bluuebunny/crossref_metadata_2025_split huggingface dataset:
Correlation of hypoxic signalling to histological grade and outcome in cartilage tumours
Authors: Boeuf Stephane , Bovée Judith V M G , Lehner Burkhard , Hogendoorn Pancras C W , Richter Wiltrud 
Published: March 2010

Boeuf S, Bovée J V M G, Lehner B, Hogendoorn P C W & Richter W (2010) Histopathology56, 641–651 Correlation of hypoxic signalling to histological grade and outcome in cartilage tumours Aims:  The molecular mechanisms underlying the progression of central chondrosarcoma are so far poorly understood. The aim of this study was to identify genes involved in the progression of these tumours by comparison of gene expression and correlation of expression profiles to histological grade and clinical outcome.Methods and results:  Array‐based gene expression profiling of 19 chondrosarcoma samples was performed. Beside differences in the expression of cartilage matrix molecules, high‐grade chondrosarcoma showed enhanced expression of the matrix metalloproteinase MMP‐2 and of the hypoxia‐inducible molecule galectin 1. Immunohistochemical analysis of galectin 1 and of further hypoxia‐associated proteins was performed on 68 central and peripheral tumour samples. Hypoxia‐inducible factor 1α (HIF‐1α) activation was significantly elevated in high‐grade central chondrosarcoma. A negative correlation of carbonic anhydrase IX expression to metastasis‐free survival was independent of histological grade.Conclusions:  The expression patterns identified in this study point towards a substantial role for angiogenic and hypoxic signalling in chondrosarcoma progression. The constitutive activation of the transcription factor HIF‐1α in high‐grade chondrosarcoma could play a central role in the regulation of cell metabolism and vascularization in these tumours and may, for this reason, represent a potential target for chondrosarcoma therapy.
The role of topography in structuring the demographic history of the pine processionary moth, Thaumetopoea pityocampa (Lepidoptera: Notodontidae)
Authors: Rousselet Jérôme , Zhao Ruixing , Argal Dallal , Simonato Mauro , Battisti Andrea , Roques Alain , Kerdelhué Carole 
Published: March 2010

AbstractAim  We investigated the Quaternary history of the pine processionary moth, Thaumetopoea pityocampa, an oligophagous insect currently expanding its range. We tested the potential role played by mountain ranges during the post‐glacial recolonization of western Europe.Location  Western Europe, with a focus on the Pyrenees, Massif Central and western Alps.Methods  Maternal genetic structure was investigated using a fragment of the mitochondrial cytochrome c oxidase subunit I (COI) gene. We analysed 412 individuals from 61 locations and performed maximum likelihood and maximum parsimony phylogenetic analyses and hierarchical analysis of molecular variance, and we investigated signs of past expansion.Results  A strong phylogeographic pattern was found, with two deeply divergent clades. Surprisingly, these clades were not separated by the Pyrenees but rather were distributed from western to central Iberia and from eastern Iberia to the Italian Peninsula, respectively. This latter group consisted of three shallowly divergent lineages that exhibited strong geographic structure and independent population expansions. The three identified lineages occurred: (1) on both sides of the Pyrenean range, with more genetically diverse populations in the east, (2) from eastern Iberia to western France, with a higher genetic diversity in the south, and (3) from the western Massif Central to Italy. Admixture areas were found at the foot of the Pyrenees and Massif Central.Main conclusions  The identified genetic lineages were geographically structured, but surprisingly the unsuitable high‐elevation areas of the main mountainous ranges were not responsible for the spatial separation of genetic groups. Rather than acting as barriers to dispersal, mountains appear to have served as refugia during the Pleistocene glaciations, and current distributions largely reflect expansion from these bottlenecked refugial populations. The western and central Iberian clade did not contribute to the northward post‐glacial recolonization of Europe, yet its northern limit does not correspond to the Pyrenees. The different contributions of the identified refugia to post‐glacial expansion might be explained by differences in host plant species richness. For example, the Pyrenean lineage could have been trapped elevationally by tracking montane pines, while the eastern Iberian lineage could have expanded latitudinally by tracking thermophilic lowland pine species.
Epistemology and ethics of evidence‐based medicine: putting goal‐setting in the right place
Authors: Sestini Piersante 
Published: March 2010

AbstractWhile evidence‐based medicine (EBM) is often accused on relying on a paradigm of ‘absolute truth’, it is in fact highly consistent with Karl Popper's criterion of demarcation through falsification. Even more relevant, the first three steps of the EBM process are closely patterned on Popper's evolutionary approach of objective knowledge: (1) recognition of a problem; (2) generation of solutions; and (3) selection of the best solution. This places the step 1 of the EBM process (building an answerable question) in a pivotal position for the understanding of the whole process, and underscores a few aspects which are often overlooked in EBM courses. First in this step internal evidence (including personal expertise) must be appraised and integrated in the problem. Second, issues of applicability of the possible solution should be anticipated. Third, and possibly more important, the goal of the intervention should be set at this stage (typically by choosing the outcome in a PICO question). Depending whether or not goals depend on the goals of others, and whether they concern others' voluntary behaviour, goals may be classified as self‐serving, moral, altruistic or moralistic. Thus, delicate ethical questions must be addressed at this stage, which means that patient preferences and values must be carefully sought, so that empathy, counselling and narrative medicine must be mastered to be able to formulate correctly an answerable question. The need to modify the current description of the EBM process to increase the recognition of implicit assumptions and increase the consistency of this model is discussed.
The limitations of randomized controlled trials in predicting effectiveness
Authors: Cartwright Nancy , Munro Eileen 
Published: March 2010

AbstractWhat kinds of evidence reliably support predictions of effectiveness for health and social care interventions? There is increasing reliance, not only for health care policy and practice but also for more general social and economic policy deliberation, on evidence that comes from studies whose basic logic is that of JS Mill's method of difference. These include randomized controlled trials, case–control studies, cohort studies, and some uses of causal Bayes nets and counterfactual‐licensing models like ones commonly developed in econometrics. The topic of this paper is the ‘external validity’ of causal conclusions from these kinds of studies. We shall argue two claims. Claim, negative: external validity is the wrong idea; claim, positive: ‘capacities’ are almost always the right idea, if there is a right idea to be had. If we are right about these claims, it makes big problems for policy decisions. Many advice guides for grading policy predictions give top grades to a proposed policy if it has two good Mill's‐method‐of difference studies that support it. But if capacities are to serve as the conduit for support from a method‐of‐difference study to an effectiveness prediction, much more evidence, and much different in kind, is required. We will illustrate the complexities involved with the case of multisystemic therapy, an internationally adopted intervention to try to diminish antisocial behaviour in young people.
Evidence and simplicity: why we should reject homeopathy
Authors: Sehon Scott , Stanley Donald 
Published: March 2010

AbstractHomeopathic medications are used by millions, and hundreds of millions of dollars are spent on these remedies in the USA alone. In the UK, the NHS covers homeopathic treatments. Nonetheless, homeopathy is held in considerable disrepute by much of the medical and scientific community. Many proponents of homeopathy are well aware of these criticisms but remain unimpressed. The differences of opinion run deep, and the debate seems deadlocked. We aim to shed some light on this situation. We briefly recap some of the major arguments on each side, but we try to go further by making explicit an underlying philosophical presupposition. In particular, we will claim that there is an important principle, which has ancient roots going back at least to Occam, some version of which constrains all empirical reasoning. We call this constraint the simplicity principle. We argue that this is not something specific to a scientific paradigm, but that, all of us, including proponents of homeopathy, are themselves deeply committed to the simplicity principle. However, once the simplicity principle is made explicit and applied to homeopathy, allegiance to homeopathy is clearly seen as irrational. The point is not merely the lack of clinical trials supporting homeopathy; rather, belief in the efficacy of homeopathy leaves a mountain of unexplained mysteries, and thereby flies in the face of the simplicity rule that guides the homeopaths' own reasoning and arguments. If nothing else, we hope that defenders of homeopathy will gain a greater understanding of why critics are so deeply reluctant to accept the efficacy of homeopathic interventions – and that this reluctance is not mere stubbornness or artificial allegiance to western medicine. Finally, we also hope thereby to illustrate the usefulness of philosophy in unearthing presuppositions in seemingly deadlocked debates.
Clinical judgement, expertise and skilled coping
Authors: Thornton Tim 
Published: March 2010

AbstractMedicine involves specific practical expertise as well as more general context‐independent medical knowledge. This raises the question, what is the nature of the expertise involved? Is there a model of clinical judgement or understanding that can accommodate both elements? This paper begins with a summary of a published account of the kinds of situation‐specific skill found in anaesthesia. It authors claim that such skills are often neglected because of a prejudice in favour of the ‘technical rationality’ exemplified in evidence‐based medicine but they do not themselves offer a general account of the relation of practical expertise and general medical knowledge. The philosopher Hubert Dreyfus provides one model of the relation of general knowledge to situation‐specific skilled coping. He claims that the former logically depends on the latter and provides two arguments, which I articulate in the second section, for this. But he mars those arguments by building in the further assumption that such situation‐specific responses must be understood as concept‐free and thus mindless. That assumption is held in place by three arguments all of which I criticize in the next section to give a unified account of clinical judgement as both practical and conceptually structured and thus justified in the face of a prejudice in favour of ‘technical rationality’.
Polanyi's tacit knowing and the relevance of epistemology to clinical medicine
Authors: Henry Stephen G. 
Published: March 2010

AbstractMost clinicians take for granted a simple, reductionist understanding of medical knowledge that is at odds with how they actually practice medicine; routine medical decisions incorporate more complicated kinds of information than most standard accounts of medical reasoning suggest. A better understanding of the structure and function of knowledge in medicine can lead to practical improvements in clinical medicine. This understanding requires some familiarity with epistemology, the study of knowledge and its structure, in medicine. Michael Polanyi's theory of tacit knowing is advanced as the basis for developing a more accurate understanding of medical knowledge. Tacit knowing, which explores the taken‐for‐granted background knowledge that underlies all human knowing, is explained in detail with a focus on its relevance for clinical medicine. The implications of recognizing tacit knowing in medicine and medical decisions are discussed. These include the ability to explain the importance of the clinical encounter in medical practice, mechanisms for analysing patient and doctor as persons, and the need for humility given the uncertainty that the tacit dimension injects into all medical decisions. This more robust medical epistemology allows clinicians to better articulate the nature and importance of patient‐centred care, to avoid pitfalls inherent in reductionist approaches to medical knowledge, and to think more clearly about the relationships between medicine and health care at the individual and population levels.
Whatever suits you: unpicking personalization for the NHS
Authors: Cribb Alan , Owens John 
Published: March 2010

AbstractIn this paper we argue that policy calls for personalization or ‘tailored’ services derive a large part of their appeal from the way they ‘fudge together’ different things. Using the recent policy discourses surrounding personalization in the UK NHS as a case study we illustrate the policy ‘work’ that is accomplished by this vagueness and focus in on one important fudge – that between a health service tailored to people's medically defined needs and one tailored to people's wants. Our analysis highlights some of the fundamental philosophical and political questions that need to be addressed before personalization can take shape as a coherent policy option. We also highlight the potential scale of the implications personalization has for the welfare state and argue that such implications warrant greater discussion than is currently being afforded to them. We conclude that philosophical analysis is crucial for guiding the redirection of services implied by personalization discourses. The process of selecting and justifying the way in which the personalization agenda is advanced requires both an analysis of the relationships between needs and wants in human flourishing and an explicit reconsideration of the purpose of the welfare state.
Narrative evidence and evidence‐based medicine
Authors: Misak Cheryl J. 
Published: March 2010

AbstractI argue that evidence‐based medicine (EBM) imposes methodological limits that constrain the practice and study of medicine in unfortunate ways. EBM attempts to rid the study of medicine of the subjectivity of individual judgements, while in fact, any use of any kind of evidence requires judgement. On this basis, I argue that there are compelling reasons to broaden the range of evidence employed in EBM, and in particular, to include both straightforward and evaluative narratives. This would mark a shift from the current focus of EBM on purely quantitative data to the inclusion of qualitative data as well. I conclude by emphasizing that objectivity in medicine must come not from the exclusion of wide swaths of potentially valuable evidence, but from the careful application of our critical practices.
Redox sensing by a Rex‐family repressor is involved in the regulation of anaerobic gene expression in Staphylococcus aureus
Authors: Pagels Martin , Fuchs Stephan , Pané‐Farré Jan , Kohler Christian , Menschner Leonhard , Hecker Michael , McNamarra Peter J. , Bauer Mikael C. , Von Wachenfeldt Claes , Liebeke Manuel , Lalk Michael , Sander Gunnar , Von Eiff Christof , Proctor Richard A. , Engelmann Susanne 
Published: March 2010

SummaryAn alignment of upstream regions of anaerobically induced genes in Staphylococcus aureus revealed the presence of an inverted repeat, corresponding to Rex binding sites in Streptomyces coelicolor. Gel shift experiments of selected upstream regions demonstrated that the redox‐sensing regulator Rex of S. aureus binds to this inverted repeat. The binding sequence – TTGTGAAW4TTCACAA – is highly conserved in S. aureus. Rex binding to this sequence leads to the repression of genes located downstream. The binding activity of Rex is enhanced by NAD+ while NADH, which competes with NAD+ for Rex binding, decreases the activity of Rex. The impact of Rex on global protein synthesis and on the activity of fermentation pathways under aerobic and anaerobic conditions was analysed by using a rex‐deficient strain. A direct regulatory effect of Rex on the expression of pathways that lead to anaerobic NAD+ regeneration, such as lactate, formate and ethanol formation, nitrate respiration, and ATP synthesis, is verified. Rex can be considered a central regulator of anaerobic metabolism in S. aureus. Since the activity of lactate dehydrogenase enables S. aureus to resist NO stress and thus the innate immune response, our data suggest that deactivation of Rex is a prerequisite for this phenomenon.
Human allergy to environmental pet danders: a public health perspective
Authors: Morris Daniel O. 
Published: March 2010

AbstractThe prevalence of human allergy to pet danders has increased rapidly over the past six decades, as a consequence of lifestyle changes that have enhanced ambient exposure to pet allergens. This is a problem of global public health importance, as the morbidity associated with allergic diseases disproportionately affects socio‐economically disadvantaged populations, particularly children. Although the public often seeks advice from veterinary health‐care professionals regarding healthy pet ownership practices, including strategies for reducing residential pet dander exposure, many misconceptions persist in the public domain regarding pet dander allergy, such as the belief that certain dog and cat breeds are ‘hypoallergenic’ due to their hair/coat type. This review considers the epidemiology of human exposure to the major cat and dog dander allergens, Fel d 1 and Can f 1 respectively, and the sensitization mechanisms to them, including the hygiene hypothesis and the putative role of bacterial endotoxin. The literature regarding primary and secondary exposures in different ambient environments is explored including threshold effects that influence allergen sensitization and elicitation of symptoms, and environmental intervention strategies that seek to reduce allergen exposure. Pet‐specific factors, including the aetiopathogenesis of the several cat and dog allergens that have been characterized to the molecular level, individual animal characteristics that influence Fel d 1 and Can f 1 shedding, and pet‐directed interventions intended to reduce allergen dispersal, are discussed.
Stratum corneum TARC level is a new indicator of lesional skin inflammation in atopic dermatitis
Authors: Morita E. , Takahashi H. , Niihara H. , Dekio I. , Sumikawa Y. , Murakami Y. , Matsunaka H. 
Published: March 2010

To cite this article: Morita E, Takahashi H, Niihara H, Dekio I, Sumikawa Y, Murakami Y, Matsunaka H. Stratum corneum TARC level is a new indicator of lesional skin inflammation in atopic dermatitis. Allergy 2010; 65: 1166–1172.AbstractBackground:  Management of atopic dermatitis (AD) requires judging the symptoms of local skin lesions and prescribing a suitable treatment. However, no method has been established in which objective measures can be used to evaluate the severity of local symptoms. We established a method for measuring thymus and activation‐regulated chemokine (TARC) levels in the stratum corneum (scTARC), and examined whether the scTARC can be used as an indicator of the severity of local skin lesions in patients with AD.Methods:  Stratum corneum was obtained from patients with AD by tape‐stripping, and scTARC was evaluated using a TARC‐specific antibody followed by image analysis. The scTARC was examined to determine correlation with the severity of local skin lesions (the severity of erythema, edema/papule, oozing/crusts, excoriations, lichenification, and xerosis) as well as with the severity scoring of atopic dermatitis (SCORAD) index, serum TARC level, serum IgE level, serum lactate dehydrogenase (LDH) level, interleukin (IL)‐4‐producing T cell ratio (Th2 cell ratio), and blood eosinophil count.Results:  The scTARC was correlated with the severity of local skin lesions, especially with the erythema, edema/papule, and oozing/crusts score. The scTARC in the most severe lesions was also correlated with the SCORAD index, serum TARC level, serum IgE level, and blood eosinophil count. The scTARC was not, however, correlated with the serum LDH level and Th2 cell ratio.Conclusion:  An immunofluorescent technique combined with tape‐stripping was used to measure scTARC. The scTARC can be used as an indicator of the severity of local acute inflammation in patients with AD.
Exposure to cadmium‐contaminated soils increases allergenicity of Poa annua L. pollen
Authors: Aina R. , Asero R. , Ghiani A. , Marconi G. , Albertini E. , Citterio S. 
Published: March 2010

To cite this article: Aina R, Asero R, Ghiani A, Marconi G, Albertini E, Citterio S. Exposure to cadmium‐contaminated soils increases allergenicity of Poa annua L. pollen. Allergy 2010; 65: 1313–1321.AbstractBackground:  Pollution is considered as one main cause for the increase of allergic diseases. Air pollutants may cause and worsen airway diseases and are probably able to make pollen allergens more aggressive. Previous studies looked at traffic‐related air pollution, but no data about the effects of polluted soils on pollen allergens are available. We aimed to assess the effects of plant exposure to cadmium‐contaminated soil on allergenicity of the annual blue grass, Poa annua L, pollen.Methods:  Poa plants were grown in soil contaminated or not contaminated (control) with cadmium. At flowering, mature pollen was analyzed by microscopy, to calculate the percentage of pollen grains releasing cytoplasmic granules, and by proteomic techniques to analyze allergen proteins. Allergens were identified by sera from grass pollen–allergic patients and by mass spectrometry.Results:  Pollen from Cd‐exposed plants released a higher amount of allergenic proteins than control plants. Moreover, Cd‐exposed pollen released allergens‐containing cytoplasmic grains much more promptly than control pollen. Group 1 and 5 allergens, the major grass pollen allergens, were detected both in control and Cd‐exposed extracts. These were the only allergens reacting with patient’s sera in control pollen, whereas additional proteins strengthening the signal in the gel region reacting with patient’s sera were present in Cd‐exposed pollen. These included a pectinesterase, a lipase, a nuclease, and a secretory peroxydase. Moreover, a PR3 class I chitinase‐like protein was also immunodetected in exposed plants.Conclusion:  Pollen content of plants grown in Cd‐contaminated soils is more easily released in the environment and also shows an increased propensity to bind specific IgE.