HLA-DRB1 genes and disease severity in rheumatoid arthritis. The MIRA Trial Group. Minocycline in Rheumatoid Arthritis

OBJECTIVE: To examine the effect of alleles encoding the "shared"/"rheumatoid" epitope on rheumatoid arthritis (RA) disease severity in patients who participated in the minocycline in RA (MIRA) trial. METHODS: Of 205 patients with a week-48 visit, blood was available for typing of HLA-DRB1 and HLA-DQB1 in 174 (85%) and successfully completed in 169 (82%). Baseline erosions were used to assess disease severity and new erosions at the last visit served as a proxy for progression. RESULTS: At baseline, there was no association between the presence of erosive disease or rheumatoid factor status and the dose of rheumatoid epitope (homozygous, heterozygous, none) or the specific alleles identified. At the final visit, a gradient was observed for the 3 allelic subgroups (and their gene doses) in the occurrence of new erosions among the Caucasian placebo-treated, but not the minocycline-treated, patients. A treatment group/HLA-DR4 epitope interaction was demonstrated in multivariate analyses. Approximately two-thirds of African-American patients did not have the rheumatoid epitope. CONCLUSION: HLA-DRB1 oligotyping may be useful in predicting the progression of disease in some Caucasian patients. Our study corroborates the infrequency of the epitope among African-American patients with RA.     

Improved Variational Guiding of Smoke Animations

Smoke animations are hard to art‐direct because simple changes in parameters such as simulation resolution often lead to unpredictable changes in the final result. Previous work has addressed this problem with a guiding approach which couples low‐resolution simulations – that exhibit the desired flow and behaviour – to the final, high‐resolution simulation. This is done in such a way that the desired low frequency features are to some extent preserved in the high‐resolution simulation. However, the steady (i.e. constant) guiding used often leads to a lack of sufficiently high detail, and employing time‐dependent guiding is expensive because the matrix of the resulting set of equations needs to be recomputed at every iteration. We propose an improved mathematical model for Eulerian‐based simulations which is better suited for dynamic, time‐dependent guiding of smoke animations through a novel variational coupling of the low‐ and high‐resolution simulations. Our model results in a matrix that does not require re‐computation when the guiding changes over time, and hence we can employ time‐dependent guiding more efficiently both in terms of storage and computational requirements. We demonstrate that time‐dependent guiding allows for more high frequency detail to develop without losing correspondence to the low resolution simulation. Furthermore, we explore various artistic effects made possible by time‐dependent guiding.     

A generalization of Paillier’s public-key system with applications to electronic voting

We propose a generalization of Paillier’s probabilistic public-key system, in which the expansion factor is reduced and which allows to adjust the block length of the scheme even after the public key has been fixed, without losing the homomorphic property. We show that the generalization is as secure as Paillier’s original system and propose several ways to optimize implementations of both the generalized and the original scheme. We construct a threshold variant of the generalized scheme as well as zero-knowledge protocols to show that a given ciphertext encrypts one of a set of given plaintexts, and protocols to verify multiplicative relations on plaintexts. We then show how these building blocks can be used for applying the scheme to efficient electronic voting. This reduces dramatically the work needed to compute the final result of an election, compared to the previously best known schemes. We show how the basic scheme for a yes/no vote can be easily adapted to casting a vote for up to t out of L candidates. The same basic building blocks can also be adapted to provide receipt-free elections, under appropriate physical assumptions. The scheme for 1 out of L elections can be optimized such that for a certain range of the other parameter values, the ballot size is logarithmic in L.     

Open generification

To what extent can software ‘travel’ to organizations and countries for which it was not designed for, and how important are local contexts for a successful design and implementation of generic software? Information systems researchers have differing views on this, some emphasizing the strengths of the generic and others the importance of contextual aspects. Contributing to this debate, Pollock and Williams have coined the term generification in order to describe how large vendors succeed in globalizing software packages through management by community, content and social authority. In this paper, we explore an approach that we call open generification, which extends Pollock and Williams' work in the sense that we acknowledge the need for and the feasibility of generic software, but propose an alternative model for the governance of it. Open generification is not about managing the community of users attached to a software package by homogenization or segmentation but aims at addressing the diverse needs of the community the software is expected to serve. Our empirical basis is a longitudinal study of the development of an open‐source health information system software (District Health Information software version 2), which is being used in more than 47 countries. Its success is attributed to a continuous interplay between generic and specific software and continuous cycles of embedding (implementing the global in the local context) and disembedding (taking local innovations into the global). We identify and discuss the contingent mechanisms of this interplay.     

Definition of inseparably fused ventricular myocardium in thoracopagus: fetal echocardiographic utility and pathologic refinement

Correlative echocardiographic and pathological findings in a thoracopagus with conjoined hearts are reported. One twin had tricuspid atresia with discordant atrioventricular connections and concordant ventriculoarterial connections. The morphologic right ventricle was hypoplastic and there was a large muscular ventricular septal defect. The other twin had hypoplasia of the mitral valve anulus and left ventricle with double-outlet right ventricle and pulmonary valve atresia. The tricuspid valve was severely insufficient in part because of a large orifice and redundant, elongated leaflets with abnormal chordal attachments. The left ventricles of these two twins shared a perforated common "free wall" with at least two large defects allowing mixing of the circulations at that level. Not all anatomic details were established conclusively by fetal echocardiography; however, sufficient diagnostic information was obtained to support a decision not to aggressively resuscitate these twins after elective cesarean delivery at 31 weeks' gestation.     

Definition of the Linear Region of X-Ray -Induced Cable Response

Cable response to X-rays is linear with incident fluence, provided the deposited charge in cable dielectrics is directly proportional to the X-ray flux. To estimate the level at which the linear region ends, we discuss three nonlinear processes that modify the deposited charge profile in a hypothetical cable model: field-limiting in vacuum gaps, ionization effects in air-filled gaps, and radiation-induced dielectric conductivity. The exact level at which limiting of the Norton driver in an elemental length of cable begins depends on the cable geometry and the X-ray source. Estimates of the onset of nonlinearities caused by field-limiting and by dielectric conductivity are found in terms of cable and source parameters. With air-filled gaps, the Norton driver is always nonlinear. In addition to limiting of the Norton drivers, the load response of a long cable may be limited because propagating currents are attenuated by the induced conductivity of the bulk of the dielectric.     

Strategic piggybacking--a self-subsidization strategy for nonprofit institutions

Nonprofit institutions often find that their socially worthwhile primary missions generate deficits. The author proposes a strategy for funding these shortfalls that is a synthesis of the specialization and diversified portfolio strategies. Following the method of strategic piggybacking, an organization should acquire or develop a business that is new for the institution and that may be unrelated to the institution's primary mission. The purpose of this new activity is to subsidize, at least in part, the deficit-producing primary mission.     

Professional drivers: protection needed for a high-risk occupation

"On the job" motor vehicle deaths number more than 4,000 annually in the U.S. and comprise nearly one-third of all work-related deaths. Yet the Department of Labor has set no standards relating to on-the-road safety of the millions of workers whose jobs entail large amounts of driving, and Department of Transportation standards affecting occupational safety cover only drivers in interstate commerce. Drivers of some commercial vehicles, such as heavy trucks, are at special risk of injury because trucks have usually been exempted for many years from federal motor vehicle safety standards--such as standards for brakes and seatbelts--designed to prevent crashes or protect occupants in crashes. Observations based on a series of 150 fatal crashes involving tractor trailers illustrate the need for better protection of this large population of high-risk workers. Clarification of responsibility within the various federal agencies and application of available knowledge and technology are essential.     

The organization and postnatal development of the commissural projection of the rat somatic sensory cortex

Anterograde and retrograde tracing experiments have been used to demonstrate the origin and terminal distribution of commissural fibers in the first somatosensory cortex (SI) of the rat. The commissural fibers originate from pyramidal cells of all layers, but predominantly from layers III and V. The fibers terminate in a series of approximately vertical bands. In each of these there are concentrations of terminals extending from the inner portion of the molecular layer to the deep portion of layer III as well as in the superficial part of layer V, and in layer VI. Discrete vertical bands of cortex are reciprocally connected across the midline to give both the origin and terminal regions of the projection a patchy or "columnar" appearance. The commissural fibers arise from and terminate in areas of the cortex that lie between and alongside the aggregations of granule cells that distinguish SI of the rat. No commissural fibers terminate within the aggregations of layer IV cells themselves but the more superficial terminal ramifications may come to overlie these aggregations. A heterotopic projection to the contralateral second somatosensory cortex has been observed and is similar in form to the homotopic projection to SI. Many commissural fibers have crossed the midline in the corpus callosum by the day of birth but lie in the underlying white matter and do not enter the cortical plate until at least the third postnatal day. During the first postnatal week these fibers grow somewhat diffusely into the maturing cortex and their topographic and laminar pattern of distribution attains its adult characteristics by the end of the first week. Commissural axons, thus, arise from immature cells but the maturation of cell form seems to precede the ingrowth of these axons and the acquisition of commissural synapses.