A mixture model to distinguish mortality components

We propose a new parametric model for the life table distribution of deaths. The model is a mixture of three distributions: for infant and child mortality, for accidental and premature mortality, and for adult mortality. This permits to study the characteristics of the different components analyzing the changes of the shape of their distributions. In particular we focused on the features of accidental and premature mortality, since this component, for several reasons, is not often taken into account. The model offers the advantage of computing, in explicit form, the three component's contributions to life expectancy. This is useful to understand the transformations of the distribution of deaths. Moreover, all parameters in the model have a demographic interpretation, so it is easy to study trends and compare different populations. The mixture model was tested using Swedish raw data from the Human Mortality Database and then fitted for different countries. Our results about infant, childhood and adult mortality confirm what we generally know about the tendencies of these components: decrease of deaths at age 0, disappearance of childhood mortality, compression and shifting of adult distribution. For what regards premature mortality, we observed that, over time, its function becomes flatter and more symmetric, and its mode shifts progressively. This implies that almost entirely the accidental mortality has disappeared, while the premature mortality continuous to exist. We also noted that its contribution to explain life expectancy decreased during the last century, but in recent years, for some countries, especially France, it started to grow. This means that the shape of the distribution of deaths is changed: after a compression around the adult mode, an increase of the number of deaths outside the adult distribution is registered. The model does not perform satisfactory estimates when the interval of the last open age class is too wide, in particular when the late mode of the distribution is not clearly recognizable in the death distribution. To improve the estimates we employed EM algorithm, which proved to be a good method to solve this problem. EM algorithm can also be applied to reconstruct incomplete birth cohort data. To compute confidence intervals bootstrap resampling was adopted

How to measure premature mortality? : A proposal combining "relative" and "absolute" approaches

BACKGROUND: The concept of "premature mortality" is at the heart of many national and global health measurement and benchmarking efforts. However, despite the intuitive appeal of its underlying concept, it is far from obvious how to best operationalise it. The previous work offers at least two basic approaches: an absolute and a relative one. The former-and far more widely used- approach sets a unique age threshold (e.g. 65 years), below which deaths are defined as premature. The relative approach derives the share of premature deaths from the country-specific age distribution of deaths in the country of interest. The biggest disadvantage of the absolute approach is that of using a unique, arbitrary threshold for different mortality patterns, while the main disadvantage of the relative approach is that its estimate of premature mortality strongly depends on how the senescent deaths distribution is defined in each country. METHOD: We propose to overcome some of the downsides of the existing approaches, by combining features of both, using a hierarchical model, in which senescent deaths distribution is held constant for each country as a pivotal quantity and the premature mortality distribution is allowed to vary across countries. In this way, premature mortality estimates become more comparable across countries with similar characteristics. RESULTS: The proposed hierarchical models provide results, which appear to align with related evidence from specific countries. In particular, we find a relatively high premature mortality for the United States and Denmark. CONCLUSIONS: While our hybrid approach overcomes some of the problems of previous measures, some issues require further research, in particular the choice of the group of countries that a given country is assigned to and the choice of the benchmarks within the groups. Hence, our proposed method, combined with further study addressing these issues, could provide a valid alternative way to measure and compare premature mortality across countries

Novice identification of melanoma:not quite as straightforward as the ABCDs

The “ABCD” mnemonic to assist non-experts’ diagnosis of melanoma is widely promoted; however, there are good reasons to be sceptical about public education strategies based on analytical, rule-based approaches – such as ABCD (i.e. Asymmetry, Border Irregularity, Colour Uniformity and Diameter). Evidence suggests that accurate diagnosis of skin lesions is achieved predominately through non-analytical pattern recognition (via training examples) and not by rule-based algorithms. If the ABCD are to function as a useful public education tool they must be used reliably by untrained novices, with low inter-observer and intra-diagnosis variation, but with maximal inter-diagnosis differences. The three subjective properties (the ABCs of the ABCD) were investigated experimentally: 33 laypersons scored 40 randomly selected lesions (10 lesions × 4 diagnoses: benign naevi, dysplastic naevi, melanomas, seborrhoeic keratoses) for the three properties on visual analogue scales. The results (n=3,960) suggest that novices cannot use the ABCs reliably to discern benign from malignant lesions

Towards a circular project, between architecture and exhibition design. Digital platforms for reuse practices

Sustainable development and digital transition find wide space in the debate around design disciplines that take up the theme at different paces. While architectural and urban design research has long been working towards innovating design and construction paradigms in a sustainable and circular sense, exhibition design has slowly integrated these aspects into its creation and management structures. From this perspective, the digital transition represents an excellent opportunity to develop integrated systems for circular production chains. The text explores the state of arts in architecture and exhibition design, identifying innovation trajectories within cases of emblematic collaborative platforms, and highlighting their limitations and mutual lessons learned

ConBr lectin modulates MAPKs and Akt pathways and triggers autophagic glioma cell death by a mechanism dependent upon caspase-8 activation

Glioblastoma multiforme is the most aggressive type of glioma, with limited treatment and poor prognosis. Despite some advances over the last decade, validation of novel and selective antiglioma agents remains a challenge in clinical pharmacology. Prior studies have shown that leguminous lectins may exert various biological effects, including antitumor properties. Accordingly, this study aimed to evaluate the mechanisms underlying the antiglioma activity of ConBr, a lectin extracted from the Canavalia brasiliensis seeds. ConBr at lower concentrations inhibited C6 glioma cell migration while higher levels promoted cell death dependent upon carbohydrate recognition domain (CRD) structure. ConBr increased p38MAPK and JNK and decreased ERK1/2 and Akt phosphorylation. Moreover, ConBr inhibited mTORC1 phosphorylation associated with accumulation of autophagic markers, such as acidic vacuoles and LC3 cleavage. Inhibition of early steps of autophagy with 3-methyl-adenine (3-MA) partially protected whereas the later autophagy inhibitor Chloroquine (CQ) had no protective effect upon ConBr cytotoxicity. ConBr also augmented caspase-3 activation without affecting mitochondrial function. Noteworthy, the caspase-8 inhibitor IETF-fmk attenuated ConBr induced autophagy and C6 glioma cell death. Finally, ConBr did not show cytotoxicity against primary astrocytes, suggesting a selective antiglioma activity. In summary, our results indicate that ConBr requires functional CRD lectin domain to exert antiglioma activity, and its cytotoxicity is associated with MAPKs and Akt pathways modulation and autophagy- and caspase-8- dependent cell death.Fil: Wolin, Ingrid A. V.. Universidade Federal de Santa Catarina; BrasilFil: Heinrich, Isabella A.. Universidade Federal de Santa Catarina; BrasilFil: Nascimento, Ana Paula M.. Universidade Federal de Santa Catarina; BrasilFil: Welter, Priscilla G.. Universidade Federal de Santa Catarina; BrasilFil: Sosa, Liliana del Valle. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: de Paul, Ana Lucia. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Córdoba. Instituto de Investigaciones en Ciencias de la Salud. Universidad Nacional de Córdoba. Instituto de Investigaciones en Ciencias de la Salud; ArgentinaFil: Zanotto Filho, Alfeu. Universidade Federal de Santa Catarina; BrasilFil: Nedel, Cláudia Beatriz. Universidade Federal de Santa Catarina; BrasilFil: Lima, Lara Dias. Universidade Estadual do Ceará; BrasilFil: Osterne, Vinicius Jose Silva. Universidade Estadual do Ceará; BrasilFil: Pinto Junior, Vanir Reis. Universidade Estadual do Ceará; BrasilFil: Nascimento, Kyria S.. Universidade Estadual do Ceará; BrasilFil: Cavada, Benildo S.. Universidade Estadual do Ceará; BrasilFil: Leal, Rodrigo B.. Universidade Federal de Santa Catarina; Brasi

HE-LHC: The High-Energy Large Hadron Collider: Future Circular Collider Conceptual Design Report Volume 4

In response to the 2013 Update of the European Strategy for Particle Physics (EPPSU), the Future Circular Collider (FCC) study was launched as a world-wide international collaboration hosted by CERN. The FCC study covered an energy-frontier hadron collider (FCC-hh), a highest-luminosity high-energy lepton collider (FCC-ee), the corresponding 100 km tunnel infrastructure, as well as the physics opportunities of these two colliders, and a high-energy LHC, based on FCC-hh technology. This document constitutes the third volume of the FCC Conceptual Design Report, devoted to the hadron collider FCC-hh. It summarizes the FCC-hh physics discovery opportunities, presents the FCC-hh accelerator design, performance reach, and staged operation plan, discusses the underlying technologies, the civil engineering and technical infrastructure, and also sketches a possible implementation. Combining ingredients from the Large Hadron Collider (LHC), the high-luminosity LHC upgrade and adding novel technologies and approaches, the FCC-hh design aims at significantly extending the energy frontier to 100 TeV. Its unprecedented centre-of-mass collision energy will make the FCC-hh a unique instrument to explore physics beyond the Standard Model, offering great direct sensitivity to new physics and discoveries

FCC-ee: The Lepton Collider: Future Circular Collider Conceptual Design Report Volume 2

In response to the 2013 Update of the European Strategy for Particle Physics, the Future Circular Collider (FCC) study was launched, as an international collaboration hosted by CERN. This study covers a highest-luminosity high-energy lepton collider (FCC-ee) and an energy-frontier hadron collider (FCC-hh), which could, successively, be installed in the same 100 km tunnel. The scientific capabilities of the integrated FCC programme would serve the worldwide community throughout the 21st century. The FCC study also investigates an LHC energy upgrade, using FCC-hh technology. This document constitutes the second volume of the FCC Conceptual Design Report, devoted to the electron-positron collider FCC-ee. After summarizing the physics discovery opportunities, it presents the accelerator design, performance reach, a staged operation scenario, the underlying technologies, civil engineering, technical infrastructure, and an implementation plan. FCC-ee can be built with today’s technology. Most of the FCC-ee infrastructure could be reused for FCC-hh. Combining concepts from past and present lepton colliders and adding a few novel elements, the FCC-ee design promises outstandingly high luminosity. This will make the FCC-ee a unique precision instrument to study the heaviest known particles (Z, W and H bosons and the top quark), offering great direct and indirect sensitivity to new physics