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Biomedical subjects

M Casey

Publications and source records attributed to M Casey.

At least 19 recordsLinked to original sources

Visuospatial working memory deficits in adolescent onset schizophrenia.

This study determines that visuospatial working memory (VSWM) deficits are evident in adolescent-onset schizophrenia, while the spatial strategy and spatial span components of VSWM are spared. These findings imply that frontal-striatal-parietal neural networks are dysfunctional in adolescent-onset schizophrenia, while mid-dorsolateral and ventrolateral PFC functions remain intact: the current conceptualisation of schizophrenia as a progressive neurodevelopmental disorder is consistent with these results.

Adolescent↗

Neurotoxicological and statistical analyses of a mixture of five organophosphorus pesticides using a ray design.

Environmental exposures generally involve chemical mixtures instead of single chemicals. Statistical models such as the fixed-ratio ray design, wherein the mixing ratio (proportions) of the chemicals is fixed across increasing mixture doses, allows for the detection and characterization of interactions among the chemicals. In this study, we tested for interaction(s) in a mixture of five organophosphorus (OP) pesticides (chlorpyrifos, diazinon, dimethoate, acephate, and malathion). The ratio of the five pesticides (full ray) reflected the relative dietary exposure estimates of the general population as projected by the US EPA Dietary Exposure Evaluation Model (DEEM). A second mixture was tested using the same dose levels of all pesticides, but excluding malathion (reduced ray). The experimental approach first required characterization of dose-response curves for the individual OPs to build a dose-additivity model. A series of behavioral measures were evaluated in adult male Long-Evans rats at the time of peak effect following a single oral dose, and then tissues were collected for measurement of cholinesterase (ChE) activity. Neurochemical (blood and brain cholinesterase [ChE] activity) and behavioral (motor activity, gait score, tail-pinch response score) endpoints were evaluated statistically for evidence of additivity. The additivity model constructed from the single chemical data was used to predict the effects of the pesticide mixture along the full ray (10-450 mg/kg) and the reduced ray (1.75-78.8 mg/kg). The experimental mixture data were also modeled and statistically compared to the additivity models. Analysis of the 5-OP mixture (the full ray) revealed significant deviation from additivity for all endpoints except tail-pinch response. Greater-than-additive responses (synergism) were observed at the lower doses of the 5-OP mixture, which contained non-effective dose levels of each of the components. The predicted effective doses (ED20, ED50) were about half that predicted by additivity, and for brain ChE and motor activity, there was a threshold shift in the dose-response curves. For the brain ChE and motor activity, there was no difference between the full (5-OP mixture) and reduced (4-OP mixture) rays, indicating that malathion did not influence the non-additivity. While the reduced ray for blood ChE showed greater deviation from additivity without malathion in the mixture, the non-additivity observed for the gait score was reversed when malathion was removed. Thus, greater-than-additive interactions were detected for both the full and reduced ray mixtures, and the role of malathion in the interactions varied depending on the endpoint. In all cases, the deviations from additivity occurred at the lower end of the dose-response curves.

Animals↗

Elimination of transmissible spongiform encephalopathy infectivity and decontamination of surgical instruments by using radio-frequency gas-plasma treatment.

It has now been established that transmissible spongiform encephalopathy (TSE) infectivity, which is highly resistant to conventional methods of deactivation, can be transmitted iatrogenically by contaminated stainless steel. It is important that new methods are evaluated for effective removal of protein residues from surgical instruments. Here, radio-frequency (RF) gas-plasma treatment was investigated as a method of removing both the protein debris and TSE infectivity. Stainless-steel spheres contaminated with the 263K strain of scrapie and a variety of used surgical instruments, which had been cleaned by a hospital sterile-services department, were examined both before and after treatment by RF gas plasma, using scanning electron microscopy and energy-dispersive X-ray spectroscopic analysis. Transmission of scrapie from the contaminated spheres was examined in hamsters by the peripheral route of infection. RF gas-plasma treatment effectively removed residual organic residues on reprocessed surgical instruments and gross contamination both from orthopaedic blades and from the experimentally contaminated spheres. In vivo testing showed that RF gas-plasma treatment of scrapie-infected spheres eliminated transmission of infectivity. The infectivity of the TSE agent adsorbed on metal spheres could be removed effectively by gas-plasma cleaning with argon/oxygen mixtures. This treatment can effectively remove 'stubborn' residual contamination on surgical instruments.

Animals↗

Sport safety policies and practices in two rural Victorian communities.

Australian football and netball are the predominant sports played in rural Victoria, Australia. This exploratory study is the first to report the sport safety policies and practices adopted by junior Australian football and netball clubs in small rural communities. Eleven informants from four clubs completed a semi-structured interview and survey. Whilst the clubs performed a range of injury prevention activities, they did not have formal sports safety policies. Generally, netball informants reported fewer safety practices than football informants. Crucial factors influencing safety policies and practices were the reliance on volunteers and a lack of senior players. Barriers towards the adoption of safety policies and practices appeared to be related to rural population declines, a lack of qualified people and attitudes to injury in rural areas. Future research needs to identify how widespread this lack of sport safety policies and practices is across rural Australia and to identify strategies to overcome barriers to implementing them.

Athletic Injuries↗

Dose-reducing strategies in combination offers substantial potential benefits to females requiring X-ray examination.

This work, using an adult anthropomorphic phantom, aimed to establish an optimised technique for ladies of child-bearing age undergoing antero-posterior (AP) pelvis and AP and lateral lumbar spine examinations. Phase one of the work involved introducing the following dose-reducing measures individually: increased kVp, increased focus-film distances, a carbon fibre cassette, a faster film/screen combination. The second phase established an optimised technique based on a combination of the parameters listed above. Radiation dose was measured using thermoluminescent dosimeters and image quality was evaluated using anatomical criteria. All dose-reducing methods were compared with a standard technique, currently being used in a Dublin hospital. The results demonstrated that the optimised procedure reduced effective dose by 77, 62 and 66% for AP pelvis and AP and lateral lumbar spine respectively (p < 0.05) compared with the standard technique, with no significant changes in image quality. Dose-reducing measures used in combination offer substantial potential for optimisation of radiological procedures.

Carbon↗

HeinzelCluster: accelerated reconstruction for FORE and OSEM3D.

Using iterative three-dimensional (3D) reconstruction techniques for reconstruction of positron emission tomography (PET) is not feasible on most single-processor machines due to the excessive computing time needed, especially so for the large sinogram sizes of our high-resolution research tomograph (HRRT). In our first approach to speed up reconstruction time we transform the 3D scan into the format of a two-dimensional (2D) scan with sinograms that can be reconstructed independently using Fourier rebinning (FORE) and a fast 2D reconstruction method. On our dedicated reconstruction cluster (seven four-processor systems, Intel PIII@700 MHz, switched fast ethernet and Myrinet, Windows NT Server), we process these 2D sinograms in parallel. We have achieved a speedup > 23 using 26 processors and also compared results for different communication methods (RPC, Syngo, Myrinet GM). The other approach is to parallelize OSEM3D (implementation of C Michel), which has produced the best results for HRRT data so far and is more suitable for an adequate treatment of the sinogram gaps that result from the detector geometry of the HRRT. We have implemented two levels of parallelization for four dedicated cluster (a shared memory fine-grain level on each node utilizing all four processors and a coarse-grain level allowing for 15 nodes) reducing the time for one core iteration from over 7 h to about 35 min.

Algorithms↗

Analysis of the presynaptic signaling mechanisms underlying the inhibition of LTP in rat dentate gyrus by the tyrosine kinase inhibitor, genistein.

A great deal of recent evidence points to a role for tyrosine kinase in expression of LTP. Data have been presented that are consistent with the idea that tyrosine phosphorylation of proteins occurs in both the presynaptic and postsynaptic areas. In this study, we set out to investigate the role that tyrosine kinase might play presynaptically to modulate release of glutamate in an effort to understand the mechanism underlying the persistent increase in release that accompanies LTP in perforant path-granule cell synapses. We report that LTP was associated with increased calcium influx and glutamate release. LTP was also associated with an increase in phosphorylation of the alpha-subunit of calcium channels and ERK in synaptosomes prepared from dentate gyrus, and these effects were inhibited when LTP was blocked by the tyrosine kinase inhibitor, genistein. LTP was accompanied by increased protein synthesis and increased phosphorylation of CREB in entorhinal cortex, effects that were also blocked by genistein. We conclude that tetanic stimulation leads to enhanced tyrosine phosphorylation of certain presynaptically located proteins that modulate glutamate release and contribute to expression of LTP.

Animals↗

Tissue-specific deletion of Foxa2 in pancreatic beta cells results in hyperinsulinemic hypoglycemia.

We have used conditional gene ablation to uncover a dramatic and unpredicted role for the winged-helix transcription factor Foxa2 (formerly HNF-3 beta) in pancreatic beta-cell differentiation and metabolism. Mice that lack Foxa2 specifically in beta cells (Foxa2(loxP/loxP); Ins.Cre mice) are severely hypoglycemic and show dysregulated insulin secretion in response to both glucose and amino acids. This inappropriate hypersecretion of insulin in the face of profound hypoglycemia mimics pathophysiological and molecular aspects of familial hyperinsulinism. We have identified the two subunits of the beta-cell ATP-sensitive K(+) channel (K(ATP)), the most frequently mutated genes linked to familial hyperinsulinism, as novel Foxa2 targets in islets. The Foxa2(loxP/loxP); Ins.Cre mice will serve as a unique model to investigate the regulation of insulin secretion by the beta cell and suggest the human FOXA2 as a candidate gene for familial hyperinsulinism.

Adenosine Triphosphate↗

Identification of a chromosome 11q23.2-q24 locus for familial aortic aneurysm disease, a genetically heterogeneous disorder.

BACKGROUND: Aortic aneurysms cause significant mortality, and >20% relate to hereditary disorders. Familial aortic aneurysm (FAA) has been described in such conditions as the Marfan and Ehlers-Danlos type IV syndromes, due to defects in the fibrillin-1 and type III procollagen genes, respectively. Other gene defects that cause isolated aneurysms, however, have not thus far been described. METHODS AND RESULTS: We studied 3 families affected by FAA. No family met the diagnostic criteria for either Marfan or Ehlers-Danlos syndrome. Echocardiography defined involvement of both the thoracic and abdominal aorta. In family ANA, candidate gene analysis excluded linkage to loci associated with aneurysm formation, including fibrillin-1, fibrillin-2, and type III procollagen, and chromosome 3p24.2-p25. Genome-wide linkage analysis identified a 2.3-cM FAA locus (FAA1) on chromosome 11q23.3-q24 with a maximum multipoint logarithm of the odds score of 4.4. In family ANB, FAA was linked to fibrillin-1. In family ANF, however, FAA was not linked to any locus previously associated with aneurysm formation, including fibrillin-1 and FAA1. CONCLUSIONS: FAA disease is genetically heterogeneous. We have identified a novel FAA locus at chromosome 11q23.3-q24, a critical step toward elucidating 1 gene defect responsible for aortic dilatation. Future characterization of the FAA1 gene will enhance our ability to achieve presymptomatic diagnosis of aortic aneurysms and will define molecular mechanisms to target therapeutics.

Adolescent↗

Action research from the inside: issues and challenges in doing action research in your own hospital.

BACKGROUND AND RATIONALE: Nurses are increasingly engaging in action research projects to improve aspects of nursing practice, education and management and contribute to the development of the profession. Action research involves opportunistic planned interventions in real time situations and a study of those interventions as they occur, which in turn informs further interventions. Insider action research has its own dynamics which distinguish it from an external action researcher approach. The nurse-researchers are normally already immersed in the organization and have a pre-understanding from being an actor in the processes being studied. There is a paucity of literature on the challenges that face nurse action researchers on doing action research in their own hospital. AIM: The aim of this article is to address this paucity by exploring the nature of the challenges which face nurse action researchers. Challenges facing such nurse-researchers are that they frequently need to combine their action research role with their regular organizational roles and this role duality can create the potential for role ambiguity and conflict. They need to manage the political dynamics which involve balancing the hospital's formal justification of what it wants in the project with their own tactical personal justification for the project. MAIN ISSUES: Nurse-researchers' pre-understanding, organizational role and ability to manage hospital politics play an important role in the political process of framing and selecting their action research project. In order that the action research project contribute to the organization's learning, nurse action researchers engages in interlevel processes engaging individuals, teams, the interdepartmental group and the organization in processes of learning and change. CONCLUSIONS: Consideration of these challenges enables nurse-action researchers to grasp the opportunities such research projects afford for personal learning, organizational learning and contribution to knowledge.

Bias↗

The value of digital personal dosemeters in angiography/interventional radiology: preliminary experience.

New interventional procedures tend to involve longer screening times than were hitherto used in radiology. A careful audit of technique and shielding facilities needs to be performed to ensure that patient and operator doses are optimised. This paper explores the use of digital dosemeters to evaluate operator dose. Equipment related parameters, e.g. screening time, dose-area-product (DAP) readings, were not found to be strongly correlated to operator dose. The real time display on the electronic dosemeter is a non-intrusive indicator of the efficacy of operator protection strategies.

Angiography↗

The remediation of problem-solving skills in schizophrenia.

Efforts to remediate the problem-solving deficits of patients with schizophrenia have met with circumscribed success. This could be viewed as a sign of the immutability of the deficit or, alternatively, as a reflection of the inefficacy of the training techniques used. This study examined the feasibility of using problem-solving teaching techniques developed within educational psychology for remediating the problem-solving deficits of inpatients with schizophrenia spectrum disorders. These techniques rely on intrinsic motivation and task engagement, which are promoted through contextualization, personalization, and control of learning activities. A sample of 54 patients who demonstrated problem-solving and memory deficits on psychometric testing were randomly assigned to a problem-solving group, a memory training group, or a control group. Patients who received ten sessions of problem-solving remediation showed significantly more improvement on the outcome measure that assessed problem-solving skills required for independent living. Patients who received ten sessions of memory training did not improve on problem-solving measures. These results suggest that patients with schizophrenia spectrum disorders are responsive to problem-solving training techniques that promote intrinsic motivation and task engagement.

Adult↗

State HMO accreditation and external quality review requirements: implications for HMOs serving rural areas.

The purpose of this article is to analyze state regulations regarding health maintenance organization (HMO) accreditation and external quality review; to briefly describe states' experiences implementing these regulations; and to discuss the implications of these regulations for HMOs serving rural areas. The incorporation of HMO accreditation and external quality review requirements into state HMO licensure processes and state employee contracting raises many policy issues, including several that are especially relevant to HMOs serving rural populations. A key issue is whether the linkage of accreditation and external quality review requirements to HMO licensure will be an additional deterrent to the development of new HMOs or the expansion of existing HMOs into rural areas. Other issues relate to the costs and benefits of accreditation for HMOs serving rural populations, and the potential impact of HMO accreditation requirements on efforts to expand managed care enrollment of rural Medicaid and Medicare beneficiaries and rural state employees. Nine states were identified that have regulations requiring HMOs to seek accreditation or to undergo an external quality review as a condition of licensure. Four states were identified as implementing requirements that an HMO be accredited in order to serve state employees. Many of these requirements are still in the early stages of implementation. Several states with the requirements have significant rural populations and will provide opportunities to evaluate their impact on HMOs serving rural areas, rural providers and rural consumers.

Accreditation↗

A measurement of the efficacy of anticoagulation monitoring in a general practice based setting.

With increasing numbers of patients on anticoagulant therapy and a trend towards moving certain hospital services to a primary care setting, we looked at how GPs are managing Warfarin therapy in their patients. This prospective study measured the efficacy of INR monitoring in 325 patients who were being managed in a general practice setting. 41% (415 of 1016) of readings fell strictly within the target ranges recommended by the British Society for Haematology. There was a low rate of haemorrhagic events (3.7%) in patients on Warfarin. Possible methods of improving readings include the introduction of Decision Support Services and formal training.

Anticoagulants↗