Theories of Reference: What Was the Question?

The new theory of reference has won popularity. However, a number of noted philosophers have also attempted to reply to the critical arguments of Kripke and others, and aimed to vindicate the description theory of reference. Such responses are often based on ingenious novel kinds of descriptions, such as rigidified descriptions, causal descriptions, and metalinguistic descriptions. This prolonged debate raises the doubt whether different parties really have any shared understanding of what the central question of the philosophical theory of reference is: what is the main question to which descriptivism and the causal-historical theory have presented competing answers. One aim of the paper is to clarify this issue. The most influential objections to the new theory of reference are critically reviewed. Special attention is also paid to certain important later advances in the new theory of reference, due to Devitt and others

Investigation of Neuronal Cell Type-Specific Gene Expression of Ca(2+)/Calmodulin-dependent Protein Kinase II.

The promoter activity of the rat Ca(2+)/calmodulin-dependent protein kinase II gene was analyzed using the luciferase reporter gene in neuronal and non-neuronal cell lines. Neuronal cell type-specific promoter activity was found in the 5'-flanking region of α and β isoform genes of the kinase. Silencer elements were also found further upstream of promoter regions. A brain-specific protein bound to the DNA sequence of the 5'-flanking region of the gene was found by gel mobility shift analysis in the nuclear extract of the rat brain, including the cerebellum, forebrain, and brainstem, but not in that of non-neuronal tissues, including liver, kidney and spleen. The luciferase expression system and gel shift analysis can be used as an additional and better index by which to monitor gene expression in most cell types

The knowledge and expectations of parents about the role of antibiotic treatment in upper respiratory tract infection – a survey among parents attending the primary physician with their sick child

BACKGROUND: Upper respiratory tract infections (URTI) are common. The etiologic factor is usually viral, but many physicians prescribe antibiotics. We aimed to evaluate parents' expectations of and knowledge about the role of antibiotics in childhood URTI. METHODS: The study was conducted in thirteen primary care pediatric clinics. Parents of children aged 3 months to 6 years who attended with URTI symptoms were included when it was the first attendance in the current illness. Questionnaire about the current illness, reasons for attending and expectations from the visit, knowledge about URTI was filled before the visit. RESULTS: In 122 visits the average age was 2.8 ± 1.9 years. The main reasons for the visit were to avoid complications (81%) and to be examined (78%). Expected treatment was: cough suppressants (64%), anti-congestants (57%), paracetamol (56%), natural remedies (53%) and antibiotics (25%). In 28% the child had received antibiotics in past URTI. Only 37% thought that antibiotics would not help in URTI and 27% knew that URTI is a self-limited disease. 61% knew that URTI is a viral disease. Younger parental age and higher education were associated with lower expectations to receive antibiotics (p = 0.01, p < 0.005 respectively). While previous antibiotic treatment (p < 0.001), past perceived complications (p = 0.05) and the thought that antibiotics help in URTI (p < 0.001) were associated with a greater expectation for antibiotics. CONCLUSIONS: A quarter of the parents attending the physician with URTI are expecting to get antibiotics. Predictors were lower education, older parental age, receiving antibiotics in the past and the belief that antibiotics help in URTI

Mapping gene associations in human mitochondria using clinical disease phenotypes

Nuclear genes encode most mitochondrial proteins, and their mutations cause diverse and debilitating clinical disorders. To date, 1,200 of these mitochondrial genes have been recorded, while no standardized catalog exists of the associated clinical phenotypes. Such a catalog would be useful to develop methods to analyze human phenotypic data, to determine genotype-phenotype relations among many genes and diseases, and to support the clinical diagnosis of mitochondrial disorders. Here we establish a clinical phenotype catalog of 174 mitochondrial disease genes and study associations of diseases and genes. Phenotypic features such as clinical signs and symptoms were manually annotated from full-text medical articles and classified based on the hierarchical MeSH ontology. This classification of phenotypic features of each gene allowed for the comparison of diseases between different genes. In turn, we were then able to measure the phenotypic associations of disease genes for which we calculated a quantitative value that is based on their shared phenotypic features. The results showed that genes sharing more similar phenotypes have a stronger tendency for functional interactions, proving the usefulness of phenotype similarity values in disease gene network analysis. We then constructed a functional network of mitochondrial genes and discovered a higher connectivity for non-disease than for disease genes, and a tendency of disease genes to interact with each other. Utilizing these differences, we propose 168 candidate genes that resemble the characteristic interaction patterns of mitochondrial disease genes. Through their network associations, the candidates are further prioritized for the study of specific disorders such as optic neuropathies and Parkinson disease. Most mitochondrial disease phenotypes involve several clinical categories including neurologic, metabolic, and gastrointestinal disorders, which might indicate the effects of gene defects within the mitochondrial system. The accompanying knowledgebase (http://www.mitophenome.org/) supports the study of clinical diseases and associated genes

Infrared fixed point in quantum Einstein gravity

We performed the renormalization group analysis of the quantum Einstein gravity in the deep infrared regime for different types of extensions of the model. It is shown that an attractive infrared point exists in the broken symmetric phase of the model. It is also shown that due to the Gaussian fixed point the IR critical exponent $\nu$ of the correlation length is 1/2. However, there exists a certain extension of the model which gives finite correlation length in the broken symmetric phase. It typically appears in case of models possessing a first order phase transitions as is demonstrated on the example of the scalar field theory with a Coleman-Weinberg potential.Comment: 9 pages, 7 figures, final version, to appear in JHE

Galactic and Extragalactic Samples of Supernova Remnants: How They Are Identified and What They Tell Us

Supernova remnants (SNRs) arise from the interaction between the ejecta of a supernova (SN) explosion and the surrounding circumstellar and interstellar medium. Some SNRs, mostly nearby SNRs, can be studied in great detail. However, to understand SNRs as a whole, large samples of SNRs must be assembled and studied. Here, we describe the radio, optical, and X-ray techniques which have been used to identify and characterize almost 300 Galactic SNRs and more than 1200 extragalactic SNRs. We then discuss which types of SNRs are being found and which are not. We examine the degree to which the luminosity functions, surface-brightness distributions and multi-wavelength comparisons of the samples can be interpreted to determine the class properties of SNRs and describe efforts to establish the type of SN explosion associated with a SNR. We conclude that in order to better understand the class properties of SNRs, it is more important to study (and obtain additional data on) the SNRs in galaxies with extant samples at multiple wavelength bands than it is to obtain samples of SNRs in other galaxiesComment: Final 2016 draft of a chapter in "Handbook of Supernovae" edited by Athem W. Alsabti and Paul Murdin. Final version available at https://doi.org/10.1007/978-3-319-20794-0_90-

Differential game theory for versatile physical human-robot interaction

The last decades have seen a surge of robots working in contact with humans. However, until now these contact robots have made little use of the opportunities offered by physical interaction and lack a systematic methodology to produce versatile behaviours. Here, we develop an interactive robot controller able to understand the control strategy of the human user and react optimally to their movements. We demonstrate that combining an observer with a differential game theory controller can induce a stable interaction between the two partners, precisely identify each other’s control law, and allow them to successfully perform the task with minimum effort. Simulations and experiments with human subjects demonstrate these properties and illustrate how this controller can induce different representative interaction strategies

Infliximab: 12 years of experience

Rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are immune-mediated conditions that share an inflammatory mechanism fuelled by excessive cytokines, particularly TNF. Control of inflammation and rapid suppression of cytokines are important in treating these diseases. With this understanding and the corresponding advent of TNF inhibitors, RA patients, AS patients and PsA patients have found more choices than ever before and have greater hope of sustained relief. As a widely used TNF inhibitor, infliximab has a deep and established record of efficacy and safety data. Extensive evidence - from randomised controlled clinical trials, large registries and postmarketing surveillance studies - shows that infliximab effectively treats the signs and symptoms, provides rapid and prolonged suppression of inflammation, prevents radiologically observable disease progression and offers an acceptable safety profile in RA, AS and PsA. In very recent studies, investigators have observed drug-free remission in some patients. Additionally, infliximab may interfere with rapidly progressing disease in RA by early addition to methotrexate in patients with signs of an aggressive course. Finally, infliximab has been shown to reduce PsA clinical manifestations such as nail involvement. With our current understanding, substantial data and increasing confidence regarding use in practice, infliximab can be considered a well-known drug in our continued campaign against inflammatory rheumatic diseases

The use of contextualised standardised client simulation to develop clinical reasoning in final year veterinary students

Clinical reasoning is an important skill for veterinary students to develop before graduation. Simulation has been studied in medical education as a method for developing clinical reasoning in students, but evidence supporting it is limited. This study involved the creation of a contextualized, standardized client simulation session that aimed to improve the clinical reasoning ability and confidence of final-year veterinary students. Sixty-eight participants completed three simulated primary-care consultations, with the client played by an actor and the pet by a healthy animal. Survey data showed that all participants felt that the session improved their clinical decision-making ability. Quantitative clinical reasoning self-assessment, performed using a validated rubric, triangulated this finding, showing an improvement in students’ perception of several components of their clinical reasoning skill level from before the simulation to after it. Blinded researcher analysis of the consultation video recordings found that students showed a significant increase in ability on the history-taking and making-sense-of-data (including formation of a differential diagnosis) components of the assessment rubric. Thirty students took part in focus groups investigating their experience with the simulation. Two themes arose from thematic analysis of these data: variety of reasoning methods and “It’s a different way of thinking.” The latter highlights differences between the decision making students practice during their time in education and the decision making they will use once they are in practice. Our findings suggest that simulation can be used to develop clinical reasoning in veterinary students, and they demonstrate the need for further research in this area