Operational Risk is one of the most difficult risks to model. It is a large and diverse category covering anything from cyber losses to mis-selling fines; and from processing errors to HR issues. Data is usually lacking, particularly for low frequency, high impact losses, and consequently there can be a heavy reliance on expert judgement. This paper seeks to help actuaries and other risk professionals tasked with the challenge of validating models of operational risks. It covers the loss distribution and scenario-based approaches most commonly used to model operational risks, as well as Bayesian Networks. It aims to give a comprehensive yet practical guide to how one may validate each of these and provide assurance that the model is appropriate for a firm’s operational risk profile.

Children of women with pre-eclampsia have increased risk of cardiovascular (CV) and metabolic disease in adult life. Furthermore, the risk of pregnancy complications is higher in daughters born to women affected by pre-eclampsia than in daughters born after uncomplicated pregnancies. While aberrant inflammation contributes to the pathophysiology of pregnancy complications, including pre-eclampsia, the contribution of maternal inflammation to subsequent risk of CV and metabolic disease as well as pregnancy complications in the offspring remains unclear. Here, we demonstrate that 24-week-old female rats (F1) born to dams (F0) exposed to lipopolysaccharide (LPS) during pregnancy (to induce inflammation) exhibited mild systolic dysfunction, increased cardiac growth-related gene expression, altered glucose tolerance, and coagulopathy; whereas male F1 offspring exhibited altered glucose tolerance and increased visceral fat accumulation compared with F1 sex-matched offspring born to saline-treated dams. Both male and female F1 offspring born to LPS-treated dams had evidence of anemia. Fetuses (F2) from F1 females born to LPS-treated dams were growth restricted, and this reduction in fetal growth was associated with increased CD68 positivity (indicative of macrophage presence) and decreased expression of glucose transporter-1 in their utero-placental units. These results indicate that abnormal maternal inflammation can contribute to increased risk of CV and metabolic disease in the offspring, and that the effects of inflammation may cross generations. Our findings provide evidence in support of early screening for CV and metabolic disease, as well as pregnancy complications in offspring affected by pre-eclampsia or other pregnancy complications associated with aberrant inflammation.

This article examines the earliest examples of replication of bronze objects of complicated structure in China. It uses four quadrupeds from the Freer Gallery (National Museum of Asian Art, Smithsonian Institution), the Asian Art Museum of San Francisco, the British Museum, and the Yūrinkan Museum in Kyōto as examples to illustrate the complex technology required in replicating bronzes. It provides evidence to define identical bronzes and proves that the four quadrupeds shared the same decorated model. The application of section-mold casting, spacers, clay cores, and mold section assemblage will be examined using 3D scanning, X-ray photography, computerized tomography (CT) scanning, and alloy composition analysis.

Introduction: Acute bloody diarrhea obligates rapid and accurate diagnostic evaluation; few studies have described such cohorts of children. Methods: We conducted a planned secondary analysis employing the Alberta Provincial Pediatric EnTeric Infection TEam (APPETITE) acute gastroenteritis study cohort to describe the characteristics of children with acute bloody diarrhea, compared to a cohort of children without hematochezia. Children <18 years of age presenting to 2 pediatric tertiary care emergency departments (EDs) in Alberta, with ≥3 episodes of diarrhea and/or vomiting in the preceding 24 hours and <7 days of symptoms were consecutively recruited. Stools were tested for 17 viruses, bacteria and parasites. Primary outcomes were clinical characteristics and pathogens identified. Secondary outcomes included interventions and resource utilization. Results: Of 2257 children enrolled between October 2015 and August 2018, hematochezia before or at the index ED visit was reported in 122 (5.4%). Compared to children with nonbloody diarrhea, children with hematochezia had longer illness duration [59.5 vs. 41.5 hrs, difference 10.6, 95% CI 3.5, 19.9], more diarrheal episodes in a 24-hour period [8 vs. 5, difference 3, 95% CI 2, 4], and less vomiting [55.7% vs. 91.1%; difference -35.3%; 95% CI -44.7, -26.3]. They received more intravenous fluids [32.0% vs. 18.3%; difference 13.7%, 95% CI 5.5, 23.0], underwent non-study stool testing [53.7% vs. 4.8%; difference 49.0%, 95% CI 39.6, 58.0], experienced longer ED visits [4.1 vs. 3.3 hours, difference 0.9, 95% CI 0.3, 1.0] and were more likely to have repeat healthcare visits within 14 days [54.8% vs. 34.2%; difference 20.6%, 95% CI 10.8, 30.1]. A bacterial enteric pathogen was found in 31.9% of children with hematochezia versus 6.6% without bloody diarrhea (difference 25.4%, 95% CI 17.2, 34.7). In children with hematochezia, the most commonly detected bacteria were Salmonella spp. (N = 15), Shiga toxin-producing E. coli (N = 9), Campylobacter spp. (N = 7), and Shigella spp. (N = 5). Viruses were detected in 32.8% of children with bloody diarrhea, most commonly adenovirus (N = 15), norovirus (N = 14), sapovirus (N = 8) and rotavirus (N = 7). Conclusion: Children with hematochezia differed clinically from those without hematochezia and required more healthcare resources. While bacterial etiologies are common, several viruses were also detected.

This paper explores dependencies between operational risks and between operational risks and other risks such as market, credit and insurance risk. The paper starts by setting the regulatory context and then goes into practical aspects of operational risk dependencies. Next, methods of modelling operational risk dependencies are considered with a simulation study exploring the sensitivity of diversification benefits arising from dependency models. The following two sections consider how correlation assumptions may be set, highlighting some generic dependencies between operational risks and with non-operational risks to assist in the assessment of dependencies and correlation assumptions. Supplementary appendices provide further detail on generic dependencies as well as a case study of how business models can lead to operational risks interacting with other risks. Finally, the paper finishes with a literature review of operational risk dependency papers including correlation studies and benchmark reports.

This study investigated the effect of forage type (grass or red clover) and harvesting time (primary growth or regrowth) of silage on energy and N utilisation by sheep fed at maintenance level. Specifically, the assumption of constant loss of energy of digestible organic matter from energy losses in urine and CH4 applied in evaluation of silage metabolisable energy (ME) was investigated. Urinary excretion of high-energy phenolic compounds related to solubilisation of lignin was assumed to affect urinary energy (UE) losses from sheep fed highly digestible grass silage (GS). A total of 25 primary growth and regrowth silages of timothy (Phleum pratense) and meadow fescue (Festuca pratensis) grass mixtures and red clover (Trifolium pratense) samples collected in digestibility trials with sheep, including faecal and urine samples, were used for energy and N determinations. Urinary concentration of monophenolic compounds and CH4 emissions in vitro were also analysed. Daily faecal N output, CH4 yield (MJ/kg DM intake), proportion of CH4 energy in digestible energy (DE) and proportion of UE in DE were greater (P ≤ 0.03) in sheep fed red clover silage (RCS) than GS. Furthermore, less (P = 0.01) energy was lost as UE of DE in sheep fed primary growth GS compared with the other treatments. The relationship between UE and silage N intake or urinary N output for both silage types (i.e. grass v. red clover) was strong, but the fit of the regressions was better for GS than RCS. The CH4/DE ratio decreased (P < 0.05) and the UE/DE ratio increased (P < 0.05) with increasing organic matter digestibility in RCS. These relationships were not significant (P < 0.05) for the GS diets. The regression coefficient was higher (P < 0.05) for GS than RCS when regressing ME concentration on digestible organic matter. The results of this study imply that ME/DE ratio is not constant across first-cut GS of different maturities. The ME production response may be smaller from highly digestible first-cut GS but could not be clearly related to urinary excretion of monophenols derived from solubilisation of lignin. Furthermore, energy lost in urine was not clearly defined for RCS and was much more predictable for GS from silage N concentration.

The COllaborative project of Development of Anthropometrical measures in Twins (CODATwins) project is a large international collaborative effort to analyze individual-level phenotype data from twins in multiple cohorts from different environments. The main objective is to study factors that modify genetic and environmental variation of height, body mass index (BMI, kg/m2) and size at birth, and additionally to address other research questions such as long-term consequences of birth size. The project started in 2013 and is open to all twin projects in the world having height and weight measures on twins with information on zygosity. Thus far, 54 twin projects from 24 countries have provided individual-level data. The CODATwins database includes 489,981 twin individuals (228,635 complete twin pairs). Since many twin cohorts have collected longitudinal data, there is a total of 1,049,785 height and weight observations. For many cohorts, we also have information on birth weight and length, own smoking behavior and own or parental education. We found that the heritability estimates of height and BMI systematically changed from infancy to old age. Remarkably, only minor differences in the heritability estimates were found across cultural–geographic regions, measurement time and birth cohort for height and BMI. In addition to genetic epidemiological studies, we looked at associations of height and BMI with education, birth weight and smoking status. Within-family analyses examined differences within same-sex and opposite-sex dizygotic twins in birth size and later development. The CODATwins project demonstrates the feasibility and value of international collaboration to address gene-by-exposure interactions that require large sample sizes and address the effects of different exposures across time, geographical regions and socioeconomic status.

Hand-foot-mouth disease (HFMD) is an acute infectious disease caused by serotypes of the enterovirus (EV) family. HFMD reinfection occurs commonly in lack of cross-protection between different EV serotypes. In this study, we investigated the hazards of HFMD reinfection using Cox-proportional hazard model. Retrospective data of 95 209 HFMD cases in Wuhan during 2008–2015 was used. Kaplan–Meier survival methods and Cox-proportional hazard model were used to estimate the hazard probabilities. Of the all HFMD cases, about 2% experienced reinfection (1842/95 209). Kaplan–Meier curves revealed the reinfection risk sharply increased before 40 months from first infection. Higher hazards of reinfection were detected among those who were males, aged 3 years and below, scattered children, belonging to urban areas and first infected with coxsackievirus (CV)-A16 compared with their respective counterparts. Cox-proportional hazard model suggested that gender, age, group, living area and serotypes of first infection had significant effect on reinfection even after adjusting for potential confounding effects of other selected factors considered in the study. These results indicate that boys aged 3 years and below, especially those living in urban areas and first infected with CV-A16 are more prone to reinfection. Interventions should be imposed on these high-risk populations.

Introduction: Gastroenteritis accounts for 1.7 million emergency department visits by children annually in the United States. We conducted a double-blind trial to determine whether twice daily probiotic administration for 5 days, improves outcomes. Methods: 886 children aged 348 months with gastroenteritis were enrolled in six Canadian pediatric emergency departments. Participants were randomly assigned to twice daily Lactobacillus rhamnosus R0011 and Lactobacillus helveticus R0052, 4.0 x 109 CFU, in a 95:5 ratio or placebo. Primary outcome was development of moderate-severe disease within 14 days of randomization defined by a Modified Vesikari Scale score 9. Secondary outcomes included duration of diarrhea and vomiting, subsequent physician visits and adverse events. Results: Moderate-severe disease occurred in 108 (26.1%) participants administered probiotics and 102 (24.7%) participants allocated to placebo (OR 1.06; 95%CI: 0.77, 1.46; P=0.72). After adjustment for site, age, and frequency of vomiting and diarrhea, treatment assignment did not predict moderate-severe disease (OR, 1.11, 95%CI, 0.80 to 1.56; P=0.53). In the probiotic versus placebo groups, there were no differences in the median duration of diarrhea [52.5 (18.3, 95.8) vs. 55.5 (20.2, 102.3) hours; P=0.31], vomiting [17.7 (0, 58.6) vs. 18.7 (0, 51.6) hours; P=0.18], physician visits (30.2% vs. 26.6%; OR 1.19; 95% CI0.87. 1.62; P=0.27), or adverse events (32.9% vs. 36.8%; OR 0.83; 95%CI 0.62. 1.11; P=0.21). Conclusion: In children presenting to an emergency department with gastroenteritis, twice daily administration of 4.0 x 109 CFU of a Lactobacillus rhamnosus/helveticus probiotic does not prevent development of moderate-severe disease or improvements in other outcomes measured.

Piglets are characteristically cold intolerant and thus susceptible to high mortality. However, browning of white adipose tissue (WAT) can induce non-shivering thermogenesis as a potential strategy to facilitate the animal’s response to cold. Whether cold exposure can induce browning of subcutaneous WAT (sWAT) in piglets in a similar manner as it can in humans remains largely unknown. In this study, piglets were exposed to acute cold (4°C, 10 h) or chronic cold exposure (8°C, 15 days), and the genes and proteins of uncoupling protein 1 (UCP1)-dependent and independent thermogenesis, mitochondrial biogenesis, lipogenic and lipolytic processes were analysed. Interestingly, acute cold exposure induced browning of porcine sWAT, smaller adipocytes and the upregulated expression of UCP1, PGC1α, PGC1β, C/EBPβ, Cidea, UCP3, CKMT1 and PM20D1. Conversely, chronic cold exposure impaired the browning process, reduced mitochondrial numbers and the expression of browning markers, including UCP1, PGC1α and PRDM16. The present study demonstrated that acute cold exposure (but not chronic cold exposure) induces porcine sWAT browning. Thus, browning of porcine sWAT could be a novel strategy to balance the body temperature of piglets, and thus could be protective against cold exposure.

Galeruca daurica (Joannis) is a new outbreak pest in the Inner Mongolia grasslands in northern China. Heat shock protein 10 and 60 (Hsp10 and Hsp60) genes of G. daurica, designated as GdHsp10 and GdHsp60, were cloned by rapid amplification of cDNA ends techniques. Sequence analysis showed that GdHsp10 and GdHsp60 encoded polypeptides of 104 and 573 amino acids, respectively. Sequence alignment and phylogenetic analysis clearly revealed that the amino acids of GdHsp10 and GdHsp60 had high homology and were clustered with other Hsp10 and Hsp60 genes in insects which are highly relative with G. daurica based on morphologic taxonomy. The mRNA expression analysis by real-time PCR revealed that GdHsp10 and GdHsp60 were expressed at all development stages and in all tissues examined, but expressed highest in eggs and in adults’ abdomen; both heat and cold stresses could induce mRNA expression of GdHsp10 and GdHsp60 in the 2nd instar larvae; the two Hsp genes were expressed from high to low with the extension of treatment time in G. daurica eggs exposed to freezing point. Overall, our study provides useful information to understand temperature stress responses of Hsp60 and Hsp10 in G. daurica, and provides a basis to further study functions of Hsp60/Hsp10 relative to thermotolerance and cold hardiness mechanism.

Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.