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."

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.

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.

Using spectroscopy to probe relaxation, decoherence, and localization of photoexcited states in π-conjugated polymers.

We use the coarse-grained Frenkel-Holstein model to simulate the relaxation, decoherence, and localization of photoexcited states in conformationally disordered π-conjugated polymers. The dynamics are computed via wave-packet propagation using matrix product states and the time evolution block decimation method. The ultrafast (i.e., t < 10 fs) coupling of an exciton to C-C bond vibrations creates an exciton-polaron. The relatively short (ca. 10 monomers) exciton-phonon correlation length causes ultrafast exciton-site decoherence, which is observable on conformationally disordered chains as fluorescence depolarization. Dissipative coupling to the environment (modelled via quantum jumps) causes the localization of quasi-extended exciton states (QEESs) onto local exciton ground states (LEGSs, i.e., chromophores). This is observable as lifetime broadening of the 0-0 transition (and vibronic satellites) of the QEES in two-dimensional electronic coherence spectroscopy. However, as this process is incoherent, neither population increases of the LEGSs nor coherences with LEGSs are observable.

The relationship between endometriosis-related pelvic pain and symptom frequency, and subjective wellbeing.

BACKGROUND: This exploratory study sought to establish the relationship between endometriosis-related pelvic pain, endometriosis symptom-frequency, and women's subjective wellbeing (SWB). METHODS: A purposive sample (N = 2061) of women with endometriosis aged between 18 and 62 years (M = 30.49 ± 7.45) completed an online questionnaire containing a measure of pelvic pain (Biberoglu & Behrman Scale; B&B), endometriosis symptom frequency, and an established measure of SWB (Personal Wellbeing Index: PWI). RESULTS: Mean SWB total scores (58.35 ± 17.90) were considerably lower than those of women in the general population (western normative range = 70-80; mean = 76). On average, women reported moderate levels of pelvic pain (B&B mean = 5.96 ± 1.84), with a mean of 10.87 (± 4.81) endometriosis-related symptoms across the sample. Significant relationships were found between pelvic pain and SWB dimension and total scores (r's = - 0.20 to - 0.43, all p's < .001), and significant small to medium associations between symptom frequency and all but one of the dimensions of SWB (r's = - 0.12 to - 0.23, all p's < .007). In multivariate regression models accounting for age and delay in diagnosis, higher levels of pelvic pain were significantly associated with lower SWB scores across all eight dimensions of the PWI and total score (all p's < .002). Greater symptom frequency was significantly associated with lower levels of SWB for the dimensions of health, future security, life as a whole, and total scores (all p's < .002). CONCLUSIONS: SWB was lower in women with endometriosis than SWB in women from the general population, and endometriosis related symptoms and pelvic pain explain significant proportions of the unique variance in women's SWB scores. Psychosocial support is needed for women dealing with endometriosis-related symptoms and pain in order to improve their wellbeing and quality of life.

Learning from deep brain stimulation: the fallacy of techno-solutionism and the need for 'regimes of care'.

Deep brain stimulation (DBS) is an effective treatment for the debilitating motor symptoms of Parkinson's disease and other neurological disorders. However, clinicians and commentators have noted that DBS recipients have not necessarily experienced the improvements in quality of life that would be expected, due in large part to what have been described as the 'psychosocial' impacts of DBS. The premise of this paper is that, in order to realise the full potential of DBS and similar interventions, clinical services need to be arranged in such a way that these psychosocial dimensions are recognised and managed. Our starting point is that the psychosocial effects of DBS 'in the field' present us with analytically-useful disruptions: they disturb and foreground deeply held assumptions relating to the individual, health and its treatment, and which in a crude form manifest as the myth of technological solutionism within health care. Drawing on scholarship in medical sociology and science and technology studies (STS), we argue that DBS brings to the fore the relational dimensions of personhood, and demonstrates the emotional and social turmoil that can result if the relational dimensions of personhood are ignored by clinical services. In light of this, we argue that DBS should be implemented within a regime of care. Drawing on ethnographic research of a paediatric DBS clinical service, we provide an example of a regime of care, and conclude by reflecting on what other DBS services might learn from this paediatric service.

Accelerating Innovation in the Creation of Biovalue: The Cell and Gene Therapy Catapult.

The field of regenerative medicine (RM) has considerable therapeutic promise that is proving difficult to realize. As a result, governments have supported the establishment of intermediary agencies to "accelerate" innovation. This article examines in detail one such agency, the United Kingdom's Cell and Gene Therapy Catapult (CGTC). We describe CGTC's role as an accelerator agency and its value narrative, which combines both "health and wealth." Drawing on the notion of sociotechnical imaginaries, we unpack the tensions within this narrative and its instantiation as the CGTC cell therapy infrastructure is built and engages with other agencies, some of which have different priorities and roles to play within the RM field.

Postdispersal Infection and Disease Development of Pyrenophora semeniperda in Bromus tectorum Seeds.

The Ascomycete fungus, Pyrenophora semeniperda, attacks a broad range of cool-season grasses. While leaf and predispersal infection of seeds (i.e., florets containing caryopses) have been previously characterized, little is known about the pathogenesis of mature seeds following dispersal. In this study, we examined infection and disease development of P. semeniperda on dormant seeds of Bromus tectorum. Inoculated seeds were hydrated at 20°C for up to 28 days. Disease development was characterized using scanning electron and light microscopy. P. semeniperda conidia germinated on the seed surface within 5 to 8 h. Hyphae grew on the seed surface and produced extracellular mucilage that eventually covered the seed. Appressoria formed on the ends of hyphae and penetrated through the lemma and palea, stomatal openings, and broken trichomes. The fungus then catabolized the endosperm, resulting in a visible cavity by 8 days. Pathogenesis of the embryo was associated with progressive loss of cell integrity and proliferation of mycelium. Beginning at approximately day 11, one to several stromata (approximately 150 µm in diameter and up to 4 mm in length) emerged through the lemma and palea. Degradation of embryo tissue was completed near 14 days. Conidiophores produced conidia between 21 and 28 days and often exhibited "Y-shaped" branching. This characterization of disease development corrects previous reports which concluded that P. semeniperda is only a weak seed pathogen with infection limited to the outermost seed tissues. In addition, the time required for disease development explains why infected dormant or slow-germinating seeds are most likely to experience mortality.

The dispositions of things: the non-human dimension of power and ethics in patient-centred medicine.

This article explores power relations between clinicians, patients and families as clinicians engage in patient-centred ethical work. Specifically, we draw on actor-network theory to interrogate the role of non-human elements in distributing power relations in clinical settings, as clinicians attempt to manage the expectations of patients and families. Using the activities of a multidisciplinary team providing deep brain stimulation to children with severe movement disorders as an example, we illustrate how a patient-centred tool is implicated in establishing relations that constitute four modes of power: 'power over', 'power to', "power storage" and "power/discretion". We argue that understanding the role of non-human elements in structuring power relations can guide and inform bioethical discussions on the suitability of patient-centred approaches in clinical settings.

Why we need more research into interprofessional education.

Interprofessional education (IPE) has long been considered an important means of improving communication and interaction between health professionals and of addressing patient safety concerns. This study aimed to explore whether a high-fidelity (HF) simulator could enhance a postgraduate IPE session on team-working and communication skills. A convenience sample of six doctors and six nurses, all recently qualified and working in an acute care setting, participated in teams of one nurse and one doctor in a typical clinical case scenario using a HF simulator. Pre-and post-test questionnaires and two focus groups were used to gather views on the IPE session. All of the participants agreed that all aspects of the IPE activity-the HF simulation, the scenarios and the debriefing-were 'effective' in attracting and retaining interest and attention. Future larger-scale research needs a more objective approach, such as a consideration of patient-related impact and outcomes.

Corporal diagnostic work and diagnostic spaces: clinicians' use of space and bodies during diagnosis.

An emerging body of literature in sociology has demonstrated that diagnosis is a useful focal point for understanding the social dimensions of health and illness. This article contributes to this work by drawing attention to the relationship between diagnostic spaces and the way in which clinicians use their own bodies during the diagnostic process. As a case study, we draw upon fieldwork conducted with a multidisciplinary clinical team providing deep brain stimulation (DBS) to treat children with a movement disorder called dystonia. Interviews were conducted with team members and diagnostic examinations were observed. We illustrate that clinicians use communicative body work and verbal communication to transform a material terrain into diagnostic space, and we illustrate how this diagnostic space configures forms of embodied 'sensing-and-acting' within. We argue that a 'diagnosis' can be conceptualised as emerging from an interaction in which space, the clinician-body, and the patient-body (or body-part) mutually configure one another. By conceptualising diagnosis in this way, this article draws attention to the corporal bases of diagnostic power and counters Cartesian-like accounts of clinical work in which the patient-body is objectified by a disembodied medical discourse.

Sociology of Low Expectations: Recalibration as Innovation Work in Biomedicine.

Social scientists have drawn attention to the role of hype and optimistic visions of the future in providing momentum to biomedical innovation projects by encouraging innovation alliances. In this article, we show how less optimistic, uncertain, and modest visions of the future can also provide innovation projects with momentum. Scholars have highlighted the need for clinicians to carefully manage the expectations of their prospective patients. Using the example of a pioneering clinical team providing deep brain stimulation to children and young people with movement disorders, we show how clinicians confront this requirement by drawing on their professional knowledge and clinical expertise to construct visions of the future with their prospective patients; visions which are personalized, modest, and tainted with uncertainty. We refer to this vision-constructing work as recalibration, and we argue that recalibration enables clinicians to manage the tension between the highly optimistic and hyped visions of the future that surround novel biomedical interventions, and the exigencies of delivering those interventions in a clinical setting. Drawing on work from science and technology studies, we suggest that recalibration enrolls patients in an innovation alliance by creating a shared understanding of how the "effectiveness" of an innovation shall be judged.

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.

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.

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.

Screening for mild traumatic brain injury in OEF-OIF deployed US military: an empirical assessment of VHA's experience.

BACKGROUND: VHA screens for traumatic brain injury (TBI) among patients formerly deployed to Afghanistan or Iraq, referring those who screen positive for a Comprehensive TBI Evaluation (CTBIE). METHODS: To assess the programme, rates were calculated of positive screens for potential TBI in the population of patients screened in VHA between October 2007 through March 2009. Rates were derived of TBI confirmed by comprehensive evaluations from October 2008 through July 2009. Patient characteristics were obtained from Department of Defense and VHA administrative data. RESULTS: In the study population, 21.6% screened positive for potential TBI and 54.6% of these had electronic records of a CTBIE. Of those with CTBIE records, evaluators confirmed TBI in 57.7%, yielding a best estimate that 6.8% of all those screened were confirmed to have TBI. Three quarters of all screened patients and virtually all those evaluated (whether TBI was confirmed or not) had VHA care the following year. CONCLUSIONS: VHA's TBI screening process is inclusive and has utility in referring patients with current symptoms to appropriate care. More than 90% of those evaluated received further VHA care and confirmatory evaluations were associated with significantly higher average utilization. Generalizability is limited to those who seek VHA healthcare.

An experimental test of voluntary strategies to promote urban water demand management.

In light of the current and future threats to global water security the current research focuses on trialing interventions to promote urban water conservation. We report an experimental study designed to test the long-term impact of three different interventions on household water consumption in South East Queensland. Participants from 221 households were recruited and completed an initial survey, and their houses were fitted with smart water meters which measured total water usage at 5 s intervals. Households were allocated into one of four conditions: a control group and three interventions groups (water saving information alone, information plus a descriptive norm manipulation, and information plus tailored end-user feedback). The study is the first to use smart water metering technology as a tool for behaviour change as well as a way to test the effectiveness of demand management interventions. Growth curve modelling revealed that compared to the control, the three intervention groups all showed reduced levels of household consumption (an average reduction of 11.3 L per person per day) over the course of the interventions, and for some months afterwards. All interventions led to significant water savings, but long-term household usage data showed that in all cases, the reduction in water use resulting from the interventions eventually dissipated, with water consumption returning to pre-intervention levels after approximately 12 months. Implications for water demand management programs are discussed.

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.