Impact of mammographic screening and advanced cancer definition on the percentage of advanced-stage cancers in a steady-state breast screening programme in the Netherlands

Background: To estimate the percentages of advanced-stage breast cancers (BCs) detected during the course of a steady-state screening programme when using different definitions of advanced BC. Methods: Data of women aged 49–74 years, diagnosed with BC in 2006–2015, were selected from the Netherlands Cancer Registry and linked to the screening registry. BCs were classified as screen-detected, interval or non-screened. Three definitions of advanced BC were used for comparison: TNM stage (III–IV), NM stage (N+ and/or M+) and T size (invasive tumour ≥15 mm). Analyses were performed assuming a 10% overdiagnosis rate. In sensitivity analyses, this assumption varied from 0 to 30%. Results: We included 46,734 screen-detected, 17,362 interval and 24,189 non-screened BCs. By TNM stage, 4.9% of screen-detected BCs were advanced, compared with 19.4% and 22.8% of interval and non-screened BCs, respectively (p < 0.001). Applying the other definitions led to higher percentages of advanced BC being detected. Depending on the definition interval, non-screened BCs had a 2–5-times risk of being advanced. Conclusion: Irrespective of the definition, screen-detected BCs were less frequently in the advanced stage. These findings provide evidence of a stage shift to early detection and support the potential of mammographic screening to reduce treatment-related burdens and the mortality associated with BC

Origins and Outcomes of Electoral Institutions in African Hybrid Regimes: A Comparative Perspective

In the early 1990s most African countries carried out extensive reforms of their electoral regimes. Adopting a historical institutionalist approach, this paper critically examines the role of institutional path dependence in accounting for the setup of six African electoral regimes. For this purpose, we distinguish between different types of path dependence. The paper further analyzes the extent to which the development of electoral institutions contributed to the regime-type outcome (democratic/hybrid/autocratic). The main emphasis herein is on so-called hybrid regimes; in other words, regimes existing in the grey zone between democracy and autocracy. The paper finds that, while institutional path dependence has a limited but important impact on the setup of the electoral regimes, it is ultimately the process of decision-making during critical junctures that accounts for the regime type outcome. Hybrid regimes lack long-term institutional ownership

High-content analysis of α-synuclein aggregation and cell death in a cellular model of Parkinson's disease

Alpha-synuclein (α-SYN) aggregates represent a key feature of Parkinson's disease, but the exact relationship between α-SYN aggregation and neurodegeneration remains incompletely understood. Therefore, the availability of a cellular assay that allows medium-throughput analysis of α-SYN-linked pathology will be of great value for studying the aggregation process and for advancing α-SYN-based therapies.publisher: Elsevier articletitle: High-content analysis of α-synuclein aggregation and cell death in a cellular model of Parkinson's disease journaltitle: Journal of Neuroscience Methods articlelink: http://dx.doi.org/10.1016/j.jneumeth.2015.11.009 content_type: article copyright: Copyright © 2016 Published by Elsevier B.V.status: publishe

Efficacy and Safety of Ivacaftor in Patients Aged 6 to 11 Years with Cystic Fibrosis with a G551D Mutation

Lumacaftor/ivacaftor combination therapy has shown clinical benefits in patients with cystic fibrosis homozygous for the Phe508del CFTR mutation; however, pretreatment lung function is a confounding factor that potentially affects the efficacy and safety of this therapy. We aimed to assess the efficacy and safety of lumacaftor/ivacaftor therapy in these patients, defined by specific categories of lung function

End-On and Side-On Peroxo Derivatives of Non-Heme Iron Complexes with Pentadentate Ligands: Models for Putative Intermediates in Biological Iron/Dioxygen Chemistry

Mononuclear iron(III) species with end-on and side-on peroxide have been proposed or identified in the catalytic cycles of the antitumor drug bleomycin and a variety of enzymes, such as cytochrome P450 and Rieske dioxygenases. Only recently have biomimetic analogues of such reactive species been generated and characterized at low temperatures. We report the synthesis and characterization of a series of iron(II) complexes with pentadentate N5 ligands that react with H2O2 to generate transient low-spin FeIII-OOH intermediates. These intermediates have low-spin iron(III) centers exhibiting hydroperoxo-to-iron(III) charge-transfer bands in the 500-600-nm region. Their resonance Raman frequencies, νO-O, near 800 cm-1 are significantly lower than those observed for high-spin counterparts. The hydroperoxo-to-iron(III) charge-transfer transition blue-shifts and the νO-O of the Fe-OOH unit decreases as the N5 ligand becomes more electron donating. Thus, increasing electron density at the low-spin Fe(III) center weakens the O-O bond, in accord with conclusions drawn from published DFT calculations. The parent [(N4Py)FeIII(η1-OOH)]2+ (1a) ion in this series (N4Py = N,N-bis(2-pyridylmethyl)-N-bis(2-pyridyl)methylamine) can be converted to its conjugate base, which is demonstrated to be a high-spin iron(III) complex with a side-on peroxo ligand, [(N4Py)FeIII(η2-O2)]+ (1b). A detailed analysis of 1a and 1b by EPR and Mössbauer spectroscopy provides insights into their electronic properties. The orientation of the observed 57Fe A-tensor of 1a can be explained with the frequently employed Griffith model provided the rhombic component of the ligand field, determined by the disposition of the hydroperoxo ligand, is 45° rotated relative to the octahedral field. EXAFS studies of 1a and 1b reveal the first metrical details of the iron-peroxo units in this family of complexes: [(N4Py)FeIII(η1-OOH)]2+ has an Fe-O bond of 1.76 Å, while [(N4Py)FeIII(η2-O2)]+ has two Fe-O bonds of 1.93 Å, values which are in very good agreement with results obtained from DFT calculations.

Breast cancer screening halves the risk of breast cancer death: a case-referent study

Large-scale epidemiologic studies have consistently demonstrated the effectiveness of mammographic screening programs, however the benefits are still subject to debate. We estimated the effect of the Dutch screening program on breast cancer mortality. In a large multi-region case-referent study, we identified all breast cancer deaths in 2004 and 2005 in women aged 50-75 who had been invited for screening (cases). Cases were individually matched to referents from the population invited to screening. Conditional logistic regression was used to estimate the odds ratio (OR) of breast cancer death according to individual screening history. The OR was adjusted for self-selection bias using regional correction factors for the difference in baseline risk for breast cancer death between screened and unscreened women. A total of 1233 cases and 2090 referents were included in this study. We found a 58% reduction in breast cancer mortality in screened versus unscreened women (adjusted OR = 0.42, 95% CI 0.33-0.53). Screening, i.e. early detection and treatment, has resulted in a substantial reduction in breast cancer mortality, indicating that the Dutch breast cancer screening program is highly effectiv

Cosmopolitanism and Violence: The Limits of Global Civil Society

The problem of violence for social theory is not only a normative question which can be answered in political-ethical terms, but it is also a cognitive question relating to the definition of violence. This cognitive question is one of the main problems with the contemporary discourse of violence and it is this that makes the idea of a cosmopolitan public sphere particularly relevant since it is in public discourse that cognitive models are articulated. The real power of cosmopolitanism lies in communicative power, the problematizing, the reflexive transformation of cultural models and the raising of `voice'. Unless global civil society is based on a cosmopolitan political sphere there is the danger that it will be disembodied and helpless in the face of new forms of violence

Presidentes y características de la democracia en América Latina

El objetivo de este trabajo es buscar relaciones entre las características de la democracia de un país y los rasgos de su clase política. Para ello, se vinculan índices que miden distintos atributos de los sistemas políticos democráticos con el perfil político y social de los individuos que han ejercido la presidencia. El estudio se aplica a los presidentes latinoamericanos en el período comprendido entre 1978 y 2015. A partir de una primera observación de los datos, el análisis se centra en seis países: los tres que presentan mejores resultados y los tres que cuentan con peores puntajes en un agregado de indicadores que evalúan los sistemas democráticos. A medida que se incrementa la calidad de los sistemas políticos existe una tendencia a que también lo haga la calidad de sus políticos o, al menos, disminuye la probabilidad de que accedan líderes con menores niveles de formación y profesionalización política