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Work-based learning experiences (WBLEs) provide students with opportunities to learn about careers and gain work skills required for post-school employment. WBLEs may be especially important for students with extensive support needs (ESN) who often struggle to access competitive, integrated employment after graduation. The purpose of this study was to understand teachers' beliefs about the benefits of and barriers to school and community WBLEs for students with ESN. We invited 1,498 U.S. special education teachers with a license in ESN to participate. Eligibility criteria required teachers to have at least one high school student with ESN on their caseload. Of the 273 teachers who responded, 137 met criteria and completed the questionnaire. We used descriptive statistics, exploratory factor analyses, and nonparametric inferential statistics to analyze our data. Teachers believed students benefit from WBLEs because they learn skills and have improved outcomes; however, they rated student outcomes higher for community WBLEs (vs. school WBLEs). Barriers to WBLEs included limited resources, stakeholder support, curriculum, and support for students. Teachers rated barriers related to stakeholder support and support for students higher for community WBLEs (vs. school WBLEs). Teachers' beliefs about the benefits of and barriers to WBLEs varied by their experience with WBLEs. Implications for future research about students' experiences during WBLEs and how teachers make decisions about WBLEs are discussed.

To support professional competence development in teacher education, learning environments should allow learners to engage with professional tasks. It is crucial for knowledge and skill transfer in such learning environments to real-life context that preservice teachers perceive the task as authentic. However, due to a lack of prior knowledge, novices may have difficulties in recognizing relevant elements of practice. It is thus assumed that different factors may guide their perception of task authenticity independently of the task that has to be mastered. Such factors could be, for example, overt design features of the learning environments on a physical level or the familiarity with the learning context and learning prerequisites, which act as important links for knowledge acquisition. In this study, preservice teachers' perception of task authenticity is contrasted between two implementation types (video vs. role-play) of the same simulation aiming to foster diagnostic competence. The two types differ in approximating real-life practice concerning the professional task that has to be mastered. In an experimental, longitudinal study, N = 119 mathematics preservice teachers participated online in one type of the simulation four times during one semester (n = 66 video, n = 53 role-play). Perceived task authenticity was higher for the video simulation type and increased with repeated participation in the simulation independently of the implementation type. Further, preservice teachers' task utility value positively influenced their perception of task authenticity. The results illustrate the role of learning prerequisites as well as familiarity with the task for novices' perception. Also, they could be an initial indication that, depending on the level of learners' professional development, the way of approximating real-life practice in simulations might influence the perception of task authenticity.

Paneth cells were first described by Paneth in 1888. (1) They are normally found in the small intestine, right colon, and appendix. They are usually located at the base of [...], * Context.--Changes in Paneth cell numbers can be associated with chronic inflammatory diseases of the gastrointestinal tract. So far, no consensus has been achieved on the number of Paneth cells and their relevance to celiac disease (CD). Objectives.--To compare crypt and Paneth cell granule areas between patients with CD and those without CD (non-CD) using an artificial intelligence-based solution. Design.--Hematoxylin-eosin-stained sections of duodenal biopsies from 349 patients at the McGill University Health Centre were analyzed. Of these, 185 had a history of CD and 164 were controls. Slides were digitized, and NoCodeSeg, a code-free workflow using open-source software (QuPath, DeepMIB), was implemented to train deep learning models to segment crypts and Paneth cell granules. The total area of the entire analyzed tissue, epithelium, crypts, and Paneth cell granules was documented for all slides, and comparisons were performed. Results.--A mean intersection-over-union score of 88.76% and 91.30% was achieved for crypt areas and Paneth cell granule segmentations, respectively. On normalization to total tissue area, the crypt to total tissue area in CD was increased and the Paneth cell granule area to total tissue area decreased when compared to non-CD controls. Conclusions.--Crypt hyperplasia was confirmed in CD compared to non-CD controls. The area of Paneth cell granules, an indirect measure of Paneth cell function, decreased with increasing severity of CD. More importantly, our study analyzed complete hematoxylin-eosin slide sections using an efficient and easy to use coding-free artificial intelligence workflow. doi: 10.5858/arpa.2023-0074-OA)

The purpose of this scoping review was to examine the literature about the participation of students with intellectual disability in community-based work experiences (CBWEs). We analyzed 54 original research articles written in English, conducted in the United States, and published between 1975 and 2020 in peer-reviewed journals. We identified study characteristics (e.g., research design, participants, data sources, and CBWEs) and the focus of each study. Studies focused on five areas: descriptions of student participation in CBWEs, correlates of student participation in CBWEs, relations between student participation in CBWEs and post-CBWEs outcomes, descriptions of transition programs that include CBWEs, and descriptions of stakeholders' perceptions of student participation in CBWEs. Implications for how teachers plan CBWEs and how researchers can address gaps in the literature are discussed.

Cardiac physiologic pacing (CPP), encompassing cardiac resynchronization therapy (CRT) and conduction system pacing (CSP), has emerged as a pacing therapy strategy that may mitigate or prevent the development of heart failure (HF) in patients with ventricular dyssynchrony or pacing-induced cardiomyopathy. This clinical practice guideline is intended to provide guidance on indications for CRT for HF therapy and CPP in patients with pacemaker indications or HF, patient selection, pre-procedure evaluation and preparation, implant procedure management, follow-up evaluation and optimization of CPP response, and use in pediatric populations. Gaps in knowledge, pointing to new directions for future research, are also identified.

Abstract By presenting the most up‐to‐date findings and incorporating the latest evidence, this article seeks to present a comprehensive guide for navigating the complexities inherent in the management of colorectal liver metastasis. It aims to serve as a valuable resource offering clinicians and healthcare professionals an understanding of the diverse modalities and approaches available for treating this challenging and multifaceted disease. In an era of rapidly evolving medical knowledge, this article examines the latest insights to make informed decisions in the realm of colorectal liver metastasis management. The article does not only highlight the up‐to‐date knowledge but also provides the evidence for existing therapeutic strategies. This practical tool provides evidence‐based recommendations to clinicians, thereby contributing to the ongoing advancement of effective treatment strategies for this challenging disease.

During its catalytic cycle, the homodimeric ATPase topoisomerase II alpha (TOP2A) cleaves double stranded DNA and remains covalently bound to 5′ ends via tyrosine phosphodiester bonds. After passing a second, intact duplex through, TOP2A rejoins the break and releases from the DNA. Thereby, TOP2A can relieve strain accumulated during transcription, replication and chromatin remodeling and disentangle sister chromatids for mitosis. Chemotherapy agents such as etoposide are poisons that trap TOP2A mid-cycle, covalently bound to cleaved DNA, leaving behind DNA double strand breaks and activating DNA damage response. While etoposide has been proposed to stabilize the TOP2A-DNA cleavage complex (TOP2Acc) via interfacial inhibition, we have elucidated a complementary mechanism mediated by the ability of etoposide and other TOP2A poisons to induce oxidative stress. Consequently, lipid peroxidation and accumulation of lipid-derived electrophiles such as 4-hydroxynonenal (HNE) results in covalent modification of TOP2A, both blocking ATPase activity and trapping TOP2Acc. HNE modifies multiple sites on human TOP2A in vitro, including alkylating Cys216 in the ATPase domain in a DNA-dependent fashion. Taken together, our data suggest an underappreciated role for TOP2A as a redox sensor in tumor cells, connecting oxidative stress to DNA damage signaling and thereby creating a target for redox-active drugs.

The purpose of this study was to describe the extent to which students with intellectual disability participate in work-based learning experiences and determine whether student characteristics (e.g., gender, race/ethnicity, grade level, and support needs) relate to student participation in these activities. An online questionnaire was emailed to high school special education teachers in four states who had a state-issued teaching license in intellectual disability. A total of 266 teachers completed the questionnaire. Descriptive and inferential statistics were used to answer the research questions. Students participated in a variety of work-based learning experiences, with more students participating in school experiences than community experiences. The majority of work experiences were in one of three career clusters: (a) hospitality and tourism; (b) business, management, and administration; or (c) general work skills. Amount of time spent in work experiences varied greatly, with students spending more time in school experiences than community experiences. Student support needs and grade level were related to participation in community experiences. Grade level was also related to the amount of time students spent in school and community experiences.

Introdução Na área da saúde, a formulação de recomendações com base em um processo adequado de síntese de evidências fornece subsídio científico para a tomada de decisão tanto para pacientes, profissionais de saúde e para gestores. A adoção de processos padronizados para o desenvolvimento de diretrizes clínicas visa garantir o rigor metodológico para garantir a reprodutibilidade e a confiabilidade no conteúdo dos documentos. O objetivo deste estudo foi descrever o programa de tutorias apoiado pelo Ministério da Saúde (MS) no desenvolvimento de diretrizes clínicas por Núcleos de Avaliação de Tecnologias em Saúde (NATS) para o Sistema Único de Saúde (SUS). Métodos O processo de tutorias foi definido em reuniões virtuais e encontros presenciais envolvendo representantes do MS, metodologistas e pesquisadores. A estrutura das tutorias consistiu em tópicos relacionados à Diretriz Metodológica de Desenvolvimento de Diretrizes Clínicas do MS, desenvolvidas a partir das indicações e recomendações do Guidelines International Network/U.S. Institute of Medicine (GIN/ IOM), para o planejamento e desenvolvimento de Protocolos Clínicos e Diretrizes Terapêuticas (PCDTs) por diferentes NATS. Resultados Resultados No triênio 2021-2023, o programa de tutorias incluiu 60 profissionais de 10 NATS para a criação ou atualização de 16 PCDTs nas áreas de psiquiatria (2), neurologia (4), oncologia (3), hematologia (2), nefrologia (1), ortopedia/traumatologia (1), endocrinologia (1), infectologia (1), e gastroenterologia (1). Ao todo, foram elaboradas 93 questões PICO (mediana, 7; intervalo interquartil [IQR], 3 a 8) nos PCDTs, focando principalmente em questões clínicas sobre tratamento (total, 87; mediana, 7; IQR, 3 a 8). A duração da fase de desenvolvimento dos PCDTs teve mediana de 317 dias (IQR, 252 a 402) enquanto que as fases de avaliação da CONITEC e consulta pública duraram uma mediana de 63 dias (IQR, 45 a 94). Nove PCDTs necessitaram de avaliação de tecnologias para incorporação ou ampliação de uso no SUS (total, 14 relatórios de recomendação [RR]; mediana, 1; IQR, 1 a 2) durante a fase de desenvolvimento de evidências, apresentando uma mediana de duração de 238 dias (IQR, 197 a 288). Oito tecnologias apresentaram parecer favorável para ampliação de uso, sendo incorporadas para a linha de cuidado das condições de saúde de interesse. Atualmente, quatro PCDTs estão em desenvolvimento, consistindo em 20 questões PICO para a síntese de evidências, necessitando 10 RR para incorporação de tecnologias no SUS e 8 RR para ampliação de uso de tecnologias. Discussão e conclusões Um programa de tutorias para o desenvolvimento de PCDTs pode melhorar o rigor metodológico, padronização e as recomendações para o diagnóstico e tratamento de condições clínicas na saúde pública. O processo sistemático de tutorias promoveu também a avaliação de tecnologias a partir de necessidades clínicas identificadas a partir do desenvolvimento dos PCDTs com participação de sociedades médicas. Desta forma, o programa de tutorias em PCDTS auxiliou para o estabelecimento de processos padronizados em diretrizes clínicas no âmbito de políticas de saúde pública tornando o processo mais sistemático, transparente e compreensível.

IntroductionTreatment with chimeric antigen receptor T (CAR-T) cells involves a large number of interdisciplinary stakeholders and is associated with complex processes ranging from patient-specific production to follow-up care. Due to the complexity, maximum process optimization is required in order to avoid efficiency losses. This study aimed at systematically determining the preconditions for a frictionless flow of the CAR-T process by surveying the stakeholders involved.MethodsA Group Concept Mapping (GCM) analysis, a mixed-methods participatory research, was conducted. CAR-T experts from different professional backgrounds went through three steps: 1) Brainstorming relevant aspects (statements) for a frictionless process, 2) Sorting the collected statements based on their similarity, and 3) Rating the importance and feasibility of each statement. A cluster map reflecting the overarching topics was derived, and mean ratings per statement and cluster were calculated.ResultsOverall, 20 CAR-T experts participated. A total of 80 statements were collected, resulting in a map of the following 10 clusters (mean importance/feasibility): Information for patients and physicians (4.16/3.77), Supportive network (4.03/3.53), Eligibility of patients (4.41/3.63), Evidence, transparency and communication (4.01/3.33), Paperwork (4.1/2.52), Interface with pharmaceutical manufacturer (4.03/2.85), Reimbursement (4.29/2.31), Quality Management (4.17/3.18), Infrastructure of CAR-T clinics (4.1/2.93), and Patient-oriented processes (4.46/3.32).DiscussionThe 80 statements underlined the complex and manifold nature of the CAR-T treatment process. Our results reflect the first step in overcoming hurdles: identifying potential hurdles and required preconditions. Decision-makers and stakeholders can use the results to derive strategies and measures to further promote a frictionless process.

This study investigated the effect of low-dose aspirin in primary adult liver transplantation (LT) on acute cellular rejection (ACR) as well as arterial patency rates. The use of low-dose aspirin after LT is practiced by many transplant centers to minimize the risk of hepatic artery thrombosis (HAT), although solid recommendations do not exist. However, aspirin also possesses potent anti-inflammatory properties and might mitigate inflammatory processes after LT, such as rejection. Therefore, we hypothesized that the use of aspirin after LT has a protective effect against ACR. This is an international, multicenter cohort study of primary adult deceased donor LT. The study included 17 high-volume LT centers and covered the 3-year period from 2013 to 2015 to allow a minimum 5-year follow-up. In this cohort of 2365 patients, prophylactic antiplatelet therapy with low-dose aspirin was administered in 1436 recipients (61%). The 1-year rejection-free survival rate was 89% in the aspirin group versus 82% in the no-aspirin group (hazard ratio [HR], 0.77; 95% confidence interval [CI], 0.63-0.94; p = 0.01). The 1-year primary arterial patency rates were 99% in the aspirin group and 96% in the no-aspirin group with an HR of 0.23 (95% CI, 0.13-0.40; p

Abstract Proton‐beam therapy (PBT) is a cutting‐edge radiation therapy modality that is currently not available in Australia. Comparative photon‐proton (CPP) planning is required for the medical treatment overseas programme (MTOP) and will be required for access to PBT in Australia in the future. Comparative planning brings professional development benefits to all members of the radiation therapy team. This service was also created to support future proposals for a PBT facility in Victoria. We report our experience developing an in‐house CPP service at Peter MacCallum Cancer Centre. A set of resources to support CPP planning was established. Training of relevant staff was undertaken after which an in‐house training programme was developed. A standard protocol for PBT planning parameters was established. All CPP plans were reviewed. Future goals for the CPP planning programme were described. In total, 62 cases were comparatively planned over 54 months. Of these, 60% were paediatric cases, 14% were adolescents and young adults (15–25 years) and 26% were adults. The vast majority (over 75%) of patients comparatively planned required irradiation to the central nervous system including brain and cranio‐spinal irradiation. A variety of proton plans were reviewed by international PBT experts to confirm their deliverability. Our team at Peter MacCallum Cancer Centre has gained significant experience in CPP planning and will continue to develop this further. Local expertise will help support decentralisation of patient selection for proton treatments in the near future and the PBT business case in Victoria.

Die wertorientierte Gesundheitsversorgung (Value-based Healthcare) gewinnt im Gesundheitswesen an Bedeutung. In diesem Ansatz wird der Patientennutzen als Verhältnis von Behandlungsergebnissen zu Kosten betrachtet, mit dem Ziel, (1) die Qualität der Versorgung zu verbessern, (2) die Kosten zu reduzieren und (3) den Zugang zu innovativen Behandlungen für Patient:innen zu erweitern. Indessen werden bei der näheren Analyse der regulatorischen Bewertungs- und Zugangsprozesse in Deutschland „Bruchstellen“ sichtbar, die einen holistischen Betrachtungsansatz von neuartigen Gesundheitstechnologien für eine wertorientierte Gesundheitsversorgung erschweren. Die aktuellen Herausforderungen werden anhand der chimären Antigenrezeptor-T-Zell- Therapie (CAR-T-Zelltherapie) beleuchtet und mögliche Lösungsansätze und Implikationen für das deutsche Gesundheitssystem abgeleitet.

In public-health crises, members of multilingual communities must be able to access, understand, trust and act upon behaviour-change messaging. The role of translators is therefore critical, not only for the relaying of information but also in the transcreation of texts, understood as adaptation to suit the characteristics of an intended audience. Failure to use transcreation may produce messaging that is culturally inappropriate and thus ineffective. This study analyses healthcare resources created by governments in Australia with a view to identifying formatting and other visual features that would benefit from transcreation. A mixed-method approach combined numerical evaluation of four documents using the Patient Education Materials Assessment Tool (PEMAT) and a bottom-up thematic analysis of the way the same texts were discussed by 58 members of a broad range of ethnocultural and linguistic groups in Victoria, Australia. The findings point to a need to go beyond the linguistic aspects of the translation and take into account the discourse organisation, layout, images and cultural appropriateness of health messaging. The implications of applying the PEMAT criteria are not only that start texts will become more accessible and better able to facilitate understanding-based trust relations, but also that translators are well placed to participate in the transcreations that may be required in the various target languages.