[11C]Flumazenil brain uptake is influenced by the blood-brain barrier efflux transporter P-glycoprotein

Background:

Climate change adaptation in European river basins

This paper contains an assessment and standardized comparative analysis of the current water management regimes in four case-studies in three European river basins: the Hungarian part of the Upper Tisza, the Ukrainian part of the Upper Tisza (also called Zacarpathian Tisza), Alentejo Region (including the Alqueva Reservoir) in the Lower Guadiana in Portugal, and Rivierenland in the Netherlands. The analysis comprises several regime elements considered to be important in adaptive and integrated water management: agency, awareness raising and education, type of governance and cooperation structures, information management and—exchange, policy development and—implementation, risk management, and finances and cost recovery. This comparative analysis has an explorative character intended to identify general patterns in adaptive and integrated water management and to determine its role in coping with the impacts of climate change on floods and droughts. The results show that there is a strong interdependence of the elements within a water management regime, and as such this interdependence is a stabilizing factor in current management regimes. For example, this research provides evidence that a lack of joint/participative knowledge is an important obstacle for cooperation, or vice versa. We argue that there is a two-way relationship between information management and collaboration. Moreover, this research suggests that bottom-up governance is not a straightforward solution to water management problems in large-scale, complex, multiple-use systems, such as river basins. Instead, all the regimes being analyzed are in a process of finding a balance between bottom-up and top–down governance. Finally, this research shows that in a basin where one type of extreme is dominant—like droughts in the Alentejo (Portugal) and floods in Rivierenland (Netherlands)—the potential impacts of other extremes are somehow ignored or not perceived with the urgency they might deserv

Delineation and Diagnostic Criteria of Oral-Facial-Digital Syndrome Type VI

Oral-Facial-Digital Syndrome type VI (OFD VI) represents a rare phenotypic subtype of Joubert syndrome and related disorders (JSRD). In the original report polydactyly, oral findings, intellectual disability, and absence of the cerebellar vermis at post-mortem characterized the syndrome. Subsequently, the molar tooth sign (MTS) has been found in patients with OFD VI, prompting the inclusion of OFD VI in JSRD. We studied the clinical, neurodevelopmental, neuroimaging, and genetic findings in a cohort of 16 patients with OFD VI. We derived the following inclusion criteria from the literature: 1) MTS and one oral finding and polydactyly, or 2) MTS and more than one typical oral finding. The OFD VI neuroimaging pattern was found to be more severe than in other JSRD subgroups and includes severe hypoplasia of the cerebellar vermis, hypoplastic and dysplastic cerebellar hemispheres, marked enlargement of the posterior fossa, increased retrocerebellar collection of cerebrospinal fluid, abnormal brainstem, and frequently supratentorial abnormalities that occasionally include characteristic hypothalamic hamartomas. Additionally, two new JSRD neuroimaging findings (ascending superior cerebellar peduncles and fused thalami) have been identified. Tongue hamartomas, additional frenula, upper lip notch, and mesoaxial polydactyly are specific findings in OFD VI, while cleft lip/palate and other types of polydactyly of hands and feet are not specific. Involvement of other organs may include ocular findings, particularly colobomas. The majority of the patients have absent motor development and profound cognitive impairment. In OFD VI, normal cognitive functions are possible, but exceptional. Sequencing of known JSRD genes in most patients failed to detect pathogenetic mutations, therefore the genetic basis of OFD VI remains unknown. Compared with other JSRD subgroups, the neurological findings and impairment of motor development and cognitive functions in OFD VI are significantly worse, suggesting a correlation with the more severe neuroimaging findings. Based on the literature and this study we suggest as diagnostic criteria for OFD VI: MTS and one or more of the following: 1) tongue hamartoma(s) and/or additional frenula and/or upper lip notch; 2) mesoaxial polydactyly of one or more hands or feet; 3) hypothalamic hamartoma

Oxidation and metal-insertion in molybdenite surfaces: evaluation of charge-transfer mechanisms and dynamics

Molybdenum disulfide (MoS2), a layered transition-metal dichalcogenide, has been of special importance to the research community of geochemistry, materials and environmental chemistry, and geotechnical engineering. Understanding the oxidation behavior and charge-transfer mechanisms in MoS2 is important to gain better insight into the degradation of this mineral in the environment. In addition, understanding the insertion of metals into molybdenite and evaluation of charge-transfer mechanism and dynamics is important to utilize these minerals in technological applications. Furthermore, a detailed investigation of thermal oxidation behavior and metal-insertion will provide a basis to further explore and model the mechanism of adsorption of metal ions onto geomedia

Hematological Parameters Outperform Plasma Markers in Predicting Long-Term Mortality After Coronary Angiography

High-sensitivity troponin I (hsTnI) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) are predictors of coronary artery disease. Recently, routine hematological parameters emerged as mortality predictors. We examined the predictive value of hematological parameters (from the Utrecht Patient Oriented Database) and hsTnI and NT-pro-BNP for mortality in a coronary angiography population (Utrecht Coronary Biobank n = 1913). Using Cox regression, receiver operating characteristics, integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI) analysis, we compared the predictive properties of hematological parameters with hsTnI and NT-pro-BNP for mortality. During a median follow-up duration of 1.8 years, 77 deaths occurred. A panel of 7 hematological parameters (leukocyte count, reticulocyte mean corpuscular hemoglobin concentration, red blood cell [RBC] green (FL1) fluorescence, %neutrophils, %large [>120 fL] RBCs, %monocytes, and coefficient of variation of neutrophil complexity) was highly predictive. Added to clinical characteristics, hematological parameters (area under the curve [AUC]: 0.855, P < .001; IDI: 0.04, P = .02; cNRI: 0.41, P < .001) were better predictors than hsTnI (AUC: 0.818) or NT-pro-BNP (AUC: 0.834) alone or combined (AUC: 0.834). Hematological parameters may provide mortality risk information following coronary angiography and may be superior to hsTnI and/or NT-pro-BNP

Emotional support, education and self-rated health in 22 European countries

<p>Abstract</p> <p>Background</p> <p>The analyses focus on three aims: (1) to explore the associations between education and emotional support in 22 European countries, (2) to explore the associations between emotional support and self-rated health in the European countries, and (3) to analyse whether the association between education and self-rated health can be partly explained by emotional support.</p> <p>Methods</p> <p>The study uses data from the European Social Survey 2003. Probability sampling from all private residents aged 15 years and older was applied in all countries. The European Social Survey includes 42,359 cases. Persons under age 25 were excluded to minimise the number of respondents whose education was not complete. Education was coded according to the International Standard Classification of Education. Perceived emotional support was assessed by the availability of a confidant with whom one can discuss intimate and personal matters with. Self-rated health was used as health indicator.</p> <p>Results</p> <p>Results of multiple logistic regression analyses show that emotional support is positively associated with education among women and men in most European countries. However, the magnitude of the association varies according to country and gender. Emotional support is positively associated with self-rated health. Again, gender and country differences in the association were observed. Emotional support explains little of the educational differences in self-rated health among women and men in most European countries.</p> <p>Conclusion</p> <p>Results indicate that it is important to consider socio-economic factors like education and country-specific contexts in studies on health effects of emotional support.</p

European Project on Osteoarthritis (EPOSA): methodological challenges in harmonization of existing data from five European population-based cohorts on aging

BackgroundThe European Project on OSteoArthritis (EPOSA), here presented for the first time, is a collaborative study involving five European cohort studies on aging. This project focuses on the personal and societal burden and its determinants of osteoarthritis (OA). The aim of the current report is to describe the purpose of the project, the post harmonization of the cross-national data and methodological challenges related to the harmonization process MethodsThe study includes data from cohort studies in five European countries (Germany, Italy, the Netherlands, Spain and the United Kingdom) on older community-dwelling persons aged ? 59 years. The study design and main characteristics of the five cohort studies are described. Post harmonization algorithms are developed by finding a "common denominator" to merge the datasets and weights are calculated to adjust for differences in age and sex distribution across the datasets. ResultsA harmonized database was developed, consisting of merged data from all participating countries. In total, 10107 persons are included in the harmonized dataset with a mean age of 72.8 years (SD 6.1). The female/male ratio is 53.3/46.7%. Some variables were difficult to harmonize due to differences in wording and categories, differences in classifications and absence of data in some countries. The post harmonization algorithms are described in detail in harmonization guidelines attached to this paper. ConclusionsThere was little evidence of agreement on the use of several core data collection instruments, in particular on the measurement of OA. The heterogeneity of OA definitions hampers comparing prevalence rates of OA, but other research questions can be investigated using high quality harmonized data. By publishing the harmonization guidelines, insight is given into (the interpretation of) all post harmonized data of the EPOSA study. <br/

Bcl-2 and β1-integrin predict survival in a tissue microarray of small cell lung cancer.

INTRODUCTION: Survival in small cell lung cancer (SCLC) is limited by the development of chemoresistance. Factors associated with chemoresistance in vitro have been difficult to validate in vivo. Both Bcl-2 and β(1)-integrin have been identified as in vitro chemoresistance factors in SCLC but their importance in patients remains uncertain. Tissue microarrays (TMAs) are useful to validate biomarkers but no large TMA exists for SCLC. We designed an SCLC TMA to study potential biomarkers of prognosis and then used it to clarify the role of both Bcl-2 and β(1)-integrin in SCLC. METHODS: A TMA was constructed consisting of 184 cases of SCLC and stained for expression of Bcl-2 and β(1)-integrin. The slides were scored and the role of the proteins in survival was determined using Cox regression analysis. A meta-analysis of the role of Bcl-2 expression in SCLC prognosis was performed based on published results. RESULTS: Both proteins were expressed at high levels in the SCLC cases. For Bcl-2 (n=140), the hazard ratio for death if the staining was weak in intensity was 0.55 (0.33-0.94, P=0.03) and for β(1)-integrin (n=151) was 0.60 (0.39-0.92, P=0.02). The meta-analysis showed an overall hazard ratio for low expression of Bcl-2 of 0.91(0.74-1.09). CONCLUSIONS: Both Bcl-2 and β(1)-integrin are independent prognostic factors in SCLC in this cohort although further validation is required to confirm their importance. A TMA of SCLC cases is feasible but challenging and an important tool for biomarker validation

Second-line treatment with irinotecan plus cisplatin vs cisplatin of patients with advanced non-small-cell lung cancer pretreated with taxanes and gemcitabine: a multicenter randomised phase II study

The aim of this study was to compare the irinotecan/cisplatin regimen with cisplatin as second-line chemotherapy in patients with advanced non-small-cell lung cancer (NSCLC) pretreated with a taxane/gemcitabine regimen. Patients (n=147) with stage IV NSCLC pretreated with a taxane/gemcitabine regimen were randomly assigned to receive either irinotecan (110 mg m−2, day 1 and 100 mg m−2, day 8) and cisplatin (80 mg m−2, day 8) (IC; n=74) or CDDP (80 mg m−2, day 1) (C; n=73) every 3 weeks. Patients treated with IC and C had a median survival of 7.8 and 8.8 months, respectively (P=0.933). The 1-year survival rate was 34.3% for IC-treated patients and 31.7% for C-treated patients. Cox's regression analysis revealed that response to treatment (hazard ratio (HR)=2.787; 95% confidence interval (CI): 1.1578–4.922) and performance status (HR=1.865; 95% CI: 1.199–2.872) was independent prognostic factors for survival. Overall response rate was 22.5% (95% CI: 12.8–32.2%) for IC-treated patients and 7.0% (95% CI: 1.15–13.6%) for C-treated patients (P=0.012); tumour growth control (partial remission (PR)+stable disease (SD)) was observed in 26 (38%) IC and 25 (36%) C patients (P=0.878). There was no difference in terms of quality of life between the two chemotherapy arms. The incidence of febrile neutropenia, grade 3 and 4 neutropenia and grade 3 and 4 diarrhoea was significantly higher in the IC- than the C-treated patients. Other toxicities were mild. There were no treatment-related deaths in either arm. The IC regimen did not confer a survival benefit compared with C as second-line treatment of patients with advanced NSCLC pretreated with a taxane/gemcitabine regimen, despite its better efficacy in terms of response rate

The Binary Protein Interactome of Treponema pallidum – The Syphilis Spirochete

Protein interaction networks shed light on the global organization of proteomes but can also place individual proteins into a functional context. If we know the function of bacterial proteins we will be able to understand how these species have adapted to diverse environments including many extreme habitats. Here we present the protein interaction network for the syphilis spirochete Treponema pallidum which encodes 1,039 proteins, 726 (or 70%) of which interact via 3,649 interactions as revealed by systematic yeast two-hybrid screens. A high-confidence subset of 991 interactions links 576 proteins. To derive further biological insights from our data, we constructed an integrated network of proteins involved in DNA metabolism. Combining our data with additional evidences, we provide improved annotations for at least 18 proteins (including TP0004, TP0050, and TP0183 which are suggested to be involved in DNA metabolism). We estimate that this “minimal” bacterium contains on the order of 3,000 protein interactions. Profiles of functional interconnections indicate that bacterial proteins interact more promiscuously than eukaryotic proteins, reflecting the non-compartmentalized structure of the bacterial cell. Using our high-confidence interactions, we also predict 417,329 homologous interactions (“interologs”) for 372 completely sequenced genomes and provide evidence that at least one third of them can be experimentally confirmed