Search

Background: The aim of this study was to develop a consensus-based set of indicators of high-quality acute moderate to severe traumatic brain injury (msTBI) clinical management that can be used to measure structure, process, and outcome factors that are likely to influence patient outcomes. This is the first stage of the PRECISION-TBI program, which is a prospective cohort study that aims to identify and promote optimal clinical management of msTBI in Australia., Methods: A preliminary set of 45 quality indicators was developed based on available evidence. An advisory committee of established experts in the field refined the initial indicator set in terms of content coverage, proportional representation, contamination, and supporting evidence. The refined indicator set was then distributed to a wider Delphi panel for assessment of each indicator in terms of validity, measurement feasibility, variability, and action feasibility. Inclusion in the final indicator set was contingent on prespecified inclusion scoring., Results: The indicator set was structured according to the care pathway of msTBI and included prehospital, emergency department, neurosurgical, intensive care, and rehabilitation indicators. Measurement domains included structure indicators, logistic indicators, and clinical management indicators. The Delphi panel consisted of 44 participants (84% physician, 12% nursing, and 4% primary research) with a median of 15 years of practice. Of the 47 indicators included in the second round of the Delphi, 32 indicators were approved by the Delphi group., Conclusions: This study identified a set of 32 quality indicators that can be used to structure data collection to drive quality improvement in the clinical management of msTBI. They will also be used to guide feedback to PRECISION-TBI's participating sites., (© 2024. The Author(s).)

Projects that aim to improve the welfare of equids worldwide usually involve people from different countries and cultures working together. Given that professionals involved with multi-stakeholder projects often work cross-culturally, this study examined their experiences regarding the challenges involved in, and their reflections on, how to work in a culturally sensitive way. Semi-structured interviews were conducted with 14 participants working in a total of 29 countries and analysed using thematic analysis. Key response themes emerged from the responses to questions covering the areas of perceptions of animal welfare, challenges working cross-culturally and embracing cultural sensitivity. The overriding theme regarding perceptions of animal welfare was that of barriers to animal welfare, under which emerged the subthemes of limited financial and material resources, limited understanding of the tenets of animal welfare, and attachment to traditional medicines and practices. Exploring the key challenges resulted in two themes: challenges regarding the local context and etiquette, and those regarding working with different stakeholders. Considering cultural sensitivity, again, two themes emerged: the importance of trust and respect, and of working with local partners. Previous works have highlighted the importance of shared linguistic knowledge, interpersonal skills and cultural knowledge, and these elements also emerged in this research. As well as providing insights into the challenges of working cross-culturally, the findings of this study have enabled the development of suggestions for how this work could be taken forward in a practical way to be of use to professionals in this sector.

One of the key welfare concerns for horses in the United Kingdom is lack of recognition of fear in horses. This study aimed to gain an understanding of how well horse care givers recognise fear and/or anxiety in horses by interviewing equine behaviourists (who interact with large numbers of horse care givers and talk to them about this topic routinely). The experiences of Animal Behaviour and Training Council (ABTC)-registered equine behaviourists working with horse caregivers were examined, including the ability of clients to recognise fear and/or anxiety in horses, how clients respond when discussing fear as the reason for their horse's behaviour, and what explanations the participants use to explain fear and anxiety. Semi-structured interviews were conducted with nine participants and analysed using thematic analysis before being written up to reflect the discussion points. When asked how well horse caregivers recognise fear and/or anxiety in horses, three key response themes emerged: caregivers are extremely poor at recognizing fear and anxiety in horses; some clients do recognise behavioural signs indicating fear and/or anxiety but only the overt signs (e.g., rearing, running away) rather than the more subtle signs (e.g., tension in face, subtle avoidance behaviours such as a hesitant gait); and fear and/or anxiety behaviour is often misinterpreted or mislabelled. These key themes recurred throughout several other interview questions. This study has provided initial insights into the lack of recognition of fear and anxiety of horses by their caregivers in the United Kingdom as well as tried and tested approaches to conversations to change this. Such synthesis of experience and techniques across the equine behaviour sector, together with the information gained regarding perception of equine caregivers, could be a valuable approach to improve the effectiveness of behaviour consultations and welfare initiatives.

Understanding early nervous system stress response mechanisms is crucial for studying developmental neurotoxicity and devising neuroprotective treatments. We used hiPSC-derived long-term self-renewing neuroepithelial stem (lt-NES) cells differentiated for up to 12 weeks as an in vitro model of human neural development. Following a transcriptome analysis to identify pathway alterations, we induced acute oxidative stress (OS) using tert-butyl hydroperoxide (TBHP) and assessed cell viability at different stages of neural differentiation. We studied NRF2 activation, autophagy, and proteasomal function to explore the contribution and interplay of these pathways in the acute stress response. With increasing differentiation, lt-NES cells showed changes in the expression of metabolic pathway-associated genes with engagement of the pentose phosphate pathway after 6 weeks, this was accompanied by a decreased susceptibility to TBHP-induced stress. Microarray analysis revealed upregulation of target genes of the antioxidant response KEAP1-NRF2-ARE pathway after 6 weeks of differentiation. Pharmacological inhibition of NRF2 confirmed its vital role in the increased resistance to stress. While autophagy was upregulated alongside differentiation, it was not further increased upon oxidative stress and had no effect on stress-induced cell loss and the activation of NRF2 downstream genes. In contrast, proteasome inhibition led to the aggravation of the stress response resulting in decreased cell viability, derangement of NRF2 and KEAP1 protein levels, and lacking NRF2-pathway activation. Our data provide detailed insight into the dynamic regulation and interaction of pathways involved in modulating stress responses across defined time points of neural differentiation.

To investigate cerebral autoregulatory status in patients with severe traumatic brain injury (TBI), guidelines now suggest active manipulation of mean arterial pressure (MAP). There is a paucity of data, however, describing the effect on intracranial pressure (ICP) when MAP is raised. Consecutive patients with TBI requiring ICP monitoring were enrolled from November 2019 to April 2020. The MAP and ICP were recorded continuously, and clinical annotations were made whenever intravenous vasopressors were commenced or adjusted to defend cerebral perfusion pressure (CPP) targets. A significant change in MAP burden was defined as MAP >100min.mm Hg over 15 min. The primary outcome was the change in ICP burden over the same 15-min period. Bedside and clinical parameters were then compared between these groups. Twenty-eight patients were enrolled, providing 212 clinical events, of which 60 were deemed significant. Over the first 15 min, 65% were associated with a net negative ICP burden. A greater reduction in ICP burden was observed with events occurring in patients without a history of hypotension at scene ( p  = 0.016), after three days post-injury ( p  = 0.0018), and where the pressure-reactivity index (PRx) was <0.25 ( p  = 0.0005) or the ICP amplitude to CPP correlation coefficient (RAC) was <-0.10 ( p  = 0.0036) at the initiation of vasopressor changes. The ICP burden in the first 15 min was highly correlated with the next 15-min period. In patients with severe TBI requiring ICP monitoring, increasing MAP to pursue a CPP target was followed by a net negative ICP burden in approximately two-thirds of events. These data suggest a MAP challenge may be a useful adjunct in managing intracranial hypertension.

A key welfare concern for the equine population in the U.K. has been identified as delayed death, leading to prolonged suffering of horses. Reasons why some horse owners fail to have their horses euthanised include financial cost, emotional attachment, peer pressure, negative attitudes towards killing and poor recognition of behavioural indicators of equine pain and stress. The Five Freedoms framework of welfare was used to build a Likert-style survey to investigate the factors underlying attitudes of horse owners towards welfare measures in an end-of-life decision. Participants were asked to respond to hypothetical welfare scenarios and to give details of any horses they had had euthanised. The survey was conducted predominantly via equestrian Facebook groups and obtained 160 participant responses. Reliability of the scale was acceptable, with Cronbach's α=0.89. Principal Component Analysis was used to load the hypothetical scenarios onto seven factors containing 62.2% of the variance. The first four factors could be categorized according to "Ethology-informed Management", "Traditional Horse Management", "Emotional Issues" and "Physical Issues". Participants were more likely to consider euthanasia for physical issues, compared with issues relating to affective state and/or ethology, although it was not clear whether this was due to disregard for welfare issues relating to mental health or failure to recognise them as such. A large number of responses stated that the scenario had no bearing on whether a horse should be euthanised, again suggesting a lack of recognition of welfare issues and their implications. When asked to state their reasons for euthanising their horses, participants cited almost exclusively physical reasons, with the exception of those citing dangerous behaviour. Only a small number of responses also included consideration of affective and/or ethological factors, suggesting that welfare issues concerning affective state and/or behaviour are at risk of omission from end-of-life decisions.

In the UK, March 2020 was a time of great uncertainty as COVID-19 became increasingly widespread. The government responded by making suggestions about how people could reduce the risk of spread on 16 March, moved swiftly into closing schools on the 18 March before announcing a mandatory lockdown on the 23rd March. This was a challenging time for UK equestrians who had to balance maintaining their equine's routine and daily care alongside the increasing biosecurity measures. A cross-sectional survey was distributed to UK equestrians via social media over two days (28 and 29 March 2020) to better understand the decisions made by UK horse, pony and donkey owners during this time. Data from 452 respondents were generated across all four countries comprising the UK, although there were no significant differences in owner response to the pandemic between locations. The changes respondents made differed between the 16th and the 18th of March 2020, with an early emphasis on improving yard biosecurity and opting to stop riding, as well as reducing the time spent at the yard. After the 18 March, respondents placed more emphasis on risk reduction by changing the activities they did with their horse, including riding, with common examples including avoiding "high risk" activities such as riding on busy roads, jumping, riding young or nervous horses. Few respondents reported having an emergency plan in place should they become ill or otherwise unable to care for their equine. The findings highlight areas that would significantly benefit from in-depth investigation in future research. Equestrian behaviour and mindset around risk-taking and risk perception have already been researched in relation to equestrian activities and sport but have received little attention in the context of wider health challenges. Understanding the uptake of emergency planning and preparation in the UK equestrian community also warrants consideration. Using this information effectively to promote forward planning is likely to be of great benefit in equestrian responses to future health or climate-related crises.

A key welfare problem for horses is that people commonly fail to recognise, and consequently neglect to resolve, equine behavioural signs of distress, worsening the welfare of the horse and potentially putting the safety of the handler at risk as a result. Members of equestrian Facebook groups were asked to view six videos and assess the horse's behaviour in each; the authors selected the videos and considered each video to demonstrate behaviour associated with negative affective states. An additional six equine behaviourists also completed the survey as an "expert comparison group" from whom we could define "correct" answers; their responses were consistent with each other and the views of the authors. Although the majority of respondents successfully recognised behaviour indicative of distress in some instances, behaviour associated with negative affective states was commonly missed; videos featuring natural horsemanship and bridle-less riding were particularly interpreted incorrectly to be positive experiences for the horses. Binary logistic regression analysis (72.1% success rate) confirmed that the different video types (ridden dressage, natural horsemanship, in-hand dressage, bridle-less riding, Western reining and behavioural rehabilitation) were strong predictors for obtaining a correct answer ( p < 0.01) but that experience of equine-ownership was not. Of the equestrian activities preferred by participants, only proponents of clicker training showed an increased likelihood of obtaining the correct answer ( p = 0.05 ) . Even when behavioural signs suggestive of negative affective states were recognised, a minority of respondents stated that they would be happy for their horse to be treated similarly. In conclusion, behavioural signs of equine distress are poorly recognised; they therefore warrant an increased prominence in education and the outreach activity of welfare organisations, in order to reduce equine suffering., Competing Interests: The authors declare no conflict of interest

Background: Rare cancers comprise almost a quarter of all cancers in Europe, and patients generally have poorer outcomes than those suffering from more common cancers. This is attributed in part to a general lack of knowledge and awareness of rare cancers. This review aims to examine the communication strategies being used throughout the world to inform on rare cancers and to highlight any opportunities for improvement., Methods: A systematic review of literature published in English prior to November 2018 will be conducted, screening articles from the electronic databases MEDLINE, PubMed, EMBASE, Web of Science, PsycINFO, CINAHL Plus and the Cochrane Database of Systematic Reviews. Grey literature databases (GreyLit, OpenGrey) will also be searched in order to screen for any unpublished works. As well as primary literature, reference lists will be examined via forward and reverse citation screening. The review will be reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). Titles and abstracts will first be examined for eligibility, with remaining studies undergoing a full-text screening before being included in the final review. Individual studies will be screened for bias, and a meta-analysis performed provided there is enough data. If insufficient homogenous literature exists, a narrative summary of the literature will be produced., Discussion: Despite the broad topic and width of study type that will be considered, this review hopes to provide a reflective summary of the communication strategies available for people living with and working with rare cancer. It aims to reveal any gaps in the resources available, to contribute to the long-term improvement of diagnosis and management of rare cancers., Systematic Review Registration: PROSPERO CRD42018099784.

Competing Interests: Conflicts of interest: None declared. It may look like my child is sponsored by Peppa Pig, but any claims to this effect are false.

Small, noncoding RNAs are short untranslated RNA molecules, some of which have been associated with cancer development. Recently we showed that a class of small RNAs generated during the maturation process of tRNAs (tRNA-derived small RNAs, hereafter "tsRNAs") is dysregulated in cancer. Specifically, we uncovered tsRNA signatures in chronic lymphocytic leukemia and lung cancer and demonstrated that the ts-4521/3676 cluster (now called " ts-101 " and " ts-53 ," respectively), ts-46 , and ts-47 are down-regulated in these malignancies. Furthermore, we showed that tsRNAs are similar to Piwi-interacting RNAs (piRNAs) and demonstrated that ts-101 and ts-53 can associate with PiwiL2, a protein involved in the silencing of transposons. In this study, we extended our investigation on tsRNA signatures to samples collected from patients with colon, breast, or ovarian cancer and cell lines harboring specific oncogenic mutations and representing different stages of cancer progression. We detected tsRNA signatures in all patient samples and determined that tsRNA expression is altered upon oncogene activation and during cancer staging. In addition, we generated a knocked-out cell model for ts-101 and ts-46 in HEK-293 cells and found significant differences in gene-expression patterns, with activation of genes involved in cell survival and down-regulation of genes involved in apoptosis and chromatin structure. Finally, we overexpressed ts-46 and ts-47 in two lung cancer cell lines and performed a clonogenic assay to examine their role in cell proliferation. We observed a strong inhibition of colony formation in cells overexpressing these tsRNAs compared with untreated cells, confirming that tsRNAs affect cell growth and survival., Competing Interests: The authors declare no conflict of interest.

The study examined the question of who should make decisions for a National Health Scheme about the allocation of health resources when the health states of beneficiaries could change because of adaptation. Eight semi-structured small group discussions were conducted. Following focus group theory, interviews commenced with general questions followed by transition questions and ended with a 'focus' or 'key' question. Participants were presented with several scenarios in which patients adapted to their health states. They were then asked their views about the appropriate role of the public, patients and health professionals in making social judgements of quality of life. After discussion and debate, all groups were asked the key question: 'In light of adaptation, who should evaluate quality of life for the purpose of setting priorities in the allocation of health care?' In all groups participants presented strong arguments for and against decision making by patients, the public and health professionals. However, most groups thought a representative body which included a range of perspectives should make the relevant judgements. This is at odds with the recommendations in most national pharmaceutical guidelines. The main conclusion of the paper is that health economists and other researchers should explore the possibility of adopting a deliberative, consensus-based approach to evaluating health-related quality of life when such judgements are to be used to inform priority setting in a public system.

This qualitative study, conducted by volunteers from the Australian Capital Territory/Southern New South Wales (ACT/SNSW) Branch of the Australian Breastfeeding Association (ABA), explored the breastfeeding experiences of younger mothers (under the age of 26 years) in the ACT by conducting three focus groups. The study aimed to gain an understanding of how, when and where younger mothers want and need to receive breastfeeding information and support. Younger mothers provided important insights into their breastfeeding experiences, which were often characterised by judgement from health professionals and the wider public. A number of key issues were identified including: breastfeeding is far from a cultural norm in our society and as such the risks of artificial baby milk are not clearly understood by many younger mothers; younger mothers are strongly influenced by their partners, mothers and peers and they rely upon them for breastfeeding information and support. Younger mothers indicated that a number of improvements could be made to the way that breastfeeding information and support is currently provided within the ACT. The findings indicated that younger mothers (and their significant others) would benefit from receiving clear, concise and consistent breastfeeding information early on in their pregnancy, that is positive in tone, not necessarily 'young mum' specific and consistent with a 'less is more' approach. Younger mothers indicated that after the birth of their baby this breastfeeding information needs to be complemented by readily accessible, seamless, respectful support for as long as they need to establish breastfeeding and overcome any breastfeeding challenges. The focus group findings were largely consistent with the existing literature available on younger mothers and breastfeeding and provide valuable insights to all stakeholders responsible for providing breastfeeding information and support to younger mothers.

McLean Hospital's College Mental Health Program was established four years ago as an institutional response to escalating, national college mental health concerns. The critical factors underlying the college mental health crisis in this country have been debated, examined, and addressed almost exclusively within college and university settings. McLean Hospital is the first psychiatric hospital to develop a comprehensive college student program that bridges the gap between a psychiatric hospital and multiple campus settings as an attempt to address the specific needs of college student-patients across levels of psychiatric care and diagnostic areas/programs. Using a bioecological systems framework, this review examines (1) the strategic clinical, education/outreach, and research efforts that collectively represent a paradigm shift to extend responsibility for addressing serious college mental health challenges beyond college and university campuses, (2) the challenges and benefits of creating stronger multi-campus/hospital collaborations in order to improve our understanding of college students with serious mental illness, and (3) the progress in addressing these needs more effectively and in establishing documented best practices and policies through effective and innovative partnerships.

Objectives: To explore female early school leaver's experience of sexual activity and sex education, and to assess the feasibility and potential impact of a peer-led sex education intervention., Methods: Forty five young female early school leavers and ten peer educators participated in the study. The ten peer educators, early school leavers who were teenage mothers, were trained to deliver the peer-led education intervention. Both quantitative (self-completed questionnaire) and qualitative (focus groups) research methods were used to evaluate the intervention., Results: The average age of participants was 17.5 years. The average age at leaving school was 15 years. Many participants were smokers and took alcohol on a regular basis. Over three quarters of the young women were sexually active. Although most used contraception in the past, over 30% had not the last time they had sex. While participants' knowledge around sexual issues showed some improvement following the pilot intervention, there was little change in attitudes to sexual behaviour., Conclusions: This feasibility study was very well received by both peer educators and participants. To assess the effectiveness of the intervention we recommend that a larger randomised control trial be conducted.

Most countries appear to believe that their health system is in a state of semi-crisis with expenditures rising rapidly, with the benefits of many services unknown and with pressure from the public to ensure access to a comprehensive range of services. But whose values should inform decision-making in the health area, and should the influence of different groups vary with the level of decision-making? These questions were put to 54 members of the public and health professionals in eight focus groups. Adopting a different perspective from other studies, participants were not asked if particular groups should be involved in decisions but rather through deliberation and discussion nominated their own potential decision makers. This delivered a clear message that participants saw a legitimate role for a broad range of stakeholders in priority-setting decisions so as to incorporate a diversity of expertise and opinion. Companion themes were the acknowledgment that decisions involve ethical judgments and are not purely technical, that the power of special interest groups (such as clinicians) should be kept in check, and that the process by which decisions are reached is important. The results suggest that qualitative methods of investigation have the potential to improve the legitimacy of policy decisions by contributing to a better understanding of the values of the public and health professionals, and by expanding the range of options available for further research.