bluuebunny/crossref_metadata_2025 huggingface dataset:
Parents as Play Date Facilitators for Preschoolers With Autism
Authors: Jull Stephanie , Mirenda Pat
Published: April 2010

Teaching children with autism to interact with their typically developing peers can be a challenge. Previous research has documented that there are many effective ways to teach social interaction; however, interventions in this regard are usually implemented by professionals.The purpose of this study was to assess the effectiveness of parent-implemented contextually supported play dates. Two parents were taught to design cooperative play arrangements to facilitate social interactions between their children with autism and typically developing peers in their homes. Two independent reversal designs were used to demonstrate functional relationships between parent-implemented, contextually supported play dates and an increase in synchronous reciprocal interactions for both participants. Social validity, both immediately after the intervention and 1 year later, was also high for both parents; however, there was no consistent impact on participant, confederate, or parent affect during the study. The results are discussed with reference to previous research, future directions, limitations, and implications for practice.
Beyond the ‘failed state’: Toward conceptual alternatives
Authors: Call Charles T.
Published: April 2010

The article advances conceptual alternatives to the ‘failed state.’ It provides reasons why the concept is deficient, showing especially how counterproductive it is to aggregate states as diverse as Colombia, Malawi, Somalia, Iraq, Haiti, and Tajikistan. I argue for distinguishing among capacity gaps, security gaps, and legitimacy gaps that states experience. Importantly, I show that these gaps often do not coincide in a given country, and that the logical responses to each of the three gaps diverge in significant ways. I offer brief case examples of the logic of response to the gaps and of the tensions that must be managed among them. The article advances the debate over an important and under-theorized emergent concept in global politics.
Return to sender?
Authors: Broeders Dennis
Published: April 2010

The expulsion of irregular migrants has become a political priority in many (northern) EU member states. In countries such as Germany and the Netherlands this has resulted in a rather puzzling situation in which the capacity for the administrative detention of irregular migrants is increasing, while the number of effective expulsions seems to be decreasing. In this article two theoretical perspectives are used to analyse these developments: a perspective emanating from the criminological framework of the ‘new penology’ and one resulting from the ‘migration control literature’. These perspectives combined offer explanations for this paradoxical situation — by highlighting the importance of identification and the frustration thereof by irregular migrants and countries of origin — and for the apparent irrationality of the use of, sometimes very lengthy, administrative detention of irregular migrants.
Immigration control, post-Fordism, and less eligibility
Authors: De Giorgi Alessandro
Published: April 2010

The apparent de-bordering of the western world under the impulse of economic globalization has been paralleled by a simultaneous process of re-bordering of late-capitalist societies against global migrations. This re-bordering is part of a broader punitive turn in the regulation of migration which has emerged, particularly in the European context, since the mid-1970s. On the one hand, non-western immigrants are targeted by prohibitionist immigration policies which in fact contribute to the reproduction of their status of illegality; on the other hand, the systematic use of incarceration (together with administrative detention and deportation) as the main strategy in the ongoing war against unauthorized immigration configures a dynamic of hyper-criminalization of immigrants, whose result is the intensification of their socioeconomic and political marginality across Europe. Following the materialist criminological approach known as political economy of punishment, this article suggests that these punitive strategies should be analyzed against the background of an increasingly flexible and de-regulated neoliberal economy: in this context, the hyper-criminalization of migrations contributes to the reproduction of a vulnerable labor force whose insecurity makes it suitable for the segmented labor markets of post-Fordist economies.
Composite material and piezoelectric coefficient uncertainty effects on structural health monitoring using feedback control gains as damage indicators
Authors: Umesh K. , Ganguli Ranjan
Published: April 2010

This article addresses uncertainty effect on the health monitoring of a smart structure using control gain shifts as damage indicators. A finite element model of the smart composite plate with surface-bonded piezoelectric sensors and actuators is formulated using first-order shear deformation theory and a matrix crack model is integrated into the finite element model. A constant gain velocity/position feedback control algorithm is used to provide active damping to the structure. Numerical results show that the response of the structure is changed due to matrix cracks and this change can be compensated by actively tuning the feedback controller. This change in control gain can be used as a damage indicator for structural health monitoring. Monte Carlo simulation is conducted to study the effect of material uncertainty on the damage indicator by considering composite material properties and piezoelectric coefficients as independent random variables. It is found that the change in position feedback control gain is a robust damage indicator.
“Incremental Speed Increases Excitement”: Bodies, Space, Movement, and Televisual Change
Authors: Giddings Seth , Kennedy Helen W.
Published: April 2010

The authors argue that both Pong in the mid-1970s and the Wii today have transformed the television set in dramatic ways that have captured the popular imagination. Through a series of case studies, the authors pay close attention to the continuities and “incremental” changes in everyday televisual culture. Informed by phenomenological approaches, they present a comparison between Breakout and Wii Sports to suggest that the short history of videogame “plesiovision” should be rethought. The Wii’s genuine novelties are worthy of analysis in their own right but also highlight the significance of kinaesthesia in popular technoculture, suggest ways of theorising and studying proprioceptive bodies (both human and nonhuman), across videogame culture and televisual history.
Lower Extremity Implant Registries
Authors: Hyer Christopher F. , Portera William B. , Haglund Emily M.
Published: April 2010

Because of the current health care environment, involved parties are requesting the assessment of patient safety and efficacy following a lower extremity operation. Many foreign countries have registries to assess postoperative patient safety. A similar system does not exist in the United States. The purpose of this study was to create a registry to assess the safety and efficacy of lower extremity implants and procedures. The EVEREST Lower Extremity Registry is an Internet-based database designed to collect clinical outcomes and survivorship data of total ankle implants, hardware implants, and soft-tissue procedures. All data are collected remotely on a secure Web site. Data are collected at defined intervals according to implant or procedure. The investigators consent patients preoperatively using a central Institutional Review Board and are encouraged to enroll consecutive patients. Routine patient reports allow sites constant feedback regarding their patients versus the entire registry population. Patient engagement begins with providing a personalized implant card and is followed with the appropriate scheduling prompts based on interval due dates. Currently, there are 15 sites contributing data to the registry. There are 47, 79, and 27 patients enrolled in the total ankle, ankle hardware, and soft-tissue registries, respectively. Longest term follow-up collected is 12 months. Early outcomes suggest that many surgeons are willing to assimilate a registry system into their practice. This registry supports the critical need for data collection in lower extremity medicine.
Improved outcome with pulses of vincristine and corticosteroids in continuation therapy of children with average risk acute lymphoblastic leukemia (ALL) and lymphoblastic non-Hodgkin lymphoma (NHL): report of the EORTC randomized phase 3 trial 58951
Authors: De Moerloose Barbara , Suciu Stefan , Bertrand Yves , Mazingue Françoise , Robert Alain , Uyttebroeck Anne , Yakouben Karima , Ferster Alice , Margueritte Geneviève , Lutz Patrick , Munzer Martine , Sirvent Nicolas , Norton Lucilia , Boutard Patrick , Plantaz Dominique , Millot Frederic , Philippet Pierre , Baila Liliana , Benoit Yves , Otten Jacques ,   for the Children's Leukemia Group (CLG) of the European Organisation for Research and Treatment of Cancer (EORTC)
Published: April 2010

The European Organisation for Research and Treatment of Cancer 58951 trial for children with acute lymphoblastic leukemia (ALL) or non-Hodgkin lymphoma (NHL) addressed 3 randomized questions, including the evaluation of dexamethasone (DEX) versus prednisolone (PRED) in induction and, for average-risk patients, the evaluation of vincristine and corticosteroid pulses during continuation therapy. The corticosteroid used in the pulses was that assigned at induction. Overall, 411 patients were randomly assigned: 202 initially randomly assigned to PRED (60 mg/m2/d), 201 to DEX (6 mg/m2/d), and 8 nonrandomly assigned to PRED. At a median follow-up of 6.3 years, there were 19 versus 34 events for pulses versus no pulses; 6-year disease-free survival (DFS) rate was 90.6% (standard error [SE], 2.1%) and 82.8% (SE, 2.8%), respectively (hazard ratio [HR] = 0.54; 95% confidence interval, 0.31-0.94; P = .027). The effect of pulses was similar in the PRED (HR = 0.56) and DEX groups (HR = 0.59) but more pronounced in girls (HR = 0.24) than in boys (HR = 0.71). Grade 3 to 4 hepatic toxicity was 30% versus 40% in pulses versus no pulses group and grade 2 to 3 osteonecrosis was 4.4% versus 2%. For average-risk patients treated according to Berlin-Frankfurt-Muenster–based protocols, pulses should become a standard component of therapy. This trial was registered at www.clinicaltrials.gov as #NCT00003728.
Human NLRP3 inflammasome activation is Nox1-4 independent
Authors: van Bruggen Robin , Köker M. Yavuz , Jansen Machiel , van Houdt Michel , Roos Dirk , Kuijpers Taco W. , van den Berg Timo K.
Published: April 2010

The NLRP3 inflammasome can be activated by pathogen-associated molecular patterns or endogenous danger-associated molecular patterns. The activation of the NLRP3 inflammasome results in proteolytic activation and secretion of cytokines of the interleukin-1 (IL-1) family. The precise mode of activation of the NLRP3 inflammasome is still elusive, but has been postulated to be mediated by reactive oxygen species (ROS) generated by an NADPH oxidase. Using primary cells from chronic granulomatous disease (CGD) patients lacking expression of p22phox, a protein that is required for the function of Nox1-4, we show that cells lacking NADPH oxidase activity are capable of secreting normal amounts of IL-1β. Thus, we provide evidence that activation of the NLRP3 inflammasome does not depend on ROS generated from an NADPH oxidase.
Showing their true colors: a practical approach to volume rendering from serial sections
Authors: Handschuh Stephan , Schwaha Thomas , Metscher Brian D
Published: April 2010

Background

In comparison to more modern imaging methods, conventional light microscopy still offers a range of substantial advantages with regard to contrast options, accessible specimen size, and resolution. Currently, tomographic image data in particular is most commonly visualized in three dimensions using volume rendering. To date, this method has only very rarely been applied to image stacks taken from serial sections, whereas surface rendering is still the most prevalent method for presenting such data sets three-dimensionally. The aim of this study was to develop standard protocols for volume rendering of image stacks of serial sections, while retaining the benefits of light microscopy such as resolution and color information.

Results

Here we provide a set of protocols for acquiring high-resolution 3D images of diverse microscopic samples through volume rendering based on serial light microscopical sections using the 3D reconstruction software Amira (Visage Imaging Inc.). We overcome several technical obstacles and show that these renderings are comparable in quality and resolution to 3D visualizations using other methods. This practical approach for visualizing 3D micro-morphology in full color takes advantage of both the sub-micron resolution of light microscopy and the specificity of histological stains, by combining conventional histological sectioning techniques, digital image acquisition, three-dimensional image filtering, and 3D image manipulation and visualization technologies.

Conclusions

We show that this method can yield "true"-colored high-resolution 3D views of tissues as well as cellular and sub-cellular structures and thus represents a powerful tool for morphological, developmental, and comparative investigations. We conclude that the presented approach fills an important gap in the field of micro-anatomical 3D imaging and visualization methods by combining histological resolution and differentiation of details with 3D rendering of whole tissue samples. We demonstrate the method on selected invertebrate and vertebrate specimens, and propose that reinvestigation of historical serial section material may be regarded as a special benefit.
Large genomic differences between the morphologically indistinguishable diplomonads Spironucleus barkhanus and Spironucleus salmonicida
Authors: Roxström-Lindquist Katarina , Jerlström-Hultqvist Jon , Jørgensen Anders , Troell Karin , Svärd Staffan G , Andersson Jan O
Published: April 2010

Background

Microbial eukaryotes show large variations in genome structure and content between lineages, indicating extensive flexibility over evolutionary timescales. Here we address the tempo and mode of such changes within diplomonads, flagellated protists with two nuclei found in oxygen-poor environments. Approximately 5,000 expressed sequence tag (EST) sequences were generated from the fish commensal Spironucleus barkhanus and compared to sequences from the morphologically indistinguishable fish parasite Spironucleus salmonicida, and other diplomonads. The ESTs were complemented with sequence variation studies in selected genes and genome size determinations.

Results

Many genes detected in S. barkhanus and S. salmonicida are absent in the human parasite Giardia intestinalis, the most intensively studied diplomonad. For example, these fish diplomonads show an extended metabolic repertoire and are able to incorporate selenocysteine into proteins. The codon usage is altered in S. barkhanus compared to S. salmonicida. Sequence variations were found between individual S. barkhanus ESTs for many, but not all, protein coding genes. Conversely, no allelic variation was found in a previous genome survey of S. salmonicida. This difference was confirmed by sequencing of genomic DNA. Up to five alleles were identified for the cloned S. barkhanus genes, and at least nineteen highly expressed S. barkhanus genes are represented by more than four alleles in the EST dataset. This could be explained by the presence of a non-clonal S. barkhanus population in the culture, by a ploidy above four, or by duplications of parts of the genome. Indeed, genome size estimations using flow cytometry indicated similar haploid genome sizes in S. salmonicida and G. intestinalis (~12 Mb), whereas the S. barkhanus genome is larger (~18 Mb).

Conclusions

This study indicates extensive divergent genome evolution within diplomonads. Genomic traits such as codon usage, frequency of allelic sequence variation, and genome size have changed considerably between S. barkhanus and S. salmonicida. These observations suggest that large genomic differences may accumulate in morphologically indistinguishable eukaryotic microbes.
Microarray studies on effects of Pneumocystis carinii infection on global gene expression in alveolar macrophages
Authors: Cheng Bi-Hua , Liu Yunlong , Xuei Xiaoling , Liao Chung-Ping , Lu Debao , Lasbury Mark E , Durant Pamela J , Lee Chao-Hung
Published: April 2010

Background

Pneumocystispneumonia is a common opportunistic disease in AIDS patients. The alveolar macrophage is an important effector cell in the clearance ofPneumocystisorganisms by phagocytosis. However, both the number and phagocytic activity of alveolar macrophages are decreased inPneumocystisinfected hosts. To understand howPneumocystisinactivates alveolar macrophages, Affymetrix GeneChip®RG-U34A DNA microarrays were used to study the difference in global gene expression in alveolar macrophages from uninfected andPneumocystis carinii-infected Sprague-Dawley rats.

Results

Analyses of genes that were affected byPneumocystisinfection showed that many functions in the cells were affected. Antigen presentation, cell-mediated immune response, humoral immune response, and inflammatory response were most severely affected, followed by cellular movement, immune cell trafficking, immunological disease, cell-to-cell signaling and interaction, cell death, organ injury and abnormality, cell signaling, infectious disease, small molecular biochemistry, antimicrobial response, and free radical scavenging. Since rats must be immunosuppressed in order to developPneumocystisinfection, alveolar macrophages from four rats of the same sex and age that were treated with dexamethasone for the entire eight weeks of the study period were also examined. With a filter of false-discovery rate less than 0.1 and fold change greater than 1.5, 200 genes were found to be up-regulated, and 144 genes were down-regulated by dexamethasone treatment. DuringPneumocystispneumonia, 115 genes were found to be up- and 137 were down-regulated with the same filtering criteria. The top ten genes up-regulated byPneumocystisinfection were Cxcl10, Spp1, S100A9, Rsad2, S100A8, Nos2, RT1-Bb, Lcn2, RT1-Db1, and Srgn with fold changes ranging between 12.33 and 5.34; and the top ten down-regulated ones were Lgals1, Psat1, Tbc1d23, Gsta1, Car5b, Xrcc5, Pdlim1, Alcam, Cidea, and Pkib with fold changes ranging between -4.24 and -2.25.

Conclusions

In order to survive in the host,Pneumocystisorganisms change the expression profile of alveolar macrophages. Results of this study revealed thatPneumocystisinfection affects many cellular functions leading to reduced number and activity of alveolar macrophages duringPneumocystispneumonia.
Intensive expression of Bmi-1 is a new independent predictor of poor outcome in patients with ovarian carcinoma
Authors: Yang Guo-Fen , He Wei-Peng , Cai Mu-Yan , He Li-Ru , Luo Jun-Hang , Deng Hai-Xia , Guan Xin-Yuan , Zeng Mu-Sheng , Zeng Yi-Xin , Xie Dan
Published: April 2010

Background

It has been suggested that the B-cell specific moloney leukemia virus insertion site 1 (Bmi-1) gene plays an oncogenic role in several types of human cancer, but the status of Bmi-1 amplification and expression in ovarian cancer and its clinical/prognostic significance are unclear.

Methods

The methods of immunohistochemistry and fluorescence in situ hybridization were utilized to examine protein expression and amplification of Bmi-1 in 30 normal ovaries, 30 ovarian cystadenomas, 40 borderline ovarian tumors and 179 ovarian carcinomas.

Results

Intensive expression of Bmi-1 was detected in none of the normal ovaries, 3% cystadenomas, 10% borderline tumors, and 37% ovarian carcinomas, respectively. Amplification of Bmi-1 was detected in 8% of ovarian carcinomas. In ovarian carcinomas, significant positive associations were found between intensive expression of Bmi-1 and the tumors ascending histological grade, later pT/pN/pM and FIGO stages (P < 0.05). In univariate survival analysis of the ovarian carcinoma cohorts, a significant association of intensive expression of Bmi-1 with shortened patient survival (mean 49.3 months versus 100.3 months, p < 0.001) was demonstrated. Importantly, Bmi-1 expression provided significant independent prognostic parameters in multivariate analysis (p = 0.005).

Conclusions

These findings provide evidence that intensive expression of Bmi-1 might be important in the acquisition of an invasive and/or aggressive phenotype of ovarian carcinoma, and serve as a independent biomarker for shortened survival time of patients.
Breast cancer treatment and ethnicity in British Columbia, Canada
Authors: Yavari Parvin , Barroetavena Maria Cristina , Hislop T Greg , Bajdik Chris D
Published: April 2010

Background

Racial and ethnic disparities in breast cancer incidence, stage at diagnosis, survival and mortality are well documented; but few studies have reported on disparities in breast cancer treatment. This paper compares the treatment received by breast cancer patients in British Columbia (BC) for three ethnic groups and three time periods. Values for breast cancer treatments received in the BC general population are provided for reference.

Methods

Information on patients, tumour characteristics and treatment was obtained from BC Cancer Registry (BCCR) and BC Cancer Agency (BCCA) records. Treatment among ethnic groups was analyzed by stage at diagnosis and time period at diagnosis. Differences among the three ethnic groups were tested using chi-square tests, Fisher exact tests and a multivariate logistic model.

Results

There was no significant difference in overall surgery use for stage I and II disease between the ethnic groups, however there were significant differences when surgery with and without radiation were considered separately. These differences did not change significantly with time. Treatment with chemotherapy and hormone therapy did not differ among the minority groups.

Conclusion

The description of treatment differences is the first step to guiding interventions that reduce ethnic disparities. Specific studies need to examine reasons for the observed differences and the influence of culture and beliefs.
Toward characterization and definition of fibromyalgia severity
Authors: Silverman Stuart , Sadosky Alesia , Evans Chris , Yeh Yating , Alvir Jose Ma J , Zlateva Gergana
Published: April 2010

Background

There are no standard criteria for defining or assessing severity of fibromyalgia (FM) as a condition as fibromyalgia is associated with multiple symptom domains. The objective of this study was to evaluate whether patient self-reported severity of FM is associated with severity of pain and sleep interference and the presence of core co-morbidities.

Methods

We recruited individuals ≥ 18 years of age with a clinician-confirmed diagnosis of FM ≥ 3 months and a current pain rating >2 on a 0-10 numeric rating scale (NRS). Patients completed a questionnaire by mail in which they self-rated their FM severity (very mild, mild, moderate, and severe), their current pain severity and extent of sleep interference (NRS; mild, 0-3; moderate, 4-6, severe, 7-10), and provided information (yes/no) on the presence of core comorbidities (symptoms of depression, anxiety, sleep problems, back pain, neck pain) and medication use for FM. The core symptoms of FM were stratified to assist with patient characterization. Analysis of variance (ANOVA) was used to explore the relationship between self-reported FM severity and continuous variables (pain severity and sleep interference), and Mantel-Haenszel chi-square analysis was used to evaluate the trend in the proportions of patients reporting use of medications and core symptoms of FM by severity of FM. To complement patient-reported FM severity and to understand physicians' perspectives, a survey was performed among 28 physician specialists (rheumatology, neurology, anesthesiology/pain management, family practice, internal medicine, and psychiatry) to determine what they assessed when evaluating FM severity in clinical practice.

Results

The population (N = 129) of FM patients was predominantly female (89.1%), with a mean age of 49.4 ± 11.0 years, and 81.4% reported duration ≥ 2 years. Self-reported FM severity was moderate/severe in 86.0% of patients; mean current pain score was 6.40 ± 2.19 (moderate), and mean sleep interference score was 7.28 ± 2.23 (severe). Greater FM severity was significantly associated with higher levels of current pain and sleep interference (p < 0.0001), the proportion of patients reporting FM medication use (p = 0.0001), and the presence of core comorbidities (p < 0.05). Pain, functional disability, and fatigue severity were ranked as the top three criteria by the highest proportion of physicians when evaluating FM severity.

Conclusion

With higher self-reported FM severity, patients have greater pain and sleep interference as well as increased frequency of core comorbidities. Further investigation into understanding FM severity is warranted.
Can treatment of malaria be restricted to parasitologically confirmed malaria? A school-based study in Benin in children with and without fever
Authors: Faucher Jean-François , Makoutode Patrick , Abiou Grace , Béhéton Todoégnon , Houzé Pascal , Ouendo Edgard , Houzé Sandrine , Deloron Philippe , Cot Michel
Published: April 2010

Background

Applying the switch from presumptive treatment of malaria to new policies of anti-malarial prescriptions restricted to parasitologically-confirmed cases is a still unsolved challenge. Pragmatic studies can provide data on consequences of such a switch. In order to assess whether restricting anti-malarials to rapid diagnostic test (RDT)-confirmed cases in children of between five and 15 years of age is consistent with an adequate management of fevers, a school-based study was performed in Allada, Benin.

Methods

Children in the index group (with fever and a negative RDT) and the matched control group (without fever and a negative RDT) were not prescribed anti-malarials and actively followed-up during 14 days. Blood smears were collected at each assessment. Self-medication with chloroquine and quinine was assessed with blood spots. Malaria attacks during the follow-up were defined by persistent or recurrent fever concomitant to a positive malaria test.

Results

484 children were followed-up (242 in each group). At day 3, fever had disappeared in 94% of children from the index group. The incidence of malaria was similar (five cases in the index group and seven cases in the control group) between groups. Self-medication with chloroquine and quinine in this cohort was uncommon.

Conclusions

Applying a policy of restricting anti-malarials to RDT-confirmed cases is consistent with an adequate management of fevers in this population. Further studies on the management of fever in younger children are of upmost importance.
MicroRNA-184 inhibits neuroblastoma cell survival through targeting the serine/threonine kinase AKT2
Authors: Foley Niamh H. , Bray Isabella M. , Tivnan Amanda , Bryan Kenneth , Murphy Derek M. , Buckley Patrick G. , Ryan Jacqueline , O'Meara Anne , O'Sullivan Maureen , Stallings Raymond L.
Published: April 2010

Background

Neuroblastoma is a paediatric cancer of the sympathetic nervous system. The single most important genetic indicator of poor clinical outcome is amplification of the MYCN transcription factor. One of many down-stream MYCN targets is miR-184, which is either directly or indirectly repressed by this transcription factor, possibly due to its pro-apoptotic effects when ectopically over-expressed in neuroblastoma cells. The purpose of this study was to elucidate the molecular mechanism by which miR-184 conveys pro-apoptotic effects.

Results

We demonstrate that the knock-down of endogenous miR-184 has the opposite effect of ectopic up-regulation, leading to enhanced neuroblastoma cell numbers. As a mechanism of how miR-184 causes apoptosis when over-expressed, and increased cell numbers when inhibited, we demonstrate direct targeting and degradation of AKT2, a major downstream effector of the phosphatidylinositol 3-kinase (PI3K) pathway, one of the most potent pro-survival pathways in cancer. The pro-apoptotic effects of miR-184 ectopic over-expression in neuroblastoma cell lines is reproduced by siRNA inhibition of AKT2, while a positive effect on cell numbers similar to that obtained by the knock-down of endogenous miR-184 can be achieved by ectopic up-regulation of AKT2. Moreover, co-transfection of miR-184 with an AKT2 expression vector lacking the miR-184 target site in the 3'UTR rescues cells from the pro-apoptotic effects of miR-184.

Conclusions

MYCN contributes to tumorigenesis, in part, by repressing miR-184, leading to increased levels of AKT2, a direct target of miR-184. Thus, two important genes with positive effects on cell growth and survival, MYCN and AKT2, can be linked into a common genetic pathway through the actions of miR-184. As an inhibitor of AKT2, miR-184 could be of potential benefit in miRNA mediated therapeutics of MYCN amplified neuroblastoma and other forms of cancer.
Genomic alterations of primary tumor and blood in invasive ductal carcinoma of breast
Authors: Bae Ja Seong , Choi Jin Soo , Baik Seung Ho , Park Woo Chan , Song Byung Joo , Kim Jeong Soo , Lim Young , Jung Sang Seol
Published: April 2010

Background

Genomic alterations are important events in the origin and progression of various cancers, with DNA copy number changes associated with progression and treatment response in cancer. Array CGH is potentially useful in the identification of genomic alterations from primary tumor and blood in breast cancer patients. The aim of our study was to compare differences of DNA copy number changes in blood and tumor tissue in breast cancer.

Methods

DNA copy number changes in blood were compared to those in tumor tissue using array-comparative genomic hybridization in samples obtained from 30 breast cancer patients. The relative degree of chromosomal changes was analyzed using log2 ratios and data was validated by real-time polymerase chain reaction.

Results

Forty-six regions of gains present in more than 30% of the tissues and 70 regions of gains present in more than 30% of blood were identified. The most frequently gained region was chromosome 8q24. In total, agreement of DNA copy numbers between primary tumor and blood was minimal (Kappa = 0.138, p < 0.001).

Conclusion

Although there was only a slight agreement of DNA copy number alterations between the primary tumor and the blood samples, the blood cell copy number variation may have some clinical significance as compared to the primary tumor in IDC breast cancer patients.
Differential sensitivity of melanoma cell lines with BRAF
V600E
mutation to the specific Raf inhibitor PLX4032
Authors: Søndergaard Jonas N , Nazarian Ramin , Wang Qi , Guo Deliang , Hsueh Teli , Mok Stephen , Sazegar Hooman , MacConaill Laura E , Barretina Jordi G , Kehoe Sarah M , Attar Narsis , von Euw Erika , Zuckerman Jonathan E , Chmielowski Bartosz , Comin-Anduix Begoña , Koya Richard C , Mischel Paul S , Lo Roger S , Ribas Antoni
Published: April 2010

Blocking oncogenic signaling induced by the BRAF
V600E mutation is a promising approach for melanoma treatment. We tested the anti-tumor effects of a specific inhibitor of Raf protein kinases, PLX4032/RG7204, in melanoma cell lines. PLX4032 decreased signaling through the MAPK pathway only in cell lines with the BRAF
V600E mutation. Seven out of 10 BRAF
V600E mutant cell lines displayed sensitivity based on cell viability assays and three were resistant at concentrations up to 10 μM. Among the sensitive cell lines, four were highly sensitive with IC50 values below 1 μM, and three were moderately sensitive with IC50 values between 1 and 10 μM. There was evidence of MAPK pathway inhibition and cell cycle arrest in both sensitive and resistant cell lines. Genomic analysis by sequencing, genotyping of close to 400 oncogeninc mutations by mass spectrometry, and SNP arrays demonstrated no major differences in BRAF locus amplification or in other oncogenic events between sensitive and resistant cell lines. However, metabolic tracer uptake studies demonstrated that sensitive cell lines had a more profound inhibition of FDG uptake upon exposure to PLX4032 than resistant cell lines. In conclusion, BRAF
V600E mutant melanoma cell lines displayed a range of sensitivities to PLX4032 and metabolic imaging using PET probes can be used to assess sensitivity.
Chiropractic management of patients post-disc arthroplasty: eight case reports
Authors: O'Shaughnessy Julie , Drolet Marc , Roy Jean-François , Descarreaux Martin
Published: April 2010

Background

When conservative therapies for low back pain (LBP) are not effective, elective surgery may be proposed to these patients. Over the last 20 years, a new technology, disc replacement, has become increasingly popular because it is believed to maintain or restore the integrity of spinal movement and minimize the side-effects compared to fusion. Although disc replacement may relieve a patient from pain and related disability, soreness and stiffness of the lumbopelvic region seem to be common aftermaths of the surgery. This prospective case series was undertaken to identify and describe potential adverse events of lumbar spinal manipulation, a common therapy for low back pain, in a group of patients with symptoms after disc prostheses.

Cases presentation

Eight patients who underwent lumbar spine total disc replacement were referred by an orthopaedic surgeon for chiropractic treatments. These patients had 1 or 2 total lumbar disc replacements and were considered stable according to the surgical protocol but presented persistent, post-surgical, non-specific LBP or pelvic pain. They were treated with lumbar spine side posture manipulations only and received 8 to 10 chiropractic treatments based on the clinical evolution and the chiropractor's judgment. Outcome measures included benign, self-limiting, and serious adverse events after low back spinal manipulative therapy. The Oswestry Disability Index, a pain scale and the fear avoidance belief questionnaire were administered to respectively assess disability, pain and fear avoidance belief about work and physical activity. This prospective case series comprised 8 patients who all had at least 1 total disc replacement at the L4/L5 or L5/S1 level and described persistent post-surgical LBP interfering with their daily activities. Commonly-reported side-effects of a benign nature included increased pain and/or stiffness of short duration in nearly half of the chiropractic treatment period. No major or irreversible complication was noted.

Conclusions

During the short treatment period, no major complication was encountered by the patients. Moreover, the benign side-effects reported after lumbar spine manipulation were similar in nature and duration to those frequently experienced by the general population.
Protocol: a simple gel-free method for SNP genotyping using allele-specific primers in rice and other plant species
Authors: Hirotsu Naoki , Murakami Naomi , Kashiwagi Takayuki , Ujiie Kazuhiro , Ishimaru Ken
Published: April 2010

Background

Genotype analysis using multiple single nucleotide polymorphisms (SNPs) is a useful but labor-intensive or high-cost procedure in plant research. Here we describe an alternative genotyping method that is suited to multi-sample or multi-locus SNP genotyping and does not require electrophoresis or specialized equipment.

Results

We have developed a simple method for multi-sample or multi-locus SNP genotyping using allele-specific primers (ASP). More specifically, we (1) improved the design of allele-specific primers, (2) established a method to detect PCR products optically without electrophoresis, and (3) standardized PCR conditions for parallel genomic assay using various allele-specific primers. As an illustration of multi-sample SNP genotyping using ASP, we mapped the locus for lodging resistance in a typhoon (lrt5). Additionally, we successfully tested multi-locus ASP-PCR analysis using 96 SNPs located throughout the genomes of rice (Oryza sativa) cultivars 'Koshihikari' and 'Kasalath', and demonstrated its applicability to other diverse cultivars/subspecies, including wild rice (O. rufipogon).

Conclusion

Our ASP methodology allows characterization of SNPs genotypes without electrophoresis, expensive probes or specialized equipment, and is highly versatile due to the flexibility in the design of primers. The method could be established easily in any molecular biology laboratory, and is applicable to diverse organisms.
ApoE mimetic peptide decreases Aβ production in vitro and in vivo
Authors: Minami S Sakura , Cordova Antoinette , Cirrito John R , Tesoriero Joseph A , Babus Lenard W , Davis Gary C , Dakshanamurthy Sivanesan , Turner R Scott , Pak Daniel TS , Rebeck G William , Paige Mikell , Hoe Hyang-Sook
Published: April 2010

Background

Apolipoprotein E (apoE) is postulated to affect brain Aβ levels through multiple mechanisms--by altering amyloid precursor protein (APP) processing, Aβ degradation, and Aβ clearance. We previously showed that an apoE-derived peptide containing a double repeat of the receptor-binding region was similarly effective in increasing APP processing in vivo. Here, we further examined whether peptides containing tandem repeats of the apoE receptor-binding region (amino acids 141-149) affected APP trafficking, APP processing, and Aβ production.

Results

We found that peptides containing a double or triple tandem repeat of the apoE receptor-binding region, LRKLRKRLL, increased cell surface APP and decreased Aβ levels in PS1-overexpressing PS70 cells and in primary neurons. This effect was potentiated by a sequential increase in the number of apoE receptor-binding domain repeats (trimer > dimer > monomer). We previously showed that the apoE dimer increased APP CTF in vivo; to determine whether the dimer also affected secreted APP or Aβ levels, we performed a single hippocampal injection of the apoE dimer in wild-type mice and analyzed its effect on APP processing. We found increased sAPPα and decreased Aβ levels at 24 hrs after treatment, suggesting that the apoE dimer may increase α-secretase cleavage.

Conclusions

These data suggest that small peptides consisting of tandem repeats of the apoE receptor-binding region are sufficient to alter APP trafficking and processing. The potency of these peptides increased with increasing repeats of the receptor binding domain of apoE. In addition, in vivo administration of the apoE peptide (dimer) increased sAPPα and decreased Aβ levels in wild-type mice. Overall, these findings contribute to our understanding of the effects of apoE on APP processing and Aβ production both in vitro and in vivo.
Heartworm (Dirofilaria immitis) infection in a leopard (Panthera pardus pardus) housed in a zoological park in north-eastern Italy
Authors: Mazzariol Sandro , Cassini Rudi , Voltan Laura , Aresu Luca , Frangipane di Regalbono Antonio
Published: April 2010

Canine heartworm (cHW) disease is now recognised as potential cause of serious disease in cats and other felids, especially in endemic areas. In March 2009, a 23-years-old male African leopard (Panthera pardus pardus) housed in a zoological park located in the Province of Padova (Veneto Region), a cHW endemic area of the north-eastern Italy, died and was immediately necropsied. A cloth completely occluding the pyloric lumen was considered the presumptive cause of death. During necropsy, six nematodes (4 males and 2 females) were found within the right ventricle of the heart and the pulmonary artery. Diagnosis of HW (Dirofilaria immitis) infection was carried out by morphological features of adult worms and microfilariae, and then confirmed by detection of circulating HW antigens using a commercial SNAP kit (IDEXX Laboratories inc., USA). D. immitis infection was also confirmed by PCR amplification of the 5S ribosomal spacer region, performed on worm fragments and microfilaraemic blood samples obtained from the right ventricle of the heart. A glomerulonephritis of immuno-mediated origin and most likely associated with the HW infection is also reported. HW chemoprophylaxis and annual serological testing on wild felids housed outdoors in endemic cHW disease areas are recommended. This is the first diagnosis of D. immitis infection in an exotic felid in Italy.
Astrocytic expression of Parkinson's disease-related A53T α-synuclein causes neurodegeneration in mice
Authors: Gu Xing-Long , Long Cai-Xia , Sun Lixin , Xie Chengsong , Lin Xian , Cai Huaibin
Published: April 2010

Background

Parkinson's disease (PD) is the most common movement disorder. While neuronal deposition of α-synuclein serves as a pathological hallmark of PD and Dementia with Lewy Bodies, α-synuclein-positive protein aggregates are also present in astrocytes. The pathological consequence of astrocytic accumulation of α-synuclein, however, is unclear.

Results

Here we show that PD-related A53T mutant α-synuclein, when selectively expressed in astrocytes, induced rapidly progressed paralysis in mice. Increasing accumulation of α-synuclein aggregates was found in presymptomatic and symptomatic mouse brains and correlated with the expansion of reactive astrogliosis. The normal function of astrocytes was compromised as evidenced by cerebral microhemorrhage and down-regulation of astrocytic glutamate transporters, which also led to increased inflammatory responses and microglial activation. Interestingly, the activation of microglia was mainly detected in the midbrain, brainstem and spinal cord, where a significant loss of dopaminergic and motor neurons was observed. Consistent with the activation of microglia, the expression level of cyclooxygenase 1 (COX-1) was significantly up-regulated in the brain of symptomatic mice and in cultured microglia treated with conditioned medium derived from astrocytes over-expressing A53T α-synuclein. Consequently, the suppression of COX-1 activities extended the survival of mutant mice, suggesting that excess inflammatory responses elicited by reactive astrocytes may contribute to the degeneration of neurons.

Conclusions

Our findings demonstrate a critical involvement of astrocytic α-synuclein in initiating the non-cell autonomous killing of neurons, suggesting the viability of reactive astrocytes and microglia as potential therapeutic targets for PD and other neurodegenerative diseases.
One-way/one-return boundary-element method and salt internal multiples
Authors: He Yaofeng , Wu Ru-Shan
Published: April 2010

Surface-related multiples or internal multiples can produce artifacts in migrated images using one-way wave-equation methods. Salt-body-related internal-multiple removal remains a challenging problem for this approach. To investigate the effects of salt-body-related internal multiples on subsalt imaging, the boundary-element method is implemented in a one-way/one-return scheme to separate the primary transmission/reflection arrivals at the salt boundaries from the internal multiples. Numerical results demonstrate that the proposed method is effective for modeling primary transmission/reflection arrivals through/from irregular interfaces between strong-velocity-contrast media. Internal multiples are obtained through straight subtraction of primary reflection arrivals from full reflected-wave data. The image from prestack depth migration of these pure internal multiples using one-way propagators is compatible with some strong artifacts in the subsalt region from migration of full-wave data using the same one-way propagators. Results suggest that a significant part of artifacts in the subsalt region in the prestack image for the 2D SEG-EAGE salt model using one-way propagators might be caused by salt internal multiples.
Automatic detection of UXO magnetic anomalies using extended Euler deconvolution
Authors: Davis Kristofer , Li Yaoguo , Nabighian Misac
Published: April 2010

We have developed an algorithm for the automatic detection of prospective unexploded ordnance (UXO) anomalies in total-field or gradient magnetic data based on the concept of the structural index (SI) of a magnetic anomaly. Identifying magnetic anomalies having specific structural indices enables the direct detection of potential UXO targets. The total magnetic field produced by a dipolelike source, such as a UXO, decays with inverse distance cubed and therefore has an SI of three, whereas the gradient data have an SI of four. The developed extended Euler deconvolution method based on the Hilbert transform provides a reliable means for calculating the spatial location, depth, and SI of compact and isolated anomalies; it has enabled us to perform automatic anomaly selection for further analysis. Our method first examines the anomaly decay and selects possible UXO anomalies based on the expected SI. We refine the result further by post-Euler amplitude analysis using the relative source strength of the anomalies selected in the first stage. The amplitude analysis statistically identifies weak anomalies that are due to noise in the data. This enhances the final result and eliminates automatic picks that fall within the noise level. We have demonstrated the effectiveness of the method using synthetic and field data sets.
Rapid construction of equivalent sources using wavelets
Authors: Li Yaoguo , Oldenburg Douglas W.
Published: April 2010

We have developed a fast algorithm for generating an equivalent source by using fast wavelet transforms based on orthonormal, compactly supported wavelets. We apply a 2D wavelet transform to each row and column of the coefficient matrix and subsequently threshold the transformed matrix to generate a sparse representation in the wavelet domain. The algorithm then uses this sparse matrix to construct the the equivalent source directly in the wavelet domain. Performing an inverse wavelet transform then yields the equivalent source in the space domain. Using upward continuation of total-field magnetic data between uneven surfaces as examples, we have compared this approach with the direct solution using the dense matrix in the space domain. We have shown that the wavelet approach can reduce the CPU time by as many as two orders of magnitude.
Determining the orientation of marine CSEM receivers using orthogonal Procrustes rotation analysis
Authors: Key Kerry , Lockwood Andrew
Published: April 2010

Electromagnetic receivers deployed to the seafloor for CSEM surveys can have unknown orientations because of the unavailability of compass and tilt recordings. In such situations, only the orientation-independent parameters derived from the measured CSEM field vector can be interpreted, and this may result in less structural resolution than possible when the sensor orientations are known. An orthogonal Procrustes rotation analysis (OPRA) technique can be used to estimate the full 3D receiver orientation for inline and off-line CSEM receivers. The generality of this method allows it to be easily embedded into nonlinear CSEM inversion routines so that they iteratively search for both the receiver orientation and a seafloor electrical-conductivity model compatible with the data. Synthetic tests using the OPRA method jointly with a 1D inversion demonstrate that it can recover the rotation and tilt angles to about one degree accuracy for 1D data and to within a few degrees for 2D data. Application of this method to real survey data shows good agreement with a previous orientation method that is suitable only for determining the horizontal rotation of inline receivers. CSEM data collected over the Pluto gas field offshore the northwest coast of Australia were used to demonstrate how the OPRA method can be used to orient CSEM receivers prior to inversion of only the inline electric- and crossline magnetic-field components.