Reconsidering the role of interpersonal stress in eating pathology: Sensitivity to rejection might be more important than actual experiences of peer stress.

Rejection sensitivity (i.e., the tendency to anxiously expect, readily perceive, and overreact to real or perceived rejection) is theorized to play a role in the onset and maintenance of disordered eating. Although rejection sensitivity has repeatedly been associated with eating pathology in clinical and community samples, the pathways through which this psychological trait influences eating pathology have been not fully established. The current study investigated peer-related stress, which can be influenced by rejection sensitivity and is associated with eating pathology, as a mechanism linking these constructs. In two samples of women - 189 first-year undergraduate students and 77 community women with binge eating - we examined whether rejection sensitivity was indirectly associated with binge eating and weight/shape concerns via ostracism and peer victimization, both cross-sectionally and longitudinally. Our hypotheses were not supported: there were no indirect associations between rejection sensitivity and eating pathology via interpersonal stress in either sample. However, we did find that rejection sensitivity was directly associated with weight/shape concerns in both samples and with binge eating in the clinical sample in cross-sectional (but not longitudinal) analyses. Our findings suggest that the association between rejection sensitivity and disordered eating is not dependent on actual experiences of interpersonal stress. That is, simply anticipating or perceiving rejection may be sufficient to play a role in eating pathology. As such, interventions targeting rejection sensitivity may be helpful in the treatment of eating pathology.

The role of self-compassion in the relationship between rejection and unhealthy eating: An ecological momentary assessment study.

Available studies suggest that experiencing interpersonal rejection heightens negative affect and, in turn, triggers unhealthy eating behaviors. Elucidating individual differences that attenuate the negative consequences of rejection could inform interventions targeting unhealthy eating. This study examined the buffering role of self-compassion in the relationship between rejection experiences and unhealthy eating behaviors, defined as snacking on junk food and overeating. Two-hundred undergraduate students (50% women) completed ecological momentary assessments measuring rejection experiences, emotions, and unhealthy eating seven times a day for 10 consecutive days. Self-compassion was measured after the 10-day assessment period. Reports of rejection were low (2.6%) in our university sample. Multilevel mediation analyses examined whether the relationship between experiencing rejection and subsequent unhealthy eating was mediated by negative affect. Multilevel moderated mediation analyses further considered whether relationships between rejection and negative affect and between negative affect and unhealthy eating were moderated by self-compassion. Experiencing rejection predicted more unhealthy eating behaviors at the next time point, and this relationship was fully explained by increases in negative affect. Participants with high levels of self-compassion experienced less intense negative affect after rejection and reported less unhealthy eating behaviors when feeling negative emotions, compared to their counterparts with lower levels of self-compassion. The indirect effect of rejection on unhealthy eating was moderated by self-compassion, and there was no statistically significant relationship between rejection and unhealthy eating behaviors among highly self-compassionate participants. Findings suggest that cultivating self-compassion may help attenuate the negative impact of rejection experiences on emotions and unhealthy eating behaviors.

Hunger games: Associations between core eating disorder symptoms and responses to rejection by peers during competition.

OBJECTIVE: Individuals with eating disorder (ED) symptoms are sensitive to social threat and report maladaptive interpersonal styles that may contribute to and exacerbate negative evaluation from others. Research in this area has relied primarily on self-report. The current study examined associations between behavioral responses to social threat and core ED symptoms using a behavioral paradigm. Based on previous findings that individuals with binge-eating report being more reactive and confrontational, whereas individuals with dietary restriction tend to be more submissive and avoidant of conflict, we hypothesized that binge eating would be associated with a greater tendency to retaliate against rejection perpetrators, whereas dietary restriction would be associated with a lower tendency to retaliate when rejected. METHOD: Undergraduate women (N = 132) completed a self-report measure of ED symptoms and participated in an online "Survivor"-type game in which they voted to either accept or reject computerized coplayers, while also receiving acceptance or rejection feedback from others. RESULTS: Neither ED symptom was associated with how often participants retaliated against coplayers who rejected them. However, dietary restriction was related to more rejection votes overall (i.e., the tendency to reject others regardless of how others voted). DISCUSSION: Findings suggest that individuals with dietary restriction may rely on a maladaptive defensive strategy aimed at pre-empting rejection, or alternatively, have difficulty shifting from habitual self-isolating behavior that results from over-involvement with restricting symptoms. Interventions targeting hypersensitivity to social threat or interpersonal flexibility may help reduce interpersonal stress and mitigate its impact on restricting symptoms.

Extending the scope of the interpersonal psychotherapy model of eating disorders: Integrating the role of 'feeling fat'.

The interpersonal psychotherapy model of eating disorders (IPT-ED) argues that interpersonal problems result in negative affect, and that an inability to cope with this negative affect triggers ED symptoms. Relatedly, it is theorized that 'feeling fat' (i.e., the somatic experience of being overweight not entirely explained by one's body mass) results from shifting negative affect onto one's body, which can then be controlled via ED symptoms. Research has yet to identify why negative affect caused by interpersonal problems may trigger ED symptoms as opposed to other maladaptive behaviours. Integrating 'feeling fat' into the IPT-ED may help to explain this relationship. This study examined whether interpersonal problems positively related to ED symptoms via negative affect and 'feeling fat' in 190 undergraduate women (mean age [SD] = 19.05 [1.23]; mean BMI [SD] = 21.76 [3.17]; 72.8% Caucasian). Using both cross-sectional and longitudinal path analyses, we tested the indirect effects of ostracism and peer victimization on binge eating and restricting via negative affect and 'feeling fat' using serial indirect effects analyses. Cross-sectional path analysis revealed significant indirect effects of ostracism on both binge eating and restricting sequentially via negative affect and 'feeling fat', such that ostracism related to negative affect, which related to 'feeling fat', which was ultimately associated with disordered eating behaviours. Longitudinal path analysis replicated the significant indirect effects of ostracism on binge eating sequentially via negative affect and 'feeling fat'. Results suggest that individuals may displace negative feelings that result from ostracism onto their body, triggering 'feelings of fatness' and prompting ED symptoms. Future research should examine 'feeling fat' within the IPT-ED in a sample of individuals with EDs to determine its clinical utility beyond an undergraduate sample.

The Covert and Overt Reassurance Seeking Inventory (CORSI): Development, validation and psychometric analyses.

BACKGROUND: Reassurance seeking (RS) is motivated by perceived general and social/relational threats across disorders, yet is often under-recognized because it occurs in covert (i.e. subtle) and overt forms. Covert safety-seeking behaviour may maintain disorders by preventing corrective learning and is therefore important to identify effectively. AIMS: This study presents the validation and psychometric analyses of a novel measure of covert and overt, general and social/relational threat-related interpersonal RS. METHOD: An initial 30-item measure was administered to an undergraduate sample (N = 1626), as well as to samples of individuals diagnosed with obsessive compulsive disorder (OCD; n = 50), anxiety disorders (n = 60) and depression (n = 30). The data were subjected to exploratory and confirmatory factor analyses, and validation analyses. RESULTS: An exploratory factor analysis using principal axis factoring with oblique rotation yielded five interpretable factors, after removing four complex items. The resulting 26-item measure, the Covert and Overt Reassurance Seeking Inventory (CORSI), evidenced good convergent and divergent validity and accounted for 54.99% of the total variance after extraction. Factor correlations ranged from r = .268 to .736, suggesting that they may be tapping into unique facets of RS behaviour. In comparison with undergraduate participants, all clinical groups had significantly higher total scores [t (51.80-840) = 3.92-5.84, p < .001]. The CFA confirmed the five-factor model with good fit following the addition of four covariance terms (goodness of fit index = .897, comparative fit index = .918, Tucker-Lewis index = .907, root mean square error approximation = .061). CONCLUSION: The CORSI is a brief, yet comprehensive and psychometrically strong measure of problematic RS. With further validation, the CORSI has potential for use within clinical and research contexts.

Extending the Acquired Preparedness model of binge eating: Testing the indirect effects of high-risk personality traits on binge eating via positive and negative reinforcement expectancies.

According to the Acquired Preparedness (AP) model of binge eating, individuals high in negative urgency are more likely to develop the expectancy that eating alleviates negative affect, which in turn increases the likelihood of binge eating. Although both cross-sectional and longitudinal studies have provided strong support for the negative urgency version of the AP model, there are likely other personality traits and expectancies that may transact to increase risk for binge eating. We extended the AP model to examine how other high-risk personality traits related to reward and impulsivity might lead to binge eating via learned expectancies about eating. In a large sample of male and female college students (N = 998; 54.6% female), we tested the indirect effects of reward responsiveness, fun seeking, and sensation seeking on binge eating via expectancies related to positive and negative reinforcement from eating. Our results suggested an indirect effect of reward responsiveness on binge eating via the expectancy that eating is rewarding and an indirect effect of fun seeking on binge eating via the expectancies that eating is rewarding and eating alleviates boredom. In contrast, sensation seeking had neither direct nor indirect effects on binge eating. Findings suggest that there are multiple pathways from personality to binge eating that depend on differential learning experiences and should be considered in terms of prevention and treatment efforts.

Memory T-cell enriched haploidentical transplantation with NK cell addback results in promising long-term outcomes: a phase II trial.

BACKGROUND: Relapse remains a challenge after transplantation in pediatric patients with hematological malignancies. Myeloablative regimens used for disease control are associated with acute and long-term adverse effects. We used a CD45RA-depleted haploidentical graft for adoptive transfer of memory T cells combined with NK-cell addback and hypothesized that maximizing the graft-versus-leukemia (GVL) effect might allow for reduction in intensity of conditioning regimen. METHODS: In this phase II clinical trial (NCT01807611), 72 patients with hematological malignancies (complete remission (CR)1: 25, ≥ CR2: 28, refractory disease: 19) received haploidentical CD34 + enriched and CD45RA-depleted hematopoietic progenitor cell grafts followed by NK-cell infusion. Conditioning included fludarabine, thiotepa, melphalan, cyclophosphamide, total lymphoid irradiation, and graft-versus-host disease (GVHD) prophylaxis consisted of a short-course sirolimus or mycophenolate mofetil without serotherapy. RESULTS: The 3-year overall survival (OS) and event-free-survival (EFS) for patients in CR1 were 92% (95% CI:72-98) and 88% (95% CI: 67-96); ≥ CR2 were 81% (95% CI: 61-92) and 68% (95% CI: 47-82) and refractory disease were 32% (95% CI: 11-54) and 20% (95% CI: 6-40). The 3-year EFS for all patients in morphological CR was 77% (95% CI: 64-87) with no difference amongst recipients with or without minimal residual disease (P = 0.2992). Immune reconstitution was rapid, with mean CD3 and CD4 T-cell counts of 410/µL and 140/µL at day + 30. Cumulative incidence of acute GVHD and chronic GVHD was 36% and 26% but most patients with acute GVHD recovered rapidly with therapy. Lower rates of grade III-IV acute GVHD were observed with NK-cell alloreactive donors (P = 0.004), and higher rates of moderate/severe chronic GVHD occurred with maternal donors (P = 0.035). CONCLUSION: The combination of a CD45RA-depleted graft and NK-cell addback led to robust immune reconstitution maximizing the GVL effect and allowed for use of a submyeloablative, TBI-free conditioning regimen that was associated with excellent EFS resulting in promising long-term outcomes in this high-risk population. The trial is registered at ClinicalTrials.gov (NCT01807611).

"Anti-smoking data are exaggerated" versus "the data are clear and indisputable": examining letters to the editor about tobacco.

Media advocacy plays a unique role in tobacco control policy development. Letters to the editor in particular are an interesting form of media advocacy because they reflect community sentiment regarding the policy agenda and provide insight into the public debate. The authors used ethnographic context analysis to examine the techniques used by writers of 262 tobacco-related letters to the editor published in 61 newspapers across Missouri over a 2-year period when tobacco tax and smoke-free indoor air initiatives were occurring across the state. The authors found that pro-tobacco control letter writers often used didactic strategies, citing numbers and reports, to convey information and presented their training or experience as a health professional (e.g., M.D., Ph.D.) to add legitimacy to their arguments. Anti-tobacco control letter writers, in contrast, used narrative strategies to support their stance, claimed authority as a smoker or small business owner to legitimize their claims by relating to the audience, and used collectivity to capture the attention of policymakers. These results present the importance of strategic media advocacy in tobacco control. Tobacco control advocates should increase their use of narrative strategies and collectivity in order to better connect with the public and policymakers.

Associations between different facets of anhedonia and neural response to monetary, social, and food reward in emerging adults.

Anhedonia is present in diverse psychiatric disorders and has been linked to reduced neural responses to reward. However, most studies of anhedonia have used monetary reward, making it unclear whether previously-observed deficits represent broad domain-general impairments, or whether associations with anhedonia might vary across incentive types. The present study (N = 120) investigated associations between multiple measures of self-reported anhedonia and reward responsiveness and the reward positivity (RewP), a neural index of reward processing, following monetary, social, and food reward. Greater social anhedonia was associated with a smaller RewP following positive social feedback, whereas reduced consummatory pleasure was associated with a smaller RewP following food reward. Associations among both self-report and neural measures of reward sensitivity were generally modest. Our findings suggest that neither anhedonia nor neural reward sensitivity are unidimensional constructs, and that category-specific reward deficits might better capture specific problems in hedonic functioning.

Sub-myeloablative Second Transplantations with Haploidentical Donors and Post-Transplant Cyclophosphamide have limited Anti-Leukemic Effects in Pediatric Patients.

Pediatric patients with high-risk hematologic malignancies who experience relapse after a prior allogeneic hematopoietic cell transplant (HCT) have an exceedingly poor prognosis. A second allogeneic HCT offers the potential for long-term cure but carries high risks of both subsequent relapse and HCT-related morbidity and mortality. Using haploidentical donors for HCT (haploHCT) can expand the donor pool and potentially enhance the graft-versus-leukemia effect but is accompanied by a risk of graft-versus-host disease (GVHD). The goal of this protocol was to intensify the antileukemia effect of haploHCT for pediatric patients with hematologic malignancies that relapsed after prior allogeneic HCT, while limiting regimen-associated toxicities. This phase II clinical trial evaluated a sub-myeloablative preparative regimen consisting of anti-thymocyte globulin, clofarabine, cytarabine, busulfan, and cyclophosphamide, in combination with plerixafor to sensitize leukemic blasts. Participants received a mobilized peripheral blood unmanipulated haploidentical donor graft with one dose of post-transplant cyclophosphamide as GVHD prophylaxis, followed by natural killer (NK) cell addback. Here we report the clinical outcomes and immune reconstitution of 17 participants treated on the study and 5 additional patients treated on similar single-patient treatment plans. Of the 22 participants analyzed, 12 (55%) had active disease at the time of HCT. The regimen provided robust immune reconstitution, with 21 participants (95%) experiencing neutrophil engraftment at a median of 14 days after HCT. In this high-risk population, the overall survival was 45% (95% confidence interval [CI], 24%-64%), with a 12-month event-free survival of 31% (95% CI, 14%-51%) and cumulative incidence of relapse at 12 months of 50% (95% CI, 27%-69%). Four participants (18%) remain in remission at >5 years follow-up. Expected HCT-related organ-specific toxicities were observed, and 13 participants (59%) experienced acute or chronic GVHD. This intensified but sub-myeloablative regimen, followed by a high-dose unmanipulated haploidentical graft, post-transplantation cyclophosphamide, and NK cell infusion, resulted in adequate immune reconstitution but failed to overcome the elevated risks of relapse and treatment-related morbidity in this high-risk population.

Preferential expansion of CD8+ CD19-CAR T cells postinfusion and the role of disease burden on outcome in pediatric B-ALL.

T cells expressing CD19-specific chimeric antigen receptors (CD19-CARs) have potent antileukemia activity in pediatric and adult patients with relapsed and/or refractory B-cell acute lymphoblastic leukemia (B-ALL). However, not all patients achieve a complete response (CR), and a significant percentage relapse after CD19-CAR T-cell therapy due to T-cell intrinsic and/or extrinsic mechanisms. Thus, there is a need to evaluate new CD19-CAR T-cell products in patients to improve efficacy. We developed a phase 1/2 clinical study to evaluate an institutional autologous CD19-CAR T-cell product in pediatric patients with relapsed/refractory B-ALL. Here we report the outcome of the phase 1 study participants (n = 12). Treatment was well tolerated, with a low incidence of both cytokine release syndrome (any grade, n = 6) and neurotoxicity (any grade, n = 3). Nine out of 12 patients (75%) achieved a minimal residual disease-negative CR in the bone marrow (BM). High disease burden (≥40% morphologic blasts) before CAR T-cell infusion correlated with increased side effects and lower response rate, but not with CD19-CAR T-cell expansion. After infusion, CD8+ CAR T cells had a proliferative advantage over CD4+ CAR T cells and at peak expansion, had an effector memory phenotype with evidence of antigen-driven differentiation. Patients that proceeded to allogeneic hematopoietic cell transplantation (AlloHCT) had sustained, durable responses. In summary, the initial evaluation of our institutional CD19-CAR T-cell product demonstrates safety and efficacy while highlighting the impact of pre-infusion disease burden on outcomes. This trial was registered at www.clinicaltrials.gov as #NCT03573700.

Dimensions of unhealthy exercise and their associations with restrictive eating and binge eating.

Unhealthy exercise is a core symptom of eating disorders that predicts greater chronicity and risk of relapse. A detailed conceptualization of unhealthy exercise in the context of eating disorders is only beginning to emerge, and associations between specific dimensions of unhealthy exercise and eating disorder symptoms have received little attention. The aim of the current study was to examine associations between three key dimensions of unhealthy exercise - compulsive exercise (i.e., rule-driven exercise to avoid negative affect), exercise to control weight/shape, and exercise to compensate for recent food intake - with restrictive eating and binge eating. Participants were 239 women drawn from two separate studies of emotions and eating behavior; 126 (52.7%) endorsed restrictive eating and/or objective binge eating episodes in the past three months. Unhealthy exercise dimensions were measured using the Compulsive Exercise Test and investigator-designed items, and eating disorder symptoms were assessed using the Eating Pathology Symptoms Inventory. Restrictive eating was only associated with avoidance and rule-driven exercise, whereas binge eating was significantly correlated with all unhealthy exercise variables. Multiple regression results revealed that only compensatory exercise was uniquely associated with binge eating. Unhealthy exercise consists of partially distinct dimensions with differential relations to core eating disorder symptoms. Future research should examine unhealthy exercise dimensions in patients with eating disorder diagnoses and consider whether treatments for specific unhealthy exercise forms might be beneficial.

When it's at: An examination of when cognitive change occurs during cognitive therapy for compulsive checking in obsessive-compulsive disorder.

BACKGROUND AND OBJECTIVES: The cognitive theory of compulsive checking in OCD proposes that checking behaviour is maintained by maladaptive beliefs, including those related to inflated responsibility and those related to reduced memory confidence. This study examined whether and when specific interventions (as part of a new cognitive therapy for compulsive checking) addressing these cognitive targets changed feelings of responsibility and memory confidence. METHODS: Participants were nine adults with a primary or secondary diagnosis of OCD who reported significant checking symptoms (at least one hour per day) on the Yale-Brown Obsessive-Compulsive Scale. A single-case multiple baseline design was used, after which participants received 12 sessions of cognitive therapy. From the start of the baseline period through to the 1 month post-treatment follow-up assessment session, participants completed daily monitoring of feelings of responsibility, memory confidence, and their time spent engaging in compulsive checking. RESULTS: Results revealed that feelings of responsibility significantly reduced and memory confidence significantly increased from baseline to immediately post-treatment, with very high effect sizes. Multilevel modelling revealed significant linear changes in feelings of responsibility (i.e., reductions over time) and memory confidence (i.e., increases over time) occurred following the sessions when these were addressed. Finally, we found that improvements in these over the course of the treatment significantly predicted reduced time spent checking. LIMITATIONS: The small sample size limits our ability to generalize our results. CONCLUSIONS: Results are discussed in terms of a focus on the timing of change in cognitive therapy.

Cognitive therapy for compulsive checking in obsessive-compulsive disorder: A pilot trial.

We evaluated a novel, empirically-based cognitive therapy for compulsive checking - a common form of obsessive-compulsive disorder. Twelve adults completed 12 sessions of the therapy. Significant reductions in checking-related symptoms were found pre- to post-treatment, and pre-treatment to 6-month follow-up (moderate to large effect sizes). Participants reported high treatment acceptability after the third session, which was maintained at post-treatment. This pilot trial provides preliminary support for treating compulsive checking using this novel cognitive approach.

Is all nonhomeostatic eating the same? Examining the latent structure of nonhomeostatic eating processes in women and men.

Nonhomeostatic eating is a complex (presumably) multidimensional construct associated with negative health outcomes. However, little research has examined the latent structure of nonhomeostatic eating processes, interrelationships among nonhomeostatic eating constructs, and differential associations between nonhomeostatic eating constructs and external correlates. This study adopted a construct validation approach to investigate these research questions in a large sample of undergraduate women and men (N = 998; 54.6% female). Exploratory and confirmatory factor analyses were conducted on items from 8 measures representing numerous nonhomeostatic eating process constructs (e.g., binge eating, loss of control [LOC] over eating, "food addiction"). The 7-factor retained solution included the following: (1) emotional eating, (2) external eating, (3) LOC over eating, (4) overeating, (5) distress over nonhomeostatic eating, (6) hedonic hunger, and (7) food addiction. LOC over eating was the nonhomeostatic eating factor most strongly related to other factors (M rs = .71 and .65 in women and men, respectively). Factor score multiple regressions conducted separately by sex indicated that distress over nonhomeostatic eating was related to body mass index, depressive symptoms, and eating-related clinical impairment in both women and men. In women, food addiction demonstrated unique associations with depressive symptoms, emotion dysregulation, and clinical impairment, whereas overeating uniquely predicted these outcomes in men. This is the first comprehensive analysis of the latent structure of nonhomeostatic eating processes and associations with external correlates, and results suggest that LOC over eating, distress over nonhomeostatic eating, food addiction (in women), and overeating (in men) exhibited the strongest relations with psychosocial impairment. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

An Improved Method With High Specificity for KIR2DL1 Functional Allele Typing.

As new killer-cell immunoglobulin-like receptor (KIR) alleles are discovered, a challenge in KIR typing is maintaining sensitivity and specificity. A single nucleotide polymorphism assay can be used to type functional KIR2DL1 alleles. We improved recently on the earlier method by using a higher-specificity assay. The major modifications include the development of sequence-specific primers to selectively amplify the transmembrane domain of all known KIR2DL1 alleles via polymerase chain reaction with sequence-specific primers (PCR-SSP), and using the PCR products as the template for a revised KIR2DL1 functional allele-typing assay. This modified method allows high-throughput typing with high specificity.

NK cell genotype and phenotype at diagnosis of acute lymphoblastic leukemia correlate with postinduction residual disease.

PURPOSE: Not all natural killer (NK) cells are equally cytotoxic against leukemia because of differences in receptor gene content and surface expression. We correlated NK cell genotype and phenotype at diagnosis of childhood acute lymphoblastic leukemia (ALL) with minimal residual disease (MRD) after induction chemotherapy. EXPERIMENTAL DESIGN: The NK cells and leukemia blasts of 244 patients were analyzed at diagnosis by killer-cell immunoglobulin-like receptor (KIR) typing and immunophenotyping. The results were correlated statistically with postinduction MRD status. RESULTS: The odds of being MRD positive in patients with KIR telomeric (Tel)-A/B genotype were 2.85 times the odds in those with Tel-A/A genotype (P = 0.035). MRD-positive patients were more likely to have KIR2DL5A (P = 0.006) and expressed less activating receptor NKp46 and FASL on their NK cells (P = 0.0074 and P = 0.029, respectively). The odds of being MRD positive increased by 2.01-fold for every percentage increase in NK cells expressing KIR2DL1 in the presence of HLA-C2 ligand (P = 0.034). The quantity of granzyme B inhibitor PI-9 in the leukemia blasts was greater in patients who were MRD positive (P = 0.038). Collectively, five NK cell-related factors (Tel-B-associated KIR2DL5A, NKp46, FASL, granzyme B, and PI-9) are strongly associated with MRD positivity at the end of induction with 100% sensitivity and 80% specificity. CONCLUSIONS: Our data support the hypothesis that NK cells with a strong effector phenotype in the setting of decreased leukemia resistance are associated with better leukemia control.

Public health program capacity for sustainability: a new framework.

BACKGROUND: Public health programs can only deliver benefits if they are able to sustain activities over time. There is a broad literature on program sustainability in public health, but it is fragmented and there is a lack of consensus on core constructs. The purpose of this paper is to present a new conceptual framework for program sustainability in public health. METHODS: This developmental study uses a comprehensive literature review, input from an expert panel, and the results of concept-mapping to identify the core domains of a conceptual framework for public health program capacity for sustainability. The concept-mapping process included three types of participants (scientists, funders, and practitioners) from several public health areas (e.g., tobacco control, heart disease and stroke, physical activity and nutrition, and injury prevention). RESULTS: The literature review identified 85 relevant studies focusing on program sustainability in public health. Most of the papers described empirical studies of prevention-oriented programs aimed at the community level. The concept-mapping process identified nine core domains that affect a program's capacity for sustainability: Political Support, Funding Stability, Partnerships, Organizational Capacity, Program Evaluation, Program Adaptation, Communications, Public Health Impacts, and Strategic Planning. Concept-mapping participants further identified 93 items across these domains that have strong face validity-89% of the individual items composing the framework had specific support in the sustainability literature. CONCLUSIONS: The sustainability framework presented here suggests that a number of selected factors may be related to a program's ability to sustain its activities and benefits over time. These factors have been discussed in the literature, but this framework synthesizes and combines the factors and suggests how they may be interrelated with one another. The framework presents domains for public health decision makers to consider when developing and implementing prevention and intervention programs. The sustainability framework will be useful for public health decision makers, program managers, program evaluators, and dissemination and implementation researchers.

Antibody-dependent cell-mediated cytotoxicity overcomes NK cell resistance in MLL-rearranged leukemia expressing inhibitory KIR ligands but not activating ligands.

PURPOSE: Leukemias with MLL gene rearrangement are associated with a poor prognosis. Natural killer (NK) cell therapy is a potential treatment, but leukemia cells may be resistant. Here, we sought to determine the susceptibility of MLL-rearranged leukemia cells to NK cell lysis and to develop a novel immunotherapeutic approach to optimize NK cell therapy, including the use of an antibody against leukemia-associated antigen and the elimination of killer-cell immunoglobulin-like receptor (KIR)-mediated inhibition. EXPERIMENTAL DESIGN: Three MLL-rearranged leukemia cell lines (RS4;11, SEM, and MV4-11) and primary leukemia blasts were assessed for surface phenotype and susceptibility to NK cell lysis with or without antibodies against CD19 (XmAb5574), CD33 (lintuzumab), or KIR ligands. RESULTS: All three cell lines were resistant to NK cell lysis, had some inhibitory KIR ligands and protease inhibitor-9, and expressed low levels of NKG2D activating ligands and adhesion molecules. After treatment with XmAb5574 or lintuzumab, MLL-rearranged leukemia cells were efficiently killed by NK cells. The addition of pan-major histocompatibility complex class I antibody, which blocked inhibitory KIR-HLA interaction, further augmented degranulation in all three KIR2DL1, KIR2DL2/3, and KIR3DL1 subsets of NK cells based on the rule of missing-self recognition. A mouse model showed a decreased rate of leukemia progression in vivo as monitored by bioluminescence imaging and longer survival after antibody treatment. CONCLUSION: Our data support the use of a triple immunotherapy approach, including an antibody directed against tumor-associated antigen, KIR-mismatched NK cell transplantation, and inhibitory KIR blockade, for the treatment of NK cell-resistant MLL-rearranged leukemias.