Hand preference trajectories as predictors of language outcomes above and beyond SES: Infant patterns explain more variance than toddler patterns at 5 years of age.

Prior studies found hand preference trajectories predict preschool language outcomes. However, this approach has been limited to examining bimanual manipulation in toddlers. It is not known whether hand preference during infancy for acquiring objects (i.e., reach-to-grasp) similarly predicts childhood language ability. The current study explored this motor-language developmental cascade in 90 children. Hand preference for acquiring objects was assessed monthly from 6 to 14 months and language skill was assessed at 5 years. Latent class growth analysis identified three infant hand preference classes: left, early right, and late right. Infant hand preference classes predicted 5-year language skills. Children in the left and early right classes, who were categorized as having a consistent hand preference, had higher expressive and receptive language scores relative to children in the inconsistent late right class. Consistent classes did not differ from each other on language outcomes. Infant hand preference patterns explained more variance for expressive and receptive language relative to previously reported toddler hand preference patterns, above and beyond socioeconomic status (SES). Results suggest that hand preference, measured at different time points across development using a trajectory approach, is reliably linked to later language.

Time-independent relationship between digits closure velocity and hand transport acceleration during reach-to-grasp movements.

Prehension movements in primates have been extensively studied for decades, and hand transport and hand grip adjustment are usually considered as the main components of any object reach-to-grasp action. Evident temporal patterns were found for the velocity of the hand during the transport phase and for the digits kinematics during pre-shaping and enclosing phases. However, such kinematics were always analysed separately in regard to time, and never studied in terms of dependence one from another. Nevertheless, if a reliable one-to-one relationship is proven, it would allow reconstructing the digit velocity (and position) simply by knowing the hand acceleration during reaching motions towards the target object, ceasing the usual dependence seen in literature from time of movement and distance from the target. In this study, the aim was precisely to analyse reach-to-grasp motions to explore if such relationship exists and how it can be formulated. Offline and real-time results not only seem to suggest the existence of a time-independent, one-to-one relationship between hand transport and hand grip adjustment, but also that such relationship is quite resilient to the different intrinsic and extrinsic properties of the target objects such as size, shape and position.

A stepped wedge cluster randomized trial to evaluate the effectiveness of a multisite family caregiver skills training program.

OBJECTIVE: To assess the effects of an evidence-based family caregiver training program (implementation of Helping Invested Families Improve Veteran Experiences Study [iHI-FIVES]) in the Veterans Affairs healthcare system on Veteran days not at home and family caregiver well-being. DATA SOURCES AND STUDY SETTING: Participants included Veterans referred to home- and community-based services with an identified caregiver across 8 medical centers and confirmed family caregivers of eligible Veterans. STUDY DESIGN: In a stepped wedge cluster randomized trial, sites were randomized to a 6-month time interval for starting iHI-FIVES and received standardized implementation support. The primary outcome, number of Veteran "days not at home," and secondary outcomes, changes over 3 months in measures of caregiver well-being, were compared between pre- and post-iHI-FIVES intervals using generalized linear models including covariates. DATA COLLECTION/EXTRACTION METHODS: Patient data were extracted from the electronic health record. Caregiver data were collected from 2 telephone-based surveys. PRINCIPAL FINDINGS: Overall, n = 898 eligible Veterans were identified across pre-iHI-FIVES (n = 327) and post-iHI-FIVES intervals (n = 571). Just under one fifth (17%) of Veterans in post-iHI-FIVES intervals had a caregiver enroll in iHI-FIVES. Veteran and caregiver demographics in pre-iHI-FIVES intervals were similar to those in post-iHI-FIVES intervals. In adjusted models, the estimated rate of days not at home over 6-months was 42% lower (rate ratio = 0.58 [95% confidence interval: 0.31-1.09; p = 0.09]) post-iHI-FIVES compared with pre-iHI-FIVES. The estimated mean days not at home over a 6-month period was 13.0 days pre-iHI-FIVES and 7.5 post-iHI-FIVES. There were no differences between pre- and post-iHI-FIVES in change over 3 months in caregiver well-being measures. CONCLUSIONS: Reducing days not at home is consistent with effectiveness because more time at home increases quality of life. In this study, after adjusting for Veteran characteristics, we did not find evidence that implementation of a caregiver training program yielded a reduction in Veteran's days not at home.

Citations in Wikipedia for understanding research reach.

Objective: Wikipedia is the most frequently accessed online health information resource and is well positioned as a valuable tool for public health communication and knowledge translation. The authors aimed to explore their institution's health and medical research reach by analyzing its presence in Wikipedia articles. Methods: In October 2022, a comprehensive database search was constructed in PubMed to retrieve clinical evidence syntheses published by at least one author affiliated with McMaster University from 2017 to 2022, inclusive. Altmetric Explorer was queried using PubMed Identifiers and article titles to access metadata and Wikipedia citation data. 3,582 health evidence syntheses from at least one McMaster University affiliated author were analyzed. Results: Six percent (n=219) of health evidence syntheses from the authors' institution were cited 568 times in 524 unique Wikipedia articles across 28 different language editions. 45% of citations appeared in English Wikipedia, suggesting a broad global reach for the institutions' research outputs. When adjusted for open access publications, 8% of McMaster University's health evidence syntheses appear in Wikipedia. Conclusion: Altmetric Explorer is a valuable tool for exploring the reach of an institution's research outputs. Isolating Altmetric data to focus on Wikipedia citations has value for any institution wishing to gain more insight into the global, community-level reach of its contributions to the latest health and medical evidence.

Lessons learned from rebranding a radiology education facebook page.

OBJECTIVE: In May 2009, we created a Facebook page for radiology education. While we shared a host of learning materials such as case images, quiz questions, and medical illustrations, we also posted world news, music, and memes. In February 2023, we eliminated everything from the site not related to radiology education. Our aim was to determine how focusing on radiology education alone would affect audience growth for our Facebook page. MATERIALS AND METHODS: We exported our Facebook post data for the dates March 1, 2023 through February 29, 2024, to represent the full calendar year after we revised our content presentation, which we compared to data from November 1, 2020 to October 31, 2021. The mean and standard deviation for each post type's reach for 2023/24 were analyzed and compared against the 2020/21 statistics, and Wilcoxon rank sum tests were used to obtain p-values. Linear regressions for each year were performed to understand the relationship between reach and engagement. RESULTS: A total of 4,270 posts were included in our new analysis. Our average number of posts per day decreased from 24.8 to 11.71, reducing by more than half the amount of content shared to our social media page. Our posts had a mean overall reach of 4,660-compared to 1,743 in 2021 (p=0.0000). There was a statistically significant increase in reach for posts on artificial intelligence, case images, medical illustrations, pearls, quiz images, quiz videos, slideshow images, and both types of instructional videos (p<0.005). For both 2021 and 2024, the linear regression slopes were positive (y=0.0687x-65.0279 and y=0.006334x+21.3425, respectively). CONCLUSIONS: Facebook and other social media have been found to be helpful sources for radiology education. Our experience and statistics with radiology education via social media may help other radiology educators better curate their own pages. To optimize experiences for students, professionals, and other users, and to reach more people, we found that providing readily accessible radiology education is preferred to the social aspects of social media.

Seated Virtual Reality-Guided Exercise Improved Gait in a Patient With Trunk Dysfunction Due to Hip Fracture: A Single-Case Design Study.

Physical therapy for mobilization after a hip fracture is effective in improving muscle strength and balance training of the lower extremities; however, effective interventions targeting the trunk muscles remain to be established. The efficacy of virtual reality (VR)-based exercise therapy has been recently reported. This case report demonstrates the effectiveness of VR-based intervention in improving the gait of a female patient in her 90s with a femoral neck fracture who had difficulty in independent gait postoperatively due to trunk dysfunction. The patient had undergone bipolar hip hemiarthroplasty for a right femoral neck fracture sustained via a fall at home. Standard physical therapy, including range of motion exercises, resistance training, and gait training, was commenced gradually the day after surgery. An improvement in lower extremity pain was reported at the two-month follow-up visit but without any improvement in the gait ability. Trunk flexion was observed during gait, and the patient had difficulty in independent gait and walking without upper limb support. Withdrawal and reversal designs (BAB) were employed, and each period lasted one week. Standard physiotherapy supplemented with trunk reach training in a seated position using VR equipment was commenced subsequently. An improvement in the maximum anterior pelvic tilt angle and sitting and standing postures, increased hip extension range of motion and step length during gait, and decreased gait speed were observed during the intervention phase. These results highlight the importance of physiotherapy interventions targeting the trunk muscle and the effectiveness of VR-guided trunk training in patients with femoral neck fractures.

Transitioning to Microplastic-Free Seed Coatings: Challenges and Solutions.

This review addresses the issue of replacing manufactured microplastics in seed coatings used in agriculture. Firstly, it focuses on the policy and regulatory actions taken on microplastics at a global level. There is no consensus within the scientific community on the definition of a microplastic and, more generally, on the classification of plastic debris. Nevertheless, several decision schemes have been proposed in an attempt to define the notion of microplastics. The different criteria relevant to this definition, such as the size, physical state, chemical structure, origin, and persistence of microplastics, are discussed, with a comparison being made between the REACH regulation and the scientific literature. Seed production and processing are also discussed, with the functions of seed coatings being explained in order to gain a better understanding of the properties to be considered in a substitution strategy for currently used microplastics. The main challenges are multiple; substitutes must provide the same performance as microplastics: (i) improving the adherence of the treatment to the seed, (ii) distributing the treatment more evenly over the seed, (iii) reducing the amount of dust-off when handling treated seed, and (iv) improving the seed flowability, which is particularly important during the sowing stage, all while preserving the physiological properties of the seed. Substitute polymers are proposed according to the desired performance and functional properties: two main chemical families of biopolymers were identified in the literature: polysaccharides and proteins. Among them, 13 and 6 polymers, respectively, complied with REACH regulation, demonstrating adhesion, dust reduction performances, and preservation of seed physiological quality in particular. This work aims to guide future studies on microplastic substitution in seed coatings, and to highlight research needs in this area. It is based on an analysis and discussion of the literature, identifying and listing potential substitutes.

Beyond microbeads: Examining the role of cosmetics in microplastic pollution and spotlighting unanswered questions.

The presence of microplastics in cosmetics and personal care products (C&PCPs) has been increasingly in the public eye since the early 2010s. Despite increasing research into the potential environmental and health effects of microplastics, most research to date on microplastics in C&PCPs has investigated "rinse-off" products, while the potential impacts of "leave-on" C&PCPs have been largely neglected, despite these products being purchased in greater volumes and often having two or more microplastic ingredients in their formulations(CosmeticsEurope, 2018b). This review aims to synthesize the current knowledge of microplastic in C&PCPs, assessing the potential environmental and human health impacts of C&PCPs and discussing the regulatory implications. The lack of studies on leave-on C&PCPs is significant, suggesting a severe knowledge gap regarding microplastic presence in, and emissions from, C&PCPs. There is a noticeable lack of studies on the (eco)toxicological consequences of microplastic exposure from C&PCPs. As a result, significant aspects of microplastic contamination may be overlooked in the microplastic legislations emerging globally (including from the European Commission), which intend to restrict microplastic use in C&PCPs but focus on rinse-off C&PCPs only. This review highlights the potential consequences of microplastics in leave-on C&PCPs for regulatory decision-making, particularly as alternatives to microplastics are considered during the phase-out periods and spotlights the need for sufficient monitoring and research on these alternatives, to avoid unforeseen consequences.

App-Based Addiction Prevention at German Vocational Schools: Implementation and Reach for a Cluster-Randomized Controlled Trial.

This article examines the implementation, participation rates, and potential determinants of participation in the digital addiction prevention program "ready4life." A two-arm cluster-randomized trial recruited German vocational students via class-based strategies. Intervention group received 16 weeks of in-app coaching; the control group received health behavior information, with coaching offered after 12 months. Potential determinants of participation were analyzed based on class and individual characteristics. Out of 525 contacted schools, 35 participated, enrolling 376 classes. Implementation during the pandemic required flexible adjustments, with 49.7% of introductions conducted in person, 43.1% digitally via online streaming, and 7.2% received a video link via email. Despite challenges, 72.3% of the vocational students downloaded the app, and 46.7% gave informed consent. Participation rates were highest among (associate) professionals, vocational grammar school classes, classes introduced by females, younger individuals, members of the project team, and classes introduced face-to-face. Female gender, lower social competencies, lifetime cannabis use, higher problematic internet use, and higher perceived stress were associated with higher individual participation. The study highlights the importance of proactive outreach and personalized interventions for addiction prevention programs in vocational schools. While reached students aligned with the aims of the app, tailored recruitment strategies could enhance engagement among under-represented groups. The trial was registered in the German Clinical Trials Register (DRKS): DRKS00022328; registration date 09.10.2020.

A systematic analysis of read-across within REACH registration dossiers.

Read-across is a well-established data-gap filling technique used within analogue or category approaches. Acceptance remains an issue, mainly due to the difficulties of addressing residual uncertainties associated with a read-across prediction and because assessments are expert-driven. Frameworks to develop, assess and document read-across may help reduce variability in read-across results. Data-driven read-across approaches such as Generalised Read-Across (GenRA) include quantification of uncertainties and performance. GenRA also affords opportunities on how New Approach Method (NAM) data can be systematically incorporated to support the read-across hypothesis. Herein, a systematic investigation of differences in expert-driven read-across with data-driven approaches was pursued in terms of establishing scientific confidence in the use of read-across. A dataset of expert-driven read-across assessments that made use of registration data as disseminated in the public International Uniform Chemical Information Database (IUCLID) (version 6) of Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH) Study Results were compiled. A dataset of ~5000 read-across cases pertaining to repeated dose and developmental toxicity was extracted and mapped to content within EPA's Distributed Structure Searchable Toxicity database (DSSTox) to retrieve chemical name and structural identification information. Content could be mapped to ~3600 cases which when filtered for unique cases with curated quantitative structure-activity relationship-ready SMILES resulted in 389 target-source analogue pairs. The similarity between target and the source analogues on the basis of different contexts - from structural similarity using chemical fingerprints to metabolic similarity using predicted metabolic information was evaluated. An attempt was also made to quantify the relative contribution each similarity context played relative to the target-source analogue pairs by deriving a model which predicted known analogue pairs. Finally, point of departure values (PODs) were predicted using the GenRA approach underpinned by data extracted from the EPA's Toxicity Values Database (ToxValDB). The GenRA predicted PODs were compared with those reported within the REACH dossiers themselves. This study offers generalisable insights on how read-across is already applied for regulatory submissions and expectations on the levels of similarity necessary to make decisions.

Motor cortical inactivation impairs corrective submovements in mice performing a hold-still center-out reach task.

Holding still and aiming reaches to spatial targets may depend on distinct neural circuits. Using automated homecage training and a sensitive joystick, we trained freely-moving mice to contact a joystick, hold their forelimb still, and then reach to rewarded target locations. Mice learned the task by initiating forelimb sequences with clearly resolved submillimeter-scale micromovements followed by millimeter-scale reaches to learned spatial targets. Hundreds of thousands of trajectories were decomposed into millions of kinematic submovements, while photoinhibition was used to test roles of motor cortical areas. Inactivation of both caudal and rostral forelimb areas preserved the ability to produce aimed reaches, but reduced reach speed. Inactivation specifically of contralateral caudal forelimb area (CFA) additionally impaired the ability to aim corrective submovements to remembered locations following target undershoots. Our findings show that motor cortical inactivations reduce the gain of forelimb movements but that inactivation specifically of contralateral CFA impairs corrective movements important for reaching a target location.

Adaptation and Reach of a Pre-Exposure Prophylaxis Social Marketing Campaign for Latino, Latina, and Latinx Populations: Development Study.

BACKGROUND: Latino, Latina, and Latinx (Latino/a/x) individuals remain disproportionately impacted by HIV, particularly sexual minority men and transgender women. Pre-exposure prophylaxis (PrEP) is an effective means of biomedical HIV prevention, but awareness and uptake remain low among marginalized Latino/a/x populations. Social marketing campaigns have demonstrated promise in promoting PrEP in other populations but are poorly studied in Latino/a/x sexual minority men and transgender women. OBJECTIVE: This study aims to (1) adapt and pilot a PrEP social marketing campaign tailored to Latino/a/x populations with a focus on sexual minority men and transgender women through community-based participatory research (CBPR) and (2) evaluate the reach and ad performance of the adapted PrEP social marketing campaign. METHODS: We used the ADAPT-ITT (assessment, decision, adaptation, production, topical experts-integration, training, and testing) framework for adapting evidence-based interventions for new settings or populations. This paper presents how each phase of the ADAPT-ITT framework was applied via CBPR to create the PrEPárate ("Be PrEPared") campaign. Key community engagement strategies included shared ownership with community partners, focus groups to guide content, crowdsourcing to name the campaign, design by local Latino/a/x artists, and featuring local influencers as the faces of PrEPárate. We evaluated campaign reach and advertisement performance using social media platform metrics (paid and organic reach, impressions, unique clicks, and click-through rates [CTR]) and website use statistics from Google Analytics. RESULTS: The PrEPárate campaign ran in Cook County, Illinois, from April to September 2022. The campaign reached over 118,750 people on social media (55,750 on Facebook and Instagram [Meta Platforms Inc] and 63,000 on TikTok [ByteDance Ltd]). The Meta ads performed over the industry benchmark with ads featuring local transgender women (2% CTR) and cisgender sexual minority men (1.4% CTR). Of the different Grindr (Grindr Inc) ad formats piloted, the interstitial Grindr ads were the highest performing (1183/55,479, 2.13% CTR). YouTube (Google) ads were low performing at 0.11% (153/138,337) CTR and were stopped prematurely, given limits on sexual education-related content. In the first year, there were 5006 visitors to the website. CONCLUSIONS: Adaptation of an existing evidence-based intervention served as an effective method for developing a PrEP social marketing campaign for Latino/a/x audiences. CBPR and strong community partnerships were essential to tailor materials and provide avenues to systematically address barriers to PrEP access. Social marketing is a promising strategy to promote PrEP among underserved Latino/a/x populations.

Evaluating the Balancing Ability of Older Adults with Diabetes Mellitus Using the Multi-directional Reach Test.

BACKGROUND: The incidence of elderly people experiencing falls is currently increasing, which results in serious medical issues, such as fear of falling, limited physical activity, disability, and bone fractures, especially hip fractures. This study aimed to investigate balancing ability using a multi-directional reach test (MDRT) in older adults with and without diabetes mellitus. METHODS: 72 older adults with and without diabetes mellitus were recruited, and divided into two groups, including older adults without diabetes mellitus (n = 36) and older adults with diabetes mellitus (n = 36). All subjects completed all directions of the MDRT. RESULTS: There were no significant differences in MDRT scores in all directions between the two groups (p>0.05). Both groups achieved the highest MDRT scores in the forward direction. In contrast, the two groups had the lowest scores of MDRT in a backward direction. Furthermore, older adults with diabetes mellitus had lower MDRT scores in all directions than older adults without diabetes mellitus. CONCLUSION: The current study indicated that MDRT could be used to investigate the ability of balance in individuals with diabetes mellitus.

Comparison of resistance training vs static stretching on flexibility and maximal strength in healthy physically active adults, a randomized controlled trial.

BACKGROUND: The aim of the present study was to compare the effects of resistance training through full range of motion and static stretching (SS) of the hip and lower back extensors on flexibility and strength in healthy, physically active, adults. METHODS: Eighteen participants (age: 24.2 ± 3.0 years, body mass: 71.3 ± 8.9 kg, height: 172.8 ± 7.5 cm) were randomly assigned to either a Resistance Training (RT) (n = 6), SS (n = 6), or control (CON) group (n = 6). The sit & reach (S&R) flexibility test and maximum isometric straight legged deadlift (ISLDL) at 95% and 50% range of motion (ROM) were tested pre- and post-intervention with significance set at p < 0.05. Both groups conducted four to eight sets per session. Within each set, the RT group performed eight repetitions each lasting four seconds, while the SS group stretched continuously for 32 s. The rest periods between each set were 60-90 s. Consequently training volume and rest times were matched between the groups. RESULTS: The RT and SS groups achieved significant, large magnitude improvements in the S&R test compared to the CON group (p < 0.01 g = 2.53 and p = 0.01, g = 2.44), but no differences were observed between the RT and SS groups (p = 1.00). Furthermore, the RT group demonstrated a larger improvement in 50% and 95% ROM ISLDL compared to SS (p < 0.01, g = 2.69-3.36) and CON (p < 0.01, g = 2.44-2.57). CONCLUSION: Resistance training through a full ROM was equally effective as SS for improving S&R flexibility, but improved hip- and lower back extensor strength more than SS and the CON. The authors recommend using large ROM resistance training to improve hip and lower back extensor flexibility and muscle strength. TRIAL REGISTRATION: ISRCTN88839251, registered 24. April 2024, Retrospectively registered.

Mapping implementation strategies to reach community-dwelling older adults in Northwest Switzerland.

BACKGROUND: In Northwestern Switzerland, recent legislation tackles the needs of community-dwelling older adults by creating Information and Advice Centers (IACs). IACs are a new service in the community that aims to assess the needs and provide information on age-related issues to community-dwelling older adults and their families. Previous studies reported difficulties in reaching community-dwelling older adults for community-based programs. We aimed to: 1) systematically identify implementation strategies to promote the IAC among community care providers, older adults and informal caregivers; 2) monitor the delivery of these strategies by the IAC management; and 3) describe the impact of those strategies on reach of community-dwelling older adults. This study was conducted as part of the TRANS-SENIOR project. METHODS: As part of the INSPIRE feasibility assessment, we conducted a pre-test post-test study between March and September 2022. The sample included 8,840 older adults aged 65 + visiting/calling or being referred to the IAC for the first time. Implementation strategies were selected using implementation mapping and organized in bundles for each group of community care providers and older adults/caregivers. Our evaluation included: estimation of fidelity to the delivery of implementation strategies and bundles by the IAC management and their coverage; referral source of older adults to the IAC; and impact of the strategies on reach of the IAC on the 65 + population living in the care region. Adaptations to the strategies were documented using the FRAME-IS. Descriptive statistics were calculated and reported. RESULTS: Seven implementation strategies were selected and organized in bundles for each community care provider and older adults and their caregivers. The lowest fidelity score was found in implementation strategies selected for nursing homes whereas the highest score corresponded to strategies targeting older adults and caregivers. "Informational visits" was the strategy with the lowest coverage (2.5% for nursing homes and 10.5% for hospitals and specialized clinics). The main referral sources were self-referrals and referrals by caregivers, followed by nursing homes. The IAC reach among the 65 + population was 5.4%. CONCLUSION: We demonstrated the use of implementation mapping to select implementation strategies to reach community-dwelling older adults. The reach was low suggesting that higher fidelity to the delivery of the strategies, and reflection on the causal pathway of the implementation strategies might be needed.

Influence of gaze, vision, and memory on hand kinematics in a placement task.

People usually reach for objects to place them in some position and orientation, but the placement component of this sequence is often ignored. For example, reaches are influenced by gaze position, visual feedback, and memory delays, but their influence on object placement is unclear. Here, we tested these factors in a task where participants placed and oriented a trapezoidal block against two-dimensional (2-D) visual templates displayed on a frontally located computer screen. In experiment 1, participants matched the block to three possible orientations: 0° (horizontal), +45° and -45°, with gaze fixated 10° to the left/right. The hand and template either remained illuminated (closed-loop), or visual feedback was removed (open-loop). Here, hand location consistently overshot the template relative to gaze, especially in the open-loop task; likewise, orientation was influenced by gaze position (depending on template orientation and visual feedback). In experiment 2, a memory delay was added, and participants sometimes performed saccades (toward, away from, or across the template). In this task, the influence of gaze on orientation vanished, but location errors were influenced by both template orientation and final gaze position. Contrary to our expectations, the previous saccade metrics also impacted placement overshoot. Overall, hand orientation was influenced by template orientation in a nonlinear fashion. These results demonstrate interactions between gaze and orientation signals in the planning and execution of hand placement and suggest different neural mechanisms for closed-loop, open-loop, and memory delay placement.NEW & NOTEWORTHY Eye-hand coordination studies usually focus on object acquisition, but placement is equally important. We investigated how gaze position influences object placement toward a 2-D template with different levels of visual feedback. Like reach, placement overestimated goal location relative to gaze and was influenced by previous saccade metrics. Gaze also modulated hand orientation, depending on template orientation and level of visual feedback. Gaze influence was feedback-dependent, with location errors having no significant effect after a memory delay.

Hard to reach? Methodological challenges researching vulnerable, gang-involved, young people.

INTRODUCTION: Research with young people (YP) is ethically challenging and bound in a complex maze of issues relating to power, voice and representation. Such sensitivities mean that the challenges raised in researching marginalised YP are often hard to navigate. This paper reports on research carried out with YP to explore links between mental health, school exclusion and involvement in criminal gangs. It aims to provide a practical guide to negotiating some of the methodological and ethical challenges experienced. METHOD: In-depth interviews conducted with 28 YP (aged 14-24 years) who were gang involved or seen to be at risk of gang involvement. Research was conducted in youth clubs, alternative provision and youth justice settings. RESULTS: OBSERVATIONS/REFLECTIONS: We reflect on how navigating ethics can create barriers to involving YP as primary informants in research. We consider why it is important to overcome these hurdles and how public engagement work with recognised gatekeepers and the use of creative interview methods can facilitate meaningful encounters, where YP feel able to share valuable insights into their lives. CONCLUSION: Alongside a number of specific learning points, the paper reflects on theories behind research with YP, including the need for recognition of power imbalances and reflexivity. It concludes with thoughts on the practical realities of achieving meaningful participation or an 'authentic voice' with marginalised groups and the importance of this in informing policy and practice. PATIENT OR PUBLIC CONTRIBUTION: The focus of this work was to collect experiences of YP who are recognised as gang-involved or at risk of being so, with a view to informing health and education policies. The scoping study for the project involved extensive public engagement work with YP exploring and trialling suitable methods of accessing, recruiting and ultimately interviewing this target group. This is central to the discussion within the body of the paper.

The participation of hard-to-reach older people in the research and development process of health technologies from the perspective of multipliers-A qualitative analysis.

Introduction: The participation of older people in research and development processes has long been called for but has not been sufficiently put into practice. In addition, participation is often late and not particularly intensive, so that certain older groups of people are underrepresented in the development of health technologies (HT). Heterogeneity, e.g., between urban and rural populations, in access to and motivation for participation is also rarely taken into account. The aim of this study was to investigate form and phases of participation for hard-to-reach older people in the research and development process of HT. Methods: The qualitative study among multipliers was conducted using focus groups and telephone interviews and took place in a city and an adjacent rural area in northwestern Lower Saxony, Germany. A content analysis of the data was undertaken using deductive-inductive category formation. Results: Seventeen participants (13 female) took part in the study (median age 61, 33-73). Participants from both areas identified particular forms and phases of participation in the research and development process. Longer forms of participation for hard-to-reach groups and the development process of technologies for older people from the rural area were viewed as challenges. Passive and active access strategies are needed to achieve sufficient heterogeneity in the research and development process. Trusted multipliers can play an important role in gaining access to hard-to-reach older people, but also during the research process. Apart from facilitating factors (e.g., age-specific study materials), inhibiting factors such as contact anxieties are also indicated. Only urban participants mention financial/material incentives and community as possible motivations. Conclusions: The results provide important insights from the perspective of multipliers. They show specificities in access and participation for rural areas and for hard-to-reach older people. Many older people may have uncertainties about research projects and HT. Multipliers can assume a key role to help reduce these uncertainties in the future.

Ramucirumab for advanced hepatocellular carcinoma in the current real world: a Japanese single-arm study post-REACH-2 (The R-evolution study).

This study aimed to complement the results of the REACH-2 study by prospectively evaluating the safety and efficacy of ramucirumab in advanced hepatocellular carcinoma (HCC) in a real-world setting. This was an open-label, nonrandomized, multicenter, prospective study conducted at 13 institutions in Japan (jRCTs031190236). The study included Child-Pugh Class A patients with advanced HCC who had received pretreatment with atezolizumab plus bevacizumab (Atez/Bev) or lenvatinib. Ramucirumab was introduced as a second-line treatment after Atez/Bev or lenvatinib and as a third-line treatment after Atez/Bev and lenvatinib. Between May 2020 and July 2022, we enrolled 19 patients, including 17 who received ramucirumab. Additionally, seven patients received lenvatinib, another seven patients received Atez/Bev, and three patients received Atez/Bev followed by lenvatinib as prior treatment. The primary endpoint was a 6-month progression-free survival (PFS) rate, which was 14.3%. The median PFS and overall survival were 3.7 and 12.0 months, respectively. The most common grade ≥ 3 adverse events (AEs) were hypertension (23.5%), proteinuria (17.6%), and neutropenia (11.8%). The discontinuation rate due to AEs was 29.4%. Six patients progressed from Child-Pugh A to B after treatment with ramucirumab. Thirteen patients were eligible for post-ramucirumab treatment, including systemic therapy. Despite the limited number of patients, the efficacy of ramucirumab was comparable to that observed in the REACH-2 study when used after lenvatinib and Atez/Bev. However, the incidence of AEs was higher than that in the REACH-2 study.

Next generation risk assessment for occupational chemical safety - A real world example with sodium-2-hydroxyethane sulfonate.

Next Generation Risk Assessment (NGRA) is an exposure-led approach to safety assessment that uses New Approach Methodologies (NAMs). Application of NGRA has been largely restricted to assessments of consumer use of cosmetics and is not currently implemented in occupational safety assessments, e.g. under EU REACH. By contrast, a large proportion of regulatory worker safety assessments are underpinned by toxicological studies using experimental animals. Consequently, occupational safety assessment represents an area that would benefit from increasing application of NGRA to safety decision making. Here, a workflow for conducting NGRA under an occupational safety context was developed, which is illustrated with a case study chemical; sodium 2-hydroxyethane sulphonate (sodium isethionate or SI). Exposures were estimated using a standard occupational exposure model following a comprehensive life cycle assessment of SI and considering factory-specific data. Outputs of this model were then used to estimate internal exposures using a Physiologically Based Kinetic (PBK) model, which was constructed with SI specific Absorption, Distribution, Metabolism and Excretion (ADME) data. PBK modelling indicated a worst-case plasma maximum concentration (Cmax) of 0.8 µM across the SI life cycle. SI bioactivity was assessed in a battery of NAMs relevant to systemic, reproductive, and developmental toxicity; a cell stress panel, high throughput transcriptomics in three cell lines (HepG2, HepaRG and MCF-7 cells), pharmacological profiling and specific assays relating to developmental toxicity (Reprotracker and devTOX quickPredict). Points of Departure (PoDs) for SI ranged from 104 to 5044 µM. Cmax values obtained from PBK modelling of occupational exposures to SI were compared with PoDs from the bioactivity assays to derive Bioactivity Exposure Ratios (BERs) which demonstrated the safety for workers exposed to SI under current levels of factory specific risk management. In summary, the tiered and iterative workflow developed here represents an opportunity for integrating non animal approaches for a large subset of substances for which systemic worker safety assessment is required. Such an approach could be followed to ensure that animal testing is only conducted as a "last resort" e.g. under EU REACH.