Change in physical activity after smoking cessation: the Coronary Artery Risk Development in Young Adults (CARDIA) study.

AIMS: To estimate physical activity trajectories for people who quit smoking, and compare them to what would have been expected had smoking continued. DESIGN, SETTING AND PARTICIPANTS: A total of 5115 participants in the Coronary Artery Risk Development in Young Adults Study (CARDIA) study, a population-based study of African American and European American people recruited at age 18-30 years in 1985/6 and followed over 25 years. MEASUREMENTS: Physical activity was self-reported during clinical examinations at baseline (1985/6) and at years 2, 5, 7, 10, 15, 20 and 25 (2010/11); smoking status was reported each year (at examinations or by telephone, and imputed where missing). We used mixed linear models to estimate trajectories of physical activity under varying smoking conditions, with adjustment for participant characteristics and secular trends. FINDINGS: We found significant interactions by race/sex (P = 0.02 for the interaction with cumulative years of smoking), hence we investigated the subgroups separately. Increasing years of smoking were associated with a decline in physical activity in black and white women and black men [e.g. coefficient for 10 years of smoking: -0.14; 95% confidence interval (CI) = -0.20 to -0.07, P < 0.001 for white women]. An increase in physical activity was associated with years since smoking cessation in white men (coefficient 0.06; 95% CI = 0 to 0.13, P = 0.05). The physical activity trajectory for people who quit diverged progressively towards higher physical activity from the expected trajectory had smoking continued. For example, physical activity was 34% higher (95% CI = 18 to 52%; P < 0.001) for white women 10 years after stopping compared with continuing smoking for those 10 years (P = 0.21 for race/sex differences). CONCLUSIONS: Smokers who quit have progressively higher levels of physical activity in the years after quitting compared with continuing smokers.

Movement, impacts and management of plant distributions in response to climate change: insights from invasions

A major challenge in this era of rapid climate change is to predict changes in species distributions and their impacts on ecosystems, and, if necessary, to recommend management strategies for maintenance of biodiversity or ecosystem services. Biological invasions, studied in most biomes of the world, can provide useful analogs for some of the ecological consequences of species distribution shifts in response to climate change. Invasions illustrate the adaptive and interactive responses that can occur when species are confronted with new environmental conditions. Invasion ecology complements climate change research and provides insights into the following questions: i) how will species distributions respond to climate change? ii) how will species movement affect recipient ecosystems? and iii) should we, and if so how can we, manage species and ecosystems in the face of climate change? Invasion ecology demonstrates that a trait-based approach can help to predict spread speeds and impacts on ecosystems, and has the potential to predict climate change impacts on species ranges and recipient ecosystems. However, there is a need to analyse traits in the context of life-history and demography, the stage in the colonisation process (e.g., spread, establishment or impact), the distribution of suitable habitats in the landscape, and the novel abiotic and biotic conditions under which those traits are expressed. As is the case with climate change, invasion ecology is embedded within complex societal goals. Both disciplines converge on similar questions of "when to intervene?" and "what to do?" which call for a better understanding of the ecological processes and social values associated with changing ecosystems.

Absence of progression as assessed by response evaluation criteria in solid tumors predicts survival in advanced GI stromal tumors treated with imatinib mesylate: the intergroup EORTC-ISG-AGITG phase III trial.

PURPOSE: From February 2001 to February 2002, 946 patients with advanced GI stromal tumors (GISTs) treated with imatinib were included in a controlled EORTC/ISG/AGITG (European Organisation for Research and Treatment of Cancer/Italian Sarcoma Group/Australasian Gastro-Intestinal Trials Group) trial. This analysis investigates whether the response classification assessed by RECIST (Response Evaluation Criteria in Solid Tumors), predicts for time to progression (TTP) and overall survival (OS). PATIENTS AND METHODS: Per protocol, the first three disease assessments were done at 2, 4, and 6 months. For the purpose of the analysis (landmark method), disease response was subclassified in six categories: partial response (PR; > 30% size reduction), minor response (MR; 10% to 30% reduction), no change (NC) as either NC- (0% to 10% reduction) or NC+ (0% to 20% size increase), progressive disease (PD; > 20% increase/new lesions), and subjective PD (clinical progression). RESULTS: A total of 906 patients had measurable disease at entry. At all measurement time points, complete response (CR), PR, and MR resulted in similar TTP and OS; this was also true for NC- and NC+, and for PD and subjective PD. Patients were subsequently classified as responders (CR/PR/MR), NC (NC+/NC-), or PD. This three-class response categorization was found to be highly predictive of further progression or survival for the first two measurement points. After 6 months of imatinib, responders (CR/PR/MR) had the same survival prognosis as patients classified as NC. CONCLUSION: RECIST perfectly enables early discrimination between patients who benefited long term from imatinib and those who did not. After 6 months of imatinib, if the patient is not experiencing PD, the pattern of radiologic response by tumor size criteria has no prognostic value for further outcome. Imatinib needs to be continued as long as there is no progression according to RECIST.

EuroCMR (European Cardiovascular Magnetic Resonance) registry: results of the German pilot phase.

OBJECTIVES: During its German pilot phase, the EuroCMR (European Cardiovascular Magnetic Resonance) registry sought to evaluate indications, image quality, safety, and impact on patient management of routine CMR. BACKGROUND: CMR has a broad range of applications and is increasingly used in clinical practice. METHODS: This was a multicenter registry with consecutive enrollment of patients in 20 German centers. RESULTS: A total of 11,040 consecutive patients were enrolled. Eighty-eight percent of patients received gadolinium-based contrast agents. Twenty-one percent underwent adenosine perfusion, and 11% high-dose dobutamine-stress CMR. The most important indications were workup of myocarditis/cardiomyopathies (32%), risk stratification in suspected coronary artery disease/ischemia (31%), as well as assessment of viability (15%). Image quality was good in 90.1%, moderate in 8.1%, and inadequate in 1.8% of cases. Severe complications occurred in 0.05%, and were all associated with stress testing. No patient died during or due to CMR. In nearly two-thirds of patients, CMR findings impacted patient management. Importantly, in 16% of cases the final diagnosis based on CMR was different from the diagnosis before CMR, leading to a complete change in management. In more than 86% of cases, CMR was capable of satisfying all imaging needs so that no further imaging was required. CONCLUSIONS: CMR is frequently performed in clinical practice in many participating centers. The most important indications are workup of myocarditis/cardiomyopathies, risk stratification in suspected coronary artery disease/ischemia, and assessment of viability. CMR imaging as used in the centers of the pilot registry is a safe procedure, has diagnostic image quality in 98% of cases, and its results have strong impact on patient management.

Late Early Triassic climate change: Insights from carbonate carbon isotopes, sedimentary evolution and ammonoid paleobiogeography

The late Early Triassic sedimentary-facies evolution and carbonate carbon-isotope marine record (delta(13)C(carb)) of ammonoid-rich, outer platform settings show striking similarities between the South ChinaBlock (SCB) and the widely distant Northern Indian Margin (NIM). The studied sections are located within the Triassic Tethys Himalayan belt (Losar section, Himachal Pradesh, India) and the Nanpanjiang Basin in the South China Block (Jinya section, Guangxi Province), respectively. Carbon isotopes from the studied sections confirm the previously observed carbon cycle perturbations at a time of major paleoceanographic changes in the wake of the end-Permian biotic crisis. This study documents the coincidence between a sharp increase in the carbon isotope composition and the worldwide ammonoid evolutionary turnover (extinction followed by a radiation) occurring around the Smithian-Spathian boundary. Based on recent modeling studies on ammonoid paleobiogeography and taxonomic diversity, we demonstrate that the late Early Triassic (Smithian and Spathian) was a time of a major climate change. More precisely, the end Smithian climate can be characterized by a warm and equable climate underlined by a flat, pole-to-equator, sea surface temperature (SST) gradient, while the steep Spathian SST gradient suggests latitudinally differentiated climatic conditions. Moreover, sedimentary evidence suggests a transition from a humid and hot climate during the Smithian to a dryer climate from the Spathian onwards. By analogy with comparable carbon isotope perturbations in the Late Devonian, Jurassic and Cretaceous we propose that high atmospheric CO(2) levels could have been responsible for the observed carbon cycle disturbance at the Smithian-Spathian boundary. We suggest that the end Smithian ammonoid extinction has been essentially caused by a warm and equable climate related to an increased CO(2) flux possibly originating from a short eruptive event of the Siberian igneous province. This increase in atmospheric CO(2) concentrations could have additionally reduced the marine calcium carbonate oversaturation and weakened the calcification potential of marine organisms, including ammonoids, in late Smithian oceans. (c) 2006 Elsevier B.V. All rights reserved.

The politics of contaminated sites management : institutional regime change and actor's mode of participation in the environmental management of the Bonfol Chemical Waste Landfill in Switzerland

By the end of the 1970s, contaminated sites had emerged as one of the most complex and urgent environmental issues affecting industrialized countries. The authors show that small and prosperous Switzerland is no exception to the pervasive problem of sites contamination, the legacy of past practices in waste management having left some 38,000 contaminated sites throughout the country. This book outlines the problem, offering evidence that open and polycentric environmental decision-making that includes civil society actors is valuable. They propose an understanding of environmental management of contaminated sites as a political process in which institutions frame interactions between strategic actors pursuing sometimes conflicting interests. In the opening chapter, the authors describe the influences of politics and the power relationships between actors involved in decision-making in contaminated sites management, which they term a "wicked problem." Chapter Two offers a theoretical framework for understanding institutions and the environmental management of contaminated sites. The next five chapters present a detailed case study on environmental management and contaminated sites in Switzerland, focused on the Bonfol Chemical Landfill. The study and analysis covers the establishment of the landfill under the first generation of environmental regulations, its closure and early remediation efforts, and the gambling on the remediation objectives, methods and funding in the first decade of the 21st Century. The concluding chapter discusses the question of whether the strength of environmental regulations, and the type of interactions between public, private, and civil society actors can explain the environmental choices in contaminated sites management. Drawing lessons from research, the authors debate the value of institutional flexibility for dealing with environmental issues such as contaminated sites.

Current multiple myeloma treatment strategies with novel agents: a European perspective.

The treatment of multiple myeloma (MM) has undergone significant developments in recent years. The availability of the novel agents thalidomide, bortezomib, and lenalidomide has expanded treatment options and has improved the outcome of patients with MM. Following the introduction of these agents in the relapsed/refractory setting, they are also undergoing investigation in the initial treatment of MM. A number of phase III trials have demonstrated the efficacy of novel agent combinations in the transplant and nontransplant settings, and based on these results standard induction regimens are being challenged and replaced. In the transplant setting, a number of newer induction regimens are now available that have been shown to be superior to the vincristine, doxorubicin, and dexamethasone regimen. Similarly, in the front-line treatment of patients not eligible for transplantation, regimens incorporating novel agents have been found to be superior to the traditional melphalan plus prednisone regimen. Importantly, some of the novel agents appear to be active in patients with high-risk disease, such as adverse cytogenetic features, and certain comorbidities, such as renal impairment. This review presents an overview of the most recent data with these novel agents and summarizes European treatment practices incorporating the novel agents.

Les connectivites: progrès thérapeutiques et place de la biothérapie [Connective tissue diseases: news in therapy, role of biologics agents].

Systemic lupus erythematosus and primary Sjögren's syndrom are the two major connective tissue diseases. A better knowledge of their physiopathology allows us today to propose an adapted therapy. Moreover progress concerns the oldest treatment, hydroxychloroquine, and biotherapy. Hydroxychloroquine is still an actual treatment for lupus, its positive effects are better understood today. Nevertheless it does not seem to be efficient to treat primitive Sjögren. Biotherapy targeting B lymphocytes seems efficient in these two connective tissue diseases. Anti TNF therapy is not recommended and seems to induce connective tissue diseases. The real news is the recent approval and reimbursement in Switzerland of the new drug belimumab (Benlysta) in case of moderate lupus.

Strategies for the development of tdm for targeted anticancer agents

Most of the novel targeted anticancer agents share classical characteristics that define drugs as candidates for blood concentration monitoring: long-term therapy; high interindividual but restricted intraindividual variability; significant drug-drug and drug- food interactions; correlations between concentration and efficacy/ toxicity with rather narrow therapeutic index; reversibility of effects; and absence of early markers of response. Surprisingly though, therapeutic concentration monitoring has received little attention for these drugs despite reiterated suggestions from clinical pharmacologists. Several issues explain the lack of clinical research and development in this field: global tradition of empiricism regarding treatment monitoring, lack of formal conceptual framework, ethical difficulties in the elaboration of controlled clinical trials, disregard from both drug manufacturers and public funders, limited encouragement from regulatory authorities, and practical hurdles making dosage adjustment based on concentration monitoring a difficult task for prescribers. However, new technologies are soon to help us overcome these obstacles, with the advent of miniaturized measurement devices able to quantify circulating drug concentrations at the point-of-care, to evaluate their plausibility given actual dosage and sampling time, to determine their appropriateness with reference to therapeutic targets, and to advise on suitable dosage adjustment. Such evolutions could bring conceptual changes into the clinical development of drugs such as anticancer agents, while increasing the therapeutic impact of population PK-PD studies and systematic reviews. Research efforts in that direction from the clinical pharmacology community will be essential for patients to receive the greatest benefits and the least harm from new anticancer treatments. The example of imatinib, the first commercialized tyrosine kinase inhibitor, will be outlined to illustrate a potential research agenda for the rational development of therapeutic concentration monitoring.

Predictors of Weight Change in Sedentary Smokers Receiving a Standard Smoking Cessation Intervention.

INTRODUCTION: Quitting smoking is associated with weight gain, which may threaten motivation to engage or sustain a quit attempt. The pattern of weight gained by smokers treated according to smoking cessation guidelines has been poorly described. We aimed to determine the weight gained after smoking cessation and its predictors, by smokers receiving individual counseling and nicotine replacement therapies for smoking cessation. METHODS: We performed an ancillary analysis of a randomized controlled trial assessing moderate physical activity as an aid for smoking cessation in addition to standard treatment in sedentary adult smokers. We used mixed longitudinal models to describe the evolution of weight over time, thus allowing us to take every participant into account. We also fitted a model to assess the effect of smoking status and reported use of nicotine replacement therapy at each time point. We adjusted for intervention group, sex, age, nicotine dependence, and education. RESULTS: In the whole cohort, weight increased in the first 3 months, and stabilized afterwards. Mean 1-year weight gain was 3.3kg for women and 3.9kg for men (p = .002). Higher nicotine dependence and male sex were associated with more weight gained during abstinence. Age over median was associated with continuing weight gain during relapse. There was a nonsignificant trend toward slower weight gain with use of nicotine replacement therapies. CONCLUSION: Sedentary smokers receiving a standard smoking cessation intervention experience a moderate weight gain, limited to the first 3 months. Older age, male sex, and higher nicotine dependence are predictors of weight gain.