How pharmacoepidemiology networks can manage distributed analyses to improve replicability and transparency and minimize bias

Several pharmacoepidemiology networks have been developed over the past decade that use a distributed approach, implementing the same analysis at multiple data sites, to preserve privacy and minimize data sharing. Distributed networks are efficient, by interrogating data on very large populations. The structure of these networks can also be leveraged to improve replicability, increase transparency, and reduce bias. We describe some features of distributed networks using, as examples, the Canadian Network for Observational Drug Effect Studies, the Sentinel System in the USA, and the European Research Network of Pharmacovigilance and Pharmacoepidemiology. Common protocols, analysis plans, and data models, with policies on amendments and protocol violations, are key features. These tools ensure that studies can be audited and repeated as necessary. Blinding and strict conflict of interest policies reduce the potential for bias in analyses and interpretation. These developments should improve the timeliness and accuracy of information used to support both clinical and regulatory decisions

A note on the incidence of soilborne fungi in six crops used in rotation with potatoes

L'incidence des champignons telluriques a été déterminée dans les tissus immédiatement sous la ligne de sol chez le trèfle (Trifolium hybridum et T. pratense), le pois (Pisum sativum), le soya (Glycine max), le ryegrass (Lolium multiflorum) cultivés en rotation avec les pommes de terre (Solanum tuberosum). Les légumineuses avaient une incidence significativement plus élevée de Verticillium albo-atrum, Colletotrichum coccodes et Fusarium solani que les graminées. Les pois avaient l'incidence la plus élevée de V. albo-atrum et de F. solani. Le C. coccodes a été isolé plus fréquemment du soya que du trèfle, des pois, du ryegrass, de l'orge ou du blé d'automne. Le Verticillium dahliae a été isolé de toutes les cultures, excepté le trèfle. Les graminées avaient une incidence significativement plus élevée de V. dahliae que les légumineuses. L'incidence du Fusarium sambucinum était plus élevée chez le soya que chez les autres cultures. Le Fusarium oxysporum a été isolé plus fréquemment du soya et de l'orge. L'incidence la plus élevée de Rhizoctonia solani a été trouvée chez le trèfle mais il a été également isolé plus fréquemment du blé d'automne et du ryegrass que du soya et de l'orge.The incidence of soilborne fungi was determined in tissue immediately below the soil line of clover (Trifolium hybridum and T. pratense), peas (Pisum sativum), soybean (Glycine max), ryegrass (Lolium multiflorum), barley (Hordeum vulgare), and winter wheat (Triticum aestivum) grown in rotation with potatoes (Solarium tuberosum). Legume crops had significantly higher incidence of Verticillium albo-atrum, Colletotrichum coccodes, and Fusarium solani than the gramineaceous crops. Peas had the highest incidence of V. albo-atrum and F. solani.C. coccodes was isolated more frequently from soybean than from clover, peas, ryegrass, barley, or winter wheat. Verticillium dahliae was isolated from all crops except clover. Gramineaceous crops had a significantly higher incidence of V. dahliae than legume crops. The incidence of Fusarium sambucinum was higher in soybeans than all other crops. Fusarium oxysporum was isolated most frequently from soybeans and barley. The highest incidence of Rhizoctonia solani was in clover, but it was also isolated more frequently from winter wheat and ryegrass than from soybean and barley

Inhibition in multiclass classification

The role of inhibition is investigated in a multiclass support vector machine formalism inspired by the brain structure of insects. The so-called mushroom bodies have a set of output neurons, or classification functions, that compete with each other to encode a particular input. Strongly active output neurons depress or inhibit the remaining outputs without knowing which is correct or incorrect. Accordingly, we propose to use a classification function that embodies unselective inhibition and train it in the large margin classifier framework. Inhibition leads to more robust classifiers in the sense that they perform better on larger areas of appropriate hyperparameters when assessed with leave-one-out strategies. We also show that the classifier with inhibition is a tight bound to probabilistic exponential models and is Bayes consistent for 3-class problems. These properties make this approach useful for data sets with a limited number of labeled examples. For larger data sets, there is no significant comparative advantage to other multiclass SVM approaches

Inhibition in multiclass classification

The role of inhibition is investigated in a multiclass support vector machine formalism inspired by the brain structure of insects. The so-called mushroom bodies have a set of output neurons, or classification functions, that compete with each other to encode a particular input. Strongly active output neurons depress or inhibit the remaining outputs without knowing which is correct or incorrect. Accordingly, we propose to use a classification function that embodies unselective inhibition and train it in the large margin classifier framework. Inhibition leads to more robust classifiers in the sense that they perform better on larger areas of appropriate hyperparameters when assessed with leave-one-out strategies. We also show that the classifier with inhibition is a tight bound to probabilistic exponential models and is Bayes consistent for 3-class problems. These properties make this approach useful for data sets with a limited number of labeled examples. For larger data sets, there is no significant comparative advantage to other multiclass SVM approaches

The Effect of Diluted Triple and Double Antibiotic Pastes on Dental Pulp Stem Cells and Established Enterococcus faecalis Biofilm

Objectives To investigate the effect of various dilutions of antibiotic medicaments used in endodontic regeneration on the survival of human dental pulp stem cells (DPSCs) and to determine their antibacterial effect against established Enterococcus faecalis biofilm. Materials and methods The cytotoxic and antibacterial effects of different triple (TAP) and double antibiotic paste (DAP) dilutions (0.125, 0.25, 0.5, 1, and 10 mg/ml) were tested against Enterococcus faecalis established biofilm and DPSC. Established bacterial biofilm were exposed to antibiotic dilutions for 3 days. Then, biofilms were collected, spiral plated, and the numbers of bacterial colony forming units (CFU/ml) were determined. For the cytotoxic effect, lactate dehydrogenase activity assays (LDH) and cell viability assays (WST-1) were used to measure the percentage of DPSC cytotoxicity after 3-day treatment with the same antibiotic dilutions. A general linear mixed model was used for statistical analyses (α = 0.05). Results All antibiotic dilutions significantly decreased the bacterial CFU/ml. For WST-1 assays, all antibiotic dilutions except 0.125 mg/ml significantly reduced the viability of DPSC. For LDH assays, the three lowest tested concentrations of DAP (0.5, 0.25, 0.125 mg/ml) and the two lowest concentrations of TAP (0.25 and 0.125 mg/ml) were non-toxic to DPSC. Conclusions All tested dilutions had an antibacterial effect against E. faecalis. However, 0.125 mg/ml of DAP and TAP showed a significant antibacterial effect with no cytotoxic effects on DPSCs. Clinical relevance Using appropriate antibiotic concentrations of intracanal medicament during endodontic regeneration procedures is critical to disinfect root canal and decrease the adverse effects on stem cells

A small plot potato planter

A small plot potato planter. Can. Agric. Eng. 38: 145-147. A two-row planter was constructed for planting small potato research plots. For each row, seed pieces were manually placed on a cup conveyor belt system. Desired in-row seed piece spacings, per row, were obtained by controlling the speed of the conveyor belts using variable speed gearboxes. Micro-dial controllers, attached to the gearboxes, allowed for rapid adjustment of in-row seed piece spacing when required. Small fertilizer hoppers, similar in design to commercial planters, were attached to the planter when a uniform type or rate of fertilizer was required at planting. When planting required different types or rates of fertilizer, hoppers were removed and replaced by two Hege (model H80) belt cones. Fertilizer required per treatment row was placed in the cone prior to planting then applied as cones rotated. The rotation of the cones was controlled by a variable speed gearbox with micro-dial control to adjust the row length of fertilizer application when required. The planter performed well compared to commercial and other small plot planters. The coefficient of variation for seed piece spacings ranged between II to 15% and labour required for planting was 40 to 60% less compared to hand planting

Fundamental scaling laws of on-off intermittency in a stochastically driven dissipative pattern forming system

Noise driven electroconvection in sandwich cells of nematic liquid crystals exhibits on-off intermittent behaviour at the onset of the instability. We study laser scattering of convection rolls to characterize the wavelengths and the trajectories of the stochastic amplitudes of the intermittent structures. The pattern wavelengths and the statistics of these trajectories are in quantitative agreement with simulations of the linearized electrohydrodynamic equations. The fundamental $\tau^{-3/2}$ distribution law for the durations $\tau$ of laminar phases as well as the power law of the amplitude distribution of intermittent bursts are confirmed in the experiments. Power spectral densities of the experimental and numerically simulated trajectories are discussed.Comment: 20 pages and 17 figure

Balancing employee needs, project requirements and organisational priorities in team deployment

The 'people and performance' model asserts that performance is a sum of employee ability, motivation and opportunity (AMO). Despite extensive evidence of this people-performance link within manufacturing and many service sectors, studies within the construction industry are limited. Thus, a recent research project set out to explore the team deployment strategies of a large construction company with the view of establishing how a balance could be achieved between organisational strategic priorities, operational project requirements and individual employee needs and preferences. The findings suggested that project priorities often took precedence over the delivery of the strategic intentions of the organisation in meeting employees' individual needs. This approach is not sustainable in the long term because of the negative implications that such a policy had in relation to employee stress and staff turnover. It is suggested that a resourcing structure that takes into account the multiple facets of AMO may provide a more effective approach for balancing organisational strategic priorities, operational project requirements and individual employee needs and preferences more appropriately in the future

A TOMM40 poly-T variant modulates gene expression and is associated with vocabulary ability and decline in nonpathologic aging

The Translocase of Outer Mitochondrial Membrane 40 Homolog and Apolipoprotein E (TOMM40-APOE) locus has been associated with a number of age-related phenotypes in humans including nonpathologic cognitive aging, late-onset Alzheimer's disease, and longevity. Here, we investigate the influence of the TOMM40 intron 6 poly-T variant (rs10524523) on TOMM40 gene expression and cognitive abilities and decline in a cohort of 1613 community-dwelling elderly volunteers who had been followed for changes in cognitive functioning over a period of 14 years (range = 12–18 years). We showed that the shorter length poly-T variants were found to act as a repressor of luciferase gene expression in reporter gene constructs. Expression was reduced to approximately half of that observed for the very long variant. We further observed that the shorter poly-T variant was significantly associated with reduced vocabulary ability and a slower rate of vocabulary decline with age compared to the very long poly-T variants. No significant associations were observed for memory, fluid intelligence or processing speed, although the direction of effect, where the short variant was correlated with reduced ability and slower rate of decline was observed for all tests. Our results indicate that the poly-T variant has the ability to interact with transcription machinery and differentially modulate reporter gene expression and influence vocabulary ability and decline with age

The Stern-Gerlach Experiment Revisited

The Stern-Gerlach-Experiment (SGE) of 1922 is a seminal benchmark experiment of quantum physics providing evidence for several fundamental properties of quantum systems. Based on today's knowledge we illustrate the different benchmark results of the SGE for the development of modern quantum physics and chemistry. The SGE provided the first direct experimental evidence for angular momentum quantization in the quantum world and thus also for the existence of directional quantization of all angular momenta in the process of measurement. It measured for the first time a ground state property of an atom, it produced for the first time a `spin-polarized' atomic beam, it almost revealed the electron spin. The SGE was the first fully successful molecular beam experiment with high momentum-resolution by beam measurements in vacuum. This technique provided a new kinematic microscope with which inner atomic or nuclear properties could be investigated. The original SGE is described together with early attempts by Einstein, Ehrenfest, Heisenberg, and others to understand directional quantization in the SGE. Heisenberg's and Einstein's proposals of an improved multi-stage SGE are presented. The first realization of these proposals by Stern, Phipps, Frisch and Segr\`e is described. The set-up suggested by Einstein can be considered an anticipation of a Rabi-apparatus. Recent theoretical work is mentioned in which the directional quantization process and possible interference effects of the two different spin states are investigated. In full agreement with the results of the new quantum theory directional quantization appears as a general and universal feature of quantum measurements. One experimental example for such directional quantization in scattering processes is shown. Last not least, the early history of the `almost' discovery of the electron spin in the SGE is revisited.Comment: 50pp, 17 fig