Sciences Po Bordeaux

BACKGROUND: The prevalence of dementia is expected to soar as the average life expectancy increases, but recent estimates suggest that the age-specific incidence of dementia is declining in high-income countries. Temporal trends are best derived through continuous monitoring of a population over a long period with the use of consistent diagnostic criteria. We describe temporal trends in the incidence of dementia over three decades among participants in the Framingham Heart Study. METHODS: Participants in the Framingham Heart Study have been under surveillance for incident dementia since 1975. In this analysis, which included 5205 persons 60 years of age or older, we used Cox proportional-hazards models adjusted for age and sex to determine the 5-year incidence of dementia during each of four epochs. We also explored the interactions between epoch and age, sex, apolipoprotein E ε4 status, and educational level, and we examined the effects of these interactions, as well as the effects of vascular risk factors and cardiovascular disease, on temporal trends. RESULTS: The 5-year age- and sex-adjusted cumulative hazard rates for dementia were 3.6 per 100 persons during the first epoch (late 1970s and early 1980s), 2.8 per 100 persons during the second epoch (late 1980s and early 1990s), 2.2 per 100 persons during the third epoch (late 1990s and early 2000s), and 2.0 per 100 persons during the fourth epoch (late 2000s and early 2010s). Relative to the incidence during the first epoch, the incidence declined by 22%, 38%, and 44% during the second, third, and fourth epochs, respectively. This risk reduction was observed only among persons who had at least a high school diploma (hazard ratio, 0.77; 95% confidence interval, 0.67 to 0.88). The prevalence of most vascular risk factors (except obesity and diabetes) and the risk of dementia associated with stroke, atrial fibrillation, or heart failure have decreased over time, but none of these trends completely explain the decrease in the incidence of dementia. CONCLUSIONS: Among participants in the Framingham Heart Study, the incidence of dementia has declined over the course of three decades. The factors contributing to this decline have not been completely identified. (Funded by the National Institutes of Health.).

The world of climate politics is increasingly no longer confined to the activities of national governments and international negotiations. Critical to this transformation of the politics of climate change has been the emergence of new forms of transnational governance that cut across traditional state-based jurisdictions and operate across public and private divides. This book provides the first comprehensive, cutting-edge account of the world of transnational climate change governance. Co-authored by a team of the world's leading experts in the field and based on a survey of sixty case studies, the book traces the emergence, nature and consequences of this phenomenon, and assesses the implications for the field of global environmental politics. It will prove invaluable for researchers, graduate students and policy makers in climate change, political science, international relations, human geography, sociology and ecological economics.

Over a 6-month period, 23 members of the International Microvascular Research Group participated in a prospective survey of their microvascular free-flap practice. Data were recorded with each case for 60 variables covering patient characteristics, surgical technique, pharmacologic treatment, and postoperative outcome. A total of 493 free flaps were reported with a representative demographic distribution for age, sex, indications for surgery, risk factors, flap type, surgical technique, and pharmacologic intervention. Mixed effects logistic regression modeling was used to determine predictors of flap failure and associated complications. The overall incidence of flap failure was 4.1 percent (20 of 493). Reconstruction of an irradiated recipient site and the use of a skin-grafted muscle flap were the only statistically significant predictors of flap failure, with increased odds of failure of 4.2 (p = 0.01) and 11.1 (p = 0.03), respectively. A postoperative thrombosis requiring re-exploration surgery occurred in 9.9 percent of the flaps. The incidence of this complication was significantly higher when the flap was transferred to a chronic wound and when vein grafts were needed, with increased odds of failure of 2.9 (p = 0.02) and 2.5 (p = 0.02), respectively. There was a lower incidence of postoperative thrombosis when rectus/transverse rectus abdominis muscle (TRAM) flaps were used, where odds of failure decreased by 0.36 (p = 0.04), and when subcutaneous heparin was administered in the postoperative period, where odds decreased by 0.27 (p = 0.04). There was an overall 69-percent salvage rate for flaps identified with a postoperative thrombosis. Intraoperative thrombosis occurred in 41 cases (8.3 percent) and was observed more frequently in myocutaneous flaps or when vein grafts were needed (5.5 and 5.0 greater odds, respectively; p < 0.001) but was not associated with higher flap failure (2 of 41 cases; 4.9-percent failure rate). The incidence of a hematoma and/or hemorrhage was increased in obese patients and when vein grafts were needed [2.7 (p = 0.02) and 2.6 (p = 0.03) greater odds, respectively], whereas this complication was significantly decreased in muscle flaps (myocutaneous or skin-grafted muscle), in tobacco users, when a heparinized solution was used for general wound irrigation, and when the attending surgeon performed the arterial anastomosis (in contrast to the resident or fellow on staff) (p < 0.05 for each factor). With the multivariable analysis, many factors were found not to have a significant effect on flap outcome, including the recipient site (e.g., head/neck, breast, lower limb, etc.); indications for surgery (trauma, cancer, etc.); flap transfer in extremes of age, smokers, or diabetics; arterial anastomosis with an end-to-end versus end-to-side technique; irrigation of the vessel without or with heparin added to the irrigation solution; and a wide spectrum of antithrombotic drug therapies. These results present a current baseline for free-flap surgery to which future advances and improvements in technique and practice may be compared. (Plast. Reconstr. Surg. 102: 711, 1998.)

Ben Fine and Zavareh Rustomjee, The Political Economy of South Africa: from minerals—energy complex to industrialisation.London: Hurst, 1997, 278 pp., £35.00, ISBN 1 85065 258 9 hard covers, £14.95, ISBN 1 85065 257 0 paperback. - Volume 70 Issue 1

CRISPR-Cas9 is a promising technology for genome editing. Here we use Cas9 nuclease-induced double-strand break DNA (DSB) at the UROS locus to model and correct congenital erythropoietic porphyria. We demonstrate that homology-directed repair is rare compared with NHEJ pathway leading to on-target indels and causing unwanted dysfunctional protein. Moreover, we describe unexpected chromosomal truncations resulting from only one Cas9 nuclease-induced DSB in cell lines and primary cells by a p53-dependent mechanism. Altogether, these side effects may limit the promising perspectives of the CRISPR-Cas9 nuclease system for disease modeling and gene therapy. We show that the single nickase approach could be safer since it prevents on- and off-target indels and chromosomal truncations. These results demonstrate that the single nickase and not the nuclease approach is preferable, not only for modeling disease but also and more importantly for the safe management of future CRISPR-Cas9-mediated gene therapies.

Sixty-two patients with advanced measurable gastric cancer were treated with a combination chemotherapy program of 5-fluorouracil, doxorubicin, and mitomycin (FAM). Forty-two percent of patients achieved an objective partial response. The median duration of remission was 9 months and the median survival for responding patients, 12.5 months. The median survival for nonresponding patients was 3.5 months; all patients were dead by 8 months after initiation of therapy. The median survival of all 62 patients treated with FAM was 5.5 months. An analysis of possible prognostic variables including initial performance status, resectability of the primary gastric tumor, and histologic differentiation of the neoplasm failed to account for differences in patient response and survival. The FAM regimen was well tolerated, producing only moderate bone marrow suppression. These results show that patients with metastatic gastric cancer can be effectively palliated with FAM chemotherapy. The efficacy of this regimen should now be tested in patients with less advanced stages of this disease.

Different duplications of the APP locus have been identified in five families with autosomal dominant early onset Alzheimer's disease (ADEOAD) and Abeta-related cerebral amyloid angiopathy (CAA). This study describes the phenotype of this new entity. Clinical, neuropsychological, imagery and neuropathological data were reviewed. The phenotype was not dependent on the size of the duplication and there was no clinical feature of Down's syndrome. Dementia was observed in all cases; intracerebral haemorrhage (ICH) was reported in 6 (26%) and seizures occurred in 12 (57%) of 21 patients. Age of onset of dementia ranged from 42 to 59 years, ICH from 53 to 64 years and age at death from 46 to 75 years. The neuropathological findings in five cases demonstrated Alzheimer's disease and severe CAA lesions that were reminiscent from those reported in brains of Down's syndrome patients. A striking feature consisted in intraneuronal Abetax-40 accumulation located in the granular cell layer of the dentate gyrus and in the pyramidal cell layer of the Ammon's horn.

With this paper we present an analysis of sixty transnational governance initiatives and assess the implications for our understanding of the roles of public and private actors, the legitimacy of governance ‘beyond’ the state, and the North–South dimensions of governing climate change. In the first part of the paper we examine the notion of transnational governance and its applicability in the climate change arena, reflecting on the history and emergence of transnational governance initiatives in this issue area and key areas of debate. In the second part of the paper we present the findings from the database and its analysis. Focusing on three core issues, the roles of public and private actors in governing transnationally, the functions that such initiatives perform, and the ways in which accountability for governing global environmental issues might be achieved, we suggest that significant distinctions are emerging in the universe of transnational climate governance which may have considerable implications for the governing of global environmental issues. In conclusion, we reflect on these findings and the subsequent consequences for the governance of climate change.

Using a multilevel framework, we hypothesized that (a) individual perceptions of transformational leadership and (b) team-level transformational leadership climate would be positively related to individual adaptive performance. We also hypothesized that a stronger climate for innovation would enhance the association between transformational leadership and adaptive performance at the individual level. Hierarchical linear modeling conducted on data collected from 120 employees belonging to 35 teams and their managers in an organization operating in the aerospace industry confirmed our predictions. The significance and relevance of these findings for future research on transformational leadership and adaptive performance are discussed.

BACKGROUND AND OBJECTIVE: Many acne grading methods exist; however, there is no agreed-upon standard. Our objective was to create and validate a reproducible acne assessment scale for rating the severity of juvenile facial acne suitable for use in France and Europe. METHODS: The scale we created described the different types of acne lesions in a manner similar to global assessment scales used in clinical trials. The scale was then validated by seven expert dermatologists in the field of acne [the Global Evaluation Acne (GEA) group] first on 34 photographic cases of Caucasian acne patients and second by clinical examination of 22 acne patients. RESULTS: There was good agreement in Investigators' assessments of acne both on photographs and patients (R = 0.8057; P < 0.0001, and R = 0.8437; P = 0.0015). CONCLUSION: The GEA Scale is a global scale validated both on photographs and acne patients which can be used either in clinical research or by the dermatologist in his office.

Studies with low statistical power increase the likelihood that a statistically significant finding represents a false positive result. We conducted a review of meta-analyses of studies investigating the association of biological, environmental or cognitive parameters with neurological, psychiatric and somatic diseases, excluding treatment studies, in order to estimate the average statistical power across these domains. Taking the effect size indicated by a meta-analysis as the best estimate of the likely true effect size, and assuming a threshold for declaring statistical significance of 5%, we found that approximately 50% of studies have statistical power in the 0-10% or 11-20% range, well below the minimum of 80% that is often considered conventional. Studies with low statistical power appear to be common in the biomedical sciences, at least in the specific subject areas captured by our search strategy. However, we also observe evidence that this depends in part on research methodology, with candidate gene studies showing very low average power and studies using cognitive/behavioural measures showing high average power. This warrants further investigation.

There is a striking contrast between the dissemination of the concept of neopatrimonial rule in Africa and its more parsimonious mobilisation outside the continent. The increasing assimilation of the African neopatrimonial state to integral and predatory forms of politics has contributed to its perception as a global prototype of the ‘anti-developmental’ state. The article contrasts this trajectory with those observed in Latin America, South East Asia, Russia and Central Asia. There, patrimonialism and neopatrimonialism have been associated with a greater axiological neutrality than in Africa due, inter alia, to the preservation of an analytical dichotomy between regulated and predatory forms of neopatrimonialism. Neglected for all too long, the study of regulated forms of neopatrimonialism in Africa calls for fresh empirical and theoretical attention.

Abstract Purpose: Gastric carcinomas are heterogeneous, and the current therapy remains essentially based on surgery with conventional chemotherapy and radiotherapy. This study aimed to characterize biomarkers allowing the detection of cancer stem cells (CSC) in human gastric carcinoma of different histologic types. Experimental Design: The primary tumors from 37 patients with intestinal- or diffuse-type noncardia gastric carcinoma were studied, and patient-derived tumor xenograft (PDX) models in immunodeficient mice were developed. The expressions of 10 putative cell surface markers of CSCs, as well as aldehyde dehydrogenase (ALDH) activity, were studied, and the tumorigenic properties of cells were evaluated by in vitro tumorsphere assays and in vivo xenografts by limiting dilution assays. Results: We found that a subpopulation of gastric carcinoma cells expressing EPCAM, CD133, CD166, CD44, and a high ALDH activity presented the properties to generate new heterogeneous tumorspheres in vitro and tumors in vivo. CD44 and CD166 were coexpressed, representing 6.1% to 37.5% of the cells; ALDH activity was detected in 1.6% to 15.4% of the cells; and the ALDH+ cells represented a core within the CD44+/CD166+ subpopulation that contained the highest frequency of tumorigenic CSCs in vivo. The ALDH+ cells possessed drug efflux properties and were more resistant to standard chemotherapy than the ALDH− cells, a process that was partially reversed by verapamil treatment. Conclusions: CD44 and ALDH are the most specific biomarkers to detect and isolate tumorigenic and chemoresistant gastric CSCs in noncardia gastric carcinomas independently of the histologic classification of the tumor. Clin Cancer Res; 23(6); 1586–97. ©2016 AACR.

Due to the diversity of its players, the American healthcare sector has experimented with different types of integrated supply chain management systems for medical supplies. In the 1980s, US distributors were offering customers the so‐called stockless replenishment method, whereby the distributor picks and packs products according to the particular needs of each patient care unit and, in most cases, delivers them directly. By the late 1990s, stockless agreements had run out of steam, as distributors sought to optimize the balance between their efforts expended in hospital replenishment and the hospitals’ inventory savings. Among the various reflections and initiatives aimed at finding such a new balance, we focused on the experience of a Quebec (Canada) hospital adopting a hybrid version of the stockless system, under which the distributor supplied high‐volume products for the patient care unit in case quantities, leaving the institution’s central stores to break down bulk purchases of low‐volume products into point‐of‐use format (eaches). The study reveals marginal benefits from the hybrid method for both the institution and the distributor. However, it also reveals the importance of the manufacturer’s role with respect to packing formats, and demonstrates that the rearrangement of storage areas can generate substantial savings, opening the way to means for improving the healthcare sector supply chain.

BACKGROUND: Therapeutic communities (TCs) are drug-free residential settings, focused on psychosocial rehabilitation. While TCs are considered an effective method, the bulk of the research evidence is from poorly controlled studies. The goal of this study was to evaluate TC effectiveness in terms of abstinence and to determine if there were predictive factors of abstinence. METHODS: The search used Medline up to January 30, 2011 and was based on a systematic review method. Studies on retention in treatment and/or substance use were considered. RESULTS: Of the 321 studies retrieved from Medline, 12 met selection criteria including overall 3,271 participants from 61 TCs. On average, subjects stayed in TC a third of the planned time. The completion rate ranged from 9 to 56%. All studies showed that substance use decreased during TC, but relapse was frequent after TC. Treatment completion was the most predictive factor of abstinence at follow-up. Surprisingly, psychiatric comorbidities did not appear associated with relapse or with dropout. CONCLUSIONS: There was a drop in consumption after TC, but long-lasting benefits were uncertain. Further studies are needed in order to compare the efficacy of TC programs and other types of treatment settings for substance-related disorders.

AIMS: Clinical trials constitute the gold standard to assess the efficacy and safety of new medicines. However, because they are conducted in standardized conditions far from the real world of prescription and use, discrepancies in patient selection or treatment conditions may alter both the effectiveness and risks. On the basis of three examples, our objectives were to study the differences between the characteristics of treated populations and treatment patterns in clinical trials and in postmarketing settings and to discuss the potential consequences on actual efficacy and safety. METHODS: Treated populations were compared with patients included in premarketing clinical trials. Comparisons were made on the basis of demographic characteristics and treatment patterns. RESULTS: Whatever the indicator and the drug studied, differences were observed: from 0.04% to 63% for tacrine, from 0% to 37% for celecoxib and from 6% to 52% for simvastatin, with possible consequences on the effectiveness and safety of the drug concerned. Our results confirm the under-representation of women and elderly patients in premarketing clinical trials, e.g. an M : F ratio of 4.6 in clinical trails of simvastatin vs 1.0 in the joint population. Moreover, the concomitant use of medicines was made extremely restrictive by the protocols of these trials while this was not the case in the postmarketing phase. This has possible consequences on the effectiveness and safety of the drug concerned. CONCLUSIONS: These results plead for systematic ad hoc observational postmarketing studies for any novel and/or expensive medicine to assess the relevance of premarketing data.

Abstract Purpose: Regorafenib is synergistic with immune checkpoint inhibition in colorectal cancer preclinical models. Patients and Methods: This was a single-arm, multicentric phase II trial. Regorafenib was given 3 weeks on/1 week off, 160 mg every day; avelumab 10 mg/kg i.v. was given every 2 weeks, beginning at cycle 1, day 15 until progression or unacceptable toxicity. The primary endpoint was the confirmed objective response rate under treatment, as per RECIST 1.1. The secondary endpoints included a 1-year nonprogression rate, progression-free survival (PFS), and overall survival (OS), safety and biomarkers studies performed on sequential tumor samples obtained at baseline and at cycle 2 day 1. Results: Forty-eight patients were enrolled in four centers. Forty-three were assessable for efficacy after central radiological review. Best response was stable disease for 23 patients (53.5%) and progressive disease for 17 patients (39.5%). The median PFS and OS were 3.6 months [95% confidence interval (CI), 1.8–5.4] and 10.8 months (95% CI, 5.9–NA), respectively. The most common grade 3 or 4 adverse events were palmar-plantar erythrodysesthesia syndrome (n = 14, 30%), hypertension (n = 11, 23%), and diarrhea (n = 6, 13%). High baseline infiltration by tumor-associated macrophages was significantly associated with adverse PFS (1.8 vs. 3.7 months; P = 0.002) and OS (3.7 months vs. not reached; P = 0.002). Increased tumor infiltration by CD8+ T cells at cycle 2, day 1 as compared with baseline was significantly associated with better outcome. Conclusions: The combination of regorafenib + avelumab mobilizes antitumor immunity in a subset of patients with microsatellite stable colorectal cancer. Computational pathology through quantification of immune cell infiltration may improve patient selection for further studies investigating this approach.

Major structural changes have been taking place in European local government systems around the turn of the millennium. Changes that have already had substantial consequences for local political leadership and are likely to bring about further change in the future. A number of such restructuring trends are sweeping over the continent, but from different starting points, at varying pace and in various mixed configurations. The research was designed to assess how, by playing on these different contexts, the restructuring trends and reforms inscribed in the wider framework of increasing global exchanges impact on the concept and praxis of political representation at local level. Four different trends of change are in focus: structural transformations in terms of privatisation, contracting out and general mimicry of private sector institutional arrangements ('New Public Management'); changes in central-local relations, most often in form of decentralisation, whereby new tasks have been allocated to the local level; the importance of political parties; internal institutional arrangements of local authorities. Central topics in the study are recruitment processes, perspectives on democracy, leadership styles, networks, intergovernmental relations, the importance of the party system and horizontal power relations in the local government organization.

This article analyses the immediate and long term causes of the outbreak of religious violence between Muslims and Christians in Kaduna State, Nigeria, in 1987. The author argues that the crisis arose from the politicisation of religion in the regional contest for power. On the one hand is the issue of the rise of fundamentalist Christianity and Islam. On the other is the struggle for political power by the ‘northern Oligarchy’ within the north and against the south in which religion has become a means for forging new coalitions.

BACKGROUND AND PURPOSE: On top of functional outcome, accurate prediction of cognitive outcome for stroke patients is an unmet need with major implications for clinical management. We investigated whether stroke location may contribute independent prognostic value to multifactorial predictive models of functional and cognitive outcomes. METHODS: Four hundred twenty-eight consecutive patients with ischemic stroke were prospectively assessed with magnetic resonance imaging at 24 to 72 hours and at 3 months for functional outcome using the modified Rankin Scale and cognitive outcome using the Montreal Cognitive Assessment (MoCA). Statistical maps of functional and cognitive eloquent regions were derived from the first 215 patients (development sample) using voxel-based lesion-symptom mapping. We used multivariate logistic regression models to study the influence of stroke location (number of eloquent voxels from voxel-based lesion-symptom mapping maps), age, initial National Institutes of Health Stroke Scale and stroke volume on modified Rankin Scale and MoCA. The second part of our cohort was used as an independent replication sample. RESULTS: In univariate analyses, stroke location, age, initial National Institutes of Health Stroke Scale, and stroke volume were all predictive of poor modified Rankin Scale and MoCA. In multivariable analyses, stroke location remained the strongest independent predictor of MoCA and significantly improved the prediction compared with using only age, initial National Institutes of Health Stroke Scale, and stroke volume (area under the curve increased from 0.697-0.771; difference=0.073; 95% confidence interval, 0.008-0.155). In contrast, stroke location did not persist as independent predictor of modified Rankin Scale that was mainly driven by initial National Institutes of Health Stroke Scale (area under the curve going from 0.840 to 0.835). Similar results were obtained in the replication sample. CONCLUSIONS: Stroke location is an independent predictor of cognitive outcome (MoCA) at 3 months post stroke.