2,266 research outputs found

    Easy Ontology without Deflationary Metaontology

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    This is a contribution to a symposium on Amie Thomasson’s Ontology Made Easy (2015). Thomasson defends two deflationary theses: that philosophical questions about the existence of numbers, tables, properties, and other disputed entities can all easily be answered, and that there is something wrong with prolonged debates about whether such objects exist. I argue that the first thesis (properly understood) does not by itself entail the second. Rather, the case for deflationary metaontology rests largely on a controversial doctrine about the possible meanings of ‘object’. I challenge Thomasson's argument for that doctrine, and I make a positive case for the availability of the contested, unrestricted use of ‘object’

    Priority monism and essentiality of fundamentality: a reply to Steinberg

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    Steinberg has recently proposed an argument against Schaffer’s priority monism. The argument assumes the principle of Necessity of Monism, which states that if priority monism is true, then it is necessarily true. In this paper, I argue that Steinberg’s objection can be eluded by giving up Necessity of Monism for an alternative principle, that I call Essentiality of Fundamentality, and that such a principle is to be preferred to Necessity of Monism on other grounds as well

    Persistence and Adherence to Cardiovascular Medicines in Australia

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    BACKGROUND: The burden of cardiovascular disease is increasing, with many people treated for multiple cardiovascular conditions. We examined persistence and adherence to medicines for cardiovascular disease treatment or prevention in Australia. METHODS AND RESULTS: Using national dispensing claims for a 10% random sample of people, we identified adults (≥18 years) initiating antihypertensives, statins, oral anticoagulants, or antiplatelets in 2018. We measured persistence to therapy using a 60-day permissible gap, and adherence using the proportion of days covered up to 3 years from initiation, and from first to last dispensing. We reported outcomes by age, sex, and cardiovascular multimedicine use. We identified 83 687 people initiating antihypertensives (n=37 941), statins (n=34 582), oral anticoagulants (n=15 435), or antiplatelets (n=7726). Around one-fifth of people discontinued therapy within 90 days, with 50% discontinuing within the first year. Although many people achieved high adherence (proportion of days covered ≥80%) within the first year, these rates were higher when measured from first to last dispensing (40.5% and 53.2% for statins; 55.6% and 80.5% for antiplatelets, respectively). Persistence was low at 3 years (17.5% antiplatelets to 37.3% anticoagulants). Persistence and adherence increased with age, with minor differences by sex. Over one-third of people had cardiovascular multimedicine use (reaching 92% among antiplatelet users): they had higher persistence and adherence than people using medicines from only 1 cardiovascular group. CONCLUSIONS: Persistence to cardiovascular medicines decreases substantially following initiation, but adherence remains high while people are using therapy. Cardiovascular multimedicine use is common, and people using multiple cardiovascular medicines have higher rates of persistence and adherence

    Priority monism and part/whole dependence

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    Priority monism is the view that the cosmos is the only independent concrete object. The paper argues that, pace its proponents, Priority monism is in conflict with the dependence of any whole on any of its parts: if the cosmos does not depend on its parts, neither does any smaller composit

    Population Dynamics Constrain the Cooperative Evolution of Cross-Feeding

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    Cross-feeding is the exchange of nutrients among species of microbes. It has two potential evolutionary origins, one as an exchange of metabolic wastes or byproducts among species, the other as a form of cooperation known as reciprocal altruism. This paper explores the conditions favoring the origin of cooperative cross-feeding between two species. There is an extensive literature on the evolution of cooperation, and some of the requirements for the evolution of cooperative cross-feeding follow from this prior work–specifically the requirement that interactions be limited to small groups of individuals, such as colonies in a spatially structured environment. Evolution of cooperative cross-feeding by a species also requires that cross-feeding from the partner species already exists, so that the cooperating mutant will automatically be reciprocated for its actions. Beyond these considerations, some unintuitive dynamical constraints apply. In particular, the benefit of cooperative cross-feeding applies only in the range of intermediate cell densities. At low density, resource concentrations are too low to offset the cost of cooperation. At high density, resources shared by both species become limiting, and the two species become competitors. These considerations suggest that the evolution of cooperative cross-feeding in nature may be more challenging than for other types of cooperation. However, the principles identified here may enable the experimental evolution of cross-feeding, as born out by a recent study

    The effect of radio-adaptive doses on HT29 and GM637 cells

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    <p>Abstract</p> <p>Background</p> <p>The shape of the dose-response curve at low doses differs from the linear quadratic model. The effect of a radio-adaptive response is the centre of many studies and well known inspite that the clinical applications are still rarely considered.</p> <p>Methods</p> <p>We studied the effect of a low-dose pre-irradiation (0.03 Gy – 0.1 Gy) alone or followed by a 2.0 Gy challenging dose 4 h later on the survival of the HT29 cell line (human colorectal cancer cells) and on the GM637 cell line (human fibroblasts).</p> <p>Results</p> <p>0.03 Gy given alone did not have a significant effect on both cell lines, the other low doses alone significantly reduced the cell survival. Applied 4 h before the 2.0 Gy fraction, 0.03 Gy led to a significant induced radioresistance in GM637 cells, but not in HT29 cells, and 0.05 Gy led to a significant hyperradiosensitivity in HT29 cells, but not in GM637 cells.</p> <p>Conclusion</p> <p>A pre-irradiation with 0.03 Gy can protect normal fibroblasts, but not colorectal cancer cells, from damage induced by an irradiation of 2.0 Gy and the application of 0.05 Gy prior to the 2.0 Gy fraction can enhance the cell killing of colorectal cancer cells while not additionally damaging normal fibroblasts. If these findings prove to be true in vivo as well this may optimize the balance between local tumour control and injury to normal tissue in modern radiotherapy.</p

    Dynamics of HPV vaccination initiation in Flanders (Belgium) 2007-2009: a Cox regression model

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    <p>Abstract</p> <p>Background</p> <p>We investigated dynamic patterns and predictors of HPV vaccination initiation in Flanders (Belgium) by girls aged 12 to 18, between 2007 and 2009, the period immediately after the introduction of the HPV vaccines on the Belgian market. During this period the initiative for vaccination was taken by the girl, her family or the general practitioner/pediatrician/gynecologist.</p> <p>Methods</p> <p>We used a Cox regression model with time constant and time varying predictors to model hazard rates of HPV vaccination initiation. The sample existed of 117,151 female members of the National Alliance of Christian Mutualities, the largest sickness fund in Flanders.</p> <p>Results</p> <p>The study showed that the hazard of HPV vaccination initiation was higher (1) for older girls, (2) for girls with a more favorable socio-economic background, (3) under more generous reimbursement regimes (with this effect being more pronounced for girls with weak socioeconomic backgrounds), (4) for girls that were informed personally about the reimbursement rules.</p> <p>Conclusions</p> <p>When the initiative for HPV vaccination lies with the girls, their families or the physicians (no organized setting) the uptake of the vaccines is affected by both individual and organizational factors.</p

    Analysis and Practical Guideline of Constraint-Based Boolean Method in Genetic Network Inference

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    Boolean-based method, despite of its simplicity, would be a more attractive approach for inferring a network from high-throughput expression data if its effectiveness has not been limited by high false positive prediction. In this study, we explored factors that could simply be adjusted to improve the accuracy of inferring networks. Our work focused on the analysis of the effects of discretisation methods, biological constraints, and stringency of Boolean function assignment on the performance of Boolean network, including accuracy, precision, specificity and sensitivity, using three sets of microarray time-series data. The study showed that biological constraints have pivotal influence on the network performance over the other factors. It can reduce the variation in network performance resulting from the arbitrary selection of discretisation methods and stringency settings. We also presented the master Boolean network as an approach to establish the unique solution for Boolean analysis. The information acquired from the analysis was summarised and deployed as a general guideline for an efficient use of Boolean-based method in the network inference. In the end, we provided an example of the use of such a guideline in the study of Arabidopsis circadian clock genetic network from which much interesting biological information can be inferred

    Mechanical Circulatory Support as a Bridge to Transplant or for Destination Therapy

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    Mechanical circulatory support (MCS) frequently is used to treat medically refractory end-stage heart failure. Initially designed to be a bridge to transplantation, MCS also has proven itself as a durable therapy for patients who are not transplant candidates. As outcomes for patients with MCS have improved, research interest in device development has flourished, with many new device types under investigation. In addition to improvement of MCS devices, investigational work continues to achieve appropriate patient selection and complication management
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