consumption nor that of BAT 18F-FDG uptake × time elapsed after meal consumption had any significant influence on appetite-related sensations after breakfast or after meal consumption (all P > 0.3)., Conclusions: Neither BAT volume, nor BAT 18F-FDG uptake after cold stimulation, are related to appetite regulation in young adults. These results suggest BAT plays no important role in the regulation of energy intake in humans.This trial was registered at clinicaltrials.gov as NCT02365129., (Copyright © The Author(s) 2019.)

Objective: Whole-genome sequencing is being implemented in research and clinical care, yet tools to assess patients' knowledge are lacking. Our aim was to develop a robust measure of whole-genome sequencing knowledge suitable for patients and other stakeholders including research participants, public, students, and healthcare professionals., Methods: An initial set of 17 items was developed via an iterative process including literature review, expert consultation, focus groups, and cognitive interviews with patients, and then administered to 243 individuals. We used exploratory factor analysis and item-response theory to confirm the psychometric suitability of the candidate items for assessing whole-genome sequencing knowledge., Results: There was a strong main component after removing 5 items with low factor loadings. Item and scale homogeneity was achieved using Mokken scale analysis. Three further items were removed because they were misfits, inverse duplicates or resulted in local dependency. The remaining nine items fitted the two-parameter logistic IRT model which achieved excellent fit to the observed data. Cronbach's alpha was 0.79 indicating acceptable reliability., Conclusion: The KOGS, developed using a rigorous psychometric approach, is a brief and reliable tool., Practice Implications: The KOGS may prove useful for researchers and healthcare professionals using whole-genome sequencing with patients and other stakeholders., (Copyright © 2018. Published by Elsevier B.V.)

Background & Aims: Alternate day fasting (ADF; 25% energy intake "fast day", alternated with an ad libitum intake "feed day") is effective for weight loss. Whether or not ADF modulates hunger, fullness and gut peptides in a way that enhances dietary compliance and weight loss, remains unknown. Accordingly, this study examined the effect of ADF on postprandial appetite ratings and gut peptides., Methods: Obese subjects (n = 59) participated in an 8-week ADF protocol where food was provided on the fast day., Results: Body weight decreased (P < 0.0001) by 3.9 ± 0.6 kg after 8 weeks of diet. Reductions (P < 0.05) in fat mass (-2.2 ± 0.2 kg), fat free mass (-1.4 ± 0.2 kg), visceral fat mass (-0.1 ± 0.1 kg), and resting metabolic rate (RMR; -104 ± 28 kcal/day) were also observed. Fasting leptin and insulin decreased (P < 0.05), while AUC ghrelin levels increased (P < 0.05). Despite these metabolic changes, there was no increase in subjective hunger by the end of the study. Furthermore, fullness and PYY increased (P < 0.05). Fat free mass and RMR were not related to hunger or ghrelin at any time point., Conclusion: These findings suggest that the absence of a compensatory increase in hunger in conjunction with an increase in sensations of fullness may contribute to the weight loss efficacy of an 8-week ADF regimen., (Copyright © 2016 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Aims: As the proportion of people with multiple chronic conditions grows, so does the complexity of patient care. Although office-based visits to subspecialists are expected to be intense, due to the focused nature of the visit, the complexity of office-based visits to primary care physicians has yet to be explored in depth. To explore complexity, we looked at diabetes as a case study to determine whether and how the complexity of office-based visits varies by physician specialty type, as measured by the number of diagnoses reported per visits., Methods: The Medical Expenditure Panel Survey data is used to create a nationally-representative sample of adults who self-report a diabetes diagnosis, the specialty of the treating physician for their care, and the number of diagnoses for each visit. Using cross tabulations, the distribution of office-based visits are analyzed based on a categorization of patients by number of visit diagnoses, number of conditions reported, and type of physician seen., Results: Almost 80 percent of visits made by adults with diabetes to subspecialist involved care for that single diagnosis; while 55 percent of visits to primary care involved care for at least one additional diagnosis. Almost 70 percent of visits in which only one diagnosis was reported were to subspecialist physicians. Almost 90 percent of visits in which four diagnoses were reported were to primary care physicians., Conclusions: Office-based visits to primary care physicians are made increasingly complex by growing population morbidity. Adults with diabetes report more conditions being cared for per visit with primary care physicians than with subspecialty physicians. Future studies into where our results hold for other chronic conditions would be beneficial. As recent United States legislation moves health care payment toward paying for value and population health, encounter complexity should be accommodated., (Copyright © 2015 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.)

Individuals with severe motor impairments commonly enter text using a single binary switch and symbol scanning methods. We present a new scanning method -Huffman scanning - which uses Huffman coding to select the symbols to highlight during scanning, thus minimizing the expected bits per symbol. With our method, the user can select the intended symbol even after switch activation errors. We describe two varieties of Huffman scanning - synchronous and asynchronous -and present experimental results, demonstrating speedups over row/column and linear scanning.

Background: There are strong logical reasons why energy expended in metabolism should influence the energy acquired in food-intake behavior. However, the relation has never been established, and it is not known why certain people experience hunger in the presence of large amounts of body energy., Objective: We investigated the effect of the resting metabolic rate (RMR) on objective measures of whole-day food intake and hunger., Design: We carried out a 12-wk intervention that involved 41 overweight and obese men and women [mean ± SD age: 43.1 ± 7.5 y; BMI (in kg/m(2)): 30.7 ± 3.9] who were tested under conditions of physical activity (sedentary or active) and dietary energy density (17 or 10 kJ/g). RMR, daily energy intake, meal size, and hunger were assessed within the same day and across each condition., Results: We obtained evidence that RMR is correlated with meal size and daily energy intake in overweight and obese individuals. Participants with high RMRs showed increased levels of hunger across the day (P < 0.0001) and greater food intake (P < 0.00001) than did individuals with lower RMRs. These effects were independent of sex and food energy density. The change in RMR was also related to energy intake (P < 0.0001)., Conclusions: We propose that RMR (largely determined by fat-free mass) may be a marker of energy intake and could represent a physiologic signal for hunger. These results may have implications for additional research possibilities in appetite, energy homeostasis, and obesity. This trial was registered under international standard identification for controlled trials as ISRCTN47291569.

Killer-cell immunoglobulin-like receptor (KIR) proteins are expressed on natural killer (NK) cells and appear important in innate and adaptive immunity. There are about 14 KIR genes on chromosome 19q13.4, composed of those that inhibit and those that activate NK cell killing. Haplotypes have different combinations of these genes meaning that not all genes are present in a subject. There are two main classes of cognate human leukocyte antigen (HLA) ligands (HLA-Bw4 and HLA-C1/C2) that bind to the inhibitory/activating receptors. As a general rule, the inhibitory state is maintained except when virally infected or tumor cells are encountered; however, both increased activation and inhibition states have been associated with susceptibility and protection against numerous disease states including cancer, arthritis, and psoriasis. Utilizing DNA from 158 Caucasian subjects with autism and 176 KIR control subjects we show for the first time a highly significant increase in four activating KIR genes (2DS5, 3DS1, 2DS1 and 2DS4) as measured by chi square values and odds ratios. In addition, our data suggests a highly significant increase in the activating KIR gene 2DS1 and its cognate HLA-C2 ligand (2DS1+C2; p = 0.00003 [Odds ratio = 2.87]). This information ties together two major immune gene complexes, the human leukocyte complex and the leukocyte receptor complex, and may partially explain immune abnormalities observed in many subjects with autism., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Objective: Aneurysm growth after endovascular aneurysm repair (EVAR) in patients with type II endoleak is associated with adverse outcomes. This study evaluated the long-term success of embolization of type II endoleaks in preventing aneurysm sac growth., Methods: We retrospectively reviewed outcomes of patients who underwent infrarenal EVAR who were treated for a type II endoleak between 2000 and 2008. Computed tomography scans were evaluated for aneurysm sac growth or shrinkage from the time of treatment of the endoleak. The embolization material used, graft type, target vessel embolized, and comorbidities were evaluated for their association with sac growth or shrinkage., Results: Ninety-five patients underwent 140 embolization procedures. The mean time from EVAR to embolization was 26.1 ± 22.2 months, and the average increase in size of the aneurysm sac from EVAR to treatment was 0.7 × 0.5 cm. Patients underwent an average of 1.6 ± 0.8 embolization procedures after EVAR. Thirteen patients underwent initial simultaneous embolization of two targets. Embolization was with glue (61%), coils (29%), glue and coils (7%), and Gelfoam (3%; Pfizer Inc, New York, NY). No abdominal aortic aneurysms (AAA) ruptured. Eight patients (8.4%) underwent graft explant and open repair; 19 (20%) required two or more embolization procedures. There was no difference in the target vessel treated or the treatment used in halting sac expansion (>5 mm). Coil embolization alone resulted in more second procedures. The 5-year cumulative survival was 65% (95% confidence interval [CI], 52%-77%), freedom from explant was 89% (95% CI, 81%-97%), freedom from second embolization was 76% (95% CI, 66%-86%), and freedom from sac expansion >5 mm was 44% (95% CI 30%-50%). Univariable analysis identified continued tobacco use (hazard ratio [HR], 2.30; 95% CI, 1.02-5.13; P = .04) was associated with continued sac expansion, and hyperlipidemia (HR, 9.64; 95% CI, 2.22-41.86) was associated with patients requiring a second embolization procedure., Conclusions: Embolization of type II endoleaks is successful early in preventing aneurysm sac growth and rupture after EVAR. However, a significant number of patients require more than one procedure, and at 5 years, many patients who underwent embolization of a type II endoleak continued to experience sac growth. Patients with hyperlipidemia who undergo coil embolization are more likely to require a second embolization procedure, and patients who smoke have a higher likelihood of AAA sac expansion after embolization. Continued long-term surveillance is necessary in this cohort of patients., (Copyright © 2012 Society for Vascular Surgery. Published by Mosby, Inc. All rights reserved.)

Although interaction between programmed death-1 (PD-1) and the ligand PD-L1 has been shown to mediate CD8 cell exhaustion in the setting of chronic infection or the absence of CD4 help, a role for this pathway in attenuating early alloreactive CD8 cell responses has not been identified. We demonstrate that the PD-1/PD-L1 pathway is needed to rapidly tolerize alloreactive CD8 cells in a model that requires CD4 cells and culminates in CD8 cell deletion. This protocol involves allogeneic bone marrow transplantation (BMT) following conditioning with low-dose total body irradiation and anti-CD154 antibody. Tolerized donor-reactive T-cell receptor transgenic CD8 cells are shown to be in an abortive activation state prior to their deletion, showing early and prolonged expression of activation markers (compared with rejecting CD8 cells) while being functionally silenced by day 4 after transplantation. Although both tolerized and rejecting alloreactive CD8 cells up-regulate PD-1, CD8 cell tolerance is dependent on the PD-1/PD-L1 pathway. In contrast, CD4 cells are tolerized independently of this pathway following BMT with anti-CD154. These studies demonstrate a dichotomy between the requirements for CD4 and CD8 tolerance and identify a role for PD-1 in the rapid tolerization of an alloreactive T-cell population via a deletional mechanism.

A nested case-control study found that the excess of leukemia, identified among the male members of the Health Watch cohort, was associated with benzene exposure. Exposure had been retrospectively estimated for each individual occupational history using an algorithm in a relational database. Benzene exposure measurements, supplied by Australian petroleum companies, were used to estimate exposure for specific tasks. The tasks carried out within each job, the products handled, and the technology used, were identified from structured interviews with contemporary colleagues. More than half of the subjects started work after 1965 and had an average exposure period of 20 years. Exposure was low; nearly 85% of the cumulative exposure estimates were at or below 10 ppm-years. Matched analyses showed that leukemia risk increased with increasing cumulative benzene exposures and with increasing exposure intensity of the highest-exposed job. Non-Hodgkin lymphoma and multiple myeloma were not associated with benzene exposure. A reanalysis reported here, showed that for the 7 leukemia case-sets with greater than 16 ppm-years cumulative exposure, the odds ratio was 51.9 (5.6-477) when compared to the 2 lowest exposed categories combined to form a new reference category. The addition of occasional high exposures, e.g. as a result of spillages, increased exposure for 25% of subjects but for most, the increase was less than 5% of total exposure. The addition of these exposures reduced the odds ratios. Cumulative exposures did not range as high as those in comparable studies; however, the recent nature of the cohort and local handling practices can explain these differences.

Reducing dietary sodium reduces blood pressure (BP), a major risk factor for cardiovascular disease, but few studies have specifically examined the effect on BP of altering dietary sodium in the context of a high potassium diet. This randomized, crossover study compared BP values in volunteer subjects self-selecting food intake and consuming low levels of sodium (Na+; 50 mmol/d) with those consuming high levels of sodium (> or =120 mmol/d), in the context of a diet rich in potassium (K+). Sodium supplementation (NaSp) produced the difference in Na+ intake. Subjects (n = 108; 64 women, 44 men; 16 on antihypertensive therapy) had a mean age of 47.0 +/- 10.1 y. Subjects were given dietary advice to achieve a low sodium (LS) diet with high potassium intake (50 mmol Na+/d, >80 mmol K+/d) and were allocated to NaSp (120 mmol Na+/d) or placebo treatment for 4 wk before crossover. The LS diet decreased urinary Na+ from baseline, 138.7 +/- 5.3 mmol/d to 57.8 +/- 3.8 mmol/d (P < 0.001). The NaSp treatment returned urinary Na+ to baseline levels 142.4 +/- 3.7 mmol/d. Urinary K+ increased from baseline, 78.6 +/- 2.3 to 86.6 +/- 2.1 mmol/d with the LS diet and to 87.1 +/- 2.1 mmol/d with NaSp treatment (P < 0.001). The LS diet reduced home systolic blood pressure (SBP) by 2.5 +/- 0.8 mm Hg (P = 0.004), compared with the NaSp treatment. Hence, reducing Na+ intake from 140 to 60 mmol/d significantly decreased home SBP in subjects dwelling in a community setting who consumed a self-selected K+-rich diet, and this dietary modification could assist in lowering blood pressure in the general population.