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The purpose of this essay is to share the voices of EdD graduates who are often underrepresented or missing in the literature. To begin, we invited EdD graduates to co-author this article about the connection among their EdD program experiences and interactions and their activism. We included our definition of activism and posed three open-ended questions. Six program graduates and one professor agreed to organize the graduates' responses by the question topics and salient themes. We asked about our experiences in the EdD program and how these influence--positively and negatively--what we are doing now (post-program). We found (a) relationships with faculty and cohort mattered; (b) instructional scaffolding was vital; and (c) faculty and cohorts reflected how lived experiences cultivated a sense of belonging and collectiveness. We also asked about our interactions with peers, cohort, advisor(s), instructors, or mentors, as well as, in what ways did these interactions affect--positively and negatively--what we are doing now (post-program). Lastly, we asked, in what ways, did the EdD program affect--positively or negatively--our activism in the classroom, community, or place of employment. We found examples of how we are shifting the landscape of academia to honor more voices in research and publication, more culturally responsive to impacted communities, and challenging the status quo. We focused on our experiences and interactions in an EdD program and how these experiences and interactions prompted activism in our current practice so that having a diversity of voices not only challenge other students, regardless of their background, to think differently about who creates, produces, and defines knowledge, as well as, support faculty that say they want to expand their curriculum and instruction, yet rely on what they know or what was taught to them in their courses.

The wide variety of clinical manifestations of the genetic syndrome neurofibromatosis type 1 (NF1) are driven by overactivation of the RAS pathway. Mitogen-activated protein kinase kinase inhibitors (MEKi) block downstream targets of RAS. The recent regulatory approvals of the MEKi selumetinib for inoperable symptomatic plexiform neurofibromas in children with NF1 have made it the first medical therapy approved for this indication in the United States, the European Union, and elsewhere. Several recently published and ongoing clinical trials have demonstrated that MEKi may have potential benefits for a variety of other NF1 manifestations, and there is broad interest in the field regarding the appropriate clinical use of these agents. In this review, we present the current evidence regarding the use of existing MEKi for a variety of NF1-related manifestations, including tumor (neurofibromas, malignant peripheral nerve sheath tumors, low-grade glioma, and juvenile myelomonocytic leukemia) and non-tumor (bone, pain, and neurocognitive) manifestations. We discuss the potential utility of MEKi in related genetic conditions characterized by overactivation of the RAS pathway (RASopathies). In addition, we review practical treatment considerations for the use of MEKi as well as provide consensus recommendations regarding their clinical use from a panel of experts.

Too often youth from vulnerable communities see themselves talked about in academic research, but are rarely involved as co-researchers or co-authors of research. The purpose of this article is to share our reflections on engaging youth, their experiences and their perspectives on the multi-levels of impact of participatory action research methodologies, such as community-based action research or youth participatory action research. This article discusses more broadly how our participatory methodologies have impacted our co-researchers and ourselves. In it, we provide additional details about our past research projects, as well as theorizing those details in terms of how critical theory serves as a tool within participatory methodologies. We reflect on the experiences engaging participatory methodologies in two different contexts and examine the collective impacts, comparing and contrasting the findings. We draw on our field research: one researcher worked with co-researchers from Kakuma Refugee Camp, Kenya, and the other worked alongside youth co-researchers from an alternative secondary school in the USA. Two of our co-authors are also co-researchers, and they offer a deeper insight into how these methodologies impacted their lives.

PURPOSE: Patients with B-cell acute lymphoblastic leukemia who experience relapse after or are resistant to CD19-targeted immunotherapies have limited treatment options. Targeting CD22, an alternative B-cell antigen, represents an alternate strategy. We report outcomes on the largest patient cohort treated with CD22 chimeric antigen receptor (CAR) T cells. PATIENTS AND METHODS: We conducted a single-center, phase I, 3 + 3 dose-escalation trial with a large expansion cohort that tested CD22-targeted CAR T cells for children and young adults with relapsed/refractory CD22+ malignancies. Primary objectives were to assess the safety, toxicity, and feasibility. Secondary objectives included efficacy, CD22 CAR T-cell persistence, and cytokine profiling. RESULTS: Fifty-eight participants were infused; 51 (87.9%) after prior CD19-targeted therapy. Cytokine release syndrome occurred in 50 participants (86.2%) and was grade 1-2 in 45 (90%). Symptoms of neurotoxicity were minimal and transient. Hemophagocytic lymphohistiocytosis-like manifestations were seen in 19/58 (32.8%) of subjects, prompting utilization of anakinra. CD4/CD8 T-cell selection of the apheresis product improved CAR T-cell manufacturing feasibility as well as heightened inflammatory toxicities, leading to dose de-escalation. The complete remission rate was 70%. The median overall survival was 13.4 months (95% CI, 7.7 to 20.3 months). Among those who achieved a complete response, the median relapse-free survival was 6.0 months (95% CI, 4.1 to 6.5 months). Thirteen participants proceeded to stem-cell transplantation. CONCLUSION: In the largest experience of CD22 CAR T-cells to our knowledge, we provide novel information on the impact of manufacturing changes on clinical outcomes and report on unique CD22 CAR T-cell toxicities and toxicity mitigation strategies. The remission induction rate supports further development of CD22 CAR T cells as a therapeutic option in patients resistant to CD19-targeted immunotherapy.

RASopathies caused by germline pathogenic variants in genes that encode RAS pathway proteins. These disorders include neurofibromatosis type 1 (NF1), Noonan syndrome (NS), cardiofaciocutaneous syndrome (CFC), and Costello syndrome (CS), and others. RASopathies are characterized by heterogenous manifestations, including congenital heart disease, failure to thrive, and increased risk of cancers. Previous work led by the NCI Pediatric Oncology Branch has altered the natural course of one of the key manifestations of the RASopathy NF1. Through the conduct of a longitudinal cohort study and early phase clinical trials, the MEK inhibitor selumetinib was identified as the first active therapy for the NF1-related peripheral nerve sheath tumors called plexiform neurofibromas (PNs). As a result, selumetinib was granted breakthrough therapy designation by the FDA for the treatment of PN. Other RASopathy manifestations may also benefit from RAS targeted therapies. The overall goal of Advancing RAS/RASopathy Therapies (ART), a new NCI initiative, is to develop effective therapies and prevention strategies for the clinical manifestations of the non-NF1 RASopathies and for tumors characterized by somatic RAS mutations. This report reflects discussions from a February 2019 initiation meeting for this project, which had broad international collaboration from basic and clinical researchers and patient advocates.

Neurofibromatosis type 1 (NF1) is associated with below average writing achievement. However, little is known about specific aspects of written language impacted by NF1, changes in writing over time, and associations between cognitive aspects of the NF1 phenotype and writing. At three timepoints over six years, children with NF1 and plexiform neurofibromas (PNs) completed Woodcock-Johnson tests of writing mechanics (Spelling, Punctuation & Capitalization, handwriting), written expression of ideas (Writing Samples), writing speed (Writing Fluency), and tests of general cognitive ability, executive function, memory, and attention. Children (N = 76, mean age = 12.8 ± 3.4 years) completed at least one baseline writing subtest. Overall writing scores were in the Average range (M = 93.4, SD = 17.4), but lower than population norms (p = 0.002). Scores were highest on Writing Samples (M = 95.2, SD = 17.3), and lowest for Punctuation & Capitalization (M = 87.9, SD = 18.8, p = 0.034). Writing scores were mostly stable over time. Nonverbal reasoning was related to some tests of writing mechanics and written expression of ideas. Short-term memory and inattention explained additional variance in Writing Samples and Spelling. Poor handwriting was associated with writing content beyond the impact of cognitive factors. Children with NF1 and PNs may benefit from early screening and writing support. Interventions should address the contribution of both cognitive and handwriting difficulties in written language. [ABSTRACT FROM AUTHOR]

Organized and hosted by the Children's Tumor Foundation (CTF), the Neurofibromatosis (NF) conference is the premier annual gathering for clinicians and researchers interested in neurofibromatosis type 1 (NF1), neurofibromatosis type 2 (NF2), and schwannomatosis (SWN). The 2016 edition constituted a blend of clinical and basic aspects of NF research that helped in clarifying different advances in the field. The incorporation of next generation sequencing is changing the way genetic diagnostics is performed for NF and related disorders, providing solutions to problems like genetic heterogeneity, overlapping clinical manifestations, or the presence of mosaicism. The transformation from plexiform neurofibroma (PNF) to malignant peripheral nerve sheath tumor (MPNST) is being clarified, along with new management and treatments for benign and premalignant tumors. Promising new cellular and in vivo models for understanding the musculoskeletal abnormalities in NF1, the development of NF2 or SWN associated schwannomas, and clarifying the cells that give rise to NF1-associated optic pathway glioma were presented. The interaction of neurofibromin and SPRED1 was described comprehensively, providing functional insight that will help in the interpretation of pathogenicity of certain missense variants identified in NF1 and Legius syndrome patients. Novel promising imaging techniques are being developed, as well as new integrative and holistic management models for patients that take into account psychological, social, and biological factors. Importantly, new therapeutic approaches for schwannomas, meningiomas, ependymomas, PNF, and MPNST are being pursued. This report highlights the major advances that were presented at the 2016 CTF NF conference.

Sickle cell disease (SCD) is associated with increased risk of neurocognitive deficits. However, whether functioning changes following nonmyeloablative hematopoietic stem cell transplant (HSCT) remains unclear. This study aimed to examine changes in neuropsychological functioning pre- to post-transplant among patients with SCD and compare patients and siblings. Adults with SCD (n = 47; Mage = 31.8 ± 8.9) and their sibling stem cell donors (n = 22; Mage = 30.5± 9.2) enrolled on a nonmyeloablative HCST protocol completed cognitive and patient-reported outcome assessments at baseline and 12 months post-transplant. Path analyses were used to assess associations between pre-transplant variables and sibling/patient group status and post-transplant function. Mean patient cognitive scores were average at both timepoints. Patient processing speed and somatic complaints improved from baseline to follow-up. Baseline performance predicted follow-up performance across cognitive variables; patient/sibling status predicted follow-up performance on some processing speed measures. Results suggest that patients with SCD demonstrate slower processing speed than siblings. Processing speed increased pre- to post-HSCT among patients and siblings, and on some measures patients demonstrated greater improvement. Thus, HSCT may improve processing speed in patients, although further confirmation is needed. Findings provide promising evidence that neurocognitive functioning remains stable without detrimental effects from pre- to 12-months post nonmyeloablative HSCT in individuals with SCD. [ABSTRACT FROM AUTHOR]

ObjectiveTumors and other disease complications of neurofibromatosis (NF) can cause pain and negatively affect physical functioning. To document the clinical benefit of treatment in NF trials targeting these manifestations, patient-reported outcomes (PROs) assessing pain and physical functioning should be included as study endpoints. Currently, there is no consensus on the selection and use of such measures in the NF population. This article presents the recommendations of the PRO group of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration for assessing the domains of pain and physical functioning for NF clinical trials.MethodsThe REiNS PRO group reviewed and rated existing PRO measures assessing pain intensity, pain interference, and physical functioning using their systematic method. Final recommendations are based primarily on 4 main criteria: patient characteristics, item content, psychometric properties, and feasibility for clinical trials.ResultsThe REiNS PRO group chose the Numeric Rating Scale-11 (≥8 years) to assess pain intensity, the Pain Interference Index (6-24 years) and the Patient-Reported Outcome Measurement Information System (PROMIS) Pain Interference Scale (≥18 years) to evaluate pain interference, and the PROMIS Physical Functioning Scale to measure upper extremity function and mobility (≥5 years) for NF clinical trials.ConclusionsThe REiNS Collaboration currently recommends these PRO measures to assess the domains of pain and physical functioning for NF clinical trials; however, further research is needed to evaluate their use in individuals with NF. A final consensus recommendation for the pain interference measure will be disseminated in a future publication based on findings from additional published research.

Neurofibromatosis type 1 (NF1) is associated with neurocognitive deficits that can impact everyday functioning of children, adolescents, and adults with this disease. However, there is little agreement regarding measures to use as cognitive endpoints in clinical trials. This article describes the work of the Neurocognitive Committee of the Response Evaluation in Neurofibromatosis and Schwannomatosis (REiNS) International Collaboration. The goal of this committee is to identify standardized and specific cognitive assessment tools for use in NF clinical trials. The committee first identified cognitive domains relevant to NF1 and prioritized attention as the first domain of focus given prior and current trends in NF1 cognitive clinical trials. Performance measures and behavioral rating questionnaires of attention were reviewed by the group using established criteria to assess patient characteristics, psychometric properties, and feasibility. The highest rated tests underwent side-by-side comparison. The Digit Span subtest from the Wechsler scales was given the highest ratings of the performance measures due to its good psychometrics, feasibility, utility across a wide age range, and extensive use in previous research. The Conners scales achieved the highest ratings of the behavioral questionnaires for similar reasons. Future articles will focus on other cognitive domains, with the ultimate goal of achieving agreement for cognitive endpoints that can be used across NF clinical trials.

For both Sophomore Inquiry (SINQ) faculty and graduate peer mentors, online education offers a chance to explore pedagogical approaches and adapt to new or different technology solutions to communicate with students. The purpose of this article is to explore how online SINQ faculty and graduate peer mentors instruct, build relationships, and interrupt oppressive situations while delivering an online course. The research examined how SINQ faculty and graduate peer mentors' pedagogy and practices evolved when translated from brick and mortar classrooms to online contexts. Semi-structured interviews were conducted. Transcripts were coded and thematic analysis was done. Critical hope was used as the conceptual framework. Four themes were identified: online instruction, SINQ faculty and graduate peer mentor relationships, interrupting oppressive language and behaviors, and online strategies. The last theme is presented as a table of participants' online strategies that highlights the effective practices in creating, nurturing, and sustaining equitable online learning environments.

Proficiency in writing is crucial for success in graduate school. While doctoral student writing has received attention in the research literature, little research has focused on master's student writing. Master's students need to be skilled writers in their professional lives, and have the same if not greater need for writing instruction as other graduate students. When writing is taught in graduate school, the instruction often focuses on content and text, not on the writing context and process. Recent research on academic writing suggests the importance of focusing on the behaviors, motivations, and cognitions that surround student writing, especially metacognitive awareness and self-regulation of the writing processes. This qualitative case study examined MA TESOL students' reactions to classroom activities designed to teach metacognitive awareness of writing strategies, self-regulation of writing practices, and text strategies. Data collected included surveys and students' writing plans. Five themes emerged from the data analysis. Students benefitted from: Increased metacognitive awareness of writing practices, the focus on the social support of writing, the opportunity to review peers' papers, discussion of the stress points around writing, and instruction about the text structures underlying academic writing. Suggestions for application of instructional practices to other writing programs are included.

Neurofibromatosis Type 1 (NF1) is an autosomal dominant genetic disorder that can cause an individual significant chronic pain (CP). CP affects quality of life and daily functioning, yet there are limited effective treatments for CP within NF1. The current study describes the impact of CP using the Neurofibromatosis Pain Module (NFPM). The NFPM is a self‐reported clinical assessment that evaluates the impact of CP across multiple domains (e.g., interference, severity, tolerance, and symptomology) and three prioritized pain regions. A cross‐sectional study (N = 242) asked adults with NF1 to describe and rate their pain using the NFPM. The results indicated that they reported moderate pain severity (M = 6.6, SD = 2.0) on a 0–10 scale, that 54% (n = 131) had been in pain at least 24 days in the last 30, for 75% (n = 181) sleep was affected, and 16% reported that nothing was effective in reducing their CP for their primary pain region. The current results extend previously published work on CP within adults with NF1 and indicate that more emphasis on understanding and ameliorating CP is required. The NFPM is a sensitive clinical measure that provides qualitative and quantitative responses to inform medical providers about changes in CP. [ABSTRACT FROM AUTHOR]

Objectives Neurofibromatosis type 1 (NF1) is a genetic cancer predisposition syndrome that can impact multiple organ systems and is associated with plexiform neurofibroma tumors, requiring care from birth through adulthood. Adolescents and young adults (AYAs) with NF1 face several barriers to transition from pediatric to adult care. This cross-sectional study aimed to assess transition readiness in this population and to evaluate relationships between specific NF1 symptoms and transition readiness. Methods AYAs (aged 16–24) enrolled in existing studies related to NF1 were eligible. AYAs and their parents completed measures of transition readiness (Transition Readiness Assessment Questionnaire version 4 [TRAQ-4]), and AYAs also completed a transition readiness interview (UNC TRxANSITION). Results Thirty-eight AYAs (mean age = 19.95 ± 2.68 years) participated in the study. Average TRAQ scores indicated that AYAs were still learning Self-Management skills (M  = 3.37, SD  = 1.08) and Self-Advocacy skills (M  = 3.98, SD  = 0.67). Older AYAs had higher TRAQ scores for Self-Management (r  = 0.70, p <.001) and Self-Advocacy (r  = 0.41, p =.011) than younger AYAs. Parents and AYAs had similar TRAQ scores. About one third of AYAs (37.8%, n  = 14) expressed uncertainty about how NF1 might affect them in the future. The remaining AYAs mostly expressed concerns regarding tumor growth, pain, or cancer. Conclusions In this small study, preliminary findings suggest that AYAs with NF1 express confidence in many areas of transition readiness but continue to require support, particularly with Self-Management skills. Given the gaps in understanding of future health risks, AYAs with NF1 would benefit from early assessment, psychoeducation, and support for transition readiness to adult care. [ABSTRACT FROM AUTHOR]

Background/Aims: We developed an observer disfigurement severity scale for neurofibroma-related plexiform neurofibromas to assess change in plexiform neurofibroma–related disfigurement and evaluated its feasibility, reliability, and validity. Methods: Twenty-eight raters, divided into four cohorts based on neurofibromatosis type 1 familiarity and clinical experience, were shown photographs of children in a clinical trial (NCT01362803) at baseline and 1 year on selumetinib treatment for plexiform neurofibromas (n = 20) and of untreated participants with plexiform neurofibromas (n = 4). Raters, blinded to treatment and timepoint, completed the 0–10 disfigurement severity score for plexiform neurofibroma on each image (0 = not at all disfigured, 10 = very disfigured). Raters evaluated the ease of completing the scale, and a subset repeated the procedure to assess intra-rater reliability. Results: Mean baseline disfigurement severity score for plexiform neurofibroma ratings were similar for the selumetinib group (6.23) and controls (6.38). Mean paired differences between pre- and on-treatment ratings was −1.01 (less disfigurement) in the selumetinib group and 0.09 in the control (p = 0.005). For the disfigurement severity score for plexiform neurofibroma ratings, there was moderate-to-substantial agreement within rater cohorts (weighted kappa range = 0.46–0.66) and agreement between scores of the same raters at repeat sessions (p > 0.05). In the selumetinib group, change in disfigurement severity score for plexiform neurofibroma ratings was moderately correlated with change in plexiform neurofibroma volume with treatment (r = 0.60). Conclusion: This study demonstrates that our observer-rated disfigurement severity score for plexiform neurofibroma was feasible, reliable, and documented improvement in disfigurement in participants with plexiform neurofibroma shrinkage. Prospective studies in larger samples are needed to validate this scale further. [ABSTRACT FROM AUTHOR]

Background/Aims: Individuals with neurofibromatosis, including neurofibromatosis 1 (NF1), neurofibromatosis 2 (NF2)–related schwannomatosis (SWN), and other forms of SWN, often experience disease manifestations and mental health difficulties for which psychosocial interventions may help. An anonymous online survey of adults with neurofibromatosis assessed their physical, social, and emotional well-being and preferences about psychosocial interventions to inform clinical trial design. Methods: Neurofibromatosis clinical researchers and patient representatives from the Response Evaluation in Neurofibromatosis and Schwannomatosis International Collaboration developed the survey. Eligibility criteria included age ≥ 18 years, self-reported diagnosis of NF1, NF2, or SWN, and ability to read and understand English. The online survey was distributed internationally by the Neurofibromatosis Registry and other neurofibromatosis foundations from June to August 2020. Results: Surveys were completed by 630 adults (18–81 years of age; M = 45.5) with NF1 (78%), NF2 (14%), and SWN (8%) who were mostly White, not Hispanic/Latino, female, and from the United States. The majority (91%) reported that their neurofibromatosis symptoms had at least some impact on daily life. In the total sample, 51% endorsed a mental health diagnosis, and 27% without a diagnosis believed they had an undiagnosed mental health condition. Participants indicated that neurofibromatosis affected their emotional (44%), physical (38%), and social (35%) functioning to a high degree. Few reported ever having participated in a drug (6%) or psychosocial (7%) clinical trial, yet 68% reported they "probably" or "definitely" would want to participate in a psychosocial trial if it targeted a relevant concern. Top treatment targets were anxiety, healthier lifestyle, and daily stress. Top barriers to participating in psychosocial trials were distance to clinic, costs, and time commitment. Respondents preferred interventions delivered by clinicians via individual sessions or a combination of group and individual sessions, with limited in-person and mostly remote participation. There were no significant group differences by neurofibromatosis type in willingness to participate in psychosocial trials (p = 0.27). Regarding interest in intervention targets, adults with SWN were more likely to prefer psychosocial trials for pain support compared to those with NF1 (p < 0.001) and NF2 (p < 0.001). Conclusion: This study conducted the largest survey assessing physical symptoms, mental health needs, and preferences for psychosocial trials in adults with neurofibromatosis. Results indicate a high prevalence of disease manifestations, psychosocial difficulties, and untreated mental health problems in adults with neurofibromatosis and a high degree of willingness to participate in psychosocial clinical trials. Patient preferences should be considered when designing and implementing psychosocial interventions to develop the most feasible and meaningful studies. [ABSTRACT FROM AUTHOR]

Background/Aims: Individuals with neurofibromatosis 1 may experience changes in their appearance due to physical manifestations of the disorders and/or treatment sequelae. Appearance concerns related to these physical changes can lead to psychological distress and poorer quality of life. While many neurofibromatosis 1 clinical trials focus on assessing changes in tumor volume, evaluating patients' perspectives on corresponding changes in symptoms such as physical appearance can be key secondary outcomes. We aimed to determine whether any existing patient-reported outcome measures are appropriate for evaluating changes in appearance concerns within neurofibromatosis 1 clinical trials. Methods: After updating our previously published systematic review process, we used it to identify and rate existing patient-reported outcome measures related to disfigurement and appearance. Using a systematic literature search and initial triage process, we focused on identifying patient-reported outcome measures that could be used to evaluate changes in appearance concerns in plexiform or cutaneous neurofibroma clinical trials in neurofibromatosis 1. Our revised Patient-Reported Outcome Rating and Acceptance Tool for Endpoints then was used to evaluate each published patient-reported outcome measures in five domains, including (1) respondent characteristics, (2) content validity, (3) scoring format and interpretability, (4) psychometric data, and (5) feasibility. The highest-rated patient-reported outcome measures were then re-reviewed in a side-by-side comparison to generate a final consensus recommendation. Results: Eleven measures assessing appearance concerns were reviewed and rated; no measures were explicitly designed to assess appearance concerns related to neurofibromatosis 1. The FACE-Q Craniofacial Module—Appearance Distress scale was the top-rated measure for potential use in neurofibromatosis 1 clinical trials. Strengths of the measure included that it was rigorously developed, included individuals with neurofibromatosis 1 in the validation sample, was applicable to children and adults, covered item topics deemed important by neurofibromatosis 1 patient representatives, exhibited good psychometric properties, and was feasible for use in neurofibromatosis 1 trials. Limitations included a lack of validation in older adults, no published information regarding sensitivity to change in clinical trials, and limited availability in languages other than English. Conclusion: The Response Evaluation in Neurofibromatosis and Schwannomatosis patient-reported outcome working group currently recommends the FACE-Q Craniofacial Module Appearance Distress scale to evaluate patient-reported changes in appearance concerns in clinical trials for neurofibromatosis 1-related plexiform or cutaneous neurofibromas. Additional research is needed to validate this measure in people with neurofibromatosis 1, including older adults and those with tumors in various body locations, and explore the effects of nontumor manifestations on appearance concerns in people with neurofibromatosis 1 and schwannomatosis. [ABSTRACT FROM AUTHOR]

Chimeric antigen receptor (CAR) T cells targeting CD19 mediate potent effects in relapsed and/or refractory pre-B cell acute lymphoblastic leukemia (B-ALL), but antigen loss is a frequent cause of resistance to CD19-targeted immunotherapy. CD22 is also expressed in most cases of B-ALL and is usually retained following CD19 loss. We report results from a phase 1 trial testing a new CD22-targeted CAR (CD22-CAR) in 21 children and adults, including 17 who were previously treated with CD19-directed immunotherapy. Dose-dependent antileukemic activity was observed, with complete remission obtained in 73% (11/15) of patients receiving [greater than equal ro]1 x 10[sup.6] CD22-CAR T cells per kg body weight, including 5 of 5 patients with CD19[sup.dim] or CD19[sup.-] B-ALL. Median remission duration was 6 months. Relapses were associated with diminished CD22 site density that likely permitted CD22[sup.+] cell escape from killing by CD22-CAR T cells. These results are the first to establish the clinical activity of a CD22-CAR in B-ALL, including leukemia resistant to anti-CD19 immunotherapy, demonstrating potency against B-ALL comparable to that of CD19-CAR at biologically active doses. Our results also highlight the critical role played by antigen density in regulating CAR function., Author(s): Terry J Fry (corresponding author) [1]; Nirali N Shah [1]; Rimas J Orentas [1]; Maryalice Stetler-Stevenson [2]; Constance M Yuan [2]; Sneha Ramakrishna [1]; Pamela Wolters [1]; Staci Martin [...]

Objective: To examine how executive functioning (EF) relates to academic achievement longitudinally in children with neurofibromatosis type 1 (NF1) and plexiform neurofibromas (PNs) and whether age at baseline moderates this relationship. Method: Participants included 88 children with NF1 and PNs (ages 6–18 years old, M = 12.05, SD = 3.62, 50 males) enrolled in a natural history study. Neuropsychological assessments were administered three times over 6 years. EF (working memory, inhibitory control, cognitive flexibility, and attention) was assessed by performance-based (PB) and parent-reported (PR) measures. Multilevel growth modeling was used to examine how EF at baseline related to initial levels and changes in broad math, reading, and writing across time, controlling for demographic variables. Results: The relationship between EF and academic achievement varied across EF and academic domains. Cognitive flexibility (PB) uniquely explained more variances in initial math, reading, and writing scores; working memory (PB) uniquely explained more variances in initial levels of reading and writing. The associations between EF and academic achievement tended to remain consistent across age groups with one exception: Lower initial levels of inhibitory control (PR) were related to a greater decline in reading scores. This pattern was more evident among younger (versus older) children. Conclusions: Findings emphasize the heterogeneous nature of academic development in NF1 and that EF skills could help explain the within-group variability in this population. Routine cognitive/academic monitoring via comprehensive assessments and early targeted treatments consisting of medication and/or systematic cognitive interventions are important to evaluate for improving academic performance in children with NF1 and PNs. [ABSTRACT FROM AUTHOR]

This case study describes collaboration between business executives and superintendents to influence local/regional K-12 educational change. Specifically, we examine participant like-mindedness about the ethics and appropriate focus of K-12 intermediary collaboration, the extent of democratic functioning, and key individuals to involve. Data sources consist of existing semistructured interviews with 6 superintendents and 28 business executives involved in intermediary organizations (i.e., chambers of commerce, business-education roundtables, educational nonprofits) within a metropolitan area of the U.S. Southwest. Furman's (2004) ethic of community frames the analysis. Participants narrate common moral purpose motivated by civic duty for the public good over profit-driven interests. Moreover, deficiencies in democratic collaborative processes formed divergent views on how this should be operationalized and thus caused some voices to be silenced. Superintendent inattention to democratic processes reinforced deficiencies despite the enabling potential of certain business executives.

Children with Diffuse Intrinsic Pontine Gliomas (DIPG), a malignant brainstem tumor, experience poor prognosis. Because of the disease's rarity and highly aggressive course, there is a dearth of research on cognitive and psychosocial outcomes in this underserved, vulnerable population. However, evaluating effects of the disease and treatment on the cognitive and daily functioning of these patients is important to better understand their specific needs and improve their quality of life. The current longitudinal study administered prospective neuropsychological assessments to children diagnosed with CNS malignancies, including the largest sample of children with DIPG to date (n = 21, mean age = 7.86 years, range = 3–16) in neurocognitive, behavioral, social-emotional, and adaptive functioning at baseline, two weeks post-radiation, and six months later. The results describe population-based, cross-sectional characteristics and within-patient longitudinal changes. Prior to radiation, children with DIPG exhibited significant weaknesses compared to normative samples in both parent-report and performance-based measures of attention, and tests of processing speed and verbal learning/memory. Younger children demonstrated poorer inhibitory control on performance tests and worse parent-reported behavioral regulation, depression, and social withdrawal compared to older children. Six-months post-radiation, older children exhibited poorer socialization than younger children. Longitudinally, children with DIPG exhibited short-term improvements immediately post-radiation in performance-based attention tests and parent-reported behavior, including attention, hyperactivity, behavioral regulation, and executive function. However, these improvements did not persist and significant decline was documented on tests of attention by six months. Clinical implications for professionals working with children with DIPG and recommendations for cognitive remediation and quality of life interventions are provided. [ABSTRACT FROM AUTHOR]

Children with Smith-Magenis Syndrome (SMS) exhibit deficits in adaptive behavior but systematic studies using objective measures are lacking. This descriptive study assessed adaptive functioning in 19 children with SMS using the Vineland Adaptive Behavior Scales (VABS). Maladaptive behavior was examined through parent questionnaires and the Childhood Autism Rating Scale. Cognitive functioning was evaluated with an age-appropriate test. Children scored below average on VABS Communication, Daily Living Skills, and Socialization scales. Learning problems and hyperactivity scales on the Conner's Parent Rating Scale were elevated, and girls were more impulsive than boys. Stereotypic and self-injurious behaviors were present in all children. Cognitive functioning was delayed and consistent with communication and daily living skills, while socialization scores were higher than IQ.