The validation of an activity monitor for use with type 1 and 2 gait patterns in cerebral palsy

methods in which this can be achieved is through evidence based practice. The current climate within the NHS has clear manifestations of such practice, the most visible perhaps being the increase in audit within practice. The facilitation of high quality care also requires practitioners to partake in multiprofessional treatment planning and embrace such plans into their every day practice. In line with the above it is essential that during the emergence of such practice audit occurs to measure the effectiveness of such approaches.One of the areas that could greatly benefit from such practice is that of Cerebral Palsy. Management of children with cerebral palsy is the focus of considerable resources in many countries so that the evaluation of the efficacy of new and established treatments is imperative (Boyd 2001).Cerebral Palsy is a lifelong condition with a significant impact on the individual and their carers. Most subjects with mild or moderately severe CP survive into adult life and have a normal life expectancy (Bhusan 1993). Although the brain pathology that underlies the clinical manifestations of CP is non-progressive, the functional abilities of the individuals and their health and social needs usually change (Bakheit 2001).With the above philosophy of evidence based practice in mind and the current need for valid and reliable tools to achieve this goal, it is the aim of this thesis to validate an activity monitor, the activPAL, for use with cerebral palsy (CP). It will establish whether or not the activPAL activity monitor is a valid and reliable tool with which to measure this population. A review of existing activity monitor research shall take place and outcome measures currently adopted within cerebral palsy studies shall be reviewed

Implementation of compact calving at the farm level: A qualitative analysis of farmers operating pasture-based dairy systems in Ireland

peer-reviewedPasture-based dairy systems aim to maximize the proportion of grazed pasture in the cow's diet by having a compact calving season that coincides with the onset of the grass growing season. In Ireland, where pasture-based systems are dominant, a key performance indicator that reflects the degree of compact calving is referred to as 6-wk calving rate (6-wk CR). Although the industry target is 90%, the national average 6-wk CR in Ireland is currently 67%. The aim of this study was to use qualitative research to understand in depth farmers' experiences in implementing a high 6-wk CR. Ten case-study dairy farmers were interviewed using the biographical narrative interpretive method. We identified 5 broad and often interrelated themes evoked by farmers regarding 6-wk CR: the “good” farmer; support networks; free time and family time; simplicity of a structured system; and profitability and monetary gain. The findings of this study identify complexities and challenges at farm level when it comes to increasing 6-wk CR, such as increased workload and challenges associated with large numbers of male calves born during a condensed calving season. Benefits experienced by farmers as a result of increasing 6-wk CR included increased days in milk and consequently improved cash flow as well as increased grass utilization. Our findings are of interest to researchers and extension agents involved in programs concerned with reproductive management in pasture-based dairy systems

Prescribing and sales of intramammary antimicrobials in Ireland in 2019 and 2020: the role of milk purchasers

Background: In Ireland between 2008 and 2022, intramammary antimicrobial (AM) products could be prescribed by a veterinary practitioner under what was known as Schedule 8 (or remote) prescribing. Under this prescribing route, an annual herd visit was not required when criteria were met as outlined in Animal Remedies Regulation 2007 to 2017 (statutory instruments No. 786/2007 and 558/2017). Under this prescribing route, the responsibilities of the milk purchaser, the farmer and the veterinary practitioner were each outlined, and a written mastitis control programme (MCP) was required. Milk purchasers implemented MCPs on participating farms (so-called MCP herds) with support from veterinary practitioner(s) who undertook Schedule 8 prescribing of intramammary AM tubes. This study seeks a clearer understanding of the role of milk purchasers in the prescribing and sale of intramammary AM products in Ireland during 2019 and 2020, whilst this Regulation was in force. Specifically, the study sought insights into the role of milk purchasers in the prescribing and sale of intramammary AM products in the Irish dairy industry during 2019 and 2020, using anonymised and highly aggregated milk purchaser data. The study also provided insights into milk quality among supplying herds during this period. Methods: For this study, we had access to anonymised, highly aggregated data from all milk purchasers that operated a MCP on at least some of their supplying herds during 2019 or 2020. Data collection was undertaken by the Department of Agriculture, Food and Marine. Data analysis was primarily descriptive. Results: Data were available on 11 milk purchasers (64.7% of all) and 13,251 supplying herds. Of these, 52% were MCP herds. The quality of milk from supplying herds varied significantly by month, year and milk purchaser. During 2019 and 2020, there was a single Schedule 8 prescriber (a private veterinary practitioner prescribing intramammary AMs as part of a MCP), on average, for 549.3 herds. The sale of intramammary AM products through milk purchasers represented 15.2% and 26.9% of national sales in in-lactation and dry cow tubes, respectively. There was an overall 2% increase in sales through milk purchasers between 2019 and 2020. Few European Medicines Agency (EMA) category B (‘Restrict’) intramammary AM products were sold by milk purchasers. For both in-lactation and dry cow tubes, there was a statistically significant association between EMA classification and route of sale (through milk purchasers or otherwise).Department of Agriculture, Food and the Marin

CaMKK2 as an emerging treatment target for bipolar disorder

Current pharmacological treatments for bipolar disorder are inadequate and based on serendipitously discovered drugs often with limited efficacy, burdensome side-effects, and unclear mechanisms of action. Advances in drug development for the treatment of bipolar disorder remain incremental and have come largely from repurposing drugs used for other psychiatric conditions, a strategy that has failed to find truly revolutionary therapies, as it does not target the mood instability that characterises the condition. The lack of therapeutic innovation in the bipolar disorder field is largely due to a poor understanding of the underlying disease mechanisms and the consequent absence of validated drug targets. A compelling new treatment target is the Ca2+-calmodulin dependent protein kinase kinase-2 (CaMKK2) enzyme. CaMKK2 is highly enriched in brain neurons and regulates energy metabolism and neuronal processes that underpin higher order functions such as long-term memory, mood, and other affective functions. Loss-of-function polymorphisms and a rare missense mutation in human CAMKK2 are associated with bipolar disorder, and genetic deletion of Camkk2 in mice causes bipolar-like behaviours similar to those in patients. Furthermore, these behaviours are ameliorated by lithium, which increases CaMKK2 activity. In this review, we discuss multiple convergent lines of evidence that support targeting of CaMKK2 as a new treatment strategy for bipolar disorder

Blocking AMPK β1 myristoylation enhances AMPK activity and protects mice from high-fat diet-induced obesity and hepatic steatosis

AMP-activated protein kinase (AMPK) is a master regulator of cellular energy homeostasis and a therapeutic target for metabolic diseases. Co/post-translational N-myristoylation of glycine-2 (Gly2) of the AMPK β subunit has been suggested to regulate the distribution of the kinase between the cytosol and membranes through a “myristoyl switch” mechanism. However, the relevance of AMPK myristoylation for metabolic signaling in cells and in vivo is unclear. Here, we generated knockin mice with a Gly2-to-alanine point mutation of AMPKβ1 (β1-G2A). We demonstrate that non-myristoylated AMPKβ1 has reduced stability but is associated with increased kinase activity and phosphorylation of the Thr172 activation site in the AMPK α subunit. Using proximity ligation assays, we show that loss of β1 myristoylation impedes colocalization of the phosphatase PPM1A/B with AMPK in cells. Mice carrying the β1-G2A mutation have improved metabolic health with reduced adiposity, hepatic lipid accumulation, and insulin resistance under conditions of high-fat diet-induced obesity