The president has gone out on a very precarious limb to find the consensus necessary to effect change.He has promised Americans that they can have more security and peace ofmind about their health care coverage, including improved benefits and a higher quality of care, simply by wringing savings out of the fat of the current system.This has led to charges from some quarters that the president is trying to get something for nothing.That assessment is too harsh.But it is true that the president is trying to convince the American people to sit still for fairly nasty surgery by promising that it will not hurt very much.How much pain the "haves" in the current system believe reform will bring will determine the fate of Clinton's plan.Small businesses are already yelling loudly that a mandate to cover workers will cost jobs and lots of them.Although the tobacco industry is not what it once was, it is still a force to be reckoned with in American politics, and big increases in vice taxes will not sit well with them or their concerned and ready to lobby cousins in the alcohol, gambling, and food industries.Advocates for elderly people and the very poor will vigorously protest if their current entitlement programmes are targeted for more than minimal cuts.And, as eager as many Americans are for lower costs, many will wince over the notion of capping of the rate at which insurance premiums for the basic or baseline package of health care services can rise-a strategy that some fear will deny them access to the next generation of medical technology and breakthroughs.Once the euphoria over the fact that the nation has finally managed to talk seriously about doing something about its
Clinical and anatomical characteristics are often considered key factors in deciding between percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) in patients with complex coronary artery disease (CAD) such as left-main CAD or 3-vessel disease. However, little is known about the interaction between self-reported preprocedural physical/mental health and clinical outcomes after revascularization.This subgroup analysis of the SYNTAXES trial (SYNTAX Extended Survival), which is the extended follow-up of the randomized SYNTAX trial (Synergy Between PCI With Taxus and Cardiac Surgery) comparing PCI with CABG in patients with left-main CAD or 3-vessel disease, stratified patients by terciles of Physical (PCS) or Mental Component Summary (MCS) scores derived from the preprocedural 36-Item Short Form Health Survey, with higher PCS and MCS scores representing better physical and mental health, respectively. The primary end point was all-cause death at 10 years.A total of 1656 patients with preprocedural 36-Item Short Form Health Survey data were included in the present study. Both higher PCS and MCS were independently associated with lower 10-year mortality (10-point increase in PCS adjusted hazard ratio, 0.84 [95% CI, 0.73-0.97]; P=0.021; in MCS adjusted hazard ratio, 0.85 [95% CI, 0.76-0.95]; P=0.005). A significant survival benefit with CABG over PCI was observed in the highest PCS (>45.5) and MCS (>52.3) terciles with significant treatment-by-subgroup interactions (PCS Pinteraction=0.033, MCS Pinteraction=0.015). In patients with both high PCS (>45.5) and MCS (>52.3), 10-year mortality was significantly higher with PCI compared with CABG (30.5% versus 12.2%; hazard ratio, 2.87 [95% CI, 1.55-5.30]; P=0.001), whereas among those with low PCS (≤45.5) or low MCS (≤52.3), there were no significant differences in 10-year mortality between PCI and CABG, resulting in a significant treatment-by-subgroup interaction (Pinteraction=0.002).Among patients with left-main CAD or 3-vessel disease, patient-reported preprocedural physical and mental health status was strongly associated with long-term mortality and modified the relative treatment effects of PCI versus CABG. Patients with the best physical and mental health had better 10-year survival with CABG compared with PCI. Assessment of self-reported physical and mental health is important when selecting the optimal revascularization strategy.URL: https://www.gov; SYNTAXES Unique identifier: NCT03417050. URL: https://www.gov; SYNTAX Unique identifier: NCT00114972.
<p> Under-deck cable-stayed bridges are innovative bridge configurations in which stays are located underneath the deck. This bridge typology can lead to highly efficient and slender decks, resulting in a large reduction of the amount of materials employed. Nevertheless, if very slender decks are designed, vibration problems can arise potentially compromising the comfort of bridge users. The dynamic response of an under-deck cable-stayed bridge with a steel-concrete composite deck under the action of moving loads is studied. After an initial modal analysis, the contribution of each mode is identified. Loads applied eccentrically on the cross-section of the deck are found to increase accelerations substantially. Amplification and cancellation speeds are observed to govern the maximum accelerations registered on the deck. A parametric analysis reveals the maximum slendernesses that can be achieved to satisfy different comfort criteria.</p>
A novel analytical framework for the inclusion of active damaging processes in a structural stability analysis is presented. The framework considers quasi-static deformation processes and is formulated in terms of a discrete coordinate approach, employing an extended total potential energy functional, where the current damage state is expressed in terms of geometric configuration and applied loading. Within the current framework, an efficient analysis of structures prone to buckling instability and material damage is enabled particularly where damage initiates once structural instability has been triggered. Composite panels with multiple damage mechanisms (e.g. delaminations, matrix cracks) are studied to showcase its application.
Drug eluting stents represent one of the fastest growing fields in interventional cardiology today. At the congress of the European Society of Cardiology in Amsterdam in 2000, I (PWS) was asked to give the Andreas Gruentzig Lecture. In the week preceding the lecture, we re-angiographied patients 32 and 33 of the initial cohort of patients who had received a rapamycin eluting stent in Sao Paulo and in Rotterdam. Scrutinising the 4–6 month angiographic and ultrasonic results of these patients, I became overwhelmingly convinced that we were the privileged witnesses of a new phenomenon: the almost complete abolition of intra-stent neointimal proliferation. Colleagues, invasive and non-invasive cardiologists, old friends, and financial analysts were surprised by the unusual “excess of enthusiasm” coming from somebody who has built over the years a reputation as a critical assessor, never one to be carried away by the hype of a new wave in interventional cardiology. In the history of this field I have recognised (and “got excited” by, as my American colleagues used to put it) only two revolutionary developments: the introduction of the moveable and steerable guidewire by John Simpson, and the advent of the stent (Palmaz-Schatz, Wallstent). The drug eluting stent is the third such development, and almost one year later I would like to restate the fact that we are entering a new era in interventional cardiology. Why? Because the principle of an eluting stent is sound, and because the three major technical challenges have been mastered—the controlled release of an efficient drug from a stable coating. Drug administration for the prevention of restenosis has been tested in the past—with disappointing results throughout. A proposed explanation for the repeated failure of clinical drug studies has been that agents given systematically cannot reach sufficient concentrations in injured arteries, which has a signficant impact …
The prostanoid receptor(s) that mediates inhibition of bacterial lipopolysaccharide (LPS)‐induced tumour necrosis factor‐α (TNFα) generation from human peripheral blood monocytes was classified by use of naturally occurring and synthetic prostanoid agonists and antagonists. In human monocytes that were adherent to plastic, neither prostaglandin D 2 (PGD 2 ), prostaglandin E 2 (PGE 2 ), prostaglandin F 2α (PGF 2α ) nor the stable prostacyclin and thromboxane mimetics, cicaprost and U‐46619, respectively, promoted the elaboration of TNFα‐like immunoreactivity, as assessed with a specific ELISA, indicating the absence of excitatory prostanoid receptors on these cells. Exposure of human monocytes to LPS (3 ng ml −1 , ∼ EC 84 ) resulted in a time‐dependent elaboration of TNFα which was suppressed in cells pretreated with prostaglandin E 1 (PGE 1 ), PGE 2 and cicaprost. This effect was concentration‐dependent with mean pIC 50 values of 7.14, 7.34 and 8.00 for PGE 1 , PGE 2 and cicaprost, respectively. PGD 2 , PGF 2α and U‐46619 failed to inhibit the generation of TNFα at concentrations up to 10 μ M . With respect to PGE 2 , the EP‐receptor agonists, 16,16‐dimethyl PGE 2 (non‐selective), misoprostol (EP 2 /EP 3 ‐selective), 11‐deoxy PGE 1 (EP 2 ‐selective) and butaprost (EP 2 ‐selective) were essentially full agonists as inhibitors of LPS‐induced TNFα generation with mean pIC 50 values of 6.21, 6.02, 5.67 and 5.59, respectively. In contrast to the results obtained with butaprost and 11‐deoxy PGE 1 , another EP 2 ‐selective agonist, AH 13205, inhibited TNFα generation by only 21% at the highest concentration (10 μ M ) examined. EP‐receptor agonists which have selectivity for the EP 1 ‐ (17‐phenyl‐ω‐trinor PGE 2 ) and EP 3 ‐receptor (MB 28,767, sulprostone) were inactive or only weakly active as inhibitors of TNFα generation. Pretreatment of human monocytes with the TP/EP 4 ‐receptor antagonist, AH 23848B, at 10, 30 and 100 μ M suppressed LPS‐induced TNFα generation by 10%, 28% and 77%, respectively, but failed to shift significantly the location of the PGE 2 concentration‐response curves. Given that AH 13205 was a poor inhibitor of TNFα generation, studies were performed to determine if it was a partial agonist and whether it could antagonize the inhibitory effect of PGE 2 . Pretreatment of human monocytes with 10 and 30 μ M AH 13205 inhibited the generation of TNFα by 31% and 53%, respectively, but failed to shift significantly the location of the PGE 2 concentration‐response curves at either concentration examined. Since PGD 2 and 17‐phenyl‐ω‐trinor PGE 2 (EP 1 ‐agonist) did not suppress TNFα generation, the EP 1 /EP 2 /DP‐receptor antagonist, AH 6809, was employed to assess if EP 2 ‐receptors mediated the inhibitory effect of PGE 2 . Pretreatment of human monocytes with 10 μ M AH 6809 did not affect LPS‐induced TNFα generation but produced a parallel 3.5 fold rightwards shift of the PGE 2 concentration‐response curve. Collectively, these data suggest that human peripheral blood monocytes express at least two distinct populations of inhibitory prostanoid receptors that mediate inhibition of LPS‐induced TNFα generation. One of these probably represents IP receptors based upon the selectivity of cicaprost for this subtype. The other population has the pharmacology of EP‐receptors, but the rank order of potency for a range of synthetic EP‐receptor agonists was inconsistent with an interaction with any of the currently defined subtypes. Given the pharmacological behaviour of butaprost, AH 6809 and AH 23848B in these cells, we propose that multiple (EP 2 ‐ and/or EP 4 ‐ and/or IP) or novel EP‐receptors mediate the inhibitory effect of PGE 2 on TNFα generation. British Journal of Pharmacology (1997) 122 , 149–157; doi: 10.1038/sj.bjp.0701360
