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Jessica E Morgan,1,2 Bob Phillips,1,2 Gabrielle M Haeusler,3– 6 Julia C Chisholm7 1Centre for Reviews and Dissemination, University of York, Heslington, YO10 5DD, UK; 2Department of Paediatric Oncology, Leeds Teaching Hospitals NHS Trust, Leeds, LS1 3EX, UK; 3NHMRC National Centre for Infections in Cancer, Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, 3010, Australia; 4Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Victoria, 3010, Australia; 5Infection Diseases Unit, Department of General Medicine, Royal Children’s Hospital, Parkville, Victoria, 3168, Australia; 6Murdoch Children’s Research Institute, Parkville, Victoria, 3052, Australia; 7Royal Marsden Hospital and Institute of Cancer Research, Sutton, SM2 5PT, UKCorrespondence: Jessica E MorganCentre for Reviews and Dissemination, University of York, Heslington, YO10 5DD, UKTel +44 01904 321082Email jess.morgan@york.ac.ukAbstract: Febrile neutropenia (FN) is a frequent complication of cancer treatment in children. Owing to the potential for overwhelming bacterial sepsis, the recognition and management of FN requires rapid implementation of evidenced-based management protocols. Treatment paradigms have progressed from hospitalisation with broad spectrum antibiotics for all patients, through to risk adapted approaches to management. Such risk adapted approaches aim to provide safe care through incorporating antimicrobial stewardship (AMS) principles such as implementation of comprehensive clinical pathways incorporating de-escalation strategies with the imperative to reduce hospital stay and antibiotic exposure where possible in order to improve patient experience, reduce costs and diminish the risk of nosocomial infection. This review summarises the principles of risk stratification in FN, the current key considerations for optimising empiric antimicrobial selection including knowledge of antimicrobial resistance patterns and emerging technologies for rapid diagnosis of specific infections and summarises existing evidence on time to treatment, investigations required and duration of treatment. To aid treating physicians we suggest the key features based on current evidence that should be part of any FN management guideline and highlight areas for future research. The focus is on treatment of bacterial infections although fungal and viral infections are also important in this patient group.Keywords: paediatric, febrile neutropenia, antimicrobials

Simon Read,1 Heather Waterman,1 James E Morgan,2 Robert A Harper,3,4 Anne Fiona Spencer,3 Penelope Stanford5 1School of Healthcare Sciences, Cardiff University, Cardiff, UK; 2School of Optometry and Vision Sciences, Cardiff University, Cardiff, UK; 3Manchester Royal Eye Hospital, Manchester University NHS Foundation Trust, Manchester, UK; 4Division of Pharmacy and Optometry, School of Health Sciences, University of Manchester, Manchester Academic Health Science Centre, Manchester, UK; 5Division of Nursing, Midwifery and Social Work, School of Health Sciences, University of Manchester, Manchester, UK Purpose: “She wouldn’t remember. Even when I go through, and she’s decided to go to bed, I’ll say I’ll come and do her drops. If I didn’t say that, they wouldn’t be done.” Dementia is widely considered as a key factor in whether patients take their medication as prescribed. However, few studies have examined the effect of dementia on medication management strategies for glaucoma including how patient and carer needs impact adherence and long-term prognosis. We report findings from a qualitative grounded theory study incorporating the views of patients, carers, and healthcare professionals. Methods: Eighty-three semistructured interviews were conducted with 35 patients, 22 lay carers, and nine healthcare professionals across sites in Wales and Scotland. These explored understanding of eye drop regimens, barriers, and facilitators to drop administration, as well as attitudes toward glaucoma, dementia, and other comorbidities. Results: Using Pound’s synthesis of adherence behavior, we identified categories of active and passive acceptance of medicines, alongside modification or rejection of eye drop regimens. In relation to dementia, participants highlighted transitions between such categories, with a shift from active to passive acceptance commonly reported. This loss of self-medicating capability was referred to as the precipice of care, where entwinement of multiple conditions (eg, heart disease, glaucoma, and dementia) and sociocultural influences (eg, living alone) contributed to accelerated health declines. That said, numerous factors mitigated this, with a key role being the lay carer. Spouses and family members often acted as the monitor of eye drops for patients, seeking intervention when any behavioral changes influenced their administration. Conclusion: Though dementia was associated with progression toward the precipice of care, factors such as communication with healthcare professionals appeared to affect patient adherence. Recommendations for healthcare practice include better recording of dementia diagnoses and integrating eye drops into preexisting routines. Keywords: memory loss, compliance, eye drops, qualitative research, grounded theory

Cet article interroge la place accordée aux dimensions sensibles (au sens d’attachement, de ce qui « fait sens », ce à quoi l’on tient) ainsi que leur rôle au sein des dispositifs et expérimentations qui visent la transition écologique dans et par les systèmes alimentaires, à travers six cas situés dans différentes régions de France. Plus précisément, il sonde ces attachements afin de voir ce qu’ils peuvent apporter à la participation de publics à première vue éloignés des enjeux de transition écologique, et en explore la portée en matière de politisation. Il montre que la prise en compte de ces attachements offre un contrepoint aux approches technicistes et normatives de la transition écologique, tout en permettant de traiter les enjeux de la démocratie et de la justice alimentaires. Il identifie trois voies de politisation, diversement combinées dans les six expérimentations étudiées : la capacitation/l’augmentation du pouvoir d’agir (empowerment), la valorisation des pratiques et/ou des savoirs, et la formation de collectifs. Il suggère, enfin, qu’en dépit des limites que nous identifions, la prise en compte de ces dimensions sensibles favorise, sous certaines conditions, l’inclusion et la participation de ces publics. Cette prise en compte offre en outre une voie privilégiée pour l’articulation des enjeux de justice et de démocratie alimentaires aux enjeux environnementaux, ce qui mériterait d’être davantage considéré ou du moins discuté dans le cadre des politiques de transition écologique.

Animal health laboratories are an increasingly important part of safeguarding animal and public health due to their role in surveillance and diagnostics of animal diseases, food safety, and in the development and production of medicinal products, vaccines, and diagnostic tools. Despite their importance, the global distribution of veterinary laboratory expertise is uneven, with greater concentration of reference laboratories in wealthier countries. To address this issue, the World Organization for Animal Health (WOAH, founded as OIE) created a Laboratory Twinning Programme in 2006. The paper will briefly review this Programme in the context of an increasingly populated global health security field, based on a literature review and on a combination of public and internal WOAH data and describe the implementation of the Programme in the past 16 years, noting the drivers for project implementation, its links with the global livestock biomass distribution and with the current distribution of veterinary laboratory expertise. There has been broad uptake and diversity in the focus of the twinning projects implemented in WOAH Member Countries. The Laboratory Twinning Programme would benefit from an evaluation that looks at its outcomes and quantifiable impact in beneficiary countries. A case is made for the development of a monitoring and evaluation system tailored to the Programme's specificities.

BackgroundWith current medical advancements, more adolescents with neurodevelopmental disorders are transitioning from child- to adult-centred health care services. Therefore, there is an increasing demand for transitional services to help navigate this transition. Health care transitions can be further complicated by mental health challenges prevalent among individuals with cerebral palsy (CP), spina bifida (SB), and childhood onset acquired brain injury (ABI). Offering evidence-based psychological interventions for these populations may improve overall outcomes during transition period(s) and beyond. The objective of this scoping review is to identify key characteristics of psychological interventions being used to treat the mental health challenges of adolescents and adults with CP, SB, and childhood onset ABI.MethodsMethodological frameworks by Arksey and O'Malley, and Levac and colleagues were used to explore studies published between 2009 and 2019. Included studies were required to be written in English and report on a psychological intervention(s) administered to individuals at least 12 years of age with a diagnosis of CP, SB, or childhood onset ABI. All study designs were included.ResultsA total of 11 studies were identified. Of these, eight reported psychological interventions for childhood onset ABI, while three reported on CP. No studies reporting on SB were identified. Commonly used interventions included acceptance and commitment therapy (ACT), psychotherapy, and cognitive behavioral therapy (CBT).ConclusionsThere are a limited number of studies investigating psychological interventions for individuals with childhood onset ABI and CP, and none for individuals with SB. Further research into effective psychological interventions for these populations will improve mental health outcomes and transitional services.

Smart city environments, when applied to healthcare, improve the quality of people's lives, enabling, for instance, disease prediction and treatment monitoring. In medical settings, case prioritization is of great importance, with beneficial outcomes both in terms of patient health and physicians' daily work. Recommender systems are an alternative to automatically integrate the data generated in such environments with predictive models and recommend actions, content, or services. The data produced by smart devices are accurate and reliable for predictive and decision-making contexts. This study main purpose is to assist patients and doctors in the early detection of disease or prediction of postoperative worsening through constant monitoring. To achieve this objective, this study proposes an architecture for recommender systems applied to healthcare, which can prioritize emergency cases. The architecture brings an ensemble approach for prediction, which adopts multiple Machine Learning algorithms. The methodology used to carry out the study followed three steps. First, a systematic literature mapping, second, the construction and development of the architecture, and third, the evaluation through two case studies. The results demonstrated the feasibility of the proposal. The predictions are promising and adherent to the application context for accurate datasets with a low amount of noises or missing values.

Knowledge of a population’s abundance is of primary importance for conservation management. However, robust estimates of abundance are often difficult to obtain, especially for cetaceans which spend most of their lives submerged. Cetacean abundance is commonly estimated using aerial or vessel-based line transect surveys and distance sampling methods. During 2012–2014, the first line transect surveys to estimate cetacean abundance were conducted in Namibian waters. Surveys took place in the Namibian Islands’ Marine Protected Area (NIMPA), a large MPA located along the southern Namibian coastline. A combined visual and acoustic double-platform survey configuration was used to investigate the factors affecting detectability of the endemic Heaviside’s dolphin (Cephalorhynchus heavisidii) and dusky dolphin (Lagenorhynchus obscurus obscurus). The present analysis estimates the probability of detection on the transect line (g(0)) for these two species and generates density and abundance estimates which incorporate a correction for both animals missed on the transect line and attractive responsive movement. The average annual baseline density and abundance estimates for Heaviside’s dolphins in the NIMPA region during 2012–2014 were 0.08 individuals/km2 (CV = 28.6%, 95% CI = 0.04–0.15 individuals/km2) and 1594 individuals (CV = 28.6%, 95% CI = 776–3275), respectively. The average annual baseline density and abundance estimates for dusky dolphins in the NIMPA region during 2012–2014 were 0.16 individuals/km2 (CV = 26.2%, 95% CI = 0.10–0.28 individuals/km2) and 3493 individuals (CV = 26.2%, 95% CI: 2015–6052), respectively. A discussion on the distribution of Heaviside’s and dusky dolphins is provided for this region where such information is urgently needed. Based on existing knowledge of the species and area, these estimates are regarded as reasonable. They indicate moderate sized populations of animals within the NIMPA and provide an important first baseline on which future estimates can build.

Laser-induced breakdown spectroscopy (LIBS) is a form of optical emission spectroscopy that can be used for the rapid analysis of geological materials in the field under ambient environmental conditions. We describe here the innovative use of handheld LIBS for the in situ analysis of rock varnish. This thinly laminated and compositionally complex veneer forms slowly over time on rock surfaces in dryland regions and is particularly abundant across the Mojave Desert climatic region of east-central California (USA). Following the depth profiling examination of a varnished clast from colluvial gravel in Death Valley in the laboratory, our in situ analysis of rock varnish and visually similar coatings on rock surfaces was undertaken in the Owens and Deep Spring valleys in two contexts, element detection/identification and microchemical mapping. Emission peaks were recognized in the LIBS spectra for the nine elements most abundant in rock varnish—Mn, Fe, Si, Al, Na, Mg, K, Ca and Ba, as well as for H, Li, C, O, Ti, V, Sr and Rb. Focused follow-up laboratory and field studies will help understand rock varnish formation and its utility for weathering and chronological studies.

For over two decades, the World Organisation for Animal Health (OIE) has engaged in combatting antimicrobial resistance (AMR) through a One Health approach. Monitoring of antimicrobial use (AMU) is an important source of information that together with surveillance of AMR can be used for the assessment and management of risks related to AMR. In the framework of the Global Action Plan on AMR, the OIE has built a global database on antimicrobial agents intended for use in animals, supported by the Tripartite (World Health Organization (WHO), Food and Agriculture Organization of the United Nations (FAO) and OIE) collaboration. The OIE launched its first annual data collection in 2015 and published the Report in 2016. The second Report, published in 2017, introduced a new methodology to report quantitative data in the context of relevant animal populations, and included for the first time an annual analysis of antimicrobial quantities adjusted for animal biomass on a global and regional level. A continuing annual increase of countries participating in the data collection demonstrates the countries engagement for the global development of monitoring and surveillance systems in line with OIE international standards. Where countries are not yet able to contribute their quantitative data, their reports also highlight the barriers that impede them in data collection, analysis and/or reporting. The OIE Reports show annual global and regional estimates of antimicrobial agents intended for use in animals adjusted for animal biomass, as represented by the quantitative data reported by countries to the OIE. The OIE advises caution in interpretation of estimates made in the first few years of reporting recognizing some important limitations faced by countries as they develop their monitoring systems. The OIE remains strongly committed to supporting its Members in developing robust and transparent measurement and reporting mechanisms for AMU.

Background: Transfusion of blood at the limits of approved storage time is associated with lower red blood cell (RBC) post-transfusion recovery and hemolysis, which increases plasma cell-free hemoglobin and iron, proposed to induce endothelial dysfunction and impair host defense. There is noted variability among donors in the intrinsic rate of storage changes and RBC post-transfusion recovery, yet genetic determinants that modulate this process are unclear. Methods: We explore RBC storage stability and post-transfusion recovery in murine models of allogeneic and xenogeneic transfusion using blood from humanized transgenic sickle cell hemizygous mice (Hbatm1PazHbbtm1TowTg(HBA-HBBs)41Paz/J) and human donors with a common genetic mutation sickle cell trait (HbAS). Findings: Human and transgenic HbAS RBCs demonstrate accelerated storage time-dependent hemolysis and reduced post-transfusion recovery in mice. The rapid post-transfusion clearance of stored HbAS RBC is unrelated to macrophage-mediated uptake or intravascular hemolysis, but by enhanced sequestration in the spleen, kidney and liver. HbAS RBCs are intrinsically different from HbAA RBCs, with reduced membrane deformability as cells age in cold storage, leading to accelerated clearance of transfused HbAS RBCs by entrapment in organ microcirculation. Interpretation: The common genetic variant HbAS enhances RBC storage dysfunction and raises provocative questions about the use of HbAS RBCs at the limits of approved storage.

Traditionally, museums have been visual - ‘Do Not Touch’ - spaces. However, interactive and multisensory media are increasingly being used to help pursue wider democratic goals of appealing to new and more diverse audiences. This essay examines how one museum, Kelvingrove Art Gallery and Museum in Glasgow (Scotland), has sought to reconfigure its sensory regimes of display. It discusses the incorporation of multiple sensory logics and queries whether one potential result of such mixings is a kind of sensory disorientation.

Abstract Background Excess alcohol consumption has serious adverse effects on health and violence-related harm. In the UK around 37% of men and 29% of women drink to excess and 20% and 13% report binge drinking. The potential impact on population health from a reduction in consumption is considerable. One proposed method to reduce consumption is to reduce availability through controls on alcohol outlet density. In this study we investigate the impact of a change in the density of alcohol outlets on alcohol consumption and alcohol-related harms to health in the community. Methods/Design A natural experiment of the effect of change in outlet density between 2005–09, in Wales, UK; population 2.4 million aged 16 years and over. Data on outlets are held by the 22 local authorities in Wales under The Licensing Act 2003. The study outcomes are change in (1) alcohol consumption using data from annual Welsh Health Surveys, (2) alcohol-related hospital admissions using the Patient Episode Database for Wales, (3) Accident & Emergency department attendances between midnight–6am, and (4) alcohol-related violent crime against the person, using Police data. The data will be anonymously record-linked within the Secure Anonymised Information Linkage Databank at individual and 2001 Census Lower Super Output Area levels. New methods of network analysis will be used to estimate outlet density. Longitudinal statistical analysis will use (1) multilevel ordinal models of consumption and logistic models of admissions and Accident & Emergency attendance as a function of change in individual outlet exposure, adjusting for confounding variables, and (2) spatial models of the change in counts/rates of each outcome measure and outlet density. We will assess the impact on health inequalities and will correct for population migration. Discussion This inter-disciplinary study requires expertise in epidemiology and public health, health informatics, medical statistics, geographical information science, and research into alcohol-related violence. Information governance requirements for the use of record-linked data have been approved together with formal data access agreements for the use of the Welsh Health Survey and Police data. The dissemination strategy will include policy makers in national and local government. Public engagement will be through the Clinical Research Collaboration-Cymru "Involving People" network, which will provide input into the implementation of the research.

Abstract Background Rhipicephalus (Boophilus) microplus (Rmi) a major cattle ectoparasite and tick borne disease vector, impacts on animal welfare and industry productivity. In arthropod research there is an absence of a complete Chelicerate genome, which includes ticks, mites, spiders, scorpions and crustaceans. Model arthropod genomes such as Drosophila and Anopheles are too taxonomically distant for a reference in tick genomic sequence analysis. This study focuses on the de-novo assembly of two R. microplus BAC sequences from the understudied R microplus genome. Based on available R. microplus sequenced resources and comparative analysis, tick genomic structure and functional predictions identify complex gene structures and genomic targets expressed during tick-cattle interaction. Results In our BAC analyses we have assembled, using the correct positioning of BAC end sequences and transcript sequences, two challenging genomic regions. Cot DNA fractions compared to the BAC sequences confirmed a highly repetitive BAC sequence BM-012-E08 and a low repetitive BAC sequence BM-005-G14 which was gene rich and contained short interspersed elements (SINEs). Based directly on the BAC and Cot data comparisons, the genome wide frequency of the SINE Ruka element was estimated. Using a conservative approach to the assembly of the highly repetitive BM-012-E08, the sequence was de-convoluted into three repeat units, each unit containing an 18S, 5.8S and 28S ribosomal RNA (rRNA) encoding gene sequence (rDNA), related internal transcribed spacer and complex intergenic region. In the low repetitive BM-005-G14, a novel gene complex was found between to 2 genes on the same strand. Nested in the second intron of a large 9 Kb papilin gene was a helicase gene. This helicase overlapped in two exonic regions with the papilin. Both these genes were shown expressed in different tick life stage important in ectoparasite interaction with the host. Tick specific sequence differences were also determined for the papilin gene and the protein binding sites of the 18S subunit in a comparison to Bos taurus. Conclusion In the absence of a sequenced reference genome we have assembled two complex BAC sequences, characterised novel gene structure that was confirmed by gene expression and sequencing analyses. This is the first report to provide evidence for 2 eukaryotic genes with exon regions that overlap on the same strand, the first to describe Rhipicephalinae papilin, and the first to report the complete ribosomal DNA repeated unit sequence structure for ticks. The Cot data estimation of genome wide sequence frequency means this research will underpin future efforts for genome sequencing and assembly of the R. microplus genome.