The fixation of the cemented femoral component. Effects of stem stiffness, cement thickness and roughness of the cement-bone surface.

After cemented total hip arthroplasty (THA) there may be failure at either the cement-stem or the cement-bone interface. This results from the occurrence of abnormally high shear and compressive stresses within the cement and excessive relative micromovement. We therefore evaluated micromovement and stress at the cement-bone and cement-stem interfaces for a titanium and a chromium-cobalt stem. The behaviour of both implants was similar and no substantial differences were found in the size and distribution of micromovement on either interface with respect to the stiffness of the stem. Micromovement was minimal with a cement mantle 3 to 4 mm thick but then increased with greater thickness of the cement. Abnormally high micromovement occurred when the cement was thinner than 2 mm and the stem was made of titanium. The relative decrease in surface roughness augmented slipping but decreased debonding at the cement-bone interface. Shear stress at this site did not vary significantly for the different coefficients of cement-bone friction while compressive and hoop stresses within the cement increased slightly.

Tightening force and torque of nonlocking screws in a reverse shoulder prosthesis.

BACKGROUND: Reversed shoulder arthroplasty is an accepted treatment for glenohumeral arthritis associated to rotator cuff deficiency. For most reversed shoulder prostheses, the baseplate of the glenoid component is uncemented and its primary stability is provided by a central peg and peripheral screws. Because of the importance of the primary stability for a good osteo-integration of the baseplate, the optimal fixation of the screws is crucial. In particular, the amplitude of the tightening force of the nonlocking screws is clearly associated to this stability. Since this force is unknown, it is currently not accounted for in experimental or numerical analyses. Thus, the primary goal of this work is to measure this tightening force experimentally. In addition, the tightening torque was also measured, to estimate an optimal surgical value. METHODS: An experimental setup with an instrumented baseplate was developed to measure simultaneously the tightening force, tightening torque and screwing angle, of the nonlocking screws of the Aquealis reversed prosthesis. In addition, the amount of bone volume around each screw was measured with a micro-CT. Measurements were performed on 6 human cadaveric scapulae. FINDINGS: A statistically correlated relationship (p<0.05, R=0.83) was obtained between the maximal tightening force and the bone volume. The relationship between the tightening torque and the bone volume was not statistically significant. INTERPRETATION: The experimental relationship presented in this paper can be used in numerical analyses to improve the baseplate fixation in the glenoid bone.

Soft tissue artifact distribution on lower limbs during treadmill gait: Influence of skin markers' location on cluster design.

Segment poses and joint kinematics estimated from skin markers are highly affected by soft tissue artifact (STA) and its rigid motion component (STARM). While four marker-clusters could decrease the STA non-rigid motion during gait activity, other data, such as marker location or STARM patterns, would be crucial to compensate for STA in clinical gait analysis. The present study proposed 1) to devise a comprehensive average map illustrating the spatial distribution of STA for the lower limb during treadmill gait and 2) to analyze STARM from four marker-clusters assigned to areas extracted from spatial distribution. All experiments were realized using a stereophotogrammetric system to track the skin markers and a bi-plane fluoroscopic system to track the knee prosthesis. Computation of the spatial distribution of STA was realized on 19 subjects using 80 markers apposed on the lower limb. Three different areas were extracted from the distribution map of the thigh. The marker displacement reached a maximum of 24.9mm and 15.3mm in the proximal areas of thigh and shank, respectively. STARM was larger on thigh than the shank with RMS error in cluster orientations between 1.2° and 8.1°. The translation RMS errors were also large (3.0mm to 16.2mm). No marker-cluster correctly compensated for STARM. However, the coefficient of multiple correlations exhibited excellent scores between skin and bone kinematics, as well as for STARM between subjects. These correlations highlight dependencies between STARM and the kinematic components. This study provides new insights for modeling STARM for gait activity.

Rational design of an organometallic glutathione transferase inhibitor.

Double trouble: A hybrid organic-inorganic (organometallic) inhibitor was designed to target glutathione transferases. The metal center is used to direct protein binding, while the organic moiety acts as the active-site inhibitor (see picture). The mechanism of inhibition was studied using a range of biophysical and biochemical methods.

Using active learning for monitoring networks design: The example of wind power plants sites evaluation

Locating new wind farms is of crucial importance for energy policies of the next decade. To select the new location, an accurate picture of the wind fields is necessary. However, characterizing wind fields is a difficult task, since the phenomenon is highly nonlinear and related to complex topographical features. In this paper, we propose both a nonparametric model to estimate wind speed at different time instants and a procedure to discover underrepresented topographic conditions, where new measuring stations could be added. Compared to space filling techniques, this last approach privileges optimization of the output space, thus locating new potential measuring sites through the uncertainty of the model itself.

Coronary magnetic resonance angiography for assessment of the stent lumen: a phantom study.

PURPOSE: To evaluate the feasibility of visualizing the stent lumen using coronary magnetic resonance angiography in vitro. MATERIAL AND METHODS: Nineteen different coronary stents were implanted in plastic tubes with an inner diameter of 3 mm. The tubes were positioned in a plastic container filled with gel and included in a closed flow circuit (constant flow 18 cm/sec). The magnetic resonance images were obtained with a dual inversion fast spin-echo sequence. For intraluminal stent imaging, subtraction images were calculated from scans with and without flow. Subsequently, intraluminal signal properties were objectively assessed and compared. RESULTS: As a function of the stent type, various degrees of in-stent signal attenuation were observed. Tantalum stents demonstrated minimal intraluminal signal attenuation. For nitinol stents, the stent lumen could be identified, but the intraluminal signal was markedly reduced. Steel stents resulted in the most pronounced intraluminal signal voids. CONCLUSIONS: With the present technique, radiofrequency penetration into the stents is strongly influenced by the stent material. Thesefindings may have important implicationsforfuture stent design and stent imaging strategies.

Design and evaluation of a solid sampler for the monitoring of airborne 1,6-hexamethylene diisocyanate (HDI) and its prepolymers in 2-component spray painting

An active, solvent-free solid sampler was developed for the collection of 1,6-hexamethylene diisocyanate (HDI) aerosol and prepolymers. The sampler was made of a filter impregnated with 1-(2-methoxyphenyl)piperazine contained in a filter holder. Interferences with HDI were observed when a set of cellulose acetate filters and a polystyrene filter holder were used; a glass fiber filter and polypropylene filter cassette gave better results. The applicability of the sampling and analytical procedure was validated with a test chamber, constructed for the dynamic generation of HDI aerosol and prepolymers in commercial two-component spray paints (Desmodur(R) N75) used in car refinishing. The particle size distribution, temporal stability, and spatial uniformity of the simulated aerosol were established in order to test the sample. The monitoring of aerosol concentrations was conducted with the solid sampler paired to the reference impinger technique (impinger flasks contained 10 mL of 0.5 mg/mL 1-(2-methoxyphenyl)piperazine in toluene) under a controlled atmosphere in the test chamber. Analyses of derivatized HDI and prepolymers were carried out by using high-performance liquid chromatography and ultraviolet detection. The correlation between the solvent-free and the impinger techniques appeared fairly good (Y = 0.979X - 0.161; R = 0.978), when the tests were conducted in the range of 0.1 to 10 times the threshold limit value (TLV) for HDI monomer and up to 60-mu-g/m3 (3 U.K. TLVs) for total -N = C = O groups.

Experimental design for acquiring relevant data to address the issue of comparing consecutively manufactured tools and firearms

The comparison of consecutively manufactured tools and firearms has provided much, but not all, of the basis for the profession of firearm and toolmark examination. The authors accept the fundamental soundness of this approach but appeal to the experimental community to close two minor gaps in the experimental procedure. We suggest that "blinding" and attention to appropriateness of other experimental conditions that would consolidate the foundations of our profession. We do not suggest that previous work is unsound.

New concepts for the design of dermal substitutes

Objectives: Skin can be partially regenerated after full thickness defects by collagen matrices, In this study, we identified the main limitations of induced regeneration aiming to improve the design of dermal matrices. Methods: Single mice received a 1 cm2, full thickness skin wound on the dorsum, which were grafted with collagen-GAG matrices or left ungrafted. The healing modulation induced by the collagen-GAG matrices was compared to spontaneous healing and to custom designed, bioactive, poly-N-Acetyl- Glucosamine (NAG) matrices. Wound staging was based on macroscopic, histological and immunhistochemical analysis on days 3, 7, 10 and 21 post wounding. Results: Cell density was higher in spontaneously granulating wounds compared to grafted wounds. While grafted wounds exhibited increased levels of cell proliferation on days 7 and 10, vascularity was dramatically reduced. NAG scaffolds accelerated both angiogenesis and wound re-epithelialization. Conclusions: Since slow integration and revascularization severely limit the engraftment of clinically used dermal scaffolds, the design of dermal matrices using bioactive materials represent the next step in skin regeneration.

The impact of iron supplementation efficiency in female blood donors with a decreased ferritin level and no anaemia. Rationale and design of a randomised controlled trial: a study protocol.

ABSTRACT: BACKGROUND: There is no recommendation to screen ferritin level in blood donors, even though several studies have noted the high prevalence of iron deficiency after blood donation, particularly among menstruating females. Furthermore, some clinical trials have shown that non-anaemic women with unexplained fatigue may benefit from iron supplementation. Our objective is to determine the clinical effect of iron supplementation on fatigue in female blood donors without anaemia, but with a mean serum ferritin </= 30 ng/ml. METHODS/DESIGN: In a double blind randomised controlled trial, we will measure blood count and ferritin level of women under age 50 yr, who donate blood to the University Hospital of Lausanne Blood Transfusion Department, at the time of the donation and after 1 week. One hundred and forty donors with a ferritin level </= 30 ng/ml and haemoglobin level >/= 120 g/l (non-anaemic) a week after the donation will be included in the study and randomised. A one-month course of oral ferrous sulphate (80 mg/day of elemental iron) will be introduced vs. placebo. Self-reported fatigue will be measured using a visual analogue scale. Secondary outcomes are: score of fatigue (Fatigue Severity Scale), maximal aerobic power (Chester Step Test), quality of life (SF-12), and mood disorders (Prime-MD). Haemoglobin and ferritin concentration will be monitored before and after the intervention. DISCUSSION: Iron deficiency is a potential problem for all blood donors, especially menstruating women. To our knowledge, no other intervention study has yet evaluated the impact of iron supplementation on subjective symptoms after a blood donation. TRIAL REGISTRATION: NCT00689793.

Design and analysis of ChIP-Seq experiments for nuclear factor I DNA-binding proteins

SUMMARY : Eukaryotic DNA interacts with the nuclear proteins using non-covalent ionic interactions. Proteins can recognize specific nucleotide sequences based on the sterical interactions with the DNA and these specific protein-DNA interactions are the basis for many nuclear processes, e.g. gene transcription, chromosomal replication, and recombination. New technology termed ChIP-Seq has been recently developed for the analysis of protein-DNA interactions on a whole genome scale and it is based on immunoprecipitation of chromatin and high-throughput DNA sequencing procedure. ChIP-Seq is a novel technique with a great potential to replace older techniques for mapping of protein-DNA interactions. In this thesis, we bring some new insights into the ChIP-Seq data analysis. First, we point out to some common and so far unknown artifacts of the method. Sequence tag distribution in the genome does not follow uniform distribution and we have found extreme hot-spots of tag accumulation over specific loci in the human and mouse genomes. These artifactual sequence tags accumulations will create false peaks in every ChIP-Seq dataset and we propose different filtering methods to reduce the number of false positives. Next, we propose random sampling as a powerful analytical tool in the ChIP-Seq data analysis that could be used to infer biological knowledge from the massive ChIP-Seq datasets. We created unbiased random sampling algorithm and we used this methodology to reveal some of the important biological properties of Nuclear Factor I DNA binding proteins. Finally, by analyzing the ChIP-Seq data in detail, we revealed that Nuclear Factor I transcription factors mainly act as activators of transcription, and that they are associated with specific chromatin modifications that are markers of open chromatin. We speculate that NFI factors only interact with the DNA wrapped around the nucleosome. We also found multiple loci that indicate possible chromatin barrier activity of NFI proteins, which could suggest the use of NFI binding sequences as chromatin insulators in biotechnology applications. RESUME : L'ADN des eucaryotes interagit avec les protéines nucléaires par des interactions noncovalentes ioniques. Les protéines peuvent reconnaître les séquences nucléotidiques spécifiques basées sur l'interaction stérique avec l'ADN, et des interactions spécifiques contrôlent de nombreux processus nucléaire, p.ex. transcription du gène, la réplication chromosomique, et la recombinaison. Une nouvelle technologie appelée ChIP-Seq a été récemment développée pour l'analyse des interactions protéine-ADN à l'échelle du génome entier et cette approche est basée sur l'immuno-précipitation de la chromatine et sur la procédure de séquençage de l'ADN à haut débit. La nouvelle approche ChIP-Seq a donc un fort potentiel pour remplacer les anciennes techniques de cartographie des interactions protéine-ADN. Dans cette thèse, nous apportons de nouvelles perspectives dans l'analyse des données ChIP-Seq. Tout d'abord, nous avons identifié des artefacts très communs associés à cette méthode qui étaient jusqu'à présent insoupçonnés. La distribution des séquences dans le génome ne suit pas une distribution uniforme et nous avons constaté des positions extrêmes d'accumulation de séquence à des régions spécifiques, des génomes humains et de la souris. Ces accumulations des séquences artéfactuelles créera de faux pics dans toutes les données ChIP-Seq, et nous proposons différentes méthodes de filtrage pour réduire le nombre de faux positifs. Ensuite, nous proposons un nouvel échantillonnage aléatoire comme un outil puissant d'analyse des données ChIP-Seq, ce qui pourraient augmenter l'acquisition de connaissances biologiques à partir des données ChIP-Seq. Nous avons créé un algorithme d'échantillonnage aléatoire et nous avons utilisé cette méthode pour révéler certaines des propriétés biologiques importantes de protéines liant à l'ADN nommés Facteur Nucléaire I (NFI). Enfin, en analysant en détail les données de ChIP-Seq pour la famille de facteurs de transcription nommés Facteur Nucléaire I, nous avons révélé que ces protéines agissent principalement comme des activateurs de transcription, et qu'elles sont associées à des modifications de la chromatine spécifiques qui sont des marqueurs de la chromatine ouverte. Nous pensons que lés facteurs NFI interagir uniquement avec l'ADN enroulé autour du nucléosome. Nous avons également constaté plusieurs régions génomiques qui indiquent une éventuelle activité de barrière chromatinienne des protéines NFI, ce qui pourrait suggérer l'utilisation de séquences de liaison NFI comme séquences isolatrices dans des applications de la biotechnologie.

Giant extraskeletal myxoid chondrosarcoma of the thigh treated by wide extraarticular resection and reconstruction with a tumor prosthesis

Introduction: Extraskeletal myxoid chondrosarcoma (EMC) is a rare soft tissue tumour with a high risk for local recurrence and metastases. While this entity is resistant to radio- or chemo-therapy, wide resection remains the treatment of choice. Case report: A 60 year old man presented to our service with a large mass in his right thigh, slowly evolving over the past 7 years. His main complaint was the volume of his thigh. Imaging showed a 23x13x14 cm tumour in the quadriceps, eroding the cortical bone and with potential contamination of the knee joint. The risk of a pathological fracture was estimated considerable. A CT-guided core-needle biopsy revealed a FNCLCC grade 2 EMC. A thoraco-abdominal CT scan showed multiple pulmonary metastases. Due to the palliative situation with a very slow disease progression, a wide extraarticular resection of the distal femur and reconstruction with a megaprosthesis were performed. Extensive skin necrosis necessitated three revision procedures for débridement and confection of a pediculated lateral gastrocnemius muscle flap. No complementary treatment was possible for the pulmonary metastases. At 18 months follow-up, he walked without crutches, was able to do his activities of daily living. He was painfree and highly satisfied with the result. During the follow-up, slow progression of the pulmonary metastases was noted, which remained asymptomatic. Conclusion: Extraskeletal myxoid chondrosarcoma is a rare soft tissue tumour, and wide excision remains the treatment of choice. Whenever possible, limb salvage should be proposed to preserve function and quality of life.

Study design for technology assessment: critical issues.

The epidemiological methods have become useful tools for the assessment of the effectiveness and safety of health care technologies. The experimental methods, namely the randomized controlled trials (RCT), give the best evidence of the effect of a technology. However, the ethical issues and the very nature of the intervention under study sometimes make it difficult to carry out an RCT. Therefore, quasi-experimental and non-experimental study designs are also applied. The critical issues concerning these designs are discussed. The results of evaluative studies are of importance for decision-makers in health policy. The measurements of the impact of a medical technology should go beyond a statement of its effectiveness, because the essential outcome of an intervention or programme is the health status and quality of life of the individuals and populations concerned.

Docking, virtual high throughput screening and in silico fragment-based drug design.

ABSTRACT The drug discovery process has been profoundly changed recently by the adoption of computational methods helping the design of new drug candidates more rapidly and at lower costs. In silico drug design consists of a collection of tools helping to make rational decisions at the different steps of the drug discovery process, such as the identification of a biomolecular target of therapeutical interest, the selection or the design of new lead compounds and their modification to obtain better affinities, as well as pharmacokinetic and pharmacodynamic properties. Among the different tools available, a particular emphasis is placed in this review on molecular docking, virtual high throughput screening and fragment-based ligand design.