No surgical innovation without evaluation: the IDEAL recommendations

Surgery and other invasive therapies are complex interventions, the assessment of which is challenged by factors that depend on operator, team, and setting, such as learning curves, quality variations, and perception of equipoise. We propose recommendations for the assessment of surgery based on a five-stage description of the surgical development process. We also encourage the widespread use of prospective databases and registries. Reports of new techniques should be registered as a professional duty, anonymously if necessary when outcomes are adverse. Case series studies should be replaced by prospective development studies for early technical modifications and by prospective research databases for later pre-trial evaluation. Protocols for these studies should be registered publicly. Statistical process control techniques can be useful in both early and late assessment. Randomised trials should be used whenever possible to investigate efficacy, but adequate pre-trial data are essential to allow power calculations, clarify the definition and indications of the intervention, and develop quality measures. Difficulties in doing randomised clinical trials should be addressed by measures to evaluate learning curves and alleviate equipoise problems. Alternative prospective designs, such as interrupted time series studies, should be used when randomised trials are not feasible. Established procedures should be monitored with prospective databases to analyse outcome variations and to identify late and rare events. Achievement of improved design, conduct, and reporting of surgical research will need concerted action by editors, funders of health care and research, regulatory bodies, and professional societies.

The heatwaves in Switzerland in summer 1947

In 1947, Switzerland was affected by a heat period of large spatial and temporal extent and rare occurrence. The heatwaves of 1947 can be compared with the events of 2003 in terms of intensity and duration. The summer of 1947 is studied based on the analysis of MeteoSwiss station data as well as the “Twentieth Century Reanalysis” (20CR) data set. Heatwaves were defined as six consecutive exceedances of the local 90th percentile of temperature. Five different heatwaves were identified which struck Switzerland during the summer of 1947. The most intense heatwave event is analysed in more detail. The meteorological situation was characterized by a high-pressure bridge over Central Europe. Based on a comparison with literature and with observations, the applicability of the 20CR dataset for the meteorological analysis of heatwave events could be demonstrated. The representation of the heat period in summer 1947 in 20CR is satisfactory when compared with station data, albeit with a temperature bias due to differences in topography. Hence, heatwaves cannot be defined using an absolute threshold. We conclude that 20CR is applicable for an overview of the meteorological patterns characterizing a heat wave but may not reproduce local details.

Exemestane Versus Anastrozole in Postmenopausal Women With Early Breast Cancer: NCIC CTG MA.27—A Randomized Controlled Phase III Trial

PURPOSE In patients with hormone-dependent postmenopausal breast cancer, standard adjuvant therapy involves 5 years of the nonsteroidal aromatase inhibitors anastrozole and letrozole. The steroidal inhibitor exemestane is partially non-cross-resistant with nonsteroidal aromatase inhibitors and is a mild androgen and could prove superior to anastrozole regarding efficacy and toxicity, specifically with less bone loss. PATIENTS AND METHODS We designed an open-label, randomized, phase III trial of 5 years of exemestane versus anastrozole with a two-sided test of superiority to detect a 2.4% improvement with exemestane in 5-year event-free survival (EFS). Secondary objectives included assessment of overall survival, distant disease-free survival, incidence of contralateral new primary breast cancer, and safety. RESULTS In the study, 7,576 women (median age, 64.1 years) were enrolled. At median follow-up of 4.1 years, 4-year EFS was 91% for exemestane and 91.2% for anastrozole (stratified hazard ratio, 1.02; 95% CI, 0.87 to 1.18; P = .85). Overall, distant disease-free survival and disease-specific survival were also similar. In all, 31.6% of patients discontinued treatment as a result of adverse effects, concomitant disease, or study refusal. Osteoporosis/osteopenia, hypertriglyceridemia, vaginal bleeding, and hypercholesterolemia were less frequent on exemestane, whereas mild liver function abnormalities and rare episodes of atrial fibrillation were less frequent on anastrozole. Vasomotor and musculoskeletal symptoms were similar between arms. CONCLUSION This first comparison of steroidal and nonsteroidal classes of aromatase inhibitors showed neither to be superior in terms of breast cancer outcomes as 5-year initial adjuvant therapy for postmenopausal breast cancer by two-way test. Less toxicity on bone is compatible with one hypothesis behind MA.27 but requires confirmation. Exemestane should be considered another option as up-front adjuvant therapy for postmenopausal hormone receptor-positive breast cancer.

Iron fluxes to Talos Dome, Antarctica, over the past 200 kyr

Atmospheric fluxes of iron (Fe) over the past 200 kyr are reported for the coastal Antarctic Talos Dome ice core, based on acid leachable Fe concentrations. Fluxes of Fe to Talos Dome were consistently greater than those at Dome C, with the greatest difference observed during interglacial climates. We observe different Fe flux trends at Dome C and Talos Dome during the deglaciation and early Holocene, attributed to a combination of deglacial activation of dust sources local to Talos Dome and the reorganisation of atmospheric transport pathways with the retreat of the Ross Sea ice shelf. This supports similar findings based on dust particle sizes and fluxes and Rare Earth Element fluxes. We show that Ca and Fe should not be used as quantitative proxies for mineral dust, as they all demonstrate different deglacial trends at Talos Dome and Dome C. Considering that a 20 ppmv decrease in atmospheric CO2 at the coldest part of the last glacial maximum occurs contemporaneously with the period of greatest Fe and dust flux to Antarctica, we confirm that the maximum contribution of aeolian dust deposition to Southern Ocean sequestration of atmospheric CO2 is approximately 20 ppmv.�

Direct male-male competition can facilitate invasion of new colour types in Lake Victoria cichlids

The possibility that disruptive sexual selection alone can cause sympatric speciation is currently a subject of much debate. The initial difficulty for new and rare ornament phenotypes to invade a population, and the stabilisation of the resulting polymorphism in trait and preference make this hypothesis problematic. Recent theoretical work indicates that the invasion is facilitated if males with the new phenotype have an initial advantage in male-male competition. We studied a pair of sympatric incipient species of cichlids from Lake Victoria, in which the red (Pundamilia nyererei) and blue males (P. pundamilia) vigorously defend territories. Other studies suggested that red phenotypes may have repeatedly invaded blue populations in independent episodes of speciation. We hypothesised that red coloration confers an advantage in male-male competition, assisting red phenotypes to invade. To test this hypothesis, we staged contests between red and blue males from a population where the phenotypes are interbreeding morphs or incipient species. We staged contests under both white and green light condition. Green light effectively masks the difference between red and blue coloration. Red males dominated blue males under white light, but their competitive advantage was significantly diminished under green light. Contests were shorter when colour differences were visible. Experience of blue males with red males did not affect the outcome of a contest. The advantage of red over blue in combats may assist the red phenotype to invade blue populations. The apparently stable co-existence of red and blue incipient species in many populations of Lake Victoria cichlids is discussed.

Does Land-Use Intensification Decrease Plant Phylogenetic Diversity in Local Grasslands?

Phylogenetic diversity (PD) has been successfully used as a complement to classical measures of biological diversity such as species richness or functional diversity. By considering the phylogenetic history of species, PD broadly summarizes the trait space within a community. This covers amongst others complex physiological or biochemical traits that are often not considered in estimates of functional diversity, but may be important for the understanding of community assembly and the relationship between diversity and ecosystem functions. In this study we analyzed the relationship between PD of plant communities and land-use intensification in 150 local grassland plots in three regions in Germany. Specifically we asked whether PD decreases with land-use intensification and if so, whether the relationship is robust across different regions. Overall, we found that species richness decreased along land-use gradients the results however differed for common and rare species assemblages. PD only weakly decreased with increasing land-use intensity. The strength of the relationship thereby varied among regions and PD metrics used. From our results we suggest that there is no general relationship between PD and land-use intensification probably due to lack of phylogenetic conservatism in land- use sensitive traits. Nevertheless, we suggest that depending on specific regional idiosyncrasies the consideration of PD as a complement to other measures of diversity can be useful.

Subtile und direkte Mechanismen der sozialen Konstruktion von Geschlecht in Schulbüchern. Vorstellung eines Kategoriensystems zur Analyse der Geschlechter(un)gerechtigkeit von Texten und Bildern

Ausgehend von der Frauenbewegung in Deutschland wurden bereits vor über 40 Jahren erste Analysen zur Darstellung der Geschlechter in Schulbüchern vorgelegt. Sie haben gezeigt, dass weibliche Charaktere im Vergleich zu männlichen seltener und oft in geschlechterstereotypen Rollen dargestellt werden. Heute besteht auf gesellschaftlicher Ebene deutlich mehr Geschlechtergerechtigkeit, dennoch existieren nach wie vor subtile Formen von Diskriminierung in Schulbüchern. Der vorliegende Beitrag dokumentiert die Entwicklung eines Kategoriensystems, das geeignet ist, das Ausmaß von Geschlechter(un)gerechtigkeit in Texten und Bildern aus aktuell in deutschen Schulen verwendeten Deutsch- und Mathematikbüchern zu analysieren. Neben den Häufigkeiten der Darstellungen von weiblichen und männlichen Charakteren und der Geschlechtstypizität ihrer Rollen und Aktivitäten können hiermit zwei subtile Mechanismen der Herstellung von Geschlechterungleichheiten untersucht werden: geschlechter(un)gerechte Sprache und die räumliche Darstellung weiblicher und männlicher Charaktere. Erste Ergebnisse der Anwendung des Kategoriensystems für Deutsch- und Mathematikbücher werden in der Diskussion dargestellt.

Das Repertorium Academicum Germanicum (RAG). Ein digitales Forschungsvorhaben zur Geschichte der Gelehrten des alten Reiches (1250-1550)

This article aims at presenting an already existing research project. The Repertorium Academicum Germanicum (RAG) is supposed to be a "Who’s who" of the graduated and noble scholars of the late medieval Empire. It is designed to record biographical and social data of graduated theologians, jurists, physicians and Masters of Art as well as data of nobles from universities between 1250 and 1550. Furthermore, the project focuses on their examinations, networks, fields of activity in ecclesiastical and secular offices as well as their achievements and legacies (books, treatises, tombs etc). Right now, over 49.000 prosopographic entries are stored in the RAG database, partly available online (www.rag-online.org) and combined with digital maps (infographics), which already provide a basis for research in academic mobility determined by the top scholars of the time. In a next step, it should be possible to draw conclusions not only about personnel and knowledge transfer from university to society, its effects on political systems, daily life, the emergence of new occupational groups and professions, but also about cultural exchange within Europe.

Functional data analysis approaches for genotype-phenotype association studies from next-generation sequencing

Next-generation DNA sequencing platforms can effectively detect the entire spectrum of genomic variation and is emerging to be a major tool for systematic exploration of the universe of variants and interactions in the entire genome. However, the data produced by next-generation sequencing technologies will suffer from three basic problems: sequence errors, assembly errors, and missing data. Current statistical methods for genetic analysis are well suited for detecting the association of common variants, but are less suitable to rare variants. This raises great challenge for sequence-based genetic studies of complex diseases.^ This research dissertation utilized genome continuum model as a general principle, and stochastic calculus and functional data analysis as tools for developing novel and powerful statistical methods for next generation of association studies of both qualitative and quantitative traits in the context of sequencing data, which finally lead to shifting the paradigm of association analysis from the current locus-by-locus analysis to collectively analyzing genome regions.^ In this project, the functional principal component (FPC) methods coupled with high-dimensional data reduction techniques will be used to develop novel and powerful methods for testing the associations of the entire spectrum of genetic variation within a segment of genome or a gene regardless of whether the variants are common or rare.^ The classical quantitative genetics suffer from high type I error rates and low power for rare variants. To overcome these limitations for resequencing data, this project used functional linear models with scalar response to develop statistics for identifying quantitative trait loci (QTLs) for both common and rare variants. To illustrate their applications, the functional linear models were applied to five quantitative traits in Framingham heart studies. ^ This project proposed a novel concept of gene-gene co-association in which a gene or a genomic region is taken as a unit of association analysis and used stochastic calculus to develop a unified framework for testing the association of multiple genes or genomic regions for both common and rare alleles. The proposed methods were applied to gene-gene co-association analysis of psoriasis in two independent GWAS datasets which led to discovery of networks significantly associated with psoriasis.^

n-fatty acids of shale partings in the Franciscan bedded cherts

Normal saturated fatty acid (n-fatty acid) in marine sediments from coastal and pelagic environments were analyzed. The coastal sediments contain both short-chained n-fatty acids with carbon numbers from 12 to 18 and long-chained acids from 22 to 32, whereas the pelagic sediments contain predominantly short-chained acids. The relative abundance of short-chained to long-chained n-fatty acids, expressed by the molar ratio C16/C26, can be an indicator to assess the depositional environment of sedimentary rocks. The ratio of long-chained n-fatty acids (C22-C32) to the total n-fatty acids also has the potential to discriminate sedimentary environments. The indicators based on the n-fatty acids were applied to the Franciscan bedded cherts. The result shows that the bedded cherts had deposited in continuous environments from the pelagic to the coastal. This is in harmony with the same inference based on major, trace and rare earth elements and normal paraffins.

(Table 1) Composition of DSDP Hole 37-334 clinopyroxenes

Recent studies of abyssal peridotites (Johnson et al., 1990, doi:10.1029/JB095iB03p02661), mid-ocean-ridge basalts (MORBs) (McKenzie, 1985, doi:10.1016/0012-821X(85)90001-9) and their entrained melt inclusions (Sobolev and Shimizu, 1993, doi:10.1038/363151a0; Humler and Whitechurch, 1988, doi:10.1016/0012-821X(88)90055-6) have shown that fractional melting of the upwelling sub-oceanic mantle produces magmas with a much wider range of compositions than erupted MORBs. In particular, it seems that strongly depleted primary magmas are routinely produced by melting beneath ridges (Johnson et al., 1990, doi:10.1029/JB095iB03p02661). The absence of strongly depleted melts as erupted lavas prompts the question of how long such magmas survive beneath ridges, before their distinctive compositions are concealed by mixing with more enriched magmas. Here we report mineral compositions from a unique suite of oceanic cumulates recovered from DSDP Site 334 (Aumento et al., doi:10.2973/dsdp.proc.37.1977), which indicate that the rocks crystallized from basaltic liquids that were strongly depleted in Na, Ti, Zr, Y, Sr and rare-earth elements relative to any erupted MORB. It thus appears that the magmatic plumbing system beneath the Mid-Atlantic Ridge permitted strongly depleted magmas to accumulate in a magma chamber and remain sufficiently isolated to produce cumulate rocks. Even so, spatial heterogeneity in the compositions of high-calcium pyroxenes suggests that in the later stages of solidification these rocks reacted with infiltrating enriched basaltic liquids.

Literatura juvenil, un viaje de descubrimiento

Iniciado el siglo XXI, la denominación Literatura Juvenil y el campo epistemológico específico y de investigación que abarca, no han sido todavía suficientemente definidos. Con este estudio se pretende aproximar algunas de las características más notorias de esta área de la Literatura, que tiene como principales destinatarios los lectores adolescentes. Sin duda, fue Paul Hazard, con Los libros, los niños y los hombres (trad. 1950) quien se atrevió a defender la enseñanza a través de libros recreativos y de imaginación para la infancia, desplazando así el centro de lo didáctico moralizante al ámbito abierto y rico del sentimiento y de la fantasía. Ocho años más tarde, Enzo Petrini, con su Estudio crítico de la Literatura Juvenil (1958), asentó las primeras bases de diferenciación de literatura para niños y literatura para jóvenes estudian-do los orígenes y evolución de la Literatura Juvenil y destacando la contribución de la pedagogía y de la crítica.

Memoria del mundo clásico en Funes el Memorioso

El presente estudio tiene por objetivo comprobar la gravitación de determinados referentes de la cultura clásica en “Funes el memorioso". Estos referentes se incorporan estratégicamente en la versión definitiva del relato. Los elementos fundamentales son la articulación retórica y mnemotécnica, el latín como lengua de cultura y los libros que hacen posible su aprendizaje, el capítulo XIV del libro VII de la Historia natural de Plinio el Viejo y el inicio de la “Oda XXX" del Libro tercero, de Horacio. Estos elementos no operan sólo como fuentes sino que inciden los dos momentos básicos de la enunciación, en la construcción de la fábula, en la configuración de los personajes y en la organización del discurso. A la vez, proveen ciertas incitaciones en cuanto a la correlación de los contenidos y determinan la comprensión de la memoria por contraste a la del protagonista. La presencia de determinados referentes de la cultura clásica está relacionada con experiencias del propio Borges quien las transforma ficcionalmente y las pone en boca del narrador, para generar un pacto de lectura autobiográfico con efectos específicos de realce de lo fantástico.

La asthéneia en la antropología cristiana primitiva

La Patrística cristiana recibió la noción veterotestamentaria de asthéneia de la versión griega de los LXX. Entendida como “debilidad" y “falta de fuerza", se la asoció con “enfermedad" o “estado general de debilidad", significado que se conservó tanto en los libros históricos como en los poéticos. El término aparece con frecuencia también en los Evangelios y en los escritos de Pablo, posibilitando así una comprensión de la enfermedad en clave filosófico-teológica por parte de los Padres, entre los que se destaca el Patriarca de Constantinopla San Juan Crisóstomo, quien recurriendo a una exégesis literal de la Escritura según los principios de la escuela antioquena, analiza el concepto en sus comentarios a las Epístolas llamadas “Mayores" de San Pablo y, particularmente, a la Segunda Carta a los Corintios. De esta lectura se desprende la necesidad de considerar la asthéneia de manera inseparable de la antropología cristiana. En los orígenes del cristianismo la concepción de hombre resultaba extremadamente compleja, oscilando desde la antropología tripartita de San Pablo (I Tes. 5, 23) a la quíntuple presentada por ciertos textos gnósticos (Carta esotérica de Santiago 11, 36-12, 17; 14, 24-36) y a la década de Clemente de Alejandría (Strómata VI, 16, 135, 1-2). El estudio de la aplicación del concepto de asthéneia a los distintos componentes del hombre en la polifacética literatura cristiana primitiva, permite comprender la importancia asignada a cada uno de ellos según las distintas corrientes interpretativas.