As part of the Surrogate Markers for Micro- and Macrovascular Hard Endpoints for Innovative Diabe... more As part of the Surrogate Markers for Micro- and Macrovascular Hard Endpoints for Innovative Diabetes Tools (SUMMIT) programme we previously reported that large panels of biomarkers derived from three analytical platforms maximised prediction of progression of renal decline in type 2 diabetes. Here, we hypothesised that smaller (n ≤ 5), platform-specific combinations of biomarkers selected from these larger panels might achieve similar prediction performance when tested in three additional type 2 diabetes cohorts. We used 657 serum samples, held under differing storage conditions, from the Scania Diabetes Registry (SDR) and Genetics of Diabetes Audit and Research Tayside (GoDARTS), and a further 183 nested case-control sample set from the Collaborative Atorvastatin in Diabetes Study (CARDS). We analysed 42 biomarkers measured on the SDR and GoDARTS samples by a variety of methods including standard ELISA, multiplexed ELISA (Luminex) and mass spectrometry. The subset of 21 Luminex bio...
Identification of sequence variants robustly associated with predisposition to diabetic kidney di... more Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined (T1D+T2D) GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 diabetic subjects (and 18,582 DKD cases).Analysis of specific DKD phenotypes identified a novel signal near (rs9942471, =4.5×10) associated with 'microalbuminuria' in European T2D cases. However, no replication of this signal was observed in Asian subjects with T2D, or in the equivalent T1D analysis. Th...
It is well known that antioxidants are able to confer some protective effect against numerous pat... more It is well known that antioxidants are able to confer some protective effect against numerous pathologies such as cardiovascular disease. Alcoholic beverages such as red wine have thus attracted particular attention in recent years due to their high concentration of antioxidants such as phenolic compounds. However, research and information on the in vitro total antioxidant capacity (TAC) of beer has been limited, despite human studies suggesting that antioxidants in such beverages are bioavailable. In this chapter, we provide comprehensive protocols for four commonly used assays for TAC: the oxygen radical absorbance capacity (ORAC), ferric reducing ability of plasma (FRAP), Trolox® equivalent antioxidant capacity (TEAC) and total phenols by Folin–Ciocalteu reagent (TP-FCR) assays. We have tested these assays for linearity and precision, finding excellent correlations and coefficients of variation, and furthermore applied these assays to measure the TAC of beers, red wines and orange juices. We found that the mean TAC of a number of ales (mean TEAC, 7.02 ± 0.08 mM Trolox® equivalents (TE); FRAP 2.71 ± 0.18 mM; ORAC, 7,516 ± 404μM TE; TP-FCR, 398 ± 30 mg/l) was several-fold lower than that of red wines (mean TEAC, 36.87 ± 1.04 mM TE; FRAP, 19.77 ± 1.25 mM; ORAC, 27,963 ± 908 μM TE; TP-FCR, 1,807 ± 94mg/l) but comparable to that of commercially available orange juices (mean TEAC, 6.86 ± 0.28 mM TE; FRAP, 2.88 ± 0.94 mM; ORAC, 5,662 ± 630 μM TE; TP-FCR, 648 ± 45mg/l). In addition, all of the assays showed strong linear correlations with one another (mean r2 = 0.96, range 0.91–0.99). The availability of comprehensive protocols for these assays will enhance research into TAC of beers and augment the evidence base for their benefit in health and wellbeing.
The Basel capital is a “margin” requirement imposed by regulators to cushion banks against extrem... more The Basel capital is a “margin” requirement imposed by regulators to cushion banks against extreme falls in prices of assets held, and is often a function of value-at-risk (VaR). The way banks adjust their balance sheets to maintain the requirement is equivalent to leverage targeting that has been shown to cause procyclical risk. The 2008 crisis revealed that Basel 2 capital was insufficient to protect banks against crisis losses, but the industry believes the current Basel 3 requirements are too high for sustainable business. Is there an optimal capital?Balance sheet rebalancing with a target leverage can be described by a multiplicative game or process. Most players will lose money even if the game has a positive expectation because excessive leverage causes the majority to get wiped out over time and the system achieves a “winner takes all” effect. Fortunately, the Kelly criterion provides an optimal leverage that prevents this. By using empirical data for balance sheet simulation, we show that the Kelly criterion gives an optimal capital vis-a-vis Basel 2, Basel 2.5 and expected shortfall. This capital approach provides the best survival strategy over the economic cycle. The article suggests how this can be computed in practice for an actual bank. Also the Kelly-based capital is potentially countercyclical, which addresses procyclical risks and could also reinforce the central bank monetary policy transmission mechanism.
As part of the Surrogate Markers for Micro- and Macrovascular Hard Endpoints for Innovative Diabe... more As part of the Surrogate Markers for Micro- and Macrovascular Hard Endpoints for Innovative Diabetes Tools (SUMMIT) programme we previously reported that large panels of biomarkers derived from three analytical platforms maximised prediction of progression of renal decline in type 2 diabetes. Here, we hypothesised that smaller (n ≤ 5), platform-specific combinations of biomarkers selected from these larger panels might achieve similar prediction performance when tested in three additional type 2 diabetes cohorts. We used 657 serum samples, held under differing storage conditions, from the Scania Diabetes Registry (SDR) and Genetics of Diabetes Audit and Research Tayside (GoDARTS), and a further 183 nested case-control sample set from the Collaborative Atorvastatin in Diabetes Study (CARDS). We analysed 42 biomarkers measured on the SDR and GoDARTS samples by a variety of methods including standard ELISA, multiplexed ELISA (Luminex) and mass spectrometry. The subset of 21 Luminex bio...
Identification of sequence variants robustly associated with predisposition to diabetic kidney di... more Identification of sequence variants robustly associated with predisposition to diabetic kidney disease (DKD) has the potential to provide insights into the pathophysiological mechanisms responsible. We conducted a genome-wide association study (GWAS) of DKD in type 2 diabetes (T2D) using eight complementary dichotomous and quantitative DKD phenotypes: the principal dichotomous analysis involved 5,717 T2D subjects, 3,345 with DKD. Promising association signals were evaluated in up to 26,827 subjects with T2D (12,710 with DKD). A combined (T1D+T2D) GWAS was performed using complementary data available for subjects with T1D, which, with replication samples, involved up to 40,340 diabetic subjects (and 18,582 DKD cases).Analysis of specific DKD phenotypes identified a novel signal near (rs9942471, =4.5×10) associated with 'microalbuminuria' in European T2D cases. However, no replication of this signal was observed in Asian subjects with T2D, or in the equivalent T1D analysis. Th...
It is well known that antioxidants are able to confer some protective effect against numerous pat... more It is well known that antioxidants are able to confer some protective effect against numerous pathologies such as cardiovascular disease. Alcoholic beverages such as red wine have thus attracted particular attention in recent years due to their high concentration of antioxidants such as phenolic compounds. However, research and information on the in vitro total antioxidant capacity (TAC) of beer has been limited, despite human studies suggesting that antioxidants in such beverages are bioavailable. In this chapter, we provide comprehensive protocols for four commonly used assays for TAC: the oxygen radical absorbance capacity (ORAC), ferric reducing ability of plasma (FRAP), Trolox® equivalent antioxidant capacity (TEAC) and total phenols by Folin–Ciocalteu reagent (TP-FCR) assays. We have tested these assays for linearity and precision, finding excellent correlations and coefficients of variation, and furthermore applied these assays to measure the TAC of beers, red wines and orange juices. We found that the mean TAC of a number of ales (mean TEAC, 7.02 ± 0.08 mM Trolox® equivalents (TE); FRAP 2.71 ± 0.18 mM; ORAC, 7,516 ± 404μM TE; TP-FCR, 398 ± 30 mg/l) was several-fold lower than that of red wines (mean TEAC, 36.87 ± 1.04 mM TE; FRAP, 19.77 ± 1.25 mM; ORAC, 27,963 ± 908 μM TE; TP-FCR, 1,807 ± 94mg/l) but comparable to that of commercially available orange juices (mean TEAC, 6.86 ± 0.28 mM TE; FRAP, 2.88 ± 0.94 mM; ORAC, 5,662 ± 630 μM TE; TP-FCR, 648 ± 45mg/l). In addition, all of the assays showed strong linear correlations with one another (mean r2 = 0.96, range 0.91–0.99). The availability of comprehensive protocols for these assays will enhance research into TAC of beers and augment the evidence base for their benefit in health and wellbeing.
The Basel capital is a “margin” requirement imposed by regulators to cushion banks against extrem... more The Basel capital is a “margin” requirement imposed by regulators to cushion banks against extreme falls in prices of assets held, and is often a function of value-at-risk (VaR). The way banks adjust their balance sheets to maintain the requirement is equivalent to leverage targeting that has been shown to cause procyclical risk. The 2008 crisis revealed that Basel 2 capital was insufficient to protect banks against crisis losses, but the industry believes the current Basel 3 requirements are too high for sustainable business. Is there an optimal capital?Balance sheet rebalancing with a target leverage can be described by a multiplicative game or process. Most players will lose money even if the game has a positive expectation because excessive leverage causes the majority to get wiped out over time and the system achieves a “winner takes all” effect. Fortunately, the Kelly criterion provides an optimal leverage that prevents this. By using empirical data for balance sheet simulation, we show that the Kelly criterion gives an optimal capital vis-a-vis Basel 2, Basel 2.5 and expected shortfall. This capital approach provides the best survival strategy over the economic cycle. The article suggests how this can be computed in practice for an actual bank. Also the Kelly-based capital is potentially countercyclical, which addresses procyclical risks and could also reinforce the central bank monetary policy transmission mechanism.
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Papers by Max Wong