Essays in Quantitative Risk Management for Financial Regulation of Operational Risk Models

An extensive amount of evolving guidance and rules are provided to banks by financial regulators. A particular set of instructions outline requirements to calculate and set aside loss-absorbing regulatory capital to ensure the solvency of a bank. Mathematical models are typically used by banks to quantify sufficient amounts of capital. In this thesis, we explore areas that advance our knowledge in regulatory risk management. In the first essay, we explore an aspect of operational risk loss modeling using scenario analysis. An actuarial modeling method is typically used to quantify a baseline capital value which is then layered with a judgemental component in order to account for and integrate what-if future potential losses into the model. We propose a method from digital signal processing using the convolution operator that views the problem of the blending of two signals. That is, a baseline loss distribution obtained from the modeling of frequency and severity of internal losses is combined with a probability distribution obtained from scenario responses to yield a final output that integrates both sets of information. In the second essay, we revisit scenario analysis and the potential impact of catastrophic events to that of the enterprise level of a bank. We generalize an algorithm to account for multiple level of intensities of events together with unique loss profiles depending on the business units effected. In the third essay, we investigate the problem of allocating aggregate capital across sub-portfolios in a fair manner when there are various forms of interdependencies. Relevant to areas of market, credit and operational risk, the multivariate shortfall allocation problem quantifies the optimal amount of capital needed to ensure that the expected loss under a convex loss penalty function remains bounded by a threshold. We first provide an application of the existing methodology to a subset of high frequency loss cells. Lastly, we provide an extension using copula models which allows for the modeling of joint fat-tailed events or asymmetries in the underlying process

A greater proportion of participants with type 2 diabetes achieve treatment targets with insulin degludec/liraglutide versus insulin glargine 100 units/mL at 26 weeks. DUAL VIII, a randomized trial designed to resemble clinical practice

This report presents the efficacy and safety of insulin degludec/liraglutide (IDegLira) versus insulin glargine 100 units/mL (IGlar U100) as initial injectable therapy at 26 weeks in the 104-week DUAL VIII durability trial (NCT02501161). Participants (N = 1012) with type 2 diabetes (T2D) uncontrolled on oral antidiabetic drugs (OADs) were randomized 1:1 to open-label IDegLira or IGlar U100. Visits were scheduled at weeks 1, 2, 4 and 12, and every 3 months thereafter. After 26 weeks, glycated haemoglobin (HbA1c) reductions were greater with IDegLira versus IGlar U100 (−21.5 vs. –16.4 mmol/mol [−2.0 vs. –1.5%]), as was the percentage of participants achieving HbA1c <53 mmol/mol (78.7% vs. 55.7%) and HbA1c targets without weight gain and/or hypoglycaemia. Estimated treatment differences for insulin dose (−13.01 U) and body weight change (−1.57 kg) significantly favoured IDegLira. The hypoglycaemia rate was 44% lower with IDegLira versus IGlar U100. Safety results were similar. In a trial resembling clinical practice, more participants receiving IDegLira than IGlar U100 met treatment targets, supporting use of IDegLira as an initial injectable therapy for people with T2D uncontrolled on OADs and eligible for insulin initiation

PENERAPAN BUDAYA KERJA INDUSTRI DALAM PEMBELAJARAN PRAKTIK PEMESINAN SMK MUHAMMADIYAH 1 SALAM, MAGELANG

Tujuan penelitian ini adalah untuk mengetahui bagaima guru mengajarkan budaya kerja industri serta penerapannya oleh siswa pada pembelajaran praktik pemesinan SMK Muhammadiyah 1 Salam. Penelitian ini merupakan penelitian deskriptif kuantitatif dan kualitatif. Subjek pada penelitian ini adalah guru pengampu mata pelajaran praktik pemesinan kelas XI dan siswa kelas XI jurusan teknik pemesinan SMK Muhammadiyah 1 Salam. Data kuantitatif didapatkan dari perolehan angket, sedangkan data kualitatif didapatkan dari hasil wawancara dan observasi. Data tersebut dianalisis dengan analisis deskriptif. Hasil penelitian menunjukkan nilai integritas sudah diterapkan 89,9% siswa. Nilai integritas diterapkan dengan berperilaku jujur dan tanggung jawab. Nilai profesional sudah diterapkan 54,8% siswa. Nilai profesional diterapkan dengan bekerja sesuai standar prosedur serta menerapkan K3 saat bekerja. Nilai produktif sudah diterapkan 50,1% siswa. Nilai produktif diterapkan dengan bekerja sesuai waktu dan kualitas yang ditentukan. Nilai inovatif hanya diterapkan 27,3% siswa. Nilai inovatif diterapkan dengan mencari alternatif baru dalam bekerja. Nilai kompetitif sudah diterapkan 52,7% siswa. Nilai kompetitif diterapkan dengan mencari informasi berkait lapangan pekerjaan serta percaya diri menunjukkan kompetensi

iGlarLixi effectively reduces residual hyperglycaemia in patients with type 2 diabetes on basal insulin: A post hoc analysis from the LixiLan-L study

Globally, nearly half of patients with type 2 diabetes (T2D) do not successfully achieve target HbA1c with basal insulin, despite meeting fasting plasma glucose (FPG) targets. In this post hoc analysis of the LixiLan-L study, we determined whether iGlarLixi, a fixed-ratio combination of insulin glargine Gla-100 (iGlar) and the glucagon-like peptide-1 receptor agonist lixisenatide (Lixi), addresses the challenge of reducing residual hyperglycaemia in patients with T2D. In LixiLan-L, a randomized, open-label study, 1018 patients with T2D on basal insulin for ≥6 months ± oral antidiabetes drugs entered a 6-week run-in period, during which they were switched to and/or optimized for a daily dose of iGlar while continuing only metformin. Following the run-in period, 736 patients were then randomized to receive iGlarLixi or were continued on iGlar for 30 weeks ± metformin. Residual hyperglycaemia was defined as HbA1c ≥ 7.0% despite FPG of <140 mg/dL. The proportion of patients with residual hyperglycaemia was similar in both treatment arms at screening (~~42%), and increased after the run-in period (~~62%). After 30 weeks, the proportion of patients with residual hyperglycaemia declined to 23.8% in the iGlarLixi versus 47.1% in the iGlar arm (P <.0001). The proportion of patients achieving both HbA1c (<7.0%) and FPG (<140 mg/dL) targets was higher in the iGlarLixi compared with the iGlar arm (50.3% vs. 27.4%, respectively; P <.0001). iGlarLixi effectively reduces residual hyperglycaemia in patients with T2D on basal insulin therapy

Glycaemic control and hypoglycaemia risk with insulin glargine 300 U/mL versus glargine 100 U/mL: A patient-level meta-analysis examining older and younger adults with type 2 diabetes

Abstract Aim Older people with type 2 diabetes (T2DM) are at an increased risk of hypoglycaemia and its consequences. However, efficacy and safety data for basal insulin therapy are limited in these individuals. This patient-level meta-analysis assessed the treatment effects of insulin glargine 300 U/mL (Gla-300) versus glargine 100 U/mL (Gla-100) in people with T2DM ≥ 65 years old. Methods Data were pooled for patients randomised to receive Gla-300 or Gla-100 in the Phase 3a, treat-to-target EDITION 1, 2 and 3 trials. Glycaemic efficacy, hypoglycaemia, changes in body weight and insulin dosage and adverse events were examined over 6 months' treatment with Gla-300 versus Gla-100 for participants aged ≥ 65 and  Results Of 2496 participants randomised, 662 were ≥ 65 years (Gla-300, n = 329; Gla-100, n = 333). Glycaemic control was comparable for Gla-300 and Gla-100 in participants ≥ 65 years (LS mean [95% CI] difference in HbA1c change from baseline to month 6: 0.00 [−0.14 to 0.15] %; 0.00 [−1.53 to 1.64] mmol/mol) and  Conclusion Gla-300 was associated with a reduced risk of nocturnal hypoglycaemia versus Gla-100, accompanied by comparable glycaemic improvement, for people aged ≥ 65 an

Early Response to Preventive Strategies in the Diabetes Prevention Program

BACKGROUND Recommendations for diabetes prevention in patients with prediabetes include lifestyle modification and metformin. However, the significance of early weight loss and glucose measurements when monitoring response to these proven interventions is unknown. OBJECTIVE To quantify the relationship between early measures of weight and glucose and subsequent diabetes in patients undergoing diabetes prevention interventions. DESIGN Analysis of results from a randomized controlled trial in 27 academic medical centers in the United States. PARTICIPANTS/INTERVENTIONS 3,041 adults with hyperglycemia randomized to lifestyle (n = 1,018), metformin (n = 1,036), or placebo (n = 987) with complete follow-up in The Diabetes Prevention Program. MAIN MEASURES Independent variables were weight loss at 6 and 12 months; fasting glucose (FG) at 6 months; hemoglobin A1c (HbA1c) at 6 months; and post-load glucose at 12 months. The main outcome was time to diabetes diagnosis. KEY RESULTS After 6 months, 604 participants developed diabetes in the lifestyle (n = 140), metformin (n = 206), and placebo (n = 258) arms over 2.7 years. In the lifestyle arm, 6-month weight loss predicted decreased diabetes risk in a graded fashion: adjusted HR (95 % CI) 0.65 (0.35–1.22), 0.62 (0.33–1.18), 0.46 (0.24–0.87), 0.34 (0.18–0.64), and 0.15 (0.07–0.30) for 0–60 % lower diabetes risk across arms. We found a significant interaction between 6-month weight loss and FG in the lifestyle arm (P = 0.038). CONCLUSION Weight and glucose at 6 and 12 months strongly predict lower subsequent diabetes risk with a lifestyle intervention; lower FG predicts lower risk even with substantial weight loss. Early reduction in glycemia is a stronger predictor of future diabetes risk than weight loss for metformin. We offer the first evidence to guide clinicians in making interval management decisions for high-risk patients undertaking measures to prevent diabetes

Achieving glycaemic control without weight gain, hypoglycaemia, or gastrointestinal adverse events in type 2 diabetes in the SUSTAIN clinical trial programme

Aim: To evaluate the potential for semaglutide to help people with type 2 diabetes (T2D) achieve glycated haemoglobin (HbA1c) targets while avoiding unwanted outcomes, such as weight gain, hypoglycaemia and gastrointestinal (GI) side effects. Materials and methods: Data from the phase IIIa SUSTAIN 1 to 5 clinical trials were analysed. Participants had inadequately controlled T2D and were drug-naïve (SUSTAIN 1) or on a range of background treatments (SUSTAIN 2 to 5). The main protocol-specified composite endpoint was the proportion of participants achieving HbA1c <53 mmol/mol (7.0%) at end of treatment (30 or 56 weeks) without weight gain and with no severe or blood glucose (BG)-confirmed symptomatic hypoglycaemia. A post hoc composite endpoint was the proportion of participants achieving the primary composite endpoint without moderate or severe GI adverse events (AEs). Results: Across the SUSTAIN trials 1 to 5, 3918 participants with T2D were randomized to once-weekly subcutaneous semaglutide 0.5 mg, 1.0 mg, or comparators (placebo, sitagliptin 100 mg, exenatide extended release 2.0 mg or insulin glargine). The proportion of participants achieving HbA1c <53 mmol/mol (7.0%) with no weight gain and no severe/BG-confirmed symptomatic hypoglycaemia was 47% to 66% (semaglutide 0.5 mg) and 57% to 74% (semaglutide 1.0 mg) vs 7% to 19% (placebo) and 16% to 29% (active comparators; all P < .0001). More participants achieved the primary composite endpoint with no moderate or severe GI AEs with semaglutide vs comparators (all P < .0001). Conclusion: Semaglutide helped more people with T2D achieve HbA1c targets than did comparators in the SUSTAIN 1 to 5 trials, while avoiding unwanted outcomes such as weight gain, hypoglycaemia and GI side effects

Exploring residual risk for diabetes and microvascular disease in the Diabetes Prevention Program Outcomes Study (DPPOS)

Aim Approximately half of the participants in the Diabetes Prevention Outcomes Study (DPPOS) had diabetes after 15 years of follow-up, whereas nearly all the others remained with pre-diabetes. We examined whether formerly unexplored factors in the DPPOS coexisted with known risk factors that posed additional risk for, or protection from, diabetes as well as microvascular disease. Methods Cox proportional hazard models were used to examine predictors of diabetes. Sequential modelling procedures considered known and formerly unexplored factors. We also constructed models to determine whether the same unexplored factors that associated with progression to diabetes also predicted the prevalence of microvascular disease. Hazard ratios (HR) are per standard deviation change in the variable. Results In models adjusted for demographics and known diabetes risk factors, two formerly unknown factors were associated with risk for both diabetes and microvascular disease: number of medications taken (HR = 1.07, 95% confidence intervals (95% CI) 1.03 to 1.12 for diabetes; odds ratio (OR) = 1.10, 95% CI 1.04 to 1.16 for microvascular disease) and variability in HbA1c (HR = 1.02, 95% CI 1.01 to 1.03 for diabetes; OR = 1.06, 95% CI 1.04 to 1.09 for microvascular disease per sd). Total comorbidities increased risk for diabetes (HR = 1.10, 95% CI 1.04 to 1.16), whereas higher systolic (OR = 1.22, 95% CI 1.13 to 1.31) and diastolic (OR = 1.14, 95% CI 1.05 to 1.22) blood pressure, as well as the use of anti-hypertensives (OR = 1.41, 95% CI 1.23 to 1.62), increased risk of microvascular disease. Conclusions Several formerly unexplored factors in the DPPOS predicted additional risk for diabetes and/or microvascular disease – particularly hypertension and the use of anti-hypertensive medications – helping to explain some of the residual disease risk in participants of the DPPOS