Software application profile: opal and mica: open-source software solutions for epidemiological data management, harmonization and dissemination

Improving the dissemination of information on existing epidemiological studies and facilitating the interoperability of study databases are essential to maximizing the use of resources and accelerating improvements in health. To address this, Maelstrom Research proposes Opal and Mica, two inter-operable open-source software packages providing out-of-the-box solutions for epidemiological data management, harmonization and dissemination.; Opal and Mica are two standalone but inter-operable web applications written in Java, JavaScript and PHP. They provide web services and modern user interfaces to access them.; Opal allows users to import, manage, annotate and harmonize study data. Mica is used to build searchable web portals disseminating study and variable metadata. When used conjointly, Mica users can securely query and retrieve summary statistics on geographically dispersed Opal servers in real-time. Integration with the DataSHIELD approach allows conducting more complex federated analyses involving statistical models.; Opal and Mica are open-source and freely available at [www.obiba.org] under a General Public License (GPL) version 3, and the metadata models and taxonomies that accompany them are available under a Creative Commons licence

Segond's fracture: a biomechanical cadaveric study using navigation

Background Segond’s fracture is a well-recognised radiological sign of an anterior cruciate ligament (ACL) tear. While previous studies evaluated the role of the anterolateral ligament (ALL) and complex injuries on rotational stability of the knee, there are no studies on the biomechanical effect of Segond’s fracture in an ACL deficient knee. The aim of this study was to evaluate the effect of a Segond’s fracture on knee rotation stability as evaluated by a navigation system in an ACL deficient knee. Materials and methods Three different conditions were tested on seven knee specimens: intact knee, ACL deficient knee and ACL deficient knee with Segond’s fracture. Static and dynamic measurements of anterior tibial translation (ATT) and axial tibial rotation (ATR) were recorded by the navigation system (2.2 OrthoPilot ACL navigation system B. Braun Aesculap, Tuttlingen, Germany). Results Static measurements at 30 showed that the mean ATT at 30 of knee flexion was 5.1 ± 2.7 mm in the ACL intact condition, 14.3 ± 3.1 mm after ACL cut (P = 0.005), and 15.2 ± 3.6 mm after Segond’s fracture (P = 0.08). The mean ATR at 30 of knee flexion was 20.7 ± 4.8 in the ACL intact condition, 26.9 ± 4.1 in the ACL deficient knee (P[0.05) and 30.9 ± 3.8 after Segond’s fracture (P = 0.005). Dynamic measurements during the pivot-shift showed that the mean ATT was 7.2 ± 2.7 mm in the intact knee, 9.1 ± 3.3 mm in the ACL deficient knee(P = 0.04) and 9.7 ± 4.3 mm in the ACL deficient knee with Segond’s fracture (P = 0.07). The mean ATR was 9.6 ± 1.8 in the intact knee, 12.3 ± 2.3 in the ACL deficient knee (P[0.05) and 19.1 ± 3.1 in the ACL deficient knee with Segond’s lesion (P = 0.016). Conclusion An isolated lesion of the ACL only affects ATT during static and dynamic measurements, while the addition of Segond’s fracture has a significant effect on ATR in both static and dynamic execution of the pivot-shift test, as evaluated with the aid of navigation

PReMod: a database of genome-wide mammalian cis-regulatory module predictions

We describe PReMod, a new database of genome-wide cis-regulatory module (CRM) predictions for both the human and the mouse genomes. The prediction algorithm, described previously in Blanchette et al. (2006) Genome Res., 16, 656–668, exploits the fact that many known CRMs are made of clusters of phylogenetically conserved and repeated transcription factors (TF) binding sites. Contrary to other existing databases, PReMod is not restricted to modules located proximal to genes, but in fact mostly contains distal predicted CRMs (pCRMs). Through its web interface, PReMod allows users to (i) identify pCRMs around a gene of interest; (ii) identify pCRMs that have binding sites for a given TF (or a set of TFs) or (iii) download the entire dataset for local analyses. Queries can also be refined by filtering for specific chromosomal regions, for specific regions relative to genes or for the presence of CpG islands. The output includes information about the binding sites predicted within the selected pCRMs, and a graphical display of their distribution within the pCRMs. It also provides a visual depiction of the chromosomal context of the selected pCRMs in terms of neighboring pCRMs and genes, all of which are linked to the UCSC Genome Browser and the NCBI. PReMod:

Tumour T1 changes in vivo are highly predictive of response to chemotherapy and reflect the number of viable tumour cells – a preclinical MR study in mice

BACKGROUND: Effective chemotherapy rapidly reduces the spin–lattice relaxation of water protons (T(1)) in solid tumours and this change (ΔT(1)) often precedes and strongly correlates with the eventual change in tumour volume (TVol). To understand the biological nature of ΔT(1), we have performed studies in vivo and ex vivo with the allosteric mTOR inhibitor, everolimus. METHODS: Mice bearing RIF-1 tumours were studied by magnetic resonance imaging (MRI) to determine TVol and T(1), and MR spectroscopy (MRS) to determine levels of the proliferation marker choline and levels of lipid apoptosis markers, prior to and 5 days (endpoint) after daily treatment with vehicle or everolimus (10 mg/kg). At the endpoint, tumours were ablated and an entire section analysed for cellular and necrotic quantification and staining for the proliferation antigen Ki67 and cleaved-caspase-3 as a measure of apoptosis. The number of blood-vessels (BV) was evaluated by CD31 staining. Mice bearing B16/BL6 melanoma tumours were studied by MRI to determine T(1) under similar everolimus treatment. At the endpoint, cell bioluminescence of the tumours was measured ex vivo. RESULTS: Everolimus blocked RIF-1 tumour growth and significantly reduced tumour T(1) and total choline (Cho) levels, and increased polyunsaturated fatty-acids which are markers of apoptosis. Immunohistochemistry showed that everolimus reduced the %Ki67(+) cells but did not affect caspase-3 apoptosis, necrosis, BV-number or cell density. The change in T(1) (ΔT(1)) correlated strongly with the changes in TVol and Cho and %Ki67(+). In B16/BL6 tumours, everolimus also decreased T(1) and this correlated with cell bioluminescence; another marker of cell viability. Receiver-operating-characteristic curves (ROC) for everolimus on RIF-1 tumours showed that ΔT(1) had very high levels of sensitivity and specificity (ROC(AUC) = 0.84) and this was confirmed for the cytotoxic patupilone in the same tumour model (ROC(AUC) = 0.97). CONCLUSION: These studies suggest that ΔT(1) is not a measure of cell density but reflects the decreased number of remaining viable and proliferating tumour cells due to perhaps cell and tissue destruction releasing proteins and/or metals that cause T(1) relaxation. ΔT(1) is a highly sensitive and specific predictor of response. This MRI method provides the opportunity to stratify a patient population during tumour therapy in the clinic

The landscape of viral associations in human cancers

Here, as part of the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, for which whole-genome and—for a subset—whole-transcriptome sequencing data from 2,658 cancers across 38 tumor types was aggregated, we systematically investigated potential viral pathogens using a consensus approach that integrated three independent pipelines. Viruses were detected in 382 genome and 68 transcriptome datasets. We found a high prevalence of known tumor-associated viruses such as Epstein–Barr virus (EBV), hepatitis B virus (HBV) and human papilloma virus (HPV; for example, HPV16 or HPV18). The study revealed significant exclusivity of HPV and driver mutations in head-and-neck cancer and the association of HPV with APOBEC mutational signatures, which suggests that impaired antiviral defense is a driving force in cervical, bladder and head-and-neck carcinoma. For HBV, HPV16, HPV18 and adeno-associated virus-2 (AAV2), viral integration was associated with local variations in genomic copy numbers. Integrations at the TERT promoter were associated with high telomerase expression evidently activating this tumor-driving process. High levels of endogenous retrovirus (ERV1) expression were linked to a worse survival outcome in patients with kidney cancer

Wegener Granulomatosis Revealed by Pleural Effusion

Pulmonary signs are common in Wegener's granulomatosis (WG). However, an initial presentation including pleural effusion has not been described. We describe a case of WG in which pleural effusion was the first clinical manifestation. A 45-year-old man with dorsal pain presented with pleural thickening and effusion, and a visible nodule on a thoracic scan. A dense chronic inflammatory infiltrate was obtained by pleural biopsy and an open lung biopsy revealed necrotizing granulomatous vasculitis. Serologies were positive for antineutrophil cytoplasmic antibodies and antiproteinase 3 antibodies. A diagnosis of WG was conducted and the patient was started on cyclophosphamide and methylprednisolone as an initial treatment, with a favorable evolution. Although pleural effusion is rarely described in WG, this pathology must be considered in the presence of this clinical manifestation

Testing the vagal withdrawal hypothesis during light exercise under autonomic blockade: a heart rate variability study

Introduction. We performed the first analysis of heart rate variability (HRV) at rest and exercise under full autonomic blockade on the same subjects, to test the conjecture that vagal tone withdrawal occurs at exercise onset. We hypothesized that, between rest and exercise: i) no differences in total power (PTOT) under parasympathetic blockade; ii) a PTOT fall under β1-sympathetic blockade; iii) no differences in PTOT under blockade of both ANS branches. Methods. 7 males (24±3 years) performed 5-min cycling (80W) supine, preceded by 5-min rest during control and with administration of atropine, metoprolol and atropine+metoprolol (double blockade). Heart rate and arterial blood pressure were continuously recorded. HRV and blood pressure variability were determined by power spectral analysis, and baroreflex sensitivity (BRS) by the sequence method. Results. At rest, PTOT and the powers of low (LF) and high (HF) frequency components of HRV were dramatically decreased in atropine and double blockade compared to control and metoprolol, with no effects on LF/HF ratio and on the normalised LF (LFnu) and HF (HFnu). At exercise, patterns were the same as at rest. Comparing exercise to rest, PTOT varied as hypothesized. For SAP and DAP, resting PTOT was the same in all conditions. At exercise, in all conditions, PTOT was lower than in control. BRS decreased under atropine and double blockade at rest, under control and metoprolol during exercise. Conclusions. The results support the hypothesis that vagal suppression determined disappearance of HRV during exercise

The O3E program: Innovative educational and communication tools for better face natural hazards and emergencies

As dramatically reminded during the last days by the Haiti disaster, earthquakes are traumatic events as storms or floods. They cause more damages when population don’t have the knowledge of these phenomena and doesn’t know how to deal with it. Presently, it’s not possible to predict an earthquakes or extreme meteorological events. Preparation stay the best and efficient way to save life. Education and training are two essential ingredients to help the population to perceive the scientific information formerly confined in the laboratories, in particular in the domain of the environmental risk. The “O3E” innovative Project (European Observatory for Education and Environment) is established after 10 years (1997-2007) of regional, national and international programs (“Sismos of the Schools”, “Rinamed Medocc”), and from Italian and Swiss experiences concerning environment tools for education. This project with cooperation between scientists of France, Italy and Switzerland, is born to promote a responsible behavior of young citizens by means of scientific information about natural risks. ARGAL (Agency for Geological Risk in the Latin Arc - France) operates the administrative and technical coordination. The first innovative output of O3E is the creation of a school network in the Alpine and Mediterranean areas equipped with environmental sensors installed direct into the educational buildings. The data by seismometers, weather stations, river’s flows and soil moisture, recorded in the schools and processed by the students, are collected on dedicated servers and then made available through a internet platform to the entire educational community. By means of coordinated activities of critical analysis of data, their comparison with the information available through other media, the awareness about the importance of knowledge and evaluation of reliable data about their own territory is promoted. This equipment’s network “O3E," is the starting point of many other activities realized by the consortium with students and teachers. The teachers attend common meetings to exchange ideas and methods. The students are involved in activities of teaching towards younger pupils. The number of involved schools can theoretically increase without limit, by means of the implemented virtual network and e-learning tools at the dedicated web site. Various general objectives are pursued. - To promote the applied sciences and new technologies. - To put in network the actors of Education and formation. - To develop the sense of the autonomy and the responsibility in the young people. - To reinforce and develop relationships with regional partners of the educational and university fields. - To support a rational awakening for the prevention of the natural risks that can make the difference during the event in terms of safety. With these premises, the “O3E” experience sets up a permanent educational network of citizens in the Alpine and Mediterranean areas, building an exchange of knowledge on natural risks prevention.PublishedVienna5.9. Formazione e informazioneope