The Risks and Weaknesses of the International Criminal Court from America’s Perspective

Bolton argues the US should raise its objections to the International Criminal Court (ICC) on every appropriate occasion, as part of its larger campaign to assert American interests against stifling, illegitimate, and unacceptable international agreements. The US has many alternative foreign policy instruments to utilize that are fully consistent with US interests, leaving the ICC to the obscurity it richly deserves

Target renal damage: the microvascular associations of increased aortic stiffness in patients with COPD

Background Although renal impairment has been described in COPD, there is opportunity to evaluate further to determine nature and consider optimal management. Increased aortic stiffness, as seen in COPD, leads to reduced buffering of pulsatile flow. We hypothesised that urinary albumin creatinine ratio (UACR) would reflect glomerular damage related to aortic stiffness. Methods Patients with COPD and controls underwent spirometry, blood pressure, arterial stiffness - aortic pulse wave velocity (PWV) and provided a spot urine sample for UACR, with other renal biomarkers measured. Results The UACR was increased in patients (n = 52): 0.80 mg/mmol compared to controls (n = 34): 0.46 mg/mmol, p < 0.05. Aortic PWV was related to log10 UACR in all subjects (r = 0.426, p < 0.001) and COPD patients alone. Aortic PWV was a significant variable for UACR with oxygen saturations, after accounting for potential confounders. Eight subjects (7 patients) reached a defined clinical microalbuminuria threshold, with aortic PWV greater in these patients compared to those patients without, although albuminuria is a continuum. Proximal tubular damage biomarkers, unlike the glomerular marker, were not different between patients and controls. Conclusions There is glomerular damage in patients with COPD evidenced by increased UACR, related to increased aortic stiffness. Besides the macrovascular prognostic implications of increased aortic stiffness, the microvascular state in COPD management should be considered

Z2SAL: a translation-based model checker for Z

Despite being widely known and accepted in industry, the Z formal specification language has not so far been well supported by automated verification tools, mostly because of the challenges in handling the abstraction of the language. In this paper we discuss a novel approach to building a model-checker for Z, which involves implementing a translation from Z into SAL, the input language for the Symbolic Analysis Laboratory, a toolset which includes a number of model-checkers and a simulator. The Z2SAL translation deals with a number of important issues, including: mapping unbounded, abstract specifications into bounded, finite models amenable to a BDD-based symbolic checker; converting a non-constructive and piecemeal style of functional specification into a deterministic, automaton-based style of specification; and supporting the rich set-based vocabulary of the Z mathematical toolkit. This paper discusses progress made towards implementing as complete and faithful a translation as possible, while highlighting certain assumptions, respecting certain limitations and making use of available optimisations. The translation is illustrated throughout with examples; and a complete working example is presented, together with performance data

Traditional and emerging indicators of cardiovascular risk in chronic obstructive pulmonary disease

With the increased cardiovascular (CV) morbidity and mortality in subjects with chronic obstructive pulmonary disease (COPD), there is a priority to identify those patients at increased risk of cardiovascular disease. Stable patients with COPD (n = 185) and controls with a smoking history (n = 106) underwent aortic pulse wave velocity (PWV), blood pressure (BP) and skin autofluorescence (AF) at clinical stability. Blood was sent for fasting lipids, soluble receptor for advanced glycation end products (sRAGE) and CV risk prediction scores were calculated. More patients (18%) had a self-reported history of CV disease than controls (8%), p = 0.02, whilst diabetes was similar (14% and 10%), p = 0.44. Mean (SD) skin AF was greater in patients: 3.1 (0.5) AU than controls 2.8 (0.6) AU, p < 0.001. Aortic PWV was greater in patients: 10.2 (2.3) m/s than controls: 9.6 (2.0) m/s, p = 0.02 despite similar BP. The CV risk prediction scores did not differentiate between patients and controls nor were the individual components of the scores different. The sRAGE levels were not statistically different. We present different indicators of CV risk alongside each other in well-defined subjects with and without COPD. Two non-invasive biomarkers associated with future CV burden: skin AF and aortic PWV are both significantly greater in patients with COPD compared to the controls. The traditional CV prediction scores used in the general population were not statistically different. We provide new data to suggest that alternative approaches for optimal CV risk detection should be employed in COPD management

Cardiovascular and inflammatory effects of simvastatin therapy in patients with COPD: a randomized controlled trial.

BACKGROUND: There is excess cardiovascular mortality in patients with chronic obstructive pulmonary disease. Aortic stiffness, an independent predictor of cardiovascular risk, and systemic and airway inflammation are increased in patients with the disease. Statins modulate aortic stiffness and have anti-inflammatory properties. A proof-of-principle, double-blind, randomized trial determined if 6 weeks of simvastatin 20 mg once daily reduced aortic stiffness and systemic and airway inflammation in patients with chronic obstructive pulmonary disease. METHODS: Stable patients (n=70) were randomized to simvastatin (active) or placebo. Pre-treatment and post-treatment aortic stiffness, blood pressure, spirometry, and circulating and airway inflammatory mediators and lipids were measured. A predefined subgroup analysis was performed where baseline aortic pulse wave velocity (PWV) was >10 m/sec. RESULTS: Total cholesterol dropped in the active group. There was no significant change in aortic PWV between the active group and the placebo group (-0.7 m/sec, P=0.24). In those with aortic stiffness >10 m/sec (n=22), aortic PWV improved in the active group compared with the placebo group (-2.8 m/sec, P=0.03). Neither systemic nor airway inflammatory markers changed. CONCLUSION: There was a nonsignificant improvement in aortic PWV in those taking simvastatin 20 mg compared with placebo, but in those with higher baseline aortic stiffness (a higher risk group) a significant and clinically relevant reduction in PWV was shown

Does pulmonary rehabilitation address cardiovascular risk factors in patients with COPD?

Background Patients with COPD have an increased risk of cardiovascular disease. Whilst pulmonary rehabilitation has proven benefit for exercise tolerance and quality of life, any effect on cardiovascular risk has not been fully investigated. We hypothesised that pulmonary rehabilitation, through the exercise and nutritional intervention, would address these factors. Methods Thirty-two stable patients with COPD commenced rehabilitation, and were compared with 20 age and gender matched controls at baseline assessment. In all subjects, aortic pulse wave velocity (PWV) an independent non-invasive predictor of cardiovascular risk, blood pressure (BP), interleukin-6 (IL-6) and fasting glucose and lipids were determined. These measures, and the incremental shuttle walk test (ISWT) were repeated in the patients who completed pulmonary rehabilitation. Results On commencement of rehabilitation aortic PWV was increased in patients compared with controls (p < 0.05), despite mean BP, age and gender being similar. The IL-6 was also increased (p < 0.05). Twenty-two patients completed study assessments. In these subjects, rehabilitation reduced mean (SD) aortic PWV (9.8 (3.0) to 9.3 (2.7) m/s (p < 0.05)), and systolic and diastolic BP by 10 mmHg and 5 mmHg respectively (p < 0.01). Total cholesterol and ISWT also improved (p < 0.05). On linear regression analysis, the reduction in aortic PWV was attributed to reducing the BP. Conclusion Cardiovascular risk factors including blood pressure and thereby aortic stiffness were improved following a course of standard multidisciplinary pulmonary rehabilitation in patients with COPD

Relational Concurrent Refinement II: Internal Operations and Outputs

Two styles of description arise naturally in formal specification: state-based and behavioural. In state-based notations, a system is characterised by a collection of variables, and their values determine which actions may occur throughout a system history. Behavioural specifications describe the chronologies of actions -- interactions between a system and its environment. The exact nature of such interactions is captured in a variety of semantic models with corresponding notions of refinement; refinement in state based systems is based on the semantics of sequential programs and is modelled relationally. Acknowledging that these viewpoints are complementary, substantial research has gone into combining the paradigms. The purpose of this paper is to do three things. First, we survey recent results linking the relational model of refinement to the process algebraic models. Specifically, we detail how variations in the relational framework lead to relational data refinement being in correspondence with traces-divergences, singleton failures and failures-divergences refinement in a process semantics. Second, we generalise these results by providing a general flexible scheme for incorporating the two main ''erroneous'' concurrent behaviours: deadlock and divergence, into relational refinement. This is shown to subsume previous characterisations. In doing this we derive relational refinement rules for specifications containing both internal operations and outputs that corresponds to failures-divergences refinement. Third, the theory has been formally specified and verified using the interactive theorem prover KIV