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Background Clinical trials comparing incretin-based therapies—glucagon-like peptide-1 receptor agonists (exenatide—twice daily and once weekly—and once-daily liraglutide) and dipeptidyl peptidase-4 inhibitors (vildagliptin, sitagliptin, saxagliptin and linagliptin)—with placebo and oral antidiabetic drugs show that these therapies effectively control glycaemia, with low risk of hypoglycaemia. Glucagon-like peptide-1 receptor agonists are associated with weight loss and reductions in systolic blood pressure, while dipeptidyl peptidase-4 inhibitors are weight-neutral. Based on this, the National Institute for Health and Clinical Excellence recommends using these agents in patients with type 2 diabetes for whom excess weight and/or hypoglycaemia are problematic. Aim of the review This review aims to help decision making when selecting and using incretin-based therapies in type 2 diabetes. Methods A search or MEDLINE and Cochrane clinical trials databases, limited to clinical trials in humans, was performed using the search criteria ‘exenatide or liraglutide or vildagliptin or sitagliptin, or saxagliptin or linagliptin’. Abstracts presented at recent American Diabetes Association and European Association for the Study of Diabetes meetings were also searched. Eighteen clinical trials directly comparing incretin-based therapies were identified. Results Glucagon-like peptide-1 receptor agonists achieved significantly greater reductions in glycated hemoglobin and weight than dipeptidyl peptidase-4 inhibitors, which have a neutral effect on weight. Between-treatment differences were clinically important. Gastrointestinal side effects were more frequent with glucagon-like peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors. Comparisons between glucagon-like peptide-1 receptor agonists and between dipeptidyl peptidase-4 inhibitors showed that differences within the available agents in the two sub-classes are small. Greater treatment satisfaction was reported with glucagon-like peptide-1 receptor agonists versus dipeptidyl peptidase-4 inhibitors. Conclusion Glucagon-like peptide-1 receptor agonists achieve greater glycated hemoglobin reductions than dipeptidyl peptidase-4 inhibitors, with concomitant weight loss. Probably due to the greater efficacy of glucagon-like peptide-1 receptor agonists, patient satisfaction is greater with these agents compared with dipeptidyl peptidase-4 inhibitors despite injectable versus oral administration and more frequent gastrointestinal side effects with the agonists.

Thymic carcinoma is rare, with resulting treatment of patients with extrathoracic metastasis being on a case-by-case basis. We describe the management of a woman in her 70s with an incidentally discovered cystic hepatic lesion with confirmation of a solitary extrathoracic metastasis from a synchronous primary thymic carcinoma. Following chemotherapy and staged resection of the metastasis and the primary tumour, the patient remained free of disease on radiological surveillance 6 months postoperatively.

Previous chapters have explored problems that are fundamental to both driving in general as well as features of driving automation systems. Potential solutions including driver monitoring and advanced human–machine interface (HMI) designs that may solve those problems have also been presented. No matter how principled, any solution is only a potential one until it is tested and evaluated. The purpose of this chapter is to provide an overview for testing various aspects of automated and connected driving automation systems, including considerations for commercial vehicle testing. This chapter will include reviews of testing methodologies (e.g., data analytics, experimentation, and naturalistic driving) and will advocate a graduated approach in which systems are tested iteratively throughout the development cycle.

A money market model is presented that substantially reduces both the difficulty of linking projected changes in nonborrowed reserves to short-term interest rates and dependence on exogenous variables. This model structure is consistent with the fact that the Federal funds rate was the principal policy instrument utilized by the Federal Reserve System during the 1970s and is specifically designed to mirror the well-documented strategy used by the Federal Reserve System to control the Federal funds rate.Although this alternative structure could be simulated with the Federal funds rate controlled exogenously to study different monetary policies, the specification presented goes further than simply replacing nonborrowed reserves with the Federal funds rate as the key policy variable. The Federal funds rate is related to endogenous variables that are of central importance to the process of monetary policy implementation. The results obtained indicate that the Federal funds rate responds negatively to the rate of unemployment and positively to inflation and the rate of money stock growth. By the introduction of the equation for the Federal funds rate, feedback from the overall model is allowed to influence predicted Federal Reserve System policy implementation, and dependence on exogenous projections of the key Federal Reserve System policy variable is reduced substantially.

The preparation, content orientation, and commitment of secondary teachers limit their abilities to teach reading adequately to the severely disabled high school reader. There may be conflict inherent in the two contents which prohibit an optimal learning situation for either. Alternatives are suggested to the present trend of teaching reading skills through content. AA

Recent trends have led to parameterization of many computing components, such as parameterized processors, caches, FPGAs or networks–on-chip, as well as parameters in design tools such as optimization flags. Tuning parameterized systems to meet design goals like performance, energy, size, or power, has become harder due to the enormous design space created by such parameters and due to the large time required to evaluate each system configuration. Previous design space exploration approaches for parameterized systems have either focused on custom or randomized search heuristics. We map such design space exploration onto a statistical paradigm known as Design of Experiments, a paradigm under development since the 1920s that uses methodical experiment selection and sophisticated analysis to obtain maximum information using a minimum number of experiments. We introduce our DPG (Design-of-experiments Pareto-point Generator) method that performs flexible exploration by allowing the designer to provide information about the number and types of parameters, the approximate time to evaluate a configuration, and the total allowable exploration time. From that information, DPG automatically determines a custom set of experiments to best explore the design space within the allowable time. Such customized design-of-experiments-based exploration represents the unique contribution of this work. We show that DPG provides competitive results across different domains, without requiring the designer to have a detailed understanding of parameter impacts. We created a web-based DPG tool to support designers from various domains, which accepts information from the designer and generates experiments that the designer conducts (iteratively), and generates data and plots from the analysis, including Pareto-points. The effectiveness of the DoE paradigm for system tuning may have broad applicability for design automation.

One of the principal uses for the Bureau of Economic Analysis (BEA) quarterly econometric model of the U.S. economy is the analysis of alternative fiscal policies. Because multiplier analyses of the BEA model structure indicate that monetary policy variables exert a significant quantitative impact, analyses of the impact of alternative fiscal policies depend critically on the values of the monetary policy variables [3]. The Federal Reserve System (FRS) has actively responded to changes in economic conditions in setting these monetary policy variables. Therefore, to obtain an internally consistent analysis of alternative fiscal policies, FRS reaction to the changes in basic economic conditions generated by these alternative policies...

I provide a novel picture of the relationship between laws of nature and causation which removes many of the perplexities which are persistent in the literature. I argue that the standard view of the content of laws which has come down from David Hume, that is, the view that individual laws report generic, local causal sequences, has obscured the way laws figure into the tracking and explanation of causal processes. I replace such a view with the more accurate picture of the construction of evolution equations from various \"law recipes\" which are used by physicists. This examination yields several important distinctions between types of laws which are not captured by the standard covering law distinctions--developed largely by Carl Hempel--between universal and statistical laws, and laws of coexistence and laws of succession. Moreover, these new distinctions which I provide are vital for an accurate understanding of the role which laws play in causal explanation. Thus, the result is a sophisticated \"covering-law theory\" which lacks the disadvantages usually associated with that theory but which nonetheless captures the core idea that laws underwrite causal processes. Once the way in which laws are used to describe causal processes is properly understood, I focus my attention upon critiques of the covering-law model. For instance, a number of philosophers have held that the laws of nature are in conflict with causation. Bertrand Russell argued that the proper view about causation was \"eliminitivism,\" the view that all causal talk should be eliminated because physics replaces causal talk with laws. More recently, Nancy Cartwright has taken exactly the opposite point of view: There is no problem with causation; the problem is with laws, I trace both views to their source in the Humean view of laws described above. Moreover, the more accurate view which I provide in terms of law recipes is not subject to the objection of Cartwright and Russell and shows in detail where such views have gone astray.