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IntroductionWhite matter hyperintensities (WMH) are associated with key dementia etiologies, in particular arteriolosclerosis and amyloid pathology. We aimed to identify WMH locations associated with vascular risk or cerebral amyloid-β1-42 (Aβ42)-positive status.MethodsIndividual patient data (n = 3,132; mean age 71.5 ± 9 years; 49.3% female) from 11 memory clinic cohorts were harmonized. WMH volumes in 28 regions were related to a vascular risk compound score (VRCS) and Aß42 status (based on cerebrospinal fluid or amyloid positron emission tomography), correcting for age, sex, study site, and total WMH volume.ResultsVRCS was associated with WMH in anterior/superior corona radiata (B = 0.034/0.038, p

IntroductionWe aim to provide guidance on outcomes and measures for use in patients with Alzheimer's clinical syndrome.MethodsA consensus group of 20 voting members nominated by 10 professional societies, and a non-voting chair, used a Delphi approach and modified GRADE criteria.ResultsConsensus was reached on priority outcomes (n = 66), measures (n = 49) and statements (n = 37) across nine domains. A number of outcomes and measurement instruments were ranked for: Cognitive abilities; Functional abilities/dependency; Behavioural and neuropsychiatric symptoms; Patient quality of life (QoL); Caregiver QoL; Healthcare and treatment-related outcomes; Medical investigations; Disease-related life events; and Global outcomes.DiscussionThis work provides indications on the domains and ideal pertinent measurement instruments that clinicians may wish to use to follow patients with cognitive impairment. More work is needed to develop instruments that are more feasible in the context of the constraints of clinical routine.

ObjectiveFamily-based treatment (FBT) is a well-established intervention for adolescent anorexia nervosa (AN). Although FBT is efficacious in promoting weight gain and improvements in psychological symptoms, for some adolescents, cognitive/attitudinal recovery lags behind weight gain. This study conducted an exploratory post hoc analysis of outcomes of adolescents who achieved weight gain by the end of FBT but continued to experience elevated psychological symptoms post-treatment.MethodsData were drawn from two randomised controlled trials (RCTs) testing two forms of FBT (conjoint/whole family and parent-focussed). Descriptive statistics and generalised estimating equations were used to examine differences in treatment outcomes between non-cognitive responders (NCRs) (those who regained weight but continued to experience psychological symptoms) and full responders (FRs) (those who achieved both weight and cognitive restoration by the end of treatment) (n = 80; 83.7% female, Agemean [SD] = 14.66 [1.73]).ResultsBy 12 months post-treatment, there were no differences in weight between NCRs and FRs. However, NCRs had a slower trajectory of weight gain than FRs and continued to have elevated levels of psychological symptoms throughout the follow-up period.ConclusionsA subset of adolescents appear to continue to experience clinically significant levels of eating pathology up to 12 months after FBT even when weight restoration is achieved.

The Eating Disorders In weight-related Therapy (EDIT) Collaboration brings together data from randomised controlled trials of behavioural weight management interventions to identify individual participant risk factors and intervention strategies that contribute to eating disorder risk. We present a protocol for a systematic review and individual participant data (IPD) meta-analysis which aims to identify participants at risk of developing eating disorders, or related symptoms, during or after weight management interventions conducted in adolescents or adults with overweight or obesity. We systematically searched four databases up to March 2022 and clinical trials registries to May 2022 to identify randomised controlled trials of weight management interventions conducted in adolescents or adults with overweight or obesity that measured eating disorder risk at pre- and post-intervention or follow-up. Authors from eligible trials have been invited to share their deidentified IPD. Two IPD meta-analyses will be conducted. The first IPD meta-analysis aims to examine participant level factors associated with a change in eating disorder scores during and following a weight management intervention. To do this we will examine baseline variables that predict change in eating disorder risk within intervention arms. The second IPD meta-analysis aims to assess whether there are participant level factors that predict whether participation in an intervention is more or less likely than no intervention to lead to a change in eating disorder risk. To do this, we will examine if there are differences in predictors of eating disorder risk between intervention and no-treatment control arms. The primary outcome will be a standardised mean difference in global eating disorder score from baseline to immediately post-intervention and at 6- and 12- months follow-up. Identifying participant level risk factors predicting eating disorder risk will inform screening and monitoring protocols to allow early identification and intervention for those at risk.

IntroductionThe spatial distribution of white matter hyperintensities (WMH) on MRI is often considered in the diagnostic evaluation of patients with cognitive problems. In some patients, clinicians may classify WMH patterns as "unusual", but this is largely based on expert opinion, because detailed quantitative information about WMH distribution frequencies in a memory clinic setting is lacking. Here we report voxel wise 3D WMH distribution frequencies in a large multicenter dataset and also aimed to identify individuals with unusual WMH patterns.MethodsIndividual participant data (N = 3525, including 777 participants with subjective cognitive decline, 1389 participants with mild cognitive impairment and 1359 patients with dementia) from eleven memory clinic cohorts, recruited through the Meta VCI Map Consortium, were used. WMH segmentations were provided by participating centers or performed in Utrecht and registered to the Montreal Neurological Institute (MNI)-152 brain template for spatial normalization. To determine WMH distribution frequencies, we calculated WMH probability maps at voxel level. To identify individuals with unusual WMH patterns, region-of-interest (ROI) based WMH probability maps, rule-based scores, and a machine learning method (Local Outlier Factor (LOF)), were implemented.ResultsWMH occurred in 82% of voxels from the white matter template with large variation between subjects. Only a small proportion of the white matter (1.7%), mainly in the periventricular areas, was affected by WMH in at least 20% of participants. A large portion of the total white matter was affected infrequently. Nevertheless, 93.8% of individual participants had lesions in voxels that were affected in less than 2% of the population, mainly located in subcortical areas. Only the machine learning method effectively identified individuals with unusual patterns, in particular subjects with asymmetric WMH distribution or with WMH at relatively rarely affected locations despite common locations not being affected.DiscussionAggregating data from several memory clinic cohorts, we provide a detailed 3D map of WMH lesion distribution frequencies, that informs on common as well as rare localizations. The use of data-driven analysis with LOF can be used to identify unusual patterns, which might serve as an alert that rare causes of WMH should be considered.

BackgroundGlobally, critical illness results in millions of deaths every year. Although many of these deaths are potentially preventable, the basic, life-saving care of critically ill patients are often overlooked in health systems. Essential Emergency and Critical Care (EECC) has been devised as the care that should be provided to all critically ill patients in all hospitals in the world. EECC includes the effective care of low cost and low complexity for the identification and treatment of critically ill patients across all medical specialties. This study aimed to specify the content of EECC and additionally, given the surge of critical illness in the ongoing pandemic, the essential diagnosis-specific care for critically ill patients with COVID-19.MethodsIn a Delphi process, consensus (>90% agreement) was sought from a diverse panel of global clinical experts. The panel iteratively rated proposed treatments and actions based on previous guidelines and the WHO/ICRC's Basic Emergency Care. The output from the Delphi was adapted iteratively with specialist reviewers into a coherent and feasible package of clinical processes plus a list of hospital readiness requirements.ResultsThe 269 experts in the Delphi panel had clinical experience in different acute medical specialties from 59 countries and from all resource settings. The agreed EECC package contains 40 clinical processes and 67 requirements, plus additions specific for COVID-19.ConclusionThe study has specified the content of care that should be provided to all critically ill patients. Implementing EECC could be an effective strategy for policy makers to reduce preventable deaths worldwide.

ObjectivePsychotropic medication use in youth with eating disorders (EDs) is poorly understood despite high co-occurrence of psychiatric disorders. This study examined characteristics associated with medication use in treatment-seeking youth with EDs.MethodYouth up to age 18 reported on medication use when presenting to an academic medical center outpatient ED service in the United States. Data presented were collected between 1998-2015.ResultsThe sample (N = 604) was predominantly female (90.6%) with a mean age of 15.3 years (SD = 2.3). Approximately one-third (30%, n = 173) were taking psychotropic medications (40%, n = 70, were taking multiple medications). Antidepressant use was most common (26%, n = 152), followed by atypical antipsychotics (8%, n = 43). Adjusting for co-occurring psychiatric disorders, non-Hispanic Whites who had received prior treatment (psychotherapy, hospitalization) were significantly more likely to be using medication. Longer illness duration and prior treatment were associated with greater antidepressant use. For atypical antipsychotics, prior hospitalization was associated with greater use.ConclusionsFindings confirm moderate psychotropic medication use among young patients with EDs despite a lack of clarity regarding optimally effective pharmacologic interventions in this population. Pharmacological trials examining the efficacy of medications for young patients with EDs are warranted to inform future prescribing practice.

BackgroundPalbociclib is highly active in oestrogen-receptor positive (ER+) metastatic breast cancer, but neutropenia is dose limiting. The goal of this study was to determine whether early neutropenia is associated with disease response to single-agent palbociclib.MethodsBlood count and disease-response data were analysed from two Phase 2 clinical trials at different institutions using single-agent palbociclib: advanced solid tumours positive for retinoblastoma protein and advanced liposarcoma. The primary endpoint was PFS. The primary exposure variable was the nadir absolute neutrophil count (ANC) during the first two cycles of treatment.ResultsOne hundred and ninety-six patients (61 breast, 135 non-breast) were evaluated between the two trials. Development of any grade neutropenia was significantly associated with longer median PFS in both the breast cancer (HR 0.29, 95% CI 0.11-0.74, p = 0.010) and non-breast cancer (HR 0.57, 95% CI 0.38-0.85, p = 0.006) cohorts. Grade 3-4 neutropenia was significantly associated with prolonged PFS in the non-breast cohort (HR 0.57, 95% CI 0.38-0.85, p = 0.006) but not in the breast cohort (HR 0.87, 95% CI 0.51-1.47, p = 0.596). Multivariate analysis yielded similar results.ConclusionsTreatment-related neutropenia in the first two cycles was significantly and independently associated with prolonged PFS, suggesting that neutropenia may be a useful pharmacodynamic marker to guide individualised palbociclib dosing.Clinical trials registration informationBasket Trial: NCT01037790; Sarcoma Trial: NCT01209598.

Given the powerful implications of relationship quality for health and well-being, a central mission of relationship science is explaining why some romantic relationships thrive more than others. This large-scale project used machine learning (i.e., Random Forests) to 1) quantify the extent to which relationship quality is predictable and 2) identify which constructs reliably predict relationship quality. Across 43 dyadic longitudinal datasets from 29 laboratories, the top relationship-specific predictors of relationship quality were perceived-partner commitment, appreciation, sexual satisfaction, perceived-partner satisfaction, and conflict. The top individual-difference predictors were life satisfaction, negative affect, depression, attachment avoidance, and attachment anxiety. Overall, relationship-specific variables predicted up to 45% of variance at baseline, and up to 18% of variance at the end of each study. Individual differences also performed well (21% and 12%, respectively). Actor-reported variables (i.e., own relationship-specific and individual-difference variables) predicted two to four times more variance than partner-reported variables (i.e., the partner's ratings on those variables). Importantly, individual differences and partner reports had no predictive effects beyond actor-reported relationship-specific variables alone. These findings imply that the sum of all individual differences and partner experiences exert their influence on relationship quality via a person's own relationship-specific experiences, and effects due to moderation by individual differences and moderation by partner-reports may be quite small. Finally, relationship-quality change (i.e., increases or decreases in relationship quality over the course of a study) was largely unpredictable from any combination of self-report variables. This collective effort should guide future models of relationships.

De novo mutations arising on the paternal chromosome make the largest known contribution to autism risk, and correlate with paternal age at the time of conception. The recurrence risk for autism spectrum disorders is substantial, leading many families to decline future pregnancies, but the potential impact of assessing parental gonadal mosaicism has not been considered. We measured sperm mosaicism using deep-whole-genome sequencing, for variants both present in an offspring and evident only in father's sperm, and identified single-nucleotide, structural and short tandem-repeat variants. We found that mosaicism quantification can stratify autism spectrum disorders recurrence risk due to de novo mutations into a vast majority with near 0% recurrence and a small fraction with a substantially higher and quantifiable risk, and we identify novel mosaic variants at risk for transmission to a future offspring. This suggests, therefore, that genetic counseling would benefit from the addition of sperm mosaicism assessment.

Objective:Neural substrates of loss of control (LOC) eating are undercharacterized. We aimed to model intermittent access to food to elicit disinhibited eating in youth undergoing neuroimaging, given evidence that restricted food access may increase subsequent food intake via enhancing reward value of food and diminishing eating-related self-control. Methods:Participants were 18 preadolescents (aged 9-12 years) who were overweight/obese with recent LOC eating (OW-LOC; n = 6); overweight/obese with no history of LOC eating (OW-CON; n = 5); or non-overweight with no history of LOC eating (NW-CON; n = 7). Participants underwent functional magnetic resonance imaging during a simulated food restriction paradigm in which they were alternately given restricted or unrestricted access to milkshake solutions. Results:There were no significant main effects of restricted versus unrestricted access to milkshake flavors. Group main effects revealed increased activation for OW-LOC relative to OW-CON in areas related to attentional processes (right middle frontal gyrus), inhibitory control/attentional shifts (right and left cuneus), and emotion regulation (left cingulate gyrus); and for OW-LOC relative to NW-CON in areas related to response inhibition (right inferior frontal gyrus). Significant block type × group interaction effects were found for the right middle frontal gyrus, left cingulate gyrus, and left cuneus, but these appeared to be accounted for primarily by group. Discussion:There were clear group differences in neural activity in brain regions related to self-regulation during a food restriction paradigm. Elevations in these regions among OW-LOC relative to OW-CON and NW-CON, respectively, may suggest that youth with LOC eating expended more cognitive effort to regulate ingestive behavior.

OBJECTIVE:Family-based treatment (FBT) is an efficacious treatment for adolescent eating disorders, yet it is not routinely implemented in clinical practice. Given that consumers play a role in treatment selection, this study sought to examine families' perspectives on FBT and remission markers associated with increased treatment satisfaction across families. METHOD:Participants were 40 adolescents and 43 caregivers who received outpatient FBT. FBT helpfulness was assessed using a treatment follow-up questionnaire, and eating disorder symptomatology was assessed using percent expected body weight (%EBW) and the eating disorder examination (EDE). Regression analyses were used to assess whether changes in symptoms from baseline to end-of-treatment (EOT) were significantly associated with helpfulness reports. RESULTS:On average, patients and their parents perceived FBT as "quite helpful" and "extremely helpful," respectively. Improvements in all EDE subscales, with the exception of restraint, were significantly associated with adolescent report of helpfulness (all p

Difficulties with executive functioning may underlie both overweight and loss of control (LOC) eating behavior across the age spectrum, but there is a relative paucity of research in children with both conditions. This study aimed to characterize general executive functioning among children with overweight and LOC eating as compared to their overweight and normal-weight peers. Participants were 75 racially diverse children (58.7% female; 81.3% African-American), aged 9-12y (M age = 10.5 ± 1.1), of whom 26 were overweight/obese and endorsed LOC eating (OW-LOC), 34 were overweight controls (OW-CON), and 15 were normal-weight controls (NW-CON). All children completed interview-based measures of eating pathology, and behavioral measures of executive functioning. Parents reported on behavioral facets of children's executive functioning. Groups were compared across parent-report measures and behavioral tasks using analyses of covariance (ANCOVAs) and multivariate analyses of covariance (MANCOVAs) which adjusted for general intellectual functioning. Significant group differences were revealed on a behavioral measure of planning, the Tower of London task [F (5,65) = 3.52; p = 0.007], and a behavioral measure of working memory, the List Sorting task [F (2,71) = 6.45; p = 0.003]. Post-hoc tests revealed that OW-LOC and OW-CON performed worse than NW-CON on the Tower of London, with relative decrements in accuracy rather than performance time. Further, OW-LOC performed worse than both OW-CON and NW-CON on the List Sorting task. Overweight with or without concomitant LOC eating in children may characterize a unique pattern of executive dysfunction. Interventions for eating- and weight-related problems in youth should address underlying deficits in planning and working memory.

American Association of Physical Anthropologists (AAPA) membership surveys from 1996 and 1998 revealed significant gender disparities in academic status. A 2014 follow-up survey showed that gender equality had improved, particularly with respect to the number of women in tenure-stream positions. However, although women comprised 70% of AAPA membership at that time, the percentage of women full professors remained low. Here, we continue to consider the status of women in biological anthropology by examining the representation of women through a quantitative analysis of their participation in annual meetings of the AAPA during the past 20 years. We also review the programmatic goals of the AAPA Committee on Diversity Women's Initiative (COD-WIN) and provide survey results of women who participated in COD-WIN professional development workshops. Finally, we examine the diversity of women's career paths through the personal narratives of 14 women biological anthropologists spanning all ranks from graduate student to Professor Emeritus. We find that over the past 20 years, the percentage of women first authors of invited symposia talks has increased, particularly in the sub-disciplines of bioarchaeology, genetics, and paleoanthropology. The percentage of women first authors on contributed talks and posters has also increased. However, these observed increases are still lower than expected given the percentage of graduate student women and women at the rank of assistant and associate professor. The personal narratives highlight first-hand the impact of mentoring on career trajectory, the challenges of achieving work-life satisfaction, and resilience in the face of the unexpected. We end with some suggestions for how to continue to improve equality and equity for women in biological anthropology.

Classifying eating disorders in youth is challenging in light of developmental considerations and high rates of diagnostic migration. Understanding the transactional relationships among eating disorder symptoms, both across the transdiagnostic spectrum and within specific diagnostic categories, may clarify which core eating disorder symptoms contribute to, and maintain, eating-related psychopathology in youth. We utilized network analysis to investigate interrelationships among eating disorder symptoms in 636 treatment-seeking children and adolescents (90.3% female) ages 6-18 years (M age = 15.4 ± 2.2). An undirected, weighted network of eating disorder symptoms was created using behavioral and attitudinal items from the Eating Disorder Examination. Across diagnostic groups, symptoms reflecting appearance-related concerns (e.g., dissatisfaction with shape and weight) and dietary restraint (e.g., a desire to have an empty stomach) were most strongly associated with other eating disorder symptoms in the network. Binge eating and compensatory behaviors (e.g., self-induced vomiting) were strongly connected to one another but not to other symptoms in the network. Network connectivity was similar across anorexia nervosa, bulimia nervosa, and otherwise specified feeding or eating disorder subgroups. Among treatment-seeking children and adolescents, dietary restraint and shape- and weight-related concerns appear to play key roles in the psychopathology of eating disorders, supporting cognitive-behavioral theories of onset and maintenance. Similarities across diagnostic categories provide support for a transdiagnostic classification scheme. Clinical interventions should seek to disrupt these symptoms early in treatment to achieve maximal outcomes. (PsycINFO Database Record

PURPOSE:Neuroimaging studies suggest that altered brain responses to food-related cues in reward-sensitive regions characterize individuals who experience binge-eating episodes. However, the absence of longitudinal data limits the understanding of whether reward-system alterations increase vulnerability to binge eating, as theorized in models of the development of this behavior. METHODS:Adolescent girls (N = 122) completed a functional magnetic resonance imaging monetary reward task at age 16 years as part of an ongoing longitudinal study. Self-report of binge eating was assessed using the Eating Attitudes Test at ages 16 and 18 years. Regression analyses examined concurrent and longitudinal associations between the blood-oxygenation-level-dependent response to anticipating and winning monetary rewards and the severity of binge eating while controlling for age 16 depressive symptoms and socioeconomic status. RESULTS:Greater ventromedial prefrontal cortex and caudate responses to winning money were correlated with greater severity of binge eating concurrently but not prospectively. CONCLUSIONS:This study is the first to examine longitudinal associations between reward responding and binge eating in community-based, mostly low-socioeconomic status adolescent girls. Ventromedial prefrontal cortex response to reward outcome-possibly reflecting an enhanced subjective reward value-appears to be a state marker of binge-eating severity rather than a predictor of future severity.

While many studies have explored the relationship between different eating disorder diagnoses and the familial social environment, current evidence does not support associations between distinct family interaction patterns (e.g. high enmeshment) and particular diagnoses (e.g. anorexia nervosa). The current study seeks to move beyond the current literature to explore whether empirically derived subtypes of family environment are associated with clinical features within a transdiagnostic sample of youth seeking treatment for eating disorders (n = 123). Latent class modelling of the Family Environment Scale identified three classes (i.e. different Family Environment Scale profiles): (1) Control-Oriented; (2) System Maintenance-Oriented; and (3) Conflict-Oriented. Data are presented to characterize the classes (e.g. age, gender, rates of different eating disorders, severity of eating disorder pathology and rates of comorbid disorders). These preliminary results suggest that family interaction types may help personalize treatment for eating disorders and encourage future research to guide such efforts. Copyright © 2017 John Wiley & Sons, Ltd and Eating Disorders Association.

ObjectiveOur research focuses on laxative misuse, which has been understudied in previous eating disorders (ED) research, to understand its prevalence and correlates among individuals seeking ED treatment. We also test the association between laxative misuse and binge eating to examine the assumption that laxative misuse is intended to compensate for binge eating.MethodParticipants were 2,295 ED treatment-seeking adults (29.5 ± 10.5) who self-reported their disordered eating behaviors on the Eating Disorder Questionnaire. Participants met DSM-5 diagnostic criteria for anorexia nervosa (AN: 11.5%, n = 264), bulimia nervosa (BN: 39.0%, n = 896), binge-eating disorder (14.9%, n = 343), or other specified feeding or eating disorder (34.5%, n = 792).ResultsNearly 25% of participants (n = 571) reported misusing laxatives during the last month. Laxative misusers with AN reported significantly higher frequency of laxative misuse relative to misusers with BN (F(1,440) = 5.226, p = .023, ηp2= .012). Among laxative misusers, there was no association between frequency of binge eating and frequency of laxative misuse.DiscussionLaxative misusers with AN tend to misuse laxatives more frequently than those with BN. Binge eating was not related to laxative misuse in our sample. Future research may use real-time data collection to understand the function of laxative misuse and to validate our cross-sectional findings.

ObjectiveIndividuals with eating disorders (ED), particularly anorexia nervosa (AN), and bulimia nervosa (BN), often wish to reduce their body weight in pursuit of a thin ideal, but no study has examined the relation between desired weight and ED pathology in a clinical population of youth. Given the potential impact of desired weight on normalization of eating patterns and weight restoration, we examined the relation between desired weight and ED pathology in youth with AN or BN.MethodsParticipants were 340 youth presenting to an outpatient ED clinical research program. Height and weight were measured, and youth completed the Eating Disorder Examination. Desired weight was operationalized as "desired weight percentage" (calculated as a percentage of expected body weight [EBW]) and "weight difference percentage" (actual weight minus desired weight, divided by actual weight and multiplied by 100).ResultsYouth with AN desired to be a lower percentage of their EBW than youth with BN (p

Purpose We assessed the safety and antitumor activity of avelumab, a fully human anti-programmed death-ligand 1 (PD-L1) IgG1 antibody, in patients with refractory metastatic urothelial carcinoma. Methods In this phase Ib, multicenter, expansion cohort, patients with urothelial carcinoma progressing after platinum-based chemotherapy and unselected for PD-L1 expression received avelumab 10 mg/kg intravenously every 2 weeks. The primary objectives were safety and tolerability. Secondary objectives included confirmed objective response rate (Response Evaluation Criteria in Solid Tumors [RECIST] version 1.1), progression-free survival, overall survival (OS), and PD-L1-associated clinical activity. PD-L1 positivity was defined as expression by immunohistochemistry on ≥ 5% of tumor cells. Results Forty-four patients were treated with avelumab and followed for a median of 16.5 months (interquartile range, 15.8 to 16.7 months). The data cutoff was March 19, 2016. The most frequent treatment-related adverse events of any grade were fatigue/asthenia (31.8%), infusion-related reaction (20.5%), and nausea (11.4%). Grades 3 to 4 treatment-related adverse events occurred in three patients (6.8%) and included asthenia, AST elevation, creatine phosphokinase elevation, and decreased appetite. The confirmed objective response rate by independent central review was 18.2% (95% CI, 8.2% to 32.7%; five complete responses and three partial responses). The median duration of response was not reached (95% CI, 12.1 weeks to not estimable), and responses were ongoing in six patients (75.0%), including four of five complete responses. Seven of eight responding patients had PD-L1-positive tumors. The median progression-free survival was 11.6 weeks (95% CI, 6.1 to 17.4 weeks); the median OS was 13.7 months (95% CI, 8.5 months to not estimable), with a 12-month OS rate of 54.3% (95% CI, 37.9% to 68.1%). Conclusion Avelumab was well tolerated and associated with durable responses and prolonged survival in patients with refractory metastatic UC.

PurposeSecretive eating, characterized by eating privately to conceal being seen, may reflect eating- and/or body-related shame, be associated with depression, and correlate with binge eating, which predicts weight gain and eating disorder onset. Increasing understanding of secretive eating in youth may improve weight status and reduce eating disorder risk. This study evaluated the prevalence and correlates of secretive eating in youth with overweight or obesity.MethodsYouth (N = 577) presented to five research/clinical institutions. Using a cross-sectional design, secretive eating was evaluated in relation to eating-related and general psychopathology via linear and logistic regression analyses.ResultsSecretive eating was endorsed by 111 youth, who were, on average, older than youth who denied secretive eating (mean age = 12.07 ± 2.83 versus 10.97 ± 2.31). Controlling for study site and age, youth who endorsed secretive eating had higher eating-related psychopathology and were more likely to endorse loss of control eating and purging than their counterparts who did not endorse secretive eating. Groups did not differ in excessive exercise or behavioral problems. Dietary restraint and purging were elevated among adolescents (≥13y) but not children (

Enteropathy-associated T cell lymphoma (EATL) is a lethal, and the most common, neoplastic complication of celiac disease. Here, we defined the genetic landscape of EATL through whole-exome sequencing of 69 EATL tumors. SETD2 was the most frequently silenced gene in EATL (32% of cases). The JAK-STAT pathway was the most frequently mutated pathway, with frequent mutations in STAT5B as well as JAK1, JAK3, STAT3, and SOCS1 We also identified mutations in KRAS, TP53, and TERT Type I EATL and type II EATL (monomorphic epitheliotropic intestinal T cell lymphoma) had highly overlapping genetic alterations indicating shared mechanisms underlying their pathogenesis. We modeled the effects of SETD2 loss in vivo by developing a T cell-specific knockout mouse. These mice manifested an expansion of γδ T cells, indicating novel roles for SETD2 in T cell development and lymphomagenesis. Our data render the most comprehensive genetic portrait yet of this uncommon but lethal disease and may inform future classification schemes.

ObjectiveEating disorder diagnostic criteria were revised from the fourth to the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV and -5, respectively). This study examines the impact of these revisions on rates of eating disorder diagnoses in treatment-seeking youth.MethodParticipants were 651 youth, ages 7-18 years, presenting to an outpatient eating disorders program who met criteria for a DSM-IV eating disorder diagnosis on intake. Patients completed well-validated semi-structured interviews to assess eating disorder psychopathology and psychiatric comorbidity.ResultsParticipants were predominantly female (n = 588; 90.3%) with an average age of 15.28 years (SD = 2.21), mean percent of median Body Mass Index (mBMI) of 101.91 (SD = 31.73), and average duration of illness of 16.74 months (SD = 17.63). Cases of DSM-IV Eating Disorder Not Otherwise Specified (EDNOS), now most consistent with DSM-5 Other Specified Feeding or Eating Disorder, decreased from 47.6% to 39.0%, Anorexia Nervosa increased from 29.6% to 33.5%, and Bulimia Nervosa increased from 22.7% to 24.7%.DiscussionConsistent with previous studies, and in keeping with the aims of the DSM-5 for eating disorders, the revised diagnostic criteria reduced cases of DSM-IV EDNOS and increased cases of specified eating disorders. © 2016 Wiley Periodicals, Inc.(Int J Eat Disord 2017; 50:578-581).

Although loss of control (LOC) while eating is a core construct of bulimia nervosa (BN), questions remain regarding its validity and prognostic significance independent of overeating. We examined trajectories of objective and subjective binge eating (OBE and SBE, respectively; i.e., LOC eating episodes involving an objectively or subjectively large amount of food) among adults participating in psychological treatments for BN-spectrum disorders (n = 80). We also explored whether changes in the frequency of these eating episodes differentially predicted changes in eating-related and general psychopathology and, conversely, whether changes in eating-related and general psychopathology predicted differential changes in the frequency of these eating episodes. Linear mixed models with repeated measures revealed that OBE decreased twice as rapidly as SBE throughout treatment and 4-month follow-up. Generalized linear models revealed that baseline to end-of-treatment reductions in SBE frequency predicted baseline to 4-month follow-up changes in eating-related psychopathology, depression, and anxiety, while changes in OBE frequency were not predictive of psychopathology at 4-month follow-up. Zero-inflation models indicated that baseline to end-of-treatment changes in eating-related psychopathology and depression symptoms predicted baseline to 4-month follow-up changes in OBE frequency, while changes in anxiety and self-esteem did not. Baseline to end-of-treatment changes in eating-related psychopathology, self-esteem, and anxiety predicted baseline to 4-month follow-up changes in SBE frequency, while baseline to end-of-treatment changes in depression did not. Based on these findings, LOC accompanied by objective overeating may reflect distress at having consumed an objectively large amount of food, whereas LOC accompanied by subjective overeating may reflect more generalized distress related to one's eating- and mood-related psychopathology. BN treatments should comprehensively target LOC eating and related psychopathology, particularly in the context of subjectively large episodes, to improve global outcomes.

The population history of Aboriginal Australians remains largely uncharacterized. Here we generate high-coverage genomes for 83 Aboriginal Australians (speakers of Pama-Nyungan languages) and 25 Papuans from the New Guinea Highlands. We find that Papuan and Aboriginal Australian ancestors diversified 25-40 thousand years ago (kya), suggesting pre-Holocene population structure in the ancient continent of Sahul (Australia, New Guinea and Tasmania). However, all of the studied Aboriginal Australians descend from a single founding population that differentiated ~10-32 kya. We infer a population expansion in northeast Australia during the Holocene epoch (past 10,000 years) associated with limited gene flow from this region to the rest of Australia, consistent with the spread of the Pama-Nyungan languages. We estimate that Aboriginal Australians and Papuans diverged from Eurasians 51-72 kya, following a single out-of-Africa dispersal, and subsequently admixed with archaic populations. Finally, we report evidence of selection in Aboriginal Australians potentially associated with living in the desert.

ObjectiveAlthough many individuals with purging disorder (PD) report loss of control (LOC) eating, it is unclear whether they differ from those who do not, or from other eating disorders involving purging and/or LOC.MethodWe compared PD with LOC (PD-LOC), PD without LOC (PD-noLOC), bulimia nervosa (BN), and anorexia nervosa-binge/purge subtype (AN-B/P) on measures of eating-related and general psychopathology in treatment-seeking adolescents.ResultsPD-LOC comprised ∼30% of PD diagnoses. PD-LOC and PD-noLOC did not differ from one another, or from BN and AN-B/P, on most measures of psychopathology, with some exceptions. PD-noLOC was similar to AN-B/P (p = 0.99) and significantly different from BN on eating concerns (p

Amphetamines elevate extracellular dopamine, but the underlying mechanisms remain uncertain. Here we show in rodents that acute pharmacological inhibition of the vesicular monoamine transporter (VMAT) blocks amphetamine-induced locomotion and self-administration without impacting cocaine-induced behaviours. To study VMAT's role in mediating amphetamine action in dopamine neurons, we have used novel genetic, pharmacological and optical approaches in Drosophila melanogaster. In an ex vivo whole-brain preparation, fluorescent reporters of vesicular cargo and of vesicular pH reveal that amphetamine redistributes vesicle contents and diminishes the vesicle pH-gradient responsible for dopamine uptake and retention. This amphetamine-induced deacidification requires VMAT function and results from net H(+) antiport by VMAT out of the vesicle lumen coupled to inward amphetamine transport. Amphetamine-induced vesicle deacidification also requires functional dopamine transporter (DAT) at the plasma membrane. Thus, we find that at pharmacologically relevant concentrations, amphetamines must be actively transported by DAT and VMAT in tandem to produce psychostimulant effects.

ObjectiveEvidence supports the presence of significant variability in the timing of affective experiences and eating disorder (ED) behaviors across ED populations. This study examined the naturalistic timing of affective states and ED behaviors in anorexia nervosa (AN).MethodsWomen (N = 118) with full or subthreshold DSM-IV AN completed 2 weeks of ecological momentary assessment (EMA) involving self-reports of affect and ED behaviors. Patterns of positive affect, negative affect, and tension/anxiety across hours of the day and days of the week were examined using linear mixed models. Variation in ED behavior occurrence (i.e., binge eating, vomiting, exercise, meal skipping, and self-weighing) across hours of the day and days of the week was examined using general estimating equations.ResultsResults revealed significant variation in tension/anxiety across hours of the day; there were no significant associations between time of day and negative or positive affect. All affective variables significantly varied across days of the week, with both negative affect and tension/anxiety highest in the middle of the week and lowest on the weekends. The ED behaviors all significantly varied across hours of the day, with binge eating and vomiting most common in later hours, exercise and self-weighing most common in earlier hours, and meal skipping most common at times corresponding to breakfast and lunch. ED behaviors did not significantly vary across days of the week.ConclusionThe significant patterns of variation in the timing of affective experiences and ED behaviors may have utility in informing theories and interventions for AN.

ObjectivePicking and nibbling (P&N), defined as eating in an unplanned and repetitious way between meals and snacks, is prevalent among adults with eating disorders (EDs), but unexamined among youth with EDs. This study sought to assess the prevalence of P&N in youth with EDs and its association with ED and comorbid pathology.MethodYouth (N = 515; ages 7-18) who presented to one outpatient ED research-clinical program were assessed for ED and comorbid pathology.ResultsTwo-fifths (n = 214, 41.6%) of youth endorsed P&N. These individuals were older (p  .05).DiscussionConsistent with research in adults, P&N is prevalent but not significantly associated with ED pathology, except for global ED pathology in youth with AN/atypical AN, or comorbid disorders.

ObjectiveTo compare dietary restriction behaviors among adults with eating disorders involving binge eating, including anorexia nervosa-binge/purge subtype (AN-BE/P), bulimia nervosa (BN), and binge eating disorder (BED), and to examine whether dietary restriction behaviors impact binge eating frequency across diagnoses.MethodParticipants included 845 treatment seeking adults (M=30.42+10.76years) who met criteria for DSM-5 AN-BE/P (7.3%;n=62), BN (59.7%;n=504), and BED (33.0%;n=279). All participants self-reported their past and current eating disorder symptoms on the Eating Disorder Questionnaire.ResultsAdults with AN-BE/P and BN reported significantly more dietary restriction behaviors (e.g. eating fewer meals per day, higher frequency of fasting, consuming small and low calorie meals) in comparison to adults with BED. Adults with AN-BE/P and BN who reported restricting food intake via eating fewer meals per day had more frequent binge eating episodes. However, adults with BN who reported restricting food intake via eating small meals and low calorie meals had less frequent binge eating episodes.DiscussionThis study provides mixed support for the restraint model by suggesting that not all dietary restriction behaviors are associated with higher levels of binge eating. It may be that adults with BN who report a higher frequency of eating small and low calorie meals display more control over their eating in general, and therefore also have lower frequency of binge eating. Clinicians should assess for dietary restriction behaviors at the start of treatment prior to assuming that all forms of strict dieting and weight control behaviors similarly impact binge eating.

ObjectiveThe current study examined behavioral, emotional, and situational factors involved in purging among women with anorexia nervosa (AN).MethodWomen with AN (n=118) completed a two-week ecological momentary assessment protocol involving daily reports of eating disorder behaviors, mood, and stressful events. Generalized estimating equations examined the likelihood and context of purging following eating episodes involving both overeating and loss of control (binge eating; BE); loss of control only (LOC); overeating only (OE); and neither loss of control nor overeating (non-pathological eating; NE).ResultsRelative to NE, purging was more likely to occur following BE, LOC, and OE (Wald chi-square = 18.05; p

ObjectiveTo describe eating patterns in youth with restricting and binge/purge type anorexia nervosa (AN) and to examine whether eating patterns are associated with binge eating or purging behaviors.MethodParticipants included 160 children and adolescents (M = 15.14 ± 2.17 years) evaluated at The University of Chicago Eating Disorders Program who met criteria for DSM-5 restrictive type AN (AN-R; 75%; n = 120) or binge eating/purging type AN (AN-BE/P; 25%; n = 40). All participants completed the eating disorder examination on initial evaluation.ResultsYouth with AN-R and AN-BE/P differed in their eating patterns, such that youth with AN-R consumed meals and snacks more regularly relative to youth with AN-BE/P. Among youth with AN-BE/P, skipping dinner was associated with a greater number of binge eating episodes (r = -.379, p

PurposePrevious studies on family meals and disordered eating have mainly drawn their samples from the general population. The goal of the current study is to determine family meal frequency among children and adolescents with anorexia nervosa (AN), bulimia nervosa (BN), and feeding or eating disorder not elsewhere classified (FED-NEC) and to examine whether family meal frequency is associated with eating disorder psychopathology.MethodsParticipants included 154 children and adolescents (M = 14.92 ± 2.62), who met criteria for AN (n = 60), BN (n = 32), or FED-NEC (n = 62). All participants completed the Eating Disorder Examination and the Family Meal Questionnaire prior to treatment at the University of Chicago Eating Disorders Program.ResultsAN and BN participants significantly differed in terms of family meal frequency. A majority of participants with AN (71.7%), compared with less than half (43.7%) of participants with BN, reported eating dinner with their family frequently (five or more times per week). Family meal frequency during dinner was significantly and negatively correlated with dietary restraints and eating concerns among participants with BN (r = -.381, r = -.366, p < .05) and FED-NEC (r = -.340, r = -.276, p < .05).ConclusionsAN patients' higher family meal frequency may be explained by their parents' relatively greater vigilance over eating, whereas families of BN patients may be less aware of eating disorder behaviors and hence less insistent upon family meals. Additionally, children and adolescents with AN may be more inhibited and withdrawn and therefore are perhaps more likely to stay at home and eat together with their families.

ObjectiveTo assess potential selection bias in participant recruitment for randomized controlled trials (RCTs) of adolescent eating disorders (EDs), we compared participants recruited for RCTs evaluating psychosocial treatments with individuals seeking fee-for-service outpatient ED treatment [clinic treatment-seeking (CTS)].MethodParticipants were 214 adolescents presenting to an outpatient ED research-clinical program (92.1% female; M age = 15.4 ± 1.8 years). ANOVA and chi-square tests assessed differences between CTS participants and those presenting for no-cost treatment through RCTs. A secondary analysis compared RCT participants to participants eligible for the RCTs that opted for fee-for-service treatment.ResultsRCT participants had greater baseline ED and general psychopathology (p < .001); however, CTS participants were more likely to present with a comorbid psychiatric disorder (p < .05) and higher family income (p < .05).DiscussionResults suggest that RCT participants did not have less pathology than CTS participants. While preliminary, results do not indicate a systematic population bias in selecting healthier patients for RCTs involving adolescent ED.

ObjectiveThis study aimed to describe and compare the demographic and clinical characteristics of children and adolescents with an eating disorder (ED) and comorbid depression or anxiety.MethodData were drawn from intake assessments of children and adolescents at a specialist ED clinic. Demographic characteristics (e.g. age and gender) and clinical characteristics (e.g. body mass, binge eating and purging) were compared between 217 ED participants without comorbidity, 32 with comorbid anxiety, 86 with comorbid depression and 36 with comorbid anxiety and depression.ResultsThe groups with comorbid depression had more complex and severe presentations compared with those with an ED and no comorbid disorder and those with comorbid anxiety alone, especially in regard to binge eating, purging, dietary restraint and weight/shape concerns.DiscussionDepression and anxiety were differentially related to clinical characteristics of EDs. The findings have implications for understanding the relations between these disorders and their potential to impact outcome of ED treatments.

A prognostic model that predicts overall survival (OS) for metastatic urothelial cancer (MetUC) patients treated with cisplatin-based chemotherapy was developed, validated, and compared with a commonly used Memorial Sloan-Kettering Cancer Center (MSKCC) risk-score model. Data from 7 protocols that enrolled 308 patients with MetUC were pooled. An external multi-institutional dataset was used to validate the model. The primary measurement of predictive discrimination was Harrell's c-index, computed with 95% confidence interval (CI). The final model included four pretreatment variables to predict OS: visceral metastases, albumin, performance status, and hemoglobin. The Harrell's c-index was 0.67 for the four-variable model and 0.64 for the MSKCC risk-score model, with a prediction improvement for OS (the U statistic and its standard deviation were used to calculate the two-sided P = .002). In the validation cohort, the c-indices for the four-variable and the MSKCC risk-score models were 0.63 (95% CI = 0.56 to 0.69) and 0.58 (95% CI = 0.52 to 0.65), respectively, with superiority of the four-variable model compared with the MSKCC risk-score model for OS (the U statistic and its standard deviation were used to calculate the two-sided P = .02).

PurposeDieting is a well-established risk factor for binge eating, yet the majority of dieters do not develop binge eating problems. The purpose of the current study was to examine psychosocial factors involved in the relation between dieting and binge eating over a 10-year follow-up period.MethodsA population-based sample (n = 1,827) completed surveys assessing eating habits, psychological functioning, and weight status at 5-year intervals spanning early/middle adolescence (time 1), late adolescence/early young adulthood (time 2), and early/middle young adulthood (time 3). Dieting, along with depression symptoms, self-esteem, and teasing experiences at time 1 and time 2, was used to predict new onset binge eating at time 2 and time 3, respectively. Interactions between dieting status and varying degrees of these psychosocial factors in relation to binge eating onset were also tested.ResultsDieters were two to three times more likely than nondieters to develop binge eating problems over 5-year follow-ups. At most time points, depression symptoms and self-esteem predicted binge eating onset beyond the effects of dieting alone. Detrimental levels of these factors among dieters (relative to nondieters) increased the likelihood of binge eating onset only during the later follow-up period.ConclusionsDepression and self-esteem appear to be particularly salient factors involved in the relation between dieting and binge eating onset among adolescents and young adults. Early identification of these factors should be a priority to prevent the development of binge eating problems among already at-risk individuals.