Deficiency of the zinc finger protein ZFP106 causes motor and sensory neurodegeneration

Acknowledgements We are indebted to Jim Humphries, JennyCorrigan, LizDarley, Elizabeth Joynson, Natalie Walters, Sara Wells and the whole necropsy, histology, genotyping and MLC ward 6 teams at MRC Harwell for excellent technical assistance. We thank the staff of the WTSI Illumina Bespoke Team for the RNA-seq data, the Sanger Mouse Genetics Project for the initial mouse characterization and Dr David Adams for critical reading of the manuscript. We also thank KOMP for the mouse embryonic stem cells carrying the knockout first promoter-less allele (tm1a(KOMP)Wtsi) within Zfp016. Conflict of Interest statement. None declared. Funding This work was funded by the UK Medical Research Council (MRC) to A.A.-A. and a Motor Neurone Disease Association (MNDA) project grant to A.A.-A. and EMCF. D.L.H.B. is a Wellcome Trust Senior Clinical Scientist Fellow and P.F. is a MRC/MNDA Lady Edith Wolfson Clinician Scientist Fellow. Funding to pay the Open Access publication charges for this article was provided by the MRC grant number: MC_UP_A390_1106.Peer reviewedPublisher PD

Ames Life Science Data Archive: Translational Rodent Research at Ames

The Life Science Data Archive (LSDA) office at Ames is responsible for collecting, curating, distributing and maintaining information pertaining to animal and plant experiments conducted in low earth orbit aboard various space vehicles from 1965 to present. The LSDA will soon be archiving data and tissues samples collected on the next generation of commercial vehicles; e.g., SpaceX & Cygnus Commercial Cargo Craft. To date over 375 rodent flight experiments with translational application have been archived by the Ames LSDA office. This knowledge base of fundamental research can be used to understand mechanisms that affect higher organisms in microgravity and help define additional research whose results could lead the way to closing gaps identified by the Human Research Program (HRP). This poster will highlight Ames contribution to the existing knowledge base and how the LSDA can be a resource to help answer the questions surrounding human health in long duration space exploration. In addition, it will illustrate how this body of knowledge was utilized to further our understanding of how space flight affects the human system and the ability to develop countermeasures that negate the deleterious effects of space flight. The Ames Life Sciences Data Archive (ALSDA) includes current descriptions of over 700 experiments conducted aboard the Shuttle, International Space Station (ISS), NASA/MIR, Bion/Cosmos, Gemini, Biosatellites, Apollo, Skylab, Russian Foton, and ground bed rest studies. Research areas cover Behavior and Performance, Bone and Calcium Physiology, Cardiovascular Physiology, Cell and Molecular Biology, Chronobiology, Developmental Biology, Endocrinology, Environmental Monitoring, Gastrointestinal Physiology, Hematology, Immunology, Life Support System, Metabolism and Nutrition, Microbiology, Muscle Physiology, Neurophysiology, Pharmacology, Plant Biology, Pulmonary Physiology, Radiation Biology, Renal, Fluid and Electrolyte Physiology, and Toxicology. These experiment descriptions and data can be accessed online via the public LSDA website (http://lsda.jsc.nasa.gov) and information can be requested via the Data Request form at http://lsda.jsc.nasa.gov/common/dataRequest/dataRequest.aspx or by contacting the ALSDA Office at: [email protected]

Do acute elevations of serum creatinine in primary care engender an increased mortality risk?

Background: The significant impact Acute Kidney Injury (AKI) has on patient morbidity and mortality emphasizes the need for early recognition and effective treatment. AKI presenting to or occurring during hospitalisation has been widely studied but little is known about the incidence and outcomes of patients experiencing acute elevations in serum creatinine in the primary care setting where people are not subsequently admitted to hospital. The aim of this study was to define this incidence and explore its impact on mortality. Methods: The study cohort was identified by using hospital data bases over a six month period. Inclusion criteria: People with a serum creatinine request during the study period, 18 or over and not on renal replacement therapy. The patients were stratified by a rise in serum creatinine corresponding to the Acute Kidney Injury Network (AKIN) criteria for comparison purposes. Descriptive and survival data were then analysed. Ethical approval was granted from National Research Ethics Service (NRES) Committee South East Coast and from the National Information Governance Board. Results: The total study population was 61,432. 57,300 subjects with ‘no AKI’, mean age 64.The number (mean age) of acute serum creatinine rises overall were, ‘AKI 1’ 3,798 (72), ‘AKI 2’ 232 (73), and ‘AKI 3’ 102 (68) which equates to an overall incidence of 14,192 pmp/year (adult). Unadjusted 30 day survival was 99.9% in subjects with ‘no AKI’, compared to 98.6%, 90.1% and 82.3% in those with ‘AKI 1’, ‘AKI 2’ and ‘AKI 3’ respectively. After multivariable analysis adjusting for age, gender, baseline kidney function and co-morbidity the odds ratio of 30 day mortality was 5.3 (95% CI 3.6, 7.7), 36.8 (95% CI 21.6, 62.7) and 123 (95% CI 64.8, 235) respectively, compared to those without acute serum creatinine rises as defined. Conclusions: People who develop acute elevations of serum creatinine in primary care without being admitted to hospital have significantly worse outcomes than those with stable kidney function

Measuring the impact and costs of a universal group based parenting programme : protocol and implementation of a trial

Background Sub-optimal parenting is a common risk factor for a wide range of negative health, social and educational outcomes. Most parenting programmes have been developed in the USA in the context of delinquency prevention for targeted or indicated groups and the main theoretical underpinning for these programmes is behaviour management. The Family Links Nurturing Programme (FLNP) focuses on family relationships as well as behaviour management and is offered on a universal basis. As a result it may be better placed to improve health and educational outcomes. Developed in the UK voluntary sector, FLNP is popular with practitioners, has impressed policy makers throughout the UK, has been found to be effective in before/after and qualitative studies, but lacks a randomised controlled trial (RCT) evidence base. Methods/Design A multi-centre, investigator blind, randomised controlled trial of the FLNP with a target sample of 288 south Wales families who have a child aged 2-4 yrs living in or near to Flying Start/Sure Start areas. Changes in parenting, parent child relations and parent and child wellbeing are assessed with validated measures immediately and at 6 months post intervention. Economic components include cost consequences and cost utility analyses based on parental ranking of states of quality of life. Attendance and completion rates and fidelity to the FLNP course delivery are assessed. A nested qualitative study will assess reasons for participation and non-participation and the perceived value of the programme to families. By the end of May 2010, 287 families have been recruited into the trial across four areas of south Wales. Recruitment has not met the planned timescales with barriers including professional anxiety about families entering the control arm of the trial, family concern about video and audio recording, programme facilitator concern about the recording of FLNP sessions for fidelity purposes and delays due to the new UK research governance procedures. Discussion Whilst there are strong theoretical arguments to support universal provision of parenting programmes, few universal programmes have been subjected to randomised controlled trials. In this paper we describe a RCT protocol with quantitative and qualitative outcome measures and an economic evaluation designed to provide clear evidence with regard to effectiveness and costs. We describe challenges implementing the protocol and how we are addressing these

Developing and enhancing biodiversity monitoring programmes: a collaborative assessment of priorities

1.Biodiversity is changing at unprecedented rates, and it is increasingly important that these changes are quantified through monitoring programmes. Previous recommendations for developing or enhancing these programmes focus either on the end goals, that is the intended use of the data, or on how these goals are achieved, for example through volunteer involvement in citizen science, but not both. These recommendations are rarely prioritized. 2.We used a collaborative approach, involving 52 experts in biodiversity monitoring in the UK, to develop a list of attributes of relevance to any biodiversity monitoring programme and to order these attributes by their priority. We also ranked the attributes according to their importance in monitoring biodiversity in the UK. Experts involved included data users, funders, programme organizers and participants in data collection. They covered expertise in a wide range of taxa. 3.We developed a final list of 25 attributes of biodiversity monitoring schemes, ordered from the most elemental (those essential for monitoring schemes; e.g. articulate the objectives and gain sufficient participants) to the most aspirational (e.g. electronic data capture in the field, reporting change annually). This ordered list is a practical framework which can be used to support the development of monitoring programmes. 4.People's ranking of attributes revealed a difference between those who considered attributes with benefits to end users to be most important (e.g. people from governmental organizations) and those who considered attributes with greatest benefit to participants to be most important (e.g. people involved with volunteer biological recording schemes). This reveals a distinction between focussing on aims and the pragmatism in achieving those aims. 5.Synthesis and applications. The ordered list of attributes developed in this study will assist in prioritizing resources to develop biodiversity monitoring programmes (including citizen science). The potential conflict between end users of data and participants in data collection that we discovered should be addressed by involving the diversity of stakeholders at all stages of programme development. This will maximize the chance of successfully achieving the goals of biodiversity monitoring programmes

Deweyan tools for inquiry and the epistemological context of critical pedagogy

This article develops the notion of resistance as articulated in the literature of critical pedagogy as being both culturally sponsored and cognitively manifested. To do so, the authors draw upon John Dewey\u27s conception of tools for inquiry. Dewey provides a way to conceptualize student resistance not as a form of willful disputation, but instead as a function of socialization into cultural models of thought that actively truncate inquiry. In other words, resistance can be construed as the cognitive and emotive dimensions of the ongoing failure of institutions to provide ideas that help individuals both recognize social problems and imagine possible solutions. Focusing on Dewey\u27s epistemological framework, specifically tools for inquiry, provides a way to grasp this problem. It also affords some innovative solutions; for instance, it helps conceive of possible links between the regular curriculum and the study of specific social justice issues, a relationship that is often under-examined. The aims of critical pedagogy depend upon students developing dexterity with the conceptual tools they use to make meaning of the evidence they confront; these are background skills that the regular curriculum can be made to serve even outside social justice-focused curricula. Furthermore, the article concludes that because such inquiry involves the exploration and potential revision of students\u27 world-ordering beliefs, developing flexibility in how one thinks may be better achieved within academic subjects and topics that are not so intimately connected to students\u27 current social lives, especially where students may be directly implicated

Family-centred music therapy with preterm infants and their parents in the Neonatal Intensive Care Unit (NICU) in Colombia – A mixed-methods study

This article reports a mixed-methods study of Music Therapy (MT) with preterm infants and their parents in a neonatal intensive care unit (NICU) in Colombia. The aim was to find out whether live MT during kangaroo care had an effect on the physiological outcomes of the neonates and would help parents to decrease their anxiety levels and improve parent–infant bonding. The participants were 36 medically stable neonates born between the 28th and 34th week of gestation and their parents. The quantitative data collection included heart rate, oxygen saturation, weight gain, length of hospitalization and re-hospitalization rate. The assessment measures for anxiety and bonding were the State-Trait Anxiety Inventory (STAI) and the Mother-to-Infant-Bonding Scale (MIBS). Thematic analysis was used to analyse the qualitative data collected with semi-structured interviews and questionnaires. The quantitative results showed statistically significant improvements in maternal state-anxiety (p = .007) and in the babies weight gain per day during the intervention period (p = .036). Positive trends were found regarding the babies’ length of hospitalization and re-hospitalization rate. Both parents improved their scores with the MIBS, but this was not statistically significant. The qualitative analysis showed that MT was important for parental well-being, for bonding and for fostering the development of the neonates. Interacting musically with their babies helped parents to experience feelings of connectedness and to distract themselves from their difficulties and from the noisy hospital environment

Unexpected medical undergraduate simulation training (UMUST): can unexpected medical simulation scenarios help prepare medical students for the transition to foundation year doctor?

BACKGROUND: Preparing medical students with the skills necessary to deal with emergency situations as junior doctors can be challenging due to the complexities of creating authentic ‘real life’ experiences in artificial environments. The following paper is an evaluation of the UMUST (Unexpected Medical Undergraduate Simulation Training) project; a high-fidelity simulation based training programme designed to emulate the experience of dealing with medical emergencies for final year medical students preparing for practice as Foundation Year trainees. METHODS: Final year medical students from Liverpool University who undertake their clinical placements at Blackpool Teaching Hospitals NHS Foundation Trust and St. Helens & Knowsley Teaching Hospitals NHS Trust were randomly allocated into groups and took part in a series of four unexpected simulation based scenarios. At the beginning of the week in which the scenarios ran, participants were issued with a hospital bleep which they carried with them during their placement. At an unknown time to them, the participants were bleeped to attend a simulated emergency scenario, and on arrival to the Clinical Skills and Simulation facility, members of the education team undertook a standardised simulation scenario. Each session was recorded on video which the participants subsequently watched as part of a debriefing process. An assessment tool was developed to gauge whether the participants made progress in their learning over the course of the four sessions. Focus groups were held with the participants in order to evaluate their experience of the programme, and questionnaires were later distributed to all participants once they had begun working as a Foundation Year trainee. The questionnaires asked them how relevant UMUST was in preparing them for dealing with medical emergencies. RESULTS: The questionnaires and the focus groups clearly showed that the doctors felt like UMUST was very valuable in preparing them to work as junior doctors. They had enjoyed taking part in UMUST and thought was a realistic and useful part of their undergraduate training. CONCLUSIONS: The feedback from the focus groups and the subsequent questionnaires clearly demonstrate that participants felt the UMUST programme helped to prepare them as junior doctors in terms of dealing with emergency situations

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy