There is substantial interest in the role of rare genetic variants in the etiology of complex hum... more There is substantial interest in the role of rare genetic variants in the etiology of complex human diseases. Several gene-based tests have been developed to simultaneously analyze multiple rare variants for association with phenotypic traits. The tests can largely be partitioned into two classes -'burden' tests and 'joint' tests -based on how they accumulate evidence of association across sites. We used the empirical joint site frequency spectra of rare, nonsynonymous variation from a large multi-population sequencing study to explore the effect of realistic rare variant population structure on gene-based tests. We observed an important difference between the two test classes: their susceptibility to population stratification. Focusing on European samples, we found that joint tests, which allow variants to have opposite directions of effect, consistently showed higher levels of P-value inflation than burden tests. We determined that the differential stratification was caused by two specific patterns in the interpopulation distribution of rare variants, each correlating with inflation in one of the test classes. The pattern that inflates joint tests is more prevalent in real data, explaining the higher levels of inflation in these tests. Furthermore, we show that the different sources of inflation between tests lead to heterogeneous responses to genomic control correction and the number of variants analyzed. Our results indicate that care must be taken when interpreting joint and burden analyses of the same set of rare variants, in particular, to avoid mistaking inflated P-values in joint tests for stronger signals of true associations.
Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology, 2002
Lipid composition of abalone was examined over a one-year interval. A feeding trial was designed ... more Lipid composition of abalone was examined over a one-year interval. A feeding trial was designed to cover a full reproductive cycle in young adult green abalone, Haliotis fulgens, consisting of five diet treatments: the macrophytic algal phaeophyte Egregia menziesii, rhodophyte Chondracanthus canaliculatus, chlorophyte Ulva lobata, a composite of the three algae and a starvation control. The lipid class, fatty acid, sterol and 1-O-alkyl glyceryl ether profiles were determined for foot, hepatopancreasygonad tissues and larvae. The major fatty acids were 16:0, 18:0, 18:1(n-7)c, 18:1(n-9)c, 20:4(n-6), 20:5(n-3) and 22:5(n-3), as well as 14:0 for abalone fed brown and red algae. 4,8,12-Trimethyltridecanoic acid, derived from algae, was detected for the first time in H. fulgens (hepatopancreas complex, 1.2-13.9%; larvae, 0.5% of total fatty acids). Diacylglyceryl ethers were present in larvae (0.6% of total lipid). The major 1-O-alkyl glycerols were 16:0, 16:1 and 18:0. Additionally, 18:1(n-9) was a major component in hepatopancreasygonad and larvae. The major sterol was cholesterol (96-100% of total sterols). Highest growth rates were linked to temperature and occurred in abalone fed the phaeophyte E. menziesii (43 mmØday , 56 mgØday yearly mean), an alga containing the -1 -1
Tardive dyskinesia is a potentially permanent and disfiguring side effect associated with the use... more Tardive dyskinesia is a potentially permanent and disfiguring side effect associated with the use of conventional, or first generation, antipsychotics. Quetiapine is a second generation antipsychotic with transient dopamine receptor occupancy, a property shared with clozapine. Quetiapine was administered to a patient who had persistent choreoathetoid movements that developed during treatment with conventional antipsychotics and remained unimproved during longterm treatment with risperidone. During 10 weeks of monotherapy with quetiapine, his Abnormal Involuntary Movement Scale score fell from 11 to 3. He was subsequently switched back to risperidone and his movements returned. The addition of quetiapine to his risperidone regimen once again resulted in a decrease of his tardive dyskinesia symptoms. The mechanism by which quetiapine improved tardive dyskinesia symptoms in this patient is not known, but differential treatment effects between the novel antipsychotics may exist. Controlled trials of quetiapine in the treatment of tardive dyskinesia should be pursued.
International journal of sport nutrition and exercise metabolism, 2004
In Delayed Onset Muscle Soreness (DOMS), muscles become sore 24 to 48 hours after eccentric and u... more In Delayed Onset Muscle Soreness (DOMS), muscles become sore 24 to 48 hours after eccentric and unaccustomed activity. Fiber stiffness, due to decreased muscle glycogen, may predispose muscle to greater damage during eccentric exercise. This study sought to determine if inadequate carbohydrate intake following a protocol to decrease muscle glycogen would increase DOMS after 15 min of downhill running. Thirty-three male subjects (age, 18-35 years) were randomized into 3 groups for testing over a 7-day period. The depletion (DEP) group (n= 12) underwent a glycogen depletion protocol prior to a 15-min downhill run designed to induce DOMS. The repletion (FED) group (n = 10) underwent a glycogen depletion protocol followed by a carbohydrate repletion protocol (>80% CHO) prior to downhill running. The third (ECC) group (n = 11) performed only the downhill running protocol. Subjective muscle soreness, isometric force production, relaxed knee angle, and thigh circumference were measured pretreatment and on days 1, 2, 3, 4, and 6 post treatment. Subjective muscle soreness for all groups increased from 0 cm pretreatment to 3.05 +/- 0.72 cm (on a 10-cm scale) on day 1 post treatment (p<.05). All groups were significantly different from baseline measurements until day 4 post treatment. Each group experienced a decline in isometric force from 281 +/- 45 N pre- to 253 +/- 13 N on day 1 post treatment (p <.05). The decrease in isometric force persisted in all groups for 4 days post treatment. Increases in thigh circumference and relaxed knee angle elevations in all 3 groups were statistically different (p <.05) from pretreatment until day 4. No differences were noted between groups for any of the parameters examined. In the current study, 15 min of downhill running is sufficient to cause DOMS with the associated functional and morphological changes; however, inadequate carbohydrate intake after a glycogen depleting exercise does not appear to exacerbate DOMS and the associated symptoms.
Quinone-reductase (Q i ) domains of cyanobacterial/ chloroplast cytochrome bf and bacterial/mitoc... more Quinone-reductase (Q i ) domains of cyanobacterial/ chloroplast cytochrome bf and bacterial/mitochondrial bc complexes differ markedly, and the cytochrome bf Q i site mechanism remains largely enigmatic. To investigate the bf Q i domain, we constructed the mutation R214H, which substitutes histidine for a conserved arginine in the cytochrome b 6 polypeptide of the cyanobacterium Synechococcus sp. SPCC 7002. At high light intensity, the R214H mutant grew ϳ2.5-fold more slowly than the wild type. Slower growth arose from correspondingly slower overall turnover of the bf complex. Specifically, as shown in single flash turnover experiments of cytochrome b 6 reduction and oxidation, the R214H mutation partially blocked electron transfer to the Q i site, mimicking the effect of the Q i site inhibitor 2-N-4-hydroxyquinoline-N-oxide. The kinetics of cytochrome b 6 oxidation were largely unaffected by hydrogen-deuterium exchange in the mutant but were slowed considerably in the wild type. This suggests that although protonation events influenced the kinetics of cytochrome b 6 oxidation at the Q i site in the wild type, electron flow limited this reaction in the R214H mutant. Redox titration of membranes revealed midpoint potentials (E m,7 ) of the two b hemes similar to those in the wild type. Our data define cytochrome b 6 Arg 214 as a key residue for Q i site catalysis and turnover of the cytochrome bf complex. In the recent cytochrome bf structures, Arg 214 lies near the Q i pocket and the newly discovered c i or x heme. We propose a model for Q i site function and a role for Arg 214 in plastoquinone binding.
DNA research : an international journal for rapid publication of reports on genes and genomes, 2010
We have developed a dense reference genetic map of Lupinus angustifolius (2n = 40) based on a set... more We have developed a dense reference genetic map of Lupinus angustifolius (2n = 40) based on a set of 106 publicly available recombinant inbred lines derived from a cross between domesticated and wild parental lines. The map comprised 1090 loci in 20 linkage groups and three small clusters, drawing together data from several previous mapping publications plus almost 200 new markers, of which 63 were gene-based markers. A total of 171 mainly gene-based, sequence-tagged site loci served as bridging points for comparing the Lu. angustifolius genome with the genome sequence of the model legume, Lotus japonicus via BLASTn homology searching. Comparative analysis indicated that the genomes of Lu. angustifolius and Lo. japonicus are highly diverged structurally but with significant regions of conserved synteny including the region of the Lu. angustifolius genome containing the pod-shatter resistance gene, lentus. We discuss the potential of synteny analysis for identifying candidate genes for domestication traits in Lu. angustifolius and in improving our understanding of Fabaceae genome evolution.
Cardiovascular disease is the leading cause of death globally. Cardiovascular risk factors predic... more Cardiovascular disease is the leading cause of death globally. Cardiovascular risk factors predict the risk of cardiovascular events in populations but have limitations in predicting individual risk. Emerging technologies that non-invasively measure carotid intima media thickness, aortic pressure and brachial artery reactivity may be useful in identifying the vulnerable patient who may benefit from more aggressive preventive therapy. These tests vary between each other in their reproducibility, cost, required operator skill, availability and patient preparation. However, all require further validation for clinical use as screening tests for cardiovascular disease.
The arterial pulse has historically been an essential source of information in the clinical asses... more The arterial pulse has historically been an essential source of information in the clinical assessment of health. With current sphygmomanometric and oscillometric devices, only the peak and trough of the peripheral arterial pulse waveform are clinically used. Several limitations exist with peripheral blood pressure. First, central aortic pressure is a better predictor of cardiovascular outcome than peripheral pressure. Second, peripherally obtained blood pressure does not accurately reflect central pressure because of pressure amplification. Lastly, antihypertensive medications have differing effects on central pressures despite similar reductions in brachial blood pressure. Applanation tonometry can overcome the limitations of peripheral pressure by determining the shape of the aortic waveform from the radial artery. Waveform analysis not only indicates central systolic and diastolic pressure but also determines the influence of pulse wave reflection on the central pressure waveform. It can serve as a useful adjunct to brachial blood pressure measurements in initiating and monitoring hypertensive treatment, in observing the hemodynamic effects of atherosclerotic risk factors, and in predicting cardiovascular outcomes and events. Radial artery applanation tonometry is a noninvasive, reproducible, and affordable technology that can be used in conjunction with peripherally obtained blood pressure to guide patient management. Keywords for the PubMed search were applanation tonometry, radial artery, central pressure, cardiovascular risk, blood pressure, and arterial pulse. Articles published from January 1, 1995, to July 1, 2009, were included in the review if they measured central pressure using radial artery applanation tonometry.
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography, 2011
Background: The value of epicardial adipose tissue (EAT) thickness as determined by echocardiogra... more Background: The value of epicardial adipose tissue (EAT) thickness as determined by echocardiography in cardiovascular risk assessment is not well understood. The aim of this study was to determine the associations between EAT thickness and Framingham risk score, carotid intima media thickness, carotid artery plaque, and computed tomographic coronary calcium score in a primary prevention population.
Genome / National Research Council Canada = Génome / Conseil national de recherches Canada, 2011
The organisation of the Sinapis alba genome, comprising 12 linkage groups (n = 12), was compared ... more The organisation of the Sinapis alba genome, comprising 12 linkage groups (n = 12), was compared with the Brassicaceae ancestral karyotype (AK) genomic blocks previously described in other crucifer species. Most of the S. alba genome falls into conserved triplicated genomic blocks that closely match the AK-defined genomic blocks found in other crucifer species including the A, B, and C genomes of closely related Brassica species. In one instance, an S. alba linkage group (S05) was completely collinear with one AK chromosome (AK1), the first time this has been observed in a member of the Brassiceae tribe. However, as observed for other members of the Brassiceae tribe, ancestral genomic blocks were fragmented in the S. alba genome, supporting previously reported comparative chromosome painting describing rearrangements of the AK karyotype prior to the divergence of the Brassiceae from other crucifers. The presented data also refute previous phylogenetic reports that suggest S. alba was more closely related to Brassica nigra (B genome) than to B. rapa (A genome) and B. oleracea (C genome). A comparison of the S. alba and Arabidopsis thaliana genomes revealed many regions of conserved gene order, which will facilitate access to the rich genomic resources available in the model species A. thaliana for genetic research in the less well-resourced crop species S. alba.
Prehospital emergency care : official journal of the National Association of EMS Physicians and the National Association of State EMS Directors
We present a case of successful resuscitation from cardiac arrest after 25 minutes of ventricular... more We present a case of successful resuscitation from cardiac arrest after 25 minutes of ventricular fibrillation (VF) secondary to peripartum cardiomyopathy. This case highlights a rare disease, but also, more importantly, the successful use of the five links of survival: early access to 9-1-1, early cardiopulmonary resuscitation (CPR), early defibrillation, early advanced life support, and postresuscitative care. We also demonstrate the importance of high-quality resuscitation practices in order to achieve a successful outcome. Manual compressions can be performed at a guidelines-compliant rate. With training, users are able to achieve high compression fractions. Pre/post shock delays can be minimized to further increase compression fraction. Nationally, CPR interruptions are often long. We recommend closer attention to uninterrupted 2-minute cycles of CPR, minimizing delays in CPR through training, and a focus on a closely choreographed approach. User review of transthoracic impedance feedback data should play a vital role in a cardiac arrest quality-improvement program.
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography, 2012
Background: Multiple vendor-specific two-dimensional speckle-tracking echocardiographic algorithm... more Background: Multiple vendor-specific two-dimensional speckle-tracking echocardiographic algorithms with which to characterize myocardial mechanics are commercially available. The purpose of this study was to compare global longitudinal strain (GLS) results between two independent software vendors using a neutral image platform.
The objective was to develop a preoperative mortality risk stratification tool for patients facin... more The objective was to develop a preoperative mortality risk stratification tool for patients facing major amputation. Patients who underwent above-knee (AKA) or below-knee amputation (BKA) from 2005 to 2010 were identified from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database. Univariate and multivariate analyses were performed to determine the association of preoperative factors with 30-day mortality. Multivariable models were used to create a computerized prediction tool. Of 9,368 patients, 4,032 underwent AKA and 5,336 BKA. The 30-day mortality rate after AKA was 12.8%, almost double that of BKA (6.5%, P < .001). The complication rate was statistically greater after AKA although numerically similar (28.5% vs 26.6%, P = .020), whereas the rate of reoperation was substantially greater after BKA (22.7% vs 11.7%, P < .001). Preoperative factors that predicted mortality after both procedures included older age, dependent functional status, dialysis, steroid use, preoperative sepsis, delirium, thrombocytopenia, increased international normalized ratio, and azotemia. Prediction tools were developed and validated, and their concordance indices were 0.75 for AKA and 0.81 for BKA, indicating good predictive accuracy. Preoperative factors predict mortality after major amputation, and the risk calculator that we have developed may facilitate informed decision-making and provide realistic expectations for surgeons and patients faced with limb-threatening disease.
We analysed 42 dierentiated thyroid tumors including 15 follicular adenomas (FA), 13 papillary th... more We analysed 42 dierentiated thyroid tumors including 15 follicular adenomas (FA), 13 papillary thyroid cancers (PTC) and 14 follicular thyroid carcinomas (FTC) with 13 microsatellite markers speci®c for the long arm of human chromosome 7 within 7q31; this region is deleted frequently in several other tumor types. Overall, 20 of the 42 samples analysed (48%) displayed LOH with one or more of the markers tested. LOH was detected most frequently (78%) in FTC, the most malignant of the thyroid tumors. A smallest common deleted region (SCDR) was de®ned in this tumor typē anked by markers D7S480 and D7S490. This SCDR is distinct from D7S522, the most commonly deleted locus in many other tumors, which was deleted in only one FTC. D7S522 did show LOH in two of six informative PTCs. None of the PTC and only two of the FAs showed LOH in the FTC SCDR. Since FA is considered a premalignant stage of FTC, our results suggest that inactivation of a putative tumor suppressor at 7q31.2 may be acquired during adenoma to carcinoma progression. The absence of LOH at this locus amongst PTC suggests that inactivation of this tumor suppressor is speci®c for FTC. In conclusion, LOH at 7q31 is a frequent event in dierentiated thyroid cancer, and we have de®ned a 2 cM SCDR speci®c for FTC.
There is substantial interest in the role of rare genetic variants in the etiology of complex hum... more There is substantial interest in the role of rare genetic variants in the etiology of complex human diseases. Several gene-based tests have been developed to simultaneously analyze multiple rare variants for association with phenotypic traits. The tests can largely be partitioned into two classes -'burden' tests and 'joint' tests -based on how they accumulate evidence of association across sites. We used the empirical joint site frequency spectra of rare, nonsynonymous variation from a large multi-population sequencing study to explore the effect of realistic rare variant population structure on gene-based tests. We observed an important difference between the two test classes: their susceptibility to population stratification. Focusing on European samples, we found that joint tests, which allow variants to have opposite directions of effect, consistently showed higher levels of P-value inflation than burden tests. We determined that the differential stratification was caused by two specific patterns in the interpopulation distribution of rare variants, each correlating with inflation in one of the test classes. The pattern that inflates joint tests is more prevalent in real data, explaining the higher levels of inflation in these tests. Furthermore, we show that the different sources of inflation between tests lead to heterogeneous responses to genomic control correction and the number of variants analyzed. Our results indicate that care must be taken when interpreting joint and burden analyses of the same set of rare variants, in particular, to avoid mistaking inflated P-values in joint tests for stronger signals of true associations.
Comparative biochemistry and physiology. Part B, Biochemistry & molecular biology, 2002
Lipid composition of abalone was examined over a one-year interval. A feeding trial was designed ... more Lipid composition of abalone was examined over a one-year interval. A feeding trial was designed to cover a full reproductive cycle in young adult green abalone, Haliotis fulgens, consisting of five diet treatments: the macrophytic algal phaeophyte Egregia menziesii, rhodophyte Chondracanthus canaliculatus, chlorophyte Ulva lobata, a composite of the three algae and a starvation control. The lipid class, fatty acid, sterol and 1-O-alkyl glyceryl ether profiles were determined for foot, hepatopancreasygonad tissues and larvae. The major fatty acids were 16:0, 18:0, 18:1(n-7)c, 18:1(n-9)c, 20:4(n-6), 20:5(n-3) and 22:5(n-3), as well as 14:0 for abalone fed brown and red algae. 4,8,12-Trimethyltridecanoic acid, derived from algae, was detected for the first time in H. fulgens (hepatopancreas complex, 1.2-13.9%; larvae, 0.5% of total fatty acids). Diacylglyceryl ethers were present in larvae (0.6% of total lipid). The major 1-O-alkyl glycerols were 16:0, 16:1 and 18:0. Additionally, 18:1(n-9) was a major component in hepatopancreasygonad and larvae. The major sterol was cholesterol (96-100% of total sterols). Highest growth rates were linked to temperature and occurred in abalone fed the phaeophyte E. menziesii (43 mmØday , 56 mgØday yearly mean), an alga containing the -1 -1
Tardive dyskinesia is a potentially permanent and disfiguring side effect associated with the use... more Tardive dyskinesia is a potentially permanent and disfiguring side effect associated with the use of conventional, or first generation, antipsychotics. Quetiapine is a second generation antipsychotic with transient dopamine receptor occupancy, a property shared with clozapine. Quetiapine was administered to a patient who had persistent choreoathetoid movements that developed during treatment with conventional antipsychotics and remained unimproved during longterm treatment with risperidone. During 10 weeks of monotherapy with quetiapine, his Abnormal Involuntary Movement Scale score fell from 11 to 3. He was subsequently switched back to risperidone and his movements returned. The addition of quetiapine to his risperidone regimen once again resulted in a decrease of his tardive dyskinesia symptoms. The mechanism by which quetiapine improved tardive dyskinesia symptoms in this patient is not known, but differential treatment effects between the novel antipsychotics may exist. Controlled trials of quetiapine in the treatment of tardive dyskinesia should be pursued.
International journal of sport nutrition and exercise metabolism, 2004
In Delayed Onset Muscle Soreness (DOMS), muscles become sore 24 to 48 hours after eccentric and u... more In Delayed Onset Muscle Soreness (DOMS), muscles become sore 24 to 48 hours after eccentric and unaccustomed activity. Fiber stiffness, due to decreased muscle glycogen, may predispose muscle to greater damage during eccentric exercise. This study sought to determine if inadequate carbohydrate intake following a protocol to decrease muscle glycogen would increase DOMS after 15 min of downhill running. Thirty-three male subjects (age, 18-35 years) were randomized into 3 groups for testing over a 7-day period. The depletion (DEP) group (n= 12) underwent a glycogen depletion protocol prior to a 15-min downhill run designed to induce DOMS. The repletion (FED) group (n = 10) underwent a glycogen depletion protocol followed by a carbohydrate repletion protocol (>80% CHO) prior to downhill running. The third (ECC) group (n = 11) performed only the downhill running protocol. Subjective muscle soreness, isometric force production, relaxed knee angle, and thigh circumference were measured pretreatment and on days 1, 2, 3, 4, and 6 post treatment. Subjective muscle soreness for all groups increased from 0 cm pretreatment to 3.05 +/- 0.72 cm (on a 10-cm scale) on day 1 post treatment (p<.05). All groups were significantly different from baseline measurements until day 4 post treatment. Each group experienced a decline in isometric force from 281 +/- 45 N pre- to 253 +/- 13 N on day 1 post treatment (p <.05). The decrease in isometric force persisted in all groups for 4 days post treatment. Increases in thigh circumference and relaxed knee angle elevations in all 3 groups were statistically different (p <.05) from pretreatment until day 4. No differences were noted between groups for any of the parameters examined. In the current study, 15 min of downhill running is sufficient to cause DOMS with the associated functional and morphological changes; however, inadequate carbohydrate intake after a glycogen depleting exercise does not appear to exacerbate DOMS and the associated symptoms.
Quinone-reductase (Q i ) domains of cyanobacterial/ chloroplast cytochrome bf and bacterial/mitoc... more Quinone-reductase (Q i ) domains of cyanobacterial/ chloroplast cytochrome bf and bacterial/mitochondrial bc complexes differ markedly, and the cytochrome bf Q i site mechanism remains largely enigmatic. To investigate the bf Q i domain, we constructed the mutation R214H, which substitutes histidine for a conserved arginine in the cytochrome b 6 polypeptide of the cyanobacterium Synechococcus sp. SPCC 7002. At high light intensity, the R214H mutant grew ϳ2.5-fold more slowly than the wild type. Slower growth arose from correspondingly slower overall turnover of the bf complex. Specifically, as shown in single flash turnover experiments of cytochrome b 6 reduction and oxidation, the R214H mutation partially blocked electron transfer to the Q i site, mimicking the effect of the Q i site inhibitor 2-N-4-hydroxyquinoline-N-oxide. The kinetics of cytochrome b 6 oxidation were largely unaffected by hydrogen-deuterium exchange in the mutant but were slowed considerably in the wild type. This suggests that although protonation events influenced the kinetics of cytochrome b 6 oxidation at the Q i site in the wild type, electron flow limited this reaction in the R214H mutant. Redox titration of membranes revealed midpoint potentials (E m,7 ) of the two b hemes similar to those in the wild type. Our data define cytochrome b 6 Arg 214 as a key residue for Q i site catalysis and turnover of the cytochrome bf complex. In the recent cytochrome bf structures, Arg 214 lies near the Q i pocket and the newly discovered c i or x heme. We propose a model for Q i site function and a role for Arg 214 in plastoquinone binding.
DNA research : an international journal for rapid publication of reports on genes and genomes, 2010
We have developed a dense reference genetic map of Lupinus angustifolius (2n = 40) based on a set... more We have developed a dense reference genetic map of Lupinus angustifolius (2n = 40) based on a set of 106 publicly available recombinant inbred lines derived from a cross between domesticated and wild parental lines. The map comprised 1090 loci in 20 linkage groups and three small clusters, drawing together data from several previous mapping publications plus almost 200 new markers, of which 63 were gene-based markers. A total of 171 mainly gene-based, sequence-tagged site loci served as bridging points for comparing the Lu. angustifolius genome with the genome sequence of the model legume, Lotus japonicus via BLASTn homology searching. Comparative analysis indicated that the genomes of Lu. angustifolius and Lo. japonicus are highly diverged structurally but with significant regions of conserved synteny including the region of the Lu. angustifolius genome containing the pod-shatter resistance gene, lentus. We discuss the potential of synteny analysis for identifying candidate genes for domestication traits in Lu. angustifolius and in improving our understanding of Fabaceae genome evolution.
Cardiovascular disease is the leading cause of death globally. Cardiovascular risk factors predic... more Cardiovascular disease is the leading cause of death globally. Cardiovascular risk factors predict the risk of cardiovascular events in populations but have limitations in predicting individual risk. Emerging technologies that non-invasively measure carotid intima media thickness, aortic pressure and brachial artery reactivity may be useful in identifying the vulnerable patient who may benefit from more aggressive preventive therapy. These tests vary between each other in their reproducibility, cost, required operator skill, availability and patient preparation. However, all require further validation for clinical use as screening tests for cardiovascular disease.
The arterial pulse has historically been an essential source of information in the clinical asses... more The arterial pulse has historically been an essential source of information in the clinical assessment of health. With current sphygmomanometric and oscillometric devices, only the peak and trough of the peripheral arterial pulse waveform are clinically used. Several limitations exist with peripheral blood pressure. First, central aortic pressure is a better predictor of cardiovascular outcome than peripheral pressure. Second, peripherally obtained blood pressure does not accurately reflect central pressure because of pressure amplification. Lastly, antihypertensive medications have differing effects on central pressures despite similar reductions in brachial blood pressure. Applanation tonometry can overcome the limitations of peripheral pressure by determining the shape of the aortic waveform from the radial artery. Waveform analysis not only indicates central systolic and diastolic pressure but also determines the influence of pulse wave reflection on the central pressure waveform. It can serve as a useful adjunct to brachial blood pressure measurements in initiating and monitoring hypertensive treatment, in observing the hemodynamic effects of atherosclerotic risk factors, and in predicting cardiovascular outcomes and events. Radial artery applanation tonometry is a noninvasive, reproducible, and affordable technology that can be used in conjunction with peripherally obtained blood pressure to guide patient management. Keywords for the PubMed search were applanation tonometry, radial artery, central pressure, cardiovascular risk, blood pressure, and arterial pulse. Articles published from January 1, 1995, to July 1, 2009, were included in the review if they measured central pressure using radial artery applanation tonometry.
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography, 2011
Background: The value of epicardial adipose tissue (EAT) thickness as determined by echocardiogra... more Background: The value of epicardial adipose tissue (EAT) thickness as determined by echocardiography in cardiovascular risk assessment is not well understood. The aim of this study was to determine the associations between EAT thickness and Framingham risk score, carotid intima media thickness, carotid artery plaque, and computed tomographic coronary calcium score in a primary prevention population.
Genome / National Research Council Canada = Génome / Conseil national de recherches Canada, 2011
The organisation of the Sinapis alba genome, comprising 12 linkage groups (n = 12), was compared ... more The organisation of the Sinapis alba genome, comprising 12 linkage groups (n = 12), was compared with the Brassicaceae ancestral karyotype (AK) genomic blocks previously described in other crucifer species. Most of the S. alba genome falls into conserved triplicated genomic blocks that closely match the AK-defined genomic blocks found in other crucifer species including the A, B, and C genomes of closely related Brassica species. In one instance, an S. alba linkage group (S05) was completely collinear with one AK chromosome (AK1), the first time this has been observed in a member of the Brassiceae tribe. However, as observed for other members of the Brassiceae tribe, ancestral genomic blocks were fragmented in the S. alba genome, supporting previously reported comparative chromosome painting describing rearrangements of the AK karyotype prior to the divergence of the Brassiceae from other crucifers. The presented data also refute previous phylogenetic reports that suggest S. alba was more closely related to Brassica nigra (B genome) than to B. rapa (A genome) and B. oleracea (C genome). A comparison of the S. alba and Arabidopsis thaliana genomes revealed many regions of conserved gene order, which will facilitate access to the rich genomic resources available in the model species A. thaliana for genetic research in the less well-resourced crop species S. alba.
Prehospital emergency care : official journal of the National Association of EMS Physicians and the National Association of State EMS Directors
We present a case of successful resuscitation from cardiac arrest after 25 minutes of ventricular... more We present a case of successful resuscitation from cardiac arrest after 25 minutes of ventricular fibrillation (VF) secondary to peripartum cardiomyopathy. This case highlights a rare disease, but also, more importantly, the successful use of the five links of survival: early access to 9-1-1, early cardiopulmonary resuscitation (CPR), early defibrillation, early advanced life support, and postresuscitative care. We also demonstrate the importance of high-quality resuscitation practices in order to achieve a successful outcome. Manual compressions can be performed at a guidelines-compliant rate. With training, users are able to achieve high compression fractions. Pre/post shock delays can be minimized to further increase compression fraction. Nationally, CPR interruptions are often long. We recommend closer attention to uninterrupted 2-minute cycles of CPR, minimizing delays in CPR through training, and a focus on a closely choreographed approach. User review of transthoracic impedance feedback data should play a vital role in a cardiac arrest quality-improvement program.
Journal of the American Society of Echocardiography : official publication of the American Society of Echocardiography, 2012
Background: Multiple vendor-specific two-dimensional speckle-tracking echocardiographic algorithm... more Background: Multiple vendor-specific two-dimensional speckle-tracking echocardiographic algorithms with which to characterize myocardial mechanics are commercially available. The purpose of this study was to compare global longitudinal strain (GLS) results between two independent software vendors using a neutral image platform.
The objective was to develop a preoperative mortality risk stratification tool for patients facin... more The objective was to develop a preoperative mortality risk stratification tool for patients facing major amputation. Patients who underwent above-knee (AKA) or below-knee amputation (BKA) from 2005 to 2010 were identified from the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) database. Univariate and multivariate analyses were performed to determine the association of preoperative factors with 30-day mortality. Multivariable models were used to create a computerized prediction tool. Of 9,368 patients, 4,032 underwent AKA and 5,336 BKA. The 30-day mortality rate after AKA was 12.8%, almost double that of BKA (6.5%, P < .001). The complication rate was statistically greater after AKA although numerically similar (28.5% vs 26.6%, P = .020), whereas the rate of reoperation was substantially greater after BKA (22.7% vs 11.7%, P < .001). Preoperative factors that predicted mortality after both procedures included older age, dependent functional status, dialysis, steroid use, preoperative sepsis, delirium, thrombocytopenia, increased international normalized ratio, and azotemia. Prediction tools were developed and validated, and their concordance indices were 0.75 for AKA and 0.81 for BKA, indicating good predictive accuracy. Preoperative factors predict mortality after major amputation, and the risk calculator that we have developed may facilitate informed decision-making and provide realistic expectations for surgeons and patients faced with limb-threatening disease.
We analysed 42 dierentiated thyroid tumors including 15 follicular adenomas (FA), 13 papillary th... more We analysed 42 dierentiated thyroid tumors including 15 follicular adenomas (FA), 13 papillary thyroid cancers (PTC) and 14 follicular thyroid carcinomas (FTC) with 13 microsatellite markers speci®c for the long arm of human chromosome 7 within 7q31; this region is deleted frequently in several other tumor types. Overall, 20 of the 42 samples analysed (48%) displayed LOH with one or more of the markers tested. LOH was detected most frequently (78%) in FTC, the most malignant of the thyroid tumors. A smallest common deleted region (SCDR) was de®ned in this tumor typē anked by markers D7S480 and D7S490. This SCDR is distinct from D7S522, the most commonly deleted locus in many other tumors, which was deleted in only one FTC. D7S522 did show LOH in two of six informative PTCs. None of the PTC and only two of the FAs showed LOH in the FTC SCDR. Since FA is considered a premalignant stage of FTC, our results suggest that inactivation of a putative tumor suppressor at 7q31.2 may be acquired during adenoma to carcinoma progression. The absence of LOH at this locus amongst PTC suggests that inactivation of this tumor suppressor is speci®c for FTC. In conclusion, LOH at 7q31 is a frequent event in dierentiated thyroid cancer, and we have de®ned a 2 cM SCDR speci®c for FTC.
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Papers by Matthew Nelson