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Abstract Introduction Post stroke elbow spasticity (PSES) affects over a third of individuals following stroke and negatively impacts on functional recovery, comfort and quality of life. Drug therapies have limited efficacy and unwanted side effects, botulinum toxin, although effective, is costly, and conventional electrical stimulation therapies are limited long term by habituation. We aim to investigate the efficacy of Sheffield Adaptive Patterned Electrical Stimulation (SHAPES), that delivers temporally and spatially varying pattern of electrical stimulation, against transcutaneous electrical stimulation (TENS) and standard care at reducing PSES. Methods and design Overall, 297 people with PSES will be randomised (1:1:1) to one of 3 arms: Standard care (no electrical stimulation), TENS (conventional patterned electrical stimulation) or SHAPES (adaptive patterned electrical stimulation). Both SHAPES and TENS are delivered using a specially designed electrical stimulation sleeve used for 60 min each day for 6-weeks. Outcome measures are completed at baseline, end of treatment (EOT 6 weeks) and then 6-weeks, 12-weeks and 24-weeks after the end of treatment. Efficacy will be determined based on the proportion of participants experiencing meaningful improvement (18%) in the 7-day Numerical Rating Scale (NRS-S) for PSES, compared between both intervention arms and standard care, and between the two intervention groups. Measures of arm motor function (Action Research Arm Test, MRC scale), and quality of life (SQoL-6D, EQ-5D) will also be measured along with a parallel health economic evaluation. Discussion The results of the SHAPES trial will inform management of elbow spasticity after stroke. The SHAPES intervention is a low cost, self-administered intervention for the management of spasticity that can be used repeatedly, and if found to be more effective than TENS or control has the potential to be widely implemented in the UK NHS healthcare setting. Furthermore, despite the wide use of TENS in the management of spasticity, this study will provide critically required evidence regarding its efficacy. The trial has been registered with the ISRCTN registry (ISRCTN26060261).

Abstract Understanding regional sea level variations is crucial for assessing coastal vulnerability, with accurate sea level data playing a pivotal role. Utilizing historical sea level marigrams can enhance datasets, but current digitization techniques face challenges such as bends and skews in paper charts, impacting sea level values. This study explores often‐overlooked issues during marigram digitization, focusing on the case study of Dún Laoghaire in Ireland (1925–1931). The methodology involves digitizing the original marigram trace and underlying grid to assess offsets at the nearest ft (foot) interval on the paper chart, corresponding to changes in the water level trace for each hour interval. Subtracting the digitized value from the known value (the actual measurement) allows for the determination of differences, which are then subtracted from each hourly trace value. After adjusting for offsets ranging from −3.962 to 13.716 mm (millimetres), the study improves the final accuracy of sea level data to approximately the 10 mm level. Notably, data from 1926 and 1931 exhibit modest offsets (9–14 mm), emphasizing the importance of adjustments for accuracy. Such 10 mm accuracy is compatible with requirements of the Global Sea Level Observing System. Comparing the adjusted digitized data with other survey data shows similar amplitudes and phases for Dún Laoghaire in both the historical and modern datasets, and there is an overall mean sea level rise of 1.5 mm/year when combined with the available data from the Dublin region.

Impracticality and cost of existing pain management strategies during surgical castration of beef cattle have limited their widespread implementation on-farm. A farmer-applied topical anaesthetic formulation, originally developed and used commercially to mitigate the pain of mulesing in lambs, was investigated for its potential use for managing pain in surgically castrated calves. This formulation contained lidocaine, bupivacaine, adrenalin and cetrimide. In this study, 24 Angus bull calves were randomly allocated to (1) surgical castration (C, n=8), (2) surgical castration with the post-operative application of topical anaesthetic (CTA, n=8) and (3) sham castration/control (CON, n=8). The experiment was conducted over 2 days, with treatment groups evenly represented across each day. Calves were habituated to handling before the experiment and blood samples were collected for plasma cortisol measurement at defined time periods before, at and post treatment, (at −0.5, 0 h, then +0.5, 1, 1.5, 2, 4 and 6 h). There was a significant effect of time on cortisol concentrations across all treatment groups (P

Background:. This study examines the rheological properties of various dermal fillers, including hyaluronic acid (HA) fillers, poly-L-lactic acid (PLLA), and calcium hydroxylapatite-carboxymethylcellulose (CaHA-CMC) gels, with a particular focus on the impact of aqueous dilution on CaHA-CMC’s rheology and potential clinical implications. Methods:. Using standardized rheological analysis, we measured and compared the elastic modulus (G′), viscous modulus (G″), and the tan δ values of different dilutions of CaHA-CMC against published values of HA and PLLA fillers. The study aimed to determine the potential clinical use of application-specific CaHA-CMC hydrogel dilutions along a range of gel strength and cohesion for hydrogel fillers in current use. Results:. The findings demonstrate that CaHA-CMC’s rheological properties can be tailored across a broad spectrum of viscoelastic parameters through titrated dilution, ranging from high elasticity to low cohesion. Varying the aqueous volume allows for the rheomodulation of CaHA-CMC, potentially matching the entire rheological spectrum of HA fillers and suggesting an expanded range of clinical applications. Conclusions:. The versatility of CaHA-CMC through dilution may offer a customizable approach for clinical applications, providing practitioners with the ability to fine-tune the properties of fillers to meet specific patient needs and treatment goals. This study lays the groundwork for the potential future use of filler dilutional rheomodulation in clinical practice, tailored to patient- and application-specific needs.

Abstract We have reconstructed baseline δ15N and δ13C of export production at Kingman Reef in the Central Equatorial Pacific (CEP) at sub-decadal resolution, nearly continuously over the last 2000 years. The changes in δ15N reflects the strength of the North Equatorial Counter Current (NECC) relative to the South Equatorial Current (SEC), and to a lesser extent, the North Equatorial Current (NEC). Seasonal to multi-decadal variation in the strength of these currents, through the redistribution of heat, have global climate impacts and influence marine and terrestrial ecosystems. We use modern El Niño-La Nina dynamics and the Tropical Pacific Decadal Variability (TPDV) pattern, which is defined in the CEP, as a framework for analyzing the isotopic data. The CEP δ15N and δ13C records exhibit multi-decadal (50–60 year) variability consistent with TPDV. A large multi-centennial feature in the CEP δ15N data, within age-model uncertainties, is consistent with one of the prolonged dry-pluvial sequences in the American west at the end of the Medieval Climate Anomaly, where low TPDV is correlated with drier conditions. This unique record shows that the strength of the NECC, as reflected in baseline δ15N and δ13C, has at quasi-predictable intervals throughout the late Holocene, toggled the phytoplankton community between prokaryotes and picoplankton versus eukaryotes.

Abstract The structure and design flexibility of aerogels make them promising for soft tissue engineering, though they tend to come with brittleness and low elasticity. While increasing crosslinking density may improve mechanics, it also imparts brittleness. In soft tissue engineering, resilience against mechanical loads from mobile tissues is paramount. We report a hybrid aerogel that consists of self-reinforcing networks of micro- and nanofibers. Nanofiber segments physically entangle microfiber pillars, allowing efficient stress distribution through the intertwined fiber networks. We show that optimized hybrid aerogels have high specific tensile moduli (~1961.3 MPa cm3 g−1) and fracture energies (~7448.8 J m−2), while exhibiting super-elastic properties with rapid shape recovery (~1.8 s). We demonstrate that these aerogels induce rapid tissue ingrowth, extracellular matrix deposition, and neovascularization after subcutaneous implants in rats. Furthermore, we can apply them for engineering soft tissues via minimally invasive procedures, and hybrid aerogels can extend their versatility to become magnetically responsive or electrically conductive, enabling pressure sensing and actuation.

Successful transition from education to the workplace is vital for young people, particularly Indigenous students from remote communities, to support their long-term economic and emotional well-being, social inclusion, physical and mental health. This paper reports findings from a three-year study undertaken collaboratively with young people at a remote Aboriginal boarding school. Motivated by the theoretical constructs of Indigenist theory and Funds of Knowledge, this research centres the voices of Aboriginal peoples. A team of Aboriginal and non-Aboriginal researchers worked "with" young Aboriginal people at the school to develop the method, to collect, and then analyse the data for this strengths-based qualitative study. Currently enrolled young people engaged in yarning with the participants, namely those who were past students from the school. This made it possible to gather stories to better understand the experiences, strengths, and motivations of Aboriginal young people from remote communities and the issues, constraints, and challenges faced when transitioning to life beyond the classroom. The findings highlight what can be improved to prepare Aboriginal people from remote communities for the workplace and for life beyond school--including their existing strengths and knowledge, aspects that occur within the parameters of the school, employer roles, skill development, and enablers of job and life success.

Background: Despite promise in preclinical models of acute respiratory distress syndrome (ARDS), mesenchymal stem cells (MSC) have failed to translate to therapeutic benefit in clinical trials. The MSC is a live cell medicine and interacts with the patient’s disease state. Here, we explored this interaction, seeking to devise strategies to enhance MSC therapeutic function. Methods: Human bone-marrow-derived MSCs were exposed to lung homogenate from healthy and E. coli-induced ARDS rat models. Apoptosis and functional assays of the MSCs were performed. Results: The ARDS model showed reduced arterial oxygenation, decreased lung compliance and an inflammatory microenvironment compared to controls. MSCs underwent more apoptosis after stimulation by lung homogenate from controls compared to E. coli, which may explain why MSCs persist longer in ARDS subjects after administration. Changes in expression of cell surface markers and cytokines were associated with lung homogenate from different groups. The anti-microbial effects of MSCs did not change with the stimulation. Moreover, the conditioned media from lung-homogenate-stimulated MSCs inhibited T-cell proliferation. Conclusions: These findings suggest that the ARDS microenvironment plays an important role in the MSC’s therapeutic mechanism of action, and changes can inform strategies to modulate MSC-based cell therapy for ARDS.

Accidental arterial embolization of hyaluronic acid (HA) fillers can lead to severe complications, including skin ischemia, blindness, and stroke. Currently, the intra-arterial dispersal and fragmentation behavior of HA gels is unknown but critical to our understanding of the pathomechanism of these injuries. This work introduces the Pulsatile Unit for the Laboratory Simulation of Arterio-embolic Restrictions (PULSAR) and evaluates the intravascular behavior of different HA gels. The fragmentation and dispersal behaviors of four HA gels with distinct rheological properties were evaluated via high-resolution videography and ImageJ particle size and morphology analysis. The gels’ elastic modulus (G′), loss modulus (G″), tan(δ), and HA concentration were subsequently correlated with their intra-arterial behaviors. This study effectively confirms the extensive fragmentation of HA gels upon arterial inoculation, with particle sizes ranging from 1 mm. Gel particle size and morphology correlated most significantly with tan(δ). Conversely, arterial flow rates did not significantly influence gel fragmentation behavior, though the probability of proximal, macrovascular obstruction was affected. Overall, this study validates the PULSAR model for simulation of arterial dynamics and the testing of intravascular filler kinematics. The findings demonstrate the ability of gels to microfragment and disseminate distally, as well as induce partial proximal occlusion depending on gel rheology and arterial flow parameters.

Abstract Noninflammatory nodules arising from the injection of biostimulatory fillers persist as an unwanted complication. Pathologically, noninflammatory nodules may arise from superficial injection, accidental boluses, or incorrect concentration of microparticles contained within the filler. This case report introduces a method for reversing calcium hydroxylapatite (CaHA) using focused mechanical vibration. An in situ hyperdilution was created by injecting saline into the nodule core to prepare it for resuspension. Topical microneedling was subsequently applied to generate vibrations, aiming to disperse the accumulated CaHA particles. The outcome demonstrated a significant reduction in the size and visibility of the nodule. This combined saline-microneedling approach offers a potential noninvasive, nonpharmacologic solution for managing superficial CaHA nodules. Level of Evidence: 5

Summary: Background: The Invasive Respiratory Infection Surveillance (IRIS) Consortium was established to assess the impact of the COVID-19 pandemic on invasive diseases caused by Streptococcus pneumoniae, Haemophilus influenzae, Neisseria meningitidis, and Streptococcus agalactiae. We aimed to analyse the incidence and distribution of these diseases during the first 2 years of the COVID-19 pandemic compared to the 2 years preceding the pandemic. Methods: For this prospective analysis, laboratories in 30 countries and territories representing five continents submitted surveillance data from Jan 1, 2018, to Jan 2, 2022, to private projects within databases in PubMLST. The impact of COVID-19 containment measures on the overall number of cases was analysed, and changes in disease distributions by patient age and serotype or group were examined. Interrupted time-series analyses were done to quantify the impact of pandemic response measures and their relaxation on disease rates, and autoregressive integrated moving average models were used to estimate effect sizes and forecast counterfactual trends by hemisphere. Findings: Overall, 116 841 cases were analysed: 76 481 in 2018–19, before the pandemic, and 40 360 in 2020–21, during the pandemic. During the pandemic there was a significant reduction in the risk of disease caused by S pneumoniae (risk ratio 0·47; 95% CI 0·40–0·55), H influenzae (0·51; 0·40–0·66) and N meningitidis (0·26; 0·21–0·31), while no significant changes were observed for S agalactiae (1·02; 0·75–1·40), which is not transmitted via the respiratory route. No major changes in the distribution of cases were observed when stratified by patient age or serotype or group. An estimated 36 289 (95% prediction interval 17 145–55 434) cases of invasive bacterial disease were averted during the first 2 years of the pandemic among IRIS-participating countries and territories. Interpretation: COVID-19 containment measures were associated with a sustained decrease in the incidence of invasive disease caused by S pneumoniae, H influenzae, and N meningitidis during the first 2 years of the pandemic, but cases began to increase in some countries towards the end of 2021 as pandemic restrictions were lifted. These IRIS data provide a better understanding of microbial transmission, will inform vaccine development and implementation, and can contribute to health-care service planning and provision of policies. Funding: Wellcome Trust, NIHR Oxford Biomedical Research Centre, Spanish Ministry of Science and Innovation, Korea Disease Control and Prevention Agency, Torsten Söderberg Foundation, Stockholm County Council, Swedish Research Council, German Federal Ministry of Health, Robert Koch Institute, Pfizer, Merck, and the Greek National Public Health Organization.

Background SARS-CoV-2 infection in Africa has been characterized by a less severe disease profile than what has been observed elsewhere, but the profile of SARS-CoV-2–specific adaptive immunity in these mainly asymptomatic patients has not, to our knowledge, been analyzed.Methods We collected blood samples from residents of rural Kenya (n = 80), who had not experienced any respiratory symptoms or had contact with individuals with COVID-19 and had not received COVID-19 vaccines. We analyzed spike-specific antibodies and T cells specific for SARS-CoV-2 structural (membrane, nucleocapsid, and spike) and accessory (ORF3a, ORF7, ORF8) proteins. Pre-pandemic blood samples collected in Nairobi (n = 13) and blood samples from mild-to-moderately symptomatic COVID-19 convalescent patients (n = 36) living in the urban environment of Singapore were also studied.Results Among asymptomatic Africans, we detected anti-spike antibodies in 41.0% of the samples and T cell responses against 2 or more SARS-CoV-2 proteins in 82.5% of samples examined. Such a pattern was absent in the pre-pandemic samples. Furthermore, distinct from cellular immunity in European and Asian COVID-19 convalescents, we observed strong T cell immunogenicity against viral accessory proteins (ORF3a, ORF8) but not structural proteins, as well as a higher IL-10/IFN-γ cytokine ratio profile.Conclusions The high incidence of T cell responses against different SARS-CoV-2 proteins in seronegative participants suggests that serosurveys underestimate SARS-CoV-2 prevalence in settings where asymptomatic infections prevail. The functional and antigen-specific profile of SARS-CoV-2–specific T cells in African individuals suggests that environmental factors can play a role in the development of protective antiviral immunity.Funding US Centers for Disease Control and Prevention, Division of Global Health Protection; the Singapore Ministry of Health’s National Medical Research Council (COVID19RF3-0060, COVID19RF-001, COVID19RF-008, MOH-StaR17Nov-0001).

IntroductionMesenchymal stromal cells (MSC) are a promising therapeutic for pneumonia-induced sepsis. Here we sought to determine the efficacy of delayed administration of naïve and activated bone marrow (BM), adipose (AD), and umbilical cord (UC) derived MSCs in organized antibiotic resistant Klebsiella pneumosepsis.MethodsHuman BM-, AD-, and UC-MSCs were isolated and expanded and used either in the naïve state or following cytokine pre-activation. The effect of MSC tissue source and activation status was assessed first in vitro. Subsequent experiments assessed therapeutic potential as a delayed therapy at 48 h post infection of rodents with Klebsiella pneumoniae, with efficacy assessed at 120 h.ResultsBM-, AD-, and UC-MSCs accelerated epithelial healing, increased phagocytosis, and reduced ROS-induced epithelial injury in vitro, with AD-MSCs less effective, and naïve MSCs more effective than pre-activated MSCs. Delayed MSC administration in pre-clinical organized Klebsiella pneumosepsis had no effect on physiologic indices, but enhanced resolution of structural lung injury. Delayed therapy with pre-activated MSCs reduced mRNA concentrations of fibrotic factors. Naïve MSC treatment reduced key circulating cell proportions and increased bacterial killing capacity in the lungs whereas pre-activated MSCs enhanced the phagocytic index of pulmonary white cells.DiscussionDelayed MSC therapy enhanced resolution of lung injury induced by antibiotic resistant Klebsiella infection and favorably modulated immune cell profile. Overall, AD-MSCs were less effective than either UC- or BM-MSCs, while naïve MSCs had a more favorable effect profile compared to pre-activated MSCs.

Abstract Photosynthesis in the surface ocean converts atmospheric CO2 into organic particles, with the fraction sinking to depth representing a major part of the ocean's biological pump. Although sinking particles are known to be altered by attached‐bacteria during transit, most prior organic geochemical data indicated only minor replacement of plankton‐derived particles by bacterial material. We exploit bacteria‐specific biomarkers (d‐amino acids) in a multi‐year sediment trap in the Pacific Ocean (1,200 m) and suggest a different view. Major d‐amino acids were consistently measured at abundance demonstrating widespread accumulation of bacterial material in sinking particles. Bacterial detritus was estimated to account for up to 19% of particulate organic carbon and up to 36% of particulate nitrogen, much higher than cell count‐based values. The bacterial relative contribution increased with decreasing export production. Our results indicate that bacterial material constitutes an underappreciated component of the biological pump, a role expected to rise as the ocean warms.

BackgroundMesenchymal stem cells (MSC) have shown immense therapeutic promise in a range of inflammatory diseases, including acute respiratory distress syndrome (ARDS), and are rapidly advancing through clinical trials. Among their multimodal mechanisms of action, MSCs exert strong immunomodulatory effects via their secretome, which contains cytokines, small molecules, extracellular vesicles, and a range of other factors. Recent studies have shown that the MSC secretome can recapitulate many of the beneficial effects of the MSC itself. We aimed to determine the therapeutic capacity of the MSC secretome in a rat bacterial pneumonia model, especially when delivered directly to the lung by nebulization which is a technique more appropriate for the ventilated patient.MethodsConditioned medium (CM) was generated from human bone marrow derived MSCs in the absence of antibiotics and serum supplements. Post-nebulization lung penetration was estimated through nebulization of CM to a cascade impactor and simulated lung and quantification of collected total protein and IL-8 cytokine. Control and nebulized CM was added to a variety of lung cell culture models and injury resolution assessed. In a rat E. coli pneumonia model, CM was instilled or administered by nebulization and lung injury and inflammation assessed at 48 h.ResultsMSC-CM was predicted to have good distal lung penetration and delivery when administered by nebulizer. Both control and nebulized CM reduced NF-κB activation and inflammatory cytokine production in lung cell culture, while promoting cell viability and would closure in oxidative stress and scratch wound models. In a rat bacterial pneumonia model, both instilled and nebulizer delivered CM improved lung function, increasing blood oxygenation and reducing carbon dioxide levels compared to unconditioned medium controls. A reduction in bacterial load was also observed in both treatment groups. Inflammatory cytokines were reduced significantly by both liquid and aerosol CM administration, with less IL-1β, IL-6, and CINC1 in these groups compared to controls.ConclusionMSC-CM is a potential therapeutic for pneumonia ARDS, and administration is compatible with vibrating mesh nebulization.

Diagnosis of tuberculosis (TB) among young children (

The study of geometric morphometrics among stocks has proven to be a valuable tool in delineating fish spatial distributions and discriminating distinct population units. Variations in fish body morphology can be linked to genetic factors or to phenotypic adaptability in response to environmental variables. The tub gurnard (Chelidonichthys lucerna) is a demersal species that usually lives in the bottom of the continental shelf, being widely distributed along the northeast Atlantic, Mediterranean and Black seas. Worldwide interest in the species has increased since 2006, when ICES recognized its potential for commercial exploitation. However, despite its broad geographic occurrence, to date, research on C. lucerna population structure at large spatial scales is still lacking. In this paper, body geometric morphometrics, using a landmark-based truss network, was applied in order to discriminate C. lucerna populations caught in three different fishery grounds areas along the northeast Atlantic: Conwy Bay (United Kingdom), Biscay Bay (Spain) and Matosinhos (Portugal). The results obtained in this study revealed a high overall relocation success (95%) of samples to their original locations, thus demonstrating the existence of significant regional differences and indicating that we are dealing with different fish population units. Moreover, the data revealed a partial overlap between individuals from Spain and United Kingdom, suggesting that in geographically distant areas these populations may inhabit similar environments. However, to corroborate these findings, future works using a holistic approach with alternative and complimentary stock assessment tools (e.g., genetic and phenotypic natural tags) are highly recommended.

BackgroundBenzodiazepines and non-benzodiazepine hypnotics (z-drugs) are commonly prescribed for their anxiolytic and hypnotic properties, though they can also be misused. In studies examining the epidemiology of prescription drug misuse, these medication classes are commonly combined, rendering inadequate knowledge of their patterns of misuse. The objective of this study was to characterize the population prevalence, conditional dependence, and sociodemographic and clinical correlates of the misuse of benzodiazepines and z-drugs.MethodsData from the National Survey on Drug Use and Health from 2015 to 2019 were used to estimate population-level prevalence and characteristics of benzodiazepine and z-drug misuse. Groups were derived based on past-year misuse of benzodiazepines alone, z-drugs alone, or both drug types. Unadjusted regression analyses were used to compare groups on characteristics of interest.ResultsExposure to benzodiazepines and/or z-drugs via prescription or misuse was common; however, only 2% of the population was estimated to have misused a benzodiazepine in the past year, and less than 0.5% misused z-drugs. People who misused only z-drugs were generally older, more likely to have health insurance, more educated, and had less severe psychiatric symptoms. This group was also more likely to report misuse to cope with sleep difficulty. Although concurrent substance use was highly prevalent in all groups, people who misused z-drugs alone generally reported less concurrent substance use than the other groups.ConclusionThe misuse of z-drugs is less common than benzodiazepines, and people who misuse only z-drugs appear to generally have lower clinical severity. Nonetheless, a substantial subgroup of people exposed to z-drugs report concurrent, past-year use of other substances. Further research on z-drug misuse, including consideration of whether it should be grouped with other anxiolytic/hypnotic drugs, is needed.

IntroductionVisual processing deficits in Alzheimer's disease are associated with diminished functional independence. While environmental adaptations have been proposed to promote independence, recent guidance gives limited consideration to such deficits and offers conflicting recommendations for people with dementia. We evaluated the effects of clutter and color contrasts on performances of everyday actions in posterior cortical atrophy and memory-led typical Alzheimer's disease.Methods15 patients with posterior cortical atrophy, 11 with typical Alzheimer's disease and 16 healthy controls were asked to pick up a visible target object as part of two pilot repeated-measures investigations from a standing or seated position. Participants picked up the target within a controlled real-world setting under varying environmental conditions: with/without clutter, with/without color contrast cue and far/near target position. Task completion time was recorded using a target-mounted inertial measurement unit.ResultsAcross both experiments, difficulties locating a target object were apparent through patient groups taking an estimated 50–90% longer to pick up targets relative to controls. There was no evidence of effects of color contrast when locating objects from standing/seated positions and of any other environmental conditions from a standing position on completion time in any participant group. Locating objects, surrounded by five distractors rather than none, from a seated position was associated with a disproportionately greater effect on completion times in the posterior cortical atrophy group relative to the control or typical Alzheimer's disease groups. Smaller, not statistically significant but directionally consistent, ratios of relative effects were seen for two distractors compared with none.DiscussionFindings are consistent with inefficient object localization in posterior cortical atrophy relative to typical Alzheimer's disease and control groups, particularly with targets presented within reaching distance among visual clutter. Findings may carry implications for considering the adverse effects of visual clutter in developing and implementing environmental modifications to promote functional independence in Alzheimer's disease.

The accuracy and flexibility of artificial intelligence (AI) systems often comes at the cost of a decreased ability to offer an intuitive explanation of their predictions. This hinders trust and discourage adoption of AI in healthcare, exacerbated by concerns over liabilities and risks to patients' health in case of misdiagnosis. Providing an explanation for a model's prediction is possible due to recent advances in the field of interpretable machine learning. We considered a data set of hospital admissions linked to records of antibiotic prescriptions and susceptibilities of bacterial isolates. An appropriately trained gradient boosted decision tree algorithm, supplemented by a Shapley explanation model, predicts the likely antimicrobial drug resistance, with the odds of resistance informed by characteristics of the patient, admission data, and historical drug treatments and culture test results. Applying this AI-based system, we found that it substantially reduces the risk of mismatched treatment compared with the observed prescriptions. The Shapley values provide an intuitive association between observations/data and outcomes; the associations identified are broadly consistent with expectations based on prior knowledge from health specialists. The results, and the ability to attribute confidence and explanations, support the wider adoption of AI in healthcare.

We demonstrate the utility and reproducibility of the saltmarsh foraminifera-based ‘geological tide gauge’ (GTG) approach by developing two independent records of relative sea-level (RSL) change for Dublin, Ireland. Our records, recovered from two different saltmarshes, indicate that RSL rose at a century-scale rate of 1.5 ± 0.9 mm yr–1 over the last 200 years. This compares favourably with the shorter, but more precise, mean sea level (MSL) record from the Dublin Port tide gauge, which indicates long-term (1953–2016 CE) rise at a rate of 1.1 ± 0.5 mm yr–1. When corrected for the influence of glacio-isostatic adjustment our saltmarsh-based reconstruction suggests sea levels in Dublin rose at a rate of 1.6 ± 0.9 mm yr–1 since the start of the 19th century, which is in excellent agreement with the regional value of MSL rise over the same period (1.5 ± 0.2 mm yr–1) calculated from a compilation of tide gauge records around Britain. Whilst our record has decadal-scale temporal resolution (1 sample every 8 years), we are currently unable to resolve multidecadal-scale variations in the rate of sea-level rise which are masked by the size of the vertical uncertainties (± 20 cm) associated with our reconstruction of palaeomarsh-surface elevation. We discuss the challenges of applying the GTG approach in the typically minerogenic saltmarshes of the NE Atlantic margin and outline potential solutions that would facilitate the production of Common Era RSL reconstructions in the region.

Developing authentic relationships as a part of service-learning projects is often considered one of the most meaningful outcomes for both student and community participants. In this project, students met with community members who were not native English speakers. The goal was for students to gain experience with linguistic diversity as they trained to become teachers, while also providing a program for community partners to practice English. I found that the competing goals of the program and its single semester timeframe limited the ability for students to invest in developing authentic relationships, despite any guidance I may have offered. Drawing from my critical examination of student reflective writing, I argue that teacher guidance and modeling do not necessarily lead to the successful development of authentic relationships. I conclude with thoughts on collaboration and suggest that students should have a choice about their participation.