Quality of life in bariatric patients up to twelve years after surgery - Results from a nationwide retrospective cohort study.

BACKGROUND: Bariatric interventions (BI, including surgical interventions) are effective in patients with massive obesity, i.e., a body mass index (BMI) > 40, and their number has steadily increased during the past decade. Yet, the stability of improvements in quality of life (QoL) in post-interventional patients is understudied and restricted to studies with small samples and short follow-ups. METHODS: Patients with BI between 2004 and 2018 were identified in a health claims database and invited to fill in a survey, comprising sociodemographic and lifestyle information and psychometric scales. QoL was assessed with the Bariatric QoL (BQL) scale with lower scores denoting worse QoL. BMI and excess weight loss (EWL) were calculated for the time soon after intervention (EWL-T1) and when filling the survey (EWL-T2). RESULTS: The majority of n = 2151 patients were female (80.7 %), had a mean age of 54.5 years and a mean BMI of 34.8. The mean EWL-T1 was 79 % (EWL-T2: 64.6 %). The mean BQL score was 47.6 and decreased with BMI (18.5-24.9: 52.6 vs. >40: 38.7), EWL-T2 (>66 %: 51.3 vs. <65 %: 42.1) and years since intervention (3-4: 48.2 vs >8: 45.1, each p < .001). For EWL-T1, the association between higher EWLs and higher BQL scores was stronger in females than in males (p < .005); for EWL at T2, both sexes did not differ in this regard (p = .848). Among normal-weight persons, males scored significantly lower on the BQL than females (44.9 vs. 54.9). CONCLUSIONS: Post-interventional QoL improvements diminish over time and depend on the weight loss, with significant differences between men and women.

Ex vivo expansion of lung cancer-derived disseminated cancer cells from lymph nodes identifies cells associated with metastatic progression.

The cellular basis of the apparent aggressiveness in lung cancer is poorly understood but likely associated with functional or molecular features of disseminated cancer cells (DCCs). DCCs from epithelial cancers are mostly detected by antibodies directed against histogenetic markers such as cytokeratin or EpCAM. It has been argued that marker-negative metastatic founder cells might escape detection. We therefore used ex vivo sphere formation for functional detection of candidate metastasis founders. We generated cell suspensions from 199 LN samples of 131 lung cancer patients and placed them into non-adherent cell culture. Sphere formation was associated with detection of DCCs using EpCAM immunocytology and with significantly poorer prognosis. The prognostic impact of sphere formation was strongly associated with high numbers of EpCAM-positive DCCs and aberrant genotypes of expanded spheres. We also noted sphere formation in patients with no evidence of lymphatic spread, however such spheres showed infrequent expression of signature genes associated with spheres from EpCAM-positive samples and displayed neither typical lung cancer mutations (KRAS, TP53, ERBB1) nor copy number variations, but might be linked to disease progression >5 years post curative surgery. We conclude that EpCAM identifies relevant disease-driving DCCs, that such cells can be expanded for model generation and that further research is needed to clarify the functional and prognostic role of rare EpCAM-negative sphere forming cells.

A Randomized Trial to Identify Accurate Measurement Methods for Adherence to Cognitive-Behavioral Therapy.

Clinician fidelity to cognitive behavioral therapy (CBT) is an important mechanism by which desired clinical outcomes are achieved and is an indicator of care quality. Despite its importance, there are few fidelity measurement methods that are efficient and have demonstrated reliability and validity. Using a randomized trial design, we compared three methods of assessing CBT adherence-a core component of fidelity-to direct observation, the gold standard. Clinicians recruited from 27 community mental health agencies (n = 126; M age = 37.69 years, SD = 12.84; 75.7% female) were randomized 1:1:1 to one of three fidelity conditions: self-report (n = 41), chart-stimulated recall (semistructured interviews with the chart available; n = 42), or behavioral rehearsal (simulated role-plays; n = 43). All participating clinicians completed fidelity assessments for up to three sessions with three different clients that were recruited from clinicians' caseloads (n = 288; M age = 13.39 years SD = 3.89; 41.7% female); sessions were also audio-recorded and coded for comparison to determine the most accurate method. All fidelity measures had parallel scales that yielded an adherence maximum score (i.e., the highest-rated intervention in a session), a mean of techniques observed, and a count total of observed techniques. Results of three-level mixed effects regression models indicated that behavioral rehearsal produced comparable scores to observation for all adherence scores (all ps > .01), indicating no difference between behavioral rehearsal and observation. Self-report and chart-stimulated recall overestimated adherence compared to observation (ps < .01). Overall, findings suggested that behavioral rehearsal indexed CBT adherence comparably to direct observation, the gold-standard, in pediatric populations. Behavioral rehearsal may at times be able to replace the need for resource-intensive direct observation in implementation research and practice.

Parental preference for webcams in neonatal intensive care units: an indicator of lacking trust?

BACKGROUND: Some neonatal intensive care units offer parents webcam systems for times when they cannot be in the ward. Leaving an infant in the ward can be challenging for parents, and trust in the neonatal healthcare professionals mitigates parents' worries of not knowing how their infant is doing while they are away. If parents lack trust in the neonatal healthcare professionals, they may attempt to compensate by using webcams. In this work, we examine whether an association exists between the parental preference to use a webcam and low trust in physicians and nursing staff. METHODS: In a nationwide, retrospective cross-sectional study, parents of infants with a birth weight below 1500 g were surveyed six to 18 months after their infant's birth. Parents who were not offered a webcam system in the ward were asked whether they would have opted for it. Trust was measured by the Trust in Physician and Trust in Nursing Staff scales. RESULTS: Of the parents who were not offered a webcam, 69% would have chosen to use a webcam if they had been granted the opportunity. The decision for or against a webcam was not significantly associated with either trust in physicians (OR = 0.654, 95% CI = 0.456, 0.937, p = .124) or trust in nursing staff (OR = 1.064, 95% CI = 0.783, 1.446, p = .932). CONCLUSIONS: While the majority of parents surveyed would opt for webcam usage, this preference should not be interpreted as an indicator of lacking trust in neonatal healthcare professionals.

Salt-inducible kinase 3 protects tumor cells from cytotoxic T-cell attack by promoting TNF-induced NF-κB activation.

BACKGROUND: Cancer immunotherapeutic strategies showed unprecedented results in the clinic. However, many patients do not respond to immuno-oncological treatments due to the occurrence of a plethora of immunological obstacles, including tumor intrinsic mechanisms of resistance to cytotoxic T-cell (TC) attack. Thus, a deeper understanding of these mechanisms is needed to develop successful immunotherapies. METHODS: To identify novel genes that protect tumor cells from effective TC-mediated cytotoxicity, we performed a genetic screening in pancreatic cancer cells challenged with tumor-infiltrating lymphocytes and antigen-specific TCs. RESULTS: The screening revealed 108 potential genes that protected tumor cells from TC attack. Among them, salt-inducible kinase 3 (SIK3) was one of the strongest hits identified in the screening. Both genetic and pharmacological inhibitions of SIK3 in tumor cells dramatically increased TC-mediated cytotoxicity in several in vitro coculture models, using different sources of tumor and TCs. Consistently, adoptive TC transfer of TILs led to tumor growth inhibition of SIK3-depleted cancer cells in vivo. Mechanistic analysis revealed that SIK3 rendered tumor cells susceptible to tumor necrosis factor (TNF) secreted by tumor-activated TCs. SIK3 promoted nuclear factor kappa B (NF-κB) nuclear translocation and inhibited caspase-8 and caspase-9 after TNF stimulation. Chromatin accessibility and transcriptome analyses showed that SIK3 knockdown profoundly impaired the expression of prosurvival genes under the TNF-NF-κB axis. TNF stimulation led to SIK3-dependent phosphorylation of the NF-κB upstream regulators inhibitory-κB kinase and NF-kappa-B inhibitor alpha on the one side, and to inhibition of histone deacetylase 4 on the other side, thus sustaining NF-κB activation and nuclear stabilization. A SIK3-dependent gene signature of TNF-mediated NF-κB activation was found in a majority of pancreatic cancers where it correlated with increased cytotoxic TC activity and poor prognosis. CONCLUSION: Our data reveal an abundant molecular mechanism that protects tumor cells from cytotoxic TC attack and demonstrate that pharmacological inhibition of this pathway is feasible.

Community Mental Health Clinicians' Perspectives on Telehealth During the COVID-19 Pandemic: Mixed Methods Study.

BACKGROUND: In March 2020, a rapid shift to telehealth occurred in community mental health settings in response to the need for physical distancing to decrease transmission of the virus causing COVID-19. Whereas treatment delivered over telehealth was previously utilized sparingly in community settings, it quickly became the primary mode of treatment delivery for the vast majority of clinicians, many of whom had little time to prepare for this shift and limited to no experience using telehealth. Little is known about community mental health clinicians' experiences using telehealth. Although telehealth may make mental health treatment more accessible for some clients, it may create additional barriers for others given the high rates of poverty among individuals seeking treatment from community mental health centers. OBJECTIVE: We examined community mental health clinicians' perspectives on using telehealth to deliver trauma-focused cognitive behavioral therapy to youth. We sought to better understand the acceptability of using telehealth, as well as barriers and facilitators to usage. METHODS: We surveyed 45 clinicians across 15 community clinics in Philadelphia. Clinicians rated their satisfaction with telehealth using a quantitative scale and shared their perspectives on telehealth in response to open-ended questions. Therapists' responses were coded using an open-coding approach wherein coders generated domains, themes, and subthemes. RESULTS: Clinicians rated telehealth relatively positively on the quantitative survey, expressing overall satisfaction with their current use of telehealth during the pandemic, and endorsing telehealth as a helpful mode of connecting with clients. Responses to open-ended questions fell into five domains. Clinicians noted that (1) telehealth affects the content (ie, what is discussed) and process (ie, how it is discussed) of therapy; (2) telehealth alters engagement, retention, and attendance; (3) technology is a crucial component of utilizing telehealth; (4) training, resources, and support are needed to facilitate telehealth usage; and (5) the barriers, facilitators, and level of acceptability of telehealth differ across individual clinicians and clients. CONCLUSIONS: First, telehealth is likely a better fit for some clients and clinicians than others, and attention should be given to better understanding who is most likely to succeed using this modality. Second, although telehealth increased convenience and accessibility of treatment, clinicians noted that across the board, it was difficult to engage clients (eg, young clients were easily distracted), and further work is needed to identify better telehealth engagement strategies. Third, for many clients, the telehealth modality may actually create an additional barrier to care, as children from families living in poverty may not have the requisite devices or quality broadband connection to make telehealth workable. Better strategies to address disparities in access to and quality of digital technologies are needed to render telehealth an equitable option for all youth seeking mental health services.

Stakeholder intention to engage in fidelity measurement methods in community mental health settings: A mixed methods study.

Background: The current gold standard for measuring fidelity (specifically, adherence) to cognitive behavioral therapy (CBT) is direct observation, a costly, resource-intensive practice that is not feasible for many community organizations to implement regularly. Recent research indicates that behavioral rehearsal (i.e., role-play between clinician and individual with regard to session delivery) and chart-stimulated recall (i.e., brief structured interview between clinician and individual about what they did in session; clinicians use the client chart to prompt memory) may provide accurate and affordable alternatives for measuring adherence to CBT in such settings, with behavioral rehearsal yielding greater correspondence with direct observation. Methods: Drawing on established causal theories from social psychology and leading implementation science frameworks, this study evaluates stakeholders' intention to use behavioral rehearsal and chart-stimulated recall. Specifically, we measured attitudes, self-efficacy, and subjective norms toward using each, and compared these factors across the two methods. We also examined the relationship between attitudes, self-efficacy, subjective norms, and intention to use each method. Finally, using an integrated approach we asked stakeholders to discuss their perception of contextual factors that may influence beliefs about using each method. These data were collected from community-based supervisors (n = 17) and clinicians (n = 66). Results: Quantitative analyses suggest moderately strong intention to use both methods across stakeholders. There were no differences in supervisors' or clinicians' attitudes, self-efficacy, subjective norms, or intention across methods. More positive attitudes and greater reported subjective norms were associated with greater reported intention to use either measure. Qualitative analyses identified participants' specific beliefs about using each fidelity measure in their organization, and results were organized using the Consolidated Framework for Implementation Research. Conclusions: Strategies are warranted to overcome or minimize potential barriers to using fidelity measurement methods and to further increase the strength of intention to use them.Plain Language Summary: The best way to measure fidelity, or how closely a clinician follows the protocol, to Cognitive Behavioral Therapy (CBT) is watching the session. This is an expensive practice that is not feasible for many community organizations to do regularly. Recent research indicates that behavioral rehearsal, or a role-play between the clinician and individual with regard to session delivery, and chart-stimulated recall, or a brief discussion between an individual and the clinician about what they did in session with the clinician having access to the chart to help them remember, may provide accurate and affordable alternatives for measuring fidelity to CBT. We just completed a study demonstrating that both methods are promising, with behavioral rehearsal offering scores that are the most similar to watching the session. Drawing on established theories from social psychology and leading implementation science frameworks, this study evaluates future supervisor and clinician motivation to use these fidelity measurement methods. Specifically, we measured supervisor (n = 17) and clinician (n = 66) attitudes, norms, self-efficacy, intentions, and anticipated barriers and facilitators to using each of these fidelity measurement tools. Quantitative and qualitative analyses suggest similar intention to use both methods, and concerns about barriers to using each method. Further research is warranted to minimize the burden associated with implementing fidelity measurement methods and deploying strategies to increase use.

Trust in medical professionals and its influence on the stress experience of parents of premature infants.

AIM: To examine parents' perceptions of stress and their trust in physicians and nursing staff and to investigate whether trust influences the parental perceptions of potential stressors resulting from their infant's hospitalisation in a neonatal intensive care unit. METHODS: Parents of very and extremely low birth weight infants were surveyed in a nationwide retrospective cross-sectional study 6-18 months after their child's birth. Parental stress was measured utilising the PSS:NICU_German/2-scales, and trust was measured by the scales Trust in Physicians and Trust in Nursing Staff. In addition to descriptive analyses, multiple linear regression models were conducted. RESULTS: The change in parents' anticipated roles was assessed as more stressful than their infant's appearance and behaviour. Trust in nursing staff significantly influenced the parental stress level. Although the level of trust in physicians was rated higher than trust in nursing staff, trust in physicians did not yield a significant effect on the parental stress experience. CONCLUSION: Efforts to foster parental trust in nursing staff may reduce the parental stress level and hence enable parents to better cope with the situation. The parental resources unleashed in this way can be employed to enhance parenting.

Retrospective cell lineage reconstruction in humans by using short tandem repeats.

Cell lineage analysis aims to uncover the developmental history of an organism back to its cell of origin. Recently, novel in vivo methods utilizing genome editing enabled important insights into the cell lineages of animals. In contrast, human cell lineage remains restricted to retrospective approaches, which still lack resolution and cost-efficient solutions. Here, we demonstrate a scalable platform based on short tandem repeats targeted by duplex molecular inversion probes. With this human cell lineage tracing method, we accurately reproduced a known lineage of DU145 cells and reconstructed lineages of healthy and metastatic single cells from a melanoma patient who matched the anatomical reference while adding further refinements. This platform allowed us to faithfully recapitulate lineages of developmental tissue formation in healthy cells. In summary, our lineage discovery platform can profile informative somatic mutations efficiently and provides solid lineage reconstructions even in challenging low-mutation-rate healthy single cells.

The TPOCS-self-reported Therapist Intervention Fidelity for Youth (TPOCS-SeRTIFY): A case study of pragmatic measure development.

Background: Developing pragmatic assessment tools to measure clinician use of evidence-based practices is critical to advancing implementation of evidence-based practices in mental health. This case study details our community-partnered process of developing the Therapy Process Observation Coding Scale-Self-Reported Therapist Intervention Fidelity for Youth (TPOCS-SeRTIFY), a pragmatic, clinician-report instrument to measure cognitive behavioral therapy (CBT) delivery. Approach: We describe a five-step community-partnered development process. Initial goals were to create a self-report instrument that paralleled an existing direct observation measure of clinician delivery of CBT use to facilitate later assessment of measure performance. Cognitive interviews with community clinicians (n = 6) and consultation with CBT experts (n = 6) were used to enhance interpretability and usability as part of an iterative refinement process. The instrument was administered to 247 community clinicians along with an established self-reported measure of clinician delivery of CBT and other treatments to assess preliminary psychometric performance. Preliminary psychometrics were promising. Conclusion: Our community-partnered development process showed promising success and can guide future development of pragmatic implementation measures both to facilitate measurement of ongoing implementation efforts and future research aimed at building learning mental health systems. Plain language summary: Developing brief, user-friendly, and accurate tools to measure how therapists deliver cognitive behavioral therapy (CBT) in routine practice is important for advancing the reach of CBT into community settings. To date, developing such "pragmatic" measures has been difficult. There is little known about how researchers can best develop these types of assessment tools so that they (1) are easy for clinicians in practice to use and (2) provide valid and useful information about implementation outcomes. As a result, there are few well-validated measures in existence that measure therapist use of CBT that are feasible for use in community practice. This paper contributes to the literature by describing our community-partnered process for developing a measure of therapist use of CBT (Therapy Process Observation Coding Scale -Self-Reported Therapist Intervention Fidelity for Youth; TPOCS-SeRTIFY). This descriptive case study outlines the community-partnered approach we took to develop this measure. This case study will contribute to future research by serving as a guide to others aiming to develop pragmatic implementation measures. In addition, the TPOCS-SeRTIFY is a pragmatic measure of clinician use of CBT that holds promise for its use by both researchers and clinicians to measure the success of CBT implementation efforts.

Interleukin-6 trans-signaling is a candidate mechanism to drive progression of human DCCs during clinical latency.

Although thousands of breast cancer cells disseminate and home to bone marrow until primary surgery, usually less than a handful will succeed in establishing manifest metastases months to years later. To identify signals that support survival or outgrowth in patients, we profile rare bone marrow-derived disseminated cancer cells (DCCs) long before manifestation of metastasis and identify IL6/PI3K-signaling as candidate pathway for DCC activation. Surprisingly, and similar to mammary epithelial cells, DCCs lack membranous IL6 receptor expression and mechanistic dissection reveals IL6 trans-signaling to regulate a stem-like state of mammary epithelial cells via gp130. Responsiveness to IL6 trans-signals is found to be niche-dependent as bone marrow stromal and endosteal cells down-regulate gp130 in premalignant mammary epithelial cells as opposed to vascular niche cells. PIK3CA activation renders cells independent from IL6 trans-signaling. Consistent with a bottleneck function of microenvironmental DCC control, we find PIK3CA mutations highly associated with late-stage metastatic cells while being extremely rare in early DCCs. Our data suggest that the initial steps of metastasis formation are often not cancer cell-autonomous, but also depend on microenvironmental signals.

Symptom scores and medication treatment patterns in children with ADHD versus autism.

Most children with autism have ADHD, and children with ADHD-Combined and children with autism have high rates of irritable, oppositional, and aggressive behavior. Despite similar symptoms, prescribing practices may differ between autism and ADHD, which has not been examined in a single study. 1407 children with autism and 1036 with ADHD without autism, 2-17 years, were compared with 186 typical peers. Symptom scores were maternal Pediatric Behavior Scale ratings in eight areas (ADHD, oppositional/aggressive, irritable/angry, anxious, depressed, and social, writing, and learning problems). Psychotropics were prescribed to 38.0% with ADHD-Combined, 33.3% with autism, and 20.2% with ADHD-Inattentive, most often an ADHD medication (22.1% stimulant, 2.3% atomoxetine), antipsychotic (7.8%), SSRI (5.5%), and alpha agonist (4.9%). ADHD medications were more often prescribed than other medications in all diagnostic groups. Compared to autism, children with ADHD-Combined were more likely to be prescribed an ADHD medication, whereas antipsychotics and SSRIs were more likely to be prescribed in autism than in ADHD-Combined. Children with ADHD-Inattentive were least impaired and least likely to be medicated. More severely impaired children were more often medicated regardless of diagnosis. Symptom scores were far worse for treated and untreated children with ADHD and with autism than for typical peers.

Pathways from early adversity to later adjustment: Tests of the additive and bidirectional effects of executive control and diurnal cortisol in early childhood.

Additive and bidirectional effects of executive control and hypothalamic-pituitary-adrenal (HPA) axis regulation on children's adjustment were examined, along with the effects of low income and cumulative risk on executive control and the HPA axis. The study utilized longitudinal data from a community sample of preschool age children (N = 306, 36-39 months at Time 1) whose families were recruited to overrepresent low-income contexts. We tested the effects of low income and cumulative risk on levels and growth of executive control and HPA axis regulation (diurnal cortisol level), the bidirectional effects of executive control and the HPA axis on each other, and their additive effects on children's adjustment problems, social competence and academic readiness. Low income predicted lower Time 4 executive control, and cumulative risk predicted lower Time 4 diurnal cortisol level. There was little evidence of bidirectional effects of executive control and diurnal cortisol. However, both executive control and diurnal cortisol predicted Time 4 adjustment, suggesting additive effects. There were indirect effects of income on all three adjustment outcomes through executive control, and of cumulative risk on adjustment problems and social competence through diurnal cortisol. The results provide evidence that executive control and diurnal cortisol additively predict children's adjustment and partially account for the effects of income and cumulative risk on adjustment.

Generation of an Oncolytic Herpes Simplex Virus 1 Expressing Human MelanA.

Robust anti-tumor immunity requires innate as well as adaptive immune responses. We have shown that plasmacytoid dendritic cells develop killer cell-like activity in melanoma cell cocultures after exposure to the infectious but replication-deficient herpes simplex virus 1 (HSV-1) d106S. To combine this innate effect with an enhanced adaptive immune response, the gene encoding human MelanA/MART-1 was inserted into HSV-1 d106S via homologous recombination to increase direct expression of this tumor antigen. Infection of Vero cells using this recombinant virus confirmed MelanA expression by Western blotting, flow cytometry, and immunofluorescence. HSV-1 d106S-MelanA induced expression of the transgene in fibroblast and melanoma cell lines not naturally expressing MelanA. Infection of a melanoma cell line with CRISPR-Cas9-mediated knockout of MelanA confirmed de novo expression of the transgene in the viral context. Dependent on MelanA expression, infected fibroblast and melanoma cell lines induced degranulation of HLA-matched MelanA-specific CD8+ T cells, followed by killing of infected cells. To study infection of immune cells, we exposed peripheral blood mononuclear cells and in vitro-differentiated macrophages to the parental HSV-1 d106S, resulting in expression of the transgene GFP in CD11c+ cells and macrophages. These data provide evidence that the application of MelanA-encoding HSV-1 d106S could enhance adaptive immune responses and re-direct MelanA-specific CD8+ T cells to tumor lesions, which have escaped adaptive immune responses via downregulation of their tumor antigen. Hence, HSV-1 d106S-MelanA harbors the potential to induce innate immune responses in conjunction with adaptive anti-tumor responses by CD8+ T cells, which should be evaluated in further studies.

Nurse-work instability and incidence of sick leave - results of a prospective study of nurses aged over 40.

BACKGROUND: The Nurse Work Instability Scale (Nurse-WIS) is an occupation-specific instrument that ascertains "work instability," the interval before restricted work ability or prolonged sick leave occurs. The objective of the study was to assess if nurses with a high risk baseline-score in the Nurse-WIS take longer periods of sick leave due to musculoskeletal diseases and/or psychological impairments than other nurses. METHODS: A total of 4500 nurses randomly selected from one of the largest health insurance funds in Germany (DAK-Gesundheit) were invited by letter to participate in the study. The participants answered a questionnaire at baseline and gave consent to a transfer of data concerning sick leave during the twelve months following completion of the questionnaire from the health insurance to the study centre. Sensitivity, specificity and positive and negative predictive values (PPV and NPV) for long-term sick leave were calculated. In order to analyze the association between the Nurse-WIS and sick leave during follow-up, a multiple ordinal logistic model (proportional odds model) was applied. RESULTS: A total of 1592 nurses took part in the study (response 35.6%). No loss of follow-up occurred. The number of nurses with a high score (20-28 points) in the Nurse-WIS was 628 (39.4%), and 639 (40.1%) had taken sick leave due to musculoskeletal diseases or psychological impairment during the follow-up period. The odds ratio for sick leave in nurses with a high Nurse-WIS score was 3.42 (95%CI 2.54-4.60). Sensitivity for long-term sick leave (< 42 days) was 64.1%, specificity 63.4%, PPV 17.0% and NPP 93.8%. CONCLUSION: The German version of the Nurse-WIS predicts long-term sick leave, but the PPV is rather low. Combining questionnaire data with secondary data from a health insurer was feasible. Therefore further studies employing this combination of data are advisable.

Parenting as a moderator of the effects of cumulative risk on children's social-emotional adjustment and academic readiness.

This study examined whether parenting moderated the association between cumulative risk and preschool children's adjustment problems, social competence and academic readiness. The sample consisted of 306 families representing the full range of income, with 29% at or near poverty and 28% lower income. Cumulative risk and observed maternal parenting behaviors were assessed when the children were 36-40 months, and teachers rated outcomes at 63-68 months. Greater cumulative risk was more strongly related to higher adjustment problems when scaffolding was low, and unrelated when it was high, suggesting a protective effect. Consistent limit setting was associated with higher academic readiness regardless of risk level, and at low levels of risk it was associated with the highest levels of social competence. A pattern potentially indicating differential effectiveness emerged for warmth, such that at lower levels of risk, higher warmth was associated with better outcomes, but at higher levels of risk, it was associated with higher levels of problems and poorer social competence and academic readiness. Results suggest that buffering effects of particular parenting behaviors, both alone and in combination, may be context-specific.