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Richard Scott

Publications and source records attributed to Richard Scott.

At least 19 recordsLinked to original sources
PubMed2025

Assessment of the variant prioritization strategy for genomic newborn screening in the Generation Study.

PURPOSE: Genomic sequencing offers the opportunity to screen for hundreds of rare genetic conditions. To minimize potential negative impact on families and clinical services, it is crucial to reduce false-positive results while prioritizing clinical utility. We present an automated variant prioritization approach in the Generation Study, a research study investigating genomic sequencing in 100,000 newborns in England. Prioritized variants will subsequently undergo manual review by a registered clinical scientist and a specialist clinician before being reported back to parents. METHODS: We assessed specificity of our automated variant prioritization approach in 34,410 samples not enriched for rare diseases and sensitivity in 546 samples from patients with diagnostic variants in genes relevant to newborn screening. We used coverage and copy-number variants callability metrics to evaluate variant detection. RESULTS: We estimated that 3% to 5% of samples will have prioritized variants that require manual review and that <1% of cases will have reportable variants requiring further confirmation of the condition. Sensitivity in genes included in the Generation Study was estimated to be approximately 80%. Gene-level specificity results led to changes in variant prioritization rules and conditions that are included. CONCLUSION: Gene-specific assessment of variant prioritization is crucial to establish analytical validity prior to inclusion in genomic newborn screening.

Humans↗
PubMed2006

Life-threatening bleeding in a patient with a lupus inhibitor and probable acquired factor VII deficiency.

We report the case of a 71-year-old man on warfarin for chronic atrial fibrillation presenting with a massive spontaneous soft tissue bleed. Despite reversing the effects of warfarin with large doses of intravenous vitamin K and fresh frozen plasma, bleeding continued, and his prothrombin time and activated partial thromboplastin time remained prolonged. The prothrombin time and activated partial thromboplastin time failed to correct with 50% normal plasma. Further investigations confirmed a lupus inhibitor with low levels of factors II, V, VII and XI. Factor II, V and XI levels normalized, however, when the patient's plasma was diluted 1:16 in buffer, suggesting the lupus inhibitor may have been interfering with these factor assays causing artefactual low results. Factor VII levels remained consistently low at all dilutions. The patient subsequently died following a massive left haemothorax despite surgical intervention and treatment with activated recombinant factor VII concentrate. We presumed the primary problem was bleeding from a local vascular lesion but the patient was never well enough to undergo confirmatory angiography. This case highlights the fact that patients with lupus inhibitors can develop severe haemorrhagic complications, and illustrates the complexities involved in both the investigation and treatment of abnormal bleeding in these patients.

Aged↗
PubMed2006

A costing model for videoconferencing in Alberta.

The Alberta Telehealth Network uses a provincial scheduling system, which allows use of the network to be monitored via reporting procedures. We developed a province-wide costing model for videoconferencing in Alberta, including administrative, clinical and educational activities. In 2003, there were 212 different videoconferencing sites. During the year, 5766 videoconferencing sessions were provided and in these sessions the sites were connected to the network a total of 21,596 times. About 27% of the connections were from providing sites and about 73% of the connections were from receiving sites. On average, one site in the telehealth system was connected to another site about 100 times, and the average videoconferencing session included about 3.8 sites, varying from mainly two sites in clinical sessions to 4.2 sites in administrative sessions and 6.1 sites in educational sessions. The total cost of videoconferencing in Alberta for administrative, clinical and educational activities was about CA $5.74 million in 2003. About 52% of the annual cost was for educational sessions, 34% for administrative meetings and 14% for clinical consultations. The average cost of videoconferencing at a single site ranged from $223.48 (for providing clinical consultations) to $278.57 (for receiving educational sessions). The costing model provides information for decision-makers about the cost of videoconferencing activities and can be used in the development of a sustainable telehealth system in Alberta.

Alberta↗
PubMed2005

Synthesis of (13)C-labeled gamma-hydroxybutyrates for EPR studies with 4-hydroxybutyryl-CoA dehydratase.

4-Hydroxybutyryl-CoA dehydratase from Clostridium aminobutyricum catalyses the reversible dehydration of its substrate 4-hydroxybutyryl-CoA (4-HB-CoA) to crotonyl CoA. The enzyme contains one [4Fe-4S](2+) cluster and one flavin adenine dinucleotide (FAD) molecule per homotetramer. Incubation of the enzyme with its substrate under equilibrium conditions followed by freezing at 77K induced the EPR-spectrum of a neutral flavin semiquinone (g=2.005, linewidth 2.1 mT), while at 10K additional signals were detected. In an attempt to characterize these signals, 4-HB-CoA molecules specifically labeled with (13)C have been synthesized. This was achieved via (13)C-labeled gamma-butyrolactones, which were obtained from (13)C-labeled bromoacetic acids by efficient synthetic routes. Incubation of the (13)C-labeled 4-hydroxybutyrate-CoA molecules with 4-hydroxybutyryl-CoA dehydratase did not lead to marked broadening of the signals.

Acyl Coenzyme A↗
PubMed2005

Deep brain stimulation for generalised dystonia and spasmodic torticollis.

Dystonia appears distinct from the other tremulous disorders in that improvement following deep brain stimulation frequently appears in a delayed and progressive manner. The rate of this improvement and the point at which no further progress can be expected are presently unknown. The establishment of these parameters is important in the provision of accurate and relevant prognostic information to these patients, their carers, and their treating physicians. We studied 12 consecutive patients with generalised dystonia (n=6) and spasmodic torticollis (n=6) who underwent bilateral globus pallidus internus (GPi) deep brain stimulation (DBS) and were followed up for a minimum of 2 years postoperatively. Standard rating scales were used to quantify their neurological improvement. Both groups experienced a statistically significant improvement in their rating scores at both one and two years following surgery. At 2 years follow-up, the spasmodic torticollis group exhibited a 59% improvement in their total Toronto Western Spasmodic Torticoilis Rating Scale (TWSTRS) rating score and the generalised dystonia group attained a 46% improvement in their overall Burke, Fahn and Marsden Dystonia Rating Scale (BFMDRS) evaluation. Ninety-five percent of the final improvement was attained by 6.4 months in the generalised dystonia group and by 6.6 months in those with spasmodic torticollis. There was no significant improvement after one year postoperatively. These findings add further support to GPi DBS as an effective treatment for generalised dystonia and spasmodic torticollis, and furnish important information as to the expected rate of improvement and the point at which no further gains can be reasonably anticipated.

Adolescent↗
PubMed2004

Balancing severe valgus deformity in total knee arthroplasty using a lateral cruciform retinacular release.

We report the technique and results of a cruciform lateral release performed on 35 consecutive knees having > or =15 degrees of valgus with minimum 2-year follow-up. The posterior cruciate ligament (PCL) was preserved in all knees. Preoperative valgus averaged 17 degrees, and range of motion averaged 10 degrees to 107 degrees. Postoperative valgus averaged 4.8 degrees, and average postoperative range of motion was 2 degrees to 110 degrees. The PCL was partially released in 5 knees, and further lateral release of the lateral collateral ligament and popliteus were required in 3 knees. Stable flexion and extension gaps were achieved in all cases, and stability was maintained at follow-up. This lateral cruciform retinacular release provides a simple surgical technique for most valgus deformities of the knee and allows for stable ligamentous balancing.

Adult↗
PubMed2004

Composition of joint fluid in patients undergoing total knee replacement and revision arthroplasty: correlation with flow properties.

The protein, phospholipid and hyaluronic acid (HA) contents of joint fluid samples were determined in specimens obtained from patients undergoing total knee arthroplasty (TKA) and revision TKA. It was hypothesized that these components would vary widely among patients undergoing TKA, and that the composition of joint fluid in patients undergoing revision would differ from that in patients undergoing revision. It was further hypothesized that HA concentration and molecular weight would principally determine the flow properties previously reported. Biochemical assays were used to assess protein and phospholipid content, and size exclusion chromatography was used to determine HA concentration and molecular weight. Sixty samples were included in the study. HA, protein, and phospholipid concentrations all varied widely in patients undergoing index TKA and revision TKA. HA concentration was lower in patients undergoing revision arthroplasty due to wear-related failure compared to patients undergoing the index procedure (0.9 +/- 0.4 mg/ml versus 1.3 +/- 0.5 mg/ml, mean +/- standard deviation, p = 0.04). Other components were not different between the groups. Flow properties at high shear rates were correlated with HA concentration and, to a lesser extent, HA molecular weight, but neither protein nor phospholipid concentration. The composition of joint fluid is highly variable in the context of arthroplasty. Much of the variation in flow properties, especially at high shear rate, is explained by large variation in HA concentration and small variation in HA molecular weight. The variation in composition and lower HA concentration in joints necessitating revision may relate to variation in arthroplasty lubrication leading to highly variable wear rates and clinical outcomes.

Aged↗
PubMed2004

Biomedical informatics: development of a comprehensive data warehouse for clinical and genomic breast cancer research.

The Windber Research Institute is an integrated high-throughput research center employing clinical, genomic and proteomic platforms to produce terabyte levels of data. We use biomedical informatics technologies to integrate all of these operations. This report includes information on a multi-year, multi-phase hybrid data warehouse project currently under development in the Institute. The purpose of the warehouse is to host the terabyte-level of internal experimentally generated data as well as data from public sources. We have previously reported on the phase I development, which integrated limited internal data sources and selected public databases. Currently, we are completing phase II development, which integrates our internal automated data sources and develops visualization tools to query across these data types. This paper summarizes our clinical and experimental operations, the data warehouse development, and the challenges we have faced. In phase III we plan to federate additional manual internal and public data sources and then to develop and adapt more data analysis and mining tools. We expect that the final implementation of the data warehouse will greatly facilitate biomedical informatics research.

Breast Neoplasms↗
PubMed2004

Risk and protective factors for adult and child hunger among low-income housed and homeless female-headed families.

OBJECTIVES: We sought to identify factors associated with adult or child hunger. METHODS: Low-income housed and homeless mothers were interviewed about socioeconomic, psychosocial, health, and food sufficiency information. Multinomial logistic regression produced models predicting adult or child hunger. RESULTS: Predictors of adult hunger included mothers' childhood sexual molestation and current parenting difficulties, or "hassles." Risk factors for child hunger included mothers' childhood sexual molestation, housing subsidies, brief local residence, having more or older children, and substandard housing. CONCLUSIONS: This study found that the odds of hunger, although affected by resource constraints in low-income female-headed families, were also worsened by mothers' poor physical and mental health. Eliminating hunger thus may require broader interventions than food programs.

Adult↗
PubMed2003

Globus pallidus internus deep brain stimulation for dystonic conditions: a prospective audit.

In the current era of functional surgery for movement disorders, deep brain stimulation (DBS) of the globus pallidus internus (GPi) is emerging as the favoured target in the treatment of patients with dystonia. The results of 25 consecutive patients with medically intractable dystonia (12 with generalised dystonia, 7 with spasmodic torticollis, and 6 with other types of dystonia) treated with GPi stimulation are reported. Although comparisons were limited by differences in their respective neurological rating scales, chronic DBS benefited all groups, resulting in clear and progressive improvements in their condition. This study clearly demonstrates that DBS of the GPi provides amelioration of intractable dystonia.

Adolescent↗
PubMed2002

Camptocormia treated with bilateral pallidal stimulation: case report.

The authors report the neurological, neurophysiological, and neuropsychological effects of using chronic bilateral pallidal high-frequency deep brain stimulation (DBS) in a case of disabling camptocormia. Deep brain stimulation electrodes were implanted stereotactically to target the globus pallidus internus (GPi) bilaterally. Local field potentials (FPs) were recorded using the DBS electrodes and concurrent abdominal flexor electromyography (EMG) potentials during camptocormic episodes. Videotaped assessments of the movement disorder and neuropsychological evaluation before implantation and at 6 months after initiation of pallidal stimulation were recorded. There was significant functional improvement following chronic pallidal stimulation, and some improvement was noted in neuropsychological scores. The GPi FPs showed temporal correlation with EMG-recorded rectus abdominis potentials. There were no treatment-related adverse effects. The authors have found that chronic pallidal stimulation was safe and offered functional benefit in this severely disabling condition. The physiological studies may help further the understanding of the pathophysiology of this rare entity.

Abdominal Muscles↗
PubMed2002

Unilateral and bilateral pallidotomy for idiopathic Parkinson's disease: a case series of 115 patients.

Lesioning of the internal pallidum is known to improve the symptoms of idiopathic Parkinson's disease (PD) and alleviate dyskinesia and motor fluctuations related to levodopa therapy. The benefit obtained contralateral to a single lesion is insufficient in some cases when symptoms are bilaterally disabling. However, reports of unacceptably high rates of adverse effects after bilateral pallidotomy have limited its use in such cases. We report on the outcome of unilateral (UPVP) and bilateral (BPVP) posteroventral pallidotomy in a consecutive case series of 115 patients with PD in the United Kingdom and Australia. After 3 months, UPVP resulted in a 27% reduction in the off medication Part III (motor) Unified Parkinson's Disease Rating Scale score and abolition of dyskinesia in 40% of cases. For BPVP, these figures were increased to 31% and 63%, respectively. Follow-up of a smaller group to 12 months found the motor scores to be worsening but benefit to dyskinesia and activities of daily living was maintained. Speech was adversely affected after BPVP, although the change was small in most cases. Unilateral and bilateral pallidotomy can be performed safely without microelectrode localisation. Bilateral pallidotomy appears to be more effective, particularly in reducing dyskinesia; in our experience, the side effects have not been as high as reported by other groups.

Aged↗
PubMed2002

Quality of life outcomes following surgical treatment of Parkinson's disease.

We assessed the impact of surgical treatment of Parkinson's disease on quality of life using generic quality of life instruments and utility scores. The Medical Outcomes Study short form health survey SF-36 and Parkinson's Disease Questionnaire PDQ-39 were used before and 3-6 months after surgery to assess quality of life, and the results were converted into utility valuations. Ninety-seven patients were studied; 33 underwent unilateral thalamotomy, 33 unilateral pallidotomy, 20 bilateral pallidotomy, six subthalamic nucleus (STN) lesions, four mixed lesions, and in one case bilateral STN stimulation. All dimensions of the SF-36 except role mental and mental health showed statistically significant improvement following surgery. The PDQ-39 recorded significant improvements in the mobility, stigma, and bodily discomfort dimensions. The rating scale and time trade-off scales showed statistically significant gains in utility of 8% and 3%, respectively. Gains were particularly marked in the bilateral pallidotomy group. Differences in patient characteristics and selection made direct comparisons between procedures unreliable. Quality of life in patients with advanced Parkinson's disease is amenable to measurement; such measurement provides tentative evidence of significant gains in quality of life following some neurosurgical procedures.

Adult↗
PubMed2002

Bipolar hemiarthroplasty in juvenile rheumatoid arthritis: long-term survivorship and outcomes.

Because controversy surrounds the management of end-stage hip disease in juvenile rheumatoid arthritis (JRA), this study evaluated the long-term outcome of bipolar hemiarthroplasty as an alternative to conventional joint arthroplasty. A total of 24 JRA patients underwent 39 hemiarthroplasties; follow-up averaged 12 years (range, 3 to 15 years). There were 14 hips (36%) revised, and 25 hips (64%) maintained the original components. Mean Harris hip scores in surviving hips improved from 29 to 69 points (P<.001). Radiographs showed progressive bipolar superomedial migration (P<.01) despite attempted augmentation. Failure defined as revision to total hip arthroplasty or definite radiographic loosening occurred in 15 hips (38%). Ten-year Kaplan-Meier survivorship for all prostheses was 78%. Independent multivariate risk factors for failure included acetabular grafting (P =.006), prosthesis type (P<.001), and unilateral replacement (P<.001).

Adolescent↗