2,218 research outputs found

    The "Artificial Mathematician" Objection: Exploring the (Im)possibility of Automating Mathematical Understanding

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    Reuben Hersh confided to us that, about forty years ago, the late Paul Cohen predicted to him that at some unspecified point in the future, mathematicians would be replaced by computers. Rather than focus on computers replacing mathematicians, however, our aim is to consider the (im)possibility of human mathematicians being joined by “artificial mathematicians” in the proving practice—not just as a method of inquiry but as a fellow inquirer

    Factorial validity and measurement invariance across gender groups of the German version of the Interpersonal Reactivity Index

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    The Interpersonal Reactivity Index (IRI) is the most widely used measure of empathy, but its factorial validity has been questioned. The present research investigates the factorial validity of the German adaptation of the IRI, the "Saarbrücker Persönlichkeitsfragebogen SPF-IRI". Confirmatory Factor Analyses (CFA) and Exploratory Structural Equation Modeling (ESEM) were used to test the theoretically predicted four-factor model. Across two subsamples ESEM outperformed CFA. Substantial cross-loadings were evident in ESEM. Measurement invariance (MI) across gender groups was tested using ESEM in the combined sample. Strict MI (invariant factor loadings, intercepts, residuals) could be established, and variances and covariances were also equal. Differences for latent means were evident. Women scored higher on fantasy, empathic concern, and personal distress. No significant differences were found for perspective taking. Mean differences were due to real differences on latent variables and not a result of measurement bias. Results support the factorial validity of the German SPF-IRI. The heterogeneity of empathy and the unclear differentiation between cognitive and emotional aspects might be a source for the unclear differentiation of scales

    Sustaining modified behaviours learnt in a diabetes prevention program in regional Australia : the role of social context

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    BackgroundThe Greater Green Triangle diabetes prevention program was conducted in primary health care setting of Victoria and South Australia in 2004--2006. This program demonstrated significant reductions in diabetes risk factors which were largely sustained at 18 month follow-up. The theoretical model utilised in this program achieved its outcomes through improvements in coping self-efficacy and planning. Previous evaluations have concentrated on the behavioural components of the intervention. Other variables external to the main research design may have contributed to the success factors but have yet to be identified. The objective of this evaluation was to identify the extent to which participants in a diabetes prevention program sustained lifestyle changes several years after completing the program and to identify contextual factors that contributed to sustaining changes.MethodsA qualitative evaluation was conducted. Five focus groups were held with people who had completed a diabetes prevention program, several years later to assess the degree to which they had sustained program strategies and to identify contributing factors.ResultsParticipants value the recruitment strategy. Involvement in their own risk assessment was a strong motivator. Learning new skills gave participants a sense of empowerment. Receiving regular pathology reports was a means of self-assessment and a motivator to continue. Strong family and community support contributed to personal motivation and sustained practice.ConclusionsFamily and local community supports constitute the contextual variables reported to contribute to sustained motivation after the program was completed. Behaviour modification programs can incorporate strategies to ensure these factors are recognised and if necessary, strengthened at the local level.<br /

    Codon usage in vertebrates is associated with a low risk of acquiring nonsense mutations

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    <p>Abstract</p> <p>Background</p> <p>Codon usage in genomes is biased towards specific subsets of codons. Codon usage bias affects translational speed and accuracy, and it is associated with the tRNA levels and the GC content of the genome. Spontaneous mutations drive genomes to a low GC content. Active cellular processes are needed to maintain a high GC content, which influences the codon usage of a species. Loss-of-function mutations, such as nonsense mutations, are the molecular basis of many recessive alleles, which can greatly affect the genome of an organism and are the cause of many genetic diseases in humans.</p> <p>Methods</p> <p>We developed an event based model to calculate the risk of acquiring nonsense mutations in coding sequences. Complete coding sequences and genomes of 40 eukaryotes were analyzed for GC and CpG content, codon usage, and the associated risk of acquiring nonsense mutations. We included one species per genus for all eukaryotes with available reference sequence.</p> <p>Results</p> <p>We discovered that the codon usage bias detected in genomes of high GC content decreases the risk of acquiring nonsense mutations (Pearson's <it>r </it>= -0.95; <it>P </it>< 0.0001). In the genomes of all examined vertebrates, including humans, this risk was lower than expected (0.93 ± 0.02; mean ± SD) and lower than the risk in genomes of non-vertebrates (1.02 ± 0.13; <it>P </it>= 0.019).</p> <p>Conclusions</p> <p>While the maintenance of a high GC content is energetically costly, it is associated with a codon usage bias harboring a low risk of acquiring nonsense mutations. The reduced exposure to this risk may contribute to the fitness of vertebrates.</p

    Design of a decision support system for multiobjective activity planning and programming using global bacteria optimization

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    The success of any project lies in a great manner on keeping costs in the estimated values, as well as meeting customer required due date. Therefore, there is a current need of developing an information system that facilitates the creation and managing of projects and their processes, including costing schemes, as well as monitoring an optimizing project’s makespan. In order to address this situation a user-friendly information system (IS) was developed. This IS includes an optimization module that reduces the project’s execution time, thus, minimizing costs and ultimately providing the manager with the right tools for the correct development of the project. Therefore, a better planning of activities in a reduced time is accomplished. In this way, the project manager is equipped with a decision support system (DSS) that allows a better decision making and, thanks to this performance optimization, a cost-effective solution can be delivered to the company. The optimization module is the main innovative component in this IS, considering that addresses the problem as a multiobjective one, considering at the same time makespan and cost. This module is based on global bacteria optimization (GBO). This becomes the most relevant improvement when compared to other ISs in the market

    Multicenter safety study of mFOLFOX6 for unresectable advanced/recurrent colorectal cancer in elderly patients

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    <p>Abstract</p> <p>Background</p> <p>Combination chemotherapy with oxaliplatin plus 5-fluorouracil/leucovorin (FOLFOX) has become a standard regimen for colorectal cancer. An increase of adverse events with combination chemotherapy is predicted in elderly patients, and it remains controversial whether they should receive the same chemotherapy as younger patients. Accordingly, this study of modified FOLFOX6 (mFOLFOX6) therapy was performed to compare its safety between elderly and non-elderly patients.</p> <p>Methods</p> <p>We prospectively studies 14 non-elderly patients aged <70 years old and 8 elderly patients aged ≥ 70 years with unresectable advanced/recurrent colorectal cancer who received mFOLFOX6 therapy during the period from March 2006 to March 2007. Adverse events and the response to treatment were compared between the elderly and non-elderly groups.</p> <p>Results</p> <p>The main adverse events were neutropenia and peripheral neuropathy, which occurred in 62.5% (≥ grade 3) and 87.5% (≥ grade 1) of elderly patients. The grade and frequency of adverse events were similar in the elderly and non-elderly groups. In some patients with neutropenia, treatment could be continued without reducing the dose of oxaliplatin by deleting bolus 5-fluorouracil. A correlation was found between the cumulative dose of oxaliplatin and the severity of neuropathy, and there were 2 elderly and 3 younger patients in whom discontinuation of treatment was necessary due to peripheral neuropathy. The median number of treatment cycles was 10.0 and 9.5 in the non-elderly and elderly groups, respectively. The response rate was 60.0% in the non-elderly and 50.0% in the elderly group, while the disease control rate was 100% and 83.3% respectively, showing no age-related difference.</p> <p>Conclusion</p> <p>mFOLFOX6 therapy was well-tolerated and effective in both non-elderly and elderly patients. However, discontinuation of treatment was sometimes necessary due to peripheral neuropathy, which is dose-limiting toxicity of this therapy.</p

    Pseudouridine profiling reveals regulated mRNA pseudouridylation in yeast and human cells

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    Post-transcriptional modification of RNA nucleosides occurs in all living organisms. Pseudouridine, the most abundant modified nucleoside in non-coding RNAs, enhances the function of transfer RNA and ribosomal RNA by stabilizing the RNA structure. Messenger RNAs were not known to contain pseudouridine, but artificial pseudouridylation dramatically affects mRNA function—it changes the genetic code by facilitating non-canonical base pairing in the ribosome decoding centre. However, without evidence of naturally occurring mRNA pseudouridylation, its physiological relevance was unclear. Here we present a comprehensive analysis of pseudouridylation in Saccharomyces cerevisiae and human RNAs using Pseudo-seq, a genome-wide, single-nucleotide-resolution method for pseudouridine identification. Pseudo-seq accurately identifies known modification sites as well as many novel sites in non-coding RNAs, and reveals hundreds of pseudouridylated sites in mRNAs. Genetic analysis allowed us to assign most of the new modification sites to one of seven conserved pseudouridine synthases, Pus1–4, 6, 7 and 9. Notably, the majority of pseudouridines in mRNA are regulated in response to environmental signals, such as nutrient deprivation in yeast and serum starvation in human cells. These results suggest a mechanism for the rapid and regulated rewiring of the genetic code through inducible mRNA modifications. Our findings reveal unanticipated roles for pseudouridylation and provide a resource for identifying the targets of pseudouridine synthases implicated in human disease.American Cancer Society (Robbie Sue Mudd Kidney Cancer Research Scholar Grant RSG-13-396-01-RMC)National Institutes of Health (U.S.) (GM094303)National Institutes of Health (U.S.) (GM081399)American Cancer Society. New England Division (Ellison Foundation Postdoctoral Fellowship)American Cancer Society (Postdoctoral Fellowship PF-13-319-01-RMC)National Institutes of Health (U.S.) (Pre-doctoral Training Grant T32GM007287

    Limitations of rupture forecasting exposed by instantaneously triggered earthquake doublet

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    Earthquake hazard assessments and rupture forecasts are based on the potential length of seismic rupture and whether or not slip is arrested at fault segment boundaries. Such forecasts do not generally consider that one earthquake can trigger a second large event, near-instantaneously, at distances greater than a few kilometers. Here we present a geodetic and seismological analysis of a magnitude 7.1 intra-continental earthquake that occurred in Pakistan in 1997. We find that the earthquake, rather than a single event as hitherto assumed, was in fact an earthquake doublet: initial rupture on a shallow, blind 2 reverse fault was followed just 19 seconds later by a second rupture on a separate reverse fault 50 km away. Slip on the second fault increased the total seismic moment by half, and doubled both the combined event duration and the area of maximum ground shaking. We infer that static Coulomb stresses at the initiation location of the second earthquake were probably reduced as a result of the first. Instead, we suggest that a dynamic triggering mechanism is likely, although the responsible seismic wave phase is unclear. Our results expose a flaw in earthquake rupture forecasts that disregard cascading, multiple-fault ruptures of this type

    Direct intra-abdominal pressure monitoring via piezoresistive pressure measurement: a technical note

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    <p>Abstract</p> <p>Background</p> <p>Piezoresistive pressure measurement technique (PRM) has previously been applied for direct IAP measurement in a porcine model using two different devices. Aim of this clinical study was to assess both devices regarding complications, reliability and agreement with IVP in patients undergoing elective abdominal surgery.</p> <p>Methods</p> <p>A prospective cohort study was performed in 20 patients randomly scheduled to receive PRM either by a Coach<sup>®</sup>-probe or an Accurate++<sup>®</sup>-probe (both MIPM, Mammendorf, Germany). Probes were placed on the greater omentum and passed through the abdominal wall paralleling routine drainages. PRM was compared with IVP measurement by t-testing and by calculating mean difference as well as limits of agreement (LA).</p> <p>Results</p> <p>There were no probe related complications. Due to technical limitations, data could be collected in 3/10 patients with Coach<sup>® </sup>and in 7/10 patients with Accurate++<sup>®</sup>. Analysis was carried out only for Accurate++<sup>®</sup>. Mean values did not differ to mean IVP values. Mean difference to IVP was 0.1 ± 2.8 mmHg (LA: -5.5 to 5.6 mmHg).</p> <p>Conclusion</p> <p>Direct IAP measurement was clinically uneventful. Although results of Accurate++<sup>® </sup>were comparable to IVP, the device might be too fragile for IAP measurements in the clinical setting. Local ethical committee trial registration: EK2024</p
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