Prosper: image and robot-guided prostate brachytherapy

Brachytherapy for localized prostate cancer consists in destroying cancer by introducing iodine radioactive seeds into the gland through hollow needles. The planning of the position of the seeds and their introduction into the prostate is based on intra-operative ultrasound (US) imaging. We propose to optimize the global quality of the procedure by: i) using 3D US; ii) enhancing US data with MRI registration; iii) using a specially designed needle-insertion robot, connected to the imaging data. The imaging methods have been successfully tested on patient data while the robot accuracy has been evaluated on a realistic deformable phantom

Analisis Karakteristik Dan Biaya Kecelakaan Lalu Lintas Di Kota Kupang

Kecelakaan lalu lintas merupakan indikator utama tingkat keselamatan jalan raya. Kota Kupang sebagai ibukota Propinsi Nusa Tenggara Timur (NTT) adalah salah satu daerah penyumbang angka kecelakaan terbesar di NTT. Penelitian ini disusun untuk mengetahui karakteristik kecelakaan lalu lintas, besar biaya kecelakaan lalu lintas pada ruas jalan di Kota Kupang, serta besar santunan yang harus dibayarkan oleh PT Jasa Raharja. Data yang digunakan adalah data jumlah kecelakaan lalu lintas Kota Kupang sepanjang tahun 2010-2013. Hasil analisis deskriptif menunjukkan bahwa karakteristik kecelakaan lalu lintas yang dominan terjadi adalah pada hari Minggu (22%), pukul 12.01–18.00 WITA (38%), posisi tabrakan depan - depan (30%), tipe tabrakan ganda (82%), jenis kelamin laki-laki (77%), usia 17 tahun - 30 tahun (64%), profesi Swasta (48%), pendidikan terakhir SMA (48%), dan tidak memiliki SIM (76%). Analisis biaya korban kecelakaan lalu lintas (BBKO) dengan metode The Gross Output menunjukkan bahwa ruas jalan Timor Raya dengan panjang 11 kilometer merupakan ruas jalan dengan BBKO terbesar yaitu Rp.13.196.013.148,-, dimana biaya kecelakaan per kilometernya yang paling tinggi adalah pada tahun 2013 yaitu sebesar Rp. 514,013,928/ km. Jumlah total santunan (maksimal) Jasa Raharja yang harus dibayarkan kepada korban kecelakaan lalu lintas di kota Kupang periode tahun 2011–2013 ialah sebesar Rp.4.905.000.000.-. Traffic accident is a major indicator of road safety level. Kupang city as the capital of East Nusa Tenggara (NTT) is one of the largest contributors to the number of traffic accidents in the province. This research was to determine the characteristics of traffic accidents, the accident cost, and the compensation to be paid by PT Jasa Raharja (the state insurance company). The data of traffic accidents were taken throughout year 2010 to 2013. The descriptive analysis results showed that the dominant traffic accidents occurred on Sunday (22 %) , at 12:01 to 18:00 pm (38 %), head-on collisions (30 %), two-vehicle collisions (82 %), involve male (77 %), 17 - 30 years old (64 %), work at private sector (48 %), senior high school graduate (48 %), and does not have a driver's license (76 %). The accident cost analysis used The Gross Output method showed that Timor Raya road, with a length of 11 kilometers, has the highest traffic accident cost that is Rp.13.196.013.148, where the highest accident cost per kilometer was in year 2013 that is Rp.514,013,928/km. The total amount of (maximum) compensation should be paid by PT Jasa Raharja, to the traffic accident victims in Kupang city at year 2011 to 2013, is Rp.4.905.000.000.-

Medical image computing and computer-aided medical interventions applied to soft tissues. Work in progress in urology

Until recently, Computer-Aided Medical Interventions (CAMI) and Medical Robotics have focused on rigid and non deformable anatomical structures. Nowadays, special attention is paid to soft tissues, raising complex issues due to their mobility and deformation. Mini-invasive digestive surgery was probably one of the first fields where soft tissues were handled through the development of simulators, tracking of anatomical structures and specific assistance robots. However, other clinical domains, for instance urology, are concerned. Indeed, laparoscopic surgery, new tumour destruction techniques (e.g. HIFU, radiofrequency, or cryoablation), increasingly early detection of cancer, and use of interventional and diagnostic imaging modalities, recently opened new challenges to the urologist and scientists involved in CAMI. This resulted in the last five years in a very significant increase of research and developments of computer-aided urology systems. In this paper, we propose a description of the main problems related to computer-aided diagnostic and therapy of soft tissues and give a survey of the different types of assistance offered to the urologist: robotization, image fusion, surgical navigation. Both research projects and operational industrial systems are discussed

MOMP from Campylobacter jejuni is a trimer of 18-stranded β–barrel monomers with a Ca2+ ion bound at the constriction zone

LGMF and SG are funded by EU FP7-PEOPLE-2013-ITN Translocation network Nr. 607694. The research leading to these results was conducted as part of the Translocation consortium (www.translocation.com) and has received support from the Innovative Medicines Initiatives Joint Undertaking under Grant Agreement n°115525, resources which are composed of financial contribution from the European Union’s seventh framework programme (FP7/2007-2013) and EFPIA companies in kind contribution. JHN is Royal Society Wolfson Merit Award holder, Senior Investigator Wellcome Trust (WT100209MA) and Chinese Academy of Science 1000 Talent Scholar.The Gram-negative organism Campylobacter jejuni is the major cause of food poisoning. Unlike Escherichia coli which has two major porins, OmpC and OmpF, C. jejuni has one, termed major outer membrane protein (MOMP) through which nutrients and antibiotics transit. We report the 2.1-Å crystal structure of C. jejuni MOMP expressed in E. coli and a lower resolution but otherwise identical structure purified directly from C. jejuni. The 2.1-Å resolution structure of recombinant MOMP showed that although the protein has timeric arrangement similar to OmpC, it is an18-stranded not 16-stranded β-barrel. The structure has identified a Ca2+ bound at the constriction zone, which molecular dynamics and single channel experiments suggest is functionally significant. The water filled channel of MOMP has a narrow constriction zone and single molecule studies show a monomeric conductivity of 0.7 ± 0.2 nS and a trimeric conductance of 2.2 ± 0.2 nS. The ion neutralizes negative charges at the constriction zone reducing the transverse electric field and reversing ion selectivity. Modelling of the transit of ciprofloxacin, an antibiotic of choice for treating Campylobacter infection, through the pore of MOMP reveals a trajectory that is dependent upon the presence metal ion.Publisher PDFPeer reviewe

Molecular Insights into an Antibiotic Enhancer Action of New Morpholine-Containing 5-Arylideneimidazolones in the Fight against MDR Bacteria

In the search for an effective strategy to overcome antimicrobial resistance, a series of new morpholine-containing 5-arylideneimidazolones differing within either the amine moiety or at position five of imidazolones was explored as potential antibiotic adjuvants against Gram-positive and Gram-negative bacteria. Compounds (7–23) were tested for oxacillin adjuvant properties in the Methicillin-susceptible S. aureus (MSSA) strain ATCC 25923 and Methicillin-resistant S. aureus MRSA 19449. Compounds 14–16 were tested additionally in combination with various antibiotics. Molecular modelling was performed to assess potential mechanism of action. Microdilution and real-time efflux (RTE) assays were carried out in strains of K. aerogenes to determine the potential of compounds 7–23 to block the multidrug efflux pump AcrAB-TolC. Drug-like properties were determined experimentally. Two compounds (10, 15) containing non-condensed aromatic rings, significantly reduced oxacillin MICs in MRSA 19449, while 15 additionally enhanced the effectiveness of ampicillin. Results of molecular modelling confirmed the interaction with the allosteric site of PBP2a as a probable MDR-reversing mechanism. In RTE, the compounds inhibited AcrAB-TolC even to 90% (19). The 4-phenylbenzylidene derivative (15) demonstrated significant MDR-reversal “dual action” for β-lactam antibiotics in MRSA and inhibited AcrAB-TolC in K. aerogenes. 15 displayed also satisfied solubility and safety towards CYP3A4 in vitro

A network analysis to identify mediators of germline-driven differences in breast cancer prognosis.

Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies ~7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis

How β-Lactam Antibiotics Enter Bacteria: A Dialogue with the Porins

BACKGROUND:Multi-drug resistant (MDR) infections have become a major concern in hospitals worldwide. This study investigates membrane translocation, which is the first step required for drug action on internal bacterial targets. beta-lactams, a major antibiotic class, use porins to pass through the outer membrane barrier of Gram-negative bacteria. Clinical reports have linked the MDR phenotype to altered membrane permeability including porin modification and efflux pump expression. METHODOLOGY/PRINCIPAL FINDINGS: Here influx of beta-lactams through the major Enterobacter aerogenes porin Omp36 is characterized. Conductance measurements through a single Omp36 trimer reconstituted into a planar lipid bilayer allowed us to count the passage of single beta-lactam molecules. Statistical analysis of each transport event yielded the kinetic parameters of antibiotic travel through Omp36 and distinguishable translocation properties of beta-lactams were quantified for ertapenem and cefepime. Expression of Omp36 in an otherwise porin-null bacterial strain is shown to confer increases in the killing rate of these antibiotics and in the corresponding bacterial susceptibility. CONCLUSIONS/SIGNIFICANCE: We propose the idea of a molecular "passport" that allows rapid transport of substrates through porins. Deciphering antibiotic translocation provides new insights for the design of novel drugs that may be highly effective at passing through the porin constriction zone. Such data may hold the key for the next generation of antibiotics capable of rapid intracellular accumulation to circumvent the further development MDR infections

International evaluation of the psychometrics of health-related quality of life questionnaires for use among long-term survivors of testicular and prostate cancer

Background: Understanding of the physical, functional and psychosocial health problems and needs of cancer survivors requires cross-national and cross-cultural standardization of health-related quality of life (HRQoL) questionnaires that capture the full range of issues relevant to cancer survivors. To our knowledge, only one study has investigated in a comprehensive way whether a questionnaire used to evaluate HRQoL in cancer patients under active treatment is also reliable and valid when used among (long-term) cancer survivors. In this study we evaluated, in an international context, the psychometrics of HRQoL questionnaires for use among long-term, disease-free, survivors of testicular and prostate cancer. Methods: In this cross-sectional study, we recruited long-term survivors of testicular and prostate cancer from Northern and Southern Europe and from the United Kingdom who had participated in two phase III EORTC clinical trials. Participants completed the SF-36 Health Survey, the EORTC QLQ-C30 questionnaire, the QLQ-PR25 (for prostate cancer) or the QLQ-TC26 (for testicular cancer) questionnaires, and the Impact of Cancer questionnaire. Testicular cancer survivors also completed subscales from the Nordic Questionnaire for Monitoring the Age Diverse Workforce. Results: Two hundred forty-two men (66% response rate) were recruited into the study. The average time since treatment was more than 10 years. Overall, there were few missing questionnaire data, although scales related to sexuality, satisfaction with care and relationship concern

pH Modulation of Efflux Pump Activity of Multi-Drug Resistant Escherichia coli: Protection During Its Passage and Eventual Colonization of the Colon

BACKGROUND:Resistance Nodulation Division (RND) efflux pumps of Escherichia coli extrude antibiotics and toxic substances before they reach their intended targets. Whereas these pumps obtain their energy directly from the proton motive force (PMF), ATP-Binding Cassette (ABC) transporters, which can also extrude antibiotics, obtain energy from the hydrolysis of ATP. Because E. coli must pass through two pH distinct environments of the gastrointestinal system of the host, it must be able to extrude toxic agents at very acidic and at near neutral pH (bile salts in duodenum and colon for example). The herein described study examines the effect of pH on the extrusion of ethidium bromide (EB). METHODOLOGY/PRINCIPAL FINDINGS:E. coli AG100 and its tetracycline induced progeny AG100(TET) that over-expresses the acrAB efflux pump were evaluated for their ability to extrude EB at pH 5 and 8, by our recently developed semi-automated fluorometric method. At pH 5 the organism extrudes EB without the need for metabolic energy (glucose), whereas at pH 8 extrusion of EB is dependent upon metabolic energy. Phe-Arg beta-naphtylamide (PAbetaN), a commonly assumed inhibitor of RND efflux pumps has no effect on the extrusion of EB as others claim. However, it does cause accumulation of EB. Competition between EB and PAbetaN was demonstrated and suggested that PAbetaN was preferentially extruded. A K(m) representing competition between PAbetaN and EB has been calculated. CONCLUSIONS/SIGNIFICANCE:The results suggest that E. coli has two general efflux systems (not to be confused with a distinct efflux pump) that are activated at low and high pH, respectively, and that the one at high pH is probably a putative ABC transporter coded by msbA, which has significant homology to the ABC transporter coded by efrAB of Enterococcus faecalis, an organism that faces similar challenges as it makes its way through the toxic intestinal system of the host