Filtering and scalability in the ECO distributed event model

Event-based communication is useful in many application domains, ranging from small, centralised applications to large, distributed systems. Many different event models have been developed to address the requirements of different application domains. One such model is the ECO model which was designed to support distributed virtual world applications. Like many other event models, ECO has event filtering capabilities meant to improve scalability by decreasing network traffic in a distributed implementation. Our recent work in event-based systems has included building a fully distributed version of the ECO model, including event filtering capabilities. This paper describes the results of our evaluation of filters as a means of achieving increased scalability in the ECO model. The evaluation is empirical and real data gathered from an actual event-based system is used

Feasibility and initial efficacy of project-based treatment for people with ABI

Background: Communication impairments are common and pervasive for people a long time following acquired brain injury (ABI). These impairments have a significant impact on a person's quality of life (QOL) post‐injury. Project‐based treatment is a treatment approach that could have an impact on communication skills and QOL for people with ABI a long‐term post‐injury. This treatment is embedded in a context of meaningful activities chosen by people with ABI, whereby, as a group, they work collaboratively to achieve a tangible end product. Aims: To evaluate the feasibility and initial efficacy of project‐based treatment on improving the communication skills and QOL for people with ABI. Methods & Procedures: An exploratory controlled trial with alternate allocation of groups, and follow‐up at 6–8 weeks, was completed. Twenty‐one people with chronic ABI were recruited in groups of two to three from community settings, allocated to either a TREATMENT (n = 11) or WAITLIST group (n = 10). Participants attended a 20‐h group‐based treatment over 6 weeks where they worked towards achieving a project that helped others. To determine feasibility, four criteria were used: demand, implementation, practicality and acceptability. A range of communication and QOL outcomes was used to determine a fifth feasibility criterion, initial efficacy. Some of these criteria were additionally used to evaluate the feasibility of the outcomes. Outcomes & Results: All participants received the treatment as allocated with high attendance and no dropouts. The treatment was feasible to deliver as intended and was highly acceptable to participants. Medium and large effect sizes were found from pre‐ to post‐treatment, and from pre‐treatment to follow‐up for measures of conversation, perceived communicative ability and QOL. Conclusions & Implications: Project‐based treatment is feasible with indications of initial efficacy for both communication skills and QOL. The treatment provides a promising new approach for improving communication skills and QOL in people with chronic acquired brain injuries in the community setting

ANALYSIS OF THE JOINT KINEMATICS OF THE 5 IRON GOLF SWING

The purpose of this study was to identify the performance determining factors of the 5-iron golf swing. Joint kinematics were obtained from thirty male golfers using a twelve camera motion analysis system. Participants were divided into two groups, based on their ball launch speed (high vs. low). Those in the high ball speed group were deemed to be the more skillful group. Statistical analysis was used to identify the variables which differed significantly between the two groups, and could therefore be classified as the performance determining factors. The following factors were important to performance success: (i) the ability of the golfer to maintain a large X Factor angle and generate large X Factor angular velocity throughout the downswing, (ii) maintain the left arm as straight as possible throughout the swing, (iii) utilise greater movement of the hips in the direction of the target and a greater extension of the right hip during the downswing and (iv) greater flexion of both shoulders and less left shoulder internal rotation during the backswing

Ultra-Long Pharmacokinetic Properties of Insulin Degludec are Comparable in Elderly Subjects and Younger Adults with Type 1 Diabetes Mellitus

BACKGROUND: Management of diabetes in elderly subjects is complex and careful management of glucose levels is of particular importance in this population because of an increased risk of diabetes-related complications and hypoglycaemia. OBJECTIVE: The aim of this study was to evaluate the pharmacokinetic and pharmacodynamic properties of insulin degludec (IDeg), a basal insulin with an ultra-long duration of action, in elderly subjects with type 1 diabetes compared with younger adults. METHODS: This trial was a randomised, double-blind, two-period, crossover trial conducted in a single centre and included both inpatient and outpatient periods. Subjects were men and women aged 18–35 years inclusive (younger adult group) or ≥65 years (elderly group) with type 1 diabetes who received IDeg (0.4 U/kg) via subcutaneous injection in the thigh once-daily for six days. Following 6-day dosing, a 26-hour euglycaemic glucose clamp procedure was conducted to evaluate the steady-state pharmacodynamic effects of IDeg. Blood samples were taken for pharmacokinetic analysis up to 120 h post-dose. Pharmacokinetic endpoints included the total exposure of IDeg, ie the area under the IDeg serum concentration curve during one dosing interval at steady state (AUC(IDeg,τ,SS)) (τ = 0–24 h, equal to one dosing interval) and the maximum IDeg serum concentration at steady state (C(max,IDeg,SS)). Pharmacodynamic endpoints included the total glucose-lowering effect of IDeg, ie the area under the glucose infusion rate (GIR) curve at steady state (AUC(GIR,τ,SS)), and the maximum GIR at steady state (GIR(max,IDeg,SS)). RESULTS: Total exposure (AUC(IDeg,τ,SS)) and maximum concentration (C(max,IDeg,SS)) of IDeg were comparable between elderly subjects and younger adults. Estimated mean age group ratios (elderly/younger adult) for AUC(IDeg,τ,SS) and C(max,IDeg,SS) and corresponding two-sided 95 % confidence intervals (CIs) were 1.04 (95 % CI 0.73–1.47) and 1.02 (95 % CI 0.74–1.39), respectively. Mean AUC(IDeg,0–12h,SS)/AUC(IDeg,τ,SS) was 53 % in both younger adult and elderly subjects, showing that in both age groups IDeg exposure was evenly distributed across the first and second 12 h of the 24-hour dosing interval. No statistically significant differences were observed between younger adult and elderly subjects with regard to AUC(GIR,τ,SS) (the primary endpoint of this study) and GIR(max,IDeg,SS). Estimated mean age group ratios (elderly/younger adult) for AUC(GIR,τ,SS) and GIR(max,IDeg,SS) and corresponding two-sided 95 % CIs were 0.78 (95 % CI 0.47–1.31) and 0.80 (95 % CI 0.54–1.17), respectively. Duration of action was beyond the clamp duration of 26 h in all subjects. CONCLUSIONS: The exposure of IDeg at steady state during once-daily dosing was similar in younger adult and elderly subjects. The glucose-lowering effect of IDeg was numerically lower in elderly subjects compared with younger adults, but no significant differences were observed between age groups. The ultra-long pharmacokinetic and pharmacodynamic properties of IDeg observed in younger adults were preserved in elderly subjects with type 1 diabetes. Clinical trials.gov number: NCT0096441

Heart rate dynamics during cardio-pulmonary exercise testing are associated with glycemic control in individuals with type 1 diabetes

IntroductionThis study investigated the degree and direction (kHR) of the heart rate to performance curve (HRPC) during cardio-pulmonary exercise (CPX) testing and explored the relationship with diabetes markers, anthropometry and exercise physiological markers in type 1 diabetes (T1DM).Material and methodsSixty-four people with T1DM (13 females; age: 34 ± 8 years; HbA1c: 7.8 ± 1% (62 ± 13 mmol.mol-1) performed a CPX test until maximum exhaustion. kHR was calculated by a second-degree polynomial representation between post-warm up and maximum power output. Adjusted stepwise linear regression analysis was performed to investigate kHR and its associations. Receiver operating characteristic (ROC) curve was performed based on kHR for groups kHR 0.20 in relation to HbA1c.ResultsWe found significant relationships between kHR and HbA1c (β = -0.70, P < 0.0001), age (β = -0.23, P = 0.03) and duration of diabetes (β = 0.20, P = 0.04). Stepwise linear regression resulted in an overall adjusted R2 of 0.57 (R = 0.79, P < 0.0001). Our data revealed also significant associations between kHR and percentage of heart rate at heart rate turn point from maximum heart rate (β = 0.43, P < 0.0001) and maximum power output relativized to bodyweight (β = 0.44, P = 0.001) (overall adjusted R2 of 0.44 (R = 0.53, P < 0.0001)). ROC curve analysis based on kHR resulted in a HbA1c threshold of 7.9% (62 mmol.mol-1).ConclusionOur data demonstrate atypical HRPC during CPX testing that were mainly related to glycemic control in people with T1DM

Understanding support systems for Parkinson's disease management in community settings: A cross-national qualitative study

Background: Health and social care systems face difficulties in managing multimorbidity, disease burden and complex needs in long-term conditions such as Parkinson's disease. Objective: This study aimed to develop a European understanding of how health and social care professionals can collaborate with stakeholders from different organizations and sectors to enhance the management of Parkinson's disease in a community setting by identifying the existing gaps in this process and how people with Parkinson's disease and their family carers could benefit from these partnerships. Methods: A mixed-methods sequential study was conducted in Denmark, Norway, Spain and the United Kingdom. The findings from the qualitative phase are presented. Individual semistructured interviews were analysed using Braun's and Clarke's thematic analysis. A meta-ethnography approach was used to analyse and synthesize cross-national findings. Results: A total of 41 healthcare professionals and 39 stakeholders from different disciplines and sectors were interviewed in the four countries. The participants acknowledged a lack of awareness of available resources and poor communication between the different support systems in the management of Parkinson's disease. To promote multiagency collaborations, the participants highlighted the need to organize services along the Parkinson's disease journey, patient involvement and strategic involvement of carers in organizing resources and Parkinson's disease care pathways. According to the participants, the benefits from multiagency partnerships could lead to an enhanced continuity of care and specialized knowledge, mobilization of resources in the community, personalized support and improved access to services. Conclusions: Policymakers are called upon to create formal structures that facilitate multisectoral collaborations to promote an integrated system of care for the management of Parkinson's disease in the community. To address this challenge, we propose five strategies showing how organizations can work together to optimize the use of resources and enhance the management of Parkinson's disease throughout the illness trajectory. Patient or public contribution: Patient and Public Involvement groups made up of stakeholders, healthcare professionals, patients with Parkinson's disease and family carers participated in the design of the study, the development of the interview guides and the validation of the findings.This work was supported by the EU Joint Programme-Neurodegenerative Disease Research (JPND). In Norway, the work was funded by the Research Council of Norway (grant number: 299762) and the DAM Foundation (project number FO296567). In Denmark, the work was funded by the Innovation Fund Denmark. In the United Kingdom, the work was funded by the Alzheimer's Society (grant number: 470). The Autonomous Universityof Madrid and the Ministry of Universities of the Spanish Government (Recovery, Transformation and Resilience Plan) were the financing entities of the researcher M. V. Navarta‐Sánchez (Grant number: CA2/RSUE/2021‐00854)S

FAM111 protease activity undermines cellular fitness and is amplified by gain-of-function mutations in human disease

Dominant missense mutations in the human serine protease FAM111A underlie perinatally lethal gracile bone dysplasia and Kenny-Caffey syndrome, yet how FAM111A mutations lead to disease is not known. We show that FAM111A proteolytic activity suppresses DNA replication and transcription by displacing key effectors of these processes from chromatin, triggering rapid programmed cell death by Caspase-dependent apoptosis to potently undermine cell viability. Patient-associated point mutations in FAM111A exacerbate these phenotypes by hyperactivating its intrinsic protease activity. Moreover, FAM111A forms a complex with the uncharacterized homologous serine protease FAM111B, point mutations in which cause a hereditary fibrosing poikiloderma syndrome, and we demonstrate that disease-associated FAM111B mutants display amplified proteolytic activity and phenocopy the cellular impact of deregulated FAM111A catalytic activity. Thus, patient-associated FAM111A and FAM111B mutations may drive multisystem disorders via a common gain-of-function mechanism that relieves inhibitory constraints on their protease activities to powerfully undermine cellular fitness