Multimodal examination of emotion processing systems associated with negative affectivity across early childhood

High Temperamental Negative Affectivity in early childhood has been found to predict later emotion dysregulation. While much work has been conducted to separately probe bio-behavioral systems associated with Negative Affectivity, very little work has examined the relations among multiple systems across age. In this study, we use multi-modal methods to index neurobiological systems associated with Negative Affectivity in 53 4-7-year-old children. Prefrontal activation during emotion regulation was measured using functional near-infrared spectroscopy over the lateral prefrontal cortex (PFC) while children played a game designed to elicit frustration in Social (Happy and Angry faces) and Nonsocial contexts. Gaze behaviors while free-viewing Happy and Angry faces were also measured. Finally, Negative Affectivity was indexed using a score composite based on factor analysis of parent-reported temperament. Using mixed-effects linear models, we found an age-dependent association between Negative Affectivity and both PFC activation during frustration and fixation duration on the mouth area of Happy faces, such that older children high in Negative Affectivity spent less time looking at the mouths of Happy faces and had lower PFC activation in response to frustration (ps\u3c0.034). These results provide further insight to how Negative Affectivity may be associated with changes in affective neurobiological systems across early childhood

Exploring Older Adult Mental Health Considerations in the Context of the COVID-19 Pandemic: A Framework Approach

Older adult mental health is a priority in Canada, especially with the deleterious effects of COVID-19. However, there is a gap in knowledge about the mental health-related considerations and concerns that are important for supporting aging Canadians. Secondary framework analysis used deductive codes constructed from a critical mental health literature review, and inductive codes generated from n=268 previously gathered free-form survey responses from older adults, caregivers, and health/social care providers in Canada. Key considerations included 1) core principles that influence the experiences and outcomes of older adults; 2) societal and system-level factors affecting older adult mental health; 3) services, supports, and programs that were identified as valuable; and 4) mental health experiences and outcomes mapped to a mental health dual continuum model. The expert-by-experience identified considerations are key elements that can be used when developing/adapting resources to ensure they are appropriate, relevant, and effective for aging Canadians’ mental health needs

Characterization of adolescent and pediatric renal cell carcinoma: A report from the Children's Oncology Group study AREN03B2

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/111918/1/cncr29368.pd

MLLT1 YEATS domain mutations in clinically distinctive Favourable Histology Wilms tumours.

Wilms tumour is an embryonal tumour of childhood that closely resembles the developing kidney. Genomic changes responsible for the development of the majority of Wilms tumours remain largely unknown. Here we identify recurrent mutations within Wilms tumours that involve the highly conserved YEATS domain of MLLT1 (ENL), a gene known to be involved in transcriptional elongation during early development. The mutant MLLT1 protein shows altered binding to acetylated histone tails. Moreover, MLLT1-mutant tumours show an increase in MYC gene expression and HOX dysregulation. Patients with MLLT1-mutant tumours present at a younger age and have a high prevalence of precursor intralobar nephrogenic rests. These data support a model whereby activating MLLT1 mutations early in renal development result in the development of Wilms tumour

Adversity is linked with decreased parent-child behavioral and neural synchrony

Parent-child synchrony-parent-child interaction patterns characterized by contingent social responding, mutual responsivity, and co-regulation-has been robustly associated with adaptive child outcomes. Synchrony has been investigated in both behavioral and biological frameworks. While it has been demonstrated that adversity can influence behavioral parent-child synchrony, the neural mechanisms by which this disruption occurs are understudied. The current study examined the association between adversity, parent-child behavioral synchrony, and parent-child neural synchrony across lateral prefrontal cortical regions using functional near-infrared spectroscopy hyperscanning during a parent-child interaction task that included a mild stress induction followed by a recovery period. Participants included 115 children (ages 4-5) and their primary caregivers. Parent-child behavioral synchrony was quantified as the amount time the dyad was synchronous (e.g., reciprocal communication, coordinated behaviors) during the interaction task. Parent-child neural synchrony was examined as the hemodynamic concordance between parent and child lateral PFC activation. Adversity was examined across two, empirically-derived domains: sociodemographic risk (e.g., family income) and familial risk (e.g., household chaos). Adversity, across domains, was associated with decreased parent-child behavioral synchrony across task conditions. Sociodemographic risk was associated with decreased parent-child neural synchrony in the context of experimentally-induced stress. These findings link adversity to decreased parent-child behavioral and neural synchrony

Is adrenalectomy necessary during unilateral nephrectomy for Wilms Tumor? A report from the Children\u27s Oncology Group.

PURPOSE: To determine whether performing adrenalectomy at the time of nephrectomy for unilateral Wilms tumor impacts clinical outcome. METHODS: We reviewed information on all patients enrolled on National Wilms Tumor Study-4 and -5. Data were abstracted on patient demographics, tumor characteristics, surgical and pathologic status of the adrenal gland, and patient outcomes. The primary endpoints were intraoperative spill and five-year event-free survival (EFS) in patients who did or did not undergo adrenalectomy. RESULTS: Of 3825 patients with complete evaluable data, the adrenal was left in situ in 2264 (57.9%) patients, and was removed completely in 1367 patients (36.7%) or partially in 194 patients (5.2%). Of the adrenal glands removed, 68 (4.4%) contained tumor. Adrenal involvement was more common in patients with stage 3 (9.8%) than stage 2 disease (1.9%; p \u3c 0.0001). After controlling for stage and histopathology, five-year EFS was similar whether or not the adrenal gland was removed (p = 0.48), or involved with tumor (p = 0.81); however, intraoperative spill rates were higher in patients undergoing adrenalectomy (26.1% vs 15.5%, p \u3c 0.0001), likely due to larger tumor size or technical factors. No patient had clinical evidence of adrenal insufficiency or tumor recurrence in the adrenal gland during follow-up (median 9.9 years). CONCLUSIONS: Sparing the adrenal gland during nephrectomy for unilateral Wilms tumor was not associated with a higher incidence of intraoperative spill and was associated with a similar oncologic outcome, on a per-stage basis, with cases where the adrenal was removed. Thus, adrenalectomy should not be considered mandatory during radical nephrectomy for Wilms tumor

Risk Factors for End Stage Renal Disease in Non-WT1-Syndromic Wilms Tumor

PURPOSE: We assessed risk factors for end stage renal disease in patients with Wilms tumor without known WT1 related syndromes. We hypothesized that patients with characteristics suggestive of a WT1 etiology (early onset, stromal predominant histology, intralobar nephrogenic rests) would have a higher risk of end stage renal disease due to chronic renal failure. We predicted a high risk of end stage renal disease due to progressive bilateral Wilms tumor in patients with metachronous bilateral disease. MATERIALS AND METHODS: End stage renal disease was ascertained in 100 of 7,950 nonsyndromic patients enrolled in a National Wilms Tumor Study during 1969 to 2002. Risk factors were evaluated with cumulative incidence curves and proportional hazard regressions. RESULTS: The cumulative incidence of end stage renal disease due to chronic renal failure 20 years after Wilms tumor diagnosis was 0.7%. For end stage renal disease due to progressive bilateral Wilms tumor the incidence was 4.0% at 3 years after diagnosis in patients with synchronous bilateral Wilms tumor and 19.3% in those with metachronous bilateral Wilms tumor. For end stage renal disease due to chronic renal failure stromal predominant histology had a HR of 6.4 relative to mixed (95% CI 3.4, 11.9; p<0.001), intralobar rests had a HR of 5.9 relative to no rests (95% CI 2.0, 17.3; p=0.001), and Wilms tumor diagnosis at less than 24 months had a HR of 1.7 relative to 24 to 48 months and 2.8 relative to greater than 48 months (p=0.003 for trend). CONCLUSIONS: Metachronous bilateral Wilms tumor is associated with high rates of end stage renal disease due to surgery for progressive Wilms tumor. Characteristics associated with a WT1 etiology markedly increased the risk of end stage renal disease due to chronic renal failure despite the low risk in non-WT1 syndromic cases overall

Surgical protocol violations in children with renal tumors provides an opportunity to improve pediatric cancer care: a report from the Children’s Oncology Group

BackgroundThe purpose of this study was to evaluate the frequency and characteristics of surgical protocol violations (SPVs) among children undergoing surgery for renal tumors who were enrolled on the Children’s Oncology Group (COG) renal tumor biology and classification study AREN03B2.MethodsAREN03B2 was opened in February 2006, and as on March 31, 2013, there were 3,664 eligible patients. The surgical review forms for 3,536 patients with unilateral disease were centrally reviewed for SPVs. The frequency, type, number of violations, institutional prevalence, and quartiles for SPVs were assessed.ResultsOf the 3,536 patients, there were a total of 505 with at least one SPV (564 total SPVs reported), for an overall incidence of 14.28%. The types of SPVs included a lack of lymph node sampling in 365 (64.7%), avoidable spill in 61 (10.8%), biopsy immediately before nephrectomy in 89 (15.8%), an incorrect abdominal incision in 32 (5.7%), and unnecessary resection of organs in 17 (3.0%). The SPVs occurred in 163 of 215 participating institutions (75.8%). For centers with at least one SPV, the mean number of SPVs reported was 3.10 ± 2.39 (mean ± standard deviation). The incidence of protocol violation per institution ranged from 0 to 67%. Centers with an average of ≤1 case/year had an incidence of SPVs of 12.2 ± 3.8%, those with an average of >1 to 0.05).ConclusionsSPVs that potentially result in additional exposure to chemotherapy and radiation therapy are not uncommon in children undergoing resection of renal malignancies.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134088/1/pbc26083.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134088/2/pbc26083_am.pd

TPS mutational status is a potential marker for risk stratification in Wilms tumour with diffuse anaplasia

Purpose The presence of diffuse anaplasia in Wilms tumours (DAWT) is associated with TP53 mutations and poor outcome. As patients receive intensified treatment, we sought to identify whetherTP53 mutational status confers additional prognostic information. Patients and Methods We studied 40 patients with DAWT with anaplasia in the tissue from which DNA was extracted and analysed for TP53 mutations and 17p loss. The majority of cases were profiled by copy number (n = 32) and gene expression (n = 36) arrays. TP53 mutational status was correlated with patient event-free and overall survival, genomic copy number instability and gene expression profiling. Results From the 40 cases, 22 (55%) had TP53 mutations (2 detected only after deep-sequencing), 20 of which also had 17p loss (91%); 18 (45%) cases had no detectable mutation but three had 17p loss. Tumours with TP53 mutations and/or 17p loss (n = 25) had an increased risk of recurrence as a first event (p = 0.03, hazard ratio (HR), 3.89; 95% confidence interval (CI), 1.26–16.0) and death (p = 0.04, HR, 4.95; 95% CI, 1.36–31.7) compared to tumours lackingTP53 abnormalities. DAWT carrying TP53 mutations showed increased copy number alterations compared to those with wild-type, suggesting a more unstable genome (p = 0.03). These tumours showed deregulation of genes associated with cell cycle and DNA repair biological processes. Conclusion This study provides evidence that TP53 mutational analysis improves risk stratification in DAWT. This requires validation in an independent cohort before clinical use as a biomarker