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To determine whether the administration of trazodone to dogs 2 hours prior to radiotherapy treatment reduced the dose of propofol required to induce anaesthesia.Retrospective, crossover, case-matched study.Records of 30 client-owned dogs.Anaesthetic records from all dogs undergoing weekly radiotherapy treatment between January 2020 and December 2020 were retrospectively assessed. All dogs were premedicated with 10 μg kgIn part 1, 15 study dogs that were administered trazodone prior to at least one anaesthetic were identified. A significant difference in propofol induction dose between groups NT and T was identified [3.3 (2.1-7.4) and 2.0 (1.5-5.0) mg kgPreanaesthetic trazodone administration reduced the induction dose of propofol compared to when it was not administered to dogs following premedication with IV atropine and alfentanil.

15 páginas.- 6 figuras.- 93 referencias, Fungi are highly diverse organisms, which provide multiple ecosystem services. However, compared with charismatic animals and plants, the distribution patterns and conservation needs of fungi have been little explored. Here, we examined endemicity patterns, global change vulnerability and conservation priority areas for functional groups of soil fungi based on six global surveys using a high-resolution, long-read metabarcoding approach. We found that the endemicity of all fungi and most functional groups peaks in tropical habitats, including Amazonia, Yucatan, West-Central Africa, Sri Lanka, and New Caledonia, with a negligible island effect compared with plants and animals. We also found that fungi are predominantly vulnerable to drought, heat and land-cover change, particularly in dry tropical regions with high human population density. Fungal conservation areas of highest priority include herbaceous wetlands, tropical forests, and woodlands. We stress that more attention should be focused on the conservation of fungi, especially root symbiotic arbuscular mycorrhizal and ectomycorrhizal fungi in tropical regions as well as unicellular early-diverging groups and macrofungi in general. Given the low overlap between the endemicity of fungi and macroorganisms, but high conservation needs in both groups, detailed analyses on distribution and conservation requirements are warranted for other microorganisms and soil organisms., The bulk of the funding is derived from the Estonian Science Foundation (grants PRG632, PRG1170, PRG1615, MOBTP198), EEA Financial Mechanism Baltic Research Programme (EMP442), and Novo Nordisk Fonden (NNF20OC0059948).

Rationale This paper concerns mortality and needs for end-of-life care in a population of adults with ID living in generic care homes. Methods Various sampling strategies were used to identify a difficult to find a population of people with ID in generic care homes. Demographic and health data were obtained for 132 people with ID. This included the Surprise Question. At T2, 12 months later, data were obtained on the survival of this sample. Findings The average age was 68.6 years, and the majority were women (55.3%). Their health was typically rated as good or better. Responses to the Surprise Question indicated that 23.3% respondents might need EoLC. At T2, 18.0% of this population had died. The average of death was 72.2 years. The majority died within the care setting (62.9%). Implications The implications for end-of-life care and mortality research are discussed.

Axonal degeneration is an early and ongoing event that causes disability and disease progression in many neurodegenerative disorders of the peripheral and central nervous systems. Chemotherapy-induced peripheral neuropathy (CIPN) is a major cause of morbidity and the main cause of dose reductions and discontinuations in cancer treatment. Preclinical evidence indicates that activation of the Wallerian-like degeneration pathway driven by sterile alpha and TIR motif containing 1 (SARM1) is responsible for axonopathy in CIPN. SARM1 is the central driver of an evolutionarily conserved programme of axonal degeneration downstream of chemical, inflammatory, mechanical or metabolic insults to the axon. SARM1 contains an intrinsic NADase enzymatic activity essential for its pro-degenerative functions, making it a compelling therapeutic target to treat neurodegeneration characterized by axonopathies of the peripheral and central nervous systems. Small molecule SARM1 inhibitors have the potential to prevent axonal degeneration in peripheral and central axonopathies and to provide a transformational disease-modifying treatment for these disorders. Using a biochemical assay for SARM1 NADase we identified a novel series of potent and selective irreversible isothiazole inhibitors of SARM1 enzymatic activity that protected rodent and human axons in vitro. In sciatic nerve axotomy, we observed that these irreversible SARM1 inhibitors decreased a rise in nerve cADPR and plasma neurofilament light chain released from injured sciatic nerves in vivo. In a mouse paclitaxel model of CIPN we determined that Sarm1 knockout mice prevented loss of axonal function, assessed by sensory nerve action potential amplitudes of the tail nerve, in a gene-dosage-dependent manner. In that CIPN model, the irreversible SARM1 inhibitors prevented loss of intraepidermal nerve fibres induced by paclitaxel and provided partial protection of axonal function assessed by sensory nerve action potential amplitude and mechanical allodynia., Bosanac et al. identify new small molecule inhibitors of SARM1, an NAD-consuming enzyme responsible for axonal degeneration, and show that they protect axons in vitro and in a paclitaxel model of chemotherapy-induced peripheral neuropathy. SARM inhibition may have therapeutic potential in peripheral neuropathies and CNS degeneration.

Over the last three decades, sociomaterial approaches to the study of health care practices have made an important contribution to the sociology of health care. Significant attention has been paid to the role of technology and artefacts in health care and the operation of actor-networks but less space has been given to questions of ontological multiplicity in health care practices. In this paper, we draw upon our study of patient experience data in five acute hospitals in England to illustrate how treating patient experience data as 'singular-multiples' can enable useful insights into patient experience data work in health care organisations. Our data was generated during 12 months of fieldwork at five participating hospitals and included organisational documents, field notes, informal and formal interviews with frontline and managerial staff and patient representatives at the study sites. We use the examples of the Friends and Family Test (FFT) and the National Cancer Patient Experience Survey (NCPES) in England to consider the multiple nature of data as it is enacted in practice and the work data does when coordinated as an entity in the singular. We argue that, and discuss how, the sociomaterial insights we discuss here are relevant to health care quality and improvement research and practice.

Background Physician associates (PAs) are one of many new mid-level health practitioner roles being introduced worldwide. They are a recent innovation in English hospitals. Patient confusion with novel mid-level practitioner titles and roles is well documented, alongside evidence of a positive association between patients' ability to identify practitioners and patient satisfaction. No prior research developed an intervention to introduce PAs or any other new practitioner role to hospital patients. Objective To develop, with patient and public involvement and engagement (PPIE), an intervention for introducing the PA role to hospital patients, and to test feasibility. Methods Intervention development was underpinned by an experience-based co-design approach. Workshop participants generated ideas for introducing PAs, subsequently explored in semi-structured interviews with hospital patients (n = 13). Interview findings were used by participants in a second workshop to design the intervention. Feasibility of the intervention was assessed in relation to its acceptability and efficacy using semi-structured interviews with hospital patients (n = 20) and PAs (n = 3). Results The intervention developed was a patient information leaflet. It was considered feasible to use in the hospital setting, helpful to patients in understanding the PA role and acceptable to both patients and PAs. The intervention was also appreciated by patients for providing reassurance of care and support. Conclusions An experience-based co-design approach enabled development of an intervention tailored to patients' experiential preferences. Positive evidence of feasibility and utility is encouraging, supporting future larger-scale testing. Patient and public contribution PPIE representatives were involved in the study design, intervention development and data interpretation.

Background Rectus sheath catheter analgesia (RSCA) and thoracic epidural analgesia (TEA) are both used for analgesia following laparotomy. The aim was to compare the analgesic effectiveness of RSCA with TEA after laparotomy for elective colorectal and urological surgery. Methods Patients undergoing elective midline laparotomy were randomized in a non-blinded fashion to receive RSCA or TEA for postoperative analgesia at a single UK teaching hospital. The primary quantitative outcome measure was dynamic pain score at 24 h after surgery. A nested qualitative study (reported elsewhere) explored the dual primary outcome of patient experience and acceptability. Secondary outcome measures included rest and movement pain scores over 72 h, functional analgesia, analgesia satisfaction, opiate consumption, functional recovery, morbidity, safety, and cost-effectiveness. Results A total of 131 patients were randomized: 66 in the RSCA group and 65 in the TEA group. The median (interquartile range; i.q.r.) dynamic pain score at 24 h was significantly lower after TEA than RSCA (33 (11–60) versus 50.5 (24.50–77.25); P = 0.018). Resting pain score at 72 h was significantly lower after RSCA (4.5 (0.25–13.75) versus 12.5 (2–13); P = 0.019). Opiate consumption on postoperative day 3 (median (i.q.r.) morphine equivalent 17 (10–30) mg versus 40 (13.25–88.50) mg; P = 0.038), hypotension, or vasopressor dependency (29.7 versus 49.2 per cent; P = 0.023) and weight gain to day 3 (median (i.q.r.) 0 (−1–2) kg versus 1 (0–3) kg; P = 0.046) were all significantly greater after TEA, compared with RSCA. There were no significant differences between groups in other secondary outcomes, although more participants experienced serious adverse events after TEA compared with RSCA, which was also the more cost-effective. Conclusions TEA provided superior initial postoperative analgesia but only for the first 24 h. By 72 hours RSCA provides superior analgesia, is associated with a lower incidence of unwanted effects, and may be more cost-effective.

Older people living in care homes are at high risk of poor health outcomes and mortality if they contract COVID-19 or other infectious diseases. Measures used to protect residents include social distancing and isolation, although implementation is challenging. This review aimed to assess the social distancing and isolation strategies used by care homes to prevent and control the transmission of COVID-19 and other infectious diseases. Seven electronic databases were searched: Medline, CINAHL, Embase, PsycINFO, HMIC, Social Care Online, and Web of Science Core Collection. Grey literature was searched using MedRxiv, PDQ-Evidence, NICE Evidence Search, LTCCovid19.org and TRIP. Extracted data were synthesised using narrative synthesis and tabulation. 103 papers were included (10 empirical studies, seven literature reviews, and 86 policy documents). Strategies used to prevent and control the transmission of COVID-19 and other infectious diseases included social distancing and isolation of residents and staff, zoning and cohorting of residents, restriction of resident movement/activities, restriction of visitors and restriction of staff working patterns. This review demonstrates a lack of empirical evidence and the limited nature of policy documentation around social distancing and isolation measures in care homes. Evaluative research on these interventions is needed urgently, focusing on the well-being of all residents, particularly those with hearing, vision or cognitive impairments.

Background Breast cancer is the most common cancer in women globally. Its negative effects on a woman’s quality of life are related to the individual and socio-cultural factors. This review aimed to identify and synthesise the reported experiences and quality of life of women with breast cancer in Arab countries. Methods PubMed, Embase, Web of Science, SCOPUS, PsychInfo, CINAHL, Allied and Complementary Medicine Database, and Index Medicus for the Eastern Mediterranean Region were searched for articles published from start to March 2019 using PRISMA guidelines. These searches were complimented by citation tracking and hand searching of relevant journals. A thematic synthesis was carried out on the ‘findings/results’ sections from the identified papers. Results Of 5228 records identified, 19 were included in the review which represented 401 women from 11 Arab countries. All used qualitative methods of data collection to produce rich descriptions of experiences. Thematic synthesis of the extracted data identified three major themes, Perceptions and reactions, Coping or enduring and Changing roles. Conclusions This review provides a rich description of the reported quality of life and experiences of women with breast cancer in Arab countries. These are influenced by the women’s and society’s views of cancer, the women’s role in society and family, religious faith and the healthcare context and access to treatment choices and information.

OBJECTIVES:\ud Older informal carers play a vital, growing role in supporting others with long-term health conditions but their support needs and experiences are poorly understood. The aim of this study was to explore the perceptions of volunteers and professionals of the experiences and support needs of older carers (aged 70+ years).\ud \ud METHODS:\ud Thirty-five volunteers and professionals working with older carers in the voluntary and statutory sectors participated in a series of focus groups in outer London, United Kingdom. Groups were audio recorded, transcribed and subjected to thematic analysis.\ud \ud FINDINGS:\ud Five main themes were identified. These included participants' perceptions of older carers' ambivalence about asking for support, their multiple losses, often restricted lives, social isolation and loneliness and concerns for their loved ones when they can no longer care. Overall, these themes are similar to those reported for adult carers in general but older carers' experiences were regarded as more challenging primarily because of their pride, attitudes to caring and because of their age, their own health was often declining making the physical aspects of caring and leaving their homes more difficult. Concerns about the future are thought to be particularly important for older carers of adult children with disabilities because they expect to be outlived by their children, although similar concerns were voiced by spouses of partners living with dementia.\ud \ud CONCLUSIONS:\ud Professionals and volunteers need to consider these additional challenges for older carers. Support with accessing services, for example from the voluntary sector, is important as is future exploration of how to support older carers in planning for the future care for their loved ones is needed.

IntroductionOlder people living in residential and nursing care homes often have complex needs and are at high risk of poor health outcomes and mortality, especially if they contract COVID-19. Care homes use infection prevention and control measures such as social distancing and isolating residents to protect them from COVID-19. The care home sector has stated that implementing social distancing and isolation when caring for residents is a significant challenge. This paper presents the protocol of a mixed-methods study to explore and understand the real-life experiences of implementing social distancing and isolation of residents in care homes for older people from the perspective of residents, families/friends and staff working in and with care homes. The study aims to develop a toolkit of resources for health and care delivery now and for future outbreaks of infectious diseases.Methods and analysisThe study will be conducted in three phases. Phase 1 is a rapid review of evidence to collate knowledge on the mechanisms and measures used by care homes and long-term facilities to socially distance and isolate older people or control the spread of other infectious and contagious diseases. The review results will contribute to participant interviews in phase 2 and toolkit development in phase 3. Phase 2 will involve case studies with six care homes in England, involving the conduct of individual interviews with residents, families and friends, and staff, collection of care home policies and protocols related to social distancing and isolation for residents, and routinely collected care home data. A focus group with a purposive sample of external key informants will also be conducted. Phase 3, synthesising findings from phases 1 and 2, will inform the codesign of a toolkit of resources for residents, families/friends and care homes.Ethics and disseminationThe study has been approved by Coventry and Warwick Research Ethics Committee (20/WM/0318). To maximise impact, we will work closely with the Study Committees and the Patient and Public Involvement group to ensure the findings reach key stakeholders, including residents, families/friends, care homes, commissioners and organisations representing care home providers. We will disseminate the study outputs in peer-reviewed and professional journals, at professional conferences and via other knowledge transfer activities with the care home sector, and resident and carer organisations. The toolkit comprising evidence-informed guidance and resources and a mosaic film will be hosted on a project webpage.Registration detailsThis project is funded by the National Institute for Health Research (NIHR) Health Services and Delivery Research Programme (Project reference NIHR132541). The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.PROSPERO registration numberCRD42021226734.

Purpose Advances in cancer treatment have led to longer cancer-free periods and overall survival. This study aimed to understand patients’ experiences of transitioning out of a state of believing to be cancer free into incurable recurrence with advanced disease. Methods Using constructivist grounded theory with in-depth interviews patients (n = 15) with solid tumors from a major US cancer center participated. Theoretical sampling enabled concepts to be developed until theme saturation. Constant comparative analysis used initial and focused coding to develop themes and concepts to describe this specific period from extended time cancer free and transition to advanced incurable disease. Results Three interrelated concepts were identified: reluctant acceptance, seeking survival through continuous treatment, and hope in the face of an uncertain future. A conceptual model of the experience was developed encompassing anger and sadness, at initial recurrence, to reluctant acceptance, and, finally, a cycle of seeking continuous treatment to prolong life leading to a sense of hope in the face of an uncertain future. Conclusion The cycle between treatment and hope creates a state of personal equilibrium, which provides insights into the importance of treatment for this population. This study provides direction for future research to understand the expectations of people experiencing advanced cancer recurrence. Implications for cancer survivors Many cancer survivors live with advanced cancer. Assessing their needs as they transition from survivor with no disease to survivor with advanced disease requires a new conceptualization of the experience which recognizes expectations and priorities for care of this patient group.

Climate change negatively impacts the livelihoods of indigenous communities across the world, including those located on the African continent. This Comment reports on how five African indigenous communities have been impacted by climate change and the adopted adaptation mechanisms.

Particulate matter (PM) presents an environmental health risk for communities residing close to uranium (U) mine sites. However, the role of the particulate form of U on its cellular toxicity is still poorly understood. Here, we investigated the cellular uptake and toxicity of C-rich U-bearing particles as a model organic particulate containing uranyl citrate over a range of environmentally relevant concentrations of U (0-445 μM). The cytotoxicity of C-rich U-bearing particles in human epithelial cells (A549) was U-dose-dependent. No cytotoxic effects were detected with soluble U doses. Carbon-rich U-bearing particles with a wide size distribution (

Ziritaxestat is a novel inhibitor of autotaxin, an enzyme responsible for the production of lysophosphatidic acid, the downstream signaling of which mediates responses to tissue injury and has been implicated in the pathogenesis of fibrotic conditions such as idiopathic pulmonary fibrosis and systemic sclerosis. This study (Clinical Trial Registration: NCT03787186) was designed to assess the absorption, distribution, metabolism, and excretion of orally administered 600-mg ziritaxestat labeled with a carbon-14 tracer (14 C-ziritaxestat). To understand the absolute bioavailability of ziritaxestat, an intravenous 100-μg microdose, labeled with a microtracer amount of 14 C radiation, was administered in a separate part of the study, following an unlabeled 600-mg therapeutic oral dose of ziritaxestat. Six healthy male subjects completed each study part. The majority of the labeled oral dose was recovered in feces (77%), with a total mass balance of 84%. The absolute bioavailability of ziritaxestat was 54%. Ziritaxestat was the main (76%) circulating drug-related product. There were 7 treatment-emergent adverse events, all of which were considered mild and not considered to be related to the study drug.

Src homology 2 domain-containing inositol phosphate phosphatase 2 (SHIP2) is one of the 10 human inositol phosphate 5-phosphatases. One of its physiological functions is dephosphorylation of phosphatidylinositol 3,4,5-trisphosphate, PtdIns(3,4,5)P3. It is therefore a therapeutic target for pathophysiologies dependent on PtdIns(3,4,5)P3 and PtdIns(3,4)P2. Therapeutic interventions are limited by the dearth of crystallographic data describing ligand/inhibitor binding. An active site-directed fluorescent probe facilitated screening of compound libraries for SHIP2 ligands. With two additional orthogonal assays, several ligands including galloflavin were identified as low micromolar Ki inhibitors. One ligand, an oxo-linked ethylene-bridged dimer of benzene 1,2,4-trisphosphate, was shown to be an uncompetitive inhibitor that binds to a regulatory site on the catalytic domain. We posit that binding of ligands to this site restrains L4 loop motions that are key to interdomain communications that accompany high catalytic activity with phosphoinositide substrate. This site may, therefore, be a future druggable target for medicinal chemistry.

ObjectivesTo compare the contribution of physician associates to the processes and outcomes of emergency medicine consultations with that of foundation year two doctors-in-training.DesignMixed-methods study: retrospective chart review using 4 months’ anonymised clinical record data of all patients seen by physician associates or foundation year two doctors-in-training in 2016; review of a subsample of 40 records for clinical adequacy; semi-structured interviews with staff and patients; observations of physician associates.SettingThree emergency departments in England.ParticipantsThe records of 8816 patients attended by 6 physician associates and 40 foundation year two doctors-in-training; of these n=3197 had the primary outcome recorded (n=1129 physician associates, n=2068 doctor); 14 clinicians and managers and 6 patients or relatives for interview; 5 physician associates for observation.Primary and secondary outcome measuresThe primary outcome was unplanned re-attendance at the same emergency department within 7 days. Secondary outcomes: consultation processes, clinical adequacy of care, and staff and patient experience.ResultsRe-attendances within 7 days (n=194 (6.1%)) showed no difference between physician associates and foundation year two doctors-in-training (OR 0.87, 95% CI 0.61 to 1.24, p=0.437). If seen by a physician associate, patients were more likely receive an X-ray investigation (OR 2.10, 95% CI 1.72 to 4.24), pConclusionsPhysician associates in emergency departments in England treated patients with a range of conditions safely, and at a similar level to foundation year two doctors-in-training, providing clinical operational efficiencies.

This study assessed self-reported heat strain symptoms in workers of a state wide electrical utility distributor to determine risk differences between age groups, geographical work regions and work units. Out of a total 3,250 workers, 918 (∼28%) outdoor staff completed an online survey, which assessed the frequency of self-reported heat strain symptoms in the work and post-work settings, factors contributing to symptoms and symptom management. Heat strain symptoms were grouped into chronic low-grade cases and isolated high-grade cases based on the severity and frequency of symptoms. The risk (likelihood) of an employee being classified as either a chronic low-grade or isolated high-grade case was calculated and compared to the mean risk of all categories to determine risk difference, expressed as -1.00 to 1.00. For chronic low-grade cases, the 41-50 years age group had significantly increased risk (+0.08, p 0.05) while the over 60 years age group had significantly decreased risk (-0.14, p 0.05). Two of the three regions (p 0.01) and three of the nine work units also demonstrated risk differences (p 0.01) for chronic low-grade cases. Work units were the sole grouping to demonstrate risk difference for isolated high-risk cases. Work units with greater exposure to heat and higher requirement for protective clothing, such as Underground (+0.19, p 0.05), Overhead - Predominantly Live Line (+0.18, p 0.01), and Overhead - Distribution and Transmission (+0.11, p 0.05) were at greater risk of reporting heat stress symptoms. This study demonstrates that the pattern of self-reported chronic low-grade heat strain cases differs to isolated high-grade cases within the electrical utility industry. Age, geographical location, and work unit independently alter the risk of chronic low-grade heat strain, while the risk of isolated high-grade heat strain was only related to work unit. These outcomes support implementation of a flexible and targeted approach to heat stress management in large and diverse organizations in which employees are routinely exposed to heat.

Local Healthwatch have been operating since 2013 as 'consumer champions' in health and social care in England. There is little evidence about how they operate and the daily practices through which they seek to represent citizen views and influence others. To explore (a) the current organizational arrangements, relationships and impact of local Healthwatch in England, and (b) to what extent do these vary across local Healthwatch organizations. An online survey of all 150 local Healthwatch in England between December 2018 and January 2019. The survey comprised 47 questions and used a combination of closed- and open-response questions. We received responses from 96 local Healthwatch (68% response rate). Most local Healthwatch reported that they are 'independent' organizations that only do Healthwatch-related work (58.3%) and are funded through a contract (79.2%). Budget cuts have affected four-fifths of local Healthwatch (79.3%) since 2013. Three-quarters (74%) of local Healthwatch currently receive funding external to that provided by their local authority for their Healthwatch functions. Most Healthwatch engage with only one CCG (56.3%), one mental health trust (82.3%) and one community health trust (62.5%), though 59.4% engage with more than one hospital trust. Healthwatch respondents overwhelmingly reported impacts that were local in nature. Geographical and historical factors, the quality and quantity of their relationships with stakeholders, and different funding arrangements all contribute to high variability in the structure and activities of local Healthwatch and to shaping the nature of their work and impact across England. [Abstract copyright: © 2020 The Authors Health Expectations published by John Wiley & Sons Ltd.]

Background: There is evidence that people with intellectual disabilities experience healthcare inequalities, including access to specialist palliative care, but to date, there has not been a systematic review of empirical evidence. Aim: To identify the palliative care needs of adults with intellectual disabilities and the barriers and facilitators they face in accessing palliative care. Design: Systematic review using a narrative synthesis approach (International prospective register of systematic reviews (PROSPERO) registration number: CRD42019138974). Data sources: Five databases were searched in June 2019 (MEDLINE, Embase, PsycINFO, the Cochrane library and CINAHL) along with hand searches and a search of the grey literature. All study designs were included. Results: A total of 52 studies were identified, all of which were conducted in high-income countries, the majority in the United Kingdom ( n = 28). From a total of 2970 participants across all studies, only 1% were people with intellectual disabilities and 1.3% were family members; the majority (97%) were health/social care professionals. Identified needs included physical needs, psychosocial and spiritual needs, and information and communication needs. Barriers and facilitators were associated with education (e.g. staff knowledge, training and experience), communication (e.g. staff skill in assessing and addressing needs of people with communication difficulties), collaboration (e.g. importance of sustained multidisciplinary approach) and health and social care delivery (e.g. staffing levels, funding and management support). Conclusion: This review highlights the specific problems in providing equitable palliative care for adults with intellectual disabilities, but there is a lack of research into strategies to improve practice. This should be prioritised using methods that include people with intellectual disabilities and families.

Short Tandem Repeats (STRs) are widely used in population and forensic genetic studies.The objective of this study was to document the level and extent of genetic variation of the FBI Combined DNA Index System (CODIS) STR loci (D3S1358, vWA, FGA, D8S1179, D21S11, D18S51, D5S818, D13S317, D7S820, D16S539, TH01, TPOX and CSF1PO) in 6 populations (British, Indian (Punjabis and Gujaratis), Pakistani, Bangladeshi and Sri Lankan) of the East Midlands (UK). There is a lack of genetic research on the migrant South Asian populations.DNA samples (N = 603) were analysed for 13 autosomal forensic STR loci along with the amelogenin locus following standard protocols. Data were analysed for genetic variation and a range of forensic indices.All loci were polymorphic in all populations with a variable degree of variation. Average observed heterozygosity was highest in Bangladeshi (0.803) and lowest in Punjabi (0.761). FGA locus had the highest power of discrimination (PD) in most populations.FGA locus was most polymorphic and discriminatory among migrant populations demonstrating it as the marker with the highest potential in forensic analyses. These results could be useful for population and forensic genomic studies.

Chiral sugar derivatives are potential cyclitol surrogates of the Ca2+-mobilizing intracellular messenger d-myo-inositol 1,4,5-trisphosphate [Ins(1,4,5)P3]. Six novel polyphosphorylated analogues derived from both d- and l-glucose were synthesized. Binding to Ins(1,4,5)P3 receptors [Ins(1,4,5)P3R] and the ability to release Ca2+ from intracellular stores via type 1 Ins(1,4,5)P3Rs were investigated. β-d-Glucopyranosyl 1,3,4-tris-phosphate, with similar phosphate regiochemistry and stereochemistry to Ins(1,4,5)P3, and α-d-glucopyranosyl 1,3,4-tris-phosphate are full agonists, being equipotent and 23-fold less potent than Ins(1,4,5)P3, respectively, in Ca2+-release assays and similar to Ins(1,4,5)P3 and 15-fold weaker in binding assays. They can be viewed as truncated analogues of adenophostin A and refine understanding of structure-activity relationships for this Ins(1,4,5)P3R agonist. l-Glucose-derived ligands, methyl α-l-glucopyranoside 2,3,6-trisphosphate and methyl α-l-glucopyranoside 2,4,6-trisphosphate, are also active, while their corresponding d-enantiomers, methyl α-d-glucopyranoside 2,3,6-trisphosphate and methyl α-d-glucopyranoside 2,4,6-trisphosphate, are inactive. Interestingly, both l-glucose-derived ligands are partial agonists: they are among the least efficacious agonists of Ins(1,4,5)P3R yet identified, providing new leads for antagonist development.

Objective To assess the effects of protocolized recombinant human erythropoietin (r-HuEPO) therapy and standardized high dose iron supplementation on hematologic and iron status measures in a cohort of extremely low gestational age newborns (ELGANs). Study design Charts of extremely low gestational age newborns admitted from 2006 to 2016 and who had received r-HuEPO per neonatal intensive care unit protocol were reviewed. The r-HuEPO was started at a dose of 900 IU/kg per week after 7 days of age and continued until 35 weeks postmenstrual age. Oral iron supplementation at 6-12 mg/kg per day was used to maintain a transferrin saturation of >20% during r-HuEPO treatment. Data on demographic features, hematologic and iron panel indices, red blood cell transfusions, and clinical outcomes were collected. Quartile groups were created based on serum ferritin levels at the conclusion of the r-HuEPO treatment and the quartiles were compared. Results The cohort included 116 infants with mean gestational age 25.8 ± 1.5 weeks and birth weight 793 ± 174.1 g. The r-HuEPO promoted erythropoiesis as indicated by increasing hemoglobin, hematocrit, and reticulocyte count. Serum ferritin decreased over time and was ≤75 ng/mL in 60.2% of infants at the conclusion of r-HuEPO therapy; 87% received packed red blood cell transfusions. Transfusion volume, total iron intake, total iron binding capacity, and transferrin concentration differed among infants in the different serum ferritin quartiles (P Conclusions In extremely low gestational age newborns, r-HuEPO therapy promoted erythropoiesis. Despite a biomarker-based standardized high-dose iron supplementation, the majority of infants had evidence of iron deficiency to a degree that is associated with reduced brain function.

Background Scoliosis in patients with neurofibromatosis type I (NF1) can manifest as dystrophic or nondystrophic curves. Dystrophic scoliosis is rapidly progressive, rendering treatment challenging. Radiographic characteristics have been reported to predict dystrophic scoliosis, but their reliability and predictive value have not been well described. The purpose of this study is to assess the interobserver reliability for eight radiographic characteristics of dystrophic scoliosis and to evaluate the sensitivity and specificity of these characteristics relative to the gold standard of a definitive clinical diagnosis. Methods Spine radiographs of 122 NF1 patients from multiple institutions were graded by five spine surgeons as dystrophic or nondystrophic, based on eight radiographic characteristics of dystrophic modulation: rib penciling, vertebral rotation, scalloping, wedging, spindling of transverse processes, short sharp angular curve, widened interpedicular distance, and atypical location. The curves were classified by each submitting institution as dystrophic or nondystrophic based on clinical outcome. Interobserver reliability analysis was performed using Fleiss kappa. Results For the 122 cases, the interrater agreement among the five readers for the diagnosis of dystrophic scoliosis was good at 0.61. The agreement for individual radiographic characteristic ranged from 0.62 for wedging to 0.14 (poor) for scalloping. Surgeons underestimated the number of dystrophic curves, rating from 45% to 67% of the curve patterns as dystrophic, compared to the gold standard, which revealed 68% of the curves to be dystrophic. On multivariate analysis, rib penciling, vertebral rotation, vertebral wedging, and atypical location were significantly associated with true dystrophic status (odds ratios of 2.4, 3.0, 2.4, and 3.0, respectively). Conclusion Overall dystrophic diagnosis can be assessed by radiographic characteristics. Better understanding of the predictive value of specific radiographic features may assist in early diagnosis of patients with dystrophic NF and assist surgeons in identifying dystrophic curve patterns and instituting prompt, appropriate treatment. Level of evidence Level III.

Background: Internationally, evidence on the support needs of family carers who look after a terminally ill adult in home settings is incomplete. Aim: To illustrate the relevance of ‘relevant background worries’ in family carers’ accounts of caring at home for a dying adult. Design: A qualitative cross-sectional observational study was conducted in England, United Kingdom, in 2011–2013 on the experiences of adult family carers ( n = 59) of older dying adults (aged 50+ years) with malignant and/or non-malignant conditions. Interviews occurred post-bereavement. This article reports on a subset of participants’ interview transcripts ( n = 30) where narrative analysis was undertaken. Setting/participants: Carers were interviewed in their home setting, having been purposively recruited via general practitioner practices in two study sites in England. The subset of participants ( n = 30) was purposively selected from the parent sample with reference to carers’ age, relationship to the patient, family circumstances and study sites. Results: Evidence is provided on the importance of what we conceptualise as carers’ ‘relevant background worries’; these varied in nature, significance and impact. Four case studies are presented where these worries constituted psychosocial factors that impacted on caregivers’ actions and emotional well-being. Two themes are discussed: (1) whether relevant background worries are important enough to be identified and responded to and (2) how such worries could be picked up and managed by professionals. Conclusion: It is argued that the quality of clinical practice could be improved if specialist palliative care teams in community contexts both identified and responded to significant support needs associated with family carers’ relevant background worries.

Background: In interactions between professional caregivers, patients and family members at the end of life, silence often becomes more prevalent. Silence is acknowledged as integral to interpersonal communication and compassionate care but is also noted as a complex and ambiguous phenomenon. This review seeks interdisciplinary experience to deepen understanding of qualities of silence as an element of care. Aim: To search for published papers which describe professional caregivers’ experience of silence as an element of care, in palliative and other clinical, spiritual and pastoral care settings and to synthesise their findings. Design: Meta-ethnography: employing a systematic search strategy and line-of-argument synthesis. Data sources: PsycINFO and seven other cross-disciplinary databases, supplemented by hand-search, review of reference lists and citation tracking. No date range was imposed. Inclusion criteria focused on reported experience of silence in professional caregiving. Selected papers ( n = 18) were appraised; none were rejected on grounds of quality. Results: International, interdisciplinary research and opinion endorses the value of silence in clinical care. As a multi-functional element of interpersonal relationships, silence operates in partnership with speech to support therapeutic communication. As a caregiving practice, silence is perceived as particularly relevant in spiritual and existential dimensions of care when words may fail. Conclusion: Experience of silence as an element of care was found in palliative and spiritual care, psychotherapy and counselling supporting existing recognition of the value of silence as a skill and practice. Because silence can present challenges for caregivers, greater understanding may offer benefits for clinical practice.

Highlights • Fe availability in three commercial bread baking process was compared. • The sourdough bread baking process fully degraded phytic acid, a main Fe chelator. • More Fe was released by simulated digestion from sourdough bread. • The highest Fe uptake was achieved with sourdough bread in a simulated mixed-meal. • The sourdough bread process could be more beneficial for iron nutrition., Myo-inositol hexakisphosphate (IP6), is the main iron chelator in cereals and bread. The aim of this study was to investigate the effect of three commercial baking processes (sourdough, conventional yeast and Chorleywood Bread Making Process (CBP)) on the IP6 content of wholemeal bread, its impact on iron uptake in Caco-2 cells and the predicted bioavailability of iron from these breads with added iron, simulating a mixed-meal. The sourdough process fully degraded IP6 whilst the CBP and conventional processes reduced it by 75% compared with wholemeal flour. The iron released in solution after a simulated digestion was 8-fold higher in sourdough bread than with others but no difference in cellular iron uptake was observed. Additionally, when iron was added to the different breads digestions only sourdough bread elicited a significant ferritin response in Caco-2 cells (4.8-fold compared to the other breads) suggesting that sourdough bread could contribute towards improved iron nutrition.

Background Determining the incidence, disease-associated serotypes and antimicrobial susceptibility of invasive pneumococcal disease (IPD) among children in Africa is essential in order to monitor the impact of these infections prior to widespread introduction of the pneumococcal conjugate vaccine (PCV). Methods To provide updated estimates of the incidence, serotype distribution, and antimicrobial susceptibility profile of Streptococcus pneumoniae causing disease in Africa, we performed a systematic review of articles published from 2000 to 2015 using Ovid Medline and Embase. We included prospective and surveillance studies that applied predefined diagnostic criteria. Meta-analysis for all pooled analyses was based on random-effects models. Results We included 38 studies consisting of 386,880 participants in 21 countries over a total of 350,613 person-years. The pooled incidence of IPD was 62.6 (95% CI 16.9, 226.5) per 100,000 person-years, including meningitis which had a pooled incidence of 24.7 (95% CI 11.9, 51.6) per 100,000 person-years. The pooled prevalence of penicillin susceptibility was 78.1% (95% CI 61.9, 89.2). Cumulatively, PCV10 and PCV13 included 66.9% (95% CI 55.9, 76.7) and 80.6% (95% CI 66.3, 90.5) of IPD serotypes, respectively. Conclusions Our study provides an integrated and robust summary of incidence data, serotype distribution and antimicrobial susceptibility for S. pneumoniae in children ≤5 years of age in Africa prior to widespread introduction of PCV on the continent. The heterogeneity of studies and wide range of incidence rates across the continent indicate that surveillance efforts should be intensified in all regions of Africa to improve the integrity of epidemiologic data, vaccine impact and cost benefit. Although the incidence of IPD in young children in Africa is substantial, currently available conjugate vaccines are estimated to cover the majority of invasive disease-causing pneumococcal serotypes. These data provide a reliable baseline from which to monitor the impact of the broad introduction of PCV.

Aims: Cardiovascular (CV) disease is a major cause of reduced life expectancy in type 1 diabetes (T1D). Intensive insulin therapy prevents CV complications but is constrained by hypoglycaemia and weight gain. Adjunct metformin reduces insulin dose requirement and stabilizes weight but there are no data on its cardiovascular effects. We have therefore initiated an international double-blind, randomized, placebo-controlled trial (REMOVAL: REducing with MetfOrmin Vascular Adverse Lesions in type 1 diabetes) to examine whether metformin reduces progression of atherosclerosis in adults with T1D. Individuals >= 40 years of age with T1D for >= 5 years are eligible if they have >= 3 of 10 specified CV risk factors. The enrolment target is 500 participants in 17 international centres.Materials and methods: After 12 weeks of single-blind placebo-controlled run-in, participants with >= 70% adherence are randomized to metformin or matching placebo for 3 years with insulin titrated towards HbA1c 7.0% (53 mmol/mol). The primary endpoint is progression of averaged mean far wall common carotid intima-media thickness (cIMT) measured by ultrasonography at baseline, 12, 24 and 36 months. This design provides 90% power to detect a mean difference of 0.0167 mm in cIMT progression between treatment arms (alpha = 0.05), assuming that up to 20% withdraw or discontinue treatment. Other endpoints include HbA1c, weight, LDL cholesterol, insulin requirement, progression of retinopathy, endothelial function and frequency of hypoglycaemia.Conclusion: REMOVAL is the largest clinical trial of adjunct metformin therapy in T1D to date and will provide clinically meaningful information on its potential to impact CV disease and other complications.

Background: Cancer-related fatigue and loss of physical functioning are distressing symptoms which negatively impact the quality of life of people with advanced cancer. Physical activity has been shown to have positive effects on these symptoms in early-stage cancer, but previous research demonstrated an incongruence between people with advanced cancer’s expressed interest and actual participation in a physical activity intervention. Aim: To gain an in-depth understanding of the experience of activity and quality of life in people with advanced cancer, using a classic grounded theory approach. Design: Through the post-positivist lens of subtle realism, and informed by classic grounded theory methods, a two-phase, cross-sectional, qualitative study was conducted. For 7 days duration, participants wore an activPAL™ activity monitor and completed a daily record sheet, which were then used as qualitative probes for face-to-face, semi-structured interviews. Setting/participants: A total of 15 people with advanced cancer, aged 18 years or older, and with a median survival of 100 days from time of study consent, were recruited from an outpatient department of a tertiary cancer centre in Alberta, Canada. Findings: Maintaining their responsibilities, no matter how small, was the prime motive for participants’ behaviour. For people with advanced cancer, the minimum level of responsibility was dynamic and unique. It was achieved through a multifaceted interaction between the perceived benefits, prevailing conditions and mechanisms. Conclusion: This grounded theory enables understanding of activity as a mechanism through which responsibility is managed and may inform future behavioural interventions in people with advanced cancer.

Background Compassion is integral to professional nursing practice worldwide and a fundamental value in healthcare. Following serious care failures at a healthcare provider in the United Kingdom, a government commissioned report (the Francis Report) made several recommendations for strengthening compassion in nursing care and consequently ‘intentional rounding’ was incorporated into nursing practice in the United Kingdom. Intentional rounding is a structured process implemented primarily in the United Kingdom, North America and Australia, whereby nurses conduct 1–2 hourly checks on every patient using a standardised protocol and documentation. Objectives To examine the role of intentional rounding in the delivery of compassionate nursing care in England from multiple perspectives. Methods This paper reports qualitative findings from one phase of a realist evaluation of intentional rounding which used a mixed-methods approach. Individual, semi-structured interviews were undertaken with 33 nursing staff, 17 senior nurse managers, 34 patients and 28 family carers from three geographically spread case study hospital sites in England. Interviews elicited detailed reflections on the contexts, mechanisms and outcomes of intentional rounding and how it impacted the interviewee and those around them. Results This study found little evidence that intentional rounding ensures the comfort, safety or dignity of patients or increases the delivery of compassionate care. The systematised approach of intentional rounding emphasises transactional care delivery in the utilisation of prescribed methods of recording or tick boxes rather than relational, individualised patient care. It has the potential to reduce the scope of nursing care to a minimum standard, leading to a focus on the fundamentals as well as the prevention of adverse events. Its documentation is primarily valued by nursing staff as a means of protecting themselves through written proof or ‘evidence’ of care delivered, rather than as a means of increasing compassionate care. Conclusions This large-scale, theoretically-driven study of intentional rounding – the first of its kind – demonstrates that intentional rounding prioritises data collection through tick boxes or a prescriptive and structured recording of care. Thus, intentional rounding neither improves the delivery of compassionate nursing care nor addresses the policy imperative it was intended to target. This study raises questions about the role, contribution and outcomes from intentional rounding and suggests a need for a wider, international debate within the nursing profession about its future use. If an intervention to increase compassionate nursing care is required, it may be better to start afresh, rather than attempting to adapt the system currently implemented.

Background Despite the high prevalence of fetal alcohol spectrum disorder (FASD), there are few interventions targeting its core neurocognitive and behavioral deficits. FASD is often conceptualized as static and permanent, but interventions that capitalize on brain plasticity and critical developmental windows are emerging. We present a long-term follow-up study evaluating the neurodevelopmental effects of choline supplementation in children with FASD 4 years after an initial efficacy trial. Methods The initial study was a randomized, double-blind, placebo-controlled trial of choline vs. placebo in 2–5-year-olds with FASD. Participants include 31 children (16 placebo; 15 choline) seen 4 years after trial completion. The mean age at follow-up was 8.6 years. Diagnoses were 12.9% fetal alcohol syndrome (FAS), 41.9% partial FAS, and 45.1% alcohol-related neurodevelopmental disorder. The follow-up included measures of intelligence, memory, executive functioning, and behavior. Results Children who received choline had higher non-verbal intelligence, higher visual-spatial skill, higher working memory ability, better verbal memory, and fewer behavioral symptoms of attention deficit hyperactivity disorder than the placebo group. No differences were seen for verbal intelligence, visual memory, or other executive functions. Conclusions These data support choline as a potential neurodevelopmental intervention for FASD and highlight the need for long-term follow-up to capture treatment effects on neurodevelopmental trajectories. Trial registration ClinicalTrials.Gov #NCT01149538; Registered: June 23, 2010; first enrollment July 2, 2010

ObjectivesOlder informal carers play an increasingly important role in supporting others with long-term health conditions. This study aimed to explore in depth the perspectives of older carers (70+ years) supporting others with a variety of conditions and disabilities focusing on their thoughts and experiences about when they are unable to continue caring.DesignQualitative with four focus groups.SettingGreater London, UK.Participants28 older carers (70+ years) recruited from the voluntary sector participated in this study. Most were women and many were spouses caring for partners with age-related conditions such as dementia, arthritis and visual impairment. Nearly a third were parents of adult children with severe physical or cognitive disabilities.FindingsThematic analysis identified two main aspects for carers when contemplating the future—when they are unable to care in the short term or long term if they die or can no longer manage. Themes included the following: the impact of age, health conditions and relationships on future planning; anxiety about future care; carers’ ambivalence and challenges in broaching the subject; interventions that might help older carers talk about and plan for the future of those they care for.ConclusionsServices need to be open to talking about this difficult topic. Our findings suggest that frank discussions about when older carers cannot care and having plans in place, whether these are financial or address other practical issues, makes it easier for all concerned. However, this issue is not easily broached and its timing and ways to access this support must be carefully and individually gauged. Future research with more diverse demographic groups is needed to improve understanding of these carers’ perspectives. Research is also needed to develop interventions to support older carers to talk about and plan for the future.

Introduction This study sought to determine pharmacy students' self-assessment of their level of competency in specified global health statements across various schools. It also evaluated attributes associated with competency and perception of importance, as well as explored students' perspectives on how best to incorporate global health content into pharmacy education. Methods Cross-sectional survey administered online to pharmacy students from three pharmacy schools in the United States. Results The self-assessed competency of pharmacy students in global health topic areas was low. Current or prior exposures outside of the PharmD curriculum to the global health content presented in the survey were significant indicators of self-assessed competency scores. Within individual participating schools, demographic characteristics such as gender, age category, speaking a non-English language, and progression through the PharmD curriculum were also significantly associated with competency scores reported. Most respondents (96%) agreed that relevant global health education should be incorporated into the pharmacy curriculum. Conclusions Pharmacy students generally perceive global health competencies to be of great importance in practice, but acknowledge their deficiencies in this area. The current burden of global health education at the schools surveyed relies on individual student experience rather than curricular support. Ensuring that future pharmacists understand their role in global health teams and are able to achieve the necessary level of competency to function in interdisciplinary initiatives will require more strategic incorporation of relevant content into the curriculum.

Background There has been an identified need for greater patient and family member involvement in healthcare. This is particularly relevant in an intensive care unit (ICU), as the family provides a key communicative and practical link between patient and clinician. Family members have been deemed a positive beneficial influence on ICU care and recovery processes, yet they themselves are often emotionally affected after discharge. There has been no standardised evidenced-based approach which explores research on family member involvement and the range and quality of contributions remain unclear. This project will undertake a systematic review to assess the evidence base for interventions designed to promote patient and family member involvement in adult intensive care settings and develop a comprehensive typology of interventions for use by clinicians, patients and carers. Methods The following databases will be searched without date restriction: MEDLINE, EMBASE and CINAHL, as well as the Cochrane Central Register of Controlled Trials, Joanna Briggs and Cochrane Libraries. Manual searches of recent back issues of leading ICU and patient experience journals will also be undertaken, as will the reference lists of included studies. Unpublished literature will be sought through grey literature databases, including GreyLit and OpenGrey. All evaluation studies that consider intervention activities to promote patient and family member involvement in adult ICUs will be included; all research designs will be eligible. We will seek to include studies that report on a mixture of relevant outcomes for patients and family members. Abstracts and papers will be independently screened by at least two members of the team to determine their inclusion. Included papers will be assessed for methodological rigour using a standard rating approach, which assesses ‘quality of study’ and ‘quality of information’. Quality assessment will be completed by at least two members of the team. Data on interventions, evaluation methods and outcomes will be collated using a predetermined extraction table. These are likely to be heterogeneous in nature, which will mean that the review will follow a narrative approach to synthesis. Discussion The review will provide valuable and rigorous insight into the range and quality of interventions available to promote patient and family member involvement in ICU. This is the first step towards addressing the absence of a synthesis of research for this context, and will, in addition, develop a typology of available interventions that will help service users and clinicians make informed decisions about the approaches to patient and family member involvement which they might want to adopt. Systematic review registration PROSPERO (CRD42018086325). Electronic supplementary material The online version of this article (10.1186/s13643-019-1102-9) contains supplementary material, which is available to authorized users.

FXR agonists are used to treat non-alcoholic fatty liver disease (NAFLD), in part because they reduce hepatic lipids. Here, we show that FXR activation with the FXR agonist GSK2324 controls hepatic lipids via reduced absorption and selective decreases in fatty acid synthesis. Using comprehensive lipidomic analyses, we show that FXR activation in mice or humans specifically reduces hepatic levels of mono- and polyunsaturated fatty acids (MUFA and PUFA). Decreases in MUFA are due to FXR-dependent repression of Scd1, Dgat2, and Lpin1 expression, which is independent of SHP and SREBP1c. FXR-dependent decreases in PUFAs are mediated by decreases in lipid absorption. Replenishing bile acids in the diet prevented decreased lipid absorption in GSK2324-treated mice, suggesting that FXR reduces absorption via decreased bile acids. We used tissue-specific FXR KO mice to show that hepatic FXR controls lipogenic genes, whereas intestinal FXR controls lipid absorption. Together, our studies establish two distinct pathways by which FXR regulates hepatic lipids.

Background: Caring for dying people can contribute to moral distress experienced by healthcare professionals. Moral distress can occur when this caring is restricted by organisational processes, resources or the provision of futile care. These factors apply to end of life care in nursing homes but research is lacking. Aim: To describe how nursing home staff experience moral distress when caring for residents during and at the end of life. Methods: An interpretive descriptive design, using the critical incident technique in semi-structured interviews to collect data from nursing home staff. Data were analysed using a thematic analysis approach. Setting: Four nursing homes in one large metropolitan area. Participants: A total of 16 staff: 2 nurse managers, 4 nurses and 10 care assistants. Findings: Participants described holding ‘good dying’ values which influenced their practice. The four practice-orientated themes of advocating, caring, communicating and relating with residents were found to influence interactions with residents, relatives, general practitioners, and colleagues. These led staff to be able to ‘do the right thing’ or to experience ‘powerlessness’, which could in turn lead to staff perceiving a ‘bad death’ for residents. Conclusion: When there are incongruent values concerning care between staff and others involved in the care of residents, staff feel powerless to ‘do the right thing’ and unable to influence care decisions in order to avoid a ‘bad death’. This powerlessness is the nature of their moral distress.

Our growing awareness of the microbial world's importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth's microbial diversity. Fil: Thompson, Luke R.. University of California at San Diego; Estados Unidos. University of Southern Mississippi; Estados Unidos. National Oceanic and Atmospheric Administration; Estados Unidos Fil: Sanders, Jon G.. University of California at San Diego; Estados Unidos Fil: McDonald, Daniel. University of California at San Diego; Estados Unidos Fil: Amir, Amnon. University of California at San Diego; Estados Unidos Fil: Ladau, Joshua. University of California San Francisco; Estados Unidos Fil: Locey, Kenneth J.. Indiana University; Estados Unidos Fil: Prill, Robert J.. IBM Almaden Research Center; Estados Unidos Fil: Tripathi, Anupriya. University of California at San Diego; Estados Unidos Fil: Gibbons, Sean M.. Massachusetts Institute of Technology; Estados Unidos Fil: Ackermann, Gail. University of California San Diego; Estados Unidos Fil: Navas Molina, Jose A.. University of California at San Diego; Estados Unidos Fil: Janssen, Stefan. University of California at San Diego; Estados Unidos Fil: Kopylova, Evguenia. University of California at San Diego; Estados Unidos Fil: Vázquez Baeza, Yoshiki. University of California at San Diego; Estados Unidos Fil: González, Antonio. University of California at San Diego; Estados Unidos Fil: Morton, James T.. University of California at San Diego; Estados Unidos Fil: Mirarab, Siavash. University of California at San Diego; Estados Unidos Fil: Xu, Zhenjiang Zech. University of California at San Diego; Estados Unidos Fil: Jiang, Lingjing. University of California at San Diego; Estados Unidos Fil: Haroon, Mohamed F.. Harvard University; Estados Unidos Fil: Kanbar, Jad. University of California at San Diego; Estados Unidos Fil: Zhu, Qiyun. University of California at San Diego; Estados Unidos Fil: Song, Se Jin. University of California at San Diego; Estados Unidos Fil: Kosciolek, Tomasz. University of California at San Diego; Estados Unidos Fil: Bokulich, Nicholas A.. Northern Arizona University; Estados Unidos Fil: Lefler, Joshua. University of California at San Diego; Estados Unidos Fil: Brislawn, Colin J.. Earth and Biological Sciences Directorate; Estados Unidos Fil: Humphrey, Gregory. University of California at San Diego; Estados Unidos Fil: Owens, Sarah M.. Argonne National Laboratory; Estados Unidos Fil: Hampton Marcell, Jarrad. Argonne National Laboratory; Estados Unidos. University of Illinois at Chicago; Estados Unidos Fil: Berg Lyons, Donna. University of Colorado; Estados Unidos Fil: McKenzie, Valerie. University of Colorado; Estados Unidos Fil: Fierer, Noah. University of Colorado; Estados Unidos Fil: Fuhrman, Jed A.. University of Colorado; Estados Unidos Fil: Clauset, Aaron. University of Colorado; Estados Unidos Fil: Stevens, Rick L.. Argonne National Laboratory; Estados Unidos. University of Chicago; Estados Unidos Fil: Shade, Ashley. Michigan State University; Estados Unidos Fil: Pollard, Katherine S.. The Gladstone Institutes; Estados Unidos. University of California San Francisco; Estados Unidos Fil: Goodwin, Kelly D.. National Oceanic and Atmospheric Administration; Estados Unidos Fil: Jansson, Janet K.. Earth and Biological Sciences Directorate; Estados Unidos Fil: Gilbert, Jack A.. Argonne National Laboratory; Estados Unidos. University of Chicago; Estados Unidos Fil: Knight, Rob. University of California San Diego; Estados Unidos Fil: Dionisi, Hebe Monica. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; Argentina Fil: Lozada, Mariana. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Centro Nacional Patagónico. Centro para el Estudio de Sistemas Marinos; Argentina Fil: Mac Cormack, Walter Patricio. Universidad de Buenos Aires; Argentina. Ministerio de Relaciones Exteriores, Comercio Interno y Culto. Dirección Nacional del Antártico. Instituto Antártico Argentino; Argentina

Objective: To examine whether non-heat acclimatized (NHA) emergency responders endure greater physiological and perceptual strain than heat acclimatized (HA) counterparts in tropical field settings. Methods: Eight HA and eight NHA men urban search and rescue personnel had physiological and perceptual responses compared during the initial 4 hours shift of a simulated disaster in tropical conditions (ambient temperature 34.0 °C, 48% relative humidity, wet bulb globe temperature [WBGT] 31.4 °C). Results: From the 90th minute through to end of shift, HA (38.5 °C) sustained a significantly higher gastrointestinal temperature than NHA (38.1 °C) (mean difference 0.4 ± 0.2 °C, 95% confidence interval [CI] 0.2 to 0.7 °C, P = 0.005) despite comparable heart rate (P = 0.30), respiratory rate (P = 0.88), and axilla skin temperature (P = 0.47). Overall, perception of body temperature was similar between cohorts (P = 0.87). Conclusions: The apparent tolerance of greater physiological strain by HA responders occurred in the absence of perceptual differences.

Background: Older people aged 80 and over are increasingly providing end of life care to spouses at home, and often do so for long periods of time, whilst also trying to manage their own illnesses and disabilities. Little of the research on older spousal carers has focussed on the oldest carers, hence the needs of this particular population are not fully known. Objective: To explore the experiences of the ‘oldest carers’ in caring for a dying spouse at home. Methods: Secondary analysis was undertaken on a subset of data from a larger qualitative interview study; this dataset comprised 17 interviews from participants aged 80 or over. Framework analysis methods were used, with items derived from the thematic analysis of the main study. Results: The oldest carers in this subset demonstrated high levels of resilience, and the ability to adapt to their caring role. Caring until death was accepted as an integral part of the commitment made to their partner as part of the ‘wedding contract’. Carers felt they benefitted from the support provided by family, friends and care services; however their own care needs were not always recognised by health and social care services. Conclusions: These findings underscore the complexity of the oldest carers’ experiences and challenges in times of illness and end of life. Healthcare professionals should be alerted to the myriad ways caregiving is enacted in serious illness and seek opportunities for developing supportive interventions specifically for older carers.

ObjectivesTo investigate the deployment of physician associates (PAs); the factors supporting and inhibiting their employment and their contribution and impact on patients’ experience and outcomes and the organisation of services.DesignMixed methods within a case study design, using interviews, observations, work diaries and documentary analysis.SettingSix acute care hospitals in three regions of England in 2016–2017.Participants43 PAs, 77 other health professionals, 28 managers, 28 patients and relatives.ResultsA key influencing factor supporting the employment of PAs in all settings was a shortage of doctors. PAs were found to be acceptable, appropriate and safe members of the medical/surgical teams by the majority of doctors, managers and nurses. They were mainly deployed to undertake inpatient ward work in the medical/surgical team during core weekday hours. They were reported to positively contribute to: continuity within their medical/surgical team, patient experience and flow, inducting new junior doctors, supporting the medical/surgical teams’ workload, which released doctors for more complex patients and their training. The lack of regulation and attendant lack of authority to prescribe was seen as a problem in many but not all specialties. The contribution of PAs to productivity and patient outcomes was not quantifiable separately from other members of the team and wider service organisation. Patients and relatives described PAs positively but most did not understand who and what a PA was, often mistaking them for doctors.ConclusionsThis study offers new insights concerning the deployment and contribution of PAs in medical and surgical specialties in English hospitals. PAs provided a flexible addition to the secondary care workforce without drawing from existing professions. Their utility in the hospital setting is unlikely to be completely realised without the appropriate level of regulation and authority to prescribe medicines and order ionising radiation within their scope of practice.

Workers that combine physical exertion with exposure to hot conditions are susceptible to heat-related illnesses, including heat stroke. Despite recognition of cold water immersion as the heat stroke treatment of choice in the peer-reviewed literature, it was not included within recommended treatments of leading Australian healthcare training organizations and was omitted from Safe Work Australia's recently updated 'Managing the risks of working in heat' guidance material. On this basis, the guidance material appears an opportunity lost to assist Australian industry transition their heat stroke management to reflect the evidence. It is recommended that Australian providers of healthcare training, and those reliant on such information, review the efficacy of their heat stroke treatments.

Exposure to windblown particulate matter (PM) arising from legacy uranium (U) mine sites in the Navajo Nation may pose a human health hazard due to their potentially high metal content, including U and vanadium (V). To assess the toxic impact of PM derived from Claim 28 (a priority U mine) compared with background PM, and consider the putative role of metal species U and V. Two representative sediment samples from Navajo Nation sites (Background PM and Claim 28 PM) were obtained, characterized in terms of chemistry and morphology, and fractioned to the respirable (≤ 10 μm) fraction. Mice were dosed with either PM sample, uranyl acetate, or vanadyl sulfate via aspiration (100 µg), with assessments of pulmonary and vascular toxicity 24 h later. Particulate matter samples were also examined for in vitro effects on cytotoxicity, oxidative stress, phagocytosis, and inflammasome induction. Claim 28 PM(10) was highly enriched with U and V and exhibited a unique nanoparticle ultrastructure compared with background PM(10). Claim 28 PM(10) exhibited enhanced pulmonary and vascular toxicity relative to background PM(10). Both U and V exhibited complementary pulmonary inflammatory potential, with U driving a classical inflammatory cytokine profile (elevated interleukin [IL]-1β, tumor necrosis factor-α, and keratinocyte chemoattractant/human growth-regulated oncogene) while V preferentially induced a different cytokine pattern (elevated IL-5, IL-6, and IL-10). Claim 28 PM(10) was more potent than background PM(10) in terms of in vitro cytotoxicity, impairment of phagocytosis, and oxidative stress responses. Resuspended PM(10) derived from U mine waste exhibit greater cardiopulmonary toxicity than background dusts. Rigorous exposure assessment is needed to gauge the regional health risks imparted by these unremediated sites.

Background Intentional rounding (IR) is a structuredprocess whereby nurses conduct one to two hourly checkswith every patient using a standardised protocol.Objective A realist synthesis of the evidence on IR wasundertaken to develop IR programme theories of whatworks, for whom, in what circumstances and why.Methods A three-stage literature search and a stakeholderconsultation event was completed. A variety of sourceswere searched, including AMED, CINAHL, MEDLINE,PsycINFO, HMIC, Google and Google Scholar, for publishedand unpublished literature. In line with realist synthesismethodology, each study’s ‘fitness for purpose’ wasassessed by considering its relevance and rigour.Results A total of 44 papers met the inclusion criteria. Tomake the programme theories underpinning IR explicit, weidentified eight a priori propositions: (1) when implementedin a comprehensive and consistent way, IR improveshealthcare quality and satisfaction, and reduces potentialharms; (2) embedding IR into daily routine practice givesnurses ‘allocated time to care’; (3) documenting IR checksincreases accountability and raises fundamental standardsof care; (4) when workload and staffing levels permit, morefrequent nurse–patient contact improves relationships andincreases awareness of patient comfort and safety needs;(5) increasing time when nurses are in the direct vicinityof patients promotes vigilance, provides reassurance andreduces potential harms; (6) more frequent nurse–patientcontact enables nurses to anticipate patient needs andtake pre-emptive action; (7) IR documentation facilitatesteamwork and communication; and (8) IR empowerspatients to ask for what they need to maintain theircomfort and well-being. Given the limited evidence base,further research is needed to test and further refine thesepropositions.Conclusions Despite widespread use of IR, thispaper highlights the paradox that there is ambiguitysurrounding its purpose and limited evidence of how itworks in practice.

Objectives Depressive symptoms are common in patients with cancer and tend to increase as death approaches. The study aims were to examine the prevalence of depressive symptoms in patients with cancer in their final 24 h, and their association with other symptoms, sociodemographic and care characteristics. Methods A stratified sample of deaths was drawn by Statistics Netherlands. Questionnaires on patient and care characteristics were sent to the physicians (N=6860) who signed the death certificates (response rate 77.8%). Adult patients with cancer with non-sudden death were included (n=1363). Symptoms during the final 24 h of life were assessed on a 1–5 scale and categorised as 1=no, 2–3=mild/moderate and 4–5=severe/very severe. Results Depressive symptoms were registered in 37.6% of the patients. Patients aged 80 years or more had a reduced risk of having mild/moderate depressive symptoms compared with those aged 17–65 years (OR 0.70; 95% CI 0.50 to 0.99). Elderly care physicians were more likely to assess patients with severe/very severe depressive symptoms than patients with no depressive symptoms (OR 4.18; 95% CI 1.48 to 11.76). Involvement of pain specialists/palliative care consultants and psychiatrists/psychologists was associated with more ratings of severe/very severe depressive symptoms. Fatigue and confusion were significantly associated with mild/moderate depressive symptoms and anxiety with severe/very severe symptoms. Conclusions More than one-third of the patients were categorised with depressive symptoms during the last 24 h of life. We recommend greater awareness of depression earlier in the disease trajectory to improve care.

There are a limited number of studies on heat stress dynamics during exercise using the photoplethysmogram (PPG). We investigate the PPG signal and its derivatives for heat stress assessment using Welch (non-parametric) and autoregressive (parametric) spectral estimation methods. The preliminary results of this study indicate that applying the first and second derivatives to PPG waveforms is useful for determining heat stress level using 20-s recordings. Interestingly, Welch's and Yule-Walker's methods in agreement that the second derivative is an improved detector for heat stress. In fact, both spectral estimation methods showed a clear separation in the frequency domain between measurements before and after simulated heat-stress induction when the second derivative is applied. Moreover, the results demonstrate superior performance of the Welch's method over the Yule-Walker's method in separating before and after the three simulated heat-stress inductions.

Question: What is the body temperature response of healthy pregnant women exercising at moderate intensity in an aqua-aerobics class where the water temperature is in the range of 28 to 33 degrees Celsius, as typically found in community swimming pools? Design: An observational study. Participants: One hundred and nine women in the second and third trimester of pregnancy who were enrolled in a standardised aqua-aerobics class. Outcome measures: Tympanic temperature was measured at rest pre-immersion (T1), after 35 minutes of moderate-intensity aqua-aerobic exercise (T2), after a further 10 minutes of light exercise while still in the water (T3) and finally on departure from the facility (T4). The range of water temperatures in seven indoor community pools was 28.8 to 33.4 degrees Celsius. Results: Body temperature increased by a mean of 0.16 degrees Celsius (SD 0.35, p