Post-trial access to implantable neural devices: an exploratory international survey.

Objectives: Clinical trials of innovative neural implants are rapidly increasing and diversifying, but little is known about participants' post-trial access to the device and ongoing clinical care. This exploratory study examines common practices in the planning and coordination of post-trial access to neurosurgical devices. We also explore the perspectives of trial investigators on the barriers to post-trial access and ongoing care, as well as ethical questions related to the responsibilities of key stakeholder groups. Design setting and participants: Trial investigators (n=66) completed a survey on post-trial access in the most recent investigational trial of a surgically implanted neural device they had conducted. Survey respondents predominantly specialized in neurosurgery, neurology and psychiatry, with a mean of 14.8 years of experience working with implantable neural devices. Main outcome measures: Outcomes of interest included rates of device explantation during or at the conclusion of the trial (pre-follow-up) and whether plans for post-trial access were described in the study protocol. Outcomes also included investigators' greatest 'barrier' and 'facilitator' to providing research participants with post-trial access to functional implants and perspectives on current arrangements for the sharing of post-trial responsibilities among key stakeholders. Results: Trial investigators reported either 'all' (64%) or 'most' (33%) trial participants had remained implanted after the end of the trial, with 'infection' and 'non-response' the most common reasons for explantation. When asked to describe the main barriers to facilitating post-trial access, investigators described limited funding, scarcity of expertise and specialist clinical infrastructure and difficulties maintaining stakeholder relationships. Notwithstanding these barriers, investigators overwhelmingly (95%) agreed there is an ethical obligation to provide post-trial access when participants individually benefit during the trial. Conclusions: On occasions when devices were explanted during or at the end of the trial, this was done out of concern for the safety and well-being of participants. Further research into common practices in the post-trial phase is needed and essential to ethical and pragmatic discussions regarding stakeholder responsibilities.

A lower connection to nature is related to lower mental health benefits from nature contact.

Increasing evidence demonstrates the psychological benefits of nature contact. However, the evidence is often established at the population level, and the individual differences in the psychological benefits gained from nature are considered negligible variations. In this study, we performed a cross-sectional online survey in Brisbane and Sydney, Australia, from April 15th and May 15th, 2021 around one year after the first covid-19 pandemic lockdowns. The results show that individuals with a stronger connection to nature are linked with a lower level of stress and anxiety with increased frequency in public greenspace visits, while such an association is less clear for individuals with a weaker connection to nature. We also find that, through the answer to an open-ended question, individuals with a lower connection to nature tend to mention nature-related words less as the reason for visiting greenspace. This indicates that a person's connection to nature is linked with how they interact with nature and thus might determine whether and how much psychological benefit a person gains from experiencing nature.

Engaging community pharmacies in practice-based research: Lessons from opioid-focused research.

There is an established need to translate evidence-based practices into real-world practice. Community pharmacists and their corresponding pharmacies are well-positioned to be effective partners as researchers seek to study and implement practice-based research. Challenges exist when partnering with community pharmacies which can vary based on the study type, the nature of the community pharmacy, and stakeholder groups (i.e., patients, staff, leadership, physicians). This commentary seeks to describe these challenges and provide recommendations that can help mitigate and/or overcome these challenges. Recommendations are provided for team structure, communication, research tools/technology, motivational factors, workflow, and sustainability. These recommendations are based on the authors' experience in partnering with community pharmacy for opioid-related research in a variety of study types, states, and pharmacy environments.

Coarse-grained versus fully atomistic machine learning for zeolitic imidazolate frameworks.

Zeolitic imidazolate frameworks are widely thought of as being analogous to inorganic AB2 phases. We test the validity of this assumption by comparing simplified and fully atomistic machine-learning models for local environments in ZIFs. Our work addresses the central question to what extent chemical information can be "coarse-grained" in hybrid framework materials.

Advancing the digital and computational capabilities of healthcare providers: A qualitative study of a hospital organisation in the NHS.

Objective: Healthcare systems require transformation to meet societal challenges and projected health demands. Digital and computational tools and approaches are fundamental to this transformation, and hospitals have a key role to play in their development and implementation. This paper reports on a study with the objective of exploring the challenges encountered by hospital leaders and innovators as they implement a strategy to become a data-driven hospital organisation. In doing so, this paper provides guidance to future leaders and innovators seeking to build computational and digital capabilities in complex clinical settings. Methods: Interviews were undertaken with 42 participants associated with a large public hospital organisation within England's National Health Service. Using the concept of institutional readiness as an analytical framework, the paper explores participants' perspectives on the organisation's capacity to support the development of, and benefit from, digital and computational approaches. Results: Participants' accounts reveal a range of specific institutional readiness criteria relating to organisational vision, technical capability, organisational agility, and talent and skills that, when met, enhance the organisations' capacity to support the development and implementation of digital and computational tools. Participant accounts also reveal challenges relating to these criteria, such as unrealistic expectations and the necessary prioritisation of clinical work in resource-constrained settings. Conclusions: The paper identifies a general set of institutional readiness criteria that can guide future hospital leaders and innovators aiming to improve their organisation's digital and computational capability. The paper also illustrates the challenges of pursuing digital and computational innovation in resource-constrained hospital environments.

Burnout in International Medical Graduate Trainees in the United Kingdom Compared to Domestic Medical Graduate Trainees. Analysis of Data from the GMC's National Training Survey in 2019 and 2021.

Introduction: International Medical Graduates (IMGs) have lower educational attainment and a higher rate of complaints against them compared to Domestic Medical Graduates (DMG). The aim of this study was to investigate the potential role of burnout on these adverse outcomes experienced by IMGs. Methods: Every year, the General Medical Council (GMC) conducts the National Training Survey of all doctors in the United Kingdom which includes optional questions on work-related burnout from the Copenhagen Burnout Inventory (CBI). Work-related burnout data for doctors in training, linked to country of Primary Medical Qualification were obtained from the GMC for the years 2019 and 2021. Burnout scores of IMGs and DMGs were compared using Chi2. Results: The total number of eligible participants in 2019 and 2021 was 56,397 and 61,313 respectively. The response rates for all doctors in training to the CBI were 35,739 (63.4%) in 2019, and 28,310 (46.2%) in 2021. IMGs were at a lower risk of burnout compared to DMGs, 2,343 (42.9%) vs 15,497 (51.2%), Odds Ratio (OR) 0.72 (CI 0.68-0.76, P < 0.001) in 2019; and 2,774 (50.2%) vs 13,000 (57.1%), OR 0.76 (CI 0.71-0.80, P < 0.001) in 2021. Discussion: IMGs, as a group, appear to be at a lower risk of work-related burnout compared to DMGs. Burnout is unlikely to be contributing to lower educational attainment and higher rates of complaints experienced by IMGs compared to DMGs.

How to validate machine-learned interatomic potentials.

Machine learning (ML) approaches enable large-scale atomistic simulations with near-quantum-mechanical accuracy. With the growing availability of these methods, there arises a need for careful validation, particularly for physically agnostic models-that is, for potentials that extract the nature of atomic interactions from reference data. Here, we review the basic principles behind ML potentials and their validation for atomic-scale material modeling. We discuss the best practice in defining error metrics based on numerical performance, as well as physically guided validation. We give specific recommendations that we hope will be useful for the wider community, including those researchers who intend to use ML potentials for materials "off the shelf."

Nature experience from yards provide an important space for mental health during Covid-19.

Urban dwellers' use of public and private green spaces may have changed during the early years of the Covid-19 pandemic due to movement restriction. A survey was deployed in Brisbane and Sydney, Australia 1 year after the start of Covid-19 restrictions (April 2021) to explore relationships of mental health and wellbeing to different patterns of private yard versus public green space visitation. More frequent yard use during the initial year of Covid-19 was correlated with lower stress, depression, and anxiety and higher wellbeing. However, greater duration of yard visits (week prior to survey) was associated with higher stress, anxiety, and depression scores, potentially because individuals may seek to use nature spaces immediately available for emotional regulation during difficult times. The results highlight the importance of yards for mental health and wellbeing during the Covid-19 pandemic and that relationships between nature interaction and mental health may be context and timeframe dependent.

Visiting Urban Green Space and Orientation to Nature Is Associated with Better Wellbeing during COVID-19.

The COVID-19 pandemic has severely challenged mental health and wellbeing. However, research has consistently reinforced the value of spending time in green space for better health and wellbeing outcomes. Factors such as an individual's nature orientation, used to describe one's affinity to nature, may influence an individual's green space visitation behaviour, and thus influence the wellbeing benefits gained. An online survey in Brisbane and Sydney, Australia (n = 2084), deployed during the COVID-19 pandemic (April 2021), explores if nature experiences and nature orientation are positively associated with personal wellbeing and if increased amounts of nature experiences are associated with improvement in wellbeing in the first year of the COVID-19 pandemic. We found that both yard and public green space visitation, as well as nature orientation scores, were correlated with high personal wellbeing scores, and individuals who spent more time in green space compared to the previous year also experienced a positive change in their health and wellbeing. Consistently, people with stronger nature orientations are also more likely to experience positive change. We also found that age was positively correlated to a perceived improvement in wellbeing over the year, and income was negatively correlated with a decreased change in wellbeing over the year, supporting other COVID-19 research that has shown that the effects of COVID-19 lifestyle changes were structurally unequal, with financially more established individuals experiencing better wellbeing. Such results highlight that spending time in nature and having high nature orientation are important for gaining those important health and wellbeing benefits and may provide a buffer for wellbeing during stressful periods of life that go beyond sociodemographic factors.

Imaginaries of the data-driven hospital in a time of crisis.

This article uses the concept of sociotechnical imaginaries to explore how public hospitals are being reimagined and reconfigured by promissory digital health. Drawing on interviews with 42 senior leaders and staff from a large NHS hospital organisation, the article describes the imaginary of a data-driven hospital and the tensions of its operationalisation. These relate to data quality, data curation and data access, and reflect a discord between the organisation's commitment to immediate patient care and its research aspirations. These tensions, however, serve to invigorate, rather than undermine, the sociotechnical imaginary of a data-driven hospital, as they prompt the translation of a general data-driven imaginary into specific sociotechnical arrangements. The article argues that the potency of the data-driven hospital imaginary must be understood in terms of its enchanting qualities: it has the capacity to excite hospital staff and to align distinct and potentially diverging hopes and expectations regarding the societal role of public hospitals. The article concludes by suggesting that the entrenchment of the data-driven imaginary can be partly explained by its strategic utility for severely resource-constrained healthcare organisations: it provides a means for organisations to position themselves towards a viable future in an otherwise dire health-care context.

Duo Shared Genomic Segment analysis identifies a genome-wide significant risk locus at 18q21.33 in myeloma pedigrees.

AIM: High-risk pedigrees (HRPs) are a powerful design to map highly penetrant risk genes. We previously described Shared Genomic Segment (SGS) analysis, a mapping method for single large extended pedigrees that also addresses genetic heterogeneity inherent in complex diseases. SGS identifies shared segregating chromosomal regions that may inherit in only a subset of cases. However, single large pedigrees that are individually powerful (at least 15 meioses between studied cases) are scarce. Here, we expand the SGS strategy to incorporate evidence from two extended HRPs by identifying the same segregating risk locus in both pedigrees and allowing for some relaxation in the size of each HRP. METHODS: Duo-SGS is a procedure to combine single-pedigree SGS evidence. It implements statistically rigorous duo-pedigree thresholding to determine genome-wide significance levels that account for optimization across pedigree pairs. Single-pedigree SGS identifies optimal segments shared by case subsets at each locus across the genome, with nominal significance assessed empirically. Duo-SGS combines the statistical evidence for SGS segments at the same genomic location in two pedigrees using Fisher's method. One pedigree is paired with all others and the best duo-SGS evidence at each locus across the genome is established. Genome-wide significance thresholds are determined through distribution-fitting and the Theory of Large Deviations. We applied the duoSGS strategy to eleven extended, myeloma HRPs. RESULTS: We identified one genome-wide significant region at 18q21.33 (0.85 Mb, P = 7.3 × 10-9) which contains one gene, CDH20. Thirteen regions were genome-wide suggestive: 1q42.2, 2p16.1, 3p25.2, 5q21.3, 5q31.1, 6q16.1, 6q26, 7q11.23, 12q24.31, 13q13.3, 18p11.22, 18q22.3 and 19p13.12. CONCLUSION: Our results provide novel risk loci with segregating evidence from multiple HRPs and offer compelling targets and specific segment carriers to focus a future search for functional variants involved in inherited risk formyeloma.

Droplet-based vitrification of adherent human induced pluripotent stem cells on alginate microcarrier influenced by adhesion time and matrix elasticity.

The gold standard in cryopreservation is still conventional slow freezing of single cells or small aggregates in suspension, although major cell loss and limitation to non-specialised cell types in stem cell technology are known drawbacks. The requirement for rapidly available therapeutic and diagnostic cell types is increasing constantly. In the case of human induced pluripotent stem cells (hiPSCs) or their derivates, more sophisticated cryopreservation protocols are needed to address this demand. These should allow a preservation in their physiological, adherent state, an efficient re-cultivation and upscaling upon thawing towards high-throughput applications in cell therapies or disease modelling in drug discovery. Here, we present a novel vitrification-based method for adherent hiPSCs, designed for automated handling by microfluidic approaches and with ready-to-use potential e.g. in suspension-based bioreactors after thawing. Modifiable alginate microcarriers serve as a growth surface for adherent hiPSCs that were cultured in a suspension-based bioreactor and subsequently cryopreserved via droplet-based vitrification in comparison to conventional slow freezing. Soft (0.35%) versus stiff (0.65%) alginate microcarriers in concert with adhesion time variation have been examined. Findings revealed specific optimal conditions leading to an adhesion time and growth surface (matrix) elasticity dependent hypothesis on cryo-induced damaging regimes for adherent cell types. Deviations from the found optimum parameters give rise to membrane ruptures assessed via SEM and major cell loss after adherent vitrification. Applying the optimal conditions, droplet-based vitrification was superior to conventional slow freezing. A decreased microcarrier stiffness was found to outperform stiffer material regarding cell recovery, whereas the stemness characteristics of rewarmed hiPSCs were preserved.

Shifting Patterns of Summer Lake Color Phenology in Over 26,000 US Lakes.

Lakes are often defined by seasonal cycles. The seasonal timing, or phenology, of many lake processes are changing in response to human activities. However, long-term records exist for few lakes, and extrapolating patterns observed in these lakes to entire landscapes is exceedingly difficult using the limited number of available in situ observations. Limited landscape-level observations mean we do not know how common shifts in lake phenology are at macroscales. Here, we use a new remote sensing data set, LimnoSat-US, to analyze U.S. summer lake color phenology between 1984 and 2020 across more than 26,000 lakes. Our results show that summer lake color seasonality can be generalized into five distinct phenology groups that follow well-known patterns of phytoplankton succession. The frequency with which lakes transition from one phenology group to another is tied to lake and landscape level characteristics. Lakes with high inflows and low variation in their seasonal surface area are generally more stable, while lakes in areas with high interannual variations in climate and catchment population density show less stability. Our results reveal previously unexamined spatiotemporal patterns in lake seasonality and demonstrate the utility of LimnoSat-US, which, with over 22 million remote sensing observations of lakes, creates novel opportunities to examine changing lake ecosystems at a national scale.

Enhancement motivations for using prescription drugs among young adults in Nigeria.

BACKGROUND: The desire for enhancement is a common motive for non-medical use of prescription drugs in Western countries. Little is known about the factors that motivate use in non-Western contexts. METHODS: The study explores access to prescription drugs and the motivations for using them among educated young adults in a city located in Anambra State, South-Eastern Nigeria. Semi-structured interviews were conducted with 23 participants aged 23-29 years. Data were thematically analysed using NVivo 12 Software. RESULTS: The data indicate that prescription drugs are widely available and easy to access without a prescription in the unregistered 'pharmacies' and medicine shops that form part of Nigeria's informal healthcare system. Social networks are also a source of drugs. Participants shared detailed perspectives on their use of prescription drugs, revealing that codeine, Rohypnol, and high doses of tramadol are used to enhance performance in several social life domains. These drugs were described as enhancing performance and productivity in the workplace, and were taken by participants working as labourers and sales representatives. Male participants also shared accounts of using high doses of tramadol to improve stamina and skill in sports. Some participants took Rohypnol to enhance their creative and academic performance. Participants stated that drug use enabled them to meet the pressures associated with work, academia, and parental expectations. CONCLUSION: The findings suggest that prescription drugs are being strategically and instrumentally deployed by users to enhance different domains of social life. This is driven by users' experiences of the drugs' bodily effects, and it is supported by a context in which self-medication and informal healthcare are common. Participants' reasons for seeking drug-induced enhancement reflect sociocultural factors within Nigeria and some West African countries, such as employment scarcity and the championing of sporting prowess. The findings can be used to inform the design of tailored approaches to reduce the harms presented by the non-medical use of pharmaceuticals among young adults.

Artificial lake expansion amplifies mercury pollution from gold mining.

Artisanal and small-scale gold mining (ASGM) is the largest global source of anthropogenic mercury emissions. However, little is known about how effectively mercury released from ASGM is converted into the bioavailable form of methylmercury in ASGM-altered landscapes. Through examination of ASGM-impacted river basins in Peru, we show that lake area in heavily mined watersheds has increased by 670% between 1985 and 2018 and that lakes in this area convert mercury into methylmercury at net rates five to seven times greater than rivers. These results suggest that synergistic increases in lake area and mercury loading associated with ASGM are substantially increasing exposure risk for people and wildlife. Similarly, marked increases in lake area in other ASGM hot spots suggest that "hydroscape" (hydrological landscape) alteration is an important and previously unrecognized component of mercury risk from ASGM.