Between Philosophy and Art

Similarity and difference, patterns of variation, consistency and coherence: these are the reference points of the philosopher. Understanding experience, exploring ideas through particular instantiations, novel and innovative thinking: these are the reference points of the artist. However, at certain points in the proceedings of our Symposium titled, Next to Nothing: Art as Performance, this characterisation of philosopher and artist respectively might have been construed the other way around. The commentator/philosophers referenced their philosophical interests through the particular examples/instantiations created by the artist and in virtue of which they were then able to engage with novel and innovative thinking. From the artists’ presentations, on the other hand, emerged a series of contrasts within which philosophical and artistic ideas resonated. This interface of philosopher-artist bore witness to the fact that just as art approaches philosophy in providing its own analysis, philosophy approaches art in being a co-creator of art’s meaning. In what follows, we discuss the conception of philosophy-art that emerged from the Symposium, and the methodological minimalism which we employed in order to achieve it. We conclude by drawing out an implication of the Symposium’s achievement which is that a counterpoint to Institutional theories of art may well be the point from which future directions will take hold, if philosophy-art gains traction

Pan-European crop modelling with EPIC: Implementation, up-scaling and regional crop yield validation

Justifiable usage of large-scale crop model simulations requires transparent, comprehensive and spatially extensive evaluations of their performance and associated accuracy. Simulated crop yields of a Pan-European implementation of the Environmental Policy Integrated Climate (EPIC) crop model were satisfactorily evaluated with reported regional yield data from EUROSTAT for four major crops, including winter wheat, rainfed and irrigated maize, spring barley and winter rye. European-wide land use, elevation, soil and daily meteorological gridded data were integrated in GIS and coupled with EPIC. Default EPIC crop and biophysical process parameter values were used with some minor adjustments according to suggestion from scientific literature. The model performance was improved by spatial calculations of crop sowing densities, potential heat units, operation schedules, and nutrient application rates. EPIC performed reasonable in the simulation of regional crop yields, with long-term averages predicted better than inter-annual variability: linear regression R2 ranged from 0.58 (maize) to 0.91 (spring barley) and relative estimation errors were between +-30% for most of the European regions. The modelled and reported crop yields demonstrated similar responses to driving meteorological variables. However, EPIC performed better in dry compared to wet years. A yield sensitivity analysis of crop nutrient and irrigation management factors and cultivar specific characteristics for contrasting regions in Europe revealed a range in model response and attainable yields. We also show that modelled crop yield is strongly dependent on the chosen PET method. The simulated crop yield variability was lower compared to reported crop yields. This assessment should contribute to the availability of harmonised and transparently evaluated agricultural modelling tools in the EU as well as the establishment of modelling benchmark as a requirement for sound and ongoing policy evaluations in the agricultural and environmental domains

Dynamic 3D shape of the plantar surface of the foot using coded structured light:a technical report

The foot provides a crucial contribution to the balance and stability of the musculoskeletal system, and accurate foot measurements are important in applications such as designing custom insoles/footwear. With better understanding of the dynamic behavior of the foot, dynamic foot reconstruction techniques are surfacing as useful ways to properly measure the shape of the foot. This paper presents a novel design and implementation of a structured-light prototype system providing dense three dimensional (3D) measurements of the foot in motion. The input to the system is a video sequence of a foot during a single step; the output is a 3D reconstruction of the plantar surface of the foot for each frame of the input. Methods Engineering and clinical tests were carried out to test the accuracy and repeatability of the system. Accuracy experiments involved imaging a planar surface from different orientations and elevations and measuring the fitting errors of the data to a plane. Repeatability experiments were done using reconstructions from 27 different subjects, where for each one both right and left feet were reconstructed in static and dynamic conditions over two different days. Results The static accuracy of the system was found to be 0.3 mm with planar test objects. In tests with real feet, the system proved repeatable, with reconstruction differences between trials one week apart averaging 2.4 mm (static case) and 2.8 mm (dynamic case). Conclusion The results obtained in the experiments show positive accuracy and repeatability results when compared to current literature. The design also shows to be superior to the systems available in the literature in several factors. Further studies need to be done to quantify the reliability of the system in clinical environment

Assessment of the sensitivity of detecting drug-induced QTc changes using subject-specific rate correction

Aims To quantify the sensitivity of QT heart-rate correction methods for detecting drug-induced QTc changes in thorough QT studies. Methods Twenty-four-hour Holter ECGs were analyzed in 66 normal subjects during placebo and moxifloxacin delivery (single oral dose). QT and RR time series were extracted. Three QTc computation methods were used: (1) Fridericia's formula, (2) Fridericia's formula with hysteresis reduction, and (3) a subject-specific approach with transfer function-based hysteresis reduction and three-parameter non-linear fitting of the QT–RR relation. QTc distributions after placebo and moxifloxacin delivery were compared in sliding time windows using receiver operating characteristic (ROC) curves. The area under the ROC curve (AUC) served as a measure to quantify the ability of each method to detect moxifloxacin-induced QTc prolongation. Results Moxifloxacin prolonged the QTc by 10.6 ± 6.6 ms at peak effect. The AUC was significantly larger after hysteresis reduction (0.87 ± 0.13 vs. 0.82 ± 0.12, p < 0.01) at peak effect, indicating a better discriminating capability. Subject-specific correction further increased the AUC to 0.91 ± 0.11 (p < 0.01 vs. Fridericia with hysteresis reduction). The performance of the subject-specific approach was the consequence of a substantially lower intra-subject QTc standard deviation (5.7 ± 1.1 ms vs. 8.8 ± 1.2 ms for Fridericia). Conclusion The ROC curve provides a tool for quantitative comparison of QT heart rate correction methods in the context of detecting drug-induced QTc prolongation. Results support a broader use of subject-specific QT correction

The Hepatitis B Virus Ribonuclease H Is Sensitive to Inhibitors of the Human Immunodeficiency Virus Ribonuclease H and Integrase Enzymes

Nucleos(t)ide analog therapy blocks DNA synthesis by the hepatitis B virus (HBV) reverse transcriptase and can control the infection, but treatment is life-long and has high costs and unpredictable long-term side effects. The profound suppression of HBV by the nucleos(t)ide analogs and their ability to cure some patients indicates that they can push HBV to the brink of extinction. Consequently, more patients could be cured by suppressing HBV replication further using a new drug in combination with the nucleos(t)ide analogs. The HBV ribonuclease H (RNAseH) is a logical drug target because it is the second of only two viral enzymes that are essential for viral replication, but it has not been exploited, primarily because it is very difficult to produce active enzyme. To address this difficulty, we expressed HBV genotype D and H RNAseHs in E. coli and enriched the enzymes by nickel-affinity chromatography. HBV RNAseH activity in the enriched lysates was characterized in preparation for drug screening. Twenty-one candidate HBV RNAseH inhibitors were identified using chemical structure-activity analyses based on inhibitors of the HIV RNAseH and integrase. Twelve anti-RNAseH and anti-integrase compounds inhibited the HBV RNAseH at 10 μM, the best compounds had low micromolar IC50 values against the RNAseH, and one compound inhibited HBV replication in tissue culture at 10 μM. Recombinant HBV genotype D RNAseH was more sensitive to inhibition than genotype H. This study demonstrates that recombinant HBV RNAseH suitable for low-throughput antiviral drug screening has been produced. The high percentage of compounds developed against the HIV RNAseH and integrase that were active against the HBV RNAseH indicates that the extensive drug design efforts against these HIV enzymes can guide anti-HBV RNAseH drug discovery. Finally, differential inhibition of HBV genotype D and H RNAseHs indicates that viral genetic variability will be a factor during drug development. © 2013 Tavis et al

Propensity scores in the presence of effect modification: A case study using the comparison of mortality on hemodialysis versus peritoneal dialysis

Purpose. To control for confounding bias from non-random treatment assignment in observational data, both traditional multivariable models and more recently propensity score approaches have been applied. Our aim was to compare a propensity score-stratified model with a traditional multivariable-adjusted model, specifically in estimating survival of hemodialysis (HD) versus peritoneal dialysis (PD) patients. Methods. Using the Dutch End-Stage Renal Disease Registry, we constructed a propensity score, predicting PD assignment from age, gender, primary renal disease, center of dialysis, and year of first renal replacement therapy. We developed two Cox proportional hazards regression models to estimate survival on PD relative to HD, a propensity score-stratified model stratifying on the propensity score and a multivariable-adjusted model, and tested several interaction terms in both models. Results. The propensity score performed well: it showed a reasonable fit, had a good c-statistic, calibrated well and balanced the covariates. The main-effects multivariable-adjusted model and the propensity score-stratified univariable Cox model resulted in similar relative mortality risk estimates of PD compared with HD (0.99 and 0.97, respectively) with fewer significant covariates in the propensity model. After introducing the missing interaction variables for effect modification in both models, the mortality risk estimates for both main effects and interactions remained comparable, but the propensity score model had nearly as many covariates because of the additional interaction variables. Conclusion. Although the propensity score performed well, it did not alter the treatment effect in the outcome model and lost its advantage of parsimony in the presence of effect modification

Impact of Expanding Access to Continuous Glucose Monitoring Systems among Insulin Users with Type 1 or Type 2 Diabetes

Background: Despite increased use of continuous glucose monitoring (CGM) systems, studies to quantify patterns of CGM use are limited. In December 2018, a policy change by a commercial insurer expanded coverage of CGM through the pharmacy benefit, creating an opportunity to evaluate the impact of this change on CGM utilization. Research Design and Methods: Pharmacy and medical claims from 2016 to 2020 were used to estimate the prevalence of CGM use among insulin users with type 1 diabetes mellitus (T1DM) or type 2 diabetes mellitus (T2DM) before and after the policy change. Change in CGM use was assessed using an interrupted time series design. Results: At the beginning of the study period, 18.8% of T1DM patients and 1.2% of T2DM patients used CGM. Use rose to 30.5% and 6.6% in the quarter before the policy change. The policy resulted in an immediate 9.5% (P &lt; 0.0001) and 2.8% (P &lt; 0.0001) change in use and increased the rate of quarterly change by 0.5% (P = 0.002) and 0.8% (P &lt; 0.0001). At the end of the study period, 58.2% and 14.9% of T1DM and T2DM patients used CGM. Conclusion: CGM use significantly increased after addition to the pharmacy benefit. Rate of change in CGM use was lower in T1DM compared to the T2DM population, but overall use remained higher among patients with T1DM. Increased CGM use in the population studied aligns with those whose clinical guidelines suggest would most likely benefit. Additional work is needed to evaluate the impact of this benefit change on health care spending and outcomes

Cancer Incidence Among Those Initiating Insulin Therapy With Glargine Versus Human NPH Insulin

OBJECTIVETo add to the evidence on comparative long-term effects of insulin analog glargine versus human NPH insulin on the risk for cancer.RESEARCH DESIGN AND METHODSWe identified cohorts of initiators of glargine and human NPH without an insulin prescription during the prior 19 months among patients covered by the Inovalon Medical Outcomes Research for Effectiveness and Economics Registry (MORE2 Registry) between January 2003 and December 2010. Patients were required to have a second prescription of the same insulin within 180 days and to be free of cancer. We balanced cohorts on risk factors for cancer outcomes based on comorbidities, comedication, and health care use during the prior 12 months using inverse probability of treatment weighting. Incident cancer was defined as having two claims for cancer (any cancer) or the same cancer (breast, prostate, colon) within 2 months. We estimated adjusted hazard ratios (HRs) and their 95% CI using weighted Cox models censoring for stopping, switching, or augmenting insulin treatment, end of enrollment, and mortality.RESULTSMore patients initiated glargine (43,306) than NPH (9,147). Initiators of glargine (NPH) were followed for 1.2 (1.1) years and 50,548 (10,011) person-years; 993 (178) developed cancer. The overall HR was 1.12 (95% CI 0.95–1.32). Results were consistent for breast cancer, prostate cancer, and colon cancer; various durations of treatment; and sensitivity analyses.CONCLUSIONSPatients initiating insulin glargine rather than NPH do not seem to be at an increased risk for cancer. While our study contributes significantly to our evidence base for long-term effects, this evidence is very limited mainly based on actual dynamics in insulin prescribing