Search

Abstract Northern regions are warming faster than the rest of the globe. It is difficult to predict ecosystem responses to warming because the thermal sensitivity of their biophysical components varies. Here, we present an analysis of the authors’ expert judgment regarding the sensitivity of six ecosystem components – permafrost, peatlands, lakes, snowpack, vegetation, and endothermic vertebrates – across northern landscapes ranging from boreal to polar biomes. We identified 28 discontinuous component states across a 3700 km latitudinal gradient in northeastern North America and quantified sensitivity as the transition time from an initial to a contrasting state following a theoretical step change increase in mean annual air temperature of 5 °C. We infer that multiple interconnected state shifts are likely to occur within a narrow subarctic latitudinal band at timescales of 10 to more than 100 years, and response times decrease with latitude. Response times differ between components and across latitudes, which is likely to impair the integrity of ecosystems.

Summary: Purpose: To understand the recurrence risk perception of stroke patients and develop a chain mediation model of recurrence risk perception and health behavior. Methods: A cross-sectional study and convenience sampling were used. Stroke survivors were recruited from the neurology departments of three tertiary hospitals. Their recurrence risk perception, behavioral decision-making, social support, self-efficacy, recurrence worry, and health behavior were measured by relevant tools. Data was analyzed through one-way analysis and regression analysis, and the AMOS 21.0 software was used to explore the mediating relationships between variables. Results: Of the 419 participants, 74.7% were aware of stroke recurrence risk. However, only 28.2% could accurately estimate their own recurrence risk. Recurrence risk perception was significantly correlated with behavioral decision-making, social support, self-efficacy, and health behavior (r = .19 ∼ .50, p

Abstract Background Nurse-initiated supported implementation of protocols to manage fever, hyperglycaemia (sugar) and swallowing (FeSS) following acute stroke reduced 90-day death and disability in the landmark Australian Quality in Acute Stroke Care (QASC)-Trial. An international interprofessional collaboration sought to evaluate the effects of nurse-led FeSS implementation on FeSS Protocol adherence in German stroke units. Methods This pre-test/post-test study was conducted in eight German stroke units between 2020 and 2022. Stroke nurses as clinical champions, supported by the project team, conducted multidisciplinary workshops discussing pre-implementation medical record audit results, barriers and facilitators to FeSS Protocol implementation, developed action plans and provided education, with ongoing support from Australia. Medical record audit data were collected by nurses, pre-implementation and three months post-implementation. Results In 771 (pre-implementation) and 679 (post-implementation) patients there were improvements in overall FeSS adherence (pre 20%, post 28%; adjusted difference in proportions (95% CI) 11%, (5.1%, 16%); p

Abstract Streptococcus pneumoniae, a medically important opportunistic bacterial pathogen of the upper respiratory tract, is a major public health concern, causing a wide range of pneumococcal illnesses, both invasive and noninvasive. It is associated with significant global morbidity and mortality, including pneumonia, meningitis, sepsis, and acute otitis media. The major purpose of this study was to determine the molecular epidemiology of Streptococcus pneumoniae strains that cause invasive and noninvasive infections in Ethiopia. A prospective study was undertaken in two regional hospitals between January 2018 and December 2019. Whole-genome sequencing was used to analyze all isolates. Serotypes and multilocus sequence types (MLST) were derived from genomic data. The E-test was used for antimicrobial susceptibility testing. Patient samples obtained 54 Streptococcus pneumoniae isolates, 33 from invasive and 21 from noninvasive specimens. Our findings identified 32 serotypes expressed by 25 Global Pneumococcal Sequence Clusters (GPSCs) and 42 sequence types (STs), including 21 new STs. The most common sequence types among the invasive isolates were ST3500, ST5368, ST11162, ST15425, ST15555, ST15559, and ST15561 (2/33, 6% each). These sequence types were linked to serotypes 8, 7 C, 15B/C, 16 F, 10 A, 15B, and 6 A, respectively. Among the noninvasive isolates, only ST15432, associated with serotype 23 A, had numerous isolates (4/21, 19%). Serotype 14 was revealed as the most resistant strain to penicillin G, whereas isolates from serotypes 3, 8, 7 C, and 10 A were resistant to erythromycin. Notably, all serotype 6 A isolates were resistant to both erythromycin and penicillin G. Our findings revealed an abnormally significant number of novel STs, as well as extremely diversified serotypes and sequence types, implying that Ethiopia may serve as a breeding ground for novel STs. Recombination can produce novel STs that cause capsular switching. This has the potential to influence how immunization campaigns affect the burden of invasive pneumococcal illness. The findings highlight the importance of continuous genetic surveillance of the pneumococcal population as a vital step toward enhancing future vaccine design.

This article explores the relationships between the American health-care system, trust in institutions, and decision-making processes that have affected COVID-19 vaccine uptake. Findings are based on an analysis of a nationally representative sample of 137 individuals who participated in semi-structured qualitative interviews during the rollout of the first publicly available vaccine in the first quarter of 2021. The vast majority of respondents reported negative experiences with American health care that predated the pandemic, which generated distrust in medical institutions, including hospitals, private health insurance corporations, the pharmaceutical industry, and related government institutions. The article considers the impact of institutional distrust on attitudes about vaccine uptake. Responses fell along a spectrum from vaccine refusal to vaccine acceptance. Sentiment across categories revealed a high degree of hesitancy framed in terms of institutional distrust. The data reveal a complex landscape of beliefs and perceptions, illustrating widespread hesitancy and ambivalence among participants.

Abstract Identifying mechanisms that drive population divergence under varying geographic and ecological scenarios can inform our understanding of evolution and speciation. In particular, analysis of genetic data from island populations with known colonisation timelines allows us to identify potential source populations of diverging island subspecies and current relationships among populations. Silvereyes (Zosterops lateralis) are a small passerine that have served as a valuable study system to investigate evolutionary patterns on both large and small geographic scales. We examined genetic relatedness and diversity of two silvereye subspecies, the mainland Z. l. cornwalli and island Z. l. chlorocephalus, and used 18 077 single nucleotide polymorphisms (SNPs), to compare locations across southeast Queensland, Australia. Although silvereyes are prolific island colonisers our findings revealed population divergence over relatively small spatial scales was strongly influenced by geographic isolation mediated by water barriers. Strong genetic connectivity was displayed between mainland sites, but minimal inter-island connectivity was shown despite comparable sampling distances. Genetic diversity analysis showed little difference in heterozygosity between island and mainland populations, but lower inbreeding scores among the island populations. Our study confirmed the range of the Z. l. chlorocephalus subspecies throughout the southern Great Barrier Reef. Our results show that water barriers and not geographic distance per se are important in driving incipient divergence in island populations. This helps to explain the relatively high number of phenotypically differentiated, but often geographically proximate, island silvereye subspecies compared to a lower number of phenotypically less well-defined Australian continental subspecies.

Abstract Background Stroke affects long-term physical and cognitive function; many survivors report unmet health needs, such as pain or depression. A hospital-led follow-up service designed to address ongoing health problems may avoid unplanned readmissions and improve quality of life. Methods This paper outlines the protocol for a registry-based, randomised controlled trial with allocation concealment of participants and outcome assessors. Based on an intention-to-treat analysis, we will evaluate the feasibility, acceptability, potential effectiveness and cost implications of a new tailored, codesigned, hospital-led follow-up service for people within 6–12 months of stroke. Participants (n = 100) from the Australian Stroke Clinical Registry who report extreme health problems on the EuroQol EQ-5D-3L survey between 90 and 180 days after stroke will be randomly assigned (1:1) to intervention (follow-up service) or control (usual care) groups. All participants will be independently assessed at baseline and 12–14-week post-randomisation. Primary outcomes for feasibility are the proportion of participants completing the trial and for intervention participants the proportion that received follow-up services. Acceptability is satisfaction of clinicians and participants involved in the intervention. Secondary outcomes include effectiveness: change in extreme health problems (EQ-5D-3L), unmet needs (Longer-term Unmet Needs questionnaire), unplanned presentations and hospital readmission, functional independence (modified Rankin Scale) and cost implications estimated from self-reported health service utilisation and productivity (e.g. workforce participation). To inform future research or implementation, the design contains a process evaluation including clinical protocol fidelity and an economic evaluation. Discussion The results of this study will provide improved knowledge of service design and implementation barriers and facilitators and associated costs and resource implications to inform a future fully powered effectiveness trial of the intervention. Trial registration ACTRN12622001015730pr. Trial sponsor Florey Institute of Neuroscience and Mental Health, 245 Burgundy Street, Heidelberg, VIC, 3084, PH: +61 3 9035 7032

Abstract Immune exhaustion corresponds to a loss of effector function of T cells that associates with cancer or chronic infection. Here, our objective was to decipher the mechanisms involved in the immune suppression of myeloid-derived suppressor cells (MDSCs) and to explore the potential to target these cells for immunotherapy to enhance checkpoint blockade efficacy in a chronic parasite infection. We demonstrated that programmed cell-death-1 (PD-1) expression was significantly upregulated and associated with T-cell dysfunction in advanced alveolar echinococcosis (AE) patients and in Echinococcus multilocularis-infected mice. PD-1 blockade ex vivo failed to reverse AE patients’ peripheral blood T-cell dysfunction. PD-1/PD-L1 blockade or PD-1 deficiency had no significant effects on metacestode in mouse model. This was due to the inhibitory capacities of immunosuppressive granulocytic MDSCs (G-MDSCs), especially in the liver surrounding the parasite pseudotumor. MDSCs suppressed T-cell function in vitro in an indoleamine 2, 3 dioxygenase 1 (IDO1)-dependent manner. Although depleting MDSCs alone restored T-cell effector functions and led to some limitation of disease progression in E. multilocularis-infected mice, combination with PD-1 blockade was better to induce antiparasitic efficacy. Our findings provide preclinical evidence in support of targeting MDSC or combining such an approach with checkpoint blockade in patients with advanced AE.

Abstract Objectives To clarify the mechanisms of interventions addressing loneliness and social isolation in older adults living in nursing homes through the involvement of primary and secondary informal caregivers. Methods This scoping review was performed by two independent reviewers, covering the period between 2011 and 2022 and the databases MEDLINE, CINAHL, PsycINFO and Scopus. It included terms related to (A) informal caregivers, (B) nursing homes, (C) psychosocial interventions, (D) involvement and (E) social isolation or loneliness. Results Thirty-three studies met the inclusion criteria. Although there were various definitions and assessment tools related to social isolation and loneliness, the studies referred to three dimensions of these concepts in nursing home residents: the quantity of social interactions, the perception of these encounters and biographical changes in social relationships. Most studies did not explicate the mechanisms of these interventions. The review uncovered the following aspects of intervention mechanisms: increasing opportunities for social contact, creating meaningful encounters, maintaining existing relationships with primary informal caregivers and establishing new ones with secondary informal caregivers. Conclusion Studies reporting on interventions addressing loneliness and social isolation in nursing home residents need to clarify and detail their intervention mechanisms in order to foster more targeted interventions. In addition, there is a need for further research on large-scale programs or care philosophies in this field and the development of intervention designs, which allow for tailored intervention formats in order to respond to the individual perception of social relationships.

Abstract Dietary protein is a critical regulator of metabolic health and aging. Low protein diets are associated with healthy aging in humans, and dietary protein restriction extends the lifespan and healthspan of mice. In this study, we examined the effect of protein restriction (PR) on metabolic health and the development and progression of Alzheimer’s disease (AD) in the 3xTg mouse model of AD. Here, we show that PR promotes leanness and glycemic control in 3xTg mice, specifically rescuing the glucose intolerance of 3xTg females. PR induces sex-specific alterations in circulating and brain metabolites, downregulating sphingolipid subclasses in 3xTg females. PR also reduces AD pathology and mTORC1 activity, increases autophagy, and improves the cognition of 3xTg mice. Finally, PR improves the survival of 3xTg mice. Our results suggest that PR or pharmaceutical interventions that mimic the effects of this diet may hold promise as a treatment for AD.

The roles of Indigenous youth in environmental research remain largely unexplored with little practical guidance for achieving meaningful engagement in environmental research. This paper aims to characterize the varying types of Inuit youth engagement in environmental research conducted in Inuit Nunangat. Findings were derived from a community-engaged participatory research approach in Mittimatalik (Pond Inlet, Nunavut). Our typology of Inuit youth engagement in environmental research suggests three types of engagements: “participate”, “conduct”, and “control”. Results highlight that Inuit youth who are interested in undertaking their own environmental research projects expect to enhance their knowledge of natural and life sciences more than those who may seek short-term supportive research roles. Strategies employed by researchers seeking to enhance youth research capacity may also vary based on youth wants and expectations. Our findings suggest that there is no one-size-fits all solution. None of the engagement types identified were necessarily and inherently considered better than the others by project contributors, unlike what has been proposed in other, hierarchical, typologies. Our proposed typology contributes to a better understanding of the varying roles that Inuit youth can play in environmental research, as well as inform potential frameworks for enhancing Inuit youth engagement and leadership in research.

ABSTRACT Background Currently, there are no agreed quality standards for post‐stroke aphasia services. Therefore, it is unknown if care reflects best practices or meets the expectations of people living with aphasia. We aimed to (1) shortlist, (2) operationalise and (3) prioritise best practice recommendations for post‐stroke aphasia care. Methods Three phases of research were conducted. In Phase 1, recommendations with strong evidence and/or known to be important to people with lived experience of aphasia were identified. People with lived experience and health professionals rated the importance of each recommendation through a two‐round e‐Delphi exercise. Recommendations were then ranked for importance and feasibility and analysed using a graph theory–based voting system. In Phase 2, shortlisted recommendations from Phase 1 were converted into quality indicators for appraisal and voting in consensus meetings. In Phase 3, priorities for implementation were established by people with lived experience and health professionals following discussion and anonymous voting. Findings In Phase 1, 23 best practice recommendations were identified and rated by people with lived experience (n = 26) and health professionals (n = 81). Ten recommendations were shortlisted. In Phase 2, people with lived experience (n = 4) and health professionals (n = 17) reached a consensus on 11 quality indicators, relating to assessment (n = 2), information provision (n = 3), communication partner training (n = 3), goal setting (n = 1), person and family‐centred care (n = 1) and provision of treatment (n = 1). In Phase 3, people with lived experience (n = 5) and health professionals (n = 7) identified three implementation priorities: assessment of aphasia, provision of aphasia‐friendly information and provision of therapy. Interpretation Our 11 quality indicators and 3 implementation priorities are the first step to enabling systematic, efficient and person‐centred measurement and quality improvement in post‐stroke aphasia services. Quality indicators will be embedded in routine data collection systems, and strategies will be developed to address implementation priorities. Patient and Public Contribution Protocol development was informed by our previous research, which explored the perspectives of 23 people living with aphasia about best practice aphasia services. Individuals with lived experience of aphasia participated as expert panel members in our three consensus meetings. We received support from consumer advisory networks associated with the Centre for Research Excellence in Aphasia Rehabilitation and Recovery and the Queensland Aphasia Research Centre.

Objective Pregnant women with COVID-19 are at elevated risk for severe outcomes, but clinical data on management of these patients are limited. Monoclonal antibodies, such as casirivimab plus imdevimab (CAS+IMD), have proven effective in treating non-pregnant adults with COVID-19, prompting further evaluation in pregnant women.Methods A phase 3 portion of an adaptive, multicentre, randomised, double-blind, placebo-controlled trial evaluated the safety, clinical outcomes, pharmacokinetics and immunogenicity of CAS+IMD (1200 mg or 2400 mg) in the treatment of pregnant outpatients with COVID-19 (NCT04425629). Participants were enrolled between December 2020 and November 2021, prior to the emergence of Omicron-lineage variants against which CAS+IMD is not active. Safety was evaluated in randomised participants who received study drug (n=80); clinical outcomes were evaluated in all randomised participants (n=82). Only two pregnant participants received placebo, limiting conclusions regarding treatment effect. Infants born to pregnant participants were followed for developmental outcomes ≤1 year of age.Results In pregnant participants, CAS+IMD was well tolerated, with no grade ≥2 hypersensitivity or infusion-related reactions reported. There were no participant deaths, and only one COVID-19–related medically attended visit. Although two pregnancies (3%) reported issues in the fetus/neonate, they were confounded by maternal history or considered to be due to an alternate aetiology. No adverse developmental outcomes in infants ≤1 year of age were considered related to in utero exposure to the study drug. CAS+IMD 1200 mg and 2400 mg rapidly and similarly reduced viral loads, with a dose-proportional increase in concentrations of CAS+IMD in serum. Pharmacokinetics were consistent with that reported in the general population. Immunogenicity incidence was low.Conclusion CAS+IMD treatment of pregnant outpatients with COVID-19 showed similar safety, clinical outcomes and pharmacokinetic profiles to that observed in non-pregnant adults. There was no evidence of an impact on developmental outcomes in infants ≤1 year of age.Trial registration number NCT04425629.

Various stakeholders, such as modelers, policy makers, farmers, and environmental regulators need reliable soil bulk density and coarse fragment content data. These two soil parameters are necessary to calculate soil carbon and nutrients stocks, to estimate water availability for plants, or to assess soil compaction. However, measuring these two parameters is labor intensive and time consuming. Therefore, many agricultural and environmental studies often miss these two soil parameters. Here, we provide four datasets, one with bulk density and coarse fragment contents of topsoil and subsoil, measured in two campaigns of the French Soil Quality Monitoring Network (RMQS for its acronym in French), a second one with the average values for bulk density and coarse fragments of the two campaigns at 0–30 cm and 30–50 cm. The third and the fourth ones are the raw data needed to calculate the two first datasets divided by campaign. In addition, the R script for calculating the depth-weighted values per soil layer is provided

The back-reef depressions, or lagoons, of Reunion Island (western Indian Ocean) host a high abundance of organisms living amongst the coral reefs and are critical sites for artisanal fishing, tourism, and shoreline stability for the island. Over time, increasing degradation of Reunionese reefs has been observed due to overexploitation, beach erosion and eutrophication. Efforts to mitigate the impact of these pressures on aquatic organisms include biodiversity surveys primarily performed through visual censuses that can be logistically complex and may unintentionally overlook organisms. Surveys integrating environmental DNA (eDNA) collections have provided rapid biodiversity assessments, while helping to circumvent some limitations of visual surveys. The present study describes the results of an exploratory eDNA survey, which aims to characterize metazoan communities of four Reunionese lagoons located along the west coast of the island. As eDNA surveys first require deliberate study design and optimization for each new context, we sought to establish a modernized workflow implementing specialized equipment to collect and preserve samples to facilitate future studies in these lagoons. During the austral summer of 2023, samples were pumped directly from surface and bottom depths at each site through self-preserving filters which were then processed for DNA metabarcoding using regions of the 12S ribosomal RNA (12S), small ribosomal subunit 18S (18S) and Cytochrome Oxidase I (COI) genes. The survey detected high species richness that varied by site, and in a single collection period, recovered the presence of 60 teleost families and numerous invertebrate taxa, including members of the coral faunal community that are less studied in Reunion. Distinct biological communities were observed at each site, and within a single lagoon, suggesting that these differences are due to site-specific factors (e.g., environmental variables, geographic distance, etc.). Although continued protocol optimization is needed, the present findings demonstrate the successful application of an eDNA-based survey for biodiversity assessment within Reunionese lagoons.

A recent assessment states that 60–70% of soils in Europe are considered degraded. Protecting such valuable resource require knowledge on soil status through monitoring systems. In Europe, different types of monitoring networks currently exist in parallel. Many EU Member states (MS) developed their own national soil information monitoring system (N-SIMS), some being in place for decades. In parallel in 2009, the European Commission extended the periodic Land Use/Land Cover Area Frame Survey (LUCAS) led by EUROSTAT to sample and analyse the main properties of topsoil in EU in order to develop a homogeneous dataset for EU.Both sources of information are needed to support European policies on soil health evaluation. However, a question remains whether the assessment obtained by using soil properties from both monitoring programs (N-SIMS and LUCAS Soil) are comparable, and what could be the limitations of using either one dataset or the other.Conducted in the context of European Joint Programme (EJP) SOIL, this study shows the results of a comparison between N-SIMS and LUCAS Soil programs among 12 different EU member states including BE, DE, DK, EE, ES, FR, DE, HU, IT, NL, PL, SE and SK. The comparison was done on: (i) the sampling strategies including site densities, land cover and soil type distribution; (ii) the statistical distribution of three soil properties (organic carbon, pH and clay content); (iii) two potential indicators of soil quality (i.e. OC/Clay ratio and pH classes). The results underlined substantial differences in soil properties statistical distributions between N-SIMS and LUCAS Soil in many member states, particularly for woodland and grassland soils, affecting the evaluation of soil health using indicators. Such differences might be explained by both the monitoring strategy and sampling or analytical protocols exposing the potential effect of data source on European and national policies. The results demonstrate the need to work towards data harmonization and in the light of the Soil Monitoring Law, to carefully design the future of soil monitoring in Europe taking into account both LUCAS Soil and N-SIMS considering the significant impact of the monitoring strategies and protocols on soil health indicators.

Marine vertebrates, particularly green sea turtles, are especially vulnerable to plastic pollution through ingestion or entanglement. This study investigated wild juvenile green sea turtles (Chelonia mydas) from two Ecuadorian national parks (Galápagos and Machallilla) to assess the prevalence of plastic pollution in their feces and its potential impact on various health metrics. We analyzed fecal samples from 46 juvenile green sea turtles using Fourier transform infrared spectroscopy (FT-IR) to quantify microplastics (MPs). A complementary methodology using pressurized liquid extraction with double-shot pyrolysis-mass spectrometry gas chromatography (Pyr-GC/MS) was also employed to quantify synthetic polymer mass concentrations. The results from these analyses were compared with blood analytes. FT-IR analysis revealed a mean of 4.4±5.2 MPs/g in fecal samples, with the highest quantities found in the Galápagos Marine Reserve (GMR). The most common MPs shape identified were fibers (x̄= 3.8±4.5 MPs/g), and the predominant synthetic polymers were polyvinyl alcohol (PVOH) and polyacrylates (PMMA). The daily intake of MPs by the sampled turtles ranged from a minimum of 312±409 MPs/day to a maximum of 430±563 MPs/day. Pyr-GC/MS analysis detected polyethylene (PE) with a mean of 367±1158 µg/g and polypropylene (PP) with a mean of 155±434 µg/g in fecal samples, with the highest pollution levels observed in the GMR. Both FT-IR and Pyr-GC/MS techniques detected plastic pollution in 98% of the sampled population. Although both FT-IR and Pyr-GC/MS are reliable methods, they produced slightly different results due to methodological variations. However, both supported the finding that turtles in the GMR were exposed to higher rates of plastic ingestion. Despite the turtles appearing clinically healthy based on blood analysis, significant differences in eleven health metrics were observed between turtles classified as less at risk and those most at risk for plastic pollution. Further research is necessary to understand the potential health implications of these findings.

We provide six short building blocks to devise adaptable soil definitions. These buiding blocks start from a simple and straightforward metaphor and progressively evolve when adopting geophysical, analytical, biogeochemical, cultural, and services-driven points of view. These progressive changes end up with a straightforward, yet most important message for a broad audience. We discuss these building blocks by comparing them to recently proposed soil definitions. Our aims are to initiate a debate on i) what should be, or should not be named soil, ii) what a soil definition should be, iii) the need for both a generic definition and a set of adaptable definitions, based on building blocks, commonly accepted by soil scientists, and iv) the need to adapt our language to diverse audiences. Finally, we propose a definition in one sentence.

Abstract Background In the context of expanding digital health tools, the health system is ready for Learning Health System (LHS) models. These models, with proper governance and stakeholder engagement, enable the integration of digital infrastructure to provide feedback to all relevant parties including clinicians and consumers on performance against best practice standards, as well as fostering innovation and aligning healthcare with patient needs. The LHS literature primarily includes opinion or consensus-based frameworks and lacks validation or evidence of benefit. Our aim was to outline a rigorously codesigned, evidence-based LHS framework and present a national case study of an LHS-aligned national stroke program that has delivered clinical benefit. Main text Current core components of a LHS involve capturing evidence from communities and stakeholders (quadrant 1), integrating evidence from research findings (quadrant 2), leveraging evidence from data and practice (quadrant 3), and generating evidence from implementation (quadrant 4) for iterative system-level improvement. The Australian Stroke program was selected as the case study as it provides an exemplar of how an iterative LHS works in practice at a national level encompassing and integrating evidence from all four LHS quadrants. Using this case study, we demonstrate how to apply evidence-based processes to healthcare improvement and embed real-world research for optimising healthcare improvement. We emphasize the transition from research as an endpoint, to research as an enabler and a solution for impact in healthcare improvement. Conclusions The Australian Stroke program has nationally improved stroke care since 2007, showcasing the value of integrated LHS-aligned approaches for tangible impact on outcomes. This LHS case study is a practical example for other health conditions and settings to follow suit.

Background: The Quality in Acute Stroke Care (QASC) Trial demonstrated that assistance to implement protocols to manage Fever, hyperglycaemia (Sugar) and Swallowing (FeSS) post-stroke reduced death and disability. In 2017, a ‘Strong Recommendation’ for use of FeSS Protocols was included in the Australian Clinical Guidelines for Stroke Management. We aimed to: i) compare adherence to FeSS Protocols pre- and post-guideline inclusion; ii) determine if adherence varied with prior participation in a treatment arm of a FeSS Intervention study, or receiving treatment in a stroke unit; and compare findings with our previous studies. Methods: Pre-test post-test study using Australian acute stroke service audit data comparing 2015/2017 (pre-guideline) versus 2019/2021 (post-guideline) adherence. Primary outcome was adherence to all six FeSS indicators (composite), with mixed-effects logistic regression adjusting for age, sex, stroke type and severity (ability to walk on admission), stroke unit care, hospital prior participation in a FeSS Intervention study, and correlation of outcomes within hospital. Additional analysis examined interaction effects. Results: Overall, 112 hospitals contributed data to ≥1 one Audit cycle for both periods (pre=7011, post=7195 cases); 42 hospitals had participated in any treatment arm of a FeSS Intervention study. Adherence to FeSS Protocols post-guideline increased (pre: composite measure 35% vs post: composite measure 40 %, aOR:1.2 95 %CI: 1.2, 1.3). Prior participation in a FeSS Intervention study (aOR:1.6, 95 %CI: 1.2, 2.0) and stroke unit care (aOR 2.3, 95 %CI: 2.0, 2.5) were independently associated with greater adherence to FeSS Protocols. There was no change in adherence over time based on prior participation in a FeSS Intervention study (p = 0.93 interaction), or stroke unit care (p = 0.07 interaction). Conclusions: There is evidence of improved adherence to FeSS Protocols following a ‘strong recommendation’ for their use in the Australian stroke guidelines. Change in adherence was similar independent of hospital prior participation in a FeSS Intervention study, or stroke unit care. However, maintenance of higher pre-guideline adherence for hospitals prior participation in a FeSS Intervention study suggests that research participation can facilitate greater guideline adherence; and confirms superior care received in stroke units. Nevertheless, less than half of Australian patients are being cared for according to the FeSS Protocols, providing impetus for additional strategies to increase uptake.

ABSTRACT Introduction Outcome measurement instruments (OMIs) are used to gauge the effects of treatment. In post‐stroke aphasia rehabilitation, benchmarks for meaningful change are needed to support the interpretation of patient outcomes. This study is part of a research programme to establish minimal important change (MIC) values (the smallest change above which patients perceive themselves as importantly changed) for core OMIs. As a first step in this process, the views of people with aphasia and clinicians were explored, and consensus was sought on a threshold for clinically meaningful change. Methods Sequential mixed‐methods design was employed. Participants included people with post‐stroke aphasia and speech pathologists. People with aphasia were purposively sampled based on time post‐stroke, age and gender, whereas speech pathologists were sampled according to their work setting (hospital or community). Each participant attended a focus group followed by a consensus workshop with a survey component. Within the focus groups, experiences and methods for measuring meaningful change during aphasia recovery were explored. Qualitative data were transcribed and analysed using reflexive thematic analysis. In the consensus workshop, participants voted on thresholds for meaningful change in core outcome constructs of language, communication, emotional well‐being and quality of life, using a six‐point rating scale (much worse, slightly worse, no change, slightly improved, much improved and completely recovered). Consensus was defined a priori as 70% agreement. Voting results were reported using descriptive statistics. Results Five people with aphasia (n = 4, > 6 months after stroke; n = 5,

BackgroundFew individuals (

Nitrogen is an essential nutrient for plants and a major determinant of plant growth and crop yield. Plants acquire nitrogen mainly in the form of nitrate and ammonium. Both nitrogen sources affect plant responses and signaling pathways in a different way, but these signaling pathways interact, complicating the study of nitrogen responses. Extensive transcriptome analyses and the construction of gene regulatory networks, mainly in response to nitrate, have significantly advanced our understanding of nitrogen signaling and responses in model plants and crops. In this study, we aimed to generate a more comprehensive gene regulatory network for the major crop, rice, by incorporating the interactions between ammonium and nitrate. To achieve this, we assessed transcriptome changes in rice roots and shoots over an extensive time course under single or combined applications of the two nitrogen sources. This dataset enabled us to construct a holistic co-expression network and identify potential key regulators of nitrogen responses. Next to known transcription factors, we identified multiple new candidates, including the transcription factors OsRLI and OsEIL1, which we demonstrated to induce the primary nitrate-responsive genes OsNRT1.1b and OsNIR1. Our network thus serves as a valuable resource to obtain novel insights in nitrogen signaling.

Many cancer cells share with yeast a preference for fermentation over respiration, which is associated with overactive glucose uptake and breakdown, a phenomenon called the Warburg effect in cancer cells. The yeast tps1Δ mutant shows even more pronounced hyperactive glucose uptake and phosphorylation causing glycolysis to stall at GAPDH, initiation of apoptosis through overactivation of Ras and absence of growth on glucose. The goal of the present work was to use the yeast tps1Δ strain to screen for novel compounds that would preferentially inhibit overactive glucose influx into glycolysis, while maintaining basal glucose catabolism. This is based on the assumption that the overactive glucose catabolism of the tps1Δ strain might have a similar molecular cause as the Warburg effect in cancer cells. We have isolated Warbicin® A as a compound restoring growth on glucose of the yeast tps1Δ mutant, showed that it inhibits the proliferation of cancer cells and isolated structural analogs by screening directly for cancer cell inhibition. The Warbicin® compounds are the first drugs that inhibit glucose uptake by both yeast Hxt and mammalian GLUT carriers. Specific concentrations did not evoke any major toxicity in mice but increase the amount of adipose tissue likely due to reduced systemic glucose uptake. Surprisingly, Warbicin® A inhibition of yeast sugar uptake depends on sugar phosphorylation, suggesting transport-associated phosphorylation as a target. In vivo and in vitro evidence confirms physical interaction between yeast Hxt7 and hexokinase. We suggest that reversible transport-associated phosphorylation by hexokinase controls the rate of glucose uptake through hydrolysis of the inhibitory ATP molecule in the cytosolic domain of glucose carriers and that in yeast tps1Δ cells and cancer cells reversibility is compromised, causing constitutively hyperactive glucose uptake and phosphorylation. Based on their chemical structure and properties, we suggest that Warbicin® compounds replace the inhibitory ATP molecule in the cytosolic domain of the glucose carriers, preventing hexokinase to cause hyperactive glucose uptake and catabolism.

Abstract Tauopathies encompass a group of neurodegenerative disorders characterised by diverse tau amyloid fibril structures. The persistence of polymorphism across tauopathies suggests that distinct pathological conditions dictate the adopted polymorph for each disease. However, the extent to which intrinsic structural tendencies of tau amyloid cores contribute to fibril polymorphism remains uncertain. Using a combination of experimental approaches, we here identify a new amyloidogenic motif, PAM4 (Polymorphic Amyloid Motif of Repeat 4), as a significant contributor to tau polymorphism. Calculation of per-residue contributions to the stability of the fibril cores of different pathologic tau structures suggests that PAM4 plays a central role in preserving structural integrity across amyloid polymorphs. Consistent with this, cryo-EM structural analysis of fibrils formed from a synthetic PAM4 peptide shows that the sequence adopts alternative structures that closely correspond to distinct disease-associated tau strains. Furthermore, in-cell experiments revealed that PAM4 deletion hampers the cellular seeding efficiency of tau aggregates extracted from Alzheimer’s disease, corticobasal degeneration, and progressive supranuclear palsy patients, underscoring PAM4’s pivotal role in these tauopathies. Together, our results highlight the importance of the intrinsic structural propensity of amyloid core segments to determine the structure of tau in cells, and in propagating amyloid structures in disease.

Abstract Background Unplanned hospital presentations may occur post-stroke due to inadequate preparation for transitioning from hospital to home. The Recovery-focused Community support to Avoid readmissions and improve Participation after Stroke (ReCAPS) trial was designed to test the effectiveness of receiving a 12-week, self-management intervention, comprising personalised goal setting with a clinician and aligned educational/motivational electronic messages. Primary outcome is as follows: self-reported unplanned hospital presentations (emergency department/admission) within 90-day post-randomisation. We present the statistical analysis plan for this trial. Methods/design Participants are randomised 1:1 in variable block sizes, with stratification balancing by age and level of baseline disability. The sample size was 890 participants, calculated to detect a 10% absolute reduction in the proportion of participants reporting unplanned hospital presentations/admissions, with 80% power and 5% significance level (two sided). Recruitment will end in December 2023 when funding is expended, and the sample size achieved will be used. Logistic regression, adjusted for the stratification variables, will be used to determine the effectiveness of the intervention on the primary outcome. Secondary outcomes will be evaluated using appropriate regression models. The primary outcome analysis will be based on intention to treat. A p-value ≤ 0.05 will indicate statistical significance. An independent Data Safety and Monitoring Committee has routinely reviewed the progress and safety of the trial. Conclusions This statistical analysis plan ensures transparency in reporting the trial outcomes. ReCAPS trial will provide novel evidence on the effectiveness of a digital health support package post-stroke. Trial registration ClinicalTrials.gov ACTRN12618001468213. Registered on August 31, 2018. SAP version 1.13 (October 12 2023) Protocol version 1.12 (October 12, 2022) SAP revisions Nil

Abstract Background Variation in hospital stroke care is problematic. The Quality in Acute Stroke (QASC) Australia trial demonstrated reductions in death and disability through supported implementation of nurse-led, evidence-based protocols to manage fever, hyperglycaemia (sugar) and swallowing (FeSS Protocols) following stroke. Subsequently, a pre-test/post-test study was conducted in acute stroke wards in 64 hospitals in 17 European countries to evaluate upscale of the FeSS Protocols. Implementation across countries was underpinned by a cascading facilitation framework of multi-stakeholder support involving academic partners and a not-for-profit health organisation, the Angels Initiative (the industry partner), that operates to promote evidence-based treatments in stroke centres. .We report here an a priori qualitative process evaluation undertaken to identify factors that influenced international implementation of the FeSS Protocols using a cascading facilitation framework. Methods The sampling frame for interviews was: (1) Executives/Steering Committee members, consisting of academics, the Angels Initiative and senior project team, (2) Angel Team leaders (managers of Angel Consultants), (3) Angel Consultants (responsible for assisting facilitation of FeSS Protocols into multiple hospitals) and (4) Country Co-ordinators (senior stroke nurses with country and hospital-level responsibilities for facilitating the introduction of the FeSS Protocols). A semi-structured interview elicited participant views on the factorsthat influenced engagement of stakeholders with the project and preparation for and implementation of the FeSS Protocol upscale. Interviews were recorded, transcribed verbatim and analysed inductively within NVivo. Results Individual (n = 13) and three group interviews (3 participants in each group) were undertaken. Three main themes with sub-themes were identified that represented key factors influencing upscale: (1) readiness for change (sub-themes: negotiating expectations; intervention feasible and acceptable; shared goal of evidence-based stroke management); (2) roles and relationships (sub-themes: defining and establishing roles; harnessing nurse champions) and (3) managing multiple changes (sub-themes: accommodating and responding to variation; more than clinical change; multi-layered communication framework). Conclusion A cascading facilitation model involving a partnership between evidence producers (academic partners), knowledge brokers (industry partner, Angels Initiative) and evidence adopters (stroke clinicians) overcame multiple challenges involved in international evidence translation. Capacity to manage, negotiate and adapt to multi-level changes and strategic engagement of different stakeholders supported adoption of nurse-initiated stroke protocols within Europe. This model has promise for other large-scale evidence translation programs.

Abstract Membraneless liquid compartments based on phase-separating biopolymers have been observed in diverse cell types and attributed to weak multivalent interactions predominantly based on intrinsically disordered domains. The design of liquid-liquid phase separated (LLPS) condensates based on de novo designed tunable modules that interact in a well-understood, controllable manner could improve our understanding of this phenomenon and enable the introduction of new features. Here we report the construction of CC-LLPS in mammalian cells, based on designed coiled-coil (CC) dimer-forming modules, where the stability of CC pairs, their number, linkers, and sequential arrangement govern the transition between diffuse, liquid and immobile condensates and are corroborated by coarse-grained molecular simulations. Through modular design, we achieve multiple coexisting condensates, chemical regulation of LLPS, condensate fusion, formation from either one or two polypeptide components or LLPS regulation by a third polypeptide chain. These findings provide further insights into the principles underlying LLPS formation and a design platform for controlling biological processes.

Background Internationally, Mobile Stroke Unit (MSU) ambulances have changed pre-hospital acute stroke care delivery. MSU clinical and cost-effectiveness studies are emerging, but little is known about important factors for achieving sustainability of this innovative model of care.Methods Mixed-methods study from the Melbourne MSU (operational since November 2017) process evaluation. Participant purposive sampling included clinical, operational and executive/management representatives from Ambulance Victoria (AV) (emergency medical service provider), the MSU clinical team, and receiving hospitals. Sustainability was defined as ongoing MSU operations, including MSU workforce and future model considerations. Theoretically-based on-line survey with Unified Theory of Acceptance and Use of Technology (UTAUT), Self Determination Theory (SDT, Intrinsic Motivation), and open-text questions targeting barriers and benefits was administered (June-September 2019). Individual/group interviews were conducted, eliciting improvement suggestions and requirements for ongoing use. Descriptive and regression analyses (quantitative data) and directed content and thematic analysis (open text and interview data) were conducted.Results There were 135 surveys completed. Identifying that the MSU was beneficial to daily work (β = 0.61), not experiencing pressure/tension about working on the MSU (β = 0.17) and thinking they did well working within the team model (β = 0.17) were significantly associated with wanting to continue working within the MSU model [R2 = 0.76; F(15, 60) = 12.76, P < .001]. Experiences varied between those on the MSU team and those working with the MSU. Advantages were identified for patients (better, faster care) and clinicians (interdisciplinary learning). Disadvantages included challenges integrating into established systems, and establishing working relationships. Themes identified from 35 interviews were MSU team composition, MSU vehicle design and layout, personnel recruitment and rostering, communication improvements between organisations, telemedicine options, MSU operations and dispatch specificity.Conclusion Important factors affecting the sustainability of the MSU model of stroke care emerged. A cohesive team approach, with identifiable benefits and good communication between participating organisations is important for clinical and operational sustainability.

IntroductionCurrent SARS-CoV-2 strains continue to mutate and attempt to evade the antibody response elicited by previous exposures and vaccinations. In September of 2022, the first updated SARS-CoV-2 vaccines, designed to create immune responses specific for the variants circulating in 2022, were approved. These new vaccines, known commonly as the bivalent boost(er), include mRNA that encodes both the original Wuhan-Hu-1 spike protein as well as the spike protein specific to the Omicron BA.4 and BA.5 variants.MethodsWe recruited volunteers from University of Massachusetts student, faculty and staff members to provide samples of blood and saliva at four different time points, including pre-boost and three times post boost and analyzed samples for antibody production as well as neutralization of virus.ResultsOur data provide a comprehensive analysis of the antibody response following a single dose of the bivalent boost over a 6-month period and support previous findings that the response induced after the bivalent boost does not create a strong BA.4/BA.5-specific antibody response.ConclusionWe found no evidence of a specific anti-BA.4/BA.5 response developing over time, including in a sub-population of individuals who become infected after a single dose of the bivalent booster. Additionally, we present data that support the use of saliva samples as a reliable alternative to blood for antibody detection against specific SARS-CoV-2 antigens.

IntroductionHuman physical growth, biological maturation, and intelligence have been documented as increasing for over 100 years. Comparing the timing of secular trends in these characteristics could provide insight into what underlies them. However, they have not been examined in parallel in the same cohort during different developmental phases. Thus, the aim of this study was to examine secular trends in body height, weight, and head circumference, biological maturation, and intelligence by assessing these traits concurrently at four points during development: the ages of 4, 9, 14, and 18 years.MethodsData derived from growth measures, bone age as an indicator of biological maturation, and full-scale intelligence tests were drawn from 236 participants of the Zurich Longitudinal Studies born between 1978 and 1993. In addition, birth weight was analyzed as an indicator of prenatal conditions.ResultsSecular trends for height and weight at 4 years were positive (0.35 SD increase per decade for height and an insignificant 0.27 SD increase per decade for weight) and remained similar at 9 and 14 years (height: 0.46 SD and 0.38 SD increase per decade; weight: 0.51 SD and 0.51 SD increase per decade, respectively) as well as for weight at age 18 years (0.36 SD increase per decade). In contrast, the secular trend in height was no longer evident at age 18 years (0.09 SD increase per decade). Secular trends for biological maturation at 14 years were similar to those of height and weight (0.54 SD increase per decade). At 18 years, the trend was non-significant (0.38 SD increase per decade). For intelligence, a positive secular trend was found at 4 years (0.54 SD increase per decade). In contrast, negative secular trends were observed at 9 years (0.54 SD decrease per decade) and 14 years (0.60 SD decrease per decade). No secular trend was observed at any of the four ages for head circumference (0.01, 0.24, 0.17, and − 0.04 SD increase per decade, respectively) and birth weight (0.01 SD decrease per decade).DiscussionThe different patterns of changes in physical growth, biological maturation, and intelligence between 1978 and 1993 indicate that distinct mechanisms underlie these secular trends.

The soil organic carbon (SOC) to clay-sized particles ratio (SOC/clay) has recently been selected as an indicator of the soil organic matter status in managed mineral soils within the framework of the European Soil Monitoring Law proposal. This indicator was initially developed to predict soil structural quality in a local study in Switzerland and was subsequently tested at national scales in England and Wales, and in Germany. In this study, we evaluated if the SOC/clay ratio was relevant to assess the structural quality of soils at the national scale in mainland France. We additionally evaluated its variant, SOC/(silt

Introduction People with aphasia following stroke experience disproportionally poor outcomes, yet there is no comprehensive approach to measuring the quality of aphasia services. The Meaningful Evaluation of Aphasia SeRvicES (MEASuRES) minimum dataset was developed in partnership with people with lived experience of aphasia, clinicians and researchers to address this gap. It comprises sociodemographic characteristics, quality indicators, treatment descriptors and outcome measurement instruments. We present a protocol to pilot the MEASuRES minimum dataset in clinical practice, describe the factors that hinder or support implementation and determine meaningful thresholds of clinical change for core outcome measurement instruments.Methods and analysis This research aims to deliver a comprehensive quality assessment toolkit for poststroke aphasia services in four studies. A multicentre pilot study (study 1) will test the administration of the MEASuRES minimum dataset within five Australian health services. An embedded mixed-methods process evaluation (study 2) will evaluate the performance of the minimum dataset and explore its clinical applicability. A consensus study (study 3) will establish consumer-informed thresholds of meaningful change on core aphasia outcome constructs, which will then be used to establish minimal important change values for corresponding core outcome measurement instruments (study 4).Ethics and dissemination Studies 1 and 2 have been registered with the Australian and New Zealand Clinical Trial Registry (ACTRN12623001313628). Ethics approval has been obtained from the Royal Brisbane and Women’s Hospital (HREC/2023/MNHB/95293) and The University of Queensland (2022/HE001946 and 2023/HE001175). Study findings will be disseminated through peer-reviewed publications, conference presentations and engagement with relevant stakeholders including healthcare providers, policy-makers, stroke and rehabilitation audit and clinical quality registry custodians, consumer support organisations, and individuals with aphasia and their families.

Abstract The stellar optoelectronic properties of metal halide perovskites provide enormous promise for next-generation optical devices with excellent conversion efficiencies and lower manufacturing costs. However, there is a long-standing ambiguity as to whether the perovskite surface/interface (e.g. structure, charge transfer or source of off-target recombination) or bulk properties are the more determining factor in device performance. Here we fabricate an array of CsPbI3 crystal and hybrid glass composites by sintering and globally visualise the property-performance landscape. Our findings reveal that the interface is the primary determinant of the crystal phases, optoelectronic quality, and stability of CsPbI3. In particular, the presence of a diffusion “alloying” layer is discovered to be critical for passivating surface traps, and beneficially altering the energy landscape of crystal phases. However, high-temperature sintering results in the promotion of a non-stoichiometric perovskite and excess traps at the interface, despite the short-range structure of halide is retained within the alloying layer. By shedding light on functional hetero-interfaces, our research offers the key factors for engineering high-performance perovskite devices.

Abstract Background Dehydration and malnutrition are common in hospitalised patients following stroke leading to poor outcomes including increased mortality. Little is known about hydration and nutrition care practices in hospital to avoid dehydration or malnutrition, and how these practices vary in different countries. This study sought to capture how the hydration and nutrition needs of patients’ post-stroke are assessed and managed in the United Kingdom (UK) and Australia (AUS). Aim To examine and compare current in-hospital hydration and nutrition care practice for patients with stroke in the UK and Australia. Methods A cross-sectional survey was conducted between April and November 2019. Questionnaires were mailed to stroke specialist nurses in UK and Australian hospitals providing post-stroke inpatient acute care or rehabilitation. Non-respondents were contacted up to five times. Results We received 150/174 (86%) completed surveys from hospitals in the UK, and 120/162 (74%) in Australia. Of the 270 responding hospitals, 96% reported undertaking assessment of hydration status during an admission, with nurses most likely to complete assessments (85%). The most common methods of admission assessment were visual assessment of the patient (UK 62%; AUS 58%), weight (UK 52%; AUS 52%), and body mass index (UK 47%; AUS 42%). Almost all (99%) sites reported that nutrition status was assessed at some point during admission, and these were mainly completed by nurses (91%). Use of standardised nutrition screening tools were more common in the UK (91%) than Australia (60%). Similar proportions of hydration management decisions were made by physicians (UK 84%; AUS 83%), and nutrition management decisions by dietitians (UK 98%; AUS 97%). Conclusion Despite broadly similar hydration and nutrition care practices after stroke in the UK and Australia, some variability was identified. Although nutrition assessment was more often informed by structured screening tools, the routine assessment of hydration was generally not. Nurses were responsible for assessment and monitoring, while dietitians and physicians undertook decision-making regarding management. Hydration care could be improved through the development of standardised assessment tools. This study highlights the need for increased implementation and use of evidence-based protocols in stroke hydration and nutrition care to improve patient outcomes.

Soil compaction is one of the most important and readily mitigated threats to soil health. Digital Soil Mapping (DSM) has emerged as an efficient method to provide broad-scale maps by combining soil information with environmental covariates. Until now, soil information input to DSM has been mainly composed of point-based quantitative measurements of soil properties and/or of soil type/horizon classes derived from laboratory analysis, point observations, or soil maps. In this study, we used field estimates of soil compaction to map soil behavior to compaction at a national scale. The results from a previous study enabled clustering of six different behaviors using the in situ field observations. Mapping potential responses to soil compaction is an effective land management tool for preventing future compaction. Random forest was used to make spatial predictions of soil behavior to compaction over cultivated soils of mainland France (about 210,000 km2). Modeling was performed at 90 m resolution. The map enabled us to spatially identify clusters of possible responses to compaction. Most clusters were consistent with known geographic distributions of some soil types and properties. This consistency was checked by comparing maps with both national and local-scale external sources of soil information. The best spatial predictors were available digital maps of soil properties (clay, silt, sand, organic carbon (SOC) content, and pH), some indicators of soil structural quality using SOC and clay content, and environmental covariates (T °C and relief-related covariates). Predicted maps were interpretable to support management recommendations to mitigate soil compactness at the soil–scape scale. Simple observational field data that are usually collected by soil surveyors, then stored and available in soil databases, provide valuable input data for digital mapping of soil behavior to compaction and assessment of inherent soil sensitivity to compaction.

Soils are a finite resource that is under threat, mainly due to human pressure. Therefore, there is an urgent need to produce maps of soil properties, functions and behaviors that can support land management and various stakeholders’ decisions. Compaction is a major threat to soil functions, such as water infiltration and storage, and crops’ root growth. However, there is no general agreement on a universal and easy-to-implement indicator of soil susceptibility to compaction. The proposed indicators of soil compaction require numerous analytical determinations (mainly bulk density measurements) that are cost prohibitive to implement. In this study, we used data collected in numerous in situ topsoil observations during conventional soil survey and compared field observations to usual indicators of soil compactness. We unraveled the relationships between field estimates of soil compactness and measured soil properties. Most of the quantitative indicators proposed by the literature were rather consistent with the ordering of soil compactness classes observed in the field. The best relationship was obtained with an indicator using bulk density and clay (BDr2) to define three classes of rooting limitation. We distinguished six clusters of topsoil behaviors using hierarchical clustering. These clusters exhibited different soil behaviors to compaction that were related to soil properties, such as particle-size fractions, pH, CaCO3 and organic carbon content, cation exchange capacity, and some BDr2 threshold values. We demonstrate and discuss the usefulness of field observations to assess topsoil behavior to compaction. The main novelty of this study is the use of large numbers of qualitative field observations of soil profiles and clustering to identify contrasting behavior. To our knowledge, this approach has almost never been implemented. Overall, analysis of qualitative and quantitative information collected in numerous profiles offers a new way to discriminate some broad categories of soil behavior that could be used to support land management and stakeholders’ decisions.

Abstract Although DNA methyltransferase inhibitors (DNMTis), such as azacitidine and decitabine, are used extensively in the treatment of myelodysplastic syndromes and acute myeloid leukemia, there remain unanswered questions about DNMTi's mechanism of action and predictors of clinical response. Because patients often remain on single‐agent DNMTis or DNMTi‐containing regimens for several months before knowing whether clinical benefit can be achieved, the development and clinical validation of response‐predictive biomarkers represents an important unmet need in oncology. In this review, we will summarize the clinical studies that led to the approval of azacitidine and decitabine, as well as the real‐world experience with these drugs. We will then focus on biomarker development for DNMTis—specifically, efforts at determining exposure–response relationships and challenges that remain impacting the broader clinical translation of these methods. We will highlight recent progress in liquid‐chromatography tandem mass spectrometry technology that has allowed for the simultaneous measurement of decitabine genomic incorporation and global DNA methylation, which has significant potential as a mechanism‐of‐action based biomarker in patients on DNMTis. Last, we will cover important research questions that need to be addressed in order to optimize this potential biomarker for clinical use.

Developments in textile and fiber engineering have allowed the development of functional clothing such as protective wear, sportswear, and medical clothing. Stimulating pressure points on the skin has a wide range of applications in manual therapy – both to eliminate functional disorders in the musculoskeletal system and to relieve pain. An acupressure-like effect can be achieved when the practitioner or the person pressures the skin with the thumb on specific pressure-points on the body. So far, there have not been any product solutions which combine (full)-body garments with an acupressure-like effect. Understanding textiles as a grid which holds pressure balls in place and making use of fiber and textile technologies for industrial knitting has enabled “trykk.” to develop four pressure-point-garments with different textile variables. The purpose of the garment is to substitute the mechanical stimulation of the acupressure-like thumb on the skin through a patent-pending 3-dimensional textile-body interface which consists of a flexible textile grid and small marble-sized semi-precious stone balls. This paper describes a study set-up where the four prototypes in five different haptic use-scenarios are compared to the average force applied in an acupressure-like intervention. Besides, data of the likeability (satisfaction) regarding the four distinctive textiles were obtained. Results demonstrated a comparable performance of the prototypes in four out of five use case scenarios. Textile variables significantly altered users’ interest in the garments, yet had no significant effect on the technical performance and the perceived intensity of stimulation.

Aims: Symptomatic spinal stenosis is a very common problem, and decompression surgery has been shown to be superior to nonoperative treatment in selected patient groups. However, performing an instrumented fusion in addition to decompression may avoid revision and improve outcomes. The aim of the SpInOuT feasibility study was to establish whether a definitive randomized controlled trial (RCT) that accounted for the spectrum of pathology contributing to spinal stenosis, including pelvic incidence-lumbar lordosis (PI-LL) mismatch and mobile spondylolisthesis, could be conducted. Methods: As part of the SpInOuT-F study, a pilot randomized trial was carried out across five NHS hospitals. Patients were randomized to either spinal decompression alone or spinal decompression plus instrumented fusion. Patient-reported outcome measures were collected at baseline and three months. The intended sample size was 60 patients. Results: Of the 90 patients screened, 77 passed the initial screening criteria. A total of 27 patients had a PI-LL mismatch and 23 had a dynamic spondylolisthesis. Following secondary inclusion and exclusion criteria, 31 patients were eligible for the study. Six patients were randomized and one underwent surgery during the study period. Given the low number of patients recruited and randomized, it was not possible to assess completion rates, quality of life, imaging, or health economic outcomes as intended. Conclusion: This study provides a unique insight into the prevalence of dynamic spondylolisthesis and PI-LL mismatch in patients with symptomatic spinal stenosis, and demonstrates that there is a need for a definitive RCT which stratifies for these groups in order to inform surgical decision-making. Nonetheless a definitive study would need further refinement in design and implementation in order to be feasible. Cite this article: Bone Jt Open 2023;4(8):573–579.

Abstract Background In New-Caledonia, at the end of each shrimp production cycle, earthen ponds are drained and dried to enhance microbial decomposition of nutrient-rich waste trapped in the sediment during the rearing. However, excessive ponds drying may not be suitable for the decomposition activities of microorganisms. Halophytes, salt tolerant plants, naturally grow at vicinity of shrimp ponds; due to their specificity, we explored whether halophytes cultivation during the pond drying period may be suitable for pond bioremediation. In addition, plants are closely associated with microorganisms, which may play a significant role in organic matter decomposition and therefore in bioremediation. Thus, in this study we aimed to determine the impact of 3 halophyte species (Suaeda australis, Sarcocornia quinqueflora and Atriplex jubata) on active sediment microbial communities and their implications on organic matter degradation. Results Drying significantly decreased the microbial diversity index compared to those of wet sediment or sediment with halophytes. Microbial profiles varied significantly over time and according to the experimental conditions (wet, dry sediment or sediment with halophyte species). Halophytes species seemed to promote putative microbial metabolism activities in the sediment. Taxa related to nitrogen removal, carbon mineralisation, sulphur reduction and sulphide oxidation were significant biomarkers in sediment harbouring halophytes and may be relevant for bioremediation. Whereas microbial communities of dry sediment were marked by soil limited-moisture taxa with no identification of microbial metabolic functions. Nitrogen reduction in sediments was evidenced in wet sediment and in sediments with halophytes cultures, along with putative microbial denitrification activities. The greatest nitrogen reduction was observed in halophytes culture. Conclusion The efficiency of sediment bioremediation by halophytes appears to be the result of both rhizosphere microbial communities and plant nutrition. Their cultures during the pond drying period may be used as aquaculture diversification by being a sustainable system.

The routes by which foreign objects enter cells is well studied; however, their fate following uptake has not been explored extensively. Following exposure to synchrotron-sourced (SS) terahertz (THz) radiation, reversible membrane permeability has been demonstrated in eukaryotic cells by the uptake of nanospheres; nonetheless, cellular localization of the nanospheres remained unclear. This study utilized silica core-shell gold nanospheres (AuSi NS) of diameter 50 ± 5 nm to investigate the fate of nanospheres inside pheochromocytoma (PC 12) cells following SS THz exposure. Fluorescence microscopy was used to confirm nanosphere internalization following 10 min of SS THz exposure in the range 0.5–20 THz. Transmission electron microscopy followed by scanning transmission electron microscopy energy-dispersive spectroscopic (STEM-EDS) analysis was used to confirm the presence of AuSi NS in the cytoplasm or membrane, as single NS or in clusters (22% and 52%, respectively), with the remainder (26%) sequestered in vacuoles. Cellular uptake of NS in response to SS THz radiation could have suitable applications in a vast number of biomedical applications, regenerative medicine, vaccines, cancer therapy, gene and drug delivery.

Objectives: Disease caused by the bacterium Neisseria meningitidis remains a worldwide public health challenge, despite the steadily decreasing incidence in Western countries. The objective of this study was to explore the epidemiology of invasive meningococcal disease in Norway over the last two decades. Design: All isolates sent to the National Reference Laboratory from patients with invasive meningococcal disease between the years 2000 and 2019 were analyzed using whole genome sequencing (total: 625). Results: A five-fold decrease in case numbers occurred over this period, and the situation has gone from being dominated by serogroup B to one where serogroups Y and W are more prevalent. Concurrently, the mean age at infection has increased from 18 to 33 years. Among the 350 serogroup B isolates, 87% were an exact match or cross-reactive with one or both the currently available serogroup B vaccines, but the proportion decreased in the past decade. Core genome analyses revealed a high variation in the number of allelic differences accumulated in epidemiologically linked isolates to the point that near-identical isolates were found several years apart. Conclusion: Allelic distance is an imprecise metric for the degree of epidemiologic linkage between isolates in N. meningitidis.

Abstract Introduction People with lived experience are rarely involved in implementation science research. This study was designed to assess the feasibility of codesigning and delivering implementation strategies with people with lived experience of stroke and health professionals to improve evidence‐based stroke rehabilitation. Methods We used Experience‐Based CoDesign to design and deliver strategies to implement Stroke Clinical Guideline recommendations at one Australian inpatient stroke rehabilitation unit. Workgroups were formed with health professionals and people with 6–12 months experience of living with stroke (survivors and carers). Feasibility of the codesign approach (focusing on acceptability, implementation fidelity, signal of promise) was evaluated using mixed methods, using data from interviews, observations and inpatient self‐reported outcomes. Results Of 18 people with stroke invited, eight (44%) agreed to join the lived experience workgroup. All disciplines with ≥1 full‐time staff members on the stroke unit were represented on the health professional workgroup. Median workgroup attendance over 6 months was n = 8 health professionals, n = 4 survivors of stroke and n = 1 carers. Workgroup members agreed to focus on two Guideline recommendations: information provision and amount of therapy. Workgroup members indicated that the codesign approach was enjoyable and facilitated effective partnerships between health professionals and lived experience workgroup members. Both cohorts reported contributing valuable input to all stages of the project, with responsibility shifting between groups at different project stages. The codesigned strategies signalled promise for improving aspects of information provision and creating additional opportunities for therapy. We could not compare patient‐reported outcomes before and after the implementation period due to high variability between the preimplementation and postimplementation patient cohorts. Conclusion It is feasible to codesign implementation strategies in inpatient rehabilitation with people with lived experience of stroke and health professionals. More research is required to determine the effect of the codesigned strategies on patient and service outcomes. Patient or Public Contribution People with lived experience of stroke codesigned and evaluated implementation strategies. Author F. C. has lived experience of stroke and being an inpatient at the inpatient rehabilitation service, and has provided input into analysis of the findings and preparation of this manuscript.

Digital soil mapping (DSM) is commonly conducted using input soil attributes derived from laboratory analyses of geographically referenced samples. Field observations are often abundant and can offer a dense source of soil data that has the potential to enhance DSM predictions. However, they are not widely used due to to concerns about subjectivity and data quality. This study investigates the usefulness of hand-feel soil texture (HFST) data for DSM. We processed HFST data obtained from forest soils in France from two inventory campaigns: (i) HFST determination from systematic 1 km2 grid observations in France utilizing a specialized soil texture triangle, and (ii) HFST observations from soil survey samples, using a different texture triangle. Both sets of HFST data were used as input soil variables, with the same covariates, for predicting topsoil texture In a sizable, forested area through a DSM method. By employing independent sampling and laboratory soil analyses in selected areas, we uncovered measurement bias in one of the datasets. However, intriguingly, these biased observations identified subtle yet highly specific and unexpected patterns of sands in terraces due to alluvial deposits along small rivers. Thus, field soil observations, even if they are biased, should not be dismissed solely based on their overall predictive performance. It is essential to carefully examine predicted maps and covariates to determine whether patterns may have pedological and/or lithological origins and if they are pertinent for enhancing DSM predictions, enhancing soil process understanding, and meeting the requirements of end users. Numerous HFST are available worldwide, these datasets are usually disregarded for DSM. Here we contend that efforts should be put in recovering these data, and their potential for enhancing DSM and deepening our understanding of soil processes.

Nitrification is a microbial process that converts ammonia (NH3) to nitrite (NO2-) and then to nitrate (NO3-). The first and rate-limiting step in nitrification is ammonia oxidation, which is conducted by both bacteria and archaea. In agriculture, it is important to control this process as high nitrification rates result in NO3- leaching, reduced nitrogen (N) availability for the plants and environmental problems such as eutrophication and greenhouse gas emissions. Nitrification inhibitors can be used to block nitrification, and as such reduce N pollution and improve fertilizer use efficiency (FUE) in agriculture. Currently applied inhibitors target the bacteria, and do not block nitrification by ammonia-oxidizing archaea (AOA). While it was long believed that nitrification in agroecosystems was primarily driven by bacteria, recent research has unveiled potential significant contributions from ammonia-oxidizing archaea (AOA), especially when bacterial activity is inhibited. Hence, there is also a need for AOA-targeting nitrification inhibitors. However, to date, almost no AOA-targeting inhibitors are described. Furthermore, AOA are difficult to handle, hindering their use to test or identify possible AOA-targeting nitrification inhibitors. To address the need for AOA-targeting nitrification inhibitors, we developed two miniaturized nitrification inhibition assays using an AOA-enriched nitrifying community or the AOA Nitrosospaera viennensis. These assays enable high-throughput testing of candidate AOA inhibitors. We here present detailed guidelines on the protocols and illustrate their use with some examples. We believe that these assays can contribute to the discovery of future AOA-targeting nitrification inhibitors, which could complement the currently applied inhibitors to increase nitrification inhibition efficiency in the field and as such contribute to a more sustainable agriculture.

Edge habitats resulting from the construction and maintenance of forest roads favour pioneer, shade-intolerant and disturbance-adapted plant species. The effect of roads on the spread of non-native species has been frequently studied, but few studies have focused upon their effects on native tree species. We studied the effect of forest roads on the expansion dynamics of trembling aspen (Populus tremuloides Michx.) in a boreal forest landscape of eastern Canada. We determined whether roads act as a habitat and dispersal corridor for trembling aspen, and whether populations that established along roads act as a starting point for aspen expansion into adjacent stands. We evaluated the effect of forest roads on the distribution of trembling aspen by surveying the vegetation along 694 km of roads. In 19 stands, we compared the density and age of individuals in 100 m transects established parallel and perpendicular to roads, to determine the role of roads. Trembling aspen is abundant along the forest road network. Forest roads act sometimes as habitat corridors for trembling aspen, but their effects on its density extend only over a short distance (10 m) on each side of the roads. The forest roads did not act as a starting point for the expansion of trembling aspen into adjacent stands. Forest roads are particularly favourable habitats for trembling aspen. Although roads did not act as a starting point for aspen dispersal away from roads, these habitats would be vulnerable to invasion following a disturbance that would reduce the thickness of the organic layer.