We assessed the relation of risk factors for cardiovascular disease to early atherosclerotic lesions in the aorta and coronary arteries in 35 persons (mean age at death, 18 years). Aortic involvement with fatty streaks was greater in blacks than in whites (37 vs. 17 percent, P less than 0.01). However, aortic fatty streaks were strongly related to antemortem levels of both total and low-density lipoprotein cholesterol (r = 0.67, P less than 0.0001 for each association), independently of race, sex, and age, and were inversely correlated with the ratio of high-density lipoprotein cholesterol to low-density plus very-low-density lipoprotein cholesterol (r = -0.35, P = 0.06). Coronary-artery fatty streaks were correlated with very-low-density lipoprotein cholesterol (r = 0.41, P = 0.04). Mean systolic blood-pressure levels also tended to be higher in the four subjects with coronary-artery fibrous plaques than in those without them: 112 mm Hg as compared with 104 (P = 0.09). These results document the importance of risk-factor levels to early anatomical changes in the aorta and coronary arteries. The progression of fatty streaks to fibrous plaques is uncertain, but these data suggest that a rational approach to the prevention of cardiovascular disease should begin early in life.

In this paper we focus on routing techniques for optimizing clock signals in small-cell (e.g., standard-cell, sea-of gate, etc...) ASICs. In previously reported work, the routin P of the clock net has been ordinary g obal routing techniques base a" erformed using on a minimum or minimal Steiner tree that have little underof clock routing problems. We F resent a novel to clock routing that all but e rminates clock yields excellent phase delay results for a wide range of chip sizes, net sizes (pin count), minimum feature sizes, and pin distributions on both randomly created and standard industrial benchmarks.For certain classes of pin distributions we have proven theoretically and observed exnerimentallv a decrease in skew with an increase in net Bize. In practice, we have observed a two to three order magnitude reduction in skew when compared to a minimum rectilinear spanning tree.

Co-innovation can be effective for complex challenges-involving interactions amongst multiple stakeholders, viewpoints, perceptions, practices and interests across programmes, sectors and national systems. Approaches to challenges in the primary sector have tended to be linear, where tools and outputs are developed by a few, mostly scientists/researchers, and then extended to stakeholders. A co-innovation approach first deciphers and delineates the biophysical, societal, regulatory, policy, economic and environmental drivers, constraints and controls influencing these challenges at multiple levels. Second, stakeholder interactions and perspectives can inform and change the focus as well as help in co-developing solutions to deliver agreed outcomes. However, there is limited systematic and comparative research on how coinnovation works out in different projects. Here we analyse the results of applying a co-innovation approach to five research projects in the New Zealand primary sector. The projects varied in depth and breadth of stakeholder engagement, availability of ready-made solutions and prevalence of interests and conflicts. The projects show how and why co-innovation approaches in some cases contributed to a shared understanding of complex problems. Our results confirm the context specificity of co-innovation practices.

Depressive disorders are a common cause of chronic and recurrent psychiatric dysfunction, constituting the fourth leading cause of global diseases. Depression is associated with a high rate of morbidity and mortality, and is a leading cause of global disability. Despite the effectiveness of most currently available antidepressants, many of them have a number of undesirable side effects. Agomelatine is the first melatonin (MT)(1)/MT(2) agonist having 5-hydroxytryptamine (5-HT)(2C) and 5-HT(2B) antagonist properties and antidepressant activity. Agomelatine is effective in several animal models of depression and anxiety. In addition, three large, multicenter, multinational, placebo-controlled studies and several double-blind, placebo-controlled trials of agomelatine have demonstrated that it is a clinically effective and well-tolerated antidepressant in acute trials. Since currently available antidepressants are not always adequate to cause complete remission of symptoms in severely depressed patients, the superior rate of response achieved with agomelatine in this group of patients underlines its future for clinical use in depressive disorders. In summary, the clinical advantage of agomelatine is attributed to its novel mechanism of action, which helps not only to exert antidepressant action, but also to regulate the sleep-wake rhythm.

The principal aim of this in vitro study was to assess the validity and reproducibility of the detection of occlusal caries using laser fluorescence (LF), prior to and following the placement of a clear fissure sealant. It also aimed to compare the manufacturer’s standard cut-off recommendations with those published for in vitro studies and to compare the validity and reproducibility of LF with clinical visual examination (CVE) for the detection of occlusal caries under sealants. Three clinicians independently examined visually and with LF 37 extracted teeth (25 molars, 12 premolars), with a range of clinical caries from apparently sound to cavitated dentinal caries. Examinations were conducted under dental surgery conditions. Subsequently, the teeth were serially sectioned to provide the validating criterion. Following placement of the sealant, the specificity generally increased but there was an associated loss of sensitivity, at both the D₁ (enamel and dentine) and D₃ (dentine) diagnostic thresholds. The LF readings were significantly lower after placement of the sealant (p < 0.05). The manufacturer’s recommended cut-offs appear to be the most appropriate to use. The CVE had superior validity and reproducibility when compared to LF. Overall, the placement of a clear sealant does influence the detection of caries by LF but does not prevent the detection of caries by this method.