... Footnotes. ↵* David Booth is Director of the Africa Power and Politics Programme (APPP) at th... more ... Footnotes. ↵* David Booth is Director of the Africa Power and Politics Programme (APPP) at the Overseas Development Institute, London. ... 76–87; Tim Kelsall and David Booth, with Diana Cammack and Frederick Golooba-Mutebi, 'Developmental patrimonialism? ...
... of 11 Towards a Theory of Local Governance and Public Goods Provision David Booth* Abstract U... more ... of 11 Towards a Theory of Local Governance and Public Goods Provision David Booth* Abstract Under-provision of essential public goods is making development in Africa slower and more inequitable than it needs to be. A ...
Page 1. Aid effectiveness: bringing country ownership (and politics) back in David Booth Overseas... more Page 1. Aid effectiveness: bringing country ownership (and politics) back in David Booth Overseas Development Institute Working Paper 336 Results of ODI research presented in preliminary form for discussion and critical comment ...
Common genetic variants of IL-7 receptor a (IL-7Ra) have recently been shown to affect susceptibi... more Common genetic variants of IL-7 receptor a (IL-7Ra) have recently been shown to affect susceptibility to multiple sclerosis (MS) and type 1 diabetes, and survival following bone marrow transplantation. Transcription of the gene produces two dominant isoforms, with or without exon 6, which code for membrane-bound or soluble IL-7Ra, respectively. The haplotypes produce different isoform ratios. We have tested IL-7Ra mRNA expression in cell subsets and in models of T cell homeostasis, activation, tolerance, and differentiation into regulatory T cell/Th1/Th2/Th17, memory, and dendritic cells (DCs) under the hypothesis that the conditions in which haplotype differences are maximal are those likely to be the basis for their association with disease pathogenesis. Maximal differences between haplotypes were found in DCs, where the ligand is mainly thymic stromal lymphopoietin (TSLP). The MS-protective haplotype produces a much lower ratio of soluble to membrane-bound receptor, and so potentially, DCs of this haplotype are more responsive to TSLP. The TSLP/IL-7Ra interaction on DCs is known to be critical for production of thymic regulatory T cells, and reduced production of these cells in MS susceptibility haplotypes may be a basis for its association with this disease. IL-7Ra mRNA expression varies greatly through cell differentiation so that it may be a useful marker for cell states. We also show that serum levels of soluble receptor are much higher for the MS susceptibility haplotype (p = 4 3 10 213 ). Because signaling through IL-7Ra controls T cell regulation, this haplotype difference is likely to affect the immunophenotype and disease pathogenesis.
... De Wet Nel, the Minister for Bantu Administration and Development, declared: I am against mix... more ... De Wet Nel, the Minister for Bantu Administration and Development, declared: I am against mixed sport meetings in principle . . . there is sufficient evidence to prove that such a policy would lead to the most distasteful racial tensions. ...
End-stage renal disease (ESRD) patients on chronic dialysis are at heightened risk for target ves... more End-stage renal disease (ESRD) patients on chronic dialysis are at heightened risk for target vessel revascularization (TVR) after coronary stenting. However, ESRD patients were excluded from the trials that demonstrated the superiority of drug-eluting stents (DES) over bare metal stents (BMS) in reducing TVR. We sought to identify the impact of stent type (DES versus BMS) on TVR and other cardiac adverse events in ESRD patients. The study included 89 consecutive ESRD patients who underwent coronary stenting and were followed for greater than or equal to 9 months. TVR was the primary endpoint, and the secondary endpoint was a composite of death, myocardial infarction (MI) and TVR. Multivariate logistic regression models were used to adjust for differences in clinical and procedural characteristics. DES were used in 24 and BMS in 65 patients. The stent diameter was smaller (p = 0.008), but the stent length was longer (p = 0.006) in the DES group. TVR was required in 1 (4%) of DES and 17 (26%) BMS patients, while 8 (33%) DES and 39 (60%) BMS patients met the secondary endpoint. By multivariate logistic regression, DES use was associated with a significant reduction in TVR (OR 0.07, 95% CI 0.006-0.844; p = 0.036) and a significant reduction in death, MI and TVR (OR 0.11, 95% CI 0.022-0.513; p = 0.005). A high rate of ischemic events was noted for ESRD patients, regardless of stent type. However, in ESRD patients undergoing coronary revascularization, DES use is effective in reducing 9-month TVR and the composite of death, MI and TVR.
A genome-wide exome association study has identified the transmembrane 6 superfamily member 2 (TM... more A genome-wide exome association study has identified the transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 variant encoding an E167K substitution as a genetic determinant of hepatic steatosis in nonalcoholic fatty liver disease (NAFLD). The role of this variant across a spectrum of liver diseases and pathologies and on serum lipids comparing viral hepatitis to NAFLD, and viral load in chronic viral hepatitis, and its intrahepatic molecular signature, have not been well characterized. We undertook detailed analyses in 3,260 subjects with viral and non-viral liver diseases and in healthy controls. Serum inflammatory markers and hepatic expression of TM6SF2 and genes regulating lipid metabolism were assessed in a subset with chronic hepatitis C (CHC). The rs58542926 T allele was more prevalent in 502 NAFLD patients than controls (p=0.02), but not different in cohorts with CHC (n = 2,023) and CHB (n = 507). The T allele was associated with alterations in serum lipids and hepatic steatosis in all diseases, and with reduced hepatic TM6SF2 and MTTP expression expression. Interestingly, the substitution was associated with reduced CHC viral load, but increased HBV-DNA. The rs58542926 T allele had no effect on inflammation, impacted on ≥F2 fibrosis in CHC and NAFLD assessed cross-sectionally (OR: 1.39 (95% CI = 1.04-1.87 and OR: 1.62, 95% CI: 1.03-2.52, respectively, p<0.03 for both), but had no effect on fibrosis progression in 1174 patients with CHC and a known duration of infection. We conclude that the TM6SF2 E167K substitution promotes steatosis and lipid abnormalities in part by altering TM6SF2 and MTTP expression and differentially impacts CHC and CHB viral load, while effects on fibrosis are marginal. This article is protected by copyright. All rights reserved.
A network of over thirty three-component digitally recording seismometers operated by Memphis Sta... more A network of over thirty three-component digitally recording seismometers operated by Memphis State University has been deployed in the New Madrid seismic zone, central USA, since October, 1989. Three major earthquakes (nr,, > 7) occurred in the zone in 18 I 1-12 and the area is subject to constant microearthquake activity at focal depths of 3 to 1.5 km. The station density and signal frequencies of 8 to IO Hz, recorded at 100 Hz, provide an opportunity for detailed analysis of shear-wave splitting from earthquake sources in an intraplate tectonic setting. This paper presents preliminary analysis of the first I9 months of data. Particular attention is given to the reduction of the effective shear-wave window by the presence of internal velocity discontinuities and a low-velocity zone. The polarization directions at most stations show a preferred orientation correlated with the ENE regional maximum compressional stress direction which is attributed to the presence of vertical stressaligned cracks. The scattered polarizations observed at the remaining stations are interpreted as due to local structural irregularities or a more complex anisotropic symmetry. Temporal trends in delay between split shear waves are investigated, but no unambiguous variations are found since these data are too sparse for definitive results. The splitting indicates differential shear-wave anisotropy of 3 to 4% over the total raypath.
The amplitudes of shear and Lg waves recorded at UK seismograph stations from local earthquakes i... more The amplitudes of shear and Lg waves recorded at UK seismograph stations from local earthquakes in the range 0-600 km have been subjected to an analysis of variance, allowing separation of the effects of earthquake size, distance and station corrections for each recording site. The propagation paths sample mainly the central to western part of the UK, with good north-south coverage. The analysis of 385 amplitude readings at 28 stations from 40 earthquakes showed that the effects of both distance and station (site) corrections were statistically significant. Tables of corrections for both distance and station effects have been derived to allow local magnitude ML to be determined more accurately from horizontal and vertical component records. One set of tables allows the estimation of an ML which is consistent with the original Richter definition of ML, with a standard deviation which is smaller than that produced by the theoretical attenuation curve, defined according to attenuation in Southern California, which has customarily been used to calculate ML in the UK. The reduction in standard deviation is mainly due to the incorporation of station terms to correct for station effects, since the theoretical and observed variations of attenuation with distance are similar. This similarity implies that Southern California and the UK show a similar variation of distance-dependent attenuation for Lg waves, which was not expected in view of the differences in geology and tectonics. Another set of tables is provided to calculate an ML which is consistent with the body wave magnitude mb determined by the International Data Centre from station records of the Comprehensive Test-Ban Treaty Organization's global monitoring network. The decay with distance of the predominantly Lg-wave amplitude values gives a value of 440 +/- 50 for Lg Q at a frequency of 3 Hz, in agreement with estimates obtained from spectral displacement amplitudes of Lg waves in the UK.
This paper focuses upon the problem of detecting outliers in a time series used to model a produc... more This paper focuses upon the problem of detecting outliers in a time series used to model a production process in the chemical industry. Significant deviations from the underlying time series pattern, i.e. outliers, indicate an adverse process change or out-of-control situation relative to the model. The underlying process is modeled using either least squares moving polynomial fit smoothing based upon the Savitzky-Golay algorithmz1 or data bounding. This makes any outliers in the original data more salient when compared to the smoothed graph. Thus outliers can be detected earlier while the process output is still within standard control limits and product specifications. The proposed algorithms improve upon and complement the conventional control chart, particularly with interdependent observations. The process control capabilities of these methods were successfully tested on an autocorrelated data set taken from a chemical production process with known adverse process changes and assigned causes. These algorithms should be of assistance to the chemical engineer or industrial chemist involved in process and quality control.
We have investigated the interleukin-7 receptor (IL-7R) a-chain gene as a positional and function... more We have investigated the interleukin-7 receptor (IL-7R) a-chain gene as a positional and functional candidate gene for susceptibility to multiple sclerosis (MS), in view of its chromosomal location on 5p14-p12, a region that has shown suggestive linkage in MS genome screens, and its role in T-and B-cell proliferation and reactivity. Amplification and DNA sequencing of the IL-7Ra gene in pooled and individual samples identified 13 single nucleotide polymorphisms (SNPs), 11 of which are novel, including three in the promoter region, three in exons encoding amino-acid changes (ACC(Thr)66ATC(Ile), ATC(Ile)244ACC(Thr), ATC(Ile)336GTC(Val)), four in introns and one in the 3 0 untranslated region. Four IL-7R haplotypes were identified for nine SNPs, showing linkage disequilibrium across the gene, and allowing haplotype frequency determination from just three of the nine SNPs. Genotyping of the À504 polymorphism in 101 MS and 90 controls showed a suggestive (P ¼ 0.1) association of the T allele with MS; however, this was not supported by transmission disequilibrium testing in 186 MS trio families (P ¼ 0.8). There were trends towards an increase of the GTG+ haplotype (odds ratio ¼ 1.45), and underrepresentation of the TTA+ haplotype (OR ¼ 0.65) in DRB1*1501-positive MS cases, suggesting that larger sample sizes and comparison in more defined MS patient groups may support an association with the IL-7R gene. These polymorphisms would also be useful for studying genetic associations with other immunologic diseases.
... Footnotes. ↵* David Booth is Director of the Africa Power and Politics Programme (APPP) at th... more ... Footnotes. ↵* David Booth is Director of the Africa Power and Politics Programme (APPP) at the Overseas Development Institute, London. ... 76–87; Tim Kelsall and David Booth, with Diana Cammack and Frederick Golooba-Mutebi, 'Developmental patrimonialism? ...
... of 11 Towards a Theory of Local Governance and Public Goods Provision David Booth* Abstract U... more ... of 11 Towards a Theory of Local Governance and Public Goods Provision David Booth* Abstract Under-provision of essential public goods is making development in Africa slower and more inequitable than it needs to be. A ...
Page 1. Aid effectiveness: bringing country ownership (and politics) back in David Booth Overseas... more Page 1. Aid effectiveness: bringing country ownership (and politics) back in David Booth Overseas Development Institute Working Paper 336 Results of ODI research presented in preliminary form for discussion and critical comment ...
Common genetic variants of IL-7 receptor a (IL-7Ra) have recently been shown to affect susceptibi... more Common genetic variants of IL-7 receptor a (IL-7Ra) have recently been shown to affect susceptibility to multiple sclerosis (MS) and type 1 diabetes, and survival following bone marrow transplantation. Transcription of the gene produces two dominant isoforms, with or without exon 6, which code for membrane-bound or soluble IL-7Ra, respectively. The haplotypes produce different isoform ratios. We have tested IL-7Ra mRNA expression in cell subsets and in models of T cell homeostasis, activation, tolerance, and differentiation into regulatory T cell/Th1/Th2/Th17, memory, and dendritic cells (DCs) under the hypothesis that the conditions in which haplotype differences are maximal are those likely to be the basis for their association with disease pathogenesis. Maximal differences between haplotypes were found in DCs, where the ligand is mainly thymic stromal lymphopoietin (TSLP). The MS-protective haplotype produces a much lower ratio of soluble to membrane-bound receptor, and so potentially, DCs of this haplotype are more responsive to TSLP. The TSLP/IL-7Ra interaction on DCs is known to be critical for production of thymic regulatory T cells, and reduced production of these cells in MS susceptibility haplotypes may be a basis for its association with this disease. IL-7Ra mRNA expression varies greatly through cell differentiation so that it may be a useful marker for cell states. We also show that serum levels of soluble receptor are much higher for the MS susceptibility haplotype (p = 4 3 10 213 ). Because signaling through IL-7Ra controls T cell regulation, this haplotype difference is likely to affect the immunophenotype and disease pathogenesis.
... De Wet Nel, the Minister for Bantu Administration and Development, declared: I am against mix... more ... De Wet Nel, the Minister for Bantu Administration and Development, declared: I am against mixed sport meetings in principle . . . there is sufficient evidence to prove that such a policy would lead to the most distasteful racial tensions. ...
End-stage renal disease (ESRD) patients on chronic dialysis are at heightened risk for target ves... more End-stage renal disease (ESRD) patients on chronic dialysis are at heightened risk for target vessel revascularization (TVR) after coronary stenting. However, ESRD patients were excluded from the trials that demonstrated the superiority of drug-eluting stents (DES) over bare metal stents (BMS) in reducing TVR. We sought to identify the impact of stent type (DES versus BMS) on TVR and other cardiac adverse events in ESRD patients. The study included 89 consecutive ESRD patients who underwent coronary stenting and were followed for greater than or equal to 9 months. TVR was the primary endpoint, and the secondary endpoint was a composite of death, myocardial infarction (MI) and TVR. Multivariate logistic regression models were used to adjust for differences in clinical and procedural characteristics. DES were used in 24 and BMS in 65 patients. The stent diameter was smaller (p = 0.008), but the stent length was longer (p = 0.006) in the DES group. TVR was required in 1 (4%) of DES and 17 (26%) BMS patients, while 8 (33%) DES and 39 (60%) BMS patients met the secondary endpoint. By multivariate logistic regression, DES use was associated with a significant reduction in TVR (OR 0.07, 95% CI 0.006-0.844; p = 0.036) and a significant reduction in death, MI and TVR (OR 0.11, 95% CI 0.022-0.513; p = 0.005). A high rate of ischemic events was noted for ESRD patients, regardless of stent type. However, in ESRD patients undergoing coronary revascularization, DES use is effective in reducing 9-month TVR and the composite of death, MI and TVR.
A genome-wide exome association study has identified the transmembrane 6 superfamily member 2 (TM... more A genome-wide exome association study has identified the transmembrane 6 superfamily member 2 (TM6SF2) rs58542926 variant encoding an E167K substitution as a genetic determinant of hepatic steatosis in nonalcoholic fatty liver disease (NAFLD). The role of this variant across a spectrum of liver diseases and pathologies and on serum lipids comparing viral hepatitis to NAFLD, and viral load in chronic viral hepatitis, and its intrahepatic molecular signature, have not been well characterized. We undertook detailed analyses in 3,260 subjects with viral and non-viral liver diseases and in healthy controls. Serum inflammatory markers and hepatic expression of TM6SF2 and genes regulating lipid metabolism were assessed in a subset with chronic hepatitis C (CHC). The rs58542926 T allele was more prevalent in 502 NAFLD patients than controls (p=0.02), but not different in cohorts with CHC (n = 2,023) and CHB (n = 507). The T allele was associated with alterations in serum lipids and hepatic steatosis in all diseases, and with reduced hepatic TM6SF2 and MTTP expression expression. Interestingly, the substitution was associated with reduced CHC viral load, but increased HBV-DNA. The rs58542926 T allele had no effect on inflammation, impacted on ≥F2 fibrosis in CHC and NAFLD assessed cross-sectionally (OR: 1.39 (95% CI = 1.04-1.87 and OR: 1.62, 95% CI: 1.03-2.52, respectively, p<0.03 for both), but had no effect on fibrosis progression in 1174 patients with CHC and a known duration of infection. We conclude that the TM6SF2 E167K substitution promotes steatosis and lipid abnormalities in part by altering TM6SF2 and MTTP expression and differentially impacts CHC and CHB viral load, while effects on fibrosis are marginal. This article is protected by copyright. All rights reserved.
A network of over thirty three-component digitally recording seismometers operated by Memphis Sta... more A network of over thirty three-component digitally recording seismometers operated by Memphis State University has been deployed in the New Madrid seismic zone, central USA, since October, 1989. Three major earthquakes (nr,, > 7) occurred in the zone in 18 I 1-12 and the area is subject to constant microearthquake activity at focal depths of 3 to 1.5 km. The station density and signal frequencies of 8 to IO Hz, recorded at 100 Hz, provide an opportunity for detailed analysis of shear-wave splitting from earthquake sources in an intraplate tectonic setting. This paper presents preliminary analysis of the first I9 months of data. Particular attention is given to the reduction of the effective shear-wave window by the presence of internal velocity discontinuities and a low-velocity zone. The polarization directions at most stations show a preferred orientation correlated with the ENE regional maximum compressional stress direction which is attributed to the presence of vertical stressaligned cracks. The scattered polarizations observed at the remaining stations are interpreted as due to local structural irregularities or a more complex anisotropic symmetry. Temporal trends in delay between split shear waves are investigated, but no unambiguous variations are found since these data are too sparse for definitive results. The splitting indicates differential shear-wave anisotropy of 3 to 4% over the total raypath.
The amplitudes of shear and Lg waves recorded at UK seismograph stations from local earthquakes i... more The amplitudes of shear and Lg waves recorded at UK seismograph stations from local earthquakes in the range 0-600 km have been subjected to an analysis of variance, allowing separation of the effects of earthquake size, distance and station corrections for each recording site. The propagation paths sample mainly the central to western part of the UK, with good north-south coverage. The analysis of 385 amplitude readings at 28 stations from 40 earthquakes showed that the effects of both distance and station (site) corrections were statistically significant. Tables of corrections for both distance and station effects have been derived to allow local magnitude ML to be determined more accurately from horizontal and vertical component records. One set of tables allows the estimation of an ML which is consistent with the original Richter definition of ML, with a standard deviation which is smaller than that produced by the theoretical attenuation curve, defined according to attenuation in Southern California, which has customarily been used to calculate ML in the UK. The reduction in standard deviation is mainly due to the incorporation of station terms to correct for station effects, since the theoretical and observed variations of attenuation with distance are similar. This similarity implies that Southern California and the UK show a similar variation of distance-dependent attenuation for Lg waves, which was not expected in view of the differences in geology and tectonics. Another set of tables is provided to calculate an ML which is consistent with the body wave magnitude mb determined by the International Data Centre from station records of the Comprehensive Test-Ban Treaty Organization's global monitoring network. The decay with distance of the predominantly Lg-wave amplitude values gives a value of 440 +/- 50 for Lg Q at a frequency of 3 Hz, in agreement with estimates obtained from spectral displacement amplitudes of Lg waves in the UK.
This paper focuses upon the problem of detecting outliers in a time series used to model a produc... more This paper focuses upon the problem of detecting outliers in a time series used to model a production process in the chemical industry. Significant deviations from the underlying time series pattern, i.e. outliers, indicate an adverse process change or out-of-control situation relative to the model. The underlying process is modeled using either least squares moving polynomial fit smoothing based upon the Savitzky-Golay algorithmz1 or data bounding. This makes any outliers in the original data more salient when compared to the smoothed graph. Thus outliers can be detected earlier while the process output is still within standard control limits and product specifications. The proposed algorithms improve upon and complement the conventional control chart, particularly with interdependent observations. The process control capabilities of these methods were successfully tested on an autocorrelated data set taken from a chemical production process with known adverse process changes and assigned causes. These algorithms should be of assistance to the chemical engineer or industrial chemist involved in process and quality control.
We have investigated the interleukin-7 receptor (IL-7R) a-chain gene as a positional and function... more We have investigated the interleukin-7 receptor (IL-7R) a-chain gene as a positional and functional candidate gene for susceptibility to multiple sclerosis (MS), in view of its chromosomal location on 5p14-p12, a region that has shown suggestive linkage in MS genome screens, and its role in T-and B-cell proliferation and reactivity. Amplification and DNA sequencing of the IL-7Ra gene in pooled and individual samples identified 13 single nucleotide polymorphisms (SNPs), 11 of which are novel, including three in the promoter region, three in exons encoding amino-acid changes (ACC(Thr)66ATC(Ile), ATC(Ile)244ACC(Thr), ATC(Ile)336GTC(Val)), four in introns and one in the 3 0 untranslated region. Four IL-7R haplotypes were identified for nine SNPs, showing linkage disequilibrium across the gene, and allowing haplotype frequency determination from just three of the nine SNPs. Genotyping of the À504 polymorphism in 101 MS and 90 controls showed a suggestive (P ¼ 0.1) association of the T allele with MS; however, this was not supported by transmission disequilibrium testing in 186 MS trio families (P ¼ 0.8). There were trends towards an increase of the GTG+ haplotype (odds ratio ¼ 1.45), and underrepresentation of the TTA+ haplotype (OR ¼ 0.65) in DRB1*1501-positive MS cases, suggesting that larger sample sizes and comparison in more defined MS patient groups may support an association with the IL-7R gene. These polymorphisms would also be useful for studying genetic associations with other immunologic diseases.
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