The matching of motivations to affordances among Maltese elected local government volunteers : implications for sustaining civil society

Purpose – The purpose of this study is to both understand the motives for volunteering in local government (a strong/structured context) and determine how such motivation and other demographics interact with organisational contexts to influence volunteering outcomes. Design/methodology/approach – The study adopts a functional approach to volunteerism. The Volunteer Functions Inventory is modified to better assess the motivations of elected local government volunteers. The responses of 152 Maltese local councillors were used to answer four research questions empirically. Findings – Exploratory and confirmatory factor analyses supported the introduction of a seventh VFI dimension, namely the political function. The study provides evidence that local councillors who received greater amounts of functionally relevant benefits reported more satisfaction and a stronger intention to continue volunteering in local government. The aggregated effect of multiple motives as well as other person-based determinants (marital status and education) produced a significant impact on volunteering outcomes in this strong/structured situational context of this public sector environment. Originality/value – This study contributes to a better understanding and assessment of the motivations of elected local government volunteers. It addresses practical recommendations for sustaining civil society, while acknowledging the potential and contribution of volunteers with various demographic characteristics

Competency level in radiotherapy across EU educational programmes: A cross-case study evaluating stakeholders' perceptions

Introduction: The education of Therapeutic Radiographers (TRs) is regulated in some countries but is not standardised across the EU, leading to differences in competencies between and within member states. This study aimed to explore stakeholders’ perceptions regarding underdeveloped competencies of TRs practising on the linear accelerator, identified in a previous study by the same research team.Methods: Interviews with stakeholders from four countries (selected based on the characteristics of their degrees) were performed as part of this cross-case study. Stakeholders were asked to provide their perception regarding the least developed competencies identified in a previous study.Results: The 27 stakeholders confirmed that Pharmacology, Quality Assurance (QA), Management and Leadership, Research (from the previous study) were underdeveloped and identified Image Verification and Critical Thinking as additional underdeveloped competencies. Suggested causes included: lack of regulation of required competencies at the national level, lack of training dedicated to radiotherapy (RT) (taught within generic modules) and lack of time within the degree programme. The ideal academic level to develop these competencies and whether they are essential varied between country and stakeholder.Conclusion: It is essential to regulate learning outcomes at the national level to ensure a high level of care is provided to all RT patients and, ideally, standardise it across Europe. Education institutions should review their curricula to ensure that sufficient time is dedicated to RT and that the essential competencies are developed. Due to time constraints within some programmes, some competencies must be developed after graduation.Implications for practice: Lack of regulation of learning outcomes (at European level and national level in many countries) and lack of RT-specific training lead to underdeveloped competencies that may compromise patient care.peer-reviewe

A duality of generalized metric spaces

AbstractWe develop a duality theory for Lawvereʼs generalized metric spaces that extends the Lawson duality for continuous dcpos and open filter reflecting maps: we prove that the category of relatively cocomplete and continuous [0,∞]-categories considered with open filter reflecting maps is self-dual

Importance of 3-dimensional imaging in the early diagnosis of chondroblastic osteosarcoma

The aim of this report is to present a case of chondroblastic osteosarcoma located in the right maxillary premolar region of a 17-year-old female patient. The initial clinical presentation and 2-dimensional (2D) radiographic methods proved inadequate for a definitive diagnosis. However, a cone-beam computed tomography scan revealed a hyperdense, heterogeneous lesion in the right maxillary premolar region, exhibiting a characteristic “sun-ray” appearance. To assess soft tissue involvement, a medical computed tomography scan was subsequently conducted. A positron emission tomography scan detected no metastasis or indications of secondary tumors. T1- and T2-weighted magnetic resonance imaging showed signal heterogeneity within the lesion, including areas of low signal intensity at the periphery. Histological examination conducted after an incisional biopsy confirmed the diagnosis of high-grade chondroblastic osteosarcoma. The patient was then referred to an oncology department for chemotherapy before surgery. In conclusion, these findings suggest that early diagnosis using 3-dimensional imaging can detect chondroblastic osteosarcoma in its early stages, such as before metastasis occurs, thereby improving the patient’s prognosis.peer-reviewe

Activation of Ventral Tegmental Area 5-HT2C Receptors Reduces Incentive Motivation

FUNDING AND DISCLOSURE The research was funded by Wellcome Trust (WT098012) to LKH; and National Institute of Health (DK056731) and the Marilyn H. Vincent Foundation to MGM. The University of Michigan Transgenic Core facility is partially supported by the NIH-funded University of Michigan Center for Gastrointestinal Research (DK034933). The remaining authors declare no conflict of interest. ACKNOWLEDGMENTS We thank Dr Celine Cansell, Ms Raffaella Chianese and the staff of the Medical Research Facility for technical assistance. We thank Dr Vladimir Orduña for the scientific advice and technical assistance.Peer reviewedPublisher PD

Unique Cardiac Purkinje Fiber Transient-Outward Current Beta-Subunit Composition: A Potential Molecular Link to Idiopathic Ventricular Fibrillation.

Rationale: A chromosomal-haplotype producing cardiac overexpression of dipeptidyl peptidase-like protein-6 (DPP6) causes familial idiopathic ventricular fibrillation (IVF). The molecular basis of transient-outward current (Ito) in Purkinje fibers (PFs) is poorly understood. We hypothesized that DPP6 contributes to PF Ito and that its overexpression might specifically alter PF Ito-properties and repolarization. Objective: To assess the potential role of DPP6 in PF-Ito. Methods and Results: Clinical data in 5 IVF-patients suggested arrhythmia-origin in the PF conducting-system. PF and ventricular-muscle (VM) Ito had similar density, but PF Ito differed from VM in having tetraethylammonium-sensitivity and slower recovery. DPP6-overexpression significantly increased, whereas DPP6-kockdown reduced, Ito-density and tetraethylammonium-sensitivity in canine PF, but not VM-cells. The K+-channel interacting beta-subunit KChIP2, essential for normal expression of transient outward current (Ito) in VM, was weakly-expressed in human PFs, whereas DPP6 and frequenin (NCS-1) were enriched. Heterologous expression of Kv4.3 in Chinese hamster ovary (CHO)-cells produced very small Ito; Ito-amplitude was greatly enhanced by co-expression with KChIP2 or DPP6. Co expression of DPP6 with Kv4.3 and KChIP2 failed to alter Ito versus Kv4.3/KChIP2 alone, but DPP6 expression with Kv4.3 and NCS-1 (to mimic PF Ito-composition), greatly enhanced Ito versus Kv4.3/NCS-1 and recapitulated characteristic PF kinetic/pharmacological properties. A mathematical model of cardiac PF action potentials showed that Ito-enhancement can greatly accelerate PF repolarization. Conclusions: These results point to a previously-unknown central role of DPP6 in PF Ito, with DPP6 gain-of-function selectively enhancing PF-current, and suggest that a DPP6-mediated PF early repolarization syndrome might be a novel molecular paradigm for some forms of IVF

Utility of Post-Mortem Genetic Testing in Cases of Sudden Arrhythmic Death Syndrome.

BACKGROUND: Sudden arrhythmic death syndrome (SADS) describes a sudden death with negative autopsy and toxicological analysis. Cardiac genetic disease is a likely etiology. OBJECTIVES: This study investigated the clinical utility and combined yield of post-mortem genetic testing (molecular autopsy) in cases of SADS and comprehensive clinical evaluation of surviving relatives. METHODS: We evaluated 302 expertly validated SADS cases with suitable DNA (median age: 24 years; 65% males) who underwent next-generation sequencing using an extended panel of 77 primary electrical disorder and cardiomyopathy genes. Pathogenic and likely pathogenic variants were classified using American College of Medical Genetics (ACMG) consensus guidelines. The yield of combined molecular autopsy and clinical evaluation in 82 surviving families was evaluated. A gene-level rare variant association analysis was conducted in SADS cases versus controls. RESULTS: A clinically actionable pathogenic or likely pathogenic variant was identified in 40 of 302 cases (13%). The main etiologies established were catecholaminergic polymorphic ventricular tachycardia and long QT syndrome (17 [6%] and 11 [4%], respectively). Gene-based rare variants association analysis showed enrichment of rare predicted deleterious variants in RYR2 (p = 5 × 10(-5)). Combining molecular autopsy with clinical evaluation in surviving families increased diagnostic yield from 26% to 39%. CONCLUSIONS: Molecular autopsy for electrical disorder and cardiomyopathy genes, using ACMG guidelines for variant classification, identified a modest but realistic yield in SADS. Our data highlighted the predominant role of catecholaminergic polymorphic ventricular tachycardia and long QT syndrome, especially the RYR2 gene, as well as the minimal yield from other genes. Furthermore, we showed the enhanced utility of combined clinical and genetic evaluation

Identification of an INa-dependent and Ito-mediated proarrhythmic mechanism in cardiomyocytes derived from pluripotent stem cells of a Brugada syndrome patient

Brugada syndrome (BrS) is an inherited cardiac arrhythmia commonly associated with SCN5A mutations, yet its ionic mechanisms remain unclear due to a lack of cellular models. Here, we used human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) from a BrS patient (BrS1) to evaluate the roles of Na+ currents (INa) and transient outward K+ currents (Ito) in BrS induced action potential (AP) changes. To understand the role of these current changes in repolarization we employed dynamic clamp to "electronically express" IK1 and restore normal resting membrane potentials and allow normal recovery of the inactivating currents, INa, ICa and Ito. HiPSC-CMs were generated from BrS1 with a compound SCN5A mutation (p. A226V & p. R1629X) and a healthy sibling control (CON1). Genome edited hiPSC-CMs (BrS2) with a milder p. T1620M mutation and a commercial control (CON2) were also studied. CON1, CON2 and BrS2, had unaltered peak INa amplitudes, and normal APs whereas BrS1, with over 75% loss of INa, displayed a loss-of-INa basal AP morphology (at 1.0 Hz) manifested by a reduced maximum upstroke velocity (by ~80%, p < 0.001) and AP amplitude (p < 0.001), and an increased phase-1 repolarization pro-arrhythmic AP morphology (at 0.1 Hz) in ~25% of cells characterized by marked APD shortening (~65% shortening, p < 0.001). Moreover, Ito densities of BrS1 and CON1 were comparable and increased from 1.0 Hz to 0.1 Hz by ~ 100%. These data indicate that a repolarization deficit could be a mechanism underlying BrS