The incidence of acute kidney injury in neonates is high and associated with up to a 50% mortalit... more The incidence of acute kidney injury in neonates is high and associated with up to a 50% mortality rate. The purpose of this review was to determine the feasibility of using serum cystatin C measurements to assist clinicians in making early and accurate diagnoses of acute kidney injury in neonates. We searched for the following seven key words within the PubMed database and the Cochrane Database of Systematic Reviews: cystatin C, neonates, newborn, preterm, premature, kidney failure, and kidney injury. The selected studies included neonates within their study populations and were published in English. We reviewed literature published between January 1990 and May 2012. Ten studies had conducted serum cystatin C measurements in neonates. The cystatin C level in neonates is not influenced by the maternal level and is highest at birth. In most studies, cystatin C levels on day 1 of life ranged between 1 and 2 mg/L, gradually declined during the first year and then remained relatively stable thereafter. Cystatin C levels did not differ between male and female infants, and no significant gestational age-dependent differences were found. Cystatin C levels were increased in cases of sepsis, acute kidney injury, and congenital renal abnormalities. Cystatin C has all of the theoretical properties needed to be an ideal marker of renal function. It can be used to determine baseline renal function on day 1 and is increasingly being used to determine renal function in sick neonates. In the majority of studies, the day 1 cystatin C level ranged between 1 and 2 mg/L, which gradually declined in the first year of life. However, the number of available studies evaluating cystatin C in sick neonates is currently limited, and there are also no studies linking cystatin C levels in sick babies with short-term and long-term outcomes.
Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 1994
Asymptotic and numerical formulae for the time integral tau which is required in the simulation o... more Asymptotic and numerical formulae for the time integral tau which is required in the simulation of a binary collision encounter are developed for some screened Coulomb potentials. These formulae are much faster to evaluate than those calculated by numerical integration and more accurate than the commonly used hard sphere approximation.
Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 2005
A mathematical model to describe processes occurring during the irradiation of semiconductor mate... more A mathematical model to describe processes occurring during the irradiation of semiconductor materials with high power pulsed ion beams is proposed. The model takes account of recombination between vacancies and interstitial atoms and the formation of defect complexes and these processes are analysed and discussed. The effect of an inhomogeneous non-stationary temperature field and mechanical quasi-static and dynamic stress fields on radiation defect profiles is also examined. Spatial profiles of the charge carrier concentration and the implanted ion distribution are calculated and a comparison made with experimental profiles obtained for the semiconductor compound Hg 1Àx Cd x Te. The results show that the defect concentration profiles near the surface are reduced with a large rate of recombination between vacancy and interstitial atoms.
Although the application of reconstructive vascular surgical procedures to the treatment of carot... more Although the application of reconstructive vascular surgical procedures to the treatment of carotid paragangliomas has made their resection the method of choice and has produced excellent cure rates, it has not obviated some of the technical problems presented by excessively vascular, adherent, or bulky lesions. Our experience with preoperative transcatheter embolization for the reduction of the vascularity in six cases of this group of lesions is presented and the conclusion is made that preoperative embolization greatly reduced operative technical difficulties.
Clinical and metabolomic investigations of complex human fluids require cost-effective methodolog... more Clinical and metabolomic investigations of complex human fluids require cost-effective methodologies that can rapidly assess the steroid hormone milieu of individual samples. The efficiency of quantification of many steroids is limited using immunoassays as these methods can only measure a single component of biological samples and are dependent upon the specificity of the antiserum used in the protocol. In this study, we optimised the solid-phase extraction protocol for the extraction of a range of steroids of varied polarity from estetrol to progesterone from human plasma. The final SPE procedure for efficient extraction of steroids was a washing mixture of 5 ml of 30% methanol and an elution solvent of 2 ml of 100% methanol using 0.5 g C-18 cartridges. This protocol resulted in a high recovery rate, ranging from 85.2 to 99.9% for both the internal standard (7,8-dimethoxyflavone) and steroids of interest. We also improved the separation methodology of our previous work using temperature dependent inclusion chromatography with a mobile phase composition of 35% acetonitrile and 12 mM of beta-cyclodextrin at 29 degrees C. Under these conditions most of the fluid components including estetrol were detected in the first 10 min with progesterone appearing at 43 min. This method is simplistic, inexpensive and reproducible with the capabilities of accurate quantification of steroids. Therefore it could have numerous clinical and metabolomic applications.
The etiology of idiopathic scoliosis remains unknown. The condition results in a characteristic d... more The etiology of idiopathic scoliosis remains unknown. The condition results in a characteristic deformity of the spine and surrounding tissues. Both Types I and II collagen are important constituents of the affected tissues, and thus defective collagens are reasonable candidates for the primary abnormality in adolescent idiopathic scoliosis (AIS). Direct analyses of the amount and solubility of collagen have revealed differences between normal individuals and those with AIS. However, these changes may be secondary to the mechanical effects of the spinal deformity. Segregation analysis was done of genetic markers linked to the structural genes encoding Types I and II collagen to test these candidate loci in four pedigrees with dominantly inherited AIS. In one pedigree, markers linked to both of the Type I collagen loci (COL1A1 and COL1A2) were found to be inherited independently of the abnormal phenotype. Two pedigrees were discordant at one of the Type I loci. The condition also segregated independently of the locus for Type II collagen (COL2A1) in three pedigrees. This is evidence against idiopathic scoliosis generally being caused by mutations in the Types I and II collagen genes.
A series of pyrrolopyridinones was designed and synthesized as constrained analogs of the pyrazol... more A series of pyrrolopyridinones was designed and synthesized as constrained analogs of the pyrazole CB-1 antagonist rimonabant. Certain examples exhibited very potent hCB-1 receptor binding affinity and functional antagonism with Ki and Kb values below 10 nM, and with high selectivity for CB-1 over CB-2 (>100-fold). A representative analog was established to cause significant appetite suppression and reduction in body weight gain in industry-standard rat models used to develop new therapeutics for obesity.
MAP kinase p38 has been implicated in cytokine signaling, and its inhibitors are potentially usef... more MAP kinase p38 has been implicated in cytokine signaling, and its inhibitors are potentially useful for the treatment of arthritis and osteoporosis. Novel small-molecule inhibitors of p38 kinase were derived from a combinatorial chemistry eort and exhibit activity in the nanomolar range. Very steep structure±activity relationships are observed within this class.
(Acy1oxy)methyl ketones, of general structure Z-[AA2]-[AA1]-CH20COAr, are potent inac-'This work ... more (Acy1oxy)methyl ketones, of general structure Z-[AA2]-[AA1]-CH20COAr, are potent inac-'This work has been supported by grants from the Natural Sciences and Engineering Research Council. R.S.P. would also like to acknowledge NSERC for graduate studies scholarships.
Aims: To evaluate the effect of automated external defibrillators (AEDs) on patient survival and ... more Aims: To evaluate the effect of automated external defibrillators (AEDs) on patient survival and to describe the performance of AEDs after in-hospital cardiac arrest. Methods: Prospectively collected data were analysed for cardiac arrests in the general patient care areas of a teaching hospital during the 3 years before and the 3 years after the deployment of AEDs. The association between availability of an AED and survival to hospital discharge was assessed using multivariate logistic regression. AED performance during automated management of the initial rhythms was assessed using information captured by the AEDs. Results: There were 84 cardiac arrests in the AED period and 82 in the pre-AED period. Patient and event characteristics were similar in each period. The initial rhythm was shockable in 16% of cases. Return of spontaneous circulation was higher in the AED period (54% vs. 35%, P = 0.02) but the proportion of hospital survivors in each period was similar (22% vs. 19%, P = 0.56). The adjusted odds ratio for hospital survival when an AED was available was 1.22 (95% CI 0.53-2.84, P = 0.64). An AED was applied in 77/84 (92%) possible cases. Median interruption to chest compressions was 12 s (inter-quartile range 12-13). An automated shock was delivered in 8/13 (62%) possible cases. Conclusions: Availability of AEDs was not independently associated with hospital survival. Shockable presenting rhythms were not common and, in keeping with the manufacturer's specifications, the AEDs did not shock all potentially shockable rhythms. The hands-off time associated with automated rhythm management was considerable.
Cold fronts frequently migrate equatorwards across Australia, penetrating deep into the subtropic... more Cold fronts frequently migrate equatorwards across Australia, penetrating deep into the subtropics. They regularly reach as far north as the Gulf of Carpentaria (around 17°S), and occasionally push northward of Darwin (12°S). (The locations of places named in the text are shown in Fig. 1.) The synoptic environment of these fronts is similar to that of the summertime cool change of southeastern Australia (Reeder and
Formal overspill schemes, linked with slum clearance programmes, have been major elements in many... more Formal overspill schemes, linked with slum clearance programmes, have been major elements in many postwar metropolitan planning strategies. Until recently few politicians or administrators involved in such exercises questioned. at least overtly, the need to redevelop comprehensively the central area slums and. in order to contain the peripheral growth of the cities. rehouse many of those who would thereby be displaced in new and expanded towns. Attitudes are now changing. Social planners have become concerned about the harm done by breaking up what they see as integrated communities. Demographers, in reassessing population predictions. have concluded that natural increase generated in the cities is now likely to be far less than was thought during the 1960s. And economists query the cost effectiveness of dealing with poor housing through the mechanism of comprehensive redevelopment and formal overspill. It is not the purpose of this paper to debate these issues. Rather the aim is to undertake a preliminary exploration into how slum clearance and overspill became galvanized in the Scottish context during the 1950s. By examining how the situation appeared to contemporaries and how the various facets for change integrated. it is hoped that some insights will be offered to parties involved in the more urgent contemporary debate. Effectively a discussion of the evolution of formal overspill policies in Scotland means discussing the evolution of formal overspill policies for Glasgow and an earlier paper has described how they came to be established in the immediate postwar years.' Glasgow, a city dominated by high density tenements, had a major overcrowding problem to contend with and a solution was offered in the 1964 Clyde Valley Regional Plan2 which recommended that 500,000 of the city's one million population should be decanted from the central areas if densities *I am grateful for information for this paper from discussions with Lord Strathclyde, the Rt. Hon. Arthur Woodburn, Dame Jean Roberts, Professor Sir Robert Grieve, Mr. J. Armour and Mr. J. H. McGuinness. However, I alone am responsible for the accuracy of all facts and interpretations.
The incidence of acute kidney injury in neonates is high and associated with up to a 50% mortalit... more The incidence of acute kidney injury in neonates is high and associated with up to a 50% mortality rate. The purpose of this review was to determine the feasibility of using serum cystatin C measurements to assist clinicians in making early and accurate diagnoses of acute kidney injury in neonates. We searched for the following seven key words within the PubMed database and the Cochrane Database of Systematic Reviews: cystatin C, neonates, newborn, preterm, premature, kidney failure, and kidney injury. The selected studies included neonates within their study populations and were published in English. We reviewed literature published between January 1990 and May 2012. Ten studies had conducted serum cystatin C measurements in neonates. The cystatin C level in neonates is not influenced by the maternal level and is highest at birth. In most studies, cystatin C levels on day 1 of life ranged between 1 and 2 mg/L, gradually declined during the first year and then remained relatively stable thereafter. Cystatin C levels did not differ between male and female infants, and no significant gestational age-dependent differences were found. Cystatin C levels were increased in cases of sepsis, acute kidney injury, and congenital renal abnormalities. Cystatin C has all of the theoretical properties needed to be an ideal marker of renal function. It can be used to determine baseline renal function on day 1 and is increasingly being used to determine renal function in sick neonates. In the majority of studies, the day 1 cystatin C level ranged between 1 and 2 mg/L, which gradually declined in the first year of life. However, the number of available studies evaluating cystatin C in sick neonates is currently limited, and there are also no studies linking cystatin C levels in sick babies with short-term and long-term outcomes.
Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 1994
Asymptotic and numerical formulae for the time integral tau which is required in the simulation o... more Asymptotic and numerical formulae for the time integral tau which is required in the simulation of a binary collision encounter are developed for some screened Coulomb potentials. These formulae are much faster to evaluate than those calculated by numerical integration and more accurate than the commonly used hard sphere approximation.
Nuclear Instruments and Methods in Physics Research Section B: Beam Interactions with Materials and Atoms, 2005
A mathematical model to describe processes occurring during the irradiation of semiconductor mate... more A mathematical model to describe processes occurring during the irradiation of semiconductor materials with high power pulsed ion beams is proposed. The model takes account of recombination between vacancies and interstitial atoms and the formation of defect complexes and these processes are analysed and discussed. The effect of an inhomogeneous non-stationary temperature field and mechanical quasi-static and dynamic stress fields on radiation defect profiles is also examined. Spatial profiles of the charge carrier concentration and the implanted ion distribution are calculated and a comparison made with experimental profiles obtained for the semiconductor compound Hg 1Àx Cd x Te. The results show that the defect concentration profiles near the surface are reduced with a large rate of recombination between vacancy and interstitial atoms.
Although the application of reconstructive vascular surgical procedures to the treatment of carot... more Although the application of reconstructive vascular surgical procedures to the treatment of carotid paragangliomas has made their resection the method of choice and has produced excellent cure rates, it has not obviated some of the technical problems presented by excessively vascular, adherent, or bulky lesions. Our experience with preoperative transcatheter embolization for the reduction of the vascularity in six cases of this group of lesions is presented and the conclusion is made that preoperative embolization greatly reduced operative technical difficulties.
Clinical and metabolomic investigations of complex human fluids require cost-effective methodolog... more Clinical and metabolomic investigations of complex human fluids require cost-effective methodologies that can rapidly assess the steroid hormone milieu of individual samples. The efficiency of quantification of many steroids is limited using immunoassays as these methods can only measure a single component of biological samples and are dependent upon the specificity of the antiserum used in the protocol. In this study, we optimised the solid-phase extraction protocol for the extraction of a range of steroids of varied polarity from estetrol to progesterone from human plasma. The final SPE procedure for efficient extraction of steroids was a washing mixture of 5 ml of 30% methanol and an elution solvent of 2 ml of 100% methanol using 0.5 g C-18 cartridges. This protocol resulted in a high recovery rate, ranging from 85.2 to 99.9% for both the internal standard (7,8-dimethoxyflavone) and steroids of interest. We also improved the separation methodology of our previous work using temperature dependent inclusion chromatography with a mobile phase composition of 35% acetonitrile and 12 mM of beta-cyclodextrin at 29 degrees C. Under these conditions most of the fluid components including estetrol were detected in the first 10 min with progesterone appearing at 43 min. This method is simplistic, inexpensive and reproducible with the capabilities of accurate quantification of steroids. Therefore it could have numerous clinical and metabolomic applications.
The etiology of idiopathic scoliosis remains unknown. The condition results in a characteristic d... more The etiology of idiopathic scoliosis remains unknown. The condition results in a characteristic deformity of the spine and surrounding tissues. Both Types I and II collagen are important constituents of the affected tissues, and thus defective collagens are reasonable candidates for the primary abnormality in adolescent idiopathic scoliosis (AIS). Direct analyses of the amount and solubility of collagen have revealed differences between normal individuals and those with AIS. However, these changes may be secondary to the mechanical effects of the spinal deformity. Segregation analysis was done of genetic markers linked to the structural genes encoding Types I and II collagen to test these candidate loci in four pedigrees with dominantly inherited AIS. In one pedigree, markers linked to both of the Type I collagen loci (COL1A1 and COL1A2) were found to be inherited independently of the abnormal phenotype. Two pedigrees were discordant at one of the Type I loci. The condition also segregated independently of the locus for Type II collagen (COL2A1) in three pedigrees. This is evidence against idiopathic scoliosis generally being caused by mutations in the Types I and II collagen genes.
A series of pyrrolopyridinones was designed and synthesized as constrained analogs of the pyrazol... more A series of pyrrolopyridinones was designed and synthesized as constrained analogs of the pyrazole CB-1 antagonist rimonabant. Certain examples exhibited very potent hCB-1 receptor binding affinity and functional antagonism with Ki and Kb values below 10 nM, and with high selectivity for CB-1 over CB-2 (>100-fold). A representative analog was established to cause significant appetite suppression and reduction in body weight gain in industry-standard rat models used to develop new therapeutics for obesity.
MAP kinase p38 has been implicated in cytokine signaling, and its inhibitors are potentially usef... more MAP kinase p38 has been implicated in cytokine signaling, and its inhibitors are potentially useful for the treatment of arthritis and osteoporosis. Novel small-molecule inhibitors of p38 kinase were derived from a combinatorial chemistry eort and exhibit activity in the nanomolar range. Very steep structure±activity relationships are observed within this class.
(Acy1oxy)methyl ketones, of general structure Z-[AA2]-[AA1]-CH20COAr, are potent inac-'This work ... more (Acy1oxy)methyl ketones, of general structure Z-[AA2]-[AA1]-CH20COAr, are potent inac-'This work has been supported by grants from the Natural Sciences and Engineering Research Council. R.S.P. would also like to acknowledge NSERC for graduate studies scholarships.
Aims: To evaluate the effect of automated external defibrillators (AEDs) on patient survival and ... more Aims: To evaluate the effect of automated external defibrillators (AEDs) on patient survival and to describe the performance of AEDs after in-hospital cardiac arrest. Methods: Prospectively collected data were analysed for cardiac arrests in the general patient care areas of a teaching hospital during the 3 years before and the 3 years after the deployment of AEDs. The association between availability of an AED and survival to hospital discharge was assessed using multivariate logistic regression. AED performance during automated management of the initial rhythms was assessed using information captured by the AEDs. Results: There were 84 cardiac arrests in the AED period and 82 in the pre-AED period. Patient and event characteristics were similar in each period. The initial rhythm was shockable in 16% of cases. Return of spontaneous circulation was higher in the AED period (54% vs. 35%, P = 0.02) but the proportion of hospital survivors in each period was similar (22% vs. 19%, P = 0.56). The adjusted odds ratio for hospital survival when an AED was available was 1.22 (95% CI 0.53-2.84, P = 0.64). An AED was applied in 77/84 (92%) possible cases. Median interruption to chest compressions was 12 s (inter-quartile range 12-13). An automated shock was delivered in 8/13 (62%) possible cases. Conclusions: Availability of AEDs was not independently associated with hospital survival. Shockable presenting rhythms were not common and, in keeping with the manufacturer's specifications, the AEDs did not shock all potentially shockable rhythms. The hands-off time associated with automated rhythm management was considerable.
Cold fronts frequently migrate equatorwards across Australia, penetrating deep into the subtropic... more Cold fronts frequently migrate equatorwards across Australia, penetrating deep into the subtropics. They regularly reach as far north as the Gulf of Carpentaria (around 17°S), and occasionally push northward of Darwin (12°S). (The locations of places named in the text are shown in Fig. 1.) The synoptic environment of these fronts is similar to that of the summertime cool change of southeastern Australia (Reeder and
Formal overspill schemes, linked with slum clearance programmes, have been major elements in many... more Formal overspill schemes, linked with slum clearance programmes, have been major elements in many postwar metropolitan planning strategies. Until recently few politicians or administrators involved in such exercises questioned. at least overtly, the need to redevelop comprehensively the central area slums and. in order to contain the peripheral growth of the cities. rehouse many of those who would thereby be displaced in new and expanded towns. Attitudes are now changing. Social planners have become concerned about the harm done by breaking up what they see as integrated communities. Demographers, in reassessing population predictions. have concluded that natural increase generated in the cities is now likely to be far less than was thought during the 1960s. And economists query the cost effectiveness of dealing with poor housing through the mechanism of comprehensive redevelopment and formal overspill. It is not the purpose of this paper to debate these issues. Rather the aim is to undertake a preliminary exploration into how slum clearance and overspill became galvanized in the Scottish context during the 1950s. By examining how the situation appeared to contemporaries and how the various facets for change integrated. it is hoped that some insights will be offered to parties involved in the more urgent contemporary debate. Effectively a discussion of the evolution of formal overspill policies in Scotland means discussing the evolution of formal overspill policies for Glasgow and an earlier paper has described how they came to be established in the immediate postwar years.' Glasgow, a city dominated by high density tenements, had a major overcrowding problem to contend with and a solution was offered in the 1964 Clyde Valley Regional Plan2 which recommended that 500,000 of the city's one million population should be decanted from the central areas if densities *I am grateful for information for this paper from discussions with Lord Strathclyde, the Rt. Hon. Arthur Woodburn, Dame Jean Roberts, Professor Sir Robert Grieve, Mr. J. Armour and Mr. J. H. McGuinness. However, I alone am responsible for the accuracy of all facts and interpretations.
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Papers by Roger Smith