Mid-term results in relation to age and analysis of predictive factors after fixation of acetabular fractures using the modified Stoppa approach.

INTRODUCTION Data concerning outcome after management of acetabular fractures by anterior approaches with focus on age and fractures associated with roof impaction, central dislocation and/or quadrilateral plate displacement are rare. METHODS Between October 2005 and April 2009 a series of 59 patients (mean age 57 years, range 13-91) with fractures involving the anterior column was treated using the modified Stoppa approach alone or for reduction of displaced iliac wing or low anterior column fractures in combination with the 1st window of the ilioinguinal approach or the modified Smith-Petersen approach, respectively. Surgical data, accuracy of reduction, clinical and radiographic outcome at mid-term and the need for endoprosthetic replacement in the postoperative course (defined as failure) were assessed; uni- and multivariate regression analysis were performed to identify independent predictive factors (e.g. age, nonanatomical reduction, acetabular roof impaction, central dislocation, quadrilateral plate displacement) for a failure. Outcome was assessed for all patients in general and in accordance to age in particular; patients were subdivided into two groups according to their age (group "<60yrs", group "≥60yrs"). RESULTS Forty-three of 59 patients (mean age 54yrs, 13-89) were available for evaluation. Of these, anatomic reduction was achieved in 72% of cases. Nonanatomical reduction was identified as being the only multivariate predictor for subsequent total hip replacement (Adjusted Hazard Ratio 23.5; p<0.01). A statistically significant higher rate of nonanatomical reduction was observed in the presence of acetabular roof impaction (p=0.01). In 16% of all patients, total hip replacement was performed and in 69% of patients with preserved hips the clinical results were excellent or good at a mean follow up of 35±10 months (range: 24-55). No statistical significant differences were observed between both groups. CONCLUSION Nonanatomical reconstruction of the articular surfaces is at risk for failure of joint-preserving management of acetabular fractures through an isolated or combined modified Stoppa approach resulting in total joint replacement at mid-term. In the elderly, joint-preserving surgery is worth considering as promising clinical and radiographic results might be obtained at mid-term.

3G network traffic sources measurement and analysis

In this paper, we show statistical analyses of several types of traffic sources in a 3G network, namely voice, video and data sources. For each traffic source type, measurements were collected in order to, on the one hand, gain better understanding of the statistical characteristics of the sources and, on the other hand, enable forecasting traffic behaviour in the network. The latter can be used to estimate service times and quality of service parameters. The probability density function, mean, variance, mean square deviation, skewness and kurtosis of the interarrival times are estimated by Wolfram Mathematica and Crystal Ball statistical tools. Based on evaluation of packet interarrival times, we show how the gamma distribution can be used in network simulations and in evaluation of available capacity in opportunistic systems. As a result, from our analyses, shape and scale parameters of gamma distribution are generated. Data can be applied also in dynamic network configuration in order to avoid potential network congestions or overflows. Copyright © 2013 John Wiley & Sons, Ltd.

Implementation of a virtual correlative light and transmission electron microscope

In the long run, the widespread use of slide scanners by pathologists requires an adaptation of teaching methods in histology and cytology in order to target these new possibilities of image processing and presentation via the internet. Accordingly, we were looking for a tool with the possibility to teach microscopic anatomy, histology, and cytology of tissue samples which would be able to combine image data from light and electron microscopes independently of microscope suppliers. With the example of a section through the villus of jejunum, we describe here how to process image data from light and electron microscopes in order to get one image-stack which allows a correlation of structures from the microscopic anatomic to the cytological level. With commercially available image-presentation software that we adapted to our needs, we present here a platform which allows for the presentation of this new but also of older material independently of microscope suppliers.

Making minimally invasive THR safe: conclusions from biomechanical simulation and analysis.

The use of smaller surgical incisions has become popularized for total hip arthroplasty (THR) because of the potential benefits of shorter recovery and improved cosmetic appearance. However, an increased incidence of serious complications has been reported. To minimize the risks of minimally invasive approaches to THR, we have developed an experimental approach which enables us to evaluate risk factors in these procedures through cadaveric simulations performed within the laboratory. During cadaveric hip replacement procedures performed via posterior and antero-lateral mini-incisions, pressures developed between the wound edges and the retractors were approximately double those recorded during conventional hip replacement using Charnley retractors (p < 0.01). In MIS procedures performed via the dual-incision approach, lack of direct visualisation of the proximal femur led to misalignment of broaches and implants with increased risk of cortical fracture during canal preparation and implant insertion. Cadaveric simulation of surgical procedures allows surgeons to measure variables affecting the technical success of surgery and to master new procedures without placing patients at risk.

Identification and phenotypic characterization of a second collagen adhesin, Scm, and genome-based identification and analysis of 13 other predicted MSCRAMMs, including four distinct pilus loci, in Enterococcus faecium.

Attention has recently been drawn to Enterococcus faecium because of an increasing number of nosocomial infections caused by this species and its resistance to multiple antibacterial agents. However, relatively little is known about the pathogenic determinants of this organism. We have previously identified a cell-wall-anchored collagen adhesin, Acm, produced by some isolates of E. faecium, and a secreted antigen, SagA, exhibiting broad-spectrum binding to extracellular matrix proteins. Here, we analysed the draft genome of strain TX0016 for potential microbial surface components recognizing adhesive matrix molecules (MSCRAMMs). Genome-based bioinformatics identified 22 predicted cell-wall-anchored E. faecium surface proteins (Fms), of which 15 (including Acm) had characteristics typical of MSCRAMMs, including predicted folding into a modular architecture with multiple immunoglobulin-like domains. Functional characterization of one [Fms10; redesignated second collagen adhesin of E. faecium (Scm)] revealed that recombinant Scm(65) (A- and B-domains) and Scm(36) (A-domain) bound to collagen type V efficiently in a concentration-dependent manner, bound considerably less to collagen type I and fibrinogen, and differed from Acm in their binding specificities to collagen types IV and V. Results from far-UV circular dichroism measurements of recombinant Scm(36) and of Acm(37) indicated that these proteins were rich in beta-sheets, supporting our folding predictions. Whole-cell ELISA and FACS analyses unambiguously demonstrated surface expression of Scm in most E. faecium isolates. Strikingly, 11 of the 15 predicted MSCRAMMs clustered in four loci, each with a class C sortase gene; nine of these showed similarity to Enterococcus faecalis Ebp pilus subunits and also contained motifs essential for pilus assembly. Antibodies against one of the predicted major pilus proteins, Fms9 (redesignated EbpC(fm)), detected a 'ladder' pattern of high-molecular-mass protein bands in a Western blot analysis of cell surface extracts from E. faecium, suggesting that EbpC(fm) is polymerized into a pilus structure. Further analysis of the transcripts of the corresponding gene cluster indicated that fms1 (ebpA(fm)), fms5 (ebpB(fm)) and ebpC(fm) are co-transcribed, a result consistent with those for pilus-encoding gene clusters of other Gram-positive bacteria. All 15 genes occurred frequently in 30 clinically derived diverse E. faecium isolates tested. The common occurrence of MSCRAMM- and pilus-encoding genes and the presence of a second collagen-binding protein may have important implications for our understanding of this emerging pathogen.

Isolation and analysis of regulatory and structural mutations in the {\it recA\/} gene of {\it Escherichia coli}

The recA gene is essential for homologous recombination and for inducible DNA repair in Escherichia coli. The level of recA expression is important for these functions. The growth defect of a lambda phage carrying a recA-lacZ fusion was used to select mutations that reduced recA expression. Nine of these mutations were single base changes in the recA promoter; each reduced both induced and basal (repressed) levels of expression, indicating that only one promoter is used under both circumstances. Deletion analysis of the promoter region and S1 mapping of transcripts confirmed that there is only one promoter responsible for both basal and induced expression. Some of the mutants, however, displayed a ratio of induced to repressed expression that was much lower than wild-type. For one of these mutants (recA1270) LexA binding studies showed that this was not due to a change in the affinity of LexA repressor for the operator site. The extent of binding of RNA polymerase to this mutant promoter, however, was much reduced, and the complexes formed were qualitatively different. Further binding experiments provided some evidence that LexA does not block RNA polymerase binding to the recA promoter, but inhibits a later step in initiation. Behavior of the mutants with altered induction ratios could be explained if LexA binding to the operator actually increases RNA polymerase binding to the promoter in a closed complex compensating for defects in polymerase binding caused by the mutations.^ In a study of mutations in the recA structural gene, site-directed mutagenesis was used to replace cysteine codons at positions 90, 116, and 129 with a number of different codons. In vivo analysis of the replacements showed that none of the cysteines is absolutely essential and that they do not have a direct role as catalysts in ATP hydrolysis. Some amino acid substitutions abolished all RecA functions, while a few resulted in partial or altered function. Amino acids at positions 90 and 129 tended to affect all functions equally, while the amino acid at position 116 appeared to have a particular effect on the protease activity of the protein. ^

Design and analysis for three level hierarchical structures with count response

In numerous intervention studies and education field trials, random assignment to treatment occurs in clusters rather than at the level of observation. This departure of random assignment of units may be due to logistics, political feasibility, or ecological validity. Data within the same cluster or grouping are often correlated. Application of traditional regression techniques, which assume independence between observations, to clustered data produce consistent parameter estimates. However such estimators are often inefficient as compared to methods which incorporate the clustered nature of the data into the estimation procedure (Neuhaus 1993).1 Multilevel models, also known as random effects or random components models, can be used to account for the clustering of data by estimating higher level, or group, as well as lower level, or individual variation. Designing a study, in which the unit of observation is nested within higher level groupings, requires the determination of sample sizes at each level. This study investigates the design and analysis of various sampling strategies for a 3-level repeated measures design on the parameter estimates when the outcome variable of interest follows a Poisson distribution. ^ Results study suggest that second order PQL estimation produces the least biased estimates in the 3-level multilevel Poisson model followed by first order PQL and then second and first order MQL. The MQL estimates of both fixed and random parameters are generally satisfactory when the level 2 and level 3 variation is less than 0.10. However, as the higher level error variance increases, the MQL estimates become increasingly biased. If convergence of the estimation algorithm is not obtained by PQL procedure and higher level error variance is large, the estimates may be significantly biased. In this case bias correction techniques such as bootstrapping should be considered as an alternative procedure. For larger sample sizes, those structures with 20 or more units sampled at levels with normally distributed random errors produced more stable estimates with less sampling variance than structures with an increased number of level 1 units. For small sample sizes, sampling fewer units at the level with Poisson variation produces less sampling variation, however this criterion is no longer important when sample sizes are large. ^ 1Neuhaus J (1993). “Estimation efficiency and Tests of Covariate Effects with Clustered Binary Data”. Biometrics , 49, 989–996^

Correlation between altered central pain processing and concentration of peritoneal fluid inflammatory cytokines in endometriosis patients with chronic pelvic pain

Translational research has not yet elucidated whether alterations in central pain processes are related to peripheral inflammatory processes in chronic pain patients. We tested the hypothesis that the concentration of cytokines in the peritoneal fluid of endometriosis patients with chronic pain correlate with parameters of hyperexcitability of the nociceptive system. The concentrations of 15 peritoneal fluid cytokines were measured in 11 patients with chronic pelvic pain and a diagnosis of endometriosis. Six parameters assessing central pain processes were recorded. Positive correlations between concentration of some cytokines in the peritoneal fluid and amplification of central pain processing were found. The results suggest that inflammatory mechanisms may be important in the pathophysiology of altered central pain processes and that cytokines produced in the environment of endometriosis could act as mediators between the peripheral lesion and changes in central nociceptive processes.

Unravelling the multiple roles of FUS in RNA processing and on ALS pathogenesis

Two genes with related functions in RNA biogenesis were recently reported in patients with familial ALS: the FUS/TLS gene at the ALS6 locus and the TARDBP/TDP-43 gene at the ALS10 locus [1, 2]. FUS has been implicated to function in several steps of gene expression, including transcription regulation [3], RNA splicing [4, 5], mRNA transport in neurons [6] and, interestingly, in microRNA (miRNA) processing [7]. The goal of this project is to identify the molecular mechanisms leading to the development of FUS mutations-associated ALS. Specifically, we want to test the hypothesis that these FUS mutations misregulate miRNA levels that in turn affect the expression of genes critical for motor neuron survival. In addition we want to test whether misregulation of the miRNA profile is a common feature in ALS. We have performed immunoprecipitations from total extracts of 293T cells expressing FLAG-tagged FUS to characterize its interactome by mass spectrometry. This proteomic study not only revealed a strong interaction of FUS with splicing factors, but shows that FUS might be involved in many, quite different pathways. To map which parts of the FUS protein contribute to the interaction with splicing factors, we have performed a set of experiments with a series of missense and deletion mutants. With this approach, we will not only gain information on the binding partners of FUS along with a map of the required domains for the interactions, but it will also help to unravel whether certain ALS-associated FUS mutations lead to a loss or gain of function due to gain or loss of interactors. Additionally, we have performed quantitative interactomics using SILAC to identify interactome differences of ALS-associated FUS mutants. To this end we have performed immunoprecipitations of total extract from 293T cells, stably transduced with constructs expressing wild-type FUS-FLAG as well as three different ALS-associated mutants (G156E, R244C, P525L). First results indicate striking differences in the interactome with certain RNA binding proteins. We are now validating these candidates in order to reveal the importance of these differential interactions in the context of ALS.

X-ray image calibration and its application to clinical orthopedics.

X-ray imaging is one of the most commonly used medical imaging modality. Albeit X-ray radiographs provide important clinical information for diagnosis, planning and post-operative follow-up, the challenging interpretation due to its 2D projection characteristics and the unknown magnification factor constrain the full benefit of X-ray imaging. In order to overcome these drawbacks, we proposed here an easy-to-use X-ray calibration object and developed an optimization method to robustly find correspondences between the 3D fiducials of the calibration object and their 2D projections. In this work we present all the details of this outlined concept. Moreover, we demonstrate the potential of using such a method to precisely extract information from calibrated X-ray radiographs for two different orthopedic applications: post-operative acetabular cup implant orientation measurement and 3D vertebral body displacement measurement during preoperative traction tests. In the first application, we have achieved a clinically acceptable accuracy of below 1° for both anteversion and inclination angles, where in the second application an average displacement of 8.06±3.71 mm was measured. The results of both applications indicate the importance of using X-ray calibration in the clinical routine.

Associative processing and paranormal belief

In the present study we introduce a novel task for the quantitative assessment of both originality and speed of individual associations. This 'BAG' (Bridge-the-Associative-Gap) task was used to investigate the relationships between creativity and paranormal belief. Twelve strong 'believers' and 12 strong 'skeptics' in paranormal phenomena were selected from a large student population (n > 350). Subjects were asked to produce single-word associations to word pairs. In 40 trials the two stimulus words were semantically indirectly related and in 40 other trials the words were semantically unrelated. Separately for these two stimulus types, response commonalities and association latencies were calculated. The main finding was that for unrelated stimuli, believers produced associations that were more original (had a lower frequency of occurrence in the group as a whole) than those of the skeptics. For the interpretation of the result we propose a model of association behavior that captures both 'positive' psychological aspects (i.e., verbal creativity) and 'negative' aspects (susceptibility to unfounded inferences), and outline its relevance for psychiatry. This model suggests that believers adopt a looser response criterion than skeptics when confronted with 'semantic noise'. Such a signal detection view of the presence/absence of judgments for loose semantic relations may help to elucidate the commonalities between creative thinking, paranormal belief and delusional ideation.

Laser ablation and induced nano-particle synthesis

Laser pulses are largely used for processing and analysis of materials and in particular for nano-particle synthesis. This paper addresses fundamentals of the generation of nano-materials following specific thermodynamic paths of the irradiated material. Computer simulations using the hydro code MULTI and the SESAME equation of state have been performed to follow the dynamics of a target initially heated by a short laser pulse over a distance comparable to the metal skin depth.