The effect of mountain bike suspensions on vibrations and off-road uphill performance.

AIM: This study evaluates the effect of front suspension (FS) and dual suspension (DS) mountain-bike on performance and vibrations during off-road uphill riding. METHODS: Thirteen male cyclists (27+/-5 years, 70+/-6 kg, VO(2max)59+/-6 mL.kg(-1).min(-1), mean+/-SD) performed, in a random sequence, at their lactate threshold, an off-road uphill course (1.69 km, 212 m elevation gain) with both type of bicycles. Variable measured: a) VO(2) consumption (K4b2 analyzer, Cosmed), b) power output (SRM) c) gain in altitude and d) 3-D accelerations under the saddle and at the wheel (Physilog, EPFL, Switzerland). Power spectral analy- sis (Fourier) was performed from the vertical acceleration data. RESULTS: Respectively for the FS and DS mountain bike: speed amounted to 7.5+/-0.7 km.h(-1) and 7.4+/-0.8 km.h(-1), (NS), energy expenditure 1.39+/-0.16 kW and 1.38+/-0.18, (NS), gross efficiency 0.161+/-0.013 and 0.159+/-0.013, (NS), peak frequency of vibration under the saddle 4.78+/-2.85 Hz and 2.27+/-0.2 Hz (P<0.01) and median-frequency of vertical displacements of the saddle 9.41+/-1.47 Hz and 5.78+/-2.27 Hz (P<0.01). CONCLUSION: Vibrations at the saddle level of the DS bike are of low frequencies whereas those of the FS bike are mostly of high frequencies. In the DS bike, the torque produced by the cyclist at the pedal level may generate low frequency vibrations. We conclude that the DS bike absorbs more high frequency vibrations, is more comfortable and performs as well as the FS bicycle.

Molecular investigation of lymph nodes in colon cancer patients using one-step nucleic acid amplification (OSNA): a new road to better staging?

BACKGROUND: A new diagnostic system, called one-step nucleic acid amplification (OSNA), has recently been designed to detect cytokeratin 19 mRNA as a surrogate for lymph node metastases. The objective of this prospective investigation was to compare the performance of OSNA with both standard hematoxylin and eosin (H&E) analysis and intensive histopathology in the detection of colon cancer lymph node metastases. METHODS: In total, 313 lymph nodes from 22 consecutive patients with stage I, II, and III colon cancer were assessed. Half of each lymph node was analyzed initially by H&E followed by an intensive histologic workup (5 levels of H&E and immunohistochemistry analyses, the gold standard for the assessment of sensitivity/specificity of OSNA), and the other half was analyzed using OSNA. RESULTS: OSNA was more sensitive in detecting small lymph node tumor infiltrates compared with H&E (11 results were OSNA positive/H&E negative). Compared with intensive histopathology, OSNA had 94.5% sensitivity, 97.6% specificity, and a concordance rate of 97.1%. OSNA resulted in an upstaging of 2 of 13 patients (15.3%) with lymph node-negative colon cancer after standard H&E examination. CONCLUSIONS: OSNA appeared to be a powerful and promising molecular tool for the detection of lymph node metastases in patients with colon cancer. OSNA had similar performance in the detection of lymph node metastases compared with intensive histopathologic investigations and appeared to be superior to standard histology with H&E. Most important, the authors concluded that OSNA may lead to a potential upstaging of >15% of patients with colon cancer.

Osteoid osteoma-like lesions: MDCT features and treatment by radiofrequency ablation : 46

Purpose: To assess the MDCT features of bone lesions that mimic osteoid osteoma (OO-like lesions) and evaluate their treatment by radiofrequency (RF) ablation. Methods and materials: All percutaneous RF ablations performed between May 2002 and June 2009 for a presumed (clinical and MDCT features) diagnosis of OO were retrospectively reviewed. Per-procedural biopsies were always performed and histopathological diagnoses were noted. The following MDCT features of all bone lesions were assessed by two musculoskeletal radiologists in consensus: skeletal distribution and location within the bone, size, central calcification, surrounding osteosclerosis and periosteal reaction. Clinical success was also evaluated. Results: Eighty patients (54 males, 26 females, mean age 24.1 years, range 5-48) underwent RF ablation. The histopathological diagnoses were: 54 non-contributory biopsies, 16 OO, 10 OO-like lesions (5 chronic osteomyelitis, 3 chondroblastoma, 1 eosinophilic granuloma, 1 fibrous dysplasia). The OO-like lesions were significantly greater in size (p = 0.001) and exhibited trends toward medullary location within the bone, moderate surrounding osteosclerosis and less periosteal reaction, compared to OO. Primary clinical success for OO-like lesions was 100% at 1 month, 85.7% at 6 and 12 months, and 66.7% at 24 months. Secondary success was 100%. Conclusion: Greater size, medullary location within the bone, lesser surrounding osteosclerosis and periosteal reaction on MDCT may help differentiate OO-like lesions from OO. OO-like lesions are safely and successfully treated by RF ablation.

Molecular features of hepatosplenic T-cell lymphoma unravels potential novel therapeutic targets.

The pathogenesis of hepatosplenic T-cell lymphoma (HSTL), a rare entity mostly derived from γδ T cells and usually with a fatal outcome, remains largely unknown. In this study, HSTL samples (7γδ and 2αβ) and the DERL2 HSTL cell line were subjected to combined gene-expression profiling and array-based comparative genomic hybridization. Compared with other T-cell lymphomas, HSTL had a distinct molecular signature irrespective of TCR cell lineage. Compared with peripheral T-cell lymphoma, not otherwise specified and normal γδ T cells, HSTL overexpressed genes encoding NK-cell-associated molecules, oncogenes (FOS and VAV3), the sphingosine-1-phosphatase receptor 5 involved in cell trafficking, and the tyrosine kinase SYK, whereas the tumor-suppressor gene AIM1 (absent in melanoma 1) was among the most down-expressed. We found highly methylated CpG islands of AIM1 in DERL2 cells, and decitabine treatment induced a significant increase in AIM1 transcripts. Syk was present in HSTL cells and DERL2 cells contained phosphorylated Syk and were sensitive to a Syk inhibitor in vitro. Genomic profiles confirmed recurrent isochromosome 7q (n = 6/9) without alterations at the SYK and AIM1 loci. Our results identify a distinct molecular signature for HSTL and highlight oncogenic pathways that offer rationale for exploring new therapeutic options such as Syk inhibitors and demethylating agents.

One-step nucleic acid amplification (OSNA): a new road to better staging in colon cancer patients?

Introduction: Approximately one fifth of stage I and II colon cancer patients will suffer from recurrent disease. This is partly due to the presence of small nodal tumour infiltrates, which are undetected by standard histopathology using Haematoxylin & Eosin (H&E) staining on one slice and thus may not receive beneficial adjuvant therapy. A new diagnostic, semi-automatic system, called one-step nucleic acid amplification (OSNA), was recently designed for the detection of cytokeratin 19 (CK19) mRNA as a surrogate for lymph node metastases. The objective of the present investigation was to compare the performance of OSNA with both standard H&E as well as intensive histopathologic analyses in the detection of colon cancer lymph node micro- and macro-metastases.Methods: In this prospective study 313 lymph nodes from 22 consecutive stage I - III colon cancer patients were assessed. Half of each lymph node was analysed initially based on one slice of H&E followed by an intensive histologic work-up (5 levels of H&E and immuno-histochemistry staining for each slice), the other half was analysed using OSNA.Results: All OSNA results were available after less than 40 minutes. Fifty-one lymph nodes were positive and 246 lymph nodes negative with both OSNA and standard H&E. OSNA was more sensitive to detect small nodal tumor infiltrates compared to H&E (11 OSNA pos. /H&E neg.). Compared to intensive histopathologic analyses, OSNA had a sensitivity of 94.5% and a specificity of 97.6% to detect lymph node micro- and macro-metastases with a concordance rate of 97.1%. An upstaging due to OSNA was found in 2/13 (15.3%) initially node negative colon cancer patients.Conclusion: OSNA appears to be a powerful and promising molecular tool for the detection of lymph node macro- and micro-metastases in colon cancer patients. OSNA has a similar performance in the detection of micro- and macro-metastases compared to intensive histopathologic investigations and appears to be superior to standard histology with H&E. Since the use of OSNA allows the analysis of the whole lymph node, the problem of sampling bias and undetected tumor deposits due to uninvestigated material will be overcome in the future and OSNA may thus improve staging in colon cancer patients. It is hoped that this improved staging will lead to better patient selection for adjuvant therapy and consecutively improved local and distant control as well as better overall survival.

Clinicopathological features of eyelid skin tumors. A retrospective study of 5504 cases and review of literature.

Eyelid tumors are the most common neoplasm in daily ophthalmology practice and encompass a wide variety of benign and malignant tumors. In this retrospective study, we report the clinical and histological features of 5504 eyelid skin tumors diagnosed at the Laboratory of Ophthalmopathology of the Hôpital Ophtalmique Jules Gonin, Lausanne, Switzerland, between January 1989 and December 2007. Benign tumors largely predominated over malignant ones, representing 84% of cases in this series, and the 5 most frequent subtypes were squamous cell papilloma (26%), seborrheic keratosis (21%), melanocytic nevus (20%), hidrocystoma (8%), and xanthoma/xanthelasma (6%). Basal cell carcinoma was the most frequent malignant tumor (86%), followed by squamous cell carcinoma (7%) and sebaceous carcinoma (3%). For several tumor subtypes, there was a poor correlation between clinical and histological diagnosis, stressing the numerous pitfalls in the diagnosis of eyelid tumors. We further discuss our results with reference to previously published series.

Review of CT features of saprophytic aspergillosis (Aspergilloma) and correlation with final diagnosis : P21

Purpose: 1. To review Ct features suggestive of saprophytic aspergillosis (aspergilloma) and to correlate them with the final pathological results. 2. To illustrate the wide range of differential diagnosis. Methods and materials: The electronic database of our department from 1995 to 2007 revealed CT reports of 48 patients that had been considered very suggestive of aspergilloma. Two radiologists with 6 and 12 years experience in thoracic radiology jointly reviewed the corresponding CT features including ancillary findings and the underlying lung diseases and correlated them with the final pathological diagnosis. Results: Forty patients could be included in the study (12 women, mean age 52), while in 8 patients there was no adequate clinical follow-up. In 17 patients the diagnosis "mycetoma" due to aspergillus fumigatus infection was confirmed, either by surgery, biopsy or bronchoscopy. In 23 patients, differential diagnoses were found, such as cavitating bronchial carcinoma (n = 7), bacterial abscess (n = 3), typical (n = 2) and atypical (n = 2) tuberculosis, as well as inflammatory changes due to mucoviscidosis (n = 1), Wegener's disease (n = 1) or chronic obstructive pulmonary disease (n = 3). Fibromyxoide hamartoma, lung infarction and bronchomucocele were responsible for the typical CT feature in one patient each. Conclusion: 1. The typical CT feature suggesting mycetoma is softtissue proliferation within a pre-existing wall-thickened lung cavity, oten even considered "pathognomonic". However, this diagnosis was finally confirmed by surgery or laboratory findings in less than 50% of patients only. 2. Since differential diagnoses are very large, not only including cavitating lung cancer and tuberculosis, the individual underlying lung disease needs strongly being taken into account often giving the best clue for the correct diagnosis.

Architectural features of bacterial genomes and their applications

Résumé -Caractéristiques architecturales des génomes bactériens et leurs applications Les bactéries possèdent généralement un seul chromosome circulaire. A chaque génération, ce chromosome est répliqué bidirectionnellement, par deux complexes enzymatiques de réplication se déplaçant en sens opposé depuis l'origine de réplication jusqu'au terminus, situé à l'opposé. Ce mode de réplication régit l'architecture du chromosome -l'orientation des gènes par rapport à la réplication, notamment - et est en grande partie à l'origine des pressions qui provoquent la variation de la composition en nucléotides du génome, hors des contraintes liées à la structure et à la fonction des protéines codées sur le chromosome. Le but de cette thèse est de contribuer à quantifier les effets de la réplication sur l'architecture chromosomique, en s'intéressant notamment aux gènes des ARN ribosomiques, cruciaux pour la bactérie. D'un autre côté, cette architecture est spécifique à l'espèce et donne ainsi une «identité génomique » aux gènes. Il est démontré ici qu'il est possible d'utiliser des marqueurs «naïfs » de cette identité pour détecter, notamment dans le génome du staphylocoque doré, des îlots de pathogénicité, qui concentrent un grand nombre de facteurs de virulence de la bactérie. Ces îlots de pathogénicité sont mobiles, et peuvent passer d'une bactérie à une autre, mais conservent durant un certain temps l'identité génomique de leur hôte précédent, ce qui permet de les reconnaître dans leur nouvel hôte. Ces méthodes simples, rapides et fiables seront de la plus haute importance lorsque le séquençage des génomes entiers sera rapide et disponible à très faible coût. Il sera alors possible d'analyser instantanément les déterminants pathogéniques et de résistance aux antibiotiques des agents pathogènes. Summary The bacterial genome is a highly organized structure, which may be referred to as the genome architecture, and is mainly directed by DNA replication. This thesis provides significant insights in the comprehension of the forces that shape bacterial chromosomes, different in each genome and contributing to confer them an identity. First, it shows the importance of the replication in directing the orientation of prokaryotic ribosomal RNAs, and how it shapes their nucleotide composition in a tax on-specific manner. Second, it highlights the pressure acting on the orientation of the genes in general, a majority of which are transcribed in the same direction as replication. Consequently, apparent infra-arm genome rearrangements, involving an exchange of the leading/lagging strands and shown to reduce growth rate, are very likely artifacts due to an incorrect contig assembly. Third, it shows that this genomic identity can be used to detect foreign parts in genomes, by establishing this identity for a given host and identifying the regions that deviate from it. This property is notably illustrated with Staphylococcus aureus: known pathogenicity islands and phages, and putative ancient pathogenicity islands concentrating many known pathogenicity-related genes are highlighted; the analysis also detects, incidentally, proteins responsible for the adhesion of S. aureus to the hosts' cells. In conclusion, the study of nucleotide composition of bacterial genomes provides the opportunity to better understand the genome-level pressures that shape DNA sequences, and to identify genes and regions potentially related to pathogenicity with fast, simple and reliable methods. This will be of crucial importance when whole-genome sequencing will be a rapid, inexpensive and routine tool.

Mesenteric venous thrombosis : MDCT features according to the underlying etiology : P1

Purpose: To work out certain, well-defined aetiologies frequently associated with mesenteric venous thrombosis (MVT) in order to predict a typical population at risk, since MVT is nowadays often incidentally detected on cross-sectional imaging. To demonstrate the MDCT features, frequency and extent of associated bowel ischemia according to the underlying pathology. Methods and materials: Our electronic database revealed 71 patients (25 women, mean age 55) with thrombosis of the superior and/or inferior mesenteric vein detected by MDCT between 2000 and 2008. Two radiologists jointly reviewed the corresponding MDCT features including intraluminal extension, underlying aetiology and associated bowel ischemia, if present. Results: MVT was associated with carcinoma in 31 (43.7%) patients (pancreas 21.1%, liver 9.9%, others 12.7%). Concomitant inflammation was seen in 15 (21.1%) patients (pancreatitis 11.3%, diverticulitis 4.2%, others 5.6%), whereas coagulation/hematologic disorders were found in 7 (9.9%) patients, liver cirrhosis in 6 (8.5%), mixed/miscellaneous causes in 5 (7%) and still unknown aetiologies in 5 patients (7%). MVT resulted from recent operations in 2 (2.8%) patients. MDCT features of venous bowel ischemia were present in 15 patients (21.1%). 46.5% of MVT were (sub) acute, while 53.5% chronic. The luminal extension was complete in 52.1%, subtotal (>50% of lumen) in 22.5% and partial (<50% of lumen) in 25.4% of patients, consisting either of blood clots (76.1%) or tumoral tissue (23.9%), the latter mainly due to pancreas adenocarcinoma (76.4%). Conclusion: MDCT features of MVT are seen with a wide range of underlying diseases. Signs of intestinal ischemia are infrequently associated, mostly occurring with coagulation/hematologic disorders (40%).

Ophthalmic features of PLA2G6-related paediatric neurodegeneration with brain iron accumulation.

BACKGROUND: Neurodegeneration with brain iron accumulation (NBIA) refers to genetically heterogenous paediatric neurodegenerative disorders characterised by basal ganglia iron deposition. One major cause is recessive mutations in the PLA2G6 gene. While strabismus and optic nerve pallor have been reported for PLA2G6-related disease, the ophthalmic phenotype is not carefully defined. In this study we characterise the ophthalmic phenotype of PLA2G6-related NBIA. METHODS: Prospective cohort study. RESULTS: The eight patients were 4-26 years old when examined. All had progressive cognitive and motor regression first noted between 9 months and 6 years of age that typically first manifested as difficulty walking (ataxia). Ophthalmic examination was sometimes limited by cognitive ability. Four of eight had exotropia, 7/7 bilateral supraduction defect, 5/7 poor convergence, 6/8 saccadic pursuit, 4/8 saccadic intrusions that resembled square-wave jerks, and 8/8 bilateral optic nerve head pallor. All patients lacked Bell phenomenon. CONCLUSIONS: Upgaze palsy, although not a previously reported finding, was confirmed in all patients (except in one for whom assessment could not be performed) and thus can be considered part of the phenotype in children and young adults. Other frequent findings not previously highlighted were abnormal convergence, saccadic pursuit, and saccadic intrusions. Optic nerve head pallor and strabismus, previously reported findings in the disease, were found in 100% and 50% of our cohort, respectively, and the strabismus in our series was always exotropia. Taken together, these clinical findings may be helpful in distinguishing PLA2G6-related neurodegeneration from the other major cause of NBIA, recessive PANK2 mutations.

Extensor carpi ulnaris accessory tendinous slips (ECUATS): MRI features at 3.0T and correlation with tendinosis : 49

Purpose: To assess the visibility and the features of ECUATS on 3.0-T MRI studies, and evaluate their correlation with tendinosis. Methods and materials: Our retrospective study was approved by IRB, with waiver of informed consent. Fifty wrist MRI and 48 MR arthrographies from 98 patients (55 males, 43 females, mean age 42.3 years) performed between January and November 2009 on 3.0-T units were reviewed. Images (transverse T1, T2, FS Gd T1 and VIBE) were independently analyzed by two radiologists, and a consensus reached with a third reader in case of disagreement. The visibility of ECUATS was assessed on each available transverse sequence. When present, ECUATS' origins, diameters and insertions were noted. ECU tendinosis was also evaluated. Inter-rater agreement was assessed using Cohen's Kappa coefficient. Results: ECUATS observed prevalence was 23.5% (23/98). ECUATS were more frequently noted on the VIBE sequence, with a good inter-rater agreement (Kappa = 0.72). Origins were noted in 95.7% of cases: 3 were at the level of, and 20 distal to ECU subsheath. Insertions were seen in 43.5%: 2 were on 5th metacarpal bone, 8 on extensor apparatus of 5th finger. ECUATS mean shortest and longest diameters were 0.54 and 0.85 mm respectively. ECU tendinosis was statistically more frequently noted in patients with ECUATS (p <0.05). Conclusion: ECUATS are readily visible on 3.0-T MRI studies, especially on transverse GRE VIBE images. ECU tendinosis is more frequently noted in patients bearing ECUATS.

Prevalence, prenatal diagnosis and clinical features of oculo-auriculo-vertebral spectrum: a registry-based study in Europe.

Oculo-auriculo-vertebral spectrum is a complex developmental disorder characterised mainly by anomalies of the ear, hemifacial microsomia, epibulbar dermoids and vertebral anomalies. The aetiology is largely unknown, and the epidemiological data are limited and inconsistent. We present the largest population-based epidemiological study to date, using data provided by the large network of congenital anomalies registries in Europe. The study population included infants diagnosed with oculo-auriculo-vertebral spectrum during the 1990-2009 period from 34 registries active in 16 European countries. Of the 355 infants diagnosed with oculo-auriculo-vertebral spectrum, there were 95.8% (340/355) live born, 0.8% (3/355) fetal deaths, 3.4% (12/355) terminations of pregnancy for fetal anomaly and 1.5% (5/340) neonatal deaths. In 18.9%, there was prenatal detection of anomaly/anomalies associated with oculo-auriculo-vertebral spectrum, 69.7% were diagnosed at birth, 3.9% in the first week of life and 6.1% within 1 year of life. Microtia (88.8%), hemifacial microsomia (49.0%) and ear tags (44.4%) were the most frequent anomalies, followed by atresia/stenosis of external auditory canal (25.1%), diverse vertebral (24.3%) and eye (24.3%) anomalies. There was a high rate (69.5%) of associated anomalies of other organs/systems. The most common were congenital heart defects present in 27.8% of patients. The prevalence of oculo-auriculo-vertebral spectrum, defined as microtia/ear anomalies and at least one major characteristic anomaly, was 3.8 per 100,000 births. Twinning, assisted reproductive techniques and maternal pre-pregnancy diabetes were confirmed as risk factors. The high rate of different associated anomalies points to the need of performing an early ultrasound screening in all infants born with this disorder.