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Background: Despite the promise wearable technology offers through detailed insight into mobility and fall risk, timely identification of high risk, assessment of risk severity, evaluation of clinical interventions, and potential to redefine the assessment of behaviours which influence health, they are not routinely used in clinical practice., Objective: Establish consensus on how wearable technology can be applied to support clinical care for people aged 50 and over experiencing changes to mobility and/or who are at increased risk of falling., Methods: A Delphi study was conducted among 17 hospital-based health professionals. Over three rounds, experts were asked about fall prevention, mobility assessment, the potential role of wearable sensors, and clinical considerations for implementing wearable technology into practice. Consensus was defined as 75% agreement. Data were analysed using qualitative and quantitative methods., Results: Experts found that wearable technology has short and long-term clinical utility, data should be shared with general practitioners to improve long-term health outcomes, and devices would need to fit all individuals with a preference for wrist or pendant-worn locations. Technological literacy was not a perceived barrier. However, cost and data accuracy were important for successful implementation., Conclusion: This study provides a group consensus statement and guidance on the clinical implementation of wearable technology to support care for people aged 50 and over experiencing changes to mobility and/or who are at increased risk of falling. Health professionals are receptive to using wearable technologies to advance fall risk and mobility assessment and believe wearable technology has a role in clinical practice., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 APTA Geriatrics, An Academy of the American Physical Therapy Association.)

ObjectiveThis study aimed to determine the number of visitors to an acute hospital, the time of visit, destination, and details of parking over the same period.MethodsA prospective observational pilot study in a large metropolitan public hospital in Australia was performed. The research team observed all visitors over a 14-day period between 17 and 30 October 2022 counting the people visiting relatives or friends of admitted hospital patients as well as those visiting outpatient clinics during the observation period. Other outcome measures included time of the visit, destination, and estimated costs of parking.ResultsDuring the 14 days of observation there were 18,066 visitors, averaging 1290 per day. The majority were visitors to inpatients (62.2%, 11,232, averaging 802 per day). Those attending outpatients were less (37.8%, 6834, averaging 668 per weekday). The estimated average parking cost was A$18.10 per day normally and A$11.85 for concessions.ConclusionsThis was the first known study on hospital-wide visiting in Australia or globally. These findings would be important for addressing issues such as hospital planning, and for future research including the impact of visiting on patient outcomes, the patient and community experience, and the expectations and experience of hospital visitors.

ObjectiveStaff wellness rounding (SWR) is a process in which healthcare leaders have real-time conversations with healthcare workers (HCW) to identify safety and wellness issues. This study examined the experience of multidisciplinary healthcare leaders, who were not trained in psychology, who delivered SWR during the surge phase of the COVID-19 pandemic.MethodsA mixed methods approach was used. Phase 1 included a survey of HCW who participated in SWR during July-October 2021. Phase 2 included semi-structured interviews of leaders who delivered SWR.ResultsThere were 403 respondents to the survey, with 169 participants (41.9%) being eligible for the study. More than 67% of eligible respondents would recommend SWR to other colleagues, and 77.5% reported that SWR provided an opportunity to escalate issues or concerns about COVID-19. Eleven SWR leaders were interviewed about their experience of leading SWR. Four key themes were identified: SWR (1) offered a defined process for communication between executive leaders and HCW; (2) enabled escalation and actioning of issues to and from executive teams in the organisation; (3) required flexible scheduling to meet varied work schedules of HCW; and (4) required the leaders to have a core set of skills and competencies.ConclusionThis study examined the contribution that an SWR intervention can make to support HCW wellbeing during crisis-type events. The model facilitated interactions between executive leaders, managers and frontline staff. It fostered collegiality with peers, managers and leaders, supported recognition and acknowledgment of peers and used available resources effectively to support staff wellness during the surge phase of the COVID-19 pandemic.

Incontinence-associated dermatitis poses a significant risk for sacral pressure injuries, infection and morbidity in healthcare settings. Despite the availability of best practice guidelines, implementation remains a challenge., Aim: To outline the implementation of a hospital-wide programme using the Integrated Promoting Action on Research Implementation in Health Services framework to prevent and manage incontinence-associated dermatitis and improve hospital-acquired pressure injuries., Design: This is an empirical research study using mixed methods., Method: The study, conducted across surgical, medical and critical care wards between June and October 2023, aimed to address knowledge gaps, enhance clinical practice and evaluate the effectiveness of interventions. The implementation strategy included education modules, engagement of staff through focus groups and targeted interventions such as individualised toileting plans and structured skin care regimens. Data collection involved audits, incident reporting and clinician knowledge surveys., Results: Findings indicate a reduction in hospital-acquired incontinence-associated dermatitis and pressure injuries postimplementation, with observed improvements in clinician knowledge. However, challenges including workload, skill mix and resource limitations were identified as barriers to implementation. The sustainability and scalability of the programme were emphasised, with ongoing monitoring and evaluation essential for long-term success., Conclusion: This study underscores the importance of evidence-based interventions, interdisciplinary collaboration and leadership support in improving patient outcomes and reducing healthcare costs associated with preventable skin injuries. Further research is needed to assess implementation in community settings and scale up interventions across healthcare networks., Implications for the Profession And/or Patient Care: Analysing a hospital-wide programme using the Integrated Promoting Action on Research Implementation in Health Service framework to prevent and manage incontinence-associated dermatitis and improve hospital-acquired pressure injuries, could help identify the challenges for delivering patient-centred care., Patient or Public Contribution: No patient or public involvement., Reporting Method: To describe the implementation study, we referred to the StaRI Guideline., Trial Registration: This intervention study was applied to the whole population and was therefore not a trial and did not require trial registration. The study was considered low risk and the Human Research Ethics Application (HREA) was approved., (© 2024 John Wiley & Sons Ltd.)

Purpose: To explore the views of healthcare professionals and patients about the advantages and disadvantages of rehabilitation in the home (RITH) for reconditioning, and identify factors that should contribute to the successful implementation of a consensus-based RITH model for reconditioning., Materials and Methods: Interviews with 24 healthcare professionals and 21 surveys (comprising Likert scale and free text responses) of inpatients undergoing rehabilitation for reconditioning provided study data. Interpretive thematic analysis was used to analyse interview data; descriptive statistics analysed Likert scale responses; patient written responses assisted with the interpretation of themes developed from the interview data., Results: Two major themes were elicited in this study: the home is a physical setting and the home is a lived space. Advantages and disadvantages of RITH for patients, carers and healthcare professionals were identified within these themes. Appropriate patient selection; effective communication with patients and carers, and within RITH teams; adequate patient and carer support; ensuring the safety of patients and staff; and education of patients, carers and healthcare professionals are essential for the satisfactory implementation of RITH., Conclusion: The concept of home shapes the delivery of RITH. Recognising the advantages and disadvantages of RITH highlights important considerations needed to successfully implement RITH for reconditioning.

Patient-reported outcome measures (PROMs) play an important role in the rehabilitation of people with major limb amputations. Patient-completed questionnaires help collect specific constructs on this patient population. The COMPASS and LEAD initiatives, carried out by the International Society for Prosthetics and Orthotics (ISPO), underscore the importance of regularly collecting high-quality PROMs. These are essential for the evaluation of rehabilitation needs, progress, and success. In the final report of ISPO's major international initiative, PROMs recommendations of the expert panel are tabulated. In Table 3.2 of the report, ISPO lists n=12 PROMs that were included in the narrow consensus process were considered to be of acceptable quality, and therefore recommended. The aim of this systematic review was to specifically search for these recommended PROMS regarding their availability in a German and validated version in order to identify potential gaps. All PROMs that were available in a German and validated version were then examined further with regard to the quality of the validation study, using the checklist of COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN). Through a systematic literature search, six validated German-language versions were found. Only four of these met the quality standards of the COSMIN checklist sufficiently. Overall, this review shows serious gaps in the availability in the German language of validated versions of PROMs used internationally and recommended as standard by the ISPO. This gap needs to be closed by guideline-oriented translation and subsequent validation studies in order to be able to offer and collect the PROMS recommended by the ISPO also for German-speaking patient populations., Competing Interests: Die Autorinnen/Autoren geben an, dass kein Interessenkonflikt besteht., (Thieme. All rights reserved.)

Rotary motors play key roles in energy transduction, from macroscale windmills to nanoscale turbines such as ATP synthase in cells. Despite our abilities to construct engines at many scales, developing functional synthetic turbines at the nanoscale has remained challenging. Here, we experimentally demonstrate rationally designed nanoscale DNA origami turbines with three chiral blades. These DNA nanoturbines are 24-27 nm in height and diameter and can utilize transmembrane electrochemical potentials across nanopores to drive DNA bundles into sustained unidirectional rotations of up to 10 revolutions s -1 . The rotation direction is set by the designed chirality of the turbine. All-atom molecular dynamics simulations show how hydrodynamic flows drive this turbine. At high salt concentrations, the rotation direction of turbines with the same chirality is reversed, which is explained by a change in the anisotropy of the electrophoretic mobility. Our artificial turbines operate autonomously in physiological conditions, converting energy from naturally abundant electrochemical potentials into mechanical work. The results open new possibilities for engineering active robotics at the nanoscale., (© 2023. The Author(s).)

Background: Inpatient rehabilitation services are challenged by increasing demand. Where appropriate, a shift in service models towards more community-oriented approaches may improve efficiency. We aimed to estimate the hypothetical cost of delivering a consensus-based rehabilitation in the home (RITH) model as hospital substitution for patients requiring reconditioning following medical illness, surgery or treatment for cancer, compared to the cost of inpatient rehabilitation., Methods: Data were drawn from the following sources: the results of a Delphi survey with health professionals working in the field of rehabilitation in Australia; publicly available data and reports; and the expert opinion of the project team. Delphi survey data were analysed descriptively. The costing model was developed using assumptions based on the sources described above and was restricted to the Australian National Subacute and Non-Acute Patient Classification (AN-SNAP) classes 4AR1 to 4AR4, which comprise around 73% of all reconditioning episodes in Australia. RITH cost modelling estimates were compared to the known cost of inpatient rehabilitation. Where weighted averages are provided, these were determined based on the modelled number of inpatient reconditioning episodes per annum that might be substitutable by RITH., Results: The cost modelling estimated the weighted average cost of a RITH reconditioning episode (which mirrors an inpatient reconditioning episode in intensity and duration) for AN-SNAP classes 4AR1 to 4AR4, to be A$11,371, which is 28.1% less than the equivalent weighted average public inpatient cost (of A$15,820). This represents hypothetical savings of A$4,449 per RITH reconditioning substituted episode of care., Conclusions: The hypothetical cost of a model of RITH which would provide patients with as comprehensive a rehabilitation service as received in inpatient rehabilitation, has been determined. Findings suggest potential cost savings to the public hospital sector. Future research should focus on trials which compare actual clinical and cost outcomes of RITH for patients in the reconditioning impairment category, to inpatient rehabilitation., (© 2024. The Author(s).)

Background: Understanding the psychometric strengths and limitations of outcome measures for use with people with lower limb absence (LLA) is important for selecting measures suited to evaluating patient outcomes, answering clinical and research questions, and informing health care policy. The aim of this project was to review the current psychometric evidence on outcome measures in people with LLA to determine which measures should be included in a stakeholder consensus process., Methods: An expert panel was assembled, and a 3-stage review process was used to categorize outcome measures identified in a systematic literature review into 3 distinct categories (recommended for measures with better than adequate psychometric properties; recommended with qualification; and unable to recommend). Panelists were asked to individually categorize measures based on results of a systematic review of identified measures' psychometric properties. Each measure's final categorization was based on ≥70% agreement by all panelists., Results: No outcome measure attained the ≥70% consensus threshold needed to achieve a rating of "recommend." Hence, panelists suggested combining "recommend" and "recommend with qualifications" into a single category of "recommend with qualifications." Using this approach, consensus was reached for 59 of 60 measures. Consensus could not be reached on 1 outcome measure (socket comfort score). Thirty-six outcome measures were categorized as "unable to recommend" based on available evidence; however, 23 (12 patient-reported measures and 11 performance-based measures) demonstrated adequate psychometric properties in LLA samples and were thus rated as "recommend with qualification" by the expert panel. The panel of experts were able to recommend 23 measures for inclusion in the subsequent stakeholder review. A key strength of this process was bringing together international researchers with extensive experience in developing and/or using LLA outcome measures who could assist in identifying psychometrically sound measures to include in a subsequent stakeholder consensus process., Conclusion: The above categorizations represent the current state of psychometric evidence on outcome measures for people with LLA and hence may change over time as additional research becomes available. The results will be used to achieve wider consensus from clinicians, health policymakers, health clinic managers, researchers, and end users (i.e., individuals with LLA) on outcome measures for the International Society of Prosthetics and Orthotics lower limb Consensus Outcome Measures for Prosthetic and Amputation ServiceS., (Copyright © 2023 International Society for Prosthetics and Orthotics.)

Here, the study presents a thermally activated cell-signal imaging (TACSI) microrobot, capable of photothermal actuation, sensing, and light-driven locomotion. The plasmonic soft microrobot is specifically designed for thermal stimulation of mammalian cells to investigate cell behavior under heat active conditions. Due to the integrated thermosensitive fluorescence probe, Rhodamine B, the system allows dynamic measurement of induced temperature changes. TACSI microrobots show excellent biocompatibility over 72 h in vitro, and they are capable of thermally activating single cells to cell clusters. Locomotion in a 3D workspace is achieved by relying on thermophoretic convection, and the microrobot speed is controlled within a range of 5-65 µm s -1 . In addition, light-driven actuation enables spatiotemporal control of the microrobot temperature up to a maximum of 60 °C. Using TACSI microrobots, this study targets single cells within a large population, and demonstrates thermal cell stimulation using calcium signaling as a biological output. Initial studies with human embryonic kidney 293 cells indicate a dose dependent change in intracellular calcium content within the photothermally controlled temperature range of 37-57 °C., (© 2023 The Authors. Advanced Healthcare Materials published by Wiley-VCH GmbH.)

Aim: This study aimed to explore what constitutes brilliant aged care., Background: Although many aged care services do not offer the care that older people and carers need and want, some perform better. Rather than focus on problems with aged care, this study examined brilliant aged care-practices that exceeded expectation., Design: The methodology for this study was informed by grounded theory, underpinned by constructionism to socially construct meaning., Methods: This study invited nominations for a Brilliant Award via a survey, and interviews with the nominees via web conference. After receiving survey responses from 10 nominators, interviews were conducted with 12 nominees. Data were analysed using reflexive thematic analysis and documented according to COREQ guidelines to optimise rigour and transparency., Results: According to participants, brilliant aged care involved being relationally attuned to older people, a deep understanding of the older person, recognition of aged care as more than a job, innovative practices and permission to reprioritise., Conclusions: This study suggests that, in aged care, brilliance happens. It emphasises the importance of meaningful connections and relationships in aged care, where thoughtful acts acknowledge an older person's value and humanity as well as creativity and innovation., Relevance to Clinical Practice: For those who manage and deliver aged care, the findings suggest that small practice changes can make a positive difference to older people. Brilliant aged care can involve acts of empathy; enthusiasm for aged care; innovative practices, even those that are small scale; and reprioritising workplace tasks to spend time with older people. For policymakers, this study highlights the need to recognise and raise the profile of the pockets of brilliance within the aged care sector. This might be achieved via awards and other initiatives that serve to celebrate and learn from brilliance in its myriad forms., Patient or Public Contribution: The nominees, who included carers, were invited to participate in workshops with other carers and older people to co-design a model of brilliant aged care, during which workshop participants discussed and critiqued the findings constructed from the data., (© 2023 The Authors. Journal of Clinical Nursing published by John Wiley & Sons Ltd.)

Stable and efficient high-power biohybrid light-emitting diodes (Bio-HLEDs) using fluorescent proteins (FPs) in photon downconverting filters have not been achieved yet, reaching best efficiencies of 130 lm W -1 stable for >5 h. This is related to the rise of the device temperature (70-80 °C) caused by FP-motion and quick heat-transmission in water-based filters, they lead to a strong thermal emission quenching followed by the quick chromophore deactivation via photoinduced H-transfer. To tackle both issues at once, this work shows an elegant concept of a new FP-based nanoparticle, in which the FP core is shielded by a SiO 2 -shell (FP@SiO 2 ) with no loss of the photoluminescence figures-of-merit over years in foreign environments: dry powder at 25 °C (ambient) or constant 50 °C, as well as suspensions in organic solvents. This enables the preparation of water-free photon downconverting coatings with FP@SiO 2 , realizing on-chip high-power Bio-HLEDs with 100 lm W -1 stable for >120 h. Both thermal emission quenching and H-transfer deactivation are suppressed, since the device temperature holds <40 °C and remote high-power Bio-HLEDs exhibit final stabilities of 130 days compared to reference devices with water-based FP@SiO 2 (83 days) and FP-polymer coatings (>100 h). Hence, FP@SiO 2 is a new paradigm toward water-free zero-thermal-quenching biophosphors for first-class high-power Bio-HLEDs., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Background: Outcome measures are an important part of clinical practice to assist with the care of individuals with lower-limb absence (LLA). They aid with the devising and evaluation of rehabilitation plans, and guide decisions regarding the provision and funding of prosthetic services worldwide. To date, no outcome measure has been identified as a gold standard for use in individuals with LLA. Furthermore, the large number of outcome measures available has created uncertainty regarding outcome measures that are most appropriate for individuals with LLA., Objective: To critically appraise the existing literature related to the psychometric properties of outcome measures for use in individuals with LLA and provide evidence as to which outcome measures may be most appropriate for this clinical population., Study Design: This is a systematic review protocol., Methods: CINAHL, Embase, MEDLINE (PubMed), and PsycINFO databases will be searched using a combination of Medical Subject Headings terms and keywords. Search terms that define the population (people with LLA or amputation), intervention (outcome measures), and outcome (psychometric properties) will be used to identify studies. The reference lists of included studies will be hand-search to identify other pertinent articles, with a further search conducted through Google Scholar to ensure that all studies not yet indexed through MEDLINE are captured. Full-text peer-reviewed journal studies published in English will be included, with no date limit set. Included studies will be appraised using the 2018 and 2020 COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) checklists. Data extraction and study appraisal will be completed by two authors, with a third author serving as an adjudicator. Quantitative synthesis will be used to summarize characteristics of the included studies, with kappa statistics used to determine agreement between authors for study inclusion and the application of COSMIN. Qualitative synthesis will be conducted to report on both quality of the included studies and psychometric properties of the included outcome measures., Conclusion: This protocol was designed to identify, appraise, and summarize patient-reported and performance-based outcome measures that have been psychometrically tested in people with LLA. Results from this review will be used to guide a consensus process on outcome measure use for people with LLA.Systematic review registration: PROSPERO registry number: CRD42020217820., (Copyright © 2023 International Society for Prosthetics and Orthotics.)

The European Beaver came close to extinction in France at the beginning of the twentieth century. It has since been reintroduced across the country but its gradual expansion has caused conflicts linked to its behavior, exacerbated by strict enforcement of laws against poaching or the destruction of beaver dams. We conducted field research in 2021 in three municipalities, two in the Loire basin and one in the Seine basin. Using a reconciliation ecology perspective and participatory science methodology, we investigated the dynamics of beaver rejection and approaches to defuse them by emphasizing the anthropomorphic characters of the beaver. During successive meetings with study participants, we attempted to mitigate attitudes of human/nature opposition by presenting humans as part of ecosystems, engaged in social relations with other living beings using the concept of "neighborhood," which specifically places these relationships and has proven to be more readily adopted than the more abstract concepts of ecosystem, habitat, or biotope. We used a three-stage process of reconciliation/reconnection/protection to raise environmental awareness and concerns. Our results can provide guidelines for environmental agents and officers to engage local populations in conservation efforts., Supplementary Information: The online version contains supplementary material available at 10.1007/s10745-023-00406-z., Competing Interests: Conflict of InterestThe authors declare they have no conflict of interest., (© The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2023, Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Background: Reconditioning for patients who have experienced functional decline following medical illness, surgery or treatment for cancer accounts for approximately 26% of all reported inpatient rehabilitation episodes in Australia. Rehabilitation in the home (RITH) has the potential to offer a cost-effective, high-quality alternative for appropriate patients, helping to reduce pressure on the acute care sector. This study sought to gain consensus on a model for RITH as hospital substitution for patients requiring reconditioning., Methods: A multidisciplinary group of health professionals working in the rehabilitation field was identified from across Australia and invited to participate in a three-round online Delphi survey. Survey items followed the patient journey, and also included items on practitioner roles, clinical governance, and budgetary considerations. Survey items mostly comprised statements seeking agreement on 5-point Likert scales (strongly agree to strongly disagree). Free text boxes allowed participants to qualify item answers or make comments. Analysis of quantitative data used descriptive statistics; qualitative data informed question content in subsequent survey rounds or were used in understanding item responses., Results: One-hundred and ninety-eight health professionals received an invitation to participate. Of these, 131/198 (66%) completed round 1, 101/131 (77%) completed round 2, and 78/101 (77%) completed round 3. Consensus (defined as ≥ 70% agreement or disagreement) was achieved on over 130 statements. These related to the RITH patient journey (including patient assessment and development of the care plan, case management and program provision, and patient and program outcomes); clinical governance and budgetary considerations; and included items for initial patient screening, patient eligibility and case manager roles. A consensus-based model for RITH was developed, comprising five key steps and the actions within each., Conclusions: Strong support amongst survey participants was found for RITH as hospital substitution to be widely available for appropriate patients needing reconditioning. Supportive legislative and payment systems, mechanisms that allow for the integration of primary care, and appropriate clinical governance frameworks for RITH are required, if broad implementation is to be achieved. Studies comparing clinical outcomes and cost-benefit of RITH to inpatient rehabilitation for patients requiring reconditioning are also needed., (© 2023. The Author(s).)

Background: Outcome measures (patient-reported and performance-based) are used widely but not uniformly within the clinical setting for individuals with lower-limb absence (LLA). The need for more detailed information by funding bodies, service planners and providers, and researchers requires the systematic and routine use of outcome measures. Currently, there is no consensus on which outcome measure(s) should be used for individuals with LLA. The aim of the International Society of Prosthetics and Orthotics (ISPO) lower-limb Consensus Outcome Measures for Prosthetic and Amputation Services (COMPASS) was to produce a recommended list of outcome measures to be actively promoted for routine use within clinical practice before and after an episode of care., Methods: Between May and June 2021, 46 users, clinicians, researchers, managers, and policymakers working in the field of LLA and prosthetic users met virtually. Consensus participants were first asked to complete an online survey with questions based on the results from a systematic review and the outcomes from an expert panel. A modified Delphi technique was used to determine outcome measures for use in routine clinical practice. This paper discusses the ISPO lower-limb COMPASS process from which recommendations were made., Results: The ISPO lower-limb COMPASS resulted in the following 6 recommendations: (1) Amputee Mobility Predictor, Timed Up and Go, Two-Minute Walk Test, Prosthetic Evaluation Questionnaire-Residual Limb Health, Prosthetic Evaluation Questionnaire-Utility, and Trinity Amputation and Prosthesis Experience Scales-Revised, which make up the ISPO lower-limb COMPASS ; (2) Comprehensive High-Level Activity Mobility Predictor and Six-Minute Walk Test are 2 additional outcome measures recommended for higher-activity-level individuals with LLA, which make up the COMPASS+ ; (3) Patient-Specific Function Scale makes up the COMPASS Adjunct ; (4) a generic health-related quality of life outcome measure such as the European Quality of Life-5D-5L or Patient-Reported Outcomes Measurement Information System-29 item can be used to supplement the COMPASS; (5) outcome measures suited to low- and middle-income countries need to be developed with a focus on activities such as sitting cross-legged, kneeling, squatting, and other culturally important mobility-related activities; and (6) translation, validation, and open sharing of translated outcome measures included in the COMPASS, COMPASS+, and COMPASS Adjunct occurs., Conclusion: The above recommendations represent the current status of knowledge on outcome measures for LLA based on research and international consensus and hence, will change over time. This work has been developed for clinicians and researchers to improve knowledge on outcome measures to guide clinical decision-making and future research initiatives., (Copyright © 2023 The Authors. Published by Wolters Kluwer incorporated on behalf of The International Society for Prosthetics and Orthotics.)

The growth of crystals confined in porous or cellular materials is ubiquitous in Nature and forms the basis of many industrial processes. Confinement affects the formation of biominerals in living organisms, of minerals in the Earth's crust and of salt crystals damaging porous limestone monuments, and is also used to control the growth of artificial crystals. However, the mechanisms by which confinement alters crystal shapes and growth rates are still not elucidated. Based on novel in situ optical observations of (001) surfaces of NaClO 3 and CaCO 3 crystals at nanometric distances from a glass substrate, we demonstrate that new molecular layers can nucleate homogeneously and propagate without interruption even when in contact with other solids, raising the macroscopic crystal above them. Confined growth is governed by the peculiar dynamics of these molecular layers controlled by the two-dimensional transport of mass through the liquid film from the edges to the center of the contact, with distinctive features such as skewed dislocation spirals, kinetic localization of nucleation in the vicinity of the contact edge, and directed instabilities. Confined growth morphologies can be predicted from the values of three main dimensionless parameters., (© 2022. The Author(s).)

Crystallization pressure drives deformation and damage in monuments, buildings, and the Earth's crust. Even though the phenomenon has been known for 170 years, there is no agreement between theoretical calculations of the maximum attainable pressure and experimentally measured pressures. We have therefore developed a novel experimental technique to image the nanoconfined crystallization process while controlling the pressure and applied it to calcite. The results show that displacement by crystallization pressure is arrested at pressures well below the thermodynamic limit. We use existing molecular dynamics simulations and atomic force microscopy data to construct a robust model of the disjoining pressure in this system and thereby calculate the absolute distance between the surfaces. On the basis of the high-resolution experiments and modeling, we formulate a novel mechanism for the transition between damage and adhesion by crystallization that may find application in Earth and materials sciences and in conservation of cultural heritage.

Background: Although primary care is a well suited context for conducting advance care planning (ACP), there are many barriers to initiating discussions regarding future health preference and end-of-life conversations., Methods: This qualitative study conducted 30 detailed individual interviews with senior administrators, medical and nurse practitioners of a local health district, NSW Ambulance, e-Health NSW, general practitioners and practice nurses to find out about barriers to ACP in South Western Sydney., Results: Thematic analysis was conducted on the interviews. Six major themes were identified: Prevalence; Empowerment of roles and responsibilities; Lack of training/knowledge/confidence; Fragmentation of care; Patient/family readiness; and Prognostication. Half of the participants were willing to use a prognostic tool to identify when a patient was likely to be at the end of their life and provide a prompt to initiate ACP., Conclusion: In addition to addressing training and acknowledging resource constraints, these findings suggest that if a prognostic tool was validated and practical in a primary care setting, it may provide valuable assistance to encourage everyone in society to begin discussing this issue and completing ACP.

SARS-CoV-2 infection is a major global public health concern with incompletely understood pathogenesis. The SARS-CoV-2 spike (S) glycoprotein comprises a highly conserved free fatty acid binding pocket (FABP) with unknown function and evolutionary selection advantage 1,2 . Deciphering FABP impact on COVID-19 progression is challenged by the heterogenous nature and large molecular variability of live virus. Here we create synthetic minimal virions (MiniVs) of wild-type and mutant SARS-CoV-2 with precise molecular composition and programmable complexity by bottom-up assembly. MiniV-based systematic assessment of S free fatty acid (FFA) binding reveals that FABP functions as an allosteric regulatory site enabling adaptation of SARS-CoV-2 immunogenicity to inflammation states via binding of pro-inflammatory FFAs. This is achieved by regulation of the S open-to-close equilibrium and the exposure of both, the receptor binding domain (RBD) and the SARS-CoV-2 RGD motif that is responsible for integrin co-receptor engagement. We find that the FDA-approved drugs vitamin K and dexamethasone modulate S-based cell binding in an FABP-like manner. In inflammatory FFA environments, neutralizing immunoglobulins from human convalescent COVID-19 donors lose neutralization activity. Empowered by our MiniV technology, we suggest a conserved mechanism by which SARS-CoV-2 dynamically couples its immunogenicity to the host immune response., (© 2022. The Author(s).)

Developed in partnership with GPs, a new telehealth model of care using remote monitoring, known as telemonitoring (TM), was introduced in South Western Sydney (SWS) in 2015, transmitting clinical readings taken at home to telehealth coordinators. This study explored the experiences, beliefs and attitudes of general practice staff to identify barriers to and facilitators of the SWS TM model. Responses were collected from a purposive sample of 10 participants via semistructured interviews (n = 9 interview sessions) and the resulting transcripts were analysed thematically. Four themes were identified: lack of understanding and involvement; patient-centred care and empowerment; clinical practice and process factors; and system-wide communication and collaboration. Participants recognised some actual and potential benefits of TM, but barriers to TM were identified across all themes. Feedback provided by participants has informed the ongoing formulation of a more 'GP-led' model of TM.

In biology, self-assembly of proteins and energy-consuming reaction cycles are intricately coupled. For example, tubulin is activated and deactivated for assembly by a guanosine triphosphate (GTP)-driven reaction cycle, and the emerging microtubules catalyze this reaction cycle by changing the microenvironment of the activated tubulin. Recently, synthetic analogs of chemically fueled assemblies have emerged, but examples in which assembly and reaction cycles are reciprocally coupled remain rare. In this work, we report a peptide that can be activated and deactivated for self-assembly. The emerging assemblies change the microenvironment of their building blocks, which consequently accelerate the rates of building block deactivation and reactivation. We quantitatively understand the mechanisms at play, and we are thus able to tune the catalysis by molecular design of the peptide precursor.

The methods of DNA nanotechnology enable the rational design of custom shapes that self-assemble in solution from sets of DNA molecules. DNA origami, in which a long template DNA single strand is folded by many short DNA oligonucleotides, can be employed to make objects comprising hundreds of unique DNA strands and thousands of base pairs, thus in principle providing many degrees of freedom for modelling complex objects of defined 3D shapes and sizes. Here, we address the problem of accurate structural validation of DNA objects in solution with cryo-EM based methodologies. By taking into account structural fluctuations, we can determine structures with improved detail compared to previous work. To interpret the experimental cryo-EM maps, we present molecular-dynamics-based methods for building pseudo-atomic models in a semi-automated fashion. Among other features, our data allows discerning details such as helical grooves, single-strand versus double-strand crossovers, backbone phosphate positions, and single-strand breaks. Obtaining this higher level of detail is a step forward that now allows designers to inspect and refine their designs with base-pair level interventions.

Quality improvement (QI) in health generally focuses on the provision of health services with the aim of improving service delivery. Yet QI can be applied not only to health services but also to health systems overall. This is of growing relevance considering that due to deficiencies in health systems, the main countries affected by Ebola virus disease (EVD) outbreak in West Africa (2014-2016) were insufficiently prepared for the epidemic, and according to the WHO, epidemics are increasingly becoming a threat to global health. Our objective is to analyze QI constraints in health systems during that EVD epidemic and to propose a practical framework for QI in health systems for epidemics in developing countries. We applied a framework analysis using experiences shared at the "Second International Quality Forum" organized by the University of Heidelberg and partners in July 2015 and information gathered from a systematic literature review. Empirical results revealed multiple deficiencies in the health systems. We systemized these shortfalls as well as the QI measures taken as a response during the epidemic. On the basis of these findings, we identified six specific "priority intervention areas," which ultimately resulted in the synthesis of a practical QI framework. We deem that this framework that integrates the priority intervention areas with the WHO building blocks is suitable to improve, monitor, and evaluate health system performance in epidemic contexts in developing countries., (© 2019 John Wiley & Sons, Ltd.)

Leading societies toward a more sustainable, equitably shared, and environmentally just future requires elevating and strengthening conversations on the nonmaterial and perhaps unquantifiable values of nonhuman nature to humanity. Debates among conservationists relating to the appropriateness of valuing ecosystems in terms of their human utility have eclipsed the more important and impactful task of expressing conservation concerns in terms that are meaningful to diverse stakeholders. We considered the wide global diversity of perspectives on the biosocial complex-the relationships and interactions between all living species on Earth-and argue that humanity's best chance for effective conservation is to take a pluralistic approach that engages seriously with the worldviews of all stakeholders. Many worldviews-particularly those in indigenous cultures-place a higher value on the spiritual and nonmaterial aspects than what is often represented by the discourse surrounding Western conservation policy. Alternative framings of the biosocial complex that recognize nature's intrinsic value can be powerful motivators for social change and for local-scale conservation efforts. At a national and international level, changing ethical framings of human relationships with nature have started influencing conceptions of human rights relating to the environment and of the rights of nature itself. This change has led to an increased role of the judiciary in promoting environmental sustainability and promoting justice for groups who are most often affected by environmental harms. We hope our essay will motivate the scientific community to change its own perception of what a sound and sustainable relationship between humanity and other species should be and will help citizens become active environmental subjects, connected to the ecosystems around them., (© 2019 Society for Conservation Biology.)

Background: This study develops a model-based myocardial T1 mapping technique with sparsity constraints which employs a single-shot inversion-recovery (IR) radial fast low angle shot (FLASH) cardiovascular magnetic resonance (CMR) acquisition. The method should offer high resolution, accuracy, precision and reproducibility., Methods: The proposed reconstruction estimates myocardial parameter maps directly from undersampled k-space which is continuously measured by IR radial FLASH with a 4 s breathhold and retrospectively sorted based on a cardiac trigger signal. Joint sparsity constraints are imposed on the parameter maps to further improve T1 precision. Validations involved studies of an experimental phantom and 8 healthy adult subjects., Results: In comparison to an IR spin-echo reference method, phantom experiments with T1 values ranging from 300 to 1500 ms revealed good accuracy and precision at simulated heart rates between 40 and 100 bpm. In vivo T1 maps achieved better precision and qualitatively better preservation of image features for the proposed method than a real-time CMR approach followed by pixelwise fitting. Apart from good inter-observer reproducibility (0.6% of the mean), in vivo results confirmed good intra-subject reproducibility (1.05% of the mean for intra-scan and 1.17, 1.51% of the means for the two inter-scans, respectively) of the proposed method., Conclusion: Model-based reconstructions with sparsity constraints allow for single-shot myocardial T1 maps with high spatial resolution, accuracy, precision and reproducibility within a 4 s breathhold. Clinical trials are warranted.

Introduction: The clinical phenotype of pseudohypoparathyroidism (PHP) is caused by Albright's Hereditary Osteodystrophy (AHO). Often, "round face" the only facial clinical sign reported in the literature. The aim of this study was to highlight various cranio-maxillofacial clinical findings associated with AHO., Results: Four patients presented with PHP type 1a. Only one patient exhibited the classical round face. All patients exhibited dental anomalies, class III malocclusion with maxillary retrusion, and a copper beaten appearance of the skull. One suffered from craniosynostosis., Conclusion: The frequency of craniofacial and dental features associated with malocclusion should prompt careful follow-up, particularly during facial growth, in patients with AHO.

Rab proteins are master regulators of intracellular membrane trafficking, but they also contribute to cell division, signaling, polarization, and migration. The majority of the works describing the mechanisms used by Rab proteins to regulate cell motility involve intracellular transport of key molecules important for migration. Interestingly, a few studies indicate that Rabs can modulate the activity of Rho GTPases, important regulators for the cytoskeleton rearrangements, but the mechanisms behind this crosstalk are still poorly understood. In this work, we identify Rab6 as a negative regulator of cell migration in vitro and in vivo. We show that the loss of Rab6 promotes formation of actin protrusions and influences actomyosin dynamics by upregulating Cdc42 activity and downregulating myosin II phosphorylation. We further provide the molecular mechanism behind this regulation demonstrating that Rab6 interacts with both Cdc42 and Trio, a GEF for Cdc42. In sum, our results uncover a mechanism used by Rab proteins to ensure spatial regulation of Rho GTPase activity for coordination of cytoskeleton rearrangements required in migrating cells.

DNA origami nano-objects are usually designed around generic single-stranded "scaffolds". Many properties of the target object are determined by details of those generic scaffold sequences. Here, we enable designers to fully specify the target structure not only in terms of desired 3D shape but also in terms of the sequences used. To this end, we built design tools to construct scaffold sequences de novo based on strand diagrams, and we developed scalable production methods for creating design-specific scaffold strands with fully user-defined sequences. We used 17 custom scaffolds having different lengths and sequence properties to study the influence of sequence redundancy and sequence composition on multilayer DNA origami assembly and to realize efficient one-pot assembly of multiscaffold DNA origami objects. Furthermore, as examples for functionalized scaffolds, we created a scaffold that enables direct, covalent cross-linking of DNA origami via UV irradiation, and we built DNAzyme-containing scaffolds that allow postfolding DNA origami domain separation.

Background:: International Classification of Function, Health and Disability provides a common framework and universal language for rehabilitation professionals across the globe., Objectives:: To identify problems in functioning and mobility relevant to persons with lower-limb amputation from an expert's point of view and quantify these problems using the International Classification of Function, Health and Disability., Study Design:: Qualitative study using electronic and paper surveys., Methods:: Electronic or paper survey was done across six countries targeting clinicians involved in pre- and post-amputation care. Meaningful concepts were extracted from the responses and linked to suitable second-level and where applicable third-level International Classification of Function, Health and Disability categories. Categorical frequency analysis was completed for the combined data and for each location., Results:: A total of 183 experts from 6 different countries responded to the survey. A total of 2171 concepts were identified, 82% of which could be linked to a second-level International Classification of Function, Health and Disability category. The categorical frequency analysis revealed that the categories of walking, design and construction of buildings for public and private use and sensation of pain were the most frequently occurring concepts and was similar across the six countries., Conclusion:: The International Classification of Function, Health and Disability can be utilised as a common framework for communication among clinicians involved in rehabilitation of persons with lower-limb amputation across the globe. The most important factors that were identified by experts in amputee rehabilitation working in different international locations were similar., Clinical Relevance: The challenges faced by the clinicians involved in care of persons with lower extremity amputation vary across different parts of the world. The overarching goal for the clinician irrespective of the location is to improve mobility and quality of life of their clients. The International Classification of Function, Health and Disability provides a common language between the various stakeholders in amputee rehabilitation across the globe.

Background/aims: Medication non-adherence is common in inflammatory bowel diseases (IBD). The short-term consequences of non-adherence include increased disease relapse but the long-term impact upon patients in terms of daily functional impairment are less well characterized. Identifying negative outcomes, such as disability, may encourage adherence., Methods: Consecutive ambulatory IBD subjects completed the Medication Adherence Rating Scale (MARS; non-adherence defined as ≤16), Inflammatory Bowel Diseases Disability Index (IBD-DI; disability: <3.5) and Beliefs about Medicines Questionnaire (high necessity/concerns: ≥16). The primary outcome was the association between medication non-adherence and disability. Secondary outcomes were the predictors of these outcomes., Results: A total of 173 subjects on IBD maintenance medications were recruited (98 Crohn's disease, 75 ulcerative colitis: median IBD-DI, -5.0; interquartile range [IQR], -14.0 to 4.0 and median MARS, 19.0; IQR, 18 to 20) of whom 24% were non-adherent. Disability correlated significantly with medication non-adherence (r=0.38, P<0.0001). Median IBD-DI for non-adherers was significantly lower than adherers (-16.0 vs. -2.0, P<0.0001). Predictors of disability included female sex (P=0.002), previous hospitalization (P=0.023), management in a referral hospital clinic (P=0.008) and medication concerns (P<0.0001). Non-adherence was independently associated with difficulty managing bowel movements (odds ratio [OR], 3.71; 95% confidence interval [CI], 1.50-9.16, P=0.005), rectal bleeding (OR, 2.69; 95% CI, 1.14-6.36; P=0.024) and arthralgia/arthritis (OR, 2.56; 95% CI, 1.11-5.92; P=0.028)., Conclusions: Medication non-adherence was associated with significantly increased disability in IBD. Female gender, higher disease severity and medication concerns were additional predictors of disability.

Clinical application of tissue engineering products requires the exclusion of immune responses after implantation. We used jaw periosteal cells (JPCs) as a suitable stem cell source and analyzed herein the effects of JPCs on dendritic cell maturation after co-culturing of both cell types. Peripheral blood mononuclear cells (PBMCs) were differentiated to dendritic cells (DCs) by the addition of differentiation cocktails for 7 days in co-culture with undifferentiated and osteogenically induced JPCs. The effects of JPCs on DC maturation were analyzed at the beginning (day 7), in the middle (day 14), and at the end (day 21) of the osteogenesis process. We detected significantly lower DC numbers after co-culturing with JPCs that have previously been left untreated or osteogenically differentiated for 7, 14, and 21 days. Using gene expression analyses, significantly lower IL-12p35 and -p40 and pro-inflammatory cytokine (IFN-γ and TNF-α) levels were detected, whereas IL-8 mRNA levels were significantly higher in DCs. Furthermore, osteogenic media conditions enhanced significantly IL-10 gene expression. We concluded that undifferentiated and osteogenically differentiated JPCs had an overall inhibiting influence on dendritic cell maturation. Further studies should clarify the underlaying mechanism in depth.

Growing crystals form a cavity when placed against a wall. The birth of the cavity is observed both by optical microscopy of sodium chlorate crystals (NaClO&#95;{3}) growing in the vicinity of a glass surface, and in simulations with a thin film model. The cavity appears when growth cannot be maintained in the center of the contact region due to an insufficient supply of growth units through the liquid film between the crystal and the wall. We obtain a nonequilibrium morphology diagram characterizing the conditions under which a cavity appears. Cavity formation is a generic phenomenon at the origin of the formation of growth rims observed in many experiments, and is a source of complexity for the morphology of growing crystals in natural environments. Our results also provide restrictions for the conditions under which compact crystals can grow in confinement.

Increased awareness, interest and use of assistive technology (AT) presents substantial opportunities for many citizens to become, or continue being, meaningful participants in society. However, there is a significant shortfall between the need for and provision of AT, and this is patterned by a range of social, demographic and structural factors. To seize the opportunity that assistive technology offers, regional, national and sub-national assistive technology policies are urgently required. This paper was developed for and through discussion at the Global Research, Innovation and Education on Assistive Technology (GREAT) Summit; organized under the auspices of the World Health Organization's Global Collaboration on Assistive Technology (GATE) program. It outlines some of the key principles that AT polices should address and recognizes that AT policy should be tailored to the realities of the contexts and resources available. AT policy should be developed as a part of the evolution of related policy across a number of different sectors and should have clear and direct links to AT as mediators and moderators for achieving the Sustainable Development Goals. The consultation process, development and implementation of policy should be fully inclusive of AT users, and their representative organizations, be across the lifespan, and imbued with a strong systems-thinking ethos. Six barriers are identified which funnel and diminish access to AT and are addressed systematically within this paper. We illustrate an example of good practice through a case study of AT services in Norway, and we note the challenges experienced in less well-resourced settings. A number of economic factors relating to AT and economic arguments for promoting AT use are also discussed. To address policy-development the importance of active citizenship and advocacy, the need to find mechanisms to scale up good community practices to a higher level, and the importance of political engagement for the policy process, are highlighted. Policy should be evidence-informed and allowed for evidence-making; however, it is important to account for other factors within the given context in order for policy to be practical, authentic and actionable. Implications for Rehabilitation The development of policy in the area of asssitive technology is important to provide an overarching vision and outline resourcing priorities. This paper identifies some of the key themes that should be addressed when developing or revising assistive technology policy. Each country should establish a National Assistive Technology policy and develop a theory of change for its implementation.

To determine whether spa therapy has a beneficial effect on pain and disability in patients with chronic shoulder pain, this single-blind randomised controlled clinical trial included patients with chronic shoulder pain due to miscellaneous conditions attending one of four spa centres as outpatients. Patients were randomised into two groups: spa therapy (18 days of standardised treatment combining thermal therapy together with supervised mobilisation in a thermal pool) and controls (spa therapy delayed for 6 months: 'immediate versus delayed treatment' paradigm). All patients continued usual treatments during the 6-month follow-up period. The main endpoint was the mean change in the French-Quick DASH (F-QD) score at 6 months. The effect size of spa therapy was calculated, and the proportion of patients reaching minimal clinically important improvement (MCII) was compared. Secondary endpoints were the mean change in SF-36, treatment use and tolerance. One hundred eighty-six patients were included (94 patients as controls, 92 in the spa group) and analysed by intention to treat. At 6 months, the mean change in the F-QD score was statistically significantly greater among spa therapy patients than controls (- 32.6 versus - 8.15%; p < 0.001) with an effect size of 1.32 (95%CI: 0.97-1.68). A significantly greater proportion of spa therapy patients reached MCII (59.3 versus 17.9%). Spa therapy was well tolerated with a significant impact on SF-36 components but not on drug intake. Spa therapy provided a statistically significant benefit on pain, function and quality of life in patients with chronic shoulder pain after 6 months compared with usual care.

Background: Amputation of lower limb results in limitations in mobility which are amenable to multiple rehabilitation interventions. The challenges faced by the persons with lower limb amputation vary internationally. The International Classification of Functioning, Disability and Health provides a common language to describe the function of persons with lower limb amputation across various countries., Objectives: This article reports the concepts in mobility important to persons with lower limb amputation across six countries using the International Classification of Functioning, Disability and Health., Study Design: Qualitative study using focus groups and individual interviews., Methods: Focus groups and individual interviews of persons with lower limb amputation were organised across six countries to identify the issues faced by patients with an amputation during and after their amputation, subsequent rehabilitation and on an ongoing basis in their daily life. Meaningful concepts were extracted from the responses and linked to suitable second-level and where applicable third-level International Classification of Functioning, Disability and Health categories. International Classification of Functioning, Disability and Health categorical frequencies were analysed to represent the prevalence and spread of International Classification of Functioning, Disability and Health categories by location., Results: A total of 133 patients were interviewed. A large percentage (93%) of the identified concepts could be matched to International Classification of Functioning, Disability and Health categories for quantitative analysis., Conclusion: The important concepts in mobility were similar across different countries. The comprehensiveness of International Classification of Functioning, Disability and Health as a classification system for human function and its universality across the globe is demonstrated by the large proportion of the concepts contained in the interviews from across the study centres that could be matched to International Classification of Functioning, Disability and Health categories. Clinical relevance The activity and participation restrictions faced by a person with lower limb amputation vary internationally and are amenable to multiple rehabilitation interventions. The International Classification of Functioning, Disability and Health may provide a common language to report and quantify the various concepts important to the patient in their rehabilitation journey.

Background: To understand private consumer and clinician preferences towards different rehabilitation modes following knee or hip arthroplasty, and identify factors which influence the chosen rehabilitation pathway., Methods: Mixed methods cross-sectional study involving 95 semi-structured interviews of consumers (patients and carers) and clinicians (arthroplasty surgeons, physiotherapists and rehabilitation physicians) in Sydney, Australia, during 2014-2015. Participants were asked about the acceptability of different modes of rehabilitation provision, and factors influencing their chosen rehabilitation pathway. Interviews were in person or via the telephone. Qualitative analysis software was used to electronically manage qualitative data. An analytical approach guided data analysis., Results: Pre-operative preferences strongly influenced the type of rehabilitation chosen by consumers. Key factors that influenced this were both intrinsic and extrinsic, including; the previous experience of self or known others, the perceived benefits of the chosen mode, a sense of entitlement, the role of orthopaedic surgeons and influence of patient preference, a patient's clinical status post-surgery, the private hospital business model and insurance provider involvement. The acceptability of rehabilitation modes varied between clinician groups., Conclusions: No one rehabilitation mode provided following arthroplasty is singularly preferred by stakeholders. Factors other than the belief that a particular mode was more effective than another appear to dominate the pathway followed by private arthroplasty consumers, indicating evidence-based policies around rehabilitation provision may have limited appeal in the private sector.

Local rural and indigenous communities have assumed increasing responsibility for conservation within and between areas buffering the impacts of agricultural or resource-extraction zones and protected areas. Empowering local communities as central partners in conservation and climate-change mitigation has allowed many people to gain access to land and citizenship rights but has provided limited improvements in access to social services and economic opportunities even as expectation about their role as environmental stewards grows. These expectations, however, are inconsistent with reality. We conducted multiple field studies in Brazil since the mid-1980s to illustrate the discrepancies between conservation programs and local conditions and expectations. We suggest that public policies and conservation programs should not delegate responsibility for managing protected areas to local and indigenous communities without considering local needs and expectations and locals' attitudes toward conservation. In other words, behavior that maintains or improves the environment should not be treated as traditional based on the expectations of outsiders. Framing local populations as traditional environmentalists creates contradictions and frustrations for local populations and for conservation professionals and policy makers., (© 2016 Society for Conservation Biology.)

Importance: Formal rehabilitation programs, including inpatient programs, are often assumed to optimize recovery among patients after undergoing total knee arthroplasty. However, these programs have not been compared with any outpatient or home-based programs., Objective: To determine whether 10 days of inpatient rehabilitation followed by a monitored home-based program after total knee arthroplasty provided greater improvements than a monitored home-based program alone in mobility, function, and quality of life., Design, Setting, and Participants: In this 2-group, parallel, randomized clinical trial, including a nonrandomized observational group, conducted at 2 public, high-volume arthroplasty hospitals in Sydney, Australia (July 2012-December 2015), 940 patients with osteoarthritis undergoing primary total knee arthroplasty were screened for eligibility. Of the 525 eligible patients consecutively invited to participate, 165 were randomized either to receive inpatient hospital rehabilitation and home-based rehabilitation or to receive home-based rehabilitation alone, and 87 patients enrolled in the observation group., Interventions: Eighty-one patients were randomized to receive 10 days of hospital inpatient rehabilitation followed by an 8-week clinician-monitored home-based program, 84 were randomized to receive the home-based program alone, and 87 agreed to be in the observational group, which included only the home-based program., Main Outcomes and Measures: Mobility at 26 weeks after surgery, measured with the 6-minute walk test. Secondary outcomes included the Oxford Knee Score, which ranges from 0 (worst) to 48 (best) and has a minimal clinically important difference of 5 points; and EuroQol Group 5-Dimension Self-Report Questionnaire (EQ-5D) visual analog scale, which ranges from 0 (worst) to 100 (best), and has a minimal clinically important difference of 23 points., Results: Among the 165 randomized participants, 68% were women, and the cohort had a mean age, 66.9 years (SD, 8.4 years). There was no significant difference in the 6-minute walk test between the inpatient rehabilitation and either of the 2 home program groups (mean difference, -1.01; 95% CI, -25.56 to 23.55), nor in patient-reported pain and function (knee score mean difference, 2.06; 95% CI, -0.59 to 4.71), or quality of life (EQ-5D visual analog scale mean difference, 1.41; 95% CI, -6.42 to 3.60). The number of postdischarge complications for the inpatient group was 12 vs 9 among the home group, and there were no adverse events reported that were a result of trial participation., Conclusions and Relevance: Among adults undergoing uncomplicated total knee arthroplasty, the use of inpatient rehabilitation compared with a monitored home-based program did not improve mobility at 26 weeks after surgery. These findings do not support inpatient rehabilitation for this group of patients., Trial Registration: clinicaltrials.gov Identifier: NCT01583153.

Background: Increased levels of monocytic angiotensin-converting enzyme (ACE) found in haemodialysis (HD) patients may directly participate in the pathogenesis of atherosclerosis. We demonstrated recently that uremia triggers the development of highly pro-atherogenic monocytes via an angiotensin II (AngII)–dependent mechanism. Opposing actions of the AngII-degrading ACE2 remain largely unknown. We examined the status of both ACEs and related receptors in circulating leukocytes of HD, not-dialyzed CKD and healthy individuals. Furthermore, we tested the possible impact of monocytic ACEs on atherogenesis and behaviour of the cells under conditions mimicking chronic renal failure., Methods: Expression of ACE, ACE2, AT1R, AT2R and MASR was investigated on circulating leukocytes from 71 HD (62 ± 14 years), 24 CKD stage 3–5 (74 ± 10 years) patients and 37 healthy control subjects (53 ± 6 years) and isolated healthy monocytes treated with normal and uremic serum. Analyses of ACE, ACE2, ICAM-1, VCAM-1, MCSF and endothelial adhesion were tested on ACE-overexpressing THP-1 monocytes treated with captopril or losartan. ACE2-overexpressing monocytes were subjected to transmigration and adhesion assays and investigated for MCP-1, ICAM-1, VCAM-1, MCSF, AT1R and AT2R expression., Results: The ACE mRNA level was significantly increased in HD and CKD stage 3–5 leukocytes. Correspondingly, ACE2 was downregulated and AngII as well as MAS receptor expression was upregulated in these cells. Healthy monocytes preconditioned with uremic serum reflected the same expressional regulation of ACE/ACE2, MAS and AngII receptors as those observed in HD and CKD stage 3–5 leukocytes. Overexpression of monocytic ACE dramatically decreased levels of ACE2 and induced a pro-atherogenic phenotype, partly reversed by AngII-modifying treatments, leading to an increase in ACE2. Overexpression of ACE2 in monocytes led to reduced endothelial adhesion, transmigration and downregulation of adhesion-related molecules., Conclusions: HD and not-dialyzed CKD stage 3–5 patients show enhanced ACE and decreased ACE2 expression on monocytes. This constellation renders the cells endothelial adhesive and likely supports the development of atherosclerosis.

In Australia, little is known about how the incidence rate (IR) of lower limb amputation (LLA) varies across the country. While studies in other economically developed countries have shown considerable geographic variation in the IR-LLA, mostly these have not considered whether the effect of common risk factors are the same across regions. Mapping variation of the IR-LLA, and the effect of common risk factors, is an important first step to focus research into areas of greatest need and support the development of regional specific hypotheses for in-depth examination. The aim of this study was to describe the geographic variation in the IR-LLA across Australia and understand whether the effect of common risk factors was the same across regions. Using hospital episode data from the Australian National Hospital Morbidity database and Australian Bureau of Statistics, the all-cause crude and age-standardised IR-LLA in males and females were calculated for the nation and each state and territory. Generalised Linear Models were developed to understand which factors influenced geographic variation in the crude IR-LLA. While the crude and age-standardised IR-LLA in males and females were similar in most states and territories, they were higher in the Northern Territory. The effect of older age, being male and the presence of type 2 diabetes was associated with an increase of IR-LLA in most states and territories. In the Northern Territory, the younger age at amputation confounded the effect of sex and type 2 diabetes. There are likely to be many factors not included in this investigation, such as Indigenous status, that may explain part of the variation in the IR-LLA not captured in our models. Further research is needed to identify regional- and population- specific factors that could be modified to reduce the IR-LLA in all states and territories of Australia., Competing Interests: The authors have declared that no competing interests exist.

Background: Monocytic products, such as lipoprotein-associated phospholipase A2 (Lp-PLA2), may participate in the development of atherosclerosis. Heterogeneity of monocytes is widely acknowledged. Classical, intermediate, and non-classical subsets can be discerned. Recently, an inflammatory, pro-atherogenic monocyte population could be identified in hemodialysis patients. In this study, we investigated the expression of Lp-PLA2 on leucocytes and different monocyte subpopulations and their possible role in uremia, inflammation, and atherosclerosis., Methods: Chronic kidney disease stage 5-D (CKD5-D; n = 57), healthy control subjects with hs-C-reactive protein (CRP) levels ≤1 mg/L (CO-N, n = 22) and a control group with inflammatory activation (CRP levels >1 mg/L, CO-I, n = 29) were enrolled in this cross-sectional observation. The CKD5-D cohort was dichotomized into patients with (A+) and without subclinical atherosclerosis (A-) by carotid artery ultrasound measurement. Lp-PLA2 activity was determined in plasma samples, Lp-PLA2 mRNA expression analysis in leucocytes, and sorted monocyte subsets. Effects of Lp-PLA2 overexpression were studied in classical vs. intermediate and non-classical subsets., Results: The classical monocytes expressed the highest Lp-PLA2 mRNA levels as compared to other subpopulations. CKD5-D patients revealed significantly higher Lp-PLA2 transcripts, as well as higher Lp-PLA2 plasma activity as compared to healthy and "inflammatory" controls. In vitro data confirmed that uremia significantly contributes to Lp-PLA2 mRNA upregulation. Non-classical monocytes of A+ patients revealed significant higher Lp-PLA2 mRNA compared to A-., Conclusion: Uremic environment but not inflammation per se increases plasma Lp-PLA2 activity and upregulates monocytic Lp-PLA2 mRNA expression. The highest Lp-PLA2 levels were found in the classical and not in the inflammatory subsets. Atherosclerosis also contributes to a subset-specific increase in Lp-PLA2 mRNA expression., (© 2016 S. Karger AG, Basel.)

The PREDICTS project-Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)-has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity.

The molecular processes of particle binding and endocytosis are influenced by the locally changing mobility of the particle nearby the plasma membrane of a living cell. However, it is unclear how the particle's hydrodynamic drag and momentum vary locally and how they are mechanically transferred to the cell. We have measured the thermal fluctuations of a 1 μm-sized polystyrene sphere, which was placed in defined distances to plasma membranes of various cell types by using an optical trap and fast three-dimensional (3D) interferometric particle tracking. From the particle position fluctuations on a 30 μs timescale, we determined the distance-dependent change of the viscous drag in directions perpendicular and parallel to the cell membrane. Measurements on macrophages, adenocarcinoma cells, and epithelial cells revealed a significantly longer hydrodynamic coupling length of the particle to the membrane than those measured at giant unilamellar vesicles (GUVs) or a plane glass interface. In contrast to GUVs, there is also a strong increase in friction and in mean first passage time normal to the cell membrane. This hydrodynamic coupling transfers a different amount of momentum to the interior of living cells and might serve as an ultra-soft stimulus triggering further reactions., (Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Objectives: To determine the effectiveness of an Early Rehabilitation Intervention (ERI ) versus a Brief Education Intervention (BEI) following road trauma., Primary Objective: return to work or usual activities at 12 weeks (for minor/moderate injury) and 24 weeks for major injury., Secondary Objectives: Reduction in pain, anxiety, depression, disability and incidence of Post Traumatic Stress Disorder and improved quality of life., Design: A multi-site single-blinded stratified randomized clinical trial (RCT)., Methods: 184 patients (92 in each arm) were recruited over 18 months and followed for 12 weeks (minor/moderate injury) and 24 weeks (major injury). Screening questionnaires at 2-4 weeks and follow-up interviews by phone for all outcome measures were undertaken. For those in the ERI group with a positive screen for high risk of persistent symptoms, an early assessment and intervention by a Rehabilitation Physician was offered. Those in the BEI group were sent written information and advised to see their GP., Results: 89.4% of injuries were mild in this cohort. At 12 weeks 73.8% and 69.1% of patients in the ERI and the BEI groups respectively had returned to work or usual activities. There were no significant differences between the two intervention groups with respect to the primary or any secondary outcome measures., Conclusion: This is the first RCT of an ERI following road trauma in Australia. A targeted ERI is as effective as a BEI in assisting those with mild/moderate trauma to return to work or usual activities., (© The Author(s) 2014.)

Filopodia perform cellular functions such as environmental sensing or cell motility, but they also grab for particles and withdraw them leading to an increased efficiency of phagocytic uptake. Remarkably, withdrawal of micron-sized particles is also possible without noticeable movements of the filopodia. Here, we demonstrate that polystyrene beads connected by optical tweezers to the ends of adherent filopodia of J774 macrophages, are transported discontinuously toward the cell body. After a typical resting time of 1-2 min, the cargo is moved with alternating velocities, force constants, and friction constants along the surface of the filopodia. This surfing-like behavior along the filopodium is recorded by feedback-controlled interferometric three-dimensional tracking of the bead motions at 10-100 kHz. We measured transport velocities of up to 120 nm/s and transport forces of ∼ 70 pN. Small changes in position, fluctuation width, and temporal correlation, which are invisible in conventional microscopy, indicate molecular reorganization of transport-relevant proteins in different phases of the entire transport process. A detailed analysis implicates a controlled particle transport with fingerprints of a nanoscale unbinding/binding behavior. The manipulation and analysis methods presented in our study may also be helpful in other fields of cellular biophysics., (Copyright © 2015 Biophysical Society. Published by Elsevier Inc. All rights reserved.)