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Designing for Knowledge Generalisation in Medical Device Instructions: A Qualitative Study with Healthcare Professionals
No full textBACKGROUND:
Instructional documents are crucial for safely operating medical devices. However, few studies have explicitly considered designing instructions for healthcare professionals (HCPs). Psychological research suggests that advanced learners with prior expertise in a domain are better able to generalise their existing knowledge to new areas compared to those with little prior expertise, resulting in different informational needs.
OBJECTIVE:
We aimed to understand how HCPs learn from, and utilize their existing expertise when interacting with IFUs to familiarize themselves with a novel medical device. This would allow us to understand how explore how instructional documents could be designed to better accommodate HCPs’ needs as experienced learners with prior knowledge in the domain.
METHODS:
We conducted our studies centred around a novel liver support system, the HepatiCan™ and its current instructions for use. We conducted three user studies, first using semi-structured interviews and think-aloud protocols to understand HCPs’ expectations for the process of setting up the HepatiCan™ and how training for the use of medical devices typically takes place. We followed this up with an observational study to understand HCPs’ actual experience in practice and corresponding instructional design needs.
RESULTS:
Our results showed that HCPs’ prior expertise allowed them to prioritise key areas for attention, but also led them to make assumptions, and potentially skim and miss important information. Visual representations and communications were preferred, as well as designs which supported memorization, as this was an essential function of using instruction manuals.
CONCLUSIONS:
Developers must be aware of what is considered ‘common’, and potentially ignored knowledge, within a specific domain in order to clearly emphasise important, safety-relevant information. We also recommend developers focus on utilizing images with attached appendices where possible. This allows advanced users to process information more efficiently without compromising the needs of less familiar users for greater instructional details
From silence into song: an art–science collaboration with survivor trees and laryngectomy singers
No full textINTRODUCTION:
This paper presents an immersive art–science project that unites nature, voice, and technology to examine the dual role of radiation as both a force for destruction and a means of healing, through the experiences of two survivor communities: Hibakujumoku (trees that survived the atomic bombings of Hiroshima and Nagasaki) and individuals who lost their voices to head and neck cancer and rebuilt communication through radiotherapy, surgery, and rehabilitation.
METHODS:
Ten adults, post-laryngectomy, were recruited via Shout at Cancer, a UK charity focused on alaryngeal speech recovery. Over ten weeks, they attended six workshops combining group singing, creative writing, and reflective dialogue. Participants listened and responded to recordings of survivor trees from Japan, captured with contact microphones, accelerometers, and hydrophones. Infrared and thermal imaging revealed hidden vitality. These materials, integrated with participant vocal recordings, formed hybrid works presented as live performances and multimedia installations. Analysed data comprised workshop audio recordings and notes, participant reflections, creative texts where functioning as reflective accounts, researcher field notes and reflexive memos, and written reflections from collaborating artists. Data were analysed using reflexive thematic analysis within an interpretivist, arts-based participatory design.
RESULTS:
Reflexive thematic analysis identified three themes: (1)
Parallel Survivorship
—encounters with trees’ “voices” prompted awe and reframed silence as endurance; (2)
Reclaimed Agency
—co-writing and performance supported identity, confidence, and public presence; (3)
Collective Embodiment
—shared vocal practice with human and non-human sounds fostered synchrony, joy, and social connection. Reflections from collaborating artists described reciprocal change, noting shifts toward listening, service, and shared authorship.
DISCUSSION:
Where radiation carries complex cultural meanings, these findings highlight the importance of reframing it within clinical and public health contexts—as both a source of harm, and a means of healing. The results demonstrate that immersive, nature-linked co-creation not only assists in meaning-making and relational wellbeing for individuals recovering from voice-altering cancer treatments, but also underscores the potential of such approaches to complement healthcare interventions by fostering emotional recovery and social connectedness. The study furthermore strengthens the existing underpinnings for future mixed-methods and longitudinal research to examine the broader impacts of arts–health collaborations
The Discovery of the Hippocampal Place Cells
No full textThis paper describes the events leading up to the discovery of the place cells in 1971 for which the author received the Nobel Prize in Physiology and Medicine in 2014, together with May-Britt and Edvard Moser. In addition, it explores some of the ideas and influences that contributed to the interpretation of that finding as evidence for the Hippocampus as a Cognitive Map. Crucial to the acceptance of the idea of place cells and cognitive maps has been the development of recording technologies, and some of these are covered in the middle section. The final section tries to draw some lessons that the author has reached from his experiences
An adaptive, youth-centred co-design methodology: place-based co-design centring youth and community participation
No full textBACKGROUND: Co-design approaches are increasingly used in efforts to address complex challenges, such as adolescent mental health. Benefits of these approaches are multifaceted and include strategies that better reflect local perspectives and needs, as well as the potential for improved outcomes for those involved. However, the literature has highlighted challenges and unintended consequences of co-design, such as issues with inclusivity and undue burden being placed on participants. This paper examines the methods used in the 'Deeper Discovery and Co-design phase' of Kailo, a place-based research and design initiative aimed at tackling the social determinants of children's and young people's (CYP) mental health in their local communities. METHODS: Over approximately nine months, a co-design approach was used across two pilot sites. This involved more than 69 workshops and several ad hoc engagements with CYP and other community members. The goal was to explore structural challenges and develop strategies to address CYP mental health and wellbeing in their local context. The co-design work also aimed to bring together community knowledge and expertise, systems mapping and academic evidence. RESULTS: Over 300 local CYP, community members, professionals and practitioners participated or contributed to Kailo's Deeper Discovery phase across the two pilot sites, via group sessions, individual feedback or surveys. The study identifies key barriers (e.g. logistical constraints, limitations in accessibility of processes and participation, safeguarding and participant wellbeing concerns) and enablers (e.g. flexible and accessible participation, inclusive and adaptive facilitation, and participation and influence) that shaped conditions for implementation. Moreover, it explores the requirements and tensions for methodological implementation whilst maintaining a flexible and adaptive approach, centring CYP needs and voices, and integrating different methods into the co-design process. CONCLUSIONS: The Kailo programme prioritised the contributions of CYP and their community, aiming to foster inclusive and diverse engagement through a distinctive, adaptive, youth-centred approach. This paper outlines the co-design methodology used to support the development of locally relevant strategies addressing the social determinants of mental health. However, balancing flexibility and adaptability and centring CYP need, voices and agency, whilst maintaining a focus on broader structural issues remains a challenge
Shape matters: Predicting Huntington’s disease using progression modelling
No full textBackground:
Despite evidence of group-level differences in striatal morphometry among persons with Huntington’s Disease (PwHD), current models of HD progression used for participant selection and assessment of treatment outcomes in clinical trials do not leverage shape information.
Methods:
We first validated the capability of a discriminative deep neural network to derive descriptors of shape from all subcortical structures affected by HD, utilizing 2,932 brain scans in 615 PwHD across three longitudinal datasets (TRACK-HD, PREDICT-HD, and IMAGE-HD). We then trained a conditional generative model that used shape descriptors, alongside conventional volumetric, genetic, as well as composite cognitive, motor, and functional features at baseline to predict biomarkers of disease progression at subsequent time points.
Results:
We observed that the anatomical shapes of subcortical structures, including putamen, lateral ventricle, pallidum, caudate, thalamus, and accumbens, exhibited strong associations with HD progression, as measured by a commonly used prognostic score. Furthermore, within-stage heterogeneity, along the continuum of disease progression, was better captured: when shape descriptors were aggregated using principal component analysis, they showed a high correlation with disease stage (Spearman’s correlation: ρ = 0.72), compared to volumetric measurements in cubic millimetres (ρ = 0.45). Finally, incorporating subcortical shape into the generative model improved predictive performance, compared to the same model that relied solely on brain volumes.
Conclusion:
This study demonstrates that subcortical brain shape is associated with HD progression, enables capturing fine-grained within-stage variability, and improves the predictability of characteristic biomarkers. The findings could potentially optimize future clinical trials through more targeted participant recruitment and more objective post-intervention assessments of treatment efficacy
Aminoglycosides, vancomycin, and metronidazole for people with cirrhosis and hepatic encephalopathy
No full textRationale:
Hepatic encephalopathy is a common complication of cirrhosis. Its development is associated with increased morbidity and mortality. Its exact pathogenesis is unknown, but ammonia, produced by bacterial action in the intestine, plays a key role. Antibiotics modulate the gut flora and may reduce intestinal ammonia production. Aminoglycosides such as neomycin, paromomycin, and ribostamycin have been used to treat hepatic encephalopathy, as have other antibiotics such as vancomycin and metronidazole.
Objectives:
To assess the beneficial and harmful effects of aminoglycosides, vancomycin, and metronidazole versus placebo, no intervention, other antibiotics, or other active pharmacological interventions, for the prevention and treatment of hepatic encephalopathy in people with cirrhosis.
Search methods:
We searched the Cochrane Hepato‐Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, and three other databases to 15 April 2025. We also searched online trials registries for ongoing and unpublished trials, undertook manual searches of meeting and conference proceedings, checked bibliographies of relevant articles, and corresponded with investigators and pharmaceutical companies.
Eligibility criteria:
We included randomised clinical trials (RCTs) involving participants with cirrhosis and hepatic encephalopathy, or who were at risk of developing hepatic encephalopathy, comparing aminoglycosides, vancomycin, or metronidazole to (1) placebo or no intervention; or (2) other pharmacological agents, including non‐absorbable disaccharides, other antibiotics, or other potentially beneficial agents (e.g. branched‐chain amino acids, L‐ornithine L‐aspartate, nitazoxanide (a broad‐spectrum antiparasitic/antiviral agent), and nicotinohydroxamic acid (a potent urease inhibitor). We included trials irrespective of publication status, outcomes reported, language, or blinding. We excluded trials involving people with hepatic encephalopathy associated with acute liver failure or with non‐cirrhotic portal hypertension.
Outcomes:
The critical outcomes were all‐cause mortality, hepatic encephalopathy, and serious adverse events. The important outcomes were non‐serious adverse events and health‐related quality of life (HRQoL). Our primary time point was the maximum length of follow‐up.
Risk of bias:
We used Cochrane's original risk of bias tool (RoB 1) to assess the risk of bias.
Synthesis methods:
We used standard Cochrane methods. We undertook random‐effects meta‐analyses to calculate risk ratios (RRs) or standardised mean differences (SMDs), with 95% confidence intervals (CIs). We assessed heterogeneity with the I2 statistic, and the certainty of evidence with the GRADE framework.
Included studies:
We included 24 RCTs, involving 1405 participants experiencing 1418 hepatic encephalopathy events. Twenty‐three trials evaluated the treatment of hepatic encephalopathy and one, the secondary prevention of hepatic encephalopathy; we analysed these trials jointly. The trials assessed three aminoglycosides: neomycin (15 trials), paromomycin (three trials), and ribostamycin (one trial), as well as vancomycin (two trials), and metronidazole (three trials). Overall, 670 participants received these pharmacotherapies while 735 participants received a placebo or other potentially beneficial agents. We classified 22 of the 24 trials to be at an overall high risk of bias based on domain‐level assessments.
Synthesis of results:
The certainty of evidence for all comparisons was low to very low, mainly due to risk of bias, imprecision, and heterogeneity.
Twenty‐three of the 24 trials, involving 1383 participants, reported all‐cause mortality data. Aminoglycosides may increase mortality slightly compared to other potentially active agents (RR 1.64, 95% CI 1.03 to 2.62; I² = 0%; 3 studies, 166 participants). The evidence was very uncertain about whether aminoglycosides versus a placebo (RR 1.02, 95% CI 0.62 to 1.69; I² = 0%; 3 studies, 137 participants), non‐absorbable disaccharides (RR 1.21, 95% CI 0.57 to 2.59; I² not applicable; 4 studies, 266 participants), or other antibiotics (RR 1.00, 95% CI 0.24 to 4.23; I² = 83%; 8 studies, 496 participants) result in a difference in mortality risk. The evidence was also very uncertain when comparing vancomycin to non‐absorbable disaccharides (RR 0.94, 95% CI 0.26 to 3.40; I² not applicable; 2 studies, 72 participants), and metronidazole to other active agents (RR 0.97, 95% CI 0.14 to 6.66; I² = 0%; 3 studies, 242 participants).
Nineteen trials involving 1281 participants reported data on hepatic encephalopathy. There may be little to no difference in the effects of aminoglycosides versus non‐absorbable disaccharides (RR 0.84, 95% CI 0.67 to 1.05; I² = 0%; 3 studies, 251 participants), aminoglycosides versus other potentially active agents (RR 1.21, 95% CI 0.79 to 1.85; I² = 0%; 3 studies, 166 participants), and metronidazole versus other active agents (RR 1.50, 95% CI 0.89 to 2.54; I² = 48%; 2 studies, 208 participants). The evidence is very uncertain about the effect of aminoglycosides versus placebo, other antibiotics, and vancomycin versus non‐absorbable disaccharides.
Twenty trials, involving 1186 participants, reported a total of 328 serious adverse events. Aminoglycosides may slightly increase the risk of serious adverse events compared with other potentially active agents (RR 1.60, 95% CI 1.03 to 2.47; I² = 0%; 3 studies, 166 participants). The evidence is very uncertain when comparing aminoglycosides to placebo and other antibiotics, or when comparing vancomycin to non‐absorbable disaccharides.
Eighteen trials, involving 922 participants, reported a total of 96 non‐serious adverse events. There may be a slight increase in the risk of adverse events when comparing aminoglycosides to placebo (RR 2.80, 95% CI 1.11 to 7.04; I² not applicable; 2 studies, 98 participants), and to other antibiotics (RR 3.24, 95% CI 1.08 to 9.70; I² = 0%; 8 studies, 251 participants). The evidence is very uncertain about the effects of aminoglycosides versus non‐absorbable disaccharides or other active agents, and metronidazole versus other active agents.
Only one trial assessed HRQoL, but reported the data in a form that precluded meta‐analysis.
Eight trials received support from pharmaceutical companies while six did not. Ten trials did not provide this information.
Authors' conclusions:
Due to low‐ or very low‐certainty evidence, we do not know if aminoglycosides benefit hepatic encephalopathy compared to placebo or other potentially active agents. There may be a slight increase in the risks of mortality and serious adverse events with aminoglycosides compared to other agents, and of non‐serious adverse events when compared to placebo and other antibiotics. We do not know if vancomycin or metronidazole improve clinically relevant outcomes. Only one trial assessed health‐related quality of life.
Funding:
This Cochrane review received no specific funding
Adolescents' Relationships With Their Parents and Peers as Mediators Between Economic Circumstances and Emotional Symptoms: A Multicountry Longitudinal Analysis
No full textOBJECTIVE: Adolescents' social relationships might partly explain the increased risk of mental health problems in adolescents living in poorer economic circumstances. There are few studies in low- and middle-income countries where most of the world's adolescents live. We investigated whether adolescents' relationships with their parents and peers mediated the association between their economic circumstances and emotional symptoms in Ethiopia, India, Peru and Vietnam. METHOD: We analyzed longitudinal data of 3,529 adolescents from the Young Lives study (1,741 female [49.3%]). Household consumption expenditure and adolescents' subjective assessment of household wealth were measured at age 15. The mediators - adolescents' positive relations with their parents and peers - were measured at age 19. The outcome - emotional symptoms, characterized by low mood and anxiety - was measured at age 22. Mediation was assessed through counterfactual g-computation formula, adjusting for baseline and intermediate confounders. RESULTS: We found no evidence that adolescents' positive relations with their parents or peers mediated the association between economic circumstances and emotional symptoms in any country. Living in poorer economic circumstances was typically associated with more severe emotional symptoms. CONCLUSION: Adolescents' parent and peer relationships might not mediate the effects of poorer economic circumstances on emotional symptoms in these countries, contrasting with previous studies that highlight an important role in high-income countries. Further research is needed that addresses our study limitations and to also explore other potential mechanisms, including different aspects of social relationships, that might influence mental health outcomes for adolescents living in poverty across different settings
Beyond the Hodge theorem: Curl and asymmetric pseudodifferential projections
No full textWe develop a new approach to the study of spectral
asymmetry. Working with the operator curl ∶= ∗d on a
connected oriented closed Riemannian 3-manifold, we
construct, by means of microlocal analysis, the asymmetry operator — a scalar pseudodifferential operator
of order −3. The latter is completely determined by the
Riemannian manifold and its orientation, and encodes
information about spectral asymmetry. The asymmetry operator generalises and contains the classical eta
invariant traditionally associated with the asymmetry
of the spectrum, which can be recovered by computing its regularised operator trace. Remarkably, the whole
construction is direct and explicit
Most ventral pallidal cholinergic neurons are bursting basal forebrain cholinergic neurons with mesocorticolimbic connectivity
No full textThe ventral pallidum (VP) lies at the intersection of basal ganglia and basal forebrain circuitry, possessing attributes of both major subcortical systems. Basal forebrain cholinergic neurons are rapidly recruited by reinforcement feedback and project to cortical and subcortical forebrain targets; in contrast, striatal cholinergic cells are local interneurons exhibiting classical 'pause-burst' responses to rewards. However, VP cholinergic neurons (VPCNs) are less characterized, and it is unclear whether basal forebrain and striatal type cholinergic neurons mix in the VP. Therefore, we performed anterograde and mono-transsynaptic retrograde labeling, in vitro acute slice recordings and bulk calcium recordings of VPCNs in mice of either sex. We found that VPCNs broadly interact with the mesocorticolimbic circuit that processes rewards and punishments, targeting the basolateral amygdala, the medial prefrontal cortex and the lateral habenula, while receiving inputs from the nucleus accumbens, hypothalamus, central amygdala, bed nucleus of stria terminalis and the ventral tegmental area. Bulk calcium recordings revealed that VPCNs responded to rewards, punishments and reward-predicting cues. Acute slice recordings showed that most VPCNs resembled the bursting type of basal forebrain cholinergic neurons (BFCNs), while a few of them were of the regular rhythmic type, which differentiated most VPCNs from striatal cholinergic interneurons. These results were confirmed by in vivo electrophysiological recordings of putative VPCNs. We conclude that VPCNs show burst firing and specialized connectivity to relay aversive and appetitive stimuli to the reinforcement circuitry, possibly implicated in mood disorders and addiction.Significance statement The ventral pallidum is a special brain area, being part of both the basal ganglia system implicated in goal-directed behavior and the basal forebrain system implicated in learning and attention. It houses, among others, neurons that release the neurotransmitter acetylcholine. While these cholinergic neurons have distinct characteristics in other regions of the basal ganglia and basal forebrain, it is unclear whether those in the ventral pallidum resemble one or the other or both. Here we demonstrate that they are closer to basal forebrain cholinergic neurons both anatomically and functionally, especially resembling a burst-firing subtype thereof. In accordance, we found that they convey information about aversive and appetitive stimuli to the reinforcement circuitry, possibly implicated in mood disorders and addiction
Assessing greenspace and cardiovascular disease risk through deep learning analysis of street-view imagery in the US-based nationwide Nurses' Health Study
No full textBACKGROUND: Living near greenspace is associated with decreased cardiovascular disease (CVD). Greenspace estimates, however, typically represent all types of vegetation using top-down satellite images, which incorporate exposure misclassification and limit policy relevance. OBJECTIVE: We studied the association between street-view greenspace measures with incident CVD using a large, long-term prospective US cohort of female nurses. METHODS: We estimated the percentage of streetscapes composed of visible trees, grass, and other green (plants/flowers/fields) from 350 million street-view images using deep learning models. Estimates were applied to Nurses' Health Study participants (N = 88,788) within 500 m of their residential addresses. We used Cox models to estimate associations from 2000 to 2018 between street-view greenspace measures and risk of incident CVD, assessed through self-report, medical record review, or death certificates, and adjusted for individual- and area-level factors. RESULTS: In adjusted models, higher percentages of visible trees were associated with lower CVD incidence (hazard ratio [HR] per interquartile range [IQR] 0.96 (95% confidence interval 0.93, 1.00]), while higher percentages of visible grass (HR 1.06 [1.02, 1.11]) and other green space types (HR 1.03 [1.01, 1.04]) were associated with higher CVD incidence. We did not observe evidence of effect modification by population density, Census region, air pollution, satellite-based vegetation, or neighborhood socioeconomic status. Findings were robust to adjustment for other spatial and behavioral factors and persisted even after adjustment for traditional satellite-based vegetation indices. DISCUSSION: Specific greenspace types may be protective or harmful for CVD. Aggregating greenspace into a single exposure category limits epidemiological research and potential interventions to increase health-promoting greenspace