The KASE approach to domain-specific software systems

Designing software systems, like all design activities, is a knowledge-intensive task. Several studies have found that the predominant cause of failures among system designers is lack of knowledge: knowledge about the application domain, knowledge about design schemes, knowledge about design processes, etc. The goal of domain-specific software design systems is to explicitly represent knowledge relevant to a class of applications and use it to partially or completely automate various aspects of the designing systems within that domain. The hope is that this would reduce the intellectual burden on the human designers and lead to more efficient software development. In this paper, we present a domain-specific system built on top of KASE, a knowledge-assisted software engineering environment being developed at the Stanford Knowledge Systems Laboratory. We introduce the main ideas underlying the construction of domain specific systems within KASE, illustrate the application of the idea in the synthesis of a system for tracking aircraft from radar signals, and discuss some of the issues in constructing domain-specific systems

Software synthesis using generic architectures

A framework for synthesizing software systems based on abstracting software system designs and the design process is described. The result of such an abstraction process is a generic architecture and the process knowledge for customizing the architecture. The customization process knowledge is used to assist a designer in customizing the architecture as opposed to completely automating the design of systems. Our approach using an implemented example of a generic tracking architecture which was customized in two different domains is illustrated. How the designs produced using KASE compare to the original designs of the two systems, and current work and plans for extending KASE to other application areas are described

Software design by reusing architectures

Abstraction fosters reuse by providing a class of artifacts that can be instantiated or customized to produce a set of artifacts meeting different specific requirements. It is proposed that significant leverage can be obtained by abstracting software system designs and the design process. The result of such an abstraction is a generic architecture and a set of knowledge-based, customization tools that can be used to instantiate the generic architecture. An approach for designing software systems based on the above idea are described. The approach is illustrated through an implemented example, and the advantages and limitations of the approach are discussed

Predictors of outcome in myxoedema coma: a study from a tertiary care centre

BACKGROUND: With the easy availability of thyroid hormone assays, thyroid disorders are now recognised even in a subclinical state. However, patients are still seen with advanced manifestations of the disease, particularly in developing countries. This observational study analysed the predictors of outcome in patients with myxoedema coma and tested the validity of different modules to define morbidity and mortality in these patients. METHODS: Twenty-three consecutive patients with myxoedema coma who presented from January 1999 to August 2006 were studied. The thyroid function test and random serum cortisol were measured in all patients at the time of admission. Patients were given oral or intravenous (i.v.) thyroxine with intention to treat with the latter according to availability. Various modules that predict outcome, including Glasgow Coma Scale (GCS), Acute Physiology and Chronic Health Evaluation II (APACHE II) score, and Sequential Organ Failure Assessment (SOFA) score, were analysed. SOFA score was repeated every 2 days until the time of discharge or demise. RESULTS: Twenty-three patients (20 women; 87%) of 59.5 +/- 14.4 years of age (range, 30 to 89 years) were seen during the study period. Nine (39%) patients were diagnosed with hypothyroidism for the first time at the time of presentation of myxoedema coma, whereas 14 (70%) were diagnosed with hypothyroidism previously. However, the treatment defaulters presented early to the hospital and had more severe manifestations than de novo subjects. Nineteen (82%) had thyroprivic (primary) and 4 (17%) had trophoprivic (secondary) hypothyroidism. Fifteen (65%) patients presented in the winter and in 17 (74%) sepsis was the major accompanying comorbidity. Twelve (52%) had a history of diuretic use, thereby delaying the initial diagnosis. Patients who received oral L-thyroxine had no difference in outcome from those receiving i.v. thyroxine. Twelve (52%) subjects died and sepsis was the predominant cause of death. Various predictors of mortality included hypotension (p = 0.01) and bradycardia (p = 0.03) at presentation, need for mechanical ventilation (p = 0.00), hypothermia unresponsive to treatment (p = 0.01), sepsis (p = 0.01), intake of sedative drugs (p = 0.02), lower GCS (p = 0.03), high APACHE II score (p = 0.04), and high SOFA score (p = 0.00). However, SOFA score was more effective than other predictive models as baseline and day 3 SOFA scores of more than 6 were highly predictive of poor outcome. CONCLUSION: L-Thyroxine treatment defaulters had more severe manifestations compared with de novo subjects. Outcome was not influenced by either aetiology or route of administration of L-thyroxine, and SOFA score was the best outcome predictor model

Worsening of unrecognized tumour-induced osteomalacia with inadvertent use of recombinant human parathyroid hormone

Not required for Clinical Vignette

Tumor-induced osteomalacia: experience from three tertiary care centers in India

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by recalcitrant hypophosphatemia. Reports from the Indian subcontinent are scarce, with most being single center experiences involving few patients. Herein, we conducted a retrospective analysis of 30 patients of TIO diagnosed at three tertiary care hospitals in India. Patients with persistent hypophosphatemia (despite correction of hypovitaminosis D), normocalcemia, elevated alkaline phosphatase, low TmP/GFR and elevated or ‘inappropriately normal’ FGF23 levels were labeled as having TIO. They were sequentially subjected to functional followed by anatomical imaging. Patients with a well-localized tumor underwent excision; others were put on phosphorous and calcitriol supplementation. The mean age at presentation was 39.6 years with female:male ratio of 3:2. Bone pain (83.3%) and proximal myopathy (70%) were the chief complaints; 40% of cases had fractures. The mean delay in diagnosis was 3.8 years. Tumors were clinically detectable in four patients (13.3%). The mean serum phosphate was 0.50 mmol/L with a median serum FGF23 level of 518 RU/mL. Somatostatin receptor-based scintigraphy was found to be superior to FDG-PET in tumor localization. Lower extremities were the most common site of the tumor (72%). Tumor size was positively correlated with serum FGF23 levels. Twenty-two patients underwent tumor resection and 16 of them had phosphaturic mesenchymal tumors. Surgical excision led to cure in 72.7% of patients whereas disease persistence and disease recurrence were seen in 18.2% and 9.1% of cases, respectively. At the last follow-up, serum phosphate in the surgically treated group was significantly higher than in the medically managed group

Genome-wide association study for type 2 diabetes in Indians identifies a new susceptibility locus at 2q21.

Indians undergoing socioeconomic and lifestyle transitions will be maximally affected by epidemic of type 2 diabetes (T2D). We conducted a two-stage genome-wide association study of T2D in 12,535 Indians, a less explored but high-risk group. We identified a new type 2 diabetes-associated locus at 2q21, with the lead signal being rs6723108 (odds ratio 1.31; P = 3.32 × 10⁻⁹). Imputation analysis refined the signal to rs998451 (odds ratio 1.56; P = 6.3 × 10⁻¹²) within TMEM163 that encodes a probable vesicular transporter in nerve terminals. TMEM163 variants also showed association with decreased fasting plasma insulin and homeostatic model assessment of insulin resistance, indicating a plausible effect through impaired insulin secretion. The 2q21 region also harbors RAB3GAP1 and ACMSD; those are involved in neurologic disorders. Forty-nine of 56 previously reported signals showed consistency in direction with similar effect sizes in Indians and previous studies, and 25 of them were also associated (P < 0.05). Known loci and the newly identified 2q21 locus altogether explained 7.65% variance in the risk of T2D in Indians. Our study suggests that common susceptibility variants for T2D are largely the same across populations, but also reveals a population-specific locus and provides further insights into genetic architecture and etiology of T2D

Global, regional, and national comparative risk assessment of 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks, 1990–2015: a systematic analysis for the Global Burden of Disease Study 2015

Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defi ned criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specifi c DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI).Background The Global Burden of Diseases, Injuries, and Risk Factors Study 2015 provides an up-to-date synthesis of the evidence for risk factor exposure and the attributable burden of disease. By providing national and subnational assessments spanning the past 25 years, this study can inform debates on the importance of addressing risks in context. Methods We used the comparative risk assessment framework developed for previous iterations of the Global Burden of Disease Study to estimate attributable deaths, disability-adjusted life-years (DALYs), and trends in exposure by age group, sex, year, and geography for 79 behavioural, environmental and occupational, and metabolic risks or clusters of risks from 1990 to 2015. This study included 388 risk-outcome pairs that met World Cancer Research Fund-defi ned criteria for convincing or probable evidence. We extracted relative risk and exposure estimates from randomised controlled trials, cohorts, pooled cohorts, household surveys, census data, satellite data, and other sources. We used statistical models to pool data, adjust for bias, and incorporate covariates. We developed a metric that allows comparisons of exposure across risk factors—the summary exposure value. Using the counterfactual scenario of theoretical minimum risk level, we estimated the portion of deaths and DALYs that could be attributed to a given risk. We decomposed trends in attributable burden into contributions from population growth, population age structure, risk exposure, and risk-deleted cause-specifi c DALY rates. We characterised risk exposure in relation to a Socio-demographic Index (SDI)

Global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

As mortality rates decline, life expectancy increases, and populations age, non-fatal outcomes of diseases and injuries are becoming a larger component of the global burden of disease. The Global Burden of Diseases, Injuries, and Risk Factors Study 2016 (GBD 2016) provides a comprehensive assessment of prevalence, incidence, and years lived with disability (YLDs) for 328 causes in 195 countries and territories from 1990 to 2016