Effect of interleukin-6 polymorphisms on human longevity: A systematic review and meta-analysis

Several studies have assessed changes in frequency of -174 interleukin (IL)-6 single nucleotide polymorphism (SNP) with age. If IL-6 tracks with disability and age-related diseases, then there should be reduction, in the oldest old, of the frequency of homozgyous GG subjects, who produce higher IL-6 levels. However, discordant results have been obtained. To explore the relationship between this polymorphism and longevity, we analyzed individual data on long-living subjects and controls from eight case-control studies conducted in Europeans, using meta-analysis. There was no significant difference in the IL-6 genotype between the oldest old and controls (Odds Ratio [OR]=0.96; 95% C.I.: 0.77-1.20; p=0.71), but there was significant between-study heterogeneity (I(2)=55.5%). In a subgroup analyses when male centenarians from the three Italian studies were included, the frequency of the IL-6 -174 GG genotype was significantly lower than the other genotypes (OR=0.49; 95% C.I.: 0.31-0.80; p=0.004), with no evidence of heterogeneity (I(2)=0%). Our data supports a negative association between the GG genotype of IL-6 SNP and longevity in Italian centenarians, with males who carry the genotype being two times less likely to reach extreme old age compared with subjects carrying CC or CG genotypes. These findings were not replicated in other European groups suggesting a possible interaction between genetics, sex and environment in reaching longevity.

Paul Karl Feyerabend Las proyecciones de la proliferación teórica en la relación ciencia-metafísica

La doctrina de la Proliferación teórica de Paul Karl Feyerabend ha sido interpretada por sus especialistas como un intento de salvaguardar el ideal del progreso científico. Aunque tales estudios hacen justicia, en parte, a la intencionalidad de nuestro filósofo no explicitan la crítica fundamental que implica para Feyerabend el pluralismo teórico. La proliferación teórica constituye en sí misma una reductio ad absurdum de los distintos intentos del positivismo lógico y del racionalismo crítico por definir la ciencia a expensas de lo metafísico. Este artículo presenta la proliferación teórica como una reivindicación del papel positivo que ocupa la metafísica en el quehacer científico. Se consigna la defensa que hace Feyerabend de la metafísica en cuanto que ésta constituye la posibilidad de superar el conservadurismo conceptual, aumentar de contenido empírico de la ciencia y recuperar el valor descriptivo de las teorías científicas.

The good, the bad and the 'not so bad': reflecting on moral appraisal in practice

The aim of this paper is to facilitate reflection on the moral merit of practitioners in various contexts. Insight is gained from Aristotelian and Kantian accounts of moral character and an original framework for reflection is presented as an adjunct to ethical theory and principles considered when appraising others. In relation to states of character there is an irreconcilable difference between Kantian (deontic) and Aristotelian (aretaic) conceptions of the nature of full virtue (excellence of character), but at the same time it can be argued that in relation to practice their approaches complement each other. It is also argued that in relation to caring for the vulnerable, Aristotle’s conception of full virtue is more compelling than Kant’s. On the other hand, Kant’s notion of self - serving action is important in nursing and it therefore needs to be considered when reflecting on professional conduct. The conclusion reached is that Aristotelian and Kantian accounts of character appraisal should be used in a combined approach to moral appraisal. This approach draws on the accounts of both philosophers and offers valuable insight into moral character, professional conduct and, in a more formal setting, fitness to practise.

Bach

For nearly two centuries Johann Sebastian Bach has been regarded as a cornerstone of Western musical culture. His music inspired subsequent generations of composers and philosophers alike, and continues to capture our imaginations in many ways. Bach studies is part of this picture, often seen as providing excellent examples of musicological scholarship. The editor has chosen 31 published articles which, in his view, not only represent a broad spectrum of the scholarly discussions on Bach's life and works, but will also facilitate the on-going study of Bach's creative genius. The articles have been selected to ensure that this volume will be considered useful for not only those students who are currently engaging in Bach studies at universities but also for more seasoned Bach scholars as they consider the future direction of Bach studies. The editor contextualises the significance of each article in the introduction.

Multiple origins of European populations of giant liver fluke Fascioloides magna (Trematoda: Fasciolidae), an invasive liver parasite of ruminants

The giant liver fluke, Fascioloides magna, liver parasite of free-living and domestic ruminants of Europe and North America, was analysed in order to determine the origin of European populations and to reveal the biogeography of this originally North American parasite on the European continent. The previously selected variable fragments of the mitochondrial cytochrome c oxidase subunit I (cox1; 384 bp) and nicotinamid dehydrogenase subunit I (nad1; 405 bp) were applied as a tool. The phylogenetic trees and haplotype networks were constructed and the level of genetic structuring was evaluated using population genetic tools. In F. magna individuals originating from all European natural foci (Italy, Czech Republic, Danube floodplain forests) and from four of five major North American enzootic areas, 16 cox1 and 18 nad1 haplotypes were determined. The concatenated sequence set produced 22 distinct haplotypes. The European fluke populations were less diverse than those from North America in that they contained proportionately fewer haplotypes (8), while more substantial level of genetic diversity and higher number of haplotypes (15) were recorded in North America. Only one haplotype was shared between the European (Italy) and North American (USA/Oregon and Canada/Alberta) flukes supporting a western North American origin of the Italian F. magna population. Haplotypes found in Italy were distinct from those determined in the remaining European localities what indicates that introduction of F. magna onto the European continent is a result of more than one event. In Czech focus, a south-eastern US origin of giant liver fluke was revealed. Identical haplotypes, common for parasites from Czech Republic and from expanding focus of Danube floodplain forests, implies introduction of F. magna to the Danube region from an already established Czech focus.

Somatic point mutations in mtDNA control region are influenced by genetic background and associated with healthy aging: a GEHA stud

Tissue specific somatic mutations occurring in the mtDNA control region have been proposed to provide a survival advantage. Data on twins and on relatives of long-lived subjects suggested that the occurrence/accumulation of these mutations may be genetically influenced. To further investigate control region somatic heteroplasmy in the elderly, we analyzed the segment surrounding the nt 150 position (previously reported as specific of Leukocytes) in various types of leukocytes obtained from 195 ultra-nonagenarians sib-pairs of Italian or Finnish origin collected in the frame of the GEHA Project. We found a significant correlation of the mtDNA control region heteroplasmy between sibs, confirming a genetic influence on this phenomenon. Furthermore, many subjects showed heteroplasmy due to mutations different from the C150T transition. In these cases heteroplasmy was correlated within sibpairs in Finnish and northern Italian samples, but not in southern Italians. This suggested that the genetic contribution to control region mutations may be population specific. Finally, we observed a possible correlation between heteroplasmy and Hand Grip strength, one of the best markers of physical performance and of mortality risk in the elderly. Our study provides new evidence on the relevance of mtDNA somatic mutations in aging and longevity and confirms that the occurrence of specific point mutations in the mtDNA control region may represent a strategy for the age-related remodelling of organismal functions.

Accounting change: Explaining the outcomes, interpreting the process

Purpose: The issue of accounting change, why and how accounting evolves through time and within specific organisational settings, has been addressed by an important body of literature. This paper aims to explain why, in processes of accounting change, organisations confronting similar environmental pressures show different outcomes of change.

Design/methodology/approach: Drawing on archetype theory, the paper analyses the case of two Italian local governments. Comparative case studies were carried out, reconstructing a period of 15 years.

Findings: Although confronted with similar environmental pressures, the two cases show two different patterns of accounting change, where only one case is able to finally reach radical change. Accounting change can be prompted by external stimuli, but, once the change is prompted, the outcomes of the change are explained by the dynamics of intra-organisational conditions.

Originality/value: The study contributes to accounting change literature by adopting an approach (i.e. archetype theory) that overcomes some of the limitations of previous studies in explaining variations in organisational change. Through this, the authors are able to explain different outcomes and paces of accounting change and point out the intra-organisational factors also affecting them in the presence of similar environmental pressures. A specification of the theoretical framework in a particular setting is also provided.

Pastoral

This chapter argues that Milton’s Epitaphium Damonis, a neo-Latin pastoral lament on the death of Charles Diodati, is marked by the author's Petrarchan self-fashioning. This is achieved through intertextual engagement with Petrarch's Bucolicum Carmen (especially Ecls. 1 and 10). Milton as the wandering Thyrsis, undertaking a methaphorical and literal journey into the world of Italian humanism, appropriates and adapts the metaphorical departure from and return to a pastoral world now shattered by plague and death. Recourse to the quasi-Augustinian monasticism of Petrarchan neo-Latin pastoral facilitates the poem's crossing of a monastic limen via its subtle interaction with a hagiographic intertext, the Vita Sancti Deodati. Now pastoral saint and scholar become united in death and in subsequent apotheosis.

Epistolarum Familiarium Liber Unus in The Complete Works of John Milton: Volume XI (672pp.)

This edition of Milton’s Epistolarum Familiarium Liber Unus and of his Uncollected Letters, will appear as 672 pp. of The Complete Works of John Milton Volume XI, eds. Gordon Campbell and Edward Jones (Oxford University Press, forthcoming 2016). A diplomatic Latin text and a new facing English translation are complemented by a detailed Introduction and commentary that situate Milton’s Latin letters in relation to the classical, pedagogical and essentially humanist contexts at the heart of their composition. Now the art of epistolography advocated and exemplified by Cicero and Quintilian and embraced by Renaissance pedagogical manuals is read through a humanist filter whereby, via the precedent (and very title) of Epistolae Familiares, the Miltonic Liber is shown to engage with a neo-Latin re-invention of the classical epistola that had come to birth in quattrocento Italy in the letters of Petrarch and his contemporaries. At the same time the Epistolae are seen as offering fresh insight into Milton’s views on education, philology, his relations with Italian literati, his blindness, the poetic dimension of his Latin prose, and especially his verbal ingenuity as the ‘words’ of Latin ‘Letters’ become a self-conscious showcasing of etymological punning on the ‘letters’ of Latin ‘words’. The edition also announces several new discoveries, most notably its uncovering and collation of a manuscript of Henry Oldenburg’s transcription (in his Liber Epistolaris held in Royal Society, London) of Milton’s Ep. Fam. 25 (to Richard Jones). Oldenburg’s transcription (from the original sent to his pupil Jones) is an important find, given the loss of all but two of the manuscripts of Milton’s original Latin letters included in the 1674 volume. The edition also presents new evidence in regard to Milton’s relationships with the Italian philologist Benedetto Buonmattei, the Greek humanist Leonard Philaras, the radical pastor Jean Labadie (and the French church of London), and the elusive Peter Heimbach.

Just how controversial is evidential holism?

This paper is an examination of evidential holism, a prominent position in epistemology and the philosophy of science which claims that experiments only ever confirm or refute entire theories. The position is historically associated with W.V. Quine, and it is at once both popular and notorious, as well as being largely under-described. But even though there’s no univocal statement of what holism is or what it does, philosophers have nevertheless made substantial assumptions about its content and its truth. Moreover they have drawn controversial and important conclusions from these assumptions. In this paper I distinguish three types of evidential holism and argue that the most oft-cited and controversial thesis is entirely unmotivated. The other two theses are much overlooked, but are well-motivated and free from controversial implications.

A study of DNA fragmentation patterns in cells irradiated with charged particles: evidence for non-random distributions

Many studies have shown that the effectiveness of radiations of varying LET is similar when yields of dsb have been measured, despite large differences in biological response. Recent evidence has suggested however, that current techniques underestimate the yields of dsb. By monitoring the fragmentation of DNA over a wide range of fragment sizes ( 6 Mbp) by pulsed field electrophoresis, RBE values greater than 1.0 for radiations of around 100 keV/mm have been determined. The data provide evidence for the production of correlated breaks produced within cells as particle tracks traverse the nucleus. The highly ordered structure of DNA within mammalian cells may lead to clustering of breaks over distances related to the repeating unit structures of the chromatin. As well as these regionally damaged sites, a major contributor to radiation effectiveness will be the localised clustering of damage in the 1 - 20 bp region. A major effort is required to elucidate the relative importance of these levels of clustering and their importance in biological response.