Serial FEM/XFEM-Based Update of Preoperative Brain Images Using Intraoperative MRI

Current neuronavigation systems cannot adapt to changing intraoperative conditions over time. To overcome this limitation, we present an experimental end-to-end system capable of updating 3D preoperative images in the presence of brain shift and successive resections. The heart of our system is a nonrigid registration technique using a biomechanical model, driven by the deformations of key surfaces tracked in successive intraoperative images. The biomechanical model is deformed using FEM or XFEM, depending on the type of deformation under consideration, namely, brain shift or resection. We describe the operation of our system on two patient cases, each comprising five intraoperative MR images, and we demonstrate that our approach significantly improves the alignment of nonrigidly registered images

Sumoylation delays the ATF7 transcription factor subcellular localization and inhibits its transcriptional activity

Over the past few years, small ubiquitin-like modifier (SUMO) modification has emerged as an important regulator of diverse pathways and activities including protein localization and transcriptional regulation. We identified a consensus sumoylation motif (IKEE), located within the N-terminal activation domain of the ATF7 transcription factor and thus investigated the role of this modification. ATF7 is a ubiquitously expressed transcription factor, homologous to ATF2, that binds to CRE elements within specific promoters. This protein is able to heterodimerize with Jun or Fos proteins and its transcriptional activity is mediated by interaction with TAF12, a subunit of the general transcription factor TFIID. In the present article, we demonstrate that ATF7 is sumoylated in vitro (using RanBP2 as a E3-specific ligase) and in vivo. Moreover, we show that ATF7 sumoylation affects its intranuclear localization by delaying its entry into the nucleus. Furthermore, SUMO conjugation inhibits ATF7 transactivation activity by (i) impairing its association with TAF12 and (ii) blocking its binding-to-specific sequences within target promoters

High frequency of antitumor T cells in the blood of melanoma patients before and after vaccination with tumor antigens

After vaccination of melanoma patients with MAGE antigens, we observed that even in the few patients showing tumor regression, the frequency of anti-vaccine T cells in the blood was often either undetectable or <10−5 of CD8 T cells. This frequency being arguably too low for these cells to be sole effectors of rejection, we reexamined the contribution of T cells recognizing other tumor antigens. The presence of such antitumor T cells in melanoma patients has been widely reported. To begin assessing their contribution to vaccine-induced rejection, we evaluated their blood frequency in five vaccinated patients. The antitumor cytotoxic T lymphocyte (CTL) precursors ranged from 10−4 to 3 × 10−3, which is 10–10,000 times higher than the anti-vaccine CTL in the same patient. High frequencies were also observed before vaccination. In a patient showing nearly complete regression after vaccination with a MAGE-3 antigen, we observed a remarkably focused antitumoral response. A majority of CTL precursors (CTLp's) recognized antigens encoded by MAGE-C2, another cancer-germline gene. Others recognized gp100 antigens. CTLp's recognizing MAGE-C2 and gp100 antigens were already present before vaccination, but new clonotypes appeared afterwards. These results suggest that a spontaneous antitumor T cell response, which has become ineffective, can be reawakened by vaccination and contribute to tumor rejection. This notion is reinforced by the frequencies of anti-vaccine and antitumor CTLs observed inside metastases, as presented by Lurquin et al. (Lurquin, C., B. Lethé, V. Corbière, I. Théate, N. van Baren, P.G. Coulie, and T. Boon. 2004. J. Exp. Med. 201:249–257)

Quantifying Risk Factors for Human Brucellosis in Rural Northern Tanzania

Brucellosis is a zoonosis of veterinary, public health and economic significance in most developing countries. Human brucellosis is a severely debilitating disease that requires prolonged treatment with a combination of antibiotics. The disease can result in permanent and disabling sequel, and results in considerable medical expenses in addition to loss of income due to loss of working hours. A study was conducted in Northern Tanzania to determine the risk factors for transmission of brucellosis to humans in Tanzania. This was a matched case-control study. Any patient with a positive result by a competitive ELISA (c-ELISA) test for brucellosis, and presenting to selected hospitals with at least two clinical features suggestive of brucellosis such as headache, recurrent or continuous fever, sweating, joint pain, joint swelling, general body malaise or backache, was defined as a case. For every case in a district, a corresponding control was traced and matched by sex using multistage cluster sampling. Other criteria for inclusion as a control included a negative c-ELISA test result and that the matched individual would present to hospital if falls sick. Multivariable analysis showed that brucellosis was associated with assisted parturition during abortion in cattle, sheep or goat. It was shown that individuals living in close proximity to other households had a higher risk of brucellosis. People who were of Christian religion were found to have a higher risk of brucellosis compared to other religions. The study concludes that assisting an aborting animal, proximity to neighborhoods, and Christianity were associated with brucellosis infection. There was no association between human brucellosis and Human Immunodeficiency Virus (HIV) serostatus. Protecting humans against contact with fluids and tissues during assisted parturition of livestock may be an important means of reducing the risk of transferring brucellosis from livestock to humans. These can be achieved through health education to the communities where brucellosis is common

The Swarm Initial Field Model for the 2014 geomagnetic field

Data from the first year of ESA's Swarm constellation mission are used to derive the Swarm Initial Field Model (SIFM), a new model of the Earth's magnetic field and its time variation. In addition to the conventional magnetic field observations provided by each of the three Swarm satellites, explicit advantage is taken of the constellation aspect by including east-west magnetic intensity gradient information from the lower satellite pair. Along-track differences in magnetic intensity provide further information concerning the north-south gradient. The SIFM static field shows excellent agreement (up to at least degree 60) with recent field models derived from CHAMP data, providing an initial validation of the quality of the Swarm magnetic measurements. Use of gradient data improves the determination of both the static field and its secular variation, with the mean misfit for east-west intensity differences between the lower satellite pair being only 0.12 nT

A 2015 International Geomagnetic Reference Field (IGRF) candidate model based on <i>Swarm’s</i> experimental absolute magnetometer vector mode data

International audienceEach of the three satellites of the European Space Agency Swarm mission carries an absolute scalar magnetometer (ASM) that provides the nominal 1-Hz scalar data of the mission for both science and calibration purposes. These ASM instruments, however, also deliver autonomous 1-Hz experimental vector data. Here, we report on how ASM-only scalar and vector data from the Alpha and Bravo satellites between November 29, 2013 (a week after launch) and September 25, 2014 (for on-time delivery of the model on October 1, 2014) could be used to build a very valuable candidate model for the 2015.0 International Geomagnetic Reference Field (IGRF). A parent model was first computed, describing the geomagnetic field of internal origin up to degree and order 40 in a spherical harmonic representation and including a constant secular variation up to degree and order 8. This model was next simply forwarded to epoch 2015.0 and truncated at degree and order 13. The resulting ASM-only 2015.0 IGRF candidate model is compared to analogous models derived from the mission's nominal data and to the now-published final 2015.0 IGRF model. Differences among models mainly highlight uncertainties enhanced by the limited geographical distribution of the selected data set (essentially due to a lack of availability of data at high northern latitude satisfying nighttime conditions at the end of the time period considered). These appear to be comparable to differences classically observed among IGRF candidate models. These positive results led the ASM-only 2015.0 IGRF candidate model to contribute to the construction of the final 2015.0 IGRF model

Outcomes in newly diagnosed elderly glioblastoma patients after concomitant temozolomide administration and hypofractionated radiotherapy

This study aimed to analyze the treatment and outcomes of older glioblastoma patients. Forty-four patients older than 70 years of age were referred to the Paul Strauss Center for chemotherapy and radiotherapy. The median age was 75.5 years old (range: 70-84), and the patients included 18 females and 26 males. The median Karnofsky index (KI) was 70%. The Charlson indices varied from 4 to 6. All of the patients underwent surgery. O6-methylguanine-DNA methyltransferase (MGMT) methylation status was determined in 25 patients. All of the patients received radiation therapy. Thirty-eight patients adhered to a hypofractionated radiation therapy schedule and six patients to a normofractionated schedule. Neoadjuvant, concomitant and adjuvant chemotherapy regimens were administered to 12, 35 and 20 patients, respectively. At the time of this analysis, 41 patients had died. The median time to relapse was 6.7 months. Twenty-nine patients relapsed, and 10 patients received chemotherapy upon relapse. The median overall survival (OS) was 7.2 months and the one- and two-year OS rates were 32% and 12%, respectively. In a multivariate analysis, only the Karnofsky index was a prognostic factor. Hypofractionated radiotherapy and chemotherapy with temozolomide are feasible and acceptably tolerated in older patients. However, relevant prognostic factors are needed to optimize treatment proposals

Complete exon sequencing of all known Usher syndrome genes greatly improves molecular diagnosis

<p>Abstract</p> <p>Background</p> <p>Usher syndrome (USH) combines sensorineural deafness with blindness. It is inherited in an autosomal recessive mode. Early diagnosis is critical for adapted educational and patient management choices, and for genetic counseling. To date, nine causative genes have been identified for the three clinical subtypes (USH1, USH2 and USH3). Current diagnostic strategies make use of a genotyping microarray that is based on the previously reported mutations. The purpose of this study was to design a more accurate molecular diagnosis tool.</p> <p>Methods</p> <p>We sequenced the 366 coding exons and flanking regions of the nine known USH genes, in 54 USH patients (27 USH1, 21 USH2 and 6 USH3).</p> <p>Results</p> <p>Biallelic mutations were detected in 39 patients (72%) and monoallelic mutations in an additional 10 patients (18.5%). In addition to biallelic mutations in one of the USH genes, presumably pathogenic mutations in another USH gene were detected in seven patients (13%), and another patient carried monoallelic mutations in three different USH genes. Notably, none of the USH3 patients carried detectable mutations in the only known USH3 gene, whereas they all carried mutations in USH2 genes. Most importantly, the currently used microarray would have detected only 30 of the 81 different mutations that we found, of which 39 (48%) were novel.</p> <p>Conclusions</p> <p>Based on these results, complete exon sequencing of the currently known USH genes stands as a definite improvement for molecular diagnosis of this disease, which is of utmost importance in the perspective of gene therapy.</p