bluuebunny/crossref_metadata_2025 huggingface dataset:
Gas flow in Callovo-Oxfordian claystone (COx): results from laboratory and field-scale measurements
Authors: Harrington J. F. , de la Vaissière R. , Noy D. J. , Cuss R. J. , Talandier J.
Published: January 2013

To understand the fate and impact of gas produced within a repository for radioactive waste, a series of laboratory and field scale experiments have been performed on the Callovo-Oxfordian claystone (COx), the proposed host rock for the French repository. Results show the movement of gas is through a localized network of pathways, whose properties vary temporarily and spatially within the claystone. Significant evidence exists from detailed laboratory studies for the movement of gas along highly unstable pathways, whose aperture and geometry vary as a function of local stress, gas and porewater pressures. The coupling of these parameters results in the development of significant time-dependent effects, impacting on all aspects of COx behaviour, from gas breakthrough time, to the control of deformation processes. Variations in gas entry, breakthrough and steady-state pressures are indicative of microstructural heterogeneity which exerts an important control on the movement of gas. The localization of gas flow is also evident in preliminary results from the large scale gas injection test (PGZ) where gas flow is initially focussed within the excavation damaged zone (EDZ), which acts as a preferential pathway for gas. Numerical models based on conventional two-phase flow theory are unable to adequately describe the detailed observations from laboratory tests.
Migration and fate of 14CH4 in subsoil: tracer experiments to inform model development
Authors: Atkinson B. S. , Meredith W. , Snape C. , Steven M. , Hoch A. R. , Lever D. , Shaw G.
Published: January 2013

The degree of transport and retention of 14CH4 in soil is being investigated in a series of laboratory experiments in preparation for field scale trials at the University of Nottingham. The experimental programme focusses on the behaviour and fate of 14CH4 injected into subsoil and its subsequent incorporation into vegetation under field conditions. Due to restrictions on the use of radioactive tracers in the field, 13CH4 is being used as a surrogate gas which can be handled conveniently in the laboratory and field and which can be measured with high precision using gas chromatography with isotope ratio mass spectrometry. The laboratory data indicate significant differences between the diffusion and oxidation rates of 13CH4 in re-packed and undisturbed soil columns, with both rates appearing to be significantly lower in undisturbed soils. Data from both laboratory and field experiments will be used to inform the development of a model of 14CH4 migration and its fate in the biosphere above a geological disposal facility.
Understanding the behaviour of gas in a geological disposal facility: modelling coupled processes and key features at different scales
Authors: Towler G. , Bond A. E. , Watson S. , Norris S. , Suckling P. , Benbow S.
Published: January 2013

Understanding the behaviour of gas in a geological disposal facility (GDF) is an essential component of analysing the facility evolution and long-term (post-closure) safety performance. This includes the impacts of gas on the physico-chemical evolution of the GDF, and the release and migration of radionuclides in water and gas.

The Nuclear Decommissioning Authority Radioactive Waste Management Directorate is participating in the EC FORGE (fate of repository gases) project (www.forgeproject.org) and conducting independent research. Key research themes are modelling the impacts of different host rocks on facility evolution including coupled processes, and upscaling the effects of small scale features that can significantly influence the evolution of the whole facility.

Recent code developments have enabled coupled processes to be represented more realistically in models. This has significantly advanced understanding of facility evolution, as discussed in this paper, and will improve future assessment models. There is potential to further improve approaches to upscaling the effects of small scale features on strongly coupled processes, within the context of the EC FORGE project.
The effect of cellulose degradation products on thorium sorption onto hematite: studies of a model ternary system
Authors: Baston G. M. N. , Cowper M. M. , Heath T. G. , Marshall T. A. , Swanton S. W.
Published: January 2013

Cellulose degradation products (CDPs) can complex with radioelements causing solubility enhancement and sorption reduction, effects which are detrimental to the containment of radionuclides in the near field of a geological disposal facility and surrounding geosphere. Isosaccharinic acid (ISA) is the principal component of CDPs formed under the alkaline anaerobic conditions of a cement-based near field and appears to be largely responsible for the impact of CDPs on radionuclide solubility and sorption under near-field conditions. However, the situation appears to be more complicated under near-neutral pH geosphere conditions.

A combined experimental and modelling study was undertaken to compare the impact of a CDP leachate to ISA in a simple model ternary sorption system consisting of hematite as a single mineral substrate, thorium as the radioelement and ISA or a CDP leachate as the complexant. Thorium sorbs strongly to hematite. A triple layer model for thorium sorption to hematite was refined to fit to the experimental data in the absence of ISA or CDP leachate; the effect of ISA on thorium sorption was then predicted.

In the presence of CDP leachate, a significant reduction in thorium sorption was observed from pH 6 to 12 in good agreement with model predictions based on a high concentration of ISA. However, only a limited impact of ISA on thorium sorption was observed at pH 6 to 12, in contrast to predictions. The effects of ISA could be accounted for by assuming the formation of a ternary thorium–ISA–surface complex. The model has yet to be extended to the more complex CDP systems. Differences in the thorium speciation in solution due to the formation of a ternary calcium–thorium–ISA complex in the CDP leachate, which is absent from solutions with ISA only, provides the most likely explanation for the differences observed experimentally.
Sorption of radionuclides to a cementitious backfill material under near-field conditions
Authors: Felipe-Sotelo M. , Hinchliff J. , Evans N. , Warwick P. , Read D.
Published: January 2013

The sorption behaviour of I−, Cs+, Ni2+, Eu3+, Th4+ and UO2+2on NRVB (Nirex reference vault backfill) a possible vault backfill, at pH 12.8 was studied. Sorption isotherms generated were compared to results obtained in the presence of cellulose degradation products (CDP). Whereas Cs was not affected by the presence of the organic compounds, a notable reduction in the sorption of Th and Eu to cement was observed. The results also indicated limited removal of Ni from solution (with or without an organic ligand) by sorption, the concentration in solution seemingly being determined solely by solubility processes. In the case of uranium, the presence of CDP increased the sorption to cement by almost one order of magnitude. Further studies into the uptake of CDP by cement are being undertaken to identify the mechanism(s) responsible.
Research in support of the 2011 environmental safety case for the Low Level Waste Repository
Authors: Baker A. , Cummings R.
Published: January 2013

This paper provides a summary of the research programme undertaken in support of the Low Level Waste Repository's 2011 environmental safety case (ESC). The programme has been developed, based on an understanding of safety issues and the requirements of the ESC. The research requirements to underpin the safety case have been identified by means of an auditable process, and subjected to scrutiny by both the regulators and a peer review group. Key research priorities for the future are identified.
Interactions between the co-located intermediate-level waste/low-level waste and high-level waste/spent fuel components of a geological disposal facility
Authors: Hicks T. W. , Watson S. , Norris S. , Towler G. , Reedha D. , Paulley A. , Baldwin T. , Bond A. E.
Published: January 2013

The 2008 UK government White Paper, published as part of the Managing Radioactive Waste Safety programme, identified benefits to disposing of all of the UK's higher activity wastes at the same site. That is, a single geological disposal facility (GDF) could be constructed that consists of a module for low- and intermediate-level waste, and a module for high-level waste and spent fuel.

A safety case for a co-located GDF will have to consider the extent to which evolving thermo-hydro-mechanical-chemical and gas (THMCG) conditions in and around one module may affect conditions in the other module, including the extent to which barrier performance and radionuclide migration behaviour could be altered. Several research projects have been undertaken on behalf of Radioactive Waste Management Directorate aimed at understanding and evaluating the THMCG interactions that might occur during the disposal facility operational and post-closure phases.

This paper describes research on THMCG interactions between disposal modules based on illustrative GDF designs for different host rock environments. Interactions were evaluated using simple analytical solutions and detailed three-dimensional models. The analyses demonstrated that interactions can be controlled by design constraints.
Performance assessment and the safety case: lessons from the European Commission PAMINA project
Authors: Galson D. A. , Bailey L. E. F.
Published: January 2013

A three-year European Commission project entitled performance assessment methodologies in application to guide the development of the safety case (PAMINA) was conducted in the period 2006–2009 and brought together 27 organizations from ten European countries, including the Nuclear Decommissioning Authority and Galson Sciences Ltd from the UK. The PAMINA project had the aim of improving and developing a common understanding of performance assessment (PA) methodologies for disposal concepts for spent fuel and other long-lived radioactive wastes in a range of geological environments.

Work undertaken within PAMINA focussed on four areas: (1) review of PA methodologies in participating organizations; (2) treatment of uncertainty in PA and the safety case; (3) other methodological advancements in PA; and (4) relevance of advanced PA approaches to practical cases.

The state of development of a radioactive waste disposal programme has a strong influence on the type of safety case and supporting PA that is produced. A range of PA methodologies has been developed by different waste management organizations. This paper presents a selection of conclusions from the PAMINA project, in the context of general understanding developed on what would constitute an acceptable safety case for a geological disposal facility, and outlines areas for further development.
Planning to 'remember to forget'?
Authors: Mobbs S.
Published: January 2013

Disposal in deep geological formations aims to provide isolation of long-lived radioactive waste for hundreds of thousands of years. This raises the question of the long-term governance of the repository throughout its lifetime. In the operational phase the repository is under active regulatory control. Once closed, there will be a phase of passive management control or indirect oversight. This will be followed, at some time in the future, by a period in which there is no oversight. This may be a result of a decision to cease management control or it may occur through loss of records or a change in priorities. The importance of the main exposure scenarios (exposure as a result of the gradual transport of radionuclides in groundwater, transport of radionuclides in gas, and exposure arising from inadvertent intrusion into the repository) are discussed with reference to these different phases. An interesting question is 'How do we minimize the risk of inadvertent intrusion in the far future?' Perhaps it is better to ensure that the repository is forgotten and should we try to plan for this? The different approaches are discussed and the importance of deciding on a strategy at an early stage is emphasized.
Prevalence of medication overuse headache in an interdisciplinary pain clinic
Authors: Schmid Corinne Wanner , Maurer Konrad , Schmid Daniel M , Alon Eli , Spahn Donat R , Gantenbein Andreas R , Sandor Peter S
Published: January 2013

Background

Medication overuse headache (MOH) has been recognized as an important problem in headache patients although the pathophysiological mechanisms remain unclear. The diagnosis of MOH is based on clinical characteristics defined by the International Headache Society. The aim was the evaluation of the diagnostic criteria of MOH in a mixed population of chronic pain patients to gain information about the prevalence and possible associations with MOH.

Methods

Data of all patients referred to the interdisciplinary pain clinic at the University Hospital of Zurich between September 2005 and December 2007 were retrospectively analyzed. Demographic data (age, sex, history of migration), as well as data about duration of pain disease, category of pain disease (neurological, psychiatric, rheumatologic, other), use of medication, history of trauma, and comorbidity of depression and anxiety have been collected.

Results

Totally 178 of 187 consecutive chronic pain patients were included in the study. A total of 138 patients (78%) used analgesics on 15 or more days per month. Chronic headache was more prevalent among patients with analgesic overuse (39.8%) than without analgesic overuse (18%). The prevalence of MOH was 29%. The odds ratio (OR) for a patient with medication overuse to have chronic headache was 13.1 if he had a history of primary headache, compared to a patient without a primary headache syndrome. Furthermore, history of headache (OR 2.5, CI [1.13;5.44]), history of migration (OR 2.9, CI [1.31;6.32]) and comorbid depression (OR 3.5, CI [1.46;8.52]) were associated with overuse of acute medication, in general.

Conclusions

Primary headaches have a high risk for chronification in patients overusing analgesics for other pain disorders. Whereas history of headache, history of migration and comorbidity of depression are independentely associated with analgesic overuse in this group of patients.
HTQC: a fast quality control toolkit for Illumina sequencing data
Authors: Yang Xi , Liu Di , Liu Fei , Wu Jun , Zou Jing , Xiao Xue , Zhao Fangqing , Zhu Baoli
Published: January 2013

Background

Illumina sequencing platform is widely used in genome research. Sequence reads quality assessment and control are needed for downstream analysis. However, software that provides efficient quality assessment and versatile filtration methods is still lacking.

Results

We have developed a toolkit named HTQC - abbreviation of High-Throughput Quality Control - for sequence reads quality control, which consists of six programs for reads quality assessment, reads filtration and generation of graphic reports.

Conclusions

The HTQC toolkit can generate reads quality assessment faster than existing tools, providing guidance for reads filtration utilities that allow users to choose different strategies to remove low quality reads.
Evaluation of characteristics of CD44+CD117+ ovarian cancer stem cells in three dimensional basement membrane extract scaffold versus two dimensional monocultures
Authors: Chen Junsong , Wang Jing , Chen Dengyu , Yang Jie , Yang Cuiping , Zhang Yunxia , Zhang Hongyi , Dou Jun
Published: January 2013

Background

Cancer stem cells (CSCs) are thought to be capable of surviving conventional chemotherapeutic treatments because the cells have more resistant to anticancer drugs than common cancer cells. Most in vitro studies in experimental cancer cells have been done in a two-dimensional (2D) monocultures, while accumulating evidence suggests that cancer cells behave differently when they are grown within a three-dimensional (3D) culture system.

Results

The CD44+CD117+cells isolated from human epithelial ovarian cancer SKOV-3 cell line using magnetic-activated cell sorting were found to grow faster than the SKOV-3 cells in the 3D culture and in the nude mice. Anticancer drugs 5FU, docetaxel, cisplatin, and carboplatin were seen to inhibit growth of the CD44+CD117+ cells by 50% in the 2D culture with IC50 concentration, whereas, in the 3D culture, the four drugs inhibited the cell growth by only 34.4%, 40.8%, 34.8% and 21.9% at 3D one, respectively. Effect of paclitaxel on the CD44+CD117+cell viability indicated that fewer cells underwent apoptosis in 3D culture than that in 2D one. In addition, anticancer drugs markedly increased the expression of ABCG2 and ABCB1 of CD44+CD117+cells in 3D culture.

Conclusion

Our assay demonstrated that human epithelial ovarian cancer CD44+CD117+cells possessed the properties of CSCs that exhibited more chemoresistance in the 3D culture than that of in 2D one. The 3D culture provides a realistic model for study of the CSC response to anticancer drugs.
Genome-wide identification of soybean microRNAs and their targets reveals their organ-specificity and responses to phosphate starvation
Authors: Xu Feng , Liu Qian , Chen Luying , Kuang Jiebin , Walk Thomas , Wang Jinxiang , Liao Hong
Published: January 2013

Background

Phosphorus (P) plays important roles in plant growth and development. MicroRNAs involved in P signaling have been identified in Arabidopsis and rice, but P-responsive microRNAs and their targets in soybean leaves and roots are poorly understood.

Results

Using high-throughput sequencing-by-synthesis (SBS) technology, we sequenced four small RNA libraries from leaves and roots grown under phosphate (Pi)-sufficient (+Pi) and Pi-depleted (-Pi) conditions, respectively, and one RNA degradome library from Pi-depleted roots at the genome-wide level. Each library generated ∼21.45−28.63 million short sequences, resulting in ∼20.56−27.08 million clean reads. From those sequences, a total of 126 miRNAs, with 154 gene targets were computationally predicted. This included 92 new miRNA candidates with 20-23 nucleotides that were perfectly matched to the Glycine max genome 1.0, 70 of which belong to 21 miRNA families and the remaining 22 miRNA unassigned into any existing miRNA family in miRBase 18.0. Under both +Pi and -Pi conditions, 112 of 126 total miRNAs (89%) were expressed in both leaves and roots. Under +Pi conditions, 12 leaf- and 2 root-specific miRNAs were detected; while under -Pi conditions, 10 leaf- and 4 root-specific miRNAs were identified. Collectively, 25 miRNAs were induced and 11 miRNAs were repressed by Pi starvation in soybean. Then, stem-loop real-time PCR confirmed expression of four selected P-responsive miRNAs, and RLM-5’ RACE confirmed that a PHO2 and GmPT5, a kelch-domain containing protein, and a Myb transcription factor, respectively are targets of miR399, miR2111, and miR159e-3p. Finally, P-responsive cis-elements in the promoter regions of soybean miRNA genes were analyzed at the genome-wide scale.

Conclusions

Leaf- and root-specific miRNAs, and P-responsive miRNAs in soybean were identified genome-wide. A total of 154 target genes of miRNAs were predicted via degradome sequencing and computational analyses. The targets of miR399, miR2111, and miR159e-3p were confirmed. Taken together, our study implies the important roles of miRNAs in P signaling and provides clues for deciphering the functions for microRNA/target modules in soybean.
Validation of Canadian mothers’ recall of events in labour and delivery with electronic health records
Authors: Bat-Erdene Uilst , Metcalfe Amy , McDonald Sheila W , Tough Suzanne C
Published: January 2013

Background

Maternal report of events that occur during labour and delivery are used extensively in epidemiological research; however, the validity of these data are rarely confirmed. This study aimed to validate maternal self-report of events that occurred in labour and delivery with data found in electronic health records in a Canadian setting.

Methods

Data from the All Our Babies study, a prospective community-based cohort of women’s experiences during pregnancy, were linked to electronic health records to assess the validity of maternal recall at four months post-partum of events that occurred during labour and delivery. Sensitivity, specificity and kappa scores were calculated. Results were stratified by maternal age, gravidity and educational attainment.

Results

Maternal recall at four months post-partum was excellent for infant characteristics (gender, birth weight, gestational age, multiple births) and variables related to labour and delivery (mode of delivery, epidural, labour induction) (sensitivity and specificity >85%). Women who had completed a university degree had significantly better recall of labour induction and use of an epidural.

Conclusion

Maternal recall of infant characteristics and events that occurred during labour and delivery is excellent at four months post-partum and is a valid source of information for research purposes.
Maternal circulating leukocytes display early chemotactic responsiveness during late gestation
Authors: Gomez-Lopez Nardhy , Tanaka Satomi , Zaeem Zoya , Metz Gerlinde A , Olson David M
Published: January 2013

Background

Parturition has been widely described as an immunological response; however, it is unknown how this is triggered. We hypothesized that an early event in parturition is an increased responsiveness of peripheral leukocytes to chemotactic stimuli expressed by reproductive tissues, and this precedes expression of tissue chemotactic activity, uterine activation and the systemic progesterone/estradiol shift.

Methods

Tissues and blood were collected from pregnant Long-Evans rats on gestational days (GD) 17, 20 and 22 (term gestation). We employed a validated Boyden chamber assay, flow cytometry, quantitative real time-polymerase chain reaction, and enzyme-linked immunosorbent assays.

Results

We found that GD20 maternal peripheral leukocytes migrated more than those from GD17 when these were tested with GD22 uterus and cervix extracts. Leukocytes on GD20 also displayed a significant increase in chemokine (C-C motif) ligand 2 (Ccl2) gene expression and this correlated with an increase in peripheral granulocyte proportions and a decrease in B cell and monocyte proportions. Tissue chemotactic activity and specific chemokines (CCL2, chemokine (C-X-C motif) ligand 1/CXCL1, and CXCL10) were mostly unchanged from GD17 to GD20 and increased only on GD22. CXCL10 peaked on GD20 in cervical tissues. As expected, prostaglandin F2α receptor and oxytocin receptor gene expression increased dramatically between GD20 and 22. Progesterone concentrations fell and estradiol-17β concentrations increased in peripheral serum, cervical and uterine tissue extracts between GD20 and 22.

Conclusion

Maternal circulating leukocytes display early chemotactic responsiveness, which leads to their infiltration into the uterus where they may participate in the process of parturition.
Treatment with a combination of the ErbB (HER) family blocker afatinib and the IGF-IR inhibitor, NVP-AEW541 induces synergistic growth inhibition of human pancreatic cancer cells
Authors: Ioannou Nikolaos , Seddon Alan M , Dalgleish Angus , Mackintosh David , Modjtahedi Helmout
Published: January 2013

Background

Aberrant expression and activation of the IGF-IR have been reported in a variety of human cancers and have been associated with resistance to HER targeted therapy. In this study, we investigated the effect of simultaneous targeting of IGF-IR and HER (erbB) family, with NVP-AEW541 and afatinib, on proliferation of pancreatic cancer cells.

Methods

The sensitivity of a panel of human pancreatic cancer cell lines to treatment with NVP-AEW541 used alone or in combination with afatinib, anti-EGFR antibody ICR62, and cytotoxic agents was determined using the Sulforhodamine B colorimetric assay. Growth factor receptor expression, cell-cycle distribution and cell signalling were determined using flow cytometry and western blot analysis.

Results

All pancreatic cancer cell lines were found to be IGF-IR positive and NVP-AEW541 treatment inhibited the growth of the pancreatic cancer cell lines with IC50 values ranging from 342 nM (FA6) to 2.73 μM (PT45). Interestingly, of the various combinations examined, treatment with a combination of NVP-AEW541 and afatinib was superior in inducing synergistic growth inhibition of the majority of pancreatic cancer cells.

Conclusion

Our results indicate that co-targeting of the erbB (HER) family and IGF-IR, with a combination of afatinib and NVP-AEW541, is superior to treatment with a single agent and encourages further investigation in vivo on their therapeutic potential in IGF-IR and HER positive pancreatic cancers.
High incidence of pulmonary tuberculosis in children admitted with severe pneumonia in Uganda
Authors: Nantongo Josephine M , Wobudeya Eric , Mupere Ezekiel , Joloba Moses , Ssengooba Willy , Kisembo Harriet N , Lubega Irene R , Musoke Philippa M
Published: January 2013

Background

A high prevalence of tuberculosis (TB) in children presenting with severe pneumonia has previously been reported in South Africa. However, little is known about TB among children with pneumonia in Uganda and other resource limited countries. Moreover, TB is associated with high morbidity and mortality among such children. We conducted this study to establish the burden of pulmonary TB in children admitted with severe pneumonia in our setting.

Methods

A cross-sectional study was conducted at Mulago, a National Referral and teaching hospital in Uganda. Hospitalised children 2 months to 12 years of age with severe pneumonia based on WHO case definition were enrolledfrom February to June 2011. Children with a previous TB diagnosis or receiving anti-TB treatment were excluded. Each child was screened for TB using Tuberculin skin test, Chest X-ray, induced sputum samples and blood culture for mycobacterium. Sputum smears were examined using fluorescent microscopy, and cultured on both Lowenstein Jensen media (LJ) and Mycobacterial Growth Indicator Tubes (MGIT).

Results

Of the 270 children with severe pneumonia who were recruited over a 5-month period in 2011, the incidence ratio of pulmonary TB in children admitted with severe pneumonia was 18.9% (95% CI 14.6 – 23.9). The proportion of culture confirmed PTB was 6.3% (95% CI 3.8 – 9.7). Age group under 1 year and 1 to 5 years (OR 2.8 (95% CI 1.7 – 7.4) and OR 2.4 (95% CI 1.05 – 5.9) respectively) were more likely to be associated with pulmonary TB compared to those children over 5 years of age. A history of TB smear positive contact was associated with pulmonary TB (OR 3.0 (95% CI 1.3–6.5).

Conclusions

We found a high burden of pulmonary TB in children admitted with severe pneumonia. These data highlight the need for TB screening in children admitted with severe pneumonia so as to improve TB case finding and child survival.
Antibacterial activities of the methanol extracts of ten Cameroonian vegetables against Gram-negative multidrug-resistant bacteria
Authors: Noumedem Jaurès AK , Mihasan Marius , Lacmata Stephen T , Stefan Marius , Kuiate Jules R , Kuete Victor
Published: January 2013

Background

Many edible plants are used in Cameroon since ancient time to control microbial infections. This study was designed at evaluating the antibacterial activities of the methanol extracts of ten Cameroonian vegetables against a panel of twenty nine Gram negative bacteria including multi-drug resistant (MDR) strains.

Methods

The broth microdilution method was used to determine the Minimal Inhibitory Concentrations (MIC) and the Minimal Bactericidal Concentrations (MBC) of the studied extracts. When chloramphenicol was used as a reference antibiotic, the MICs were also determined in the presence of Phenylalanine-Arginine β- Naphtylamide (PAβN), an efflux pumps inhibitor (EPI). The phytochemical screening of the extracts was performed using standard methods.

Results

All tested extracts exhibited antibacterial activities, with the MIC values varying from 128 to 1024 mg/L. The studied extracts showed large spectra of action, those from L. sativa, S. edule, C. pepo and S. nigrum being active on all the 29 bacterial strains tested meanwhile those from Amaranthus hybridus, Vernonia hymenolepsis, Lactuca.carpensis and Manihot esculenta were active on 96.55% of the strains used. The plant extracts were assessed for the presence of large classes of secondary metabolites: alkaloids, anthocyanins, anthraquinones, flavonoids, phenols, saponins, steroids, tannins and triterpenes. Each studied plant extract was found to contain compounds belonging to at least two of the above mentioned classes.

Conclusion

These results confirm the traditional claims and provide promising baseline information for the potential use of the tested vegetables in the fight against bacterial infections involving MDR phenotypes.
Mesenchymal stem cells enhance ovarian cancer cell infiltration through IL6 secretion in an amniochorionic membrane based 3D model
Authors: Touboul Cyril , Lis Raphael , Al Farsi Halema , Raynaud Christophe M , Warfa Mohamed , Althawadi Hamda , Mery Eliane , Mirshahi Massoud , Rafii Arash
Published: January 2013

Background

The early peritoneal invasion of epithelial ovarian cancer (EOC) by tumoral aggregates presents in ascites is a major concern. The role of the microenvironment seems to be important in this process but the lack of adequate models to study cellular interactions between cancer cells and stromal cells does not allow to uncover the molecular pathways involved. Our goal was to study the interactions between ovarian cancer cells (OCC) and mesenchymal stem cells (MSC) using a 3D model.

Methods

We used millimetric pieces of amniochorionic membrane - referred to as amniotic membrane scaffold (AMS) - to create 3D peritoneal nodules mimicking EOC early invasion. We were able to measure the distribution and the depth of infiltration using confocal microsopy. We extracted MSC from the amniochorionic membrane using the markers CD34-, CD45-, CD73+, CD90+, CD105+ and CD29+ at the Fluorescence Activated Cell Sorting (FACS) analysis. We used transwell and wound healing tests to test OCC migration and invasion in vitro.

Results

Here we show that OCC tumors were located in regions rich in MSC (70%). The tumors infiltrated deeper within AMS in regions rich in MSC (p<0.001). In vitro tests revealed that higher IL6 secretion in a context of MSC-OCC co-culture could enhance migration and invasion of OCC. After IL6 receptor antagonism, OCC infiltration was significantly decreased, mostly in regions rich in MSCs, indicating that recruitment and tridimensional invasion of OCC was dependent of IL6 secretion.

Conclusions

The use of tridimensional models using AMS could be a useful tool to decipher early molecular events in ovarian cancer metastasis. Cytokine inhibitors interrupting the cross-talk between OCCs and MSCs such as IL6 should be investigated as a new therapeutic approach in ovarian cancer.
Coupled coincidence point and common coupled fixed point theorems lacking the mixed monotone property
Authors: Agarwal Ravi P , Sintunavarat Wutiphol , Kumam Poom
Published: January 2013

In this paper, we prove the coupled coincidence point theorems for a

w
∗

-compatible mapping in partially ordered cone metric spaces over a solid cone without the mixed g-monotone property. In the case of a totally ordered space, these results are automatically obvious under the assumption given. Therefore, these results can be applied in a much wider class of problems. We also prove the uniqueness of a common coupled fixed point in this setup and give some example which is not applied to the existence of a common coupled fixed point by using the mixed g-monotone property but can be applied to our results.

MSC:47H10, 54H25.
Hypofractionated stereotactic body radiation therapy as monotherapy for intermediate-risk prostate cancer
Authors: Ju Andrew W , Wang Hongkun , Oermann Eric K , Sherer Benjamin A , Uhm Sunghae , Chen Viola J , Pendharkar Arjun V , Hanscom Heather N , Kim Joy S , Lei Siyuan , Suy Simeng , Lynch John H , Dritschilo Anatoly , Collins Sean P
Published: January 2013

Background

Hypofractionated stereotactic body radiation therapy (SBRT) has been advanced as monotherapy for low-risk prostate cancer. We examined the dose distributions and early clinical outcomes using this modality for the treatment of intermediate-risk prostate cancer.

Methods

Forty-one sequential hormone-naïve intermediate-risk prostate cancer patients received 35–36.25 Gy of CyberKnife-delivered SBRT in 5 fractions. Radiation dose distributions were analyzed for coverage of potential microscopic ECE by measuring the distance from the prostatic capsule to the 33 Gy isodose line. PSA levels, toxicities, and quality of life (QOL) measures were assessed at baseline and follow-up.

Results

All patients completed treatment with a mean coverage by the 33 Gy isodose line extending >5 mm beyond the prostatic capsule in all directions except posteriorly. Clinical responses were documented by a mean PSA decrease from 7.67 ng/mL pretreatment to 0.64 ng/mL at the median follow-up of 21 months. Forty patients remain free from biochemical progression. No Grade 3 or 4 toxicities were observed. Mean EPIC urinary irritation/obstruction and bowel QOL scores exhibited a transient decline post-treatment with a subsequent return to baseline. No significant change in sexual QOL was observed.

Conclusions

In this intermediate-risk patient population, an adequate radiation dose was delivered to areas of expected microscopic ECE in the majority of patients. Although prospective studies are needed to confirm long-term tumor control and toxicity, the short-term PSA response, biochemical relapse-free survival rate, and QOL in this interim analysis are comparable to results reported for prostate brachytherapy or external beam radiotherapy.

Trial registration

The Georgetown Institutional Review Board has approved this retrospective study (IRB 2009–510).
Intramolecular H-bonding interaction in angular 3-π-EWG substituted imidazo[1,2-a]pyridines contributes to conformational preference
Authors: Velázquez-Ponce Manuel , Salgado-Zamora Héctor , Jiménez-Vázquez Hugo A , Campos-Aldrete Maria Elena , Jiménez Rogelio , Cervantes Humberto , Hadda Taibi Ben
Published: January 2013

Background

The proton at position 5 of imidazo[1,2-a]pyridines substituted with an angular electron withdrawing group (EWG) at position 3, shows an unusual downfield chemical shift, which is usually explained in terms of a peri effect. However usage of this term is sometimes confusing. In this investigation, it is proposed that the aforementioned shift is in fact a combination of several factors: Anisotropy, long-distance mesomerism and an attractive intramolecular interaction of the electrostatic hydrogen bond type.

Results

Theoretical calculations were performed aimed to obtain evidence of the existence of an intramolecular non-bonding interaction between H-5 and the oxygen atom of the EWG. Results derived from conformational and vibrational analysis at the DFT B3LYP/6-311++G(d,p) level of theory, the determination of Bond Critical Points derived from AIM theory, and the measurement of some geometrical parameters, support the hypothesis that the higher stability of the prevailing conformation in these molecules (that in which the oxygen of the EWG is oriented towards H-5) has its origin in an intramolecular interaction.

Conclusion

Computational calculations predicted correctly the conformational preferences in angular 3-π-EWG-substituted imidazo[1,2-a]pyridines. The existence of an electrostatic hydrogen bond between H-5 and the oxygen atom of the π-EWG was supported by several parameters, including X-ray crystallography. The existence of such structural array evidently impacts the H-5 chemical shift.
Sinonasal Undifferentiated Carcinoma (SNUC): The Alberta experience and literature review
Authors: Xu Caroline C , Dziegielewski Peter T , McGaw William T , Seikaly Hadi
Published: January 2013

Background

Sinonasal undifferentiated carcinoma (SNUC) is a rare malignancy with often dismal outcomes. This study set to determine provincial and literature-wide survival outcomes based on treatment modality.

Methods

Retrospective chart review of all SNUC patients in the province of Alberta from 1986–2010 was conducted. A review of the literature of SNUC patients was also performed. Patient/tumor characteristics, treatment, and follow-up/survival data were collected. Kaplan-Meier and Cox regression survival analyses were performed.

Results

20 patients were treated for SNUC in Alberta and 140 patients were identified in the literature. Pooled median disease-free survival was 12. 7 months and 5-year survival estimate was 6.25%. Cox-Regression analysis demonstrated an overall survival advantage with multimodality treatments (Log-Rank test: p = 0.015). However, no statistically significant differences in disease-free and overall survival were identified between patients treated with chemoradiation or surgery followed by adjuvant therapy.

Conclusions

Treatment of SNUC remains challenging with poor survival outcomes. There appears to be no statistically significant difference in overall, or disease-free survival between treatment modalities.
Prenatal ultrasound exposure and association with postnatal hearing outcomes
Authors: Harbarger Claude F , Weinberger Paul M , Borders Jack C , Hughes Charles A
Published: January 2013

Objective

Prenatal ultrasound exams have become increasingly frequent. Although no serious adverse effects are known, the public health implications would be enormous should adverse effects on auditory development be shown. This study looks to establish a possible correlation between hearing loss and increased prenatal ultrasound exposure.

Design

Retrospective cohort analysis.

Setting

Tertiary academic referral center.

Methods

A retrospective review of 100 children undergoing newborn hearing screening was conducted. Extensive data collection was performed, and this data was analyzed for a potential correlation between failure of newborn hearing screening and increased prenatal ultrasound exposure, as well as for a potential correlation of other variables with hearing loss.

Main outcome measures

Postnatal hearing outcomes.

Results

A higher number of both total and 3rd trimester ultrasound exams as well as a younger gestational age at birth were all found to be significantly associated with a higher likelihood of passing the newborn hearing screen (p<0.001 for each). No other factors were found to reach statistical significance.

Conclusions

Our results show that there is no correlation between a higher level of prenatal ultrasound exposure and hearing loss. Indeed, infants who had more prenatal ultrasounds in the third trimester were more likely to pass their screening hearing exams. The finding that children receiving more prenatal ultrasounds have a higher likelihood of passing newborn hearing screens serves as an excellent reminder of the classic statistics rule that correlation does not imply causation.
THREAT helps to identify epistaxis patients requiring blood transfusions
Authors: Murer Karin , Ahmad Nader , Roth Beatrice A , Holzmann David , Soyka Michael B
Published: January 2013

Objective

To analyze the characteristics of patients who needed a blood transfusion due to epistaxis-caused anemia and to define potential risk factors.

Design

Retrospective cohort study.

Setting

A total cohort of 591 epistaxis patients, prospectively included between March 2007 and April 2008 at the ENT department of the University Hospital of Zurich, was evaluated concerning the need for blood transfusions.

Methods

The clinical charts and medical histories of these patients were evaluated.

Main outcome measures

Common parameters that increase the risk for severe anemia due to epistaxis.

Results

Twenty-two patients required blood transfusions due to their medical condition. 22.7% suffered from traumatic nosebleeds. Another 27.3% had a known medical condition with an increased bleeding tendency. These proportions were significantly higher than in the group of patients without need of blood transfusion. The odds ratio for receiving a blood transfusion was 14.0 in patients with hematologic disorders, 4.3 in traumatic epistaxis and 7.7 in posterior bleeders. The transfusion-dependent epistaxis patients suffered significantly more often from severe posterior nosebleeds with the need for a surgical therapeutic approach.

Conclusions

Patients with severe nosebleeds either from the posterior part of the nose or with known hematologic disorders or traumatic epistaxis should be closely monitored by blood parameter analyses to evaluate the indication for hemotransfusion. The acronym THREAT (T rauma, H ematologic disorder, and REA r origin of bleeding → T ransfusion) helps to remember and identify the factors associated with an increased risk of receiving blood transfusion.
The inferior turbinate flap in skull base reconstruction
Authors: Yip Jonathan , Macdonald Kristian I , Lee John , Witterick Ian J , Zadeh Gelareh , Gentili Fred , Vescan Allan D
Published: January 2013

Background

As the indications for expanded endonasal approaches continue to evolve, alternative reconstructive techniques are needed to address increasingly complex surgical skull base defects. In the absence of the nasoseptal flap, we describe our experience with the posterior pedicle inferior turbinate flap (PPITF) in skull base reconstruction.

Design

Case series.

Setting

Academic tertiary care centre.

Methods

Patients who underwent reconstruction of the skull base with the PPITF were identified. Medical records were reviewed for demographic, presentation, treatment, follow-up, surgical and outcomes data.

Main outcome measures

Flap survival, adequacy of seal, and complications.

Results

Two patients with residual/recurrent pituitary adenomas met the inclusion criteria. The nasoseptal flap was unavailable in each case due to a prior septectomy. Salvage of the original nasoseptal flap was not possible, as it did not provide adequate coverage of the resultant defect due to contraction from healing. All PPITFs healed uneventfully and covered the entire defect. No complications were observed in the early post-operative period. Endoscopic techniques and limitations of the PPITF are also discussed.

Conclusions

Our clinical experience supports the PPITF to be a viable alternative for reconstruction of the skull base in the absence of the nasoseptal flap.
Reduced cilia frequencies in human renal cell carcinomas versus neighboring parenchymal tissue
Authors: Basten Sander G , Willekers Sven , Vermaat Joost SP , Slaats Gisela GG , Voest Emile E , van Diest Paul J , Giles Rachel H
Published: January 2013

Background

Cilia are essential organelles in multiple organ systems, including the kidney where they serve as important regulators of renal homeostasis. Renal nephron cilia emanate from the apical membrane of epithelia, extending into the lumen where they function in flow-sensing and ligand-dependent signaling cascades. Ciliary dysfunction underlies renal cyst formation that is in part caused by deregulation of planar cell polarity and canonical Wnt signaling. Renal cancer pathologies occur sporadically or in heritable syndromes caused by germline mutations in tumor suppressor genes including VHL. Importantly, Von Hippel-Lindau (VHL) patients frequently develop complex renal cysts that can be considered a premalignant stage. One of the well-characterized molecular functions of VHL is its requirement for the maintenance of cilia. In this study, tissue from 110 renal cancer patients who underwent nephrectomy was analyzed to determine if lower ciliary frequency is a common hallmark of renal tumorigenesis by comparing cilia frequencies in both tumor and adjacent parenchymal tissue biopsies from the same kidney.

Methods

We stained sections of human renal material using markers for cilia. Preliminary staining was performed using an immunofluorescent approach and a combination of acetylated-α-tubulin and pericentrin antibodies and DAPI. After validation of an alternative, higher throughput approach using acetylated-α-tubulin immunohistochemistry, we continued to manually quantify cilia in all tissues. Nuclei were separately counted in an automated fashion in order to determine ciliary frequencies. Similar staining and scoring for Ki67 positive cells was performed to exclude that proliferation obscures cilia formation potential.

Results

Samples from renal cell carcinoma patients deposited in our hospital tissue bank were previously used to compose a tissue microarray containing three cores of both tumor and parenchymal tissue per patient. Cilia frequencies in a total of eighty-nine clear cell, eight papillary, five chromophobe renal cell carcinomas, two sarcomatoid renal tumors and six oncocytomas were determined. A marked decrease of primary cilia across renal cell carcinoma subtypes was observed compared to adjacent nontumorigenic tissue.

Conclusions

Our study shows that cilia are predominantly lost in renal cell carcinomas compared to tissue of the tumor parenchyma. These results suggest that ciliary loss is common in renal tumorigenesis, possibly participating in the sequence of cellular events leading to malignant tumor development. Future therapies aimed at restoring or circumventing cilia signaling might therefore aid in current treatment efficacy.
Influence of oxygen on NADH recycling and oxidative stress resistance systems in Lactobacillus panis PM1
Authors: Kang Tae Sun , Korber Darren R , Tanaka Takuji
Published: January 2013

Lactobacillus panis strain PM1 is an obligatory heterofermentative and aerotolerant microorganism that also produces 1,3-propanediol from glycerol. This study investigated the metabolic responses of L. panis PM1 to oxidative stress under aerobic conditions. Growth under aerobic culture triggered an early entrance of L. panis PM1 into the stationary phase along with marked changes in end-product profiles. A ten-fold higher concentration of hydrogen peroxide was accumulated during aerobic culture compared to microaerobic culture. This H2O2 level was sufficient for the complete inhibition of L. panis PM1 cell growth, along with a significant reduction in end-products typically found during anaerobic growth. In silico analysis revealed that L. panis possessed two genes for NADH oxidase and NADH peroxidase, but their expression levels were not significantly affected by the presence of oxygen. Specific activities for these two enzymes were observed in crude extracts from L. panis PM1. Enzyme assays demonstrated that the majority of the H2O2 in the culture media was the product of NADH: H2O2 oxidase which was constitutively-active under both aerobic and microaerobic conditions; whereas, NADH peroxidase was positively-activated by the presence of oxygen and had a long induction time in contrast to NADH oxidase. These observations indicated that a coupled NADH oxidase - NADH peroxidase system was the main oxidative stress resistance mechanism in L. panis PM1, and was regulated by oxygen availability. Under aerobic conditions, NADH is mainly reoxidized by the NADH oxidase - peroxidase system rather than through the production of ethanol (or 1,3-propanediol or succinic acid production if glycerol or citric acid is available). This system helped L. panis PM1 directly use oxygen in its energy metabolism by producing extra ATP in contrast to homofermentative lactobacilli.