Punitive Damages: An Appeal for Deterrence

Nebraska is one of only four jurisdictions where punitive damages in civil suits are not recognized. It is, however, the only state which finds such damages to be unconstitutional. While punitive damages are often criticized and susceptible to abuse, this Comment outlines areas in which punitive damages are necessary for the maintenance of order and peace in society. Also a set of guidelines will be developed which best utilize the purposes of punitive damages while at the same time curbing any abuses inherent in such awards. I. Introduction … A. Brief History and Purposes of Punitive Damages … 1. Punishment/Retribution … 2. Deterrence … 3. “Private Attorney General” … B. Unconstitutionality in Nebraska II. Punitive Damages in Other Jurisdictions … A. Standard of Culpability Necessary to Trigger Punitive Damages … B. Extent of Liability III. Role of Punitive Damages: When Imposition Will Best Serve Their Purpose … A. Conduct Generally Prosecuted as a Crime … B. Conduct Which Is Criminal But Rarely Prosecuted … C. Noncriminal Conduct IV. Application of Punitive Damages … A. Vicarious Liability … B. Insurability of Punitive Damages … C. Requirement of Actual Damages … D. Requirement That Punitive Award Be Commensurate with Compensatory Award … E. Mass Disaster Litigation V. Conclusio

Delayed Sampling and Automatic Rao-Blackwellization of Probabilistic Programs

We introduce a dynamic mechanism for the solution of analytically-tractable substructure in probabilistic programs, using conjugate priors and affine transformations to reduce variance in Monte Carlo estimators. For inference with Sequential Monte Carlo, this automatically yields improvements such as locally-optimal proposals and Rao-Blackwellization. The mechanism maintains a directed graph alongside the running program that evolves dynamically as operations are triggered upon it. Nodes of the graph represent random variables, edges the analytically-tractable relationships between them. Random variables remain in the graph for as long as possible, to be sampled only when they are used by the program in a way that cannot be resolved analytically. In the meantime, they are conditioned on as many observations as possible. We demonstrate the mechanism with a few pedagogical examples, as well as a linear-nonlinear state-space model with simulated data, and an epidemiological model with real data of a dengue outbreak in Micronesia. In all cases one or more variables are automatically marginalized out to significantly reduce variance in estimates of the marginal likelihood, in the final case facilitating a random-weight or pseudo-marginal-type importance sampler for parameter estimation. We have implemented the approach in Anglican and a new probabilistic programming language called Birch.Comment: 13 pages, 4 figure

Legal uncertainty under EU acquis for the author of Graphical User Interface design - A new sui generis protection needed?

This thesis is about the legal protection of the Intellectual Property (IP) of the design of the graphical user interface (GUI) for computer programs aka software. The research into this matter of law was done by finding out and analysing how this protection is provided through international treaties, statutory law and case law. It concludes that there is a certain amount of legal uncertainty within the area researched and that full harmonization of IPRs within EU most probably would remove this issue and thereby benefit the individual author. This thesis takes the reader on a journey where we will explore the dimension where law and technology meet and merge

Nutrients and micronutrients at risk during renal replacement therapy: a scoping review.

Malnutrition is frequent in patients with acute kidney injury. Nutrient clearance during renal replacement therapy (RRT) potentially contributes to this complication. Although losses of amino acid, trace elements and vitamins have been described, there is no clear guidance regarding the role of micronutrient supplementation. A scoping review was conducted with the aim to review the existing literature on micronutrients status during RRT: 35 publications including data on effluent losses and blood concentrations were considered relevant and analysed. For completeness, we also included data on amino acids. Among trace elements, negative balances have been shown for copper and selenium: low blood levels seem to indicate potential deficiency. Smaller size water soluble vitamins were found in the effluent, but not larger size liposoluble vitamins. Low blood values were frequently reported for thiamine, folate and vitamin C, as well as for carnitine. All amino acids were detectable in effluent fluid. Duration of RRT was associated with decreasing blood values. Losses of several micronutrients and amino acids associated with low blood levels represent a real risk of deficiency for vitamins B1 and C, copper and selenium: they should be monitored in prolonged RRT. Further Research is urgently required as the data are insufficient to generate strong conclusions and prescription recommendations for clinical practice

Dimension (in)equalities and H\"older continuous curves in fractal percolation

We relate various concepts of fractal dimension of the limiting set C in fractal percolation to the dimensions of the set consisting of connected components larger than one point and its complement in C (the "dust"). In two dimensions, we also show that the set consisting of connected components larger than one point is a.s. the union of non-trivial H\"older continuous curves, all with the same exponent. Finally, we give a short proof of the fact that in two dimensions, any curve in the limiting set must have Hausdorff dimension strictly larger than 1.Comment: 22 pages, 3 figures, accepted for publication in Journal of Theoretical Probabilit

Cleaning Genotype Data from Diversity Outbred Mice.

Data cleaning is an important first step in most statistical analyses, including efforts to map the genetic loci that contribute to variation in quantitative traits. Here we illustrate approaches to quality control and cleaning of array-based genotyping data for multiparent populations (experimental crosses derived from more than two founder strains), using MegaMUGA array data from a set of 291 Diversity Outbred (DO) mice. Our approach employs data visualizations that can reveal problems at the level of individual mice or with individual SNP markers. We find that the proportion of missing genotypes for each mouse is an effective indicator of sample quality. We use microarray probe intensities for SNPs on the X and Y chromosomes to confirm the sex of each mouse, and we use the proportion of matching SNP genotypes between pairs of mice to detect sample duplicates. We use a hidden Markov model (HMM) reconstruction of the founder haplotype mosaic across each mouse genome to estimate the number of crossovers and to identify potential genotyping errors. To evaluate marker quality, we find that missing data and genotyping error rates are the most effective diagnostics. We also examine the SNP genotype frequencies with markers grouped according to their minor allele frequency in the founder strains. For markers with high apparent error rates, a scatterplot of the allele-specific probe intensities can reveal the underlying cause of incorrect genotype calls. The decision to include or exclude low-quality samples can have a significant impact on the mapping results for a given study. We find that the impact of low-quality markers on a given study is often minimal, but reporting problematic markers can improve the utility of the genotyping array across many studies

xQTL workbench: a scalable web environment for multi-level QTL analysis

Summary: xQTL workbench is a scalable web platform for the mapping of quantitative trait loci (QTLs) at multiple levels: for example gene expression (eQTL), protein abundance (pQTL), metabolite abundance (mQTL) and phenotype (phQTL) data. Popular QTL mapping methods for model organism and human populations are accessible via the web user interface. Large calculations scale easily on to multi-core computers, clusters and Cloud. All data involved can be uploaded and queried online: markers, genotypes, microarrays, NGS, LC-MS, GC-MS, NMR, etc. When new data types come available, xQTL workbench is quickly customized using the Molgenis software generator

Identification of LIMK2 as a therapeutic target in castration resistant prostate cancer

This study identified LIMK2 kinase as a disease-specific target in castration resistant prostate cancer (CRPC) pathogenesis, which is upregulated in response to androgen deprivation therapy, the current standard of treatment for prostate cancer. Surgical castration increases LIMK2 expression in mouse prostates due to increased hypoxia. Similarly, human clinical specimens showed highest LIMK2 levels in CRPC tissues compared to other stages, while minimal LIMK2 was observed in normal prostates. Most notably, inducible knockdown of LIMK2 fully reverses CRPC tumorigenesis in castrated mice, underscoring its potential as a clinical target for CRPC. We also identified TWIST1 as a direct substrate of LIMK2, which uncovered the molecular mechanism of LIMK2-induced malignancy. TWIST1 is strongly associated with CRPC initiation, progression and poor prognosis. LIMK2 increases TWIST1 mRNA levels upon hypoxia; and stabilizes TWIST1 by direct phosphorylation. TWIST1 also stabilizes LIMK2 by inhibiting its ubiquitylation. Phosphorylation-dead TWIST1 acts as dominant negative and fully prevents EMT and tumor formation in vivo, thereby highlighting the significance of LIMK2-TWIST1 signaling axis in CRPC. As LIMK2 null mice are viable, targeting LIMK2 should have minimal collateral toxicity, thereby improving the overall survival of CRPC patients