Modernising operational risk management in financial institutions via data-driven causal factors analysis: A pre-registered study

In an effort to contribute a quantitative, objective and real-time tool to proactively and precisely manage the factors underlying and exacerbating operational risks, this pre-registered study executes the empirical methodology approved in the associated pre-registered report (Cornwell et al., 2023). The application of the Bayesian network-based approach to an Australian insurance company shows that integrating a financial institution's loss and operational data in this way can effectively model the probability of an operational loss event within its interconnected operational risk environment. Further insights and efficiencies are gained by modelling multiple operational loss events together, rather than in isolation. A novel two-module framework derived specifically for causal factors analysis from the resulting operational risk model helps to highlight the relative importance of causal factors, their collective effects and critical thresholds requiring proactivity. These insights derived from the framework are expected to be strategically valuable in helping an organisation design intentional and targeted controls for and monitoring of operational risks. Given existing knowledge of the improvements quantitative risk management tools make to risk management effectiveness and subsequently firm value, the enhanced risk management and the operational efficiencies this tool seeks to afford should ultimately contribute to driving financial performance and firm value

Non-alcoholic fatty liver disease (NAFLD): a multi-system disease influenced by ageing and sex, and affected by adipose tissue and intestinal function

In recent years, a wealth of factors are associated with increased risk of developing non-alcoholic fatty liver disease (NAFLD) and NAFLD is now thought to increase the risk of multiple extra-hepatic diseases. The aim of this review is firstly to focus on the role of ageing and sex as key, poorly understood risk factors in the development and progression of NAFLD. Secondly, we aim to discuss the roles of white adipose tissue (WAT) and intestinal dysfunction, as producers of extra-hepatic factors known to further contribute to the pathogenesis of NAFLD. Finally, we aim to summarise the role of NAFLD as a multi-system disease affecting other organ systems beyond the liver. Both increased age and male sex increase the risk of NAFLD and this may be partly driven by alterations in the distribution and function of WAT. Similarly, changes in gut microbiota (GM) composition and intestinal function with ageing and chronic overnutrition are likely to contribute to the development of NAFLD both directly (i.e. by affecting hepatic function) and indirectly via exacerbating WAT dysfunction. Consequently, the presence of NAFLD significantly increases the risk of various extra-hepatic diseases including cardiovascular disease, type 2 diabetes mellitus, chronic kidney disease and certain extra-hepatic cancers. Thus changes in WAT and intestinal function with ageing and chronic overnutrition contribute to the development of NAFLD - a multi-system disease that subsequently contributes to the development of other chronic cardiometabolic diseases.</p

Heterogeneity of white adipocytes in metabolic disease

Purpose of review: this review aims to discuss the most recent evidence identifying the presence of distinct white adipocyte subpopulations in white adipose tissue (WAT) and how these may be altered with increasing adiposity and/or metabolic disease. We conceptualise how changes in adipocyte subpopulations may contribute to alterations in WAT function and the development of metabolic diseases such as type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD) and cardiovascular disease (CVD). Recent findings: studies utilising novel analytical approaches support the existence of distinct white adipocyte subpopulations in both human and murine WAT. Adipocyte subtypes are potentially functionally distinct and may have different roles in WAT function and obesity-associated metabolic diseases.Summary: the exploration of white adipocyte heterogeneity using novel analytical technologies, has unveiled a new layer of complexity in the study of WAT biology. Interrogation of potential functional differences between adipocyte subpopulations and their role in the function of different WAT depots is now needed. Through understanding the mechanisms regulating white adipocyte subtype development and potential pathophysiological consequences of changes in the presence of adipocyte subpopulations, studies could provide novel therapeutic targets for the treatment of T2DM, NAFLD and CVD.<br/

Steatotic liver disease, MASLD and risk of chronic kidney disease

With the rising tide of fatty liver disease related to metabolic dysfunction worldwide, the association of this common liver disease with chronic kidney disease (CKD) has become increasingly evident. In 2020, the more inclusive term metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed to replace the old term nonalcoholic fatty liver disease (NAFLD). In 2023, a modified Delphi process was led by three large pan-national liver associations. There was consensus to change the fatty liver disease nomenclature and definition to include the presence of at least one of five common cardiometabolic risk factors as diagnostic criteria. The name chosen to replace NAFLD was metabolic dysfunction-associated steatotic liver disease (MASLD). The change of nomenclature from NAFLD to MAFLD and then MASLD has resulted in a reappraisal of the epidemiological trends and associations with the risk of developing CKD. The observed association between MAFLD/MASLD and CKD and our understanding that CKD can be an epiphenomenon linked to underlying metabolic dysfunction support the notion that individuals with MASLD are at substantially higher risk of incident CKD than those without MASLD. This narrative review provides an overview of the literature on (a) the evolution of criteria for diagnosing this highly prevalent metabolic liver disease, (b) the epidemiological evidence linking MASLD to the risk of CKD, (c) the underlying mechanisms by which MASLD (and factors strongly linked with MASLD) may increase the risk of developing CKD, and (d) the potential drug treatments that may benefit both MASLD and CKD

The explanatory power of political risk in emerging markets

There is substantial argument that political risk is an important and increasing influence on international portfolio allocation decisions. The purpose of this paper is to investigate the relation between political risk and stock returns within the context of emerging markets. The issue is examined using a framework that controls for global and local return influences. Consistent with the paper's predictions, the findings reveal that political risk is important in explaining return variation in individual emerging markets, particularly in the Pacific Basin, but not in developed markets. At an aggregate portfolio level, supportive evidence is found of a positive relation between political risk and ex-post returns in emerging markets that is robust to alternative risk measures, and more prevalent during the 1990s

Growth differentiation factor-15 and the association between type 2 diabetes and liver fibrosis in NAFLD.

BACKGROUND: Type 2 diabetes mellitus (T2DM) is a strong risk factor for liver fibrosis in non-alcoholic fatty liver disease (NAFLD). It remains uncertain why T2DM increases the risk of liver fibrosis. It has been suggested that growth differentiation factor-15 (GDF-15) concentrations increase the risk of liver fibrosis. We aimed to investigate (a) whether GDF-15 concentrations were associated with liver fibrosis and involved in the relationship between T2DM and liver fibrosis and (b) what factors linked with T2DM are associated with increased GDF-15 concentrations. METHODS: Ninety-nine patients with NAFLD (61% men, 42.4% T2DM) were studied. Serum GDF-15 concentrations were measured by electro-chemiluminescence immunoassay. Vibration-controlled transient elastography (VCTE)-validated thresholds were used to assess liver fibrosis. Regression modelling, receiver operator characteristic curve analysis and Sobel test statistics were used to test associations, risk predictors and the involvement of GDF-15 in the relationship between T2DM and liver fibrosis, respectively. RESULTS: Patients with NAFLD and T2DM (n = 42) had higher serum GDF-15 concentrations [mean (SD): 1271.0 (902.1) vs. 640.3 (332.5) pg/ml, p < 0.0001], and a higher proportion had VCTE assessed ≥F2 fibrosis (48.8 vs. 23.2%, p = 0.01) than those without T2DM. GDF-15 was independently associated with liver fibrosis (p = 0.001), and GDF-15 was the most important single factor predicting ≥F2 or ≥F3 fibrosis (≥F2 fibrosis AUROC 0.75, (95% CI 0.63-0.86), p < 0.001, with sensitivity, specificity, positive predictive (PPV) and negative predictive (NPV) values of 56.3%, 86.9%, 69.2% and 79.1%, respectively). GDF-15 was involved in the association between T2DM and ≥F2 fibrosis (Sobel test statistic 2.90, p = 0.004). Other factors associated with T2DM explained 60% of the variance in GDF-15 concentrations (p < 0.0001). HbA1c concentrations alone explained 30% of the variance (p < 0.0001). CONCLUSIONS: GDF-15 concentrations are a predictor of liver fibrosis and potentially involved in the association between T2DM and liver fibrosis in NAFLD. HbA1c concentrations explain a large proportion of the variance in GDF-15 concentrations

Markers of adipose tissue fibrogenesis associate with clinically significant liver fibrosis and are unchanged by synbiotic treatment in patients with NAFLD

BACKGROUND AND AIMS: Subcutaneous adipose tissue (SAT) dysfunction contributes to NAFLD pathogenesis and may be influenced by the gut microbiota. Whether transcript profiles of SAT are associated with liver fibrosis and are influenced by synbiotic treatment (that changes the gut microbiome) is unknown. We investigated: (a) whether the presence of clinically significant, ≥F2 liver fibrosis associated with adipose tissue (AT) dysfunction, differential gene expression in SAT, and/or a marker of tissue fibrosis (Composite collagen gene expression (CCGE)); and (b) whether synbiotic treatment modified markers of AT dysfunction and the SAT transcriptome. METHODS: Sixty-two patients with NAFLD (60 % men) were studied before and after 12 months of treatment with synbiotic or placebo and provided SAT samples. Vibration-controlled transient elastography (VCTE)-validated thresholds were used to assess liver fibrosis. RNA-sequencing and histological analysis of SAT were performed to determine differential gene expression, CCGE and the presence of collagen fibres. Regression modelling and receiver operator characteristic curve analysis were used to test associations with, and risk prediction for, ≥F2 liver fibrosis. RESULTS: Patients with ≥F2 liver fibrosis (n = 24) had altered markers of AT dysfunction and a SAT gene expression signature characterised by enrichment of inflammatory and extracellular matrix-associated genes, compared to those with <F2 fibrosis (n = 38). Differences in transcript profiles between patients with vs without ≥F2 liver fibrosis were largely explained by adjusting for differences in HOMA-IR. Gut microbiome-modifying synbiotic treatment did not change SAT transcriptomic profiles or circulating inflammatory/adipokine markers. SAT CCGE values were independently associated with (8.38 (1.72-40.88), p = 0.009), and were a good predictor of, ≥F2 fibrosis (AUROC 0.79, 95 % CI 0.69-0.90). Associations between SAT transcriptomic profiles and ≥F2 fibrosis were reproduced using end-of-trial data. CONCLUSION: A differential gene expression signature in SAT associates with ≥F2 liver fibrosis is explained by a measure of systemic insulin resistance and is not changed by synbiotic treatment. SAT CCGE values are a good predictor of ≥F2 liver fibrosis in NAFLD