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Introduction Reduced thrombin generation is an important component of post cardiopulmonary bypass (CPB) coagulopathy. To replenish coagulation factors and enhance thrombin generation in bleeding surgical patients, frozen plasma (FP) and four-factor prothrombin complex concentrate (4F-PCC) are used. However, the efficacy–safety balance of 4F-PCC relative to FP in cardiac surgery is unconfirmed.Methods and analysis LEX-211 (FARES-II) is an active-control, randomised, phase 3 study comparing two coagulation factor replacement therapies in bleeding adult cardiac surgical patients at 12 hospitals in Canada and the USA. The primary objective is to determine whether 4F-PCC (Octaplex/Balfaxar, Octapharma) is clinically non-inferior to FP for haemostatic effectiveness. Inclusion criteria are any index (elective or non-elective) cardiac surgery employing CPB and coagulation factor replacement with 4F-PCC or FP ordered in the operating room for bleeding management. Patients will be randomised to receive 1500 or 2000 international units of 4F-PCC or 3 or 4 units of FP, depending on body weight. The primary endpoint of haemostatic treatment response is ‘effective’ if no additional haemostatic intervention is required from 60 min to 24 hours after the first initiation of 4F-PCC or FP; or ‘ineffective’ if any other haemostatic intervention (including a second dose of study drug) is required. An estimated 410 evaluable patients will be required to demonstrate non-inferiority (one-sided α of 0.025, power ≥90%, non-inferiority margin 0.10). Secondary outcomes include transfusions, bleeding-related clinical endpoints, coagulation parameters and safety.Ethics and dissemination The trial has been approved by the institutional review boards of all participating centres. Trial completion is anticipated at the end of 2024, and results will be disseminated via publications in peer-reviewed journals and conference presentations in 2025. The results will advance our understanding of coagulation management in bleeding surgical patients, potentially reducing the need for allogeneic blood products and improving outcomes in surgical patients.Trial registration number NCT05523297.

The Electron Loss and Fields Investigation with a Spatio-Temporal Ambiguity-Resolving option (ELFIN-STAR, or heretoforth simply: ELFIN) mission comprises two identical 3-Unit (3U) CubeSats on a polar (∼93∘ inclination), nearly circular, low-Earth (∼450 km altitude) orbit. Launched on September 15, 2018, ELFIN is expected to have a >2.5 year lifetime. Its primary science objective is to resolve the mechanism of storm-time relativistic electron precipitation, for which electromagnetic ion cyclotron (EMIC) waves are a prime candidate. From its ionospheric vantage point, ELFIN uses its unique pitch-angle-resolving capability to determine whether measured relativistic electron pitch-angle and energy spectra within the loss cone bear the characteristic signatures of scattering by EMIC waves or whether such scattering may be due to other processes. Pairing identical ELFIN satellites with slowly-variable along-track separation allows disambiguation of spatial and temporal evolution of the precipitation over minutes-to-tens-of-minutes timescales, faster than the orbit period of a single low-altitude satellite (Torbit ∼ 90 min). Each satellite carries an energetic particle detector for electrons (EPDE) that measures 50 keV to 5 MeV electrons with Δ E/E < 40% and a fluxgate magnetometer (FGM) on a ∼72 cm boom that measures magnetic field waves (e.g., EMIC waves) in the range from DC to 5 Hz Nyquist (nominally) with 1 MeV. This broad energy range of precipitation indicates that multiple waves are providing scattering concurrently. Many observed events show significant backscattered fluxes, which in the past were hard to resolve by equatorial spacecraft or non-pitch-angle-resolving ionospheric missions. These observations suggest that the ionosphere plays a significant role in modifying magnetospheric electron fluxes and wave-particle interactions. Routine data captures starting in February 2020 and lasting for at least another year, approximately the remainder of the mission lifetime, are expected to provide a very rich dataset to address questions even beyond the primary mission science objective.

The clinical diagnosis of new-onset type 1 diabetes has, for many years, been considered relatively straightforward. Recently, however, there is increasing awareness that within this single clinical phenotype exists considerable heterogeneity: disease onset spans the complete age range; genetic susceptibility is complex; rates of progression differ markedly, as does insulin secretory capacity; and complication rates, glycemic control, and therapeutic intervention efficacy vary widely. Mechanistic and immunopathological studies typically show considerable patchiness across subjects, undermining conclusions regarding disease pathways. Without better understanding, type 1 diabetes heterogeneity represents a major barrier both to deciphering pathogenesis and to the translational effort of designing, conducting, and interpreting clinical trials of disease-modifying agents. This realization comes during a period of unprecedented change in clinical medicine, with increasing emphasis on greater individualization and precision. For complex disorders such as type 1 diabetes, the option of maintaining the "single disease" approach appears untenable, as does the notion of individualizing each single patient's care, obliging us to conceptualize type 1 diabetes less in terms of phenotypes (observable characteristics) and more in terms of disease endotypes (underlying biological mechanisms). Here, we provide our view on an approach to dissect heterogeneity in type 1 diabetes. Using lessons from other diseases and the data gathered to date, we aim to delineate a roadmap through which the field can incorporate the endotype concept into laboratory and clinical practice. We predict that such an effort will accelerate the implementation of precision medicine and has the potential for impact on our approach to translational research, trial design, and clinical management.

A three-arm, randomized, double-masked, placebo-controlled phase 2b trial performed by the Type 1 Diabetes TrialNet Study Group previously demonstrated that low-dose anti-thymocyte globulin (ATG) (2.5 mg/kg) preserved β-cell function and reduced HbA1c for 1 year in new-onset type 1 diabetes. Subjects (N = 89) were randomized to 1) ATG and pegylated granulocyte colony-stimulating factor (GCSF), 2) ATG alone, or 3) placebo. Herein, we report 2-year area under the curve (AUC) C-peptide and HbA1c, prespecified secondary end points, and potential immunologic correlates. The 2-year mean mixed-meal tolerance test-stimulated AUC C-peptide, analyzed by ANCOVA adjusting for baseline C-peptide, age, and sex (n = 82) with significance defined as one-sided P < 0.025, was significantly higher in subjects treated with ATG versus placebo (P = 0.00005) but not ATG/GCSF versus placebo (P = 0.032). HbA1c was significantly reduced at 2 years in subjects treated with ATG (P = 0.011) and ATG/GCSF (P = 0.022) versus placebo. Flow cytometry analyses demonstrated reduced circulating CD4:CD8 ratio, increased regulatory T-cell:conventional CD4 T-cell ratios, and increased PD-1+CD4+ T cells following low-dose ATG and ATG/GCSF. Low-dose ATG partially preserved β-cell function and reduced HbA1c 2 years after therapy in new-onset type 1 diabetes. Future studies should determine whether low-dose ATG might prevent or delay the onset of type 1 diabetes.

ObjectiveA pilot study suggested that combination therapy with low-dose anti-thymocyte globulin (ATG) and pegylated granulocyte colony-stimulating factor (GCSF) preserves C-peptide in established type 1 diabetes (T1D) (duration 4 months to 2 years). We hypothesized that 1) low-dose ATG/GCSF or 2) low-dose ATG alone would slow the decline of β-cell function in patients with new-onset T1D (duration

Approximately one million children are victims of maltreatment are assessed and placed in the child welfare system. The purpose of the current study was to identify caseworker perceptions of (a) reasons for youth removal from a home environment and (b) the parameters of intolerable problem categories that prompt such decisions. Four categories of maltreatment were generated to account for over 70% of the caseworkers' 249 reasons identified for youth removal using structured interviews. Within each category, perceptions of risk factors identified as intolerable for allowing youth to remain in the home were identified for each of the categories. Results may help providers to target the areas in which future program development and treatment delivery efforts should be directed. (Contains 5 tables.)

Abstract Background Laws allowing assisted suicide and euthanasia have been implemented in many locations around the world but some individuals suffering with terminal illness receiving palliative care services are hastening death or die by suicide without assistance. This systematic review aims to summarise evidence of palliative care professionals’ experiences of patients who died by suicide or hastened death in areas where assisted dying is legal and to understand when hastened death is considered to be a suicide. Methods AMED, CINAHL Complete, PsycINFO, PubMED, and Academic Search Ultimate were searched for articles from inception through June 2018. Quality assessment used the Hawker framework. Results A total of 1518 titles were screened resulting in thirty studies meeting eligibility criteria for this review. Published studies about professionals’ experiences from areas with legalised assisted dying includes limited information about patients who hasten death outside legal guidelines, die by suicide without assistance, or if the law impacts suicide among palliative care patients. Conclusion There are a range of experiences and emotions professionals’ experience with patients who die by euthanasia, assisted suicide, or hasten death without assistance. The included literature suggests improved communication among professionals is needed but does not explicitly identify when a hastened death is deemed a suicide in areas where assisted dying is practiced. More research is needed to help clarify what hastened death means in a palliative care context and identify how and if assisted dying impacts issues of suicide in palliative care settings.

Purpose: The purpose of this paper is to report on the innovative employment of students as technology mentors as part of a Blended Learning Program (BLP) that supported a group of owner-managers of small businesses to adopt appropriate information and communication technologies (ICT) to enhance their work practices. Design/methodology/approach: This discussion uses various evaluations undertaken throughout the project to examine why the technology mentor role is vital in supporting small businesses to develop digital literacies. The participants' self-reporting of their ICT skills as well as their progress in using ICT was also assessed by technology mentors in the course of the program and reported in mentor reflections. Academic staff also evaluated the performances of technology mentors in relation to each business. Findings: Participants in the BLP pilot program singled out the technology mentors as being essential in promoting their uptake of ICT and in their ability to use specific technologies at work. Research limitations/implications: -- Findings are based on a pilot program involving six learners and two technology mentors. While this is a statistically insignificant number of evaluations, both the findings and the model of the BLP remain of interest. This model has the capacity to address a long-standing and global challenge to support small businesses in the use of ICT. A scaled up version of the program is required to validate the findings. Practical implications: In the final evaluation, participants all self-assessed as having increased ICT knowledge and skills. They provided specific examples of how they now use ICT. The BLP could be taken up by local and state governments who periodically attempt to support small businesses in the uptake of technologies. The BLP could also be applied to vocational education students in business, information technologies or information systems. As well as supporting small businesses to adopt ICT, this model also provides an important alternative to resource-intensive work-placement programs that are designed to develop students' employability skills through work-integrated learning. Originality/value: Less effective attempts to support small businesses often involve face-to-face training for unrealistic periods of time that foreground technology rather than real world, useful and relevant outcomes (IBSA, 2013). This BLP successfully supported owner operators of small businesses to identify, apply and evaluate a range of software applications ("apps") and online programs to enhance their work practices.

Within a sufficiently large bacterial population, some members will naturally adopt an alternate, metabolically-active state that favors small molecule synthesis over cell division. These isogenic “tolerant” subpopulations have variable responses during antibiotic exposure and can remain viable in the presence of typically bactericidal concentrations. In this study, we determine the ability of typical and atypical antistaphylococcal therapies to reduce the viability of mupirocin-induced tolerant Staphylococcus aureus bacteria. Overall, tolerance-induced staphylococci exhibited a markedly decreased rate and extent of killing following antibiotic exposure. However, oritavancin remained effective at maintaining a similar extent of killing. Further studies to investigate the role of oritavancin against recurrent or relapse staphylococcal infection are warranted.

Spacecraft mechanisms commonly undergo extended periods of storage, either on-ground, or in-flight and there are an increasing number of missions for which some element of long-term storage may be required. Despite the obvious potential for degradation of lubricants during storage which might impact mechanism functionality or life and so even become mission-threatening, today’s understanding of storage phenomena is rather incomplete. This paper provides consolidation and review of recent experimental studies in this area and considers the range of storage conditions and associated degradation phenomena which could impact different lubricants. Whilst some storage best practice guidelines exist, experimental verification of the impact of storage phenomena has rarely been carried out and test data is rather scarce and incomplete. Given the absence of comprehensive data to support design, lubricant selection or the development of storage protocols, it is shown that for all lubricant types careful control of storage and test environments combined with monitoring of the evolving tribological performance during periodic mechanism exercising are presently the most effective storage risk mitigations.

Background: Children with cleft lip are known to be at raised risk for socio-emotional difficulties, but the nature of these problems and their causes are incompletely understood; longitudinal studies are required that include comprehensive assessment of child functioning, and consideration of developmental mechanisms. Method: Children with cleft lip (with and without cleft palate) (N = 93) and controls (N = 77), previously studied through infancy, were followed up at 7 years, and their socio-emotional functioning assessed using teacher and maternal reports, observations of social interactions, and child social representations (doll play). Direct and moderating effects of infant attachment and current parenting were investigated, as was the role of child communication difficulties and attractiveness. Results: Children with clefts had raised rates of teacher-reported social problems, and anxious and withdrawn-depressed behaviour; direct observations and child representations also revealed difficulties in social relationships. Child communication problems largely accounted for these effects, especially in children with cleft palate as well as cleft lip. Insecure attachment contributed to risk in both index and control groups, and a poorer current parenting environment exacerbated the difficulties of those with clefts. Conclusions: Children with clefts are at raised risk for socio-emotional difficulties in the school years; clinical interventions should focus on communication problems and supporting parenting; specific interventions around the transition to school may be required. More generally, the findings reflect the importance of communication skills for children's peer relations.

This study aimed to examine the association between serum microRNAs (miRNAs) and diagnosis and growth of abdominal aortic aneurysm (AAA), and to test their diagnostic and prognostic value. The expression levels of 800 miRNA tags were assessed in 108 patients with AAA, 12 age and sex matched healthy controls (HCs), and 12 patients with peripheral artery disease (PAD) using NanoString technology. Findings were assessed in an independent sample of 66 patients with AAA and 29 age and sex matched HCs by reverse transcriptase polymerase chain reaction. AAA growth was assessed by a median of three (interquartile range [IQR] 2, 3) repeat ultrasound scans over a median follow up of 1.1 (IQR 1.0, 2.0) years. The association between the miRNA and AAA diagnosis and growth was examined by regression and linear mixed effects analyses. The diagnostic and prognostic potential of the miRNAs were examined using area under the receiver operator characteristic curve (AUC), net re-classification index (NRI), and Cox hazard analyses. In comparison with HCs, a model combining clinical risk factors, let-7b-5p and miR-548n had an AUC of 98.0% (95% confidence interval [CI] 95.6 – 100.0; p =.003) for diagnosing AAA, which was a significant improvement over clinical risk factors alone (NRI 1.74; 95% CI 1.61 – 1.87; p <.001). Compared with PAD, a model combining clinical risk factors and miR-548n had an AUC of 99.6% (95% CI 98.9 – 100.0, p =.037) for diagnosing AAA, which was a significant improvement over clinical risk factors alone (NRI 1.79, 95% CI 1.68 – 1.91; p <.001). In the longitudinal cohort, none of the miRNAs were able to predict the likelihood of reaching surgical threshold diameter better than clinical risk factors alone. Serum let-7b-5p and miR548n significantly improved the ability to diagnose AAA. None of the miRNAs had independent prognosis value in predicting AAA growth. [ABSTRACT FROM AUTHOR]

If we knew more about “music” as a human capability and its potential as an intellectual and affective force in human communication, society, and culture, we could use it more generally to enhance general education and to build peaceful, egalitarian, and prosperous societies in the twenty-first century, just as our prehistoric ancestors once used it to invent the cultures from which all civilisations evolved.(Blacking, 1995, p. 242)In December 2008 I travelled to Sierra Leone to undertake research into the role of music in effective health promotion. Situated on the coast of West Africa, Sierra Leone sits at the bottom of the UNDP human development index, and has the highest maternal mortality rates in the world; the country is recovering from a ten-year civil war which decimated infrastructure and traumatised the nation. These facts notwithstanding, I took as my premise that music continues to be a vibrant part of Sierra Leonean culture, and has a key role to play in promoting good health, but that its full potential has yet to be fully harnessed. My field research was funded by a Gerry Farrell Scholarship, awarded by the Society for Education, Music and Psychology Research (SEMPRE). This paper follows on from my field research; through a combination of ethnographic method, musical and textual analysis, and insights from the ethnomusicology literature, I examine the different ways in which music can be used to promote health and well-being in rural post-conflict Sierra Leone.

Art of Recovery explores the potential of a participatory arts engagement with place to contribute toward the recovery and reconnection of refugees who experience trauma. The study responded to the international challenge of refugees’ mental health as a global priority as they experience higher prevalence rates of severe mental health disorders in comparison with the general population. The role of participatory arts in contributing toward recovery and reconnection is growing, but policymakers and health professionals are constrained by the lack of research exploring its benefits. We worked with 14 participants in four participatory arts workshops exploring the benefits of artwork focusing on remembered or imagined healing places. A qualitative thematic analysis of the artwork drew on Herman’s theory of recovery identifying “remembrance„, “mourning„, and “reconnection„ to assess the elements of potential recovery, including aspects of the participants’ experience of transition between their homeland and the United Kingdom (UK), and new social connections. In conclusion, the study suggests that participating in a group making artworks of places associated with safety may contribute to processes of transition and social connectedness, prompting in turn feelings of wellbeing. The study offers insights into arts and health issues of interest to refugee-supporting communities, health professionals and policymakers.