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Although lesson study has been shown to improve the teaching and learning of mathematics, little research has focused on reasons for engaging in it from a teacher's perspective, particularly after sustained engagement with lesson study. This qualitative study reports on thirty-three teachers from the United States who were involved in twelve lesson study cycles during a three-year partnership aimed at improving algebraic instruction for students aged 8-14 years during a period of educational reform. It used grounded theory techniques to analyse interview data to determine the purposes of lesson study from teachers' perspectives. Results highlight six purposes for engaging in a mathematics lesson study: understand reform standards, focus on student thinking, develop pedagogy, support collaboration, develop curricular materials, and learn mathematics. Particularly noticeable was its use for focusing on student mathematical thinking and understanding of reform initiatives and requirements. Research implications suggest positioning lesson study as a useful, teacher-vetted tool for unpacking educational reforms.

Abstract An adult American Quarter Horse mare presented for pigmenturia and lethargy of 12 hours' duration and was diagnosed with silver maple leaf toxicity. The mare had intravascular hemolysis and azotemia. The mare was treated with a transfusion of whole blood, fluids administered IV, antibiotics, oxygen insufflation, and supportive care. The azotemia persisted despite conventional medical management and hemodialysis was elected. After 2 intermittent hemodialysis treatments over 3 days, the azotemia almost resolved, clinical signs improved, and the mare was discharged. The blood urea nitrogen, creatinine, and electrolyte concentrations remained normal 6 months later after examination by the referring veterinarian. Hemodialysis treatment can be feasible in horses if equipment and expertise are available and should be considered as a treatment option if indicated.

Members of the genus Scaphanocephalus mature in accipitrids, particularly osprey, Pandion haliaetus, with metacercaria causing Black Spot Syndrome in reef fishes. In most of the world, only the type species, Scaphanocephalus expansus (Creplin, 1842) has been reported. Recent molecular studies in the Western Atlantic, Mediterranean and Persian Gulf reveal multiple species of Scaphanocephalus, but have relied on 28S rDNA, mainly from metacercariae, which limits both morphological identification and resolution of closely related species. Here we combine nuclear rDNA with mitochondrial sequences from adult worms collected in osprey across North America and the Caribbean to describe species and elucidate life cycles in Scaphanocephalus. A new species described herein can be distinguished from S. expansus based on overall body shape and size. Phylogenetic analysis of the whole mitochondrial genome of Scaphanocephalus indicates a close relationship with Cryptocotyle. We conclude that at least 3 species of Scaphanocephalus are present in the Americas and 2 others are in the Old World. Specimens in the Americas have similar or identical 28S to those in the Mediterranean and Persian Gulf, but amphi-Atlantic species are unlikely in light of divergence in cytochrome c oxidase I and the lack of amphi-Atlantic avian and fish hosts. Our results provide insight into the geographic distribution and taxonomy of a little-studied trematode recently linked to an emerging pathology in ecologically important reef fishes.

Researchers increasingly recognize that the mind and culture interact at many levels to constitute our lived experience, yet we know relatively little about the extent to which culture shapes the way people appraise their experiences and the likelihood that a given experience will be reported. Experiences that involve claims regarding deities, extraordinary abilities, and/or psychopathology offer an important site for investigating the interplay of mind and culture at the population level. However, the difficulties inherent in comparing culture-laden experiences, exacerbated by the siloing of research on experiences based on discipline-specific theoretical constructs, have limited our ability to do so. We introduce the Inventory of Nonordinary Experiences (INOE), which allows researchers to compare experiences by separating the phenomenological features from how they are appraised and asking about both. It thereby offers a new means of investigating the potentially universal (etic) and culture-specific (emic) aspects of lived experiences. To ensure that the INOE survey items are understood as intended by English speakers in the US and Hindi speakers in India, and thus can serve as a basis for cross-cultural comparison, we used the Response Process Evaluation (RPE) method to collect evidence of item-level validity. Our inability to validate some items drawn from other surveys suggests that they are capturing a wider range of experiences than researchers intend. Wider use of the RPE method would increase the likelihood that survey results are due to the differences that researchers intend to measure.

Gastrostomy feeding is a route of enteral nutrition for children with feeding difficulties. This study investigated caregiver experiences of the transition to gastrostomy feeding. A survey was administered to caregivers of children

Background: Proper hand hygiene is the most important practice to reduce the transmission of infections in healthcare settings. Despite this, healthcare institutions continue to struggle to achieve and maintain high rates of hand hygiene compliance among healthcare workers with some studies estimating national healthcare worker hand hygiene compliance to be approximately 50%. Methods: We conducted an anonymous one-time survey of our Lifespan Hospital System employees to evaluate barriers and facilitators to performing hand hygiene as well as interventions to improve hand hygiene compliance. The survey was designed with guidance from the Consolidated Framework for Implementation Research and input from Lifespan infection prevention staff. Result: Over four weeks 985 (6%) Lifespan employees completed the survey. Figure 1 shows the aggregate results of the first 4 survey questions which focused on hand hygiene infrastructure at Lifespan, including availability of sanitizer, staff to manage hand hygiene supplies, and educational materials/reminders. One significant finding was >70% of respondents reported that they either did not know if their unit/department has a person assigned to replace/monitor hand hygiene supplies, or if so, who that person is. We also asked employees to rate how effective different interventions would be at improving hand hygiene compliance. Figure 2 shows of five proposed interventions, three were rated as either “moderately effective” or “very effective” by >50% of respondents. These included displaying hand hygiene instructions, making hand hygiene data available to employees, and displaying materials/reminders promoting hand hygiene. There were also 977 free-text responses regarding “barriers or facilitators to proper hand hygiene”. Major barriers identified were a lack of staff to monitor and refill supplies, slow replacement of hand hygiene products, lack of sanitizer dispensers and sinks, inconsistency of sink location and dispenser placement, lack of hand hygiene reminders/educational materials, time constraints, skin irritation from sanitizer, and an inability to have dispensers in behavioral health units. Survey responses led us to enhance the following: educational materials and reminders in work areas; staff education; leadership involvement in hand hygiene initiatives; routine auditing and feedback; conveniently placed sanitizer dispensers and sinks at the point of care; and making hand hygiene compliance data readily available to staff. Conclusion: This survey identifies important barriers and facilitators to achieving high rates of hand hygiene compliance among healthcare workers and provides the basis for interventions aimed at improving hand hygiene compliance in a large multicenter academic hospital system.

IntroductionPeripheral blood stem cell (PBSC) donation is the primary procedure used to collect hematopoietic stem and progenitor cells (HSPCs) for hematopoietic stem cell transplantation. Single bouts of exercise transiently enrich peripheral blood with HSPCs and cytolytic natural killer cells (CD56dim), which are important in preventing post-transplant complications. To provide a rationale to investigate the utility of exercise in a PBSC donation setting (≈3 h), this study aimed to establish whether interval cycling increased peripheral blood HSPC and CD56dim concentrations to a greater degree than continuous cycling.MethodsIn a randomised crossover study design, eleven males (mean ± SD: age 25 ± 7 years) undertook bouts of moderate intensity continuous exercise [MICE, 30 min, 65%–70% maximum heart rate (HRmax)], high-volume high intensity interval exercise (HV-HIIE, 4 × 4 min, 80%–85% HRmax) and low-volume HIIE (LV-HIIE, 4 × 2 min, 90%–95% HRmax). The cumulative impact of each interval on circulating HSPC (CD34+CD45dimSSClow) and CD56dim concentrations (cells/µL), and the bone marrow homing potential of HSPCs (expression of CXCR-4 and VLA-4) were determined.ResultsThere was an increase in HSPC concentration after two intervals of LV-HIIE (Rest: 1.84 ± 1.55 vs. Interval 2: 2.94 ± 1.34, P = 0.01) and three intervals of HV-HIIE only (Rest: 2.05 ± 0.86 vs. Interval 3: 2.51 ± 1.05, P = 0.04). The concentration of all leukocyte subsets increased after each trial, with this greatest for CD56dim NK cells, and in HIIE vs. MICE (LV-HIIE: 4.77 ± 2.82, HV-HIIE: 4.65 ± 2.06, MICE: 2.44 ± 0.77, P < 0.0001). These patterns were observed for concentration, not frequency of CXCR-4+ and VLA-4+ HSPCs, which was unaltered. There was a marginal decrease in VLA-4, but not CXCR-4 expression on exercise-mobilised HSPCs after all trials (P < 0.0001).DiscussionThe results of the present study indicate that HIIE caused a more marked increase in HSPC and CD56dim NK cell concentrations than MICE, with mobilised HSPCs maintaining their bone marrow homing phenotype. LV-HIIE evoked an increase in HSPC concentration after just 2 × 2-minute intervals. The feasibility and clinical utility of interval cycling in a PBSC donation context should therefore be evaluated.

Cell sedimentation in 3D hydrogel cultures refers to the vertical migration of cells towards the bottom of the space. Understanding this poorly examined phenomenon may allow us to design better protocols to prevent it, as well as provide insights into the mechanobiology of cancer development. We conducted a multiscale experimental and mathematical examination of 3D cancer growth in triple negative breast cancer cells. Migration was examined in the presence and absence of Paclitaxel, in high and low adhesion environments and in the presence of fibroblasts. The observed behaviour was modeled by hypothesizing active migration due to self-generated chemotactic gradients. Our results did not reject this hypothesis, whereby migration was likely to be regulated by the MAPK and TGF-β pathways. The mathematical model enabled us to describe the experimental data in absence (normalized error

Redox biocatalysis plays an increasingly important role in modern organic synthesis. The recent integration of novel media such as deep eutectic solvents (DESs) has significantly impacted this field of chemical biology. Alcohol dehydrogenases (ADHs) are important biocatalysts where their unique specificity is used for enantioselective synthesis.This review explores aspects of redox biocatalysis in the presence of DES both with whole cells and with isolated ADHs. In both cases, the presence of DES has a significant influence on the outcome of reactions albeit via different mechanisms. For whole cells, DES was shown to be a useful tool to direct product formation or configuration - a process of solvent engineering. Whole cells can tolerate DES as media components for the solubilization of hydrophobic substrates. In some cases, DES in the growth medium altered the enantioselectivity of whole cell transformations by solvent control. For isolated enzymes, on the other hand, the presence of DES promotes substrate solubility as well as enhancing enzyme stability and activity. DES can be employed as a smart solvent or smart cosubstrate particularly for cofactor regeneration purposes.From the literatures examined, it is suggested that DES based on choline chloride (ChCl) such as ChCl:Glycerol (Gly), ChCl:Glucose (Glu), and ChCl:1,4-butanediol (1,4-BD) are useful starting points for ADH-based redox biocatalysis. However, each specific reaction will require optimisation due to the influence of several factors on biocatalysis in DES. These include solvent composition, enzyme source, temperature, pH and ionic strength as well as the substrates and products under investigation.

Autism is a developmental condition that affects motor skill development. There is a lack of comprehensive research exploring the potential benefits of extended reality (XR) technologies, including virtual reality (VR) and augmented reality (AR), for improving motor skills in autistic children. This systematic literature review (SLR) addresses this research gap by investigating XR-based interventions targeting motor skill development in autistic children. The SLR analysed 15 primary studies published between 2012 and 2024, examining the use of VR and AR to improve motor skill development in autistic children. The interventions ranged from one session to 12 weeks, lasting 12 to 45 minutes, and targeted various body movements. XR platforms and devices used included VR headsets, motion capture systems, and exercise bikes. Recurrent neural networks, dynamic difficulty adjustment, and behaviour trees were employed to enhance intervention dynamics and extract valuable insights from collected data. The results suggest that using XR interventions has significant potential to improve physical activity levels and motor skills development among autistic children. However, the research designs varied, with only one study including their intervention framework’s generalisation and maintenance phases. This study offers an encouraging avenue for future research and intervention design in this field.

Abstract Background Questions exist regarding patient selection for surgery in anaplastic thyroid carcinoma (ATC), particularly with the advent of neoadjuvant‐targeted therapeutics. The present scoping review sought to evaluate what extent of surgical resection should be performed in ATC. Methods A scoping review was carried out in accordance with Joanna Briggs Institute and the preferred reporting items for systematic reviews and meta‐analyses extension for scoping reviews (PRISMA‐ScR) protocols. Included studies were required to provide clear description of the surgery performed for ATC. Results The final search identified 6901 articles. Ultimately only 15 articles including 1484 patients met inclusion criteria. A total of 765 patients (51.5%) underwent attempted curative intent surgery. The approach to resection of adjacent tissues varied between studies. Eight studies considered laryngeal ± pharyngeal resection (8/15, 53.3%), eight studies (53.3%) considered tracheal resection and again eight studies (53.3%) considered esophageal resection. More extensive resections increased morbidity without improving overall survival (OS) (

Abstract Metabolism, the biological processing of energy and materials, scales predictably with temperature and body size. Temperature effects on metabolism are normally studied via acute exposures, which overlooks the capacity for organisms to moderate their metabolism following chronic exposure to warming. Here, we conduct respirometry assays in situ and after transplanting salmonid fish among different streams to disentangle the effects of chronic and acute thermal exposure. We find a clear temperature dependence of metabolism for the transplants, but not the in-situ assays, indicating that chronic exposure to warming can attenuate salmonid thermal sensitivity. A bioenergetic model accurately captures the presence of fish in warmer streams when accounting for chronic exposure, whereas it incorrectly predicts their local extinction with warming when incorporating the acute temperature dependence of metabolism. This highlights the need to incorporate the potential for thermal acclimation or adaptation when forecasting the consequences of global warming on ecosystems.

Social media use is associated with poor sleep outcomes. We aimed to extend previous research by examining how measures of social media use would affect two sleep characteristics: sleep quality and insomnia symptoms. In addition, we tested a serial mediation model linking social media use to sleep through increases in negative social comparison and pre-sleep cognitive arousal. Participants were 830 emerging adults (ages 18–30) who were recruited for an online survey study in February 2024. The sample was 63.1% female, with an average age of 24. We examined three measures of social media use: duration (minutes of daily use), frequency (number of weekly visits to social media platforms), and emotional investment (attachment to and integration of social media into daily life). Consistent with our hypothesis, greater emotional investment in social media and more frequent social media use were associated with poorer sleep quality and greater insomnia severity. We also found evidence supporting our hypothesized serial mediation model: emotional investment in social media and more frequent social media use were associated with increased negative social comparison, which subsequently increased pre-sleep cognitive arousal, which then led to poorer sleep outcomes. Our findings suggest that negative social comparison and pre-sleep cognitive arousal are important mechanisms linking social media use to poor sleep outcomes. Future studies should aim to test this serial mediation model using longitudinal data and experimental methods.

This paper presents the meta-theoretical Consolidated Framework for Implementation Research (CFIR) that was adapted to structure a narrative scoping review to inform the evaluation of an Ethical Education (EE) curriculum. The CFIR is a tried and tested implementation science model used effectively within health care settings. To date, it has not been used as a framework in an educational context. The five domains of the CFIR: characteristics of the individual; inner setting; outer setting; intervention characteristics; and implementation process were interrogated and mapped to educational constructs namely: teacher characteristics; school and class settings; wider school community; curriculum characteristics; and curricular implementation, respectively. This paper illustrates how an implementation science approach, using these educational constructs, can inform a scoping review to support the evaluation of a curriculum.

The paper investigates teachers' and principals' experiences of implementing a pilot of an ethical education (EE) curriculum to a senior cycle programme in Educate Together secondary schools in Ireland. The development of this curriculum was informed by the Integrative Ethical Education Model (Lapsley and Narvaez, 2004). Thirteen teachers and two school principals were interviewed about their experiences of this curriculum and its impact on school culture and organisation. An implementation science approach informed a thematic analysis of transcripts that interrogated the perspectives of participants, and revealed the systemic factors that included barriers to, and facilitators of, EE curriculum implementation. Interviews were analysed inductively, by exploring participants' experiences, and deductively, using Narvaez's framework of ethical skills. Results were presented within the domains of school setting, wider school setting, curriculum characteristics and teacher characteristics, reflecting an implementation science approach. Findings suggest that this curriculum nurtured a positive school climate where students identified as having a greater sense of school belonging as a result of access to this curriculum.

Introduction Chimeric antigen receptor (CAR) T-cell therapies are novel, potentially curative therapies for haematological malignancies. CAR T-cell therapies are associated with severe toxicities, meaning patients require monitoring during acute and postacute treatment phases. Electronic patient-reported outcomes (ePROs), self-reports of health status provided via online questionnaires, can complement clinician observation with potential to improve patient outcomes. This study will develop and evaluate feasibility of a new ePRO system for CAR-T patients in routine care.Methods and analysis Multiphase, mixed-methods study involving multiple stakeholder groups (patients, family members, carers, clinicians, academics/researchers and policy-makers). The intervention development phase comprises a Delphi study to select PRO measures for the digital system, a codesign workshop and consensus meetings to establish thresholds for notifications to the clinical team if a patient reports severe symptoms or side effects. Usability testing will evaluate how users interact with the digital system and, lastly, we will evaluate ePRO system feasibility with 30 CAR-T patients (adults aged 18+ years) when used in addition to usual care. Feasibility study participants will use the ePRO system to submit self-reports of symptoms, treatment tolerability and quality of life at specific time points. The CAR-T clinical team will respond to system notifications triggered by patients’ submitted responses with actions in line with standard clinical practice. Feasibility measures will be collected at prespecified time points following CAR T-cell infusion. A qualitative substudy involving patients and clinical team members will explore acceptability of the ePRO system.Ethics and dissemination Favourable ethical opinion was granted by the Health and Social Care Research Ethics Committee B(HSC REC B) (ref: 23/NI/0104) on 28 September 2023. Findings will be submitted for publication in high-quality, peer-reviewed journals. Summaries of results, codeveloped with the Blood and Transplant Research Unit Patient and Public Involvement and Engagement group, will be disseminated to all interested groups.Trial registration number ISCTRN11232653.

Summary: Background: Microsurgery is a technically demanding surgical discipline with a steep learning curve. Trainees have faced several difficulties due to less hands-on theater time and pandemic-related limits on access to technical training. To overcome this, trainees engaged in self-directed training, which requires an accurate self-assessment of skill. This study aimed to assess the ability of trainees to accurately self-assess their performance while performing a simulated microvascular anastomosis. Methods: Novice and specialist plastic surgery trainees performed a simulated microvascular anastomosis on a high-fidelity chicken femoral vessel model. Each participant objectively rated the quality of their anastomosis using the Anastomosis Lapse Index (ALI). Two expert microsurgeons subsequently blindly rated each anastomosis. To determine the accuracy of self-evaluation, self-scores and expert-scores were compared using a Wilcoxon signed-rank test. Results: Twenty-seven surgical trainees completed the simulation, with a mean time to completion (TTC) of 40.3 minutes (range 14.2–106.0 minutes). For the entire cohort, the median ALI self-score was 4 (range 3–10), while the median ALI expert-score was 5.5 (range 2.5–9.5). There was a significant difference between the ALI self-score and the expert-score (p

Previous research has proven that the balance of autistic children is poor. However, the reliability of assessing balance in this cohort has been inadequately researched. This study therefore aimed to examine if field-based static and dynamic balance tests can be reliably assessed in autistic children, to determine the number of familiarisation sessions required and whether autistic severity impacts on the reliability of these balance tests. The balance of eighteen primary school-aged autistic children was assessed three times a week over five weeks, using the flamingo balance test, a modified version of the balance error scoring system (BESS), the low beam walking test, and the heel to toe walking test. Reliability criteria included an intraclass correlation coefficient (ICC) level of ≥0.75 and a coefficient of variance (CV%) of ≤46% for the low beam walking test, the heel to toe walking test, and the BESS, and a CV% of ≤82% or the flamingo balance test. Inter-session reliability was achieved and required the least number of familiarisation sessions for the flamingo balance test, compared to the low beam walking test, which required a greater number of familiarisation sessions to achieve inter-session reliability. The heel to toe walking test and the BESS achieved inter-session reliability and familiarisation in an acceptable time frame. Due to the large CV% values reported in the current study, practitioners need to be aware that balance interventions need to achieve improvements greater than the CV% in this cohort.

In educational settings, where decisions must regularly be made related to what type and focus of services to provide, having a parent/caregiver advocate in their corner can be very important to children who are deaf or hard of hearing. In this article, the author presents how to best support families and caregivers who are disconnected, alienated, and underserved so they can become involved and effective advocates.

Prostate cancer, the most common cause of cancer in men in the UK and one of the most common around the world to date, has no consensus on screening. Multiple large-scale trials from around the world have produced conflicting outcomes in cancer-specific and overall mortality. A main part of the issue is the PSA test, which has a high degree of variability, making it challenging to set PSA thresholds, as well as limited specificity. Prostate cancer has a predisposition in men from black backgrounds, and outcomes are worse in men of lower socioeconomic groups. Mobile targeted case finding, focusing on high-risk groups, may be a solution to help those that most need it. The aim of this systematic review was to review the evidence for mobile testing for prostate cancer. A review of all mobile screening studies for prostate cancer was performed in accordance with the Cochrane guidelines and the PRISMA statement. Of the 629 unique studies screened, 6 were found to be eligible for the review. The studies dated from 1973 to 2017 and came from four different continents, with around 30,275 men being screened for prostate cancer. Detection rates varied from 0.6% in the earliest study to 8.2% in the latest study. The challenge of early diagnosis of potentially lethal prostate cancer remains an issue for developed and low- and middle-income countries alike. Although further studies are needed, mobile screening of a targeted population with streamlined investigation and referral pathways combined with raising awareness in those communities may help make the case for screening for prostate cancer.

Introduction Autologous haematopoietic stem cell transplantation (aHSCT) is increasingly used as treatment for patients with active multiple sclerosis (MS), typically after failure of disease-modifying therapies (DMTs). A recent phase III trial, ‘Multiple Sclerosis International Stem Cell Transplant, MIST’, showed that aHSCT resulted in prolonged time to disability progression compared with DMTs in patients with relapsing remitting MS (RRMS). However, the MIST trial did not include many of the current high-efficacy DMTs (alemtuzumab, ocrelizumab, ofatumumab or cladribine) in use in the UK within the control arm, which are now offered to patients with rapidly evolving severe MS (RES-MS) who are treatment naïve. There remain, therefore, unanswered questions about the relative efficacy and safety of aHSCT over these high-efficacy DMTs in these patient groups. The StarMS trial (Autologous Stem Cell Transplantation versus Alemtuzumab, Ocrelizumab, Ofatumumab or Cladribine in Relapsing Remitting Multiple Sclerosis) will assess the efficacy, safety and long-term impact of aHSCT compared with high-efficacy DMTs in patients with highly active RRMS despite the use of standard DMTs or in patients with treatment naïve RES-MS.Methods and analysis StarMS is a multicentre parallel-group rater-blinded randomised controlled trial with two arms. A total of 198 participants will be recruited from 19 regional neurology secondary care centres in the UK. Participants will be randomly allocated to the aHSCT arm or DMT arm in a 1:1 ratio. Participants will remain in the study for 2 years with follow-up visits at 3, 6, 9, 12, 18 and 24 months postrandomisation. The primary outcome is the proportion of patients who achieve ‘no evidence of disease activity’ during the 2-year postrandomisation follow-up period in an intention to treat analysis. Secondary outcomes include efficacy, safety, cost-effectiveness and immune reconstitution of aHSCT and the four high-efficacy DMTs.Ethics and dissemination The study was approved by the Yorkshire and Humber—Leeds West Research Ethics Committee (20/YH/0061). Participants will provide written informed consent prior to any study specific procedures. The study results will be submitted to a peer-reviewed journal and abstracts will be submitted to relevant national and international conferences.Trial registration number ISRCTN88667898.

Background Nintedanib slows progression of lung function decline in patients with progressive fibrosing (PF) interstitial lung disease (ILD) and was recommended for this indication within the United Kingdom (UK) National Health Service in Scotland in June 2021 and in England, Wales and Northern Ireland in November 2021. To date, there has been no national evaluation of the use of nintedanib for PF-ILD in a real-world setting. Methods 26 UK centres were invited to take part in a national service evaluation between 17 November 2021 and 30 September 2022. Summary data regarding underlying diagnosis, pulmonary function tests, diagnostic criteria, radiological appearance, concurrent immunosuppressive therapy and drug tolerability were collected via electronic survey. Results 24 UK prescribing centres responded to the service evaluation invitation. Between 17 November 2021 and 30 September 2022, 1120 patients received a multidisciplinary team recommendation to commence nintedanib for PF-ILD. The most common underlying diagnoses were hypersensitivity pneumonitis (298 out of 1120, 26.6%), connective tissue disease associated ILD (197 out of 1120, 17.6%), rheumatoid arthritis associated ILD (180 out of 1120, 16.0%), idiopathic nonspecific interstitial pneumonia (125 out of 1120, 11.1%) and unclassifiable ILD (100 out of 1120, 8.9%). Of these, 54.4% (609 out of 1120) were receiving concomitant corticosteroids, 355 (31.7%) out of 1120 were receiving concomitant mycophenolate mofetil and 340 (30.3%) out of 1120 were receiving another immunosuppressive/modulatory therapy. Radiological progression of ILD combined with worsening respiratory symptoms was the most common reason for the diagnosis of PF-ILD. Conclusion We have demonstrated the use of nintedanib for the treatment of PF-ILD across a broad range of underlying conditions. Nintedanib is frequently co-prescribed alongside immunosuppressive and immunomodulatory therapy. The use of nintedanib for the treatment of PF-ILD has demonstrated acceptable tolerability in a real-world setting.

Set against the backdrop of an absence of agricultural extension in the curriculum of agriculture degree programs in Ireland between 1990 and 2010, this paper examines the knowledge exchange skills needed by the next generation of farm advisors and presents the case of a practice-based postgraduate program in Ireland that seeks to address the competency gap created. It reviews an Irish post graduate program that has been designed to equip graduates with the competencies to work effectively in advisory roles. It combines student, graduate, and manager survey results on their experience and assessment of professional development with this program. The evolving role of front-line farm advisors to facilitators of knowledge exchange and innovation is recognised while a range of essential competencies are highlighted. The value of this postgraduate education for early career farm advisors is evidenced through building competencies in a range of areas and gaining a deeper understanding through applied research of the complexities of innovation adoption and the barriers to change for farmers and their families. The paper concludes that greater attention is needed to developing core competencies of farm advisors to build strong relationships of trust and influence with farmer clients.

Allogeneic stem cell transplantation is used widely in the treatment of hematopoietic malignancy although graft versus host disease and relapse remain major complications. We measured the serum protein expression of 92 inflammation-related markers from 49 patients at Day 0 (D0) and 154 patients at Day 14 (D14) following transplantation and related values to subsequent clinical outcomes. Low levels of 7 proteins at D0 were linked to GvHD whilst high levels of 7 proteins were associated with relapse. The concentration of 38 proteins increased over 14 days and higher inflammatory response at D14 was strongly correlated with patient age. A marked increment in protein concentration during this period associated with GvHD but reduced risk of disease relapse, indicating a link with alloreactive immunity. In contrast, patients who demonstrated low dynamic elevation of inflammatory markers during the first 14 days were at increased risk of subsequent disease relapse. Multivariate time-to-event analysis revealed that high CCL23 at D14 was associative of AGvHD, CXCL10 with reduced rate of relapse, and high PD-L1 with reduced overall survival. This work identifies a dynamic pattern of inflammatory biomarkers in the very early post-transplantation period and reveals early protein markers that may help to guide patient management.

Background: The thromboxane receptor (TP) antagonist NTP42 is in clinical development for treatment of cardiopulmonary diseases, such as pulmonary arterial hypertension. In this randomized, placebo-controlled Phase I clinical trial, NTP42, administered as the oral formulation NTP42:KVA4, was evaluated for safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) in healthy males.Methods: The first-in-human trial had three Parts: A, single ascending dose (SAD) study with seven groups given 0.25–243 mg NTP42:KVA4 or placebo; B, food effect study where one SAD group (9 mg) was also given NTP42:KVA4 or placebo after a high-fat breakfast; C, multiple ascending dose study with three groups given 15–135 mg NTP42:KVA4 or placebo once-daily for 7 days.Results: Seventy-nine volunteers participated. No serious adverse events occurred, where any drug- or placebo-related adverse events were mild to moderate, with no correlation to NTP42:KVA4 dose. NTP42 was rapidly absorbed, yielding dose proportional increases in exposure after single and repeat dosing. PK confirmed that, with a clearance (T1/2) of 18.7 h, NTP42:KVA4 is suited to once-daily dosing, can be taken with or without food, and does not accumulate on repeat dosing. At doses ≥1 mg, NTP42 led to complete and sustained inhibition of thromboxane-, but not ADP-, induced platelet aggregation ex vivo, with direct correlation between NTP42 exposure and duration of PD effects.Conclusion: Orally administered NTP42:KVA4 was well tolerated, with favorable PK/PD profiles and evidence of specific TP target engagement. These findings support continued clinical development of NTP42:KVA4 for cardiopulmonary or other relevant diseases with unmet needs.Clinical Trial Registration:clinicaltrials.gov, identifier NCT04919863.