Diagnostik und Klassifikation der akuten myeloischen Leukämie (AML) beruhen auf zytologischen und zytogenetischen Charakteristika. Eine Individualisierung der Diagnostik und Therapie wird für AML mit normalem Karyotyp (CN-AML) durch den Nachweis spezifischer Genmutationen zunehmend ermöglicht. In einem systematischen Literaturreview und Metanalyse wurde die Mutation FLT3-ITD bei CN-AML untersucht. Eine systematische Literaturrecherche aller Veröffentlichungen der Datenbanken Embase, Pubmed, Healthstar, BIOSIS, ISI Web of Knowledge und Cochrane wurde für den Zeitraum 2000 bis März 2012 im Hinblick auf die Mutation FLT3-ITD bei Patienten mit (...) CN-AML und einem Alter von 15–65 Jahren durchgeführt. Der Literaturrecherche folgte eine Literaturselektion, eine Datenextraktion und eine qualitative sowie quantitative Informationssynthese in Form einer Metaanalyse. Achtzehn Veröffentlichungen konnten in die qualitative Analyse zur CN-AML eingeschlossen werden. Daten von 3 Publikationen zum Gesamtüberleben mit insgesamt 1.203 Patienten gingen mit Bezug auf den Marker FLT3-ITD in die Metaanalyse ein. Für FLT3-ITD zeigte sich eine statistisch signifikante schlechtere Prognose mit einer hazard ratio von 2,19 für das Gesamtüberleben bei CN-AML. FLT3-ITD ist im Vergleich zum Wildtyp mit einer schlechteren Prognose in Bezug auf den Krankheitsverlauf bei AML assoziiert. Die Analyse von FLT3 sollte bei der AML berücksichtigt werden. (shrink)

This paper calls fresh attention to ethical problems surrounding prenatal testing by focusing on genetic knowledge gained through evolving testing procedures. Advances in reproductive and prenatal genetic testing include non-invasive tests, such as Verifi and Materniti21, designed to gather detailed information regarding fetal DNA as early as 10 weeks. Meanwhile, a new method of chromosomal microarray has proved more reliable than karyotyping in detecting fetal abnormality. This method detects abnormalities in 1 out of every 60 pregnancies in which karyotyping identified (...) the fetus as “normal.” Chromosomal microarray directly compares fetal DNA to DNA from a presumptively “healthy person” to identify genetic deviations. The chromosomal microarray method thus assumes a human genetic blueprint—that is, a normal genotype, deviance from which is risky and open to medical diagnosis. But, according to philosopher and geneticist Jackie Leach Scully, there is no genetic blueprint for human beings. Rather, genetic variation is constant. Thus, notes Scully, genetic discourse could free medical discourse from the dictates of the binary between normal and abnormal, although mistaken belief in a genetic blueprint can foil this alternative way of speaking and thinking. Prenatal testing has received critical philosophical attention from both disability theorists and feminists. Adrienne Asch suggests that prenatal testing and diagnosis stigmatizes already-existing persons with disabilities by suggesting that bodily deviance is intolerable. Licia Carlson coined the phrase “prenatal prototypes” to describe the obfuscating results of genetic profiling carried out on the fetus. The philosophical conversation Asch and Carlson stimulate involves higher stakes now that testing uncovers fetal genotype and reveals mere genetic deviation in order to aid reproductive decision-making. I argue that prenatal testing, and especially the most recently developed testing procedures described above, forecloses Scully’s alternative discourse of genetic variation by supporting an ideal of a singular “healthy genotype,” deviance from which is to be uncovered and avoided. Mobilizing this insight by drawing on the work of feminist disability scholars like Asch and Carlson, I seek to foreground the play between norm and deviance. I expose the normalizing field of statistical risk, operating in excess of medical diagnosis, which requires potential parents to manage and avoid deviance itself. (shrink)

Polyploid cells contain multiple copies of all chromosomes. Polyploidization can be developmentally programmed to sustain tissue barrier function or to increase metabolic potential and cell size. Programmed polyploidy is normally associated with terminal differentiation and poor proliferation capacity. Conversely, non‐programmed polyploidy can give rise to cells that retain the ability to proliferate. This can fuel rapid genome rearrangements and lead to diseases like cancer. Here, the mechanisms that generate polyploidy are reviewed and the possible challenges upon polyploid cell division are (...) discussed. The discussion is framed around a recent study showing that asynchronous cell cycle progression (an event that is named “chronocrisis”) of different nuclei from a polyploid cell can generate DNA damage at mitotic entry. The potential mechanisms explaining how mitosis in non‐programmed polyploid cells can generate abnormal karyotypes and genetic instability are highlighted. (shrink)

We show that in quantum logic of closed subspaces of Hilbert space one cannot substitute quantum operations for classical (standard Hilbert space) ones and treat them as primitive operations. We consider two possible ways of such a substitution and arrive at operation algebras that are not lattices what proves the claim. We devise algorithms and programs which write down any two-variable expression in an orthomodular lattice by means of classical and quantum operations in an identical form. Our results show that (...) lattice structure and classical operations uniquely determine quantum logic underlying Hilbert space. As a consequence of our result, recent proposals for a deduction theorem with quantum operations in an orthomodular lattice as well as a, substitution of quantum operations for the usual standard Hilbert space ones in quantum logic prove to be misleading. Quantum computer quantum logic is also discussed. (shrink)

For many years, there has been a gap in our capacity to study the structure and organization of chromosomal DNA molecules. The very small genomes of some viruses and bacteriophages (≤ 50,000 bp or 50 kb) are amenable to analysis by conventional gel electrophoresis, while the extremely large DNA molecules (> 100,000 kb) comprising the chromosomes of higher eukaryotes have been analysed under the light microscope, using a range of banding and in situ hybridization techniques. However, intact DNA molecules with (...) sizes between these two extremes have been largely inaccessible experimentally. This gap has recently been bridged with the development of two‐dimensional electrophoretic procedures that allow the separation and purification of chromosome‐sized DNA molecules ranging from ∼ 50 kb to several thousand kb.1–3 There are currently two variations of the technique in use: pulsed field gradient (PFG) gel electrophoresis1,2 and orthogonal‐field‐alteration gel electrophoresis (OFAGE).3 Both are based on a common principle, differing primarily in the geometry of the electrodes. Already, they have been employed to determine the approximate chromosome sizes and numbers for a variety of lower eukaryotes, including yeast and several protozoa.2–10 These ‘molecular karyotypes’ provide fundamental information about the genomic organization of each organism, and allow very rapid construction of linkage maps. Surprisingly, they have also revealed a remarkable plasticity in the genomes of several lower eukaryotes. (shrink)

Multidrug resistance (MDR) is developed in a population of somatic mammalian cells in vivo or in vitro when they are selected for resistance to each of a large group of drugs (colchicine, adriamycin, actinomycin D, etc.). It is produced by the amplification of some unknown gene(s) whose product(s) evidently change(s) the plasma membrane permeability of a cell to a selective agent and to other unrelated compounds. A large specific genomic region (150–250 kbp) undergoes amplification in MDR cells selected for the (...) resistance to different drugs. Amplified DNA is located in homogeneously staining regions of chromosomes, double minute chromosomes and small chromatin bodies – episome‐like structures that replicate out of the S‐phase of a cell cycle. The selection of MDR cell variants is accompanied by regular karyotypic evolution specific for this type of drug resistance. (shrink)

Philologus, founded in 1846, is one of the oldest and most respected periodicals in the field of Classics. It publishes articles on Greek and Latin literature, historiography, philosophy, history of religion, linguistics, reception, and the history of scholarship. The journal aims to contribute to our understanding of Greco-Roman culture and its lasting influence on European civilization. The journal Philologus, conceived as a forum for discussion among different methodological approaches to the study of ancient texts and their reception, publishes original scholarly (...) contributions with a strong international focus. Publications languages are: German, English, Italian, French. As of 2014 the publication of supplementary volumes will be resumed. The series Philologus. Supplemente / Philologus. Supplementary Volumes will publish monographs and edited volumes pertaining to all aspects of the study of ancient literature and its reception, with a special focus on topics concerning literary theory, philosophy and the history of scholarship from an interdisciplinary perspective. (shrink)

Objective Apeiron was founded in 1966 and has developed into one of the oldest and most distinguished journals dedicated to the study of ancient philosophy, ancient science, and, in particular, of problems that concern both fields. Apeiron is committed to publishing high-quality research papers in these areas of ancient Greco-Roman intellectual history; it also welcomes submission of articles dealing with the reception of ancient philosophical and scientific ideas in the later western tradition. The journal appears quarterly. Articles are peer-reviewed on (...) a double-blind basis. Topics ancient philosophy ancient science reception of ancient philosophical and scientific ideas in the later western tradition Article formats Original Articles. (shrink)

Philologus, founded in 1846, is one of the oldest and most respected periodicals in the field of Classics. It publishes articles on Greek and Latin literature, historiography, philosophy, history of religion, linguistics, reception, and the history of scholarship. The journal aims to contribute to our understanding of Greco-Roman culture and its lasting influence on European civilization. The journal Philologus, conceived as a forum for discussion among different methodological approaches to the study of ancient texts and their reception, publishes original scholarly (...) contributions with a strong international focus. Publications languages are: German, English, Italian, French. As of 2014 the publication of supplementary volumes will be resumed. The series Philologus. Supplemente / Philologus. Supplementary Volumes will publish monographs and edited volumes pertaining to all aspects of the study of ancient literature and its reception, with a special focus on topics concerning literary theory, philosophy and the history of scholarship from an interdisciplinary perspective. (shrink)

In a text written during his stay in Paris, Leibniz, to deny ontological reality to relations, employs an argument well known to the medieval thinkers and which later would be revived by Francis H. Bradley. If one assumes that relations are real and that a relation links any property to a subject – so runs the argument – then one falls prey to an infinite regress. Leibniz seems to be well aware of the consequences that this argument has for his (...) own metaphysical views, where the relation of inherence plays such a central role. Thus, he attempts first to interpret the relation of inherence as something ‘metaphoric’, originating from our ‘spatial way’ of looking at the surrounding world; and then he tries to reduce it to the part-whole relation which clearly he considers weaker, from the ontological point of view, than that of ‘being in’. (shrink)

Formal models of appearance and reality have proved fruitful for investigating structural properties of perceptual knowledge. This paper applies the same approach to epistemic justification. Our central goal is to give a simple account of The Preface, in which justified belief fails to agglomerate. Following recent work by a number of authors, we understand knowledge in terms of normality. An agent knows p iff p is true throughout all relevant normal worlds. To model The Preface, we appeal to the (...) normality of error. Sometimes, it is more normal for reality and appearance to diverge than to match. We show that this simple idea has dramatic consequences for the theory of knowledge and justification. Among other things, we argue that a proper treatment of The Preface requires a departure from the internalist idea that epistemic justification supervenes on the appearances and the widespread idea that one knows most when free from error. (shrink)

The global response to the recent coronavirus pandemic has revealed an ethical crisis in public health. This article analyses key pandemic public health policies in light of widely accepted ethical principles: the need for evidence, the least restrictive/harmful alternative, proportionality, equity, reciprocity, due legal process, and transparency. Many policies would be considered unacceptable according to pre-pandemic norms of public health ethics. There are thus significant opportunities to develop more ethical responses to future pandemics. This paper serves as the introduction to (...) this Special Issue of Monash Bioethics Review and provides background for the other articles in this collection. (shrink)

Schools worldwide have started opening doors to welcome back students who, for almost two years, have been stuck studying at home. This study looks at the standpoint of Filipino students on going back to regular face-to-face schooling. There were 2,274 students of different tiers of education (high school, collegiate, graduate) from different major island groups of the Philippines (Luzon, Visayas, Mindanao) who participated in the study. The study used a mixed-method of descriptive statistics to present the quantitative data gathered and (...) thematic analysis of qualitative responses from the subjects. The majority of all the respondents favored going back to the physical classroom, and little only favored staying using the distance mode. In the qualitative analysis, the recurring reasons of the students varied from personal, economic, and fear of getting the virus. It was concluded that Filipino students want to go back to schooling. Moreover, a sizeable amount preferred hybrid while a small number preferred to stay in online or distance mode. Educational institutions should always observe the covid 19 protocol when students go back. (shrink)

This paper looks at the nature of normal-proper functions and the role they play in theories of representational content. More specifically: I lay down two desiderata for a theory which tries to capture what's distinctive of normal-proper functions and discuss two prominent theories which claim to satisfy them. I discuss the advantages of having normal-proper functions ground a theory of representational content. And, I look at both orthodox and heterodox versions of such theories.

Normality judgements are frequently used in everyday communication as well as in biological and social science. Moreover they became increasingly relevant to formal logic as part of defeasible reasoning. This paper distinguishes different kinds of normality statements. It is argued that normality laws like “Birds can normally fly” should be understood essentially in a statistical way. The argument has basically two parts: firstly, a statistical semantic core is mandatory for a descriptive reading of normality in order to explain the logical (...) features of normality laws. Secondly, a statistical justification of normality statements can be derived by game theoretic considerations if the normality law is understood as communication convention. (shrink)

Normality Does Not Equal Mental Health: The Need to Look Elsewhere for Standards of Good Mental Health is the first book to question the equation of psychological normality and mental health. It is also the first book to take contemporary psychiatry and clinical psychology to task for deeply flawed thinking when they accept the diagnostic system propounded by the DSM, which reifies syndromes into alleged “mental disorders.” Where Thomas Szasz argued that “mental disorders” are myths, Bartlett makes the much more (...) damaging charge that reifying mental disorders involves a provable form of fallacious thinking, producing a variety of epistemological nonsense. /// -/- -/- The author weighs the evidence, and with strict logic, compelling evidence, and careful analysis, challenges the current paradigm of mental health theorists and practitioners. Never has the case against the standard of psychological normality and against the non-scientific creation of “mental disorders” been made with such boldness, multidisciplinary knowledge, solid scholarship, and clarity of language. /// -/- -/- Normality Does Not Equal Mental HealthAlthough the need to question psychological normality as a satisfactory standard of good mental health has been staring us in the face for a long time, no one, clinical professional or scholar, has had the courage or the intellectual willingness to face with unflinching honesty the shortcomings and disappointments of psychological normality and to propose that we should look elsewhere for standards of good psychological health. /// -/- -/- Contemporary psychiatry and clinical psychology, on the contrary, base their conception of mental health on the standard of psychological normality. This supposition has come to be accepted uncritically and without question, and yet it has become fundamental to current clinical theory and practice, and forms the core of the psychiatric classification system of the DSM, which has become today’s diagnostic authority. /// -/- -/- While touting today’s scientific gold standard of “evidence-based” research, DSM’s authoritative classification of “mental disorders” is itself hardly “evidence-based,” for it is recognized, but seldom emphasized, that the majority of DSM’s “mental disorders” have no known empirical, organic basis. /// -/- -/- Normality Does Not Equal Mental Health takes DSM to task not only for its failure to adhere to today’s evidence-based standard, but for its failure to rein in its highly speculative diagnostic labeling, in accordance with the modern paradigm of rigorous science, which repudiates metaphorical reifications whose alleged validity rests only on the voting preferences of a professional membership. /// -/- -/- The book is a carefully argued critique of the dominant assumption in current psychiatry and clinical psychology that psychological normality is fundamental to mental health and therefore good. In place of this unsatisfactory presumption, Normality Does Not Equal Mental Health proposes a positive and constructive revision in our understanding of mental health and of our conception of mental disorders. (shrink)

The pandemic creates unprecedented challenges to society and to health care systems around the world. Like all crises, these provide a unique opportunity to rethink the fundamental limiting assumptions and institutional inertia of our established systems. These inertial assumptions have obscured deeply rooted problems in health care and deflected attempts to address them. As hospitals begin to welcome all patients back, they should resist the temptation to go back to business as usual. Instead, they should retain the more deliberative, explicit, (...) and transparent ways of thinking that have informed the development of crisis standards of care. The key lesson to be learned from those exercises in rational deliberation is that justice must be the ethical foundation of all standards of care. Justice demands that hospitals take a safety‐net approach to providing services that prioritizes the most vulnerable segments of society, continue to expand telemedicine in ways that improve access without exacerbating disparities, invest in community‐based care, and fully staff hospitals and clinics on nights and weekends. (shrink)