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Commutability is where the measurement response for a reference material (RM) is the same as for an individual patient sample with the same concentration of analyte measured using two or more measurement systems. Assessment of commutability is essential when the RM is used in a calibration hierarchy or to ensure that clinical measurements are comparable across different measurement procedures and at different times. The commutability of three new Standard Reference Materials ® (SRMs) for determining serum total 25-hydroxyvitamin D [25(OH)D], defined as the sum of 25-hydroxyvitamin D 2 [25(OH)D 2 ] and 25-hydroxyvitamin D 3 [25(OH)D 3 ], was assessed through an interlaboratory study. The following SRMs were assessed: (1) SRM 2969 Vitamin D Metabolites in Frozen Human Serum (Total 25-Hydroxyvitamin D Low Level), (2) SRM 2970 Vitamin D Metabolites in Frozen Human Serum (25-Hydroxyvitamin D 2 High Level), and (3) SRM 1949 Frozen Human Prenatal Serum. These SRMs represent three clinically relevant situations including (1) low levels of total 25(OH)D, (2) high level of 25(OH)D 2 , and (3) 25(OH)D levels in nonpregnant women and women during each of the three trimesters of pregnancy with changing concentrations of vitamin D-binding protein (VDBP). Twelve laboratories using 17 different ligand binding assays and eight laboratories using nine commercial and custom liquid chromatography-tandem mass spectrometry (LC-MS/MS) assays provided results in this study. Commutability of the SRMs with patient samples was assessed using the Clinical and Laboratory Standards Institute (CLSI) approach based on 95% prediction intervals or a pre-set commutability criterion and the recently introduced International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) approach based on differences in bias for the clinical and reference material samples using a commutability criterion of 8.8%. All three SRMs were deemed as commutable with all LC-MS/MS assays using both CLSI and IFCC approaches. SRM 2969 and SRM 2970 were deemed noncommutable for three and seven different ligand binding assays, respectively, when using the IFCC approach. Except for two assays, one or more of the three pregnancy levels of SRM 1949 were deemed noncommutable or inconclusive using different ligand binding assays and the commutability criterion of 8.8%. Overall, a noncommutable assessment for ligand binding assays is determined for these SRMs primarily due to a lack of assay selectivity related to 25(OH)D 2 or an increasing VDBP in pregnancy trimester materials rather than the quality of the SRMs. With results from 17 different ligand binding and nine LC-MS/MS assays, this study provides valuable knowledge for clinical laboratories to inform SRM selection when assessing 25(OH)D status in patient populations, particularly in subpopulations with low levels of 25(OH)D, high levels of 25(OH)D 2 , women only, or women who are pregnant., Competing Interests: Declarations. Human subjects ethics: The National Institute of Standards and Technology Research Protections Office reviewed the protocol for this project and determined it is “not human subjects research” as defined in 15 CFR 27, the Common Rule for the Protection of Human Subjects. The laboratory study participants agreed to the publication of their measurements data, laboratory identification, and measurement assay platform identification. Conflict of interest: S.A. Wise is an Editor of the journal Analytical and Bioanalytical Chemistry and was not involved in peer reviewing this manuscript. Some coauthors are employees of companies that produced the assays evaluated in this study. There are no financial or non-financial conflicts of interest for any of the coauthors. Disclaimer: The opinions expressed in this article are the authors’ own and do not reflect the view of the National Institutes of Health, the Department of Health and Human Services, or the United States government. Any citations of commercial organizations and trade names in this report do not constitute an official NIH, NIST, or CDC endorsement of approval of the products or services of these organizations., (© 2025. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Introduction: This scoping review investigates the extent and nature of existing evidence on the role of non-governmental organizations (NGOs) and related mechanisms of engagement and challenges in issues of caring for older persons through digital technologies. We map research and practice gaps, contributing factors and best practices in NGOs. The rising use of digital technology in health care and the role that NGOs have in supporting older people in this context is relevant to nurses and service development leaders, particularly in the context of a rapidly changing care in the 21 st century., Methods: A three-stage systematic and comprehensive search strategy based on the JBI methodology for scoping reviews was employed across multiple databases and grey literature sources., Results: In this review, 8,348 abstracts were retrieved. After deduplication, 7,099 titles and abstracts were reviewed. A total of 263 publications were selected for full-text review and 50 included for analysis. NGOs use digital tools to directly engage older adults in programs (e. g., information delivery) and indirectly to collaborate with other organizations (e.g., training programs) to promote digital inclusion. Factors such as individual capabilities, trust and access, technological factors (accessibility and user-friendliness of technology), and socio-cultural and system-wide factors affect how NGOs engage with older adults., Conclusion: Our findings are summarized in the key domains: key organizations, mode of engagement, interorganizational process and digital technology are discussed and offer current insights into the varied engagement of NGOs with older people and its challenges concerning technology. Many interrelated factors, along with barriers and facilitators that influence older persons' engagement with technology, have been identified., (Copyright © 2024. Published by Elsevier GmbH.)

Background and Aim: Communication is a key factor in intraprofessional collaboration between hospital nurses and homecare nurses in hospital-to-home transitions of older patients with complex care needs. Gaining knowledge of the nature of cross-sectoral communication is crucial for understanding how nurses collaborate to ensure a seamless patient trajectory. This study explores how cross-sectoral electronic health records communication influences collaboration between hospital nurses and homecare nurses when discharging older patients with complex care needs., Method: The study is based on qualitative group interviews with six hospital nurses and 14 homecare nurses working at different hospitals and municipalities across Denmark. Data were analysed using reflexive thematic analysis, as described by Braun and Clark., Findings: The themes Collecting pieces for the 'puzzle': Losing the holistic picture of the patient; Working blindfolded: limited provision of and access to critical information; and Bypassing the 'invisible wall': dialogue supports cohesion illustrate the impact of organisational structures within electronic health records have on hospital nurses' and homecare nurses' intraprofessional collaboration across sectors. Challenges with predefined and word-limited elements in digital communication, and inadequate and limited access to significant medical information were identified. To compensate for the inadequacy of the electronic health records, direct contact and dialogue were emphasised as ways of fostering successful collaboration and overcoming the barriers created by electronic health records., Conclusion: Despite hospital nurses' and homecare nurses' desire to conduct holistic patient assessments, their ability to collaborate was hindered by failures in electronic health record communication resulting from restrictive organisational structures across sectors. Thus, it became necessary for hospital nurses and homecare nurses to bypass the electronic health record system and engage in dialogue to provide holistic care when discharging older patients with complex care needs. However, by hospital nurses and homecare nurses compensating for counter-productive organisational structures, problems brought about by the electronic health record system paradoxically remain invisible., (© 2024 The Author(s). Scandinavian Journal of Caring Sciences published by John Wiley & Sons Ltd on behalf of Nordic College of Caring Science.)

Background: By enabling individuals with hearing loss to collect their own hearing data in their personal real-world settings, there is scope to improve clinical care, empower consumers, and support shared clinical decision-making and problem-solving. Clinician support for this approach has been established in a separate study., Objective: This study aims to explore, for consumers with hearing loss, their (1) experiences of listening difficulties, to identify the data an app could usefully collect; (2) preferences regarding the features of mobile apps in general; and (3) opinions on the potential value and desirable features of a yet-to-be designed app for documenting listening difficulties in real-world settings., Methods: A total of 3 focus groups involved 27 adults who self-reported hearing loss. Most were fitted with hearing devices. A facilitator used a topic guide to generate discussion, which was video- and audio-recorded. Verbatim transcriptions were analyzed using inductive content analysis., Results: Consumers supported the concept of a mobile app that would facilitate the documenting of listening difficulties in real-world settings important to the individual. Consumers shared valuable insights about their listening difficulties, which will help determine the data that should be collected through an app designed to document these challenges. This information included early indicators of hearing loss (eg, mishearing, difficulty communicating in groups and on the phone, and speaking overly loudly) and prompts to seek hearing devices (eg, spousal pressure and the advice or example provided by others, and needing to rely on lipreading or to constantly request others to repeat themselves). It also included the well-known factors that influence listening difficulties (eg, reverberation, background noise, group conversations) and the impacts and consequences of their difficulties (eg, negative impacts on relationships and employment, social isolation and withdrawal, and negative emotions). Consumers desired a visual-based app that provided options for how data could be collected and how the user could enter data into an app, and which enabled data sharing with a clinician., Conclusions: These findings provide directions for the future co-design and piloting of a prototype mobile app to provide data that are useful for increasing self-awareness of listening difficulties and can be shared with a clinician., (©Karyn Galvin, Dani Tomlin, Barbra H B Timmer, Zoe McNeice, Nicole Mount, Kathleen Gray, Camille E Short. Originally published in JMIR Formative Research (https://formative.jmir.org), 23.07.2024.)

Background: Collaboration is a key factor influencing the quality and safety in patients transition between sectors. However, specific collaborative practices may give rise to conflict between hospital nurses and community nurses., Aims: To gain a deeper understanding of collaborative practices which have the potential to fuel tension in collaboration between hospital nurses and community nurses during discharge of older patients from hospital to homecare., Methods: A meta-ethnography approach was used in this study and a systematic literature search was conducted in 2022., Results: Five themes were identified in the analysis. These themes revealed how uncertainty, limited confidence in information and personal attitude in communication may fuel tension between hospital nurses and community nurses. Tensions arising from a negative loop emerged because of uncertainty, causing a growing rift between hospital nurses and community nurses, leaving them as opponents rather than collaborators. The authors suggest that policy makers and managers can break this loop by underpinning shared policies and awareness of common objectives.

Background: The Hill classification characterizes the geometry of gastroesophageal junction and Hill grades (HGs) III and IV have a high association with pathologic reflux. This study aimed to understand the use of the Hill classification and correlate the prevalence of pathologic reflux across different HGs., Study Design: A retrospective review of 477 patients who underwent upper endoscopy and BRAVO pH monitoring between August 2018 and October 2021 was performed. These charts were reviewed for endoscopic findings for hiatal hernia and association of HGs with pathologic reflux, defined as an abnormal esophageal acid exposure time (AET) of ≥4.9%., Results: Of 477 patients, 252 (52.8%) had an HG documented on the endoscopy report. Of the 252 patients, 61 had HG I (24.2%), 100 had HG II (39.7%), 61 had HG III (24.2%), and 30 had HG IV (11.9%). The proportion of patients with abnormal AET increases with increasing HGs (p < 0.001) as follows: I (39.3%), II (52.5%), III (67.2%), and IV (79.3%). The mean overall AET is as follows: HG I (5.5 ± 6%), HG II (7.0 ± 5.9%), HG III (10.2 ± 10.3%), and HG IV (9.5 ± 5.5%). The proportion of patients with hiatal hernia was 18% for HG I, 28% for HG II, 39.3% for HG III, and 80% for HG IV., Conclusions: Use of the Hill classification in clinical practice is low. There is an association of increasing HGs with increasing proportion of patients with abnormal AET. There is a high proportion of patients within HGs I and II with documented pathologic reflux and the presence of a hiatal hernia as observed on endoscopic examination. Our study suggests that endoscopic grading of the gastroesophageal junction may not adequately differentiate between normal vs abnormal reflux status, particularly for HGs I and II., (Copyright © 2024 by the American College of Surgeons. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Medical schools seeking to correct and reform curricula towards anti-racist perspectives need to address anti-Black forms of racism specifically and teach students critical upstander skills to interrupt manifestations of racism. We developed a course to teach preclinical medical students basic anti-racism competencies including recognition and awareness of anti-Black racism in medicine and upstander skills to advocate for patients and colleagues., Methods: In 2021 and 2022, we designed, implemented, and evaluated an elective course for second-year medical students ( N = 149) to introduce competencies of anti-racism focusing on upstander skills for addressing anti-Blackness. We designed three patient cases and one student-centered case to illustrate manifestations of anti-Black racism in medicine and used these cases to stimulate small-group discussions and guide students toward recognizing and understanding ways of responding to racism. We designed pre- and postassessments to evaluate the effectiveness of the course and utilized anonymous feedback surveys., Results: Participants showed significant improvement in pre- to postassessment scores in both years of the course. The anonymous feedback survey showed that 97% of students rated the course at least somewhat effective, and the qualitative responses revealed five core themes: course timing, case complexity, learner differentiation, direct instruction, and access to resources., Discussion: This course reinforces upstander competencies necessary for advancing anti-racism in medicine. It addresses a gap in medical education by reckoning with the entrenched nature of anti-Black racism in the culture of medicine and seeks to empower undergraduate medical students to advocate for Black-identifying patients and colleagues., (© 2024 Williams et al.)

Objectives: Some adults experience challenges in successfully communicating their listening difficulties to their audiologist, and report feeling that they are not always listened to or understood. This project examined adults' recollections of discussions with their audiologist to explore (1) how adults report describing their listening difficulties and (2) information that adults report they do not communicate, or do not communicate successfully, to their audiologist., Design: Individual semi-structured interviews were conducted. Interview transcripts were analysed using a template analysis approach., Study Sample: Fifteen adults who self-report listening difficulties, and who had previously consulted an audiologist., Results: Four themes were identified from adults' recollections of how they describe their listening difficulties: (1) situation or context of listening difficulties, (2) behavioural responses, (3) impacts of listening difficulties and (4) contributing factors. Adults report not always successfully communicating (1) emotional concerns and impacts, (2) descriptions of sound quality and (3) descriptions of changed listening experiences., Conclusion: Results provide insights about the times when adults feel that communication with their audiologist is successful, or unsuccessful. The results are useful for informing interventions to help adults and audiologists communicate more effectively together. To further inform interventions, factors affecting adults' communication should be explored.

Objective : It is unknown how adults communicate about their experienced listening difficulties with their audiologist. This scoping review aims to explore how adults self-describe the listening difficulties that they experience, and how they communicate about them. Design : A scoping review was conducted between December 2020 and September 2022 to identify published journal articles in which adults described and communicated about their listening difficulties. Study sample : Database searches yielded 10,224 articles initially. After abstract screening and full text review, 55 articles were included for analysis. Results : The listening difficulties that adults described were varied, highlighting the fact that each person has individual experiences. Adults discussed reasons for their listening difficulties, impacts of their listening difficulties, and behavioural responses they adopted to cope with their listening difficulties. Conclusions : This review shows the broad impacts of listening difficulties, and the varied ways in which adults discuss their listening difficulties. There is no available literature reporting how adults communicate about their listening difficulties in a clinical context.

Objective: To examine willingness to consider and to pay for various one-to-one telehealth appointments and online group training/information sessions amongst hearing service clients interested in future telehealth., Design: Online survey exploring telehealth usage and attitudes more broadly., Study Sample: One-hundred-and-sixty-eight (39.8%) of the 422 survey respondents who answered the question were interested in future hearing-related telehealth. Data were analysed for the 148 providing demographic information., Results: At least some respondents were interested in each type of one-to-one appointment (∼30-60% for most types) and group training/information session (∼30-50% for most types). Some inconsistent associations were found between willingness to consider individual appointment types and a metropolitan location, younger age, and female gender. Associations with having a hearing device fitted may have been influenced by the different needs of those without devices. Younger respondents were more likely to consider a wide range of appointment types. Being younger was associated with an interest in 7 of the 9 different group session types. The acceptable price range was AUD$30-$86 (USD$22-$62) ( n  = 129) for one-to-one appointments and AUD$47-$103 (USD$34-$73) for three group sessions ( n  = 99)., Conclusions: Despite additional communication needs, hearing service clients have a strong interest in a range of individual and group telehealth services.

In North America, Hispanic migrant farmworkers are being exposed to occupational ergonomic risks. Due to cultural differences in the perception and reporting of effort and pain, it was unknown whether standardized subjective ergonomic assessment tools could accurately estimate the directly measured their physical effort. This study investigated whether the subjective scales widely used in exercise physiology were associated with the direct measures of metabolic load and muscle fatigue in this population. Twenty-four migrant apple harvesters participated in this study. The Borg RPE in Spanish and the Omni RPE with pictures of tree-fruit harvesters were used for assessing overall effort at four time points during a full-day 8-h work shift. The Borg CR10 was used for assessing local discomfort at the shoulders. To determine whether there were associations between the subjective and direct measures of overall exertion measures, we conducted linear regressions of the percentage of heart rate reserve (% HRR) on the Borg RPE and Omni RPE. In terms of local discomfort, the median power frequency (MPF) of trapezius electromyography (EMG) was used for representing muscle fatigue. Then full-day measurements of muscle fatigue were regressed on the Borg CR10 changes from the beginning to the end of the work shift. The Omni RPE were found to be correlated with the % HRR. In addition, the Borg RPE were correlated to the % HRR after the break but not after the work. These scales might be useful for certain situations. In terms of local discomfort, the Borg CR10 were not correlated with the MPF of EMG and, therefore, could not replace direct measurement.

Background: Digital technologies facilitate everyday life, social connectedness, aging at home, well-being, and dignified care. However, older adults are disproportionately excluded from these benefits. Equal digital opportunities, access, and meaningful engagement require an understanding of older adults' experience across different stages of the technological engagement life cycle from nonuse and initial adoption to sustained use, factors influencing their decisions, and how the experience changes over time., Objective: Our objectives were to identify the extent and breadth of existing literature on older adults' perspective on digital engagement and summarize the barriers to and facilitators for technological nonuse, initial adoption, and sustained digital technology engagement., Methods: We used the Arksey and O'Malley framework for the scoping review process. We searched MEDLINE, PsycINFO, CINAHL, Web of Science, and ACM digital library for primary studies published between 2005 and 2021. The inclusion and exclusion criteria were developed based on the Joanna Briggs Institute (participants, content, and context) framework. Studies that investigated the digital engagement experience as well as barriers to and facilitators of older adults' digital technology engagement were included. The characteristics of the study, types of digital technology, and digital engagement levels were analyzed descriptively. Content analysis was used to generate tentative elements using a congruent theme, and barriers and facilitators were mapped over the capability, opportunity, and motivation behavior change model (COM-B) and the theoretical domain framework. The findings were reported in accordance with the PRISMA-ScR (Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews)., Results: In total, 96 publications were eligible for the final charting and synthesis. Most of the studies were published over the past 5 years, investigated the initial adoption stage of digital engagement, and focused on everyday technologies. The most cited barriers and facilitators across the engagement stages from each COM-B component were capability (eg, physical and psychological changes and lack of skill), opportunity (eg, technological features, environmental context, and resources), and motivation (eg, optimism from perceived usefulness and beliefs about capability)., Conclusions: The COM-B model and theoretical domain framework provide a guide for identifying multiple and intertwined barriers and facilitators at each stage of digital engagement. There are limited studies looking into the whole spectrum of older adults' digital technology experience; in particular, studies on technological nonuse and sustained use stages are rare. Future research and practice should focus on tailored interventions accounting for the barriers to older adults' digital engagement and addressing capabilities, motivation, and opportunities; affordable, usable, and useful digital technologies, which address the changes and capability requirements of older adults and are cocreated with a value framework; and lifelong learning and empowerment to develop older adults' knowledge and skills to cope with digital technology development., International Registered Report Identifier (irrid): RR2-10.2196/25616., (©Abraham Sahilemichael Kebede, Lise-Lotte Ozolins, Hanna Holst, Kathleen Galvin. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 07.12.2022.)

Background: The need for dignity and compassion in healthcare is enshrined in policy, but is often difficult to enact in practice and what is precisely meant by these concepts is unclear. In this paper, we have explored theoretical underpinnings which form the basis of a lifeworld-led approach which was used in a research study to support the humanity of service providers and users alike., Aim: In this article, we share our analysis of what we have learnt after undertaking an innovative appreciative action research project with patients and staff in a stroke ward with the aim of exploring if a novel phenomenologically driven and philosophically derived humanising framework could be applied in health care. Following the research, we wanted to develop a theoretical understanding of the processes occurring during the research in order to provide a framework and language which could be used to support practical lifeworld developments in the future. We analysed the approach through Participatory and Appreciative Action Reflection., Findings: As researchers, we found that the approach was underpinned by four key existential principles. The first principle was recognising a mutually arising reality rather than a reality 'out there'. The second was recognising a reality which was constantly changing rather than 'fixed'. The third was recognising that we needed to work from within, as part of a human living system rather than trying to control reality from the 'outside'. Finally, we recognised that this reality could only be accessed through human knowing, including embodied knowing rather than intellectual knowing alone. These principles challenged many of the usual ways of thinking and working within research and healthcare contexts., Conclusion: Understanding the processes and reality in this way gave new perspectives; enhancing our understandings and views of ourselves, what is important and most importantly what is possible in caring systems., (© 2021 The Authors. Scandinavian Journal of Caring Sciences published by John Wiley & Sons Ltd on behalf of Nordic College of Caring Science.)

Background: The experience of physical activity is influenced by social relations and gendered roles. Group-based lifestyle interventions are considered effective in promoting physical activity, yet the experiences of being active with others are unknown among individuals with severe obesity., Purpose: To explore how individuals with severe obesity experience being with others during physical activity., Methods: A qualitative hermeneutic phenomenological study of repeated single-gender focus group interviews was conducted with adults living with severe obesity during group-based lifestyle intervention., Results: Three themes were developed: 1) 'Enjoying safety, kinship and belonging among peers'; 2) 'Feeling like a failure is shameful: A sense of aversion'; and 3) 'Striving to feel at home in physical activity: Needing distance from others.' The themes were drawn into an overall meaning 'Achieving wellbeing may always be a challenge: not feeling at home in the group or in body.', Conclusion: Intersubjective and spatial dimensions of experiences are central and influence how individuals with severe obesity can feel wellbeing and 'at home' in physical activity. Physiotherapists should be aware of the individuals' vulnerability regarding feelings of failure, aversion, and shame as well as awareness of gendered norms and roles.

Background: Children living in out-of-home care (OOHC) have significant unmet health care needs and use more tertiary and specialist health care services compared with children from similar social and economic backgrounds. Allied health professionals and nurses have a central role in health care; however, very little is known about the engagement of children in OOHC with nursing and allied health professionals. This scoping review addresses this knowledge gap., Methods: A scoping review methodology framework was used to search for relevant articles published between January 1970 and November 2019, identified using three databases: MEDLINE, CINAHL and ProQuest. Selection of studies was based on empirical research about the health of children in OOHC and their engagement with nursing or allied health services. A total of 37 relevant articles met the eligibility criteria for inclusion in this review., Results: Findings could be summarized under five broad themes: (1) nursing and allied health professionals engaging with children in OOHC to support their health and development, (2) opportunities and challenges for nursing and allied health professionals to engage children in OOHC in healthcare, (3) identification and complexity of healthcare needs, (4) access to healthcare services and (5) coordination of healthcare., Conclusions: Children in OOHC have multiple healthcare needs that require monitoring and treatment by allied health professionals and the health and development of these children is best supported through comprehensive health screening on entry into OOHC, and community-based, multidisciplinary healthcare while children are living in OOHC. While nurses in hospitals and community settings were found to play a role in health assessment and care coordination targeted at children in OOHC, the literature was silent on the role of allied health professionals in this healthcare approach., (© 2021 John Wiley & Sons Ltd.)

SUMOylation, the covalent conjugation of small ubiquitin-like modifier (SUMO) proteins to protein substrates, has been reported to suppress type I interferon (IFN1) responses. TAK-981, a selective small-molecule inhibitor of SUMOylation, pharmacologically reactivates IFN1 signaling and immune responses against cancers. In vivo treatment of wild-type mice with TAK-981 up-regulated IFN1 gene expression in blood cells and splenocytes. Ex vivo treatment of mouse and human dendritic cells promoted their IFN1-dependent activation, and vaccination studies in mice demonstrated stimulation of antigen cross-presentation and T cell priming in vivo. TAK-981 also directly stimulated T cell activation, driving enhanced T cell sensitivity and response to antigen ex vivo. Consistent with these observations, TAK-981 inhibited growth of syngeneic A20 and MC38 tumors in mice, dependent upon IFN1 signaling and CD8 + T cells, and associated with increased intratumoral T and natural killer cell number and activation. Combination of TAK-981 with anti-PD1 or anti-CTLA4 antibodies improved the survival of mice bearing syngeneic CT26 and MC38 tumors. In conclusion, TAK-981 is a first-in-class SUMOylation inhibitor that promotes antitumor immune responses through activation of IFN1 signaling. TAK-981 is currently being studied in phase 1 clinical trials (NCT03648372, NCT04074330, NCT04776018, and NCT04381650) for the treatment of patients with solid tumors and lymphomas.

Background: There is an ongoing negative narrative about aging that portrays older people as a socioeconomic burden on society. However, increased longevity and good health will allow older adults to contribute meaningfully to society and maximize their well-being. As such, a paradigm shift toward healthy and successful aging can be potentially facilitated by the growing digital technology use for mainstream (day-to-day activities) and assisted living (health and social care). Despite the rising digital engagement trend, digital inequality between the age groups persists., Objective: The aims of this scoping review are to identify the extent and breadth of existing literature of older people's perspectives on digital engagement and summarize the barriers and facilitators for technological nonuse, initial adoption, and sustained digital technology engagement., Methods: This review will be based on the Arksey and O'Malley framework for scoping reviews. The 6-stage framework includes: identifying research questions, identifying relevant studies, study selection, charting the data, summarizing and reporting the results, and a consultation exercise. Published literature will be searched on primary electronic databases such as the Association of Computing Machinery, Web of Science, MEDLINE, PsycINFO, CINAHL, and ScienceDirect. Common grey literature sources will complement the database search on the topic. A two-stage (title/abstract and full article) screening will be conducted to obtain eligible studies for final inclusion. A standardized data extraction tool will be used to extract variables such as the profile of the study population, technologies under investigation, stage of digital engagement, and the barriers and facilitators. Identified and eligible studies will be analyzed using a quantitative (ie, frequency analysis) and qualitative (ie, content analysis) approach suitable for comparing and evaluating literature to provide an evaluation of the current state of the older person's digital engagement. Inclusion will be based on the Joanna Briggs Institute-recommended participant, concept, and context framework. Articles on older people (65 years and older), on digital technology engagement, and from a global context will be included in our review., Results: The results of this review are expected in July 2021., Conclusions: The findings from this review will identify the extent and nature of empirical evidence on how older people digitally engage and the associated barriers and facilitators., International Registered Report Identifier (irrid): PRR1-10.2196/25616., (©Abraham Sahilemichael Kebede, Lise-Lotte Ozolins, Hanna Holst, Kathleen Galvin. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 05.07.2021.)

This study compared the observed and the self-reported engagement of 16 students who are Deaf or hard-of-hearing (DHH) attending mainstream schools to that of matched controls with typical hearing. Observed engagement was measured through observations in the classroom setting using the Mainstream Version of the Code for Instructional Structure and Student Academic Reponses. Self-reported engagement was measured using the Classroom Participation Questionnaire. The results revealed no significant differences for either observed or self-reported engagement between the DHH and the control groups; however, three individual DHH participants had lower levels of observed engagement compared to their matched controls. As such, including engagement in the evaluation of students who are DHH may be important for some individuals to provide a better understanding of the daily challenges they experience at school. Where needs are identified, the support that students who are DHH receive should include a specific focus on engagement to assist with their successful inclusion., (© The Author(s) 2021. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Much of the UK's ageing population lives in care homes, often with complex care needs including dementia. Optimal care requires strong clinical leadership, but opportunities for staff development in these settings are limited. Training using simulation can enable experiential learning in situ. In two nursing homes, Health Care Assistants (HCAs) received training in clinical communication skills (Situation-Background-Assessment-Recommendation Education through Technology and Simulation, SETS: group training with an actor simulating scenarios); and dementia (A Walk Through Dementia, AWTD: digital simulation, delivered one-to-one). In this qualitative descriptive study, we evaluated the potential of this training to enhance HCAs' clinical leadership skills, through thematic analysis of 24 semi-structured interviews with HCAs (before/after training) and their managers and mentors. Themes were checked by both interviewers. HCAs benefitted from watching colleagues respond to SETS scenarios and reported greater confidence in communicating with registered healthcare professionals. Some found role-play participation challenging. AWTD sensitised HCAs to the experiences of residents with dementia, and those with limited dementia experience gained a fuller understanding of the disease's effects. Staffing constraints affected participation in group training. Training using simulation is valuable in this setting, particularly when delivered flexibly. Further work is needed to explore its potential on a larger scale.

SUMOylation is a reversible post-translational modification that regulates protein function through covalent attachment of small ubiquitin-like modifier (SUMO) proteins. The process of SUMOylating proteins involves an enzymatic cascade, the first step of which entails the activation of a SUMO protein through an ATP-dependent process catalyzed by SUMO-activating enzyme (SAE). Here, we describe the identification of TAK-981, a mechanism-based inhibitor of SAE which forms a SUMO-TAK-981 adduct as the inhibitory species within the enzyme catalytic site. Optimization of selectivity against related enzymes as well as enhancement of mean residence time of the adduct were critical to the identification of compounds with potent cellular pathway inhibition and ultimately a prolonged pharmacodynamic effect and efficacy in preclinical tumor models, culminating in the identification of the clinical molecule TAK-981.

Objectives: The goal of this project was to determine if a mobile application displaying pesticide label information in Spanish and English was a viable approach to addressing safety and health disparities for orchard workers. This study assessed pesticide label use patterns in orchards; application user experience; and the potential of modern information systems to deliver bilingual content. Methods: Pesticide handlers and orchard managers were asked to use a mobile application prototype for a period of one month in 2016. A convenience sample of ten participants completed a 36-question interview to share their experiences. The research team summarized interview responses with summary statistics and grouped content analysis. Results: Mean participant (n=10) age was 49. Eight were Latinx and spoke Spanish as their primary language. Six used the app frequently (15 times), one used it sometimes (6 - 10 times), and three used it rarely or occasionally (1 - 5 times). All participants viewed sections about product information and personal protective equipment. Most viewed information related to emergency and first aid, hazards, and storage and disposal. Overall user experience was positive, with an emphasis on the importance of access to label information in Spanish. Conclusion: The overwhelming majority of the Pacific Northwest agricultural workforce is Spanish-speaking, despite critical pesticide safety information being provided on lengthy product label documents in technical English. This project demonstrated that the mobile application seems to be a viable approach to reducing language disparities and improving Latinx orchard worker safety.

Background: Trauma patients with burn injuries have higher morbidity and mortality rates compared with patients who solely experience burn or trauma injuries. There is a paucity of data regarding burn-trauma (BT) patient outcomes at level I (LI) trauma centers compared with level II (LII) centers. We hypothesized that BT patients at LI trauma centers have lower mortality rates than those at LII trauma centers., Methods: The Trauma Quality Improvement Program (2010-2016) was queried for patients aged ≥18 y who had BT injuries. Patients treated at an LI were compared with those at an LII center with a primary outcome of in-hospital mortality. Secondary outcomes included hospital length of stay (LOS) and intensive care unit (ICU) LOS. A multivariable logistic regression analysis was used to identify factors associated with all-cause mortality., Results: From 1971 BT patients, 1540 (78%) were treated at an LI trauma center, and 431 (22%) at an LII center. Compared with LII centers, LI BT patients had a longer median LOS (10 versus 7 d; P < 0.001) and ICU LOS (5 versus 4 d; P < 0.001). Both LI and LII centers had similar mortality rates (8.5% versus 7.0%; P = 0.300). On multivariable analysis, receiving care at an LI trauma center was not associated with decreased mortality (odds ratio 0.79, 95% confidence interval 0.42-1.48; P = 0.456)., Conclusions: We report that LI trauma center BT patients had an increased hospital and ICU LOS compared with those at LII centers. However, there was no significant difference in mortality between patients cared for at LI and LII trauma centers in risk-adjusted models., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background : In-depth understanding of the experiences of both well-being and suffering in relation to being severely obese and becoming active through lifestyle intervention is lacking. Aim : to explore and describe adults' existential experiences of being active, when living within a large body-before and during a lifestyle intervention. Methods: A longitudinal design of repeated indivi dual interviews with 16 adults with BMI ≥40, based on hermeneutic phenomenology, existential philosophy and a theory of well-being was performed. The study was approved by the Danish health authorities. Results : Two dimensions of experiences were found; "Living within a downward spiral" and "Striving for enjoyment and settlement". The themes describing suffering were: 'Sense of being thwarted and defeated ' and "Tackling energy depletion and impact of sense of self". The themes describing well-being were: "Hoping for renewal and energised resoluteness" and "Enduring discomfort and feeling safe". Conclusions : Interacting existential experiences can be facilitators or barriers for physical activity. It seems relevant for health care providers to address the individual's lifeworld experiences of well-being, lack of well-being and suffering. Well-being as a sense of feeling "at home" when physically active may break down an inactivity spiral. Promoting well-being is a legitimate aim of lifestyle intervention.

Farmworkers are exposed to physical risk factors including repetitive motions. Existing ergonomic assessment methods are primarily laboratory-based and, thus, inappropriate for use in the field. This study presents an approach to characterize the repetitive motions of the upper arms based on direct measurement using accelerometers. Repetition rates were derived from upper arm inclination data and with video recordings in the field. This method was used to investigate whether harvesting with mobile platforms (teams harvesting apples from the platform and the ground) increased the farmworkers' exposure to upper arm repetitive motions compared to traditional harvesting using ladders. The ladder workers had higher repetitive motions (13.7 cycles per minute) compared to the platform and ground workers (11.7 and 12.2 cycles per minutes). The higher repetitions in the ladder workers were likely due to their ability to work independently and the additional arm movements associated with ladder climbing and walking., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

This study compared farmworkers' exposure to non-neutral postures using a new mobile platform apple harvesting method and the traditional method using ladders. Twenty-four workers were recruited and assigned into three groups: ladder workers (n = 8) picking apples from full trees using a ladder, mobile platform workers (n = 8) picking apples from upper part of the trees while standing on a moving platform, and ground-based mobile platform workers (n = 8) picking apples from lower part of the trees which the mobile platform workers left out. Upper arm and back inclinations were continuously monitored during harvesting using tri-axial accelerometers over full work shifts (~8 h). Upper arm posture was characterized as the percentage of time that upper arm flexion and abduction exceeded 30°, 60°, and 90°. Back posture was characterized as the percentage of time that torso angles (sagittal flexion or lateral bending) exceeded 10°, 20°, and 30°. The 10th, 50th, and 90th postural percentiles were also calculated. The platform workers had lower exposures to upper arm flexion and abduction than the ground and ladder workers. There were no differences in torso angles between the ladder and mobile platform workers; however, the ground workers were exposed to more and greater percentages of time in torso flexions., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Context: People with acute-on-chronic breathlessness due to cardiorespiratory conditions frequently present to the emergency department (ED) causing burden for the person concerned, their care takers, and emergency services., Objective: To understand the reasons for ED presentation for acute-on-chronic breathlessness and how optimal care might avoid presentations., Methods: Qualitative in-depth linked interviews were conducted as part of a mixed-methods study. Transcripts of audio-recordings were subjected to thematic analysis. Consenting patients presenting to a single tertiary hospital ED with acute-on-chronic breathlessness able to be interviewed were eligible. Patient-participants (n = 18) were purposively sampled for maximum variation. Patient-participant-nominated carers (n = 9) and clinicians (n = 8) were recruited., Results: Theme 1: "The context for the decision to present to the ED" is the experience of acute-on-chronic breathlessness, in which a person faces an existential crisis not knowing where the next breath is coming from, and previous help-seeking experiences. Theme 2 ("Reasons for presentation"): Some were reluctant to seek help until crisis when family carers were often involved in the decision to present. Others had previous poor experiences of help-seeking for breathlessness in the community and turned to the ED by default. Some had supportive primary clinicians and presented to the ED either on their clinician's recommendation or because their clinician was unavailable., Conclusions: The decision to present to the ED is made in the context of serious crisis and previous experiences. Discussion of the reason for presentation may enable better management of chronic breathlessness and reduce the need for future emergency presentation., (Copyright © 2020 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Objectives: 'Dementia Friends' is a programme used to raise awareness of dementia, developed by the Alzheimer's Society, which has been delivered across the UK to diverse populations, including adolescents. However, there is little evidence available with regards to adolescents' perceptions of the programme and its impact. This study aims to explore this in a group of adolescents from the south of England., Study Design: Focus group discussions., Methods: Thirty adolescents aged between 11 and 16 years were recruited from two schools in East Sussex, England. All had participated in a Dementia Friends session in the past month. Focus group discussions were transcribed, coded and themes were created using inductive thematic analysis., Results: Four themes were identified: (1) perceptions and experiences of dementia, (2) outcomes and learning from Dementia Friends session, (3) reactions to the Dementia Friends session and (4) identified future learning needs., Conclusions: Adolescents had generally positive opinions about Dementia Friends, particularly the interactive nature of the session. Whilst they felt participating in Dementia Friends improved their attitudes and knowledge, they were often left wanting to learn more. Future research needs to empirically evaluate the extent to which Dementia Friends may improve attitudes and knowledge of dementia., (Copyright © 2020 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Background: Red meat and meat products can contribute meaningfully to the mean daily intake of vitamin D. Beef and lamb can contain vitamin D 3 and 25-hydroxyvitamin D 3 [25(OH)D 3 ] but also potentially vitamin D 2 and 25-hydroxyvitamin D 2 [25(OH)D 2 ], all of which contribute to meat's vitamin D activity., Objectives: We aimed to measure the vitamin D 3 , vitamin D 2 , 25(OH)D 3 , and 25(OH)D 2 content of Irish beef and lamb., Methods: Full striploin steaks (longissimus dorsi) ( n  = 39) from beef cattle slaughtered in winter, spring, summer, and autumn as well as lamb steaks (hind leg) from sheep slaughtered in autumn ( n  = 8) were sourced and homogenized. The contents of all 4 vitamin D-related compounds were analyzed using an LC-tandem MS method in conjunction with the National Institute of Standards and Technology's standard reference material no. 1546a-Meat Homogenate. The total vitamin D activity of meat was defined as: {vitamin D 3 + [25(OH)D 3  × 5] + vitamin D 2 + [25(OH)D 2  × 5]}., Results: The median (IQR) total vitamin D activity of striploin beef steak ( n  = 39, irrespective of season) was 0.56 (0.37-0.91) μg/100 g. The content of all 4 vitamin D compounds in beef steak varied significantly ( P  < 0.0001) with season ( n  = 8-11/season group). Median total vitamin D activity of beef steak increased in a stepwise manner ( P  < 0.0001) from winter to the following autumn (increasing from 0.31 to 1.07 μg/100 g). The mean total vitamin D activity of lamb samples ( n  = 8) from autumn was 0.47 μg/100 g., Conclusions: About one-third of the total vitamin D activity of Irish beef was attributable to its combined vitamin D 2 and 25(OH)D 2 content, estimates of which are largely or completely missed in food composition tables. There was significant seasonal variation in all 4 vitamin D compounds as well as in total vitamin D activity, which has implications for vitamin D nutrient claims for beef., (Copyright © The Author(s) on behalf of the American Society for Nutrition 2020.)

Background: Current evidence suggests that negative and stigmatising attitudes towards dementia may develop at a young age. There are a number of dementia education and awareness initiatives aimed at reducing stigma, though they have not been robustly evaluated to establish the impact on dementia attitudes or suitability in adolescent populations. This study explored the efficacy and satisfaction of one such initiative (Dementia Friends) in a British adolescent sample., Methods: 301 adolescents (M = 12.6 years old, SD = 0.73) were assigned to either receive Dementia Friends (a 60-min interactive class that teaches about dementia and its effects on people's lives) or education as usual. All participants completed a series of validated questionnaires pre- and post-intervention, related to dementia attitudes (Brief A-ADS and KIDS)., Results: Adolescents in the dementia awareness group showed little to no improvements between time-points. The change scores in the dementia awareness group did not significantly differ to the control group based on both KIDS (d = - 0.003, p = 0.98) and Brief A-ADS (d = 0.14, p = 0.13) measures. There was no Group x Time effect after controlling for confounding variables., Conclusions: Dementia Friends is successful in terms of reach and impact, though this study suggests that it may fall short of achieving its goal of improving attitudes towards dementia. Importantly, Dementia Friends did not have a negative effect on attitudes, and the majority of adolescents enjoyed the sessions. It is important that these findings are replicated in a larger randomised-controlled study.

Objectives: This study was designed to assess the content and construct validity and reliability of the Quality of Nursing Doctoral Education (QNDE) instrument for nursing doctoral programmes with a research focus., Design: A cross-sectional, survey study., Settings: Using Qualtrics survey, the research team sent emails to potential participants providing a link to the study and the QNDE instrument., Participants: A total of 234 faculty and doctoral students participated: 17 faculty from 14 countries in the first stage; 111 faculty and 106 doctoral students from 20 countries in the second stage., Methods: The content validity, internal consistency reliability, and construct validity of the four domains (program, faculty, resources, and evaluation) of the QNDE were examined in two stages. Data were collected from purposive samples of faculty and students between June 2018 and March 2019. Confirmatory factor analysis was conducted in ordinal scale using robust weighted least square mean and variance (WLSMV) adjusted estimator in MPlus 8., Results: Content validity of the items in the four domains was accepted when the item showed content validity (I-CVI > 0.78). Internal consistency reliability in four domains was computed using Cronbach's alpha, α = 0.88 to 0.97. Construct validity of the QNDE was established by confirmatory factor analysis based on model fit statistics. Factor loading coefficients for all items in each domain were statistically significant (>0.5; p < .001)., Conclusions: Participation of 234 faculty and doctoral students from 20 countries on four continents confirmed content validity, internal consistency reliability, and construct validity of the QNDE instrument. These findings support the credibility of this revised QNDE instrument for assessing the quality of nursing doctoral education with a research focus. This is a significant step forward in enhancing the capability for evaluating doctoral programmes., Competing Interests: Declaration of competing interest No conflict of interest has been declared by the authors., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Pesticide spray drift represents an important exposure pathway that may cause illness among orchard workers. To strike a balance between improving spray coverage and reducing drift, new sprayer technologies are being marketed for use in modern tree canopies to replace conventional axial fan airblast (AFA) sprayers that have been used widely since the 1950s. We designed a series of spray trials that used mixed-effects modeling to compare tracer-based drift volume levels for old and new sprayer technologies in an orchard work environment. Building on a smaller study of 6 trials (168 tree rows) that collected polyester line drift samples (n = 270 measurements) suspended on 15 vertical masts downwind of an AFA sprayer application, this study included 9 additional comparison trials (252 tree rows; n = 405 measurements) for 2 airblast tower sprayers: the directed air tower (DAT) and the multi-headed fan tower (MFT). Field-based measurements at mid (26 m) and far (52 m) distances showed that the DAT and MFT sprayers had 4-15 and 35-37% less drift than the AFA. After controlling for downwind distance, sampling height, and wind speed, model results indicated that the MFT [-35%; 95% confidence interval (CI): -22 and -49%; P < 0.001] significantly reduced drift levels compared to the AFA, but the DAT did not (-7%; 95% CI: -19 and 6%; P = 0.29). Tower sprayers appear to be a promising means by which to decrease drift levels through shorter nozzle-to-tree canopy distances and more horizontally directed aerosols that escape the tree canopy to a lesser extent. Substitution of these new technologies for AFA sprayers is likely to reduce the frequency and magnitude of pesticide drift exposures and associated illnesses. These findings, especially for the MFT, may fit United States Environmental Protection Agency's Drift Reduction Technology (DRT) one-star rating of 25-50% reduction. An 'AFA buyback' incentive program could be developed to stimulate wider adoption of new drift-reducing spray technologies. However, improved sprayer technologies alone do not eliminate drift. Applicator training, including proper sprayer calibration and maintenance, and application exclusion zones (AEZs) can also contribute to minimizing the risks of drift exposure. With regard to testing DRTs and establishing AEZs, our study findings demonstrate the need to define the impact of airblast sprayer type, orchard architecture, sampling height, and wind speed., (© The Author(s) 2019. Published by Oxford University Press on behalf of the British Occupational Hygiene Society.)

Purpose: Children's perspectives in the context of health service delivery have historically been seen as unimportant. They have been viewed as unintelligent, unable to effectively share or tell of their experiences or fully participate in their care, potentially resulting in a sense of dehumanisation. Method: The present paper illustrates children's experiences when undergoing medical procedures, using application of the eight dimensions of humanised care theoretical framework. Results: Findings from six published papers were reflectively interrogated to identify implicit findings related to the dimensions of humanised care. These implicit findings show ways of caring for childrenwhichcan lead to enhanced human sensitivity in care or conversely where the dimensions of being human are obscured to greater or lesser degrees and can result in forms of dehumanisation. Conclusions: Inadvertent dehumanising features of practice can be mediated by encouraging the inclusion of children's own lifeworld perspective and make room for their voices in both care and research. In this way the present well documented power imbalance could be addressed. Adding the value of the theoretical framework highlights areas of need for young children to be cared for as human beings.

Objective: The aim of this study was to explore the nature, potential usefulness and meaning of complaints lodged by patients and their relatives., Design: A retrospective, descriptive design was used., Setting: The study was based on a sample of formal patient complaints made through a patient complaint reporting system for publicly funded healthcare services in Sweden., Participants: A systematic random sample of 170 patient complaints was yielded from a total of 5689 patient complaints made in a Swedish county in 2015., Main Outcome Measure: Themes emerging from patient complaints analysed using a qualitative thematic method., Results: The patient complaints reported patients' or their relatives' experiences of disadvantages and problems faced when seeking healthcare services. The meanings of the complaints reflected six themes regarding access to healthcare services, continuity and follow-up, incidents and patient harm, communication, attitudes and approaches, and healthcare options pursued against the patient's wishes., Conclusions: The patient complaints analysed in this study clearly indicate a number of specific areas that commonly give rise to dissatisfaction; however, the key findings point to the significance of patients' exposure and vulnerability. The findings suggest that communication needs to be improved overall and that patient vulnerability could be successfully reduced with a strong interpersonal focus. Prerequisites for meeting patients' needs include accounting for patients' preferences and views both at the individual and organizational levels., (© The Author(s) 2018. Published by Oxford University Press in association with the International Society for Quality in Health Care. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Although mobile orchardplatforms have been developed to improve apple harvesting productivity in the US, the physical exposures of workers usingthe mobile platforms have not been well characterized, partlydue to the lack of assessment tools specific to the tree fruitorchard environment. The purpose of this study was to evaluate the feasibility and utility of different subjective and objective methods for characterizing apple harvesting workers' posture, armrepetition, heart rate, and perceived exertion during platform- and conventional ladder-based harvesting. During a regular full shiftwork (8 hours), the objective physical exposure measures (armelevation, torso inclination, and heart rate) of 6 platform, 6 ground, and 8 ladder workers were measured with tri-axial accelerometersand heart rate monitor; and subjective perceived exertion wascollected using standardized Borg RPE and CR-10 scales, translated into Spanish. The results showed that the arm elevation, torso forward bending, repetitiveness, heart rates, and perceived exertions were lower for the platform-based workers than forthe ladder-based workers. The subjective measures (Borg RPE and Borg CR-10) appeared to be similar and mirror the general trends of the objective heart rate and posture measures.These results indicate the potential benefit of these low-cost subjective measures when direct measurements are too costly,complicated, or not permitted. This study determined that field measurements of objective and subjective physical exposures were feasible for evaluating apple harvesting work. In summary, all themethods used appear to be feasible for field use in orchard-based environments..

Organophosphorus pesticides (OPs) are commonly applied to agricultural crops. Families living in these communities may have higher exposure to OPs due to take home exposures and close proximity to agricultural fields. The objectives of this study were to measure OP concentrations in home carpet dust in agricultural and non-agricultural households and examine factors that may impact OP concentrations such as occupation, housing characteristics, and resident behaviors. Agricultural households had at least one parent who worked in agriculture during the previous 5 years. Carpet dust samples were collected at two time points from 278 households in an agricultural community located in the Pacific Northwest from 2008-2011. Samples were analyzed for four types of OPs: azinphos-methyl, phosmet, malathion, and chlorpyrifos. Overall, OP detection frequencies and concentrations were higher in agricultural households compared to non-agricultural households. Factors associated with higher OP concentrations in home carpet dust were identified and included: (1) homes with two or more agricultural workers living in the home, (2) homes located in close proximity to an agricultural field or orchard, (3) having an entry floor mat, and (4) frequently vacuuming the house. Having air conditioning in the home had a protective effect with OP concentrations. While the use of these four OPs is restricted or limited for residential use in the United States, results show that they were still found in the indoor environment. The understanding of the impact of agricultural work and other factors that elevate levels of OPs in the home is crucial to mitigating pesticide exposure in agricultural communities.

Pesticide spray drift represents an important cause of crop damage and farmworker illness, especially among orchard workers. We drew upon exposure characteristics from known human illness cases to design a series of six spray trials that measured drift from a conventional axial fan airblast sprayer operating in a modern orchard work environment. Polyester line drift samples (n = 270; 45 per trial) were suspended on 15 vertical masts downwind of foliar applications of zinc, molybdenum, and copper micronutrient tracers. Samples were analyzed using inductively coupled plasma mass spectrometry and resulting masses were normalized by sprayer tank mix concentration to create tracer-based drift volume levels. Mixed-effects modeling described these levels in the context of spatial variability and buffers designed to protect workers from drift exposure. Field-based measurements showed evidence of drift up to 52 m downwind, which is approximately 1.7 times greater than the 30 m (100 ft) 'Application Exclusion Zone' defined for airblast sprayers by the United States Environmental Protection Agency Worker Protection Standard. When stratified by near (5 m), mid (26 m), and far (52 m) distances, geometric means and standard deviations for drift levels were 257 (1.8), 52 (2.0), and 20 (2.3) µl, respectively. Fixed effect model coefficients showed that higher wind speed [0.53; 95% confidence interval (CI): 0.35, 0.70] and sampling height (0.16; 95% CI: 0.11, 0.20) were positively associated with drift; increasing downwind distance (-0.05; 95% CI: -0.06, -0.04) was negatively associated with drift. Random effects showed large within-location variability, but relatively few systematic changes for individual locations across spray trials after accounting for wind speed, height, and distance. Our study findings demonstrate that buffers may offer drift exposure protection to orchard workers from airblast spraying. Variables such as orchard architecture, sampling height, and wind speed should be included in the evaluation and mitigation of risks from drift exposure. Data from our study may prove useful for estimating potential exposure and validating orchard-based bystander exposure models.

This study investigated the effects of synthetic and natural sources of vitamin D biofortification in pig diets on pork vitamin D activity and pork quality. One hundred and twenty pigs (60 male, 60 female) were assigned to one of four dietary treatments for a 55 d feeding period. The dietary treatments were (1)50 μg vitamin D₃/kg of feed; (2)50 μg of 25-hydroxvitamin D₃/kg of feed (25-OH-D₃); (3)50 μg vitamin D₂/kg of feed; (4)50 μg vitamin D₂-enriched mushrooms/kg of feed (Mushroom D₂). The pigs offered the 25-OH-D₃ diet exhibited the highest (P < 0.001) serum total 25-hydroxyvitamin D concentration and subsequently exhibited the highest (P < 0.05) Longissimus thoracis (LT) total vitamin D activity. Mushroom D 2 and 25-OH-D 3 supplementation increased pork antioxidant status. The vitamin D₂-enriched mushrooms improved (P < 0.05) pig performance, carcass weight and LT colour. In conclusion, 25-OH-D₃ is the most successful source for increasing pork vitamin D activity, while Mushroom D 2 may be a new avenue to improve animal performance and pork quality., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

What is the experience of people living with breathlessness due to medical conditions, those caring for them and those treating them, with regard to quality of life and the nature of clinical interactions?Electronic databases (Ovid MEDLINE, Embase, CINAHL Plus and PsycINFO) were searched (January 1987 to October 2017; English language), for qualitative studies exploring the experience of chronic breathlessness (patients, carers and clinicians). Two independent reviewers screened titles, abstracts and papers retrieved against inclusion criteria. Disagreements were resolved with a third reviewer. Primary qualitative data were extracted and synthesised using thematic synthesis.Inclusion and synthesis of 101 out of 2303 international papers produced four descriptive themes: 1) widespread effects of breathlessness; 2) coping; 3) help-seeking behaviour; and 4) clinicians' responsiveness to the symptom of breathlessness. The themes were combined to form the concept of "breathing space", to show how engaged coping and appropriate help-seeking (patient) and attention to symptom (clinician) helps maximise the patient's quality of living with breathlessness.Breathlessness has widespread impact on both patient and carer and affects breathing space. The degree of breathing space is influenced by interaction between the patient's coping style, their help-seeking behaviour and their clinician's responsiveness to breathlessness itself, in addition to managing the underlying disease., Competing Interests: Conflict of interest: None declared., (Copyright ©ERS 2018.)

The ubiquitin-proteasome system (UPS) comprises a network of enzymes that is responsible for maintaining cellular protein homeostasis. The therapeutic potential of this pathway has been validated by the clinical successes of a number of UPS modulators, including proteasome inhibitors and immunomodulatory imide drugs (IMiDs). Here we identified TAK-243 (formerly known as MLN7243) as a potent, mechanism-based small-molecule inhibitor of the ubiquitin activating enzyme (UAE), the primary mammalian E1 enzyme that regulates the ubiquitin conjugation cascade. TAK-243 treatment caused depletion of cellular ubiquitin conjugates, resulting in disruption of signaling events, induction of proteotoxic stress, and impairment of cell cycle progression and DNA damage repair pathways. TAK-243 treatment caused death of cancer cells and, in primary human xenograft studies, demonstrated antitumor activity at tolerated doses. Due to its specificity and potency, TAK-243 allows for interrogation of ubiquitin biology and for assessment of UAE inhibition as a new approach for cancer treatment.

The Vitamin D Standardization Program (VDSP) coordinated a study in 2012 to assess the commutability of reference materials and proficiency testing/external quality assurance materials for total 25-hydroxyvitamin D [25(OH)D] in human serum, the primary indicator of vitamin D status. A set of 50 single-donor serum samples as well as 17 reference and proficiency testing/external quality assessment materials were analyzed by participating laboratories that used either immunoassay or LC-MS methods for total 25(OH)D. The commutability test materials included National Institute of Standards and Technology Standard Reference Material 972a Vitamin D Metabolites in Human Serum as well as materials from the College of American Pathologists and the Vitamin D External Quality Assessment Scheme. Study protocols and data analysis procedures were in accordance with Clinical and Laboratory Standards Institute guidelines. The majority of the test materials were found to be commutable with the methods used in this commutability study. These results provide guidance for laboratories needing to choose appropriate reference materials and select proficiency or external quality assessment programs and will serve as a foundation for additional VDSP studies.

The Vitamin D Standardization Program (VDSP) coordinated an interlaboratory study to assess the comparability of measurements of total 25-hydroxyvitamin D [25(OH)D] in human serum, which is the primary marker of vitamin D status. A set of 50 individual donor samples were analyzed by 15 different laboratories representing national nutrition surveys, assay manufacturers, and clinical and/or research laboratories to provide results for total 25(OH)D using both immunoassays (IAs) and LC tandem MS (MS/MS). The results were evaluated relative to bias compared with the target values assigned based on a combination of measurements at Ghent University (Belgium) and the U.S. National Institute of Standards and Technology using reference measurement procedures for the determination of 25(OH)D2 and 25(OH)D3. CV and mean bias for each laboratory and assay platform were assessed and compared with previously established VDSP performance criteria, namely CV ≤ 10% and mean bias ≤ 5%. Nearly all LC-MS/MS results achieved VDSP criteria, whereas only 50% of IAs met the criterion for a ≤10% CV and only three of eight IAs achieved the ≤5% bias. These results establish a benchmark for the evaluation of 25(OH)D assay performance and standardization activities in the future.

Background: Despite numerous animal studies that have illustrated the impact of additional vitamin D in the diet of hens on the resulting egg vitamin D content, the effect of the consumption of such eggs on vitamin D status of healthy individuals has not, to our knowledge, been tested., Objective: We performed a randomized controlled trial (RCT) to investigate the effect of the consumption of vitamin D-enhanced eggs (produced by feeding hens at the maximum concentration of vitamin D3 or serum 25-hydroxyvitamin D [25(OH)D3] lawfully allowed in feed) on winter serum 25(OH)D in healthy adults., Design: We conducted an 8-wk winter RCT in adults aged 45-70 y (n = 55) who were stratified into 3 groups and were requested to consume ≤2 eggs/wk (control group, in which status was expected to decline), 7 vitamin D3-enhanced eggs/wk, or seven 25(OH)D3-enhanced eggs/wk. Serum 25(OH)D was the primary outcome., Results: Although there was no significant difference (P > 0.1; ANOVA) in the mean preintervention serum 25(OH)D in the 3 groups, it was ∼7-8 nmol/L lower in the control group than in the 2 groups who consumed vitamin D-enhanced eggs. With the use of an ANCOVA, in which baseline 25(OH)D was accounted for, vitamin D3-egg and 25(OH)D3-egg groups were shown to have had significantly higher (P ≤ 0.005) postintervention serum 25(OH)D than in the control group. With the use of a within-group analysis, it was shown that, although serum 25(OH)D in the control group significantly decreased over winter (mean ± SD: -6.4 ± 6.7 nmol/L; P = 0.001), there was no change in the 2 groups who consumed vitamin D-enhanced eggs (P > 0.1 for both)., Conclusion: Weekly consumption of 7 vitamin D-enhanced eggs has an important impact on winter vitamin D status in adults. This trial was registered at clinicaltrials.gov as NCT02678364., (© 2016 American Society for Nutrition.)

Children living in agricultural communities have a greater risk from pesticides due to para-occupational pathways. The goal of this study was to assess the impact of exposure to organophosphorus pesticides on the neurobehavioral performance of school-aged Latino children over time. Two exposure measures were used to estimate children's pesticide exposure: parent's occupation (agricultural or non-agricultural) and organophosphate residues in home carpet dust samples. During 2008-2011, 206 school-aged children completed a battery of neurobehavioral tests two times, approximately one year apart. The associations between both exposure measures and neurobehavioral performance were examined. Pesticide residues were detected in dust samples from both agricultural and non-agricultural homes, however, pesticides were detected more frequently and in higher concentrations in agricultural homes compared to non-agricultural homes. Although few differences were found between agricultural and non-agricultural children at both visits, deficits in learning from the first visit to the second visit, or less improvement, was found in agricultural children relative to non-agricultural children. These differences were significant for the Divided Attention and Purdue Pegboard tests. These findings are consistent with previous research showing deficits in motor function. A summary measure of organophosphate residues was not associated with neurobehavioral performance. Results from this study indicate that children in agricultural communities are at increased risk from pesticides as a result of a parent working in agricultural. Our findings suggest that organophosphate exposure may be associated with deficits in learning on neurobehavioral performance, particularly in tests of with motor function. In spite of regulatory phasing out of organophosphates in the U.S., we still see elevated levels and higher detection rates of several organophosphates in agricultural households than non-agricultural households, albeit lower levels than prior studies., Competing Interests: Oregon Health and Science University (OHSU) and Dr. Rohlman have a significant financial interest in Northwest Education Training and Assessment, LLC, a company that may have a commercial interest in the results of this research and technology. This potential conflict of interest was reviewed and a management plan approved by the University of Iowa and the OHSU Conflict of Interest in Research Committee was implemented., (Copyright © 2016. Published by Elsevier B.V.)

Development of the Practical Solutions for Pesticide Safety guide used participatory research strategies to identify and evaluate solutions that reduce pesticide exposures for workers and their families and to disseminate these solutions. Project principles were (1) workplace chemicals belong in the workplace, and (2) pesticide handlers and farm managers are experts, with direct knowledge of production practices. The project's participatory methods were grounded in self-determination theory. Practical solutions were identified and evaluated based on five criteria: practicality, adaptability, health and safety, novelty, and regulatory compliance. Research activities that had more personal contact provided better outcomes. The Expert Working Group, composed of farm managers and pesticide handlers, was key to the identification of solutions, as were farm site visits. Audience participation, hands-on testing, and orchard field trials were particularly effective in the evaluation of potential solutions. Small work groups in a Regional Advisory Committee provided the best direction and guidance for a "user-friendly" translational document that provided evidence-based practical solutions. The "farmer to farmer" format of the guide was endorsed by both the Expert Working Group and the Regional Advisory Committee. Managers and pesticide handlers wanted to share their solutions in order to "help others stay safe," and they appreciated attribution in the guide. The guide is now being used in educational programs across the region. The fundamental concept that farmers and farmworkers are innovators and experts in agricultural production was affirmed by this study. The success of this process demonstrates the value of participatory industrial hygiene in agriculture.

In non-clinical studies, the proteasome inhibitor ixazomib inhibits cell growth in a broad panel of solid tumor cell lines in vitro. In contrast, antitumor activity in xenograft tumors is model-dependent, with some solid tumors showing no response to ixazomib. In this study we examined factors responsible for ixazomib sensitivity or resistance using mouse xenograft models. A survey of 14 non-small cell lung cancer (NSCLC) and 6 colon xenografts showed a striking relationship between ixazomib activity and KRAS genotype; tumors with wild-type (WT) KRAS were more sensitive to ixazomib than tumors harboring KRAS activating mutations. To confirm the association between KRAS genotype and ixazomib sensitivity, we used SW48 isogenic colon cancer cell lines. Either KRAS-G13D or KRAS-G12V mutations were introduced into KRAS-WT SW48 cells to generate cells that stably express activated KRAS. SW48 KRAS WT tumors, but neither SW48-KRAS-G13D tumors nor SW48-KRAS-G12V tumors, were sensitive to ixazomib in vivo. Since activated KRAS is known to be associated with metabolic reprogramming, we compared metabolite profiling of SW48-WT and SW48-KRAS-G13D tumors treated with or without ixazomib. Prior to treatment there were significant metabolic differences between SW48 WT and SW48-KRAS-G13D tumors, reflecting higher oxidative stress and glucose utilization in the KRAS-G13D tumors. Ixazomib treatment resulted in significant metabolic regulation, and some of these changes were specific to KRAS WT tumors. Depletion of free amino acid pools and activation of GCN2-eIF2α-pathways were observed both in tumor types. However, changes in lipid beta oxidation were observed in only the KRAS WT tumors. The non-clinical data presented here show a correlation between KRAS genotype and ixazomib sensitivity in NSCLC and colon xenografts and provide new evidence of regulation of key metabolic pathways by proteasome inhibition.