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Convegni di Bologna e Bari. Arundo donax: valutazioni agronomiche, energetiche e di sostenibilità Guest Editor: Prof. Gianpietro Venturi Si ringrazia il Ministero delle Politiche Agricole Alimentari e Forestali (MiPAAF) che ha finanziato il progetto BIOSEA, Ottimizzazione delle filiere Bioenergetiche per una Sostenibilità Economica ed Ambientale.

XVI CONGRESSO NAZIONALE FADOI Firenze, 15-18 maggio 2011

Special Issue on "Broncopneumopatia cronica ostruttiva e comorbidità croniche"

Book of Abstracts - 9th International Hereditary Hemorrhagic Telangiectasia Scientific Conference, 20-24 May 2011 Kemer, Antalya – Turkey

The 6th International Symposium on Clinical Applications of Serum Free Light Chain Analysis (plus Hevylite) was held in Bath, UK on 23rd and 24th September 2010. This Symposium included measurements in monoclonal gammopathies, myeloma kidney and inflammatory diseases; data from the Multi-centre, Phase III, Randomised control trial on extended haemodialysis with the Gambro protein-leaking HCO 1100 dialyser; and presentations on Hevylite (intact immunoglobulin kappa/lambda ratios) in a variety of clinical situations.

EDITORIAL FOREWORDPage 1 Milnacipran: recent findings in depression Stuart Montgomery (London, UK) and Mike Briley (Castres, France) REVIEWSPage 3 Suicidality: risk factors and the effects of antidepressants. The example of parallel reduction of suicidality and other depressive symptoms during treatment with the SNRI, milnacipran Philippe Courtet (Montpellier, France)Page 9 Treatment of patients with comorbid depression and diabetes with metformin and milnacipran Peter Hofmann (Graz, Austria)Page 17 Antidepressant therapy with milnacipran and venlafaxine Lucilla Mansuy (Toulouse, France)Page 23 Milnacipran: a unique antidepressant? Siegfried Kasper and Gerald Pail (Vienna, Austria) This supplement is based on a symposium that took place at the 9th International Forum on Mood and Anxiety in Monte Carlo in November 2009 and is supported by an unconditional education grant from Pierre Fabre Médicament.

XXXVI Italian Congress of AIEOP (Associazione Italiana Ematologia Oncologia Pediatrica - Pisa, Italy, 6-8 June 2010

This volume includes contributions presented at the 8th International Symposium on Enchytraeidae, held in Durham, U.K., 3 to 5 July, 2008. Fifteen participants from seven European countries gave 7 talks and 7 poster presentations, most of them in the field of soil ecology. A one-day excursion to the Durham Coast was used to take soil samples from a variety of habitats. The extracted worms were the material for a workshop on enchytraeid identification the following day, monitored by R. M. Schmelz, who had prepared a text key to the identification of European species. An extended version of this handout will be published in one of the following issues of ‘Soil Organisms’. The joint identification efforts during the workshop are included in this volume (Standen et al.). We thank the University of Durham for providing rooms and logistics, and the British Ecological Society for financial support.

Appearance concerns are a pervasive issue affecting many university students and contributing to poor psychosocial and academic outcomes. To combat these, action is needed by universities to promote appearance inclusivity. The current study used inductive qualitative methods to explore students' lived and/or living experiences and concerns relating to their physical appearance and views on how to achieve an appearance inclusive university. Seventeen students aged 19-55 from a UK university participated in online semi-structured interviews (n=12) and focus groups (n=5). Thirteen participants were women, three were men, and one was non-binary. Interviews and focus groups were transcribed verbatim and analysed using reflexive thematic analysis. Students identified several ways appearance concerns had negatively impacted them and supported an increased focus on appearance inclusivity at university. Three themes were developed: 1) appearance has a big impact on my university life; 2) it's not the same for everyone (i.e., individual differences and intersectionality impact students' experiences); and 3) intentional change is needed (i.e., change is necessary to improve appearance inclusivity, but it should be consciously thought out). Strategies to improve appearance inclusivity should be prioritised and carefully considered to avoid tokenism and ensure they centre the needs of those from underrepresented groups., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Aberrant expression of HOX and MEIS1 family genes, as seen in KMT2A-rearranged, NUP98-rearranged, or NPM1-mutated leukemias leads to arrested differentiation and leukemia development. HOX family genes are essential gatekeepers of physiologic hematopoiesis, and their expression is regulated by the interaction between KMT2A and menin. Menin inhibitors block this interaction, downregulate the abnormal expression of MEIS1 and other transcription factors and thereby release the differentiation block. Menin inhibitors show significant clinical efficacy against KMT2A-rearranged and NPM1-mutated acute leukemias, with promising potential to address unmet needs in various pediatric leukemia subtypes. In this collaborative initiative, pediatric and adult hematologists/oncologists, and stem cell transplant physicians have united their expertise to explore the potential of menin inhibitors in pediatric leukemia treatment internationally. Our efforts aim to provide a comprehensive clinical overview of menin inhibitors, integrating preclinical evidence and insights from ongoing global clinical trials. Additionally, we propose future international, inclusive, and efficient clinical trial designs, integrating pediatric populations in adult trials, to ensure broad access to this promising therapy for all children and adolescents with menin-dependent leukemias., (© 2024. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Abstract: A comprehensive international consensus on the cytogenetic risk-group stratification of KMT2A-rearranged (KMT2A-r) pediatric acute myeloid leukemia (AML) is lacking. This retrospective (2005-2016) International Berlin-Frankfurt-Münster Study Group study on 1256 children with KMT2A-r AML aims to validate the prognostic value of established recurring KMT2A fusions and additional cytogenetic aberrations (ACAs) and to define additional, recurring KMT2A fusions and ACAs, evaluating their prognostic relevance. Compared with our previous study, 3 additional, recurring KMT2A-r groups were defined: Xq24/KMT2A::SEPT6, 1p32/KMT2A::EPS15, and 17q12/t(11;17)(q23;q12). Across 13 KMT2A-r groups, 5-year event-free survival probabilities varied significantly (21.8%-76.2%; P < .01). ACAs occurred in 46.8% of 1200 patients with complete karyotypes, correlating with inferior overall survival (56.8% vs 67.9%; P < .01). Multivariable analyses confirmed independent associations of 4q21/KMT2A::AFF1, 6q27/KMT2A::AFDN, 10p12/KMT2A::MLLT10, 10p11.2/KMT2A::ABI1, and 19p13.3/KMT2A::MLLT1 with adverse outcomes, but not those of 1q21/KMT2A::MLLT11 and trisomy 19 with favorable and adverse outcomes, respectively. Newly identified ACAs with independent adverse prognoses were monosomy 10, trisomies 1, 6, 16, and X, add(12p), and del(9q). Among patients with 9p22/KMT2A::MLLT3, the independent association of French-American-British-type M5 with favorable outcomes was confirmed, and those of trisomy 6 and measurable residual disease at end of induction with adverse outcomes were identified. We provide evidence to incorporate 5 adverse-risk KMT2A fusions into the cytogenetic risk-group stratification of KMT2A-r pediatric AML, to revise the favorable-risk classification of 1q21/KMT2A::MLLT11 to intermediate risk, and to refine the risk-stratification of 9p22/KMT2A::MLLT3 AML. Future studies should validate the associations between the newly identified ACAs and outcomes and unravel the underlying biological pathogenesis of KMT2A fusions and ACAs., (© 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)

Background: Adults with conditions that affect their appearance, known as visible differences, can experience appearance concerns, social anxiety, and depression. Interventions have been developed for this population to facilitate adjustment and coping skills; however, they have limited evidence of efficacy. The Expand Your Horizon [Alleva, J. M., Martijn, C., Van Breukelen, G. J., Jansen, A., & Karos, K. (2015). Expand Your Horizon: A programme that improves body image and reduces self-objectification by training women to focus on body functionality. Body Image, 15, 81-89. https://doi.org/10.1016/j.bodyim.2015.07.001] online functionality-based writing programme was adapted for adults with visible differences., Method: A pilot randomised controlled trial with a wait-list control group was carried out to assess preliminary intervention efficacy and gain information about the acceptability and feasibility of the programme. Forty-four adults aged 21-63 years ( M  = 40.21; SD  = 12.05) with visible differences took part. Various facets of body image (i.e. functionality appreciation and body appreciation) as well as depression and anxiety were assessed immediately pre- and post-intervention and at three-months., Results: Participants reported enjoying the programme, felt that the format was acceptable, and it significantly increased functionality appreciation, which was maintained at three-months. However, there were no improvements in body appreciation, depression, and anxiety., Conclusions: In future, a full trial should be carried out with an active control group., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Adolescents with the rare birthmarks congenital melanocytic naevi (CMN) experience physical and psychosocial challenges, many of which stem from looking different from the 'norm'. However, some adjust and have positive experiences. Understanding the lived experiences of adolescents who have adjusted to CMN can provide a holistic picture of adjustment and inform the development of support and interventions for others with the condition. Open, participant-driven photo-elicitation interviews were conducted with four White females (15-17 years) who self-identified as having adjusted to CMN. Participants chose five photographs which were used to guide the interviews (47-80 min). Interpretative phenomenological analysis (IPA) was used to analyse the transcribed interview data. Three superordinate themes were identified: 'Accepting My 'True' Self' (1), 'I am Not Alone in This' (2), and 'Developing as a Person' (3). The themes related to accepting CMN as part of their identity, developing a positive body image (e.g., body appreciation, broad conceptualisations of beauty, body image flexibility), feeling supported and accepted by family, friends, and others with CMN, and developing adaptive coping skills. Findings suggest positive body image may be important for adjustment and can be determined by an individual. The benefits of using photo-elicitation within appearance research are discussed., Competing Interests: Declaration of Competing Interest In accordance with Body Image policy, the authors declare that they have no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Children and young people with visible differences can experience psychosocial difficulties, such as anxiety and teasing by others. Interventions targeting difficulties have previously been reviewed by Jenkinson et al. This review aimed to identify and critically assess recent studies evaluating the effectiveness of psychosocial interventions for children and young people with visible differences on psychosocial wellbeing, self-esteem, and social experiences and compare the findings with Jenkinson et al. using a replacement review process., Methods: Inclusion criteria are as follows: studies with participants aged 0-18 years with visible differences; investigating a psychosocial intervention; including comparison with an alternative intervention, control group, or pre- and post-intervention; and including a quantitative measure assessed pre- and post-intervention. Exclusion criteria are as follows: participants with body dysmorphic disorder or appearance changes due to eating disorders or obesity and studies not written in English. MEDLINE, AMED, and PsycInfo were searched and grey literature was included. Results were reviewed against eligibility criteria, data were extracted, and studies were evaluated using the Cochrane Risk of Bias 2 tool., Results: Using Jenkinson et al. as one source of studies, 24 studies were included evaluating a range of interventions such as social interaction skills training, residential social camps, and cognitive behavioral therapy. Risk of bias was high in 20 studies and of some concern in four studies., Conclusion: There is some evidence of the effectiveness of hypnotherapy, a relaxation response resiliency program, integrative body-mind-spirit group, and therapeutic patient education, but more rigorous research is needed to confirm their impact on psychosocial outcomes., (© The Author(s) 2023. Published by Oxford University Press on behalf of the Society of Pediatric Psychology.)

Background: Patients with unmet healthcare needs are more likely to access unscheduled care. Identifying these patients through data-driven and clinical risk stratification for active case management in primary care can help address patient need and reduce demand on acute services., Aim: To determine how a proactive digital healthcare system can be used to undertake comprehensive needs analysis of patients at risk of unplanned admission and mortality., Design & Setting: Prospective cohort study of six general practices in a deprived UK city., Method: To identify those with unmet needs, the study's population underwent digitally-driven risk stratification into Escalated and Non-escalated groups using seven risk factors. The Escalated group underwent further stratification using GP clinical assessment into Concern and No concern groups. The Concern group underwent Unmet Needs Analysis (UNA)., Results: From 24 746 patients, 516 (2.1%) were triaged into the Concern group and 164 (0.7%) underwent UNA. These patients were more likely to be older ( t = 4.69, P <0.001), female (X 2 = 4.46, P <0.05), have a Patients At Risk of Re-hospitalisation (PARR) score ≥80 (X 2 = 4.31, P <0.05), be a nursing home resident (X 2 = 6.75, P <0.01), or on an end-of-life (EOL) register (X 2 = 14.55, P <0.001). Following UNA, 143 (87.2%) patients had further review planned or were referred for further input. The majority of patients had four domains of need. In those who GPs would not be surprised if they died within the next few months, n = 69 (42.1%) were not on an EOL register., Conclusion: This study showed how an integrated, patient-centred, digital care system working with GPs can highlight and implement resources to address the escalating care needs of complex individuals., (Copyright © 2023, The Authors.)

Purpose: A previous study by the International Berlin-Frankfurt-Münster Study Group (I-BFM-SG) on childhood KMT2A -rearranged ( KMT2A -r) AML demonstrated the prognostic value of the fusion partner. This I-BFM-SG study investigated the value of flow cytometry-based measurable residual disease (flow-MRD) and evaluated the benefit of allogeneic stem-cell transplantation (allo-SCT) in first complete remission (CR1) in this disease., Methods: A total of 1,130 children with KMT2A -r AML, diagnosed between January 2005 and December 2016, were assigned to high-risk (n = 402; 35.6%) or non-high-risk (n = 728; 64.4%) fusion partner-based groups. Flow-MRD levels at both end of induction 1 (EOI1) and 2 (EOI2) were available for 456 patients and were considered negative (<0.1%) or positive (≥0.1%). End points were 5-year event-free survival (EFS), cumulative incidence of relapse (CIR), and overall survival (OS)., Results: The high-risk group had inferior EFS (30.3% high risk v 54.0% non-high risk; P < .0001), CIR (59.7% v 35.2%; P < .0001), and OS (49.2% v 70.5%; P < .0001). EOI2 MRD negativity was associated with superior EFS (n = 413; 47.6% MRD negativity v n = 43; 16.3% MRD positivity; P < .0001) and OS (n = 413; 66.0% v n = 43; 27.9%; P < .0001), and showed a trend toward lower CIR (n = 392; 46.1% v n = 26; 65.4%; P = .016). Similar results were obtained for patients with EOI2 MRD negativity within both risk groups, except that within the non-high-risk group, CIR was comparable with that of patients with EOI2 MRD positivity. Allo-SCT in CR1 only reduced CIR (hazard ratio, 0.5 [95% CI, 0.4 to 0.8]; P = .00096) within the high-risk group but did not improve OS. In multivariable analyses, EOI2 MRD positivity and high-risk group were independently associated with inferior EFS, CIR, and OS., Conclusion: EOI2 flow-MRD is an independent prognostic factor and should be included as risk stratification factor in childhood KMT2A -r AML. Treatment approaches other than allo-SCT in CR1 are needed to improve prognosis.

We measured minimal residual disease (MRD) by multiparameter flow cytometry at three time points (TP) in 117 infants with KMT2A (lysine [K]-specific methyltransferase 2A)-rearranged and 58 with KMT2A-germline acute lymphoblastic leukemia (ALL) on Children's Oncology Group AALL0631 study. For KMT2A-rearranged patients, 3-year event-free survival (EFS) by MRD-positive (≥0.01%) versus MRD-negative (<0.01%) was: TP1: 25% (±6%) versus 49% (±7%; p = .0009); TP2: 21% (±8%) versus 47% (±7%; p < .0001); and TP3: 22% (±14%) versus 51% (±6%; p = .0178). For KMT2A-germline patients, 3-year EFS was: TP1: 88% (±12%) versus 87% (±5%; p = .73); TP2: 100% versus 88% (±5%; p = .24); and TP3: 100% versus 87% (±5%; p = .53). MRD was a strong independent outcome predictor in KMT2A-rearranged, but not KMT2A-germline infant ALL., (© 2023 Wiley Periodicals LLC.)

Body positive social media content aims to positively impact young women's body image and mood by challenging traditionally narrow beauty ideals. This online experiment investigated the effect of viewing body positive Instagram posts on young women's body image and mood, whilst focusing on understanding the impact of the images and captions in the posts. Overall, 195 young women (18-30 years old) were randomly assigned to view either body positive (consisting of images and captions), body positive captions only, body positive images only, or thin-ideal Instagram posts. Positive mood increased in all conditions pre to post exposure. Further, body satisfaction and negative mood improved pre-post exposure for all body positive conditions. However, when controlling for trait body appreciation significant effects only remained for the combined image and caption body positive condition. There were no significant differences in positive mood, state body appreciation, self-objectification, or broad conceptualisations of beauty between the three body positive exposure conditions. Therefore, to improve body satisfaction and mood, body positive content should include a combination of images and captions., Competing Interests: Conflicts of interest In accordance with Body Image policy, the authors declare that they have no conflicts of interest., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Objective: Ewing Sarcoma Family of Tumors (ESFT) are a highly aggressive pediatric bone and soft tissue malignancy with poor outcomes in the refractory and recurrent setting. Over 90% of Ewing Sarcoma (ES) tumors are driven by the pathognomonic EWS-ETS chimeric transcripts and their corresponding oncoproteins. It has been suggested that the EWS-ETS oncogenic action can mediate microRNA (miRNA) processing. Importantly, small extracellular vesicles (sEVs), including those frequently referred to as exosomes have been shown to be highly enriched with tumor-derived small RNAs such as miRNAs. We hypothesized that ESFT-specific sEVs are enriched with certain miRNAs which could be utilized toward an exo-miRNA biomarker signature specific to this disease. Methods: We performed miRNAseq to compare both the exo-derived and cell-derived miRNA content from 8 ESFT, 2 osteosarcoma, 2 non-cancerous cell lines, and pediatric plasma samples. Results: We found that sEVs derived from ESFT cells contained nearly 2-fold more number of unique individual miRNAs as compared to non-ESFT samples. Quantitative analysis of the differential enrichment of sEV miRNAs resulted in the identification of 62 sEV-miRNAs (exo-miRNAs) with significant ( P < .05) enrichment variation between ESFT and non-ESFT sEV samples. To determine if we could utilize this miRNA signature to diagnose ESFT patients via a liquid biopsy, we analyzed the RNA content of total circulating sEVs isolated from 500 µL plasma from 5 pediatric ESFT patients, 2 pediatric osteosarcoma patients, 2 pediatric rhabdomyosarcoma patients, and 4 non-cancer pediatric controls. Pearson's clustering of 60 of the 62 candidate exo-miRNAs correctly identified 80% (4 of 5) of pathology confirmed ESFT patients. Importantly, RNAseq analysis of tumor tissue from the 1 outlier, revealed a previously uncharacterized EWS-FLI1 translocation. Conclusions: Taken together, these findings support the development and validation of an exo-miRNA-based liquid biopsy to aid in the diagnosis and monitoring of ESFT., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Evidence shows interventions can improve positive body image in adult women. This systematic review examined the evidence of efficacy of interventions that aimed to increase positive body image in children and young people aged under 18 years. The authors followed PRISMA guidelines for the review. Searches of CINAHL Plus, Medline, PsychINFO, Wiley Online Library, SCOPUS and grey literature were conducted up to February 2021 and identified 4171 papers. Thirteen studies evaluating 12 interventions, designed for children/adolescents aged 9-18 years, were eligible and evaluated using the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool. The studies evaluated body appreciation, body-esteem, and embodiment. Studies using cognitive dissonance, peer support, and psychoeducation had evidence of improving body appreciation and body-esteem in adolescent girls. However, evidence of efficacy for younger children and boys was lacking and the studies ranged in methodological quality. Further research should rigorously evaluate positive body image interventions using second-generation measures that assess specific components of positive body image and consider how to promote positive body image in young children and boys., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Individual behaviour changes, such as hand hygiene and physical distancing, are required on a population scale to reduce transmission of infectious diseases such as COVID-19. However, little is known about effective methods of communicating risk reducing information, and how populations might respond., Objective: To synthesise evidence relating to what (1) characterises effective public health messages for managing risk and preventing infectious disease and (2) influences people's responses to messages., Design: A rapid systematic review was conducted. Protocol is published on Prospero CRD42020188704., Data Sources: Electronic databases were searched: Ovid Medline, Ovid PsycINFO and Healthevidence.org, and grey literature (PsyarXiv, OSF Preprints) up to May 2020., Study Selection: All study designs that (1) evaluated public health messaging interventions targeted at adults and (2) concerned a communicable disease spread via primary route of transmission of respiratory and/or touch were included. Outcomes included preventative behaviours, perceptions/awareness and intentions. Non-English language papers were excluded., Synthesis: Due to high heterogeneity studies were synthesised narratively focusing on determinants of intentions in the absence of measured adherence/preventative behaviours. Themes were developed independently by two researchers and discussed within team to reach consensus. Recommendations were translated from narrative synthesis to provide evidence-based methods in providing effective messaging., Results: Sixty-eight eligible papers were identified. Characteristics of effective messaging include delivery by credible sources, community engagement, increasing awareness/knowledge, mapping to stage of epidemic/pandemic. To influence intent effectively, public health messages need to be acceptable, increase understanding/perceptions of health threat and perceived susceptibility., Discussion: There are four key recommendations: (1) engage communities in development of messaging, (2) address uncertainty immediately and with transparency, (3) focus on unifying messages from sources and (4) frame messages aimed at increasing understanding, social responsibility and personal control. Embedding principles of behavioural science into public health messaging is an important step towards more effective health-risk communication during epidemics/pandemics., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: We investigated the impact of the CD33-targeted agent gemtuzumab ozogamicin (GO) on survival in pediatric patients with KMT2A -rearranged ( KMT2A -r) acute myeloid leukemia (AML) enrolled in the Children's Oncology Group trial AAML0531 (NCT01407757)., Methods: Patients with KMT2A -r AML were identified and clinical characteristics described. Five-year overall survival (OS), event-free survival (EFS), disease-free survival (DFS), and relapse risk (RR) were determined overall and for higher-risk versus not high-risk translocation partners. GO's impact on response was determined and outcomes based on consolidation approach (hematopoietic stem cell transplant [HSCT] v chemotherapy) described., Results: Two hundred fifteen (21%) of 1,022 patients enrolled had KMT2A -r AML. Five-year EFS and OS from study entry were 38% and 58%, respectively. EFS was superior with GO treatment (EFS 48% with GO v 29% without, P = .003), although OS was comparable (63% v 53%, P = .054). For patients with KMT2A -r AML who achieved complete remission, GO was associated with lower RR (40% GO v 66% patients who did not receive GO [No-GO], P = .001) and improved 5-year DFS (GO 57% v No-GO 33%, P = .002). GO benefit was observed in both higher-risk and not high-risk KMT2A -r subsets. For patients who underwent HSCT, prior GO exposure was associated with decreased relapse (5-year RR: 28% GO and HSCT v 73% No-GO and HSCT, P = .006). In multivariable analysis, GO was independently associated with improved EFS, improved DFS, and reduced RR., Conclusion: GO added to conventional chemotherapy improved outcomes for KMT2A -r AML; consolidation with HSCT may further enhance outcomes. Future clinical trials should study CD33-targeted agents in combination with HSCT for pediatric KMT2A- r AML., Competing Interests: Jessica A. PollardConsulting or Advisory Role: Syndax Pharmaceuticals, Kura Oncology Erin GuestConsulting or Advisory Role: Syndax Pharmaceuticals Mike R. LokenEmployment: Hematologics IncLeadership: Hematologics IncStock and Other Ownership Interests: Hematologics IncConsulting or Advisory Role: Newlink Genetics Lisa Eidenschink BrodersenEmployment: Hematologics Inc E. Anders KolbTravel, Accommodations, Expenses: Roche/Genentech Alan S. GamisConsulting or Advisory Role: NovartisNo other potential conflicts of interest were reported.

Inflammatory myofibroblastic tumors (IMTs) are rare in neonates. IMTs of the tongue are also very rare in infancy, with only 1 case reported in this age group. The mainstay of therapy has traditionally been surgery, which can be devastating to surrounding structures and negatively impact prognosis. Approximately 50% of IMTs harbor a translocation involving the anaplastic lymphoma kinase gene. We describe a case of IMT of the tongue in a neonate treated with debulking and an anaplastic lymphoma kinase inhibitor. The patient achieved complete response and remains disease-free 1.5 year following completion of therapy., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Public health teams need to understand how the public responds to vaccination messages in a pandemic or epidemic to inform successful campaigns encouraging the uptake of new vaccines as they become available. A rapid systematic review was performed by searching PsycINFO, MEDLINE, healthevidence.org, OSF Preprints and PsyArXiv Preprints in May 2020 for studies including at least one health message promoting vaccine uptake of airborne-, droplet- and fomite-spread viruses. Included studies were assessed for quality using the Mixed Methods Appraisal Tool (MMAT) or the Assessment of Multiple Systematic Reviews (AMSTAR), and for patient and public involvement (PPI) in the research. Thirty-five articles were included. Most reported messages for seasonal influenza ( n = 11; 31%) or H1N1 ( n = 11; 31%). Evidence from moderate to high quality studies for improving vaccine uptake included providing information about virus risks and vaccination safety, as well as addressing vaccine misunderstandings, offering vaccination reminders, including vaccination clinic details, and delivering mixed media campaigns across hospitals or communities. Behavioural influences (beliefs and intentions) were improved when: shorter, risk-reducing or relative risk framing messages were used; the benefits of vaccination to society were emphasised; and beliefs about capability and concerns among target populations (e.g., vaccine safety) were addressed. Clear, credible, messages in a language target groups can understand were associated with higher acceptability. Two studies (6%) described PPI in the research process. Future campaigns should consider the beliefs and information needs of target populations in their design, including ensuring that vaccine eligibility and availability is clear, and messages are accessible. More high quality research is needed to demonstrate the effects of messaging interventions on actual vaccine uptake.

Background: Although many cope well, the impact of supporting a child with an Appearance-Affecting Health Condition (AAHC) can place a significant demand on parents. As such, it is vital that families have access to appropriate psychosocial support to reduce any potential difficulties. Although previous reviews have explored the effectiveness of psychosocial interventions for parents of Children and Young People (CYP) with general health conditions, the evidence of effectiveness remains limited. Further, little is known about the effectiveness of such interventions specifically among parents of CYP with AAHCs. This review aimed to identify and assess the evidence of effectiveness of psychosocial interventions among parents of CYP with AAHCs., Methods: Database searches were conducted using MEDLINE, PsychARTICLES, PsychINFO, CINAHL Plus, the British Nursing Database and the Cochrane Library. Results were reviewed against the inclusion criteria and data were extracted. Methodological quality was assessed using the Effective Public Health Practice Project Quality Assessment Tool, and a narrative synthesis was conducted., Results: Fifteen studies, evaluating 10 interventions, were included and overall seven interventions were found to be effective (effect sizes and methodological quality varied)., Conclusions: This review finds moderate to strong evidence of effectiveness of the Triple P Positive Parenting Program, the Early Family Intervention Program and general parent education/training interventions. These findings offer useful insights relating to the delivery of current support, as well as for the development of future parent and family interventions. Finally, recommendations for future intervention evaluation studies in this area are made., (© 2020 The Authors. Child: Care, Health and Development published by John Wiley & Sons Ltd.)

Purpose: Patient-reported outcome measures (PROMs) identify patient needs and therapeutic progress. This paper outlines the development and validation of the CARe Burn Scale: Child Form, a parent-proxy-reported outcome measure that assesses quality of life in children aged 8 and under living with a burn injury., Methods: A literature review and interviews with 12 parents of children with a burn and seven health professionals informed the development of a conceptual framework and draft PROM. Cognitive debriefing interviews with 18 parents and eight health professionals provided feedback to ascertain content validity, and 311 parents took part in field testing. Rasch and traditional psychometric analyses were conducted to create a shortened version. Further psychometric analyses with 133 parents tested the shortened CARe Burn Scale in relation to other parent-proxy measures., Results: The final conceptual framework included 5 domains: Social and Emotional Difficulties, Social and Emotional Well-Being, Wound/Scar Discomfort, Wound/Scar Treatment and Physical Abilities. Two scales fulfilled Rasch and traditional psychometric analyses, providing evidence of construct validity, acceptability, and reliability. Three scales did not fulfil the Rasch criteria and were retained as checklists. Compared to other parent-proxy measures, individual CARe Burn Scales correlated moderately with similar constructs and had low correlations with dissimilar constructs, indicating evidence of criterion validity (concurrent and discriminant)., Conclusions: The CARe Burn Scale: Child Form can be used to measure children's quality of life after having a burn injury which can inform rehabilitation and surgical decision-making.

External and internal signals can prime the plant immune system for a faster and/or stronger response to pathogen attack. β-aminobutyric acid (BABA) is an endogenous stress metabolite that induces broad-spectrum disease resistance in plants. BABA perception in Arabidopsis is mediated by the aspartyl tRNA synthetase IBI1, which activates priming of multiple immune responses, including callose-associated cell wall defenses that are under control by abscisic acid (ABA). However, the immediate signaling components after BABA perception by IBI1, as well as the regulatory role of ABA therein, remain unknown. Here, we have studied the early signaling events controlling IBI1-dependent BABA-induced resistance (BABA-IR), using untargeted transcriptome and protein interaction analyses. Transcriptome analysis revealed that IBI1-dependent expression of BABA-IR against the biotrophic oomycete Hyaloperonospora arabidopsidis is associated with suppression of ABA-inducible abiotic stress genes. Protein interaction studies identified the VOZ1 and VOZ2 transcription factors (TFs) as IBI1-interacting partners, which are transcriptionally induced by ABA but suppress pathogen-induced expression of ABA-dependent genes. Furthermore, we show that VOZ TFs require nuclear localization for their contribution to BABA-IR by mediating augmented expression of callose-associated defense. Collectively, our study indicates that the IBI1-VOZ signaling module channels pathogen-induced ABA signaling toward cell wall defense while simultaneously suppressing abiotic stress-responsive genes., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

Leukaemia stem cells (LSCs) underlie cancer therapy resistance but targeting these cells remains difficult. The Wnt-β-catenin and PI3K-Akt pathways cooperate to promote tumorigenesis and resistance to therapy. In a mouse model in which both pathways are activated in stem and progenitor cells, LSCs expanded under chemotherapy-induced stress. Since Akt can activate β-catenin, inhibiting this interaction might target therapy-resistant LSCs. High-throughput screening identified doxorubicin (DXR) as an inhibitor of the Akt-β-catenin interaction at low doses. Here we repurposed DXR as a targeted inhibitor rather than a broadly cytotoxic chemotherapy. Targeted DXR reduced Akt-activated β-catenin levels in chemoresistant LSCs and reduced LSC tumorigenic activity. Mechanistically, β-catenin binds multiple immune-checkpoint gene loci, and targeted DXR treatment inhibited expression of multiple immune checkpoints specifically in LSCs, including PD-L1, TIM3 and CD24. Overall, LSCs exhibit distinct properties of immune resistance that are reduced by inhibiting Akt-activated β-catenin. These findings suggest a strategy for overcoming cancer therapy resistance and immune escape.

Purpose: Treatment failure from drug resistance is the primary reason for relapse in acute lymphoblastic leukemia (ALL). Improving outcomes by targeting mechanisms of drug resistance is a potential solution., Patients and Methods: We report results investigating the epigenetic modulators decitabine and vorinostat with vincristine, dexamethasone, mitoxantrone, and PEG-asparaginase for pediatric patients with relapsed or refractory B-cell ALL (B-ALL). Twenty-three patients, median age 12 years (range, 1-21) were treated in this trial., Results: The most common grade 3-4 toxicities included hypokalemia (65%), anemia (78%), febrile neutropenia (57%), hypophosphatemia (43%), leukopenia (61%), hyperbilirubinemia (39%), thrombocytopenia (87%), neutropenia (91%), and hypocalcemia (39%). Three subjects experienced dose-limiting toxicities, which included cholestasis, steatosis, and hyperbilirubinemia ( n = 1); seizure, somnolence, and delirium ( n = 1); and pneumonitis, hypoxia, and hyperbilirubinemia ( n = 1). Infectious complications were common with 17 of 23 (74%) subjects experiencing grade ≥3 infections including invasive fungal infections in 35% (8/23). Nine subjects (39%) achieved a complete response (CR + CR without platelet recovery + CR without neutrophil recovery) and five had stable disease (22%). Nine (39%) subjects were not evaluable for response, primarily due to treatment-related toxicities. Correlative pharmacodynamics demonstrated potent in vivo modulation of epigenetic marks, and modulation of biologic pathways associated with functional antileukemic effects., Conclusions: Despite encouraging response rates and pharmacodynamics, the combination of decitabine and vorinostat on this intensive chemotherapy backbone was determined not feasible in B-ALL due to the high incidence of significant infectious toxicities. This study is registered at http://www.clinicaltrials.gov as NCT01483690., (©2020 American Association for Cancer Research.)

Background: From diagnosis through to adulthood, a cleft lip and/or palate (CL/P) poses a number of challenges for those affected. Alongside the care provided by clinical teams, complementary information and support is offered by charitable organizations. In 2011, the Cleft Lip and Palate Association received funding to implement a new regional service across England and Scotland, with the aim of increasing support at a local level. The Centre for Appearance Research at the University of the West of England were commissioned to conduct an independent evaluation of the service over 7 years., Methods: A pragmatic, mixed-methods approach was utilized to assess the impact of the service from the perspective of charity volunteers; children, young people, and adults with CL/P; caregivers; and clinicians. Feedback forms were distributed to stakeholders at a variety of events, and qualitative feedback was collected via focus groups and an online survey., Results: The majority of participants indicated they had gained access to a local support network, felt more able to cope with CL/P-related challenges, and felt more confident in themselves. Qualitative investigation provided further support for these findings and highlighted additional benefits of the regional service for clinical teams., Conclusions: The evaluation provides encouraging evidence toward the contribution of a relatively small charitable organization in the context of cleft care. The importance of a pragmatic approach to community-based evaluation and the benefits of collaborative working between researchers and the charitable sector were also highlighted.

Objective: The birth of a child with a cleft lip and/or palate (CL/P) can have a significant emotional and social impact on parents. Yet, the impact on the wider family is rarely investigated. Grandparents are becoming increasingly involved in the care of their grandchildren and may therefore have support needs of their own. The aim of the current study was to explore the experiences and support needs of grandparents of children born with CL/P., Design: Individual semistructured telephone interviews were carried out with 12 grandparents of children born with CL/P and were analyzed using inductive thematic analysis., Results: Five themes were identified (1) emotional impact of CL/P on grandparents, (2) grandparents' social experiences, (3) grandparents' involvement, (4) grandparents' information needs, and (5) grandparents' support needs. Participants experienced difficult emotions around the time of diagnosis and were concerned about the child's treatment and future experiences. Participants played a significant role in supporting the whole family, but received little information or support themselves., Conclusions: Grandparents reported experiences comparable to published literature on parents. Clinicians and charitable organizations could consider how existing resources could be made more accessible to and/or adapted for wider family members, including grandparents.

Theory suggests promoting positive body image (PBI) through interventions would have a significant impact on health and well-being. However, little is known about the effectiveness of existing interventions. This review aimed to identify and assess the evidence of effectiveness of interventions to increase PBI in adults. Database searches were conducted using CINAHL Plus, Medline, PsychINFO, Wiley Online Library, and SCOPUS. Application of inclusion criteria and data extraction were conducted by two reviewers. Methodological quality was assessed using the Effective Public Health Practice Project Quality Assessment Tool, and narrative synthesis was conducted. Fifteen studies, evaluating 13 interventions, were included. Three studies, evaluating one online writing-based functionality intervention, were judged to have strong methodological quality and had evidence of improving body appreciation, body esteem, and functionality satisfaction. Six moderate quality studies found interventions using intuitive eating, CBT, self-compassion, and exercise improved PBI. There was limited evidence of effectiveness of interventions for men, suggesting future research is needed to better understand PBI mechanisms in men. Lack of heterogeneity of outcome measures is discussed as a limitation. Findings suggest existing interventions are effective at increasing aspects of PBI among women and support the development of interventions that target multiple components of PBI., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Patient-Reported Outcome Measures (PROMs) identify vital information about patient needs and therapeutic progress. This paper outlines the development and validation of the CARe Burn Scale-Adult Form: a PROM that assesses quality of life in adults living with a burn injury. Eleven patients, 10 family members and 4 health professional interviews, and a systematic review informed the development of a conceptual framework and a draft measure. Cognitive debriefing interviews conducted with three adult burn patients, one family member, and eight health professionals provided feedback to ascertain content validity of the measure. The measure was then field tested with 304 adult burn patients. Rasch psychometric analysis was conducted for scale reduction, and traditional psychometric analyses provided a comparison with other measures. Further psychometric testing with an additional 118 adult burn patients tested the shortened CARe Burn Scale in relation to other quality of life PROMs. The conceptual framework outlined 14 domains; 12 of which fulfilled Rasch and traditional psychometric analyses. Two individual scales did not fulfill the Rasch criteria and were retained as checklists. Individual CARe Burn Scales correlated moderately-to-highly with other quality of life scales measuring similar constructs, and had low-to-no correlations with dissimilar constructs and the majority of sociodemographic factors, indicating evidence of concurrent and divergent validity. The CARe Burn Scale-Adult Form can help identify patient needs and provides burns-specialist health professionals with a tool to assess quality of life and therapeutic progress after a burn event and related treatment., (© American Burn Association 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Cleft lip and/or palate (CL/P) poses many challenges for those affected throughout the school years, with recent studies pointing to a trend in poor educational outcomes. Previous research has highlighted the important role that teachers play in supporting young people with chronic health conditions yet studies in the field of CL/P suggest that teachers may lack knowledge of the condition, and underestimate pupils' academic ability. Qualitative investigation of the impact of CL/P from the teacher's perspective may provide additional insight as well as potential suggestions for improving the school experience for affected pupils., Methods: Twenty UK preschool, primary, and secondary school teachers with experience of teaching pupils with CL/P completed an open-ended survey, eliciting qualitative data., Results: Qualitative content analysis was performed. Data were presented under 5 key headings: Knowledge of CL/P and its effects, perceived impact of CL/P on education, teachers' training needs, delivery of training, and impact of CL/P on teachers. Teachers were able to identify a number of potential social, emotional, and treatment-related challenges within the school setting, yet did not believe that CL/P would have a long-term impact on pupils' educational achievement. Participating teachers reported that cleft-specific training and access to relevant resources would be highly beneficial., Conclusions: Acting as a platform for future research, this exploratory study provides insight into the challenges faced by teachers and offers suggestions for how to improve teachers' understanding of CL/P, and their confidence in dealing with cleft-related issues.

Precision oncologic medicine is an emerging approach for cancer treatment that has recently taken giant steps in solid clinical practice. Recent advances in molecular diagnostics that can analyze the individual tumor's variability in genes have provided greater understanding and additional strategies to treat cancers. Although tumors can be tested by several molecular methods, the use of next-generation sequencing (NGS) has greatly facilitated our understanding of pediatric cancer and identified additional therapeutic opportunities. Pediatric tumors have a different genetic make-up, with a fewer number of actionable targets than adult tumors. Nevertheless, precision oncology in the pediatric population has greatly improved the survival of patients with leukemia and solid tumors. This review discusses the current status of pediatric precision oncology and the different clinical scenarios in which it can be effectively applied.

Background: Decision making about breast reconstruction (BR) following a diagnosis of breast cancer, Ductal Carcinoma in Situ (DCIS), or to reduce future breast cancer risk, is difficult and complex. This paper systematically reviews interventions aiming to support patients facing the option of BR, and assesses their effectiveness in improving a range of patient outcomes., Methods: Ten databases were searched for articles published up to October 2017 that evaluated interventions to support patient decision making about BR within controlled trials. All included studies were assessed for methodological quality. Descriptive analyses of patient outcomes within included studies were performed., Results: The search yielded 3291 articles. Eight studies met the inclusion criteria resulting in the evaluation of seven distinct interventions (n = 1212). Six studies were assessed to be of weak methodological quality, with one of moderate and one of strong quality. Three out of five interventions demonstrated a reduction in decisional conflict (ds = 0.26-0.69) and two out of three interventions resulted in reductions in decisional regret (ds = 0.27-3.69) at various time points. Treatment choice was altered in two of five studies. There were no changes in patient-reported anxiety levels, whilst the impact on depression was mixed. In all studies which reported on it, improvements in patient satisfaction and involvement in decision making were found., Conclusions: Few interventions are currently available. Whilst some findings are encouraging, improvements on patient outcomes are mixed. Further research should focus on the development and evaluation of effective interventions., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Introduction: A burn can have a significant and long-lasting psychosocial impact on a patient and their family. The National Burn Care Standards (2013) recommend psychosocial support should be available in all UK burn services; however, little is known about how it is provided. The current study aimed to explore experiences of psychosocial specialists working in UK burn care, with a focus on the challenges they experience in their role., Methods: Semi-structured telephone interviews with eight psychosocial specialists (two psychotherapists and six clinical psychologists) who worked within UK burn care explored their experiences of providing support to patients and their families., Results and Discussion: Thematic analysis revealed two main themes: burn service-related experiences and challenges reflected health professionals having little time and resources to support all patients; reduced patient attendance due to them living large distances from service; psychosocial appointments being prioritised below wound-related treatments; and difficulties detecting patient needs with current outcome measures. Therapy-related experiences and challenges outlined the sociocultural and familial factors affecting engagement with support, difficulties treating patients with pre-existing mental health conditions within the burn service and individual differences in the stage at which patients are amenable to support., Conclusion: Findings provide an insight into the experiences of psychosocial specialists working in UK burn care and suggest a number of ways in which psychosocial provision in the NHS burn service could be developed., Competing Interests: Declaration of conflicting interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

The prevalence of obesity and related comorbidities in survivors of childhood acute lymphoblastic leukemia (ALL) is well established and ranges anywhere from 29% to 69% depending on the study. We sought to explore the awareness of parents of survivors of childhood ALL regarding the increased risk of obesity and their perceptions regarding the overall health of their child. One hundred twenty-one parents of 99 survivors of pediatric ALL completed surveys regarding perceptions of obesity risk in survivors. Eighty percent of parents of overweight and obese survivors correctly identified their child as "a little overweight" or "overweight." Few parents recalled discussing weight gain (21%) or obesity risk (36%) with their practitioner. Parents that did recall having these discussions and/or reported a decreased level of posttherapy activity in their child were more likely to be concerned about their child's weight status. Improved awareness and education regarding the risk of obesity and associated comorbid conditions may provide an avenue for future prevention of obesity in survivors of pediatric ALL. Discussion and education regarding a healthy lifestyle, including proper diet and exercise, should be incorporated early in routine patient visits.

Patient-reported outcome measures (PROMs) are vital for evaluating patient needs and therapeutic progress. This review aimed to identify the PROMs used in adult burn care and establish their quality. Computerized bibliographic searches of Psychinfo, Social Sciences Citation Index, Cinahl, Psycharticles, AMED, Medline, and HAPI were used to find English-language articles using English-language PROMs from January 2001 to September 2016. Psychometric quality assessment of the PROMs was conducted. A total of 117 studies achieved the entry criteria and reported using 77 different PROMs (71 generic and 6 burn-specific). Overall, the psychometric quality of the PROMs was low; only 17 (13 generic and 4 burn-specific) had psychometric evidence appropriate to adults with burn injuries completing an English language version of the PROM. Although this review identified a number of generic and burn-specific PROMs that have some psychometric evidence with adult burn patients, research is still needed to further examine these preexisting measures and validate them in different languages. This will enable researchers and clinicians to better understand the potential impact of a burn injury on adults, and evaluate the effectiveness of therapeutic interventions.

Today there exist two medical applications where relatively strong evidence exists to support the broad adoption of genome-informed precision medicine. These are the differential diagnosis of single gene diseases and genotype-based selection of patients for targeted cancer therapies. However, despite the availability of the $1000 genome and $700 exome for research, there is as yet little broad uptake of genomic medicine, even in these applications. Significant impediments to mainstream adoption exist, including unavailability in many institutions, lack of scalability in others, a dearth of physician understanding of interpreted genome or exome results or knowledge of how to translate consequent precision medicine care plans, and a lack of test reimbursement. In short, genomic medicine lacks a breakthrough application. Rapid genome sequencing of acutely ill infants with suspected genetic diseases (STATseq) may become that application when scaled to dozens of trios per day without loss of timeliness or accuracy. Also critical for broad adoption is embedding STATseq in software for timely patient ascertainment, augmented intelligence for interpretation, explanation of results for generalist physicians, and dynamic precision medicine decision support.

The elongation stage of transcription is highly regulated in metazoans. We previously purified the AFF1- and AFF4-containing super elongation complex (SEC) as a major regulator of development and cancer pathogenesis. Here, we report the biochemical isolation of SEC-like 2 (SEC-L2) and SEC-like 3 (SEC-L3) containing AFF2 and AFF3 in association with P-TEFb, ENL/MLLT1, and AF9/MLLT3. The SEC family members demonstrate high levels of polymerase II (Pol II) C-terminal domain kinase activity; however, only SEC is required for the proper induction of the HSP70 gene upon stress. Genome-wide mRNA-Seq analyses demonstrated that SEC-L2 and SEC-L3 control the expression of different subsets of genes, while AFF4/SEC plays a more dominant role in rapid transcriptional induction in cells. MYC is one of the direct targets of AFF4/SEC, and SEC recruitment to the MYC gene regulates its expression in different cancer cells, including those in acute myeloid or lymphoid leukemia. These findings suggest that AFF4/SEC could be a potential therapeutic target for the treatment of leukemia or other cancers associated with MYC overexpression.

The RNA polymerase II (Pol II) elongation factor (ELL) was the first translocation partner of mixed lineage leukaemia (MLL) for which a biochemical function was determined. It was therefore proposed that the regulation of the elongation stage of transcription could be fundamental to MLL-based leukaemogenesis. Recent studies have identified ELL complexed with several of the translocation partners of MLL in a transcriptional super elongation complex (SEC). These studies provide evidence for the importance of the regulation of Pol II elongation in disease pathogenesis and suggest that MLL chimaeras function by licensing Pol II transcription elongation without the appropriate checkpoints.