bluuebunny/crossref_metadata_2025 huggingface dataset:
Futures planning, parental expectations and sibling concern for people who have a learning disability
Authors: Davys Deborah , Mitchell Duncan , Haigh Carol
Published: November 2010

A questionnaire was e-mailed to 200 siblings on the Sibs database to explore future plans, parental expectations and sibling concerns regarding people who have a learning disability; 21 questionnaires were returned. A full discussion regarding sibling support was reported by 12 (57%) of respondents; 7 (33%) stated this discussion had not taken place, and 2 (9%) were unsure. Twelve (57%) of participants reported no clear future plan; where a plan did exist, seven (33%) of respondents claimed it was fully agreeable to both them and their parents. Eleven (52%) of respondents reported no difference between their wishes regarding their future role and parental wishes. Key themes generated were: satisfaction with services, parental influence, sibling concern about the future, futures planning, the impact of the disabled person upon sibling lives, and siblings needs. Further qualitative exploration into issues for siblings of adults who have a learning disability is required.
Effect of low Zr addition on microalloyed cast steel
Authors: Aliakbarzadeh H. , Mirdamadi Sh. , Tamizifar M.
Published: November 2010

Zirconium is rarely used as a microalloying element, although it is used to control sulphide inclusions in as killed steels. In the present work, the effect of a 0·005 wt-%Zr addition on the microstructure and mechanical properties of a cast low carbon steel following heat treatment was examined. The Zr addition was found to increase the Charpy toughness of tempered specimens from 20·1 to 38·4 J, but no changes in toughness were observed in homogenised and quenched specimens. The hardness of tempered specimens with Zr additions was increased by 60 HV60 relative to Zr free specimens. The apparent mean grain size of the homogenised Zr free samples was 15·7 μm, compared with 11·3 μm for the specimens with Zr additions, suggesting that Zr has a refining effect on the microstructure.
Autoimmune lymphoproliferative syndrome–like disease with somatic KRAS mutation
Authors: Takagi Masatoshi , Shinoda Kunihiro , Piao Jinhua , Mitsuiki Noriko , Takagi Mari , Matsuda Kazuyuki , Muramatsu Hideki , Doisaki Sayoko , Nagasawa Masayuki , Morio Tomohiro , Kasahara Yoshihito , Koike Kenichi , Kojima Seiji , Takao Akira , Mizutani Shuki
Published: November 2010

Autoimmune lymphoproliferative syndrome (ALPS) is classically defined as a disease with defective FAS-mediated apoptosis (type I-III). Germline NRAS mutation was recently identified in type IV ALPS. We report 2 cases with ALPS-like disease with somatic KRAS mutation. Both cases were characterized by prominent autoimmune cytopenia and lymphoadenopathy/splenomegaly. These patients did not satisfy the diagnostic criteria for ALPS or juvenile myelomonocytic leukemia and are probably defined as a new disease entity of RAS-associated ALPS-like disease (RALD).
On the artefactual parasitic eubacteria clan in conditioned logdet phylogenies: heterotachy and ortholog identification artefacts as explanations
Authors: Sangaralingam Ajanthah , Susko Edward , Bryant David , Spencer Matthew
Published: November 2010

Background

Phylogenetic reconstruction methods based on gene content often place all the parasitic and endosymbiotic eubacteria (parasites for short) together in a clan. Many other lines of evidence point to this parasites clan being an artefact. This artefact could be a consequence of the methods used to construct ortholog databases (due to some unknown bias), the methods used to estimate the phylogeny, or both.

We test the idea that the parasites clan is an ortholog identification artefact by analyzing three different ortholog databases (COG, TRIBES, and OFAM), which were constructed using different methods, and are thus unlikely to share the same biases. In each case, we estimate a phylogeny using an improved version of the conditioned logdet distance method. If the parasites clan appears in trees from all three databases, it is unlikely to be an ortholog identification artefact.

Accelerated loss of a subset of gene families in parasites (a form of heterotachy) may contribute to the difficulty of estimating a phylogeny from gene content data. We test the idea that heterotachy is the underlying reason for the estimation of an artefactual parasites clan by applying two different mixture models (phylogenetic and non-phylogenetic), in combination with conditioned logdet. In these models, there are two categories of gene families, one of which has accelerated loss in parasites. Distances are estimated separately from each category by conditioned logdet. This should reduce the tendency for tree estimation methods to group the parasites together, if heterotachy is the underlying reason for estimation of the parasites clan.

Results

The parasites clan appears in conditioned logdet trees estimated from all three databases. This makes it less likely to be an artefact of database construction. The non-phylogenetic mixture model gives trees without a parasites clan. However, the phylogenetic mixture model still results in a tree with a parasites clan. Thus, it is not entirely clear whether heterotachy is the underlying reason for the estimation of a parasites clan. Simulation studies suggest that the phylogenetic mixture model approach may be unsuccessful because the model of gene family gain and loss it uses does not adequately describe the real data.

Conclusions

The most successful methods for estimating a reliable phylogenetic tree for parasitic and endosymbiotic eubacteria from gene content data are still ad-hoc approaches such as the SHOT distance method. however, the improved conditioned logdet method we developed here may be useful for non-parasites and can be accessed at http://www.liv.ac.uk/~cgrbios/cond_logdet.html
A systematic review of the psychometric properties of Quality of Life measures for school aged children with cerebral palsy
Authors: Carlon Stacey , Shields Nora , Yong Katherine , Gilmore Rose , Sakzewski Leanne , Boyd Roslyn
Published: November 2010

Background

This systematic review aimed to evaluate the psychometric properties and clinical utility of all condition specific outcome measures used to assess quality of life (QOL) in school aged children with cerebral palsy (CP).

Methods

Relevant outcome measures were identified by searching 8 electronic databases, supplemented by citation tracking. Two independent reviewers completed data extraction and analysis of the measures using a modified version of the CanChild Outcome Measures Rating Form.

Results

From the 776 papers identified 5 outcome measures met the inclusion criteria: the Care and Comfort Hypertonicity Questionnaire (C&CHQ), the Caregiver Priorities and Child Health Index of Life with Disabilities (CPCHILD), CP QOL-Child, DISABKIDS and PedsQL 3.0 CP Module. There was evidence of construct validity for all five measures. Content validity was reported for all measures except PedsQL 3.0. The CPCHILD and CP QOL-Child were the only outcome measures to have reported data on concurrent validity. All measures, with the exception of one (C&CHQ) provided evidence of internal reliability. The CPCHILD and the CP-QOL-Child had evidence of test-retest reliability and DISABKIDS had evidence of inter-rater reliability. There were no published data on the responsiveness of these outcome measures.

Conclusions

The CPCHILD and the CP QOL-Child demonstrated the strongest psychometric properties and clinical utility. Further work is needed, for all measures, on data for sensitivity to change.
Acute effects of fine particulate air pollution on ST segment height: A longitudinal study
Authors: He Fan , Shaffer Michele L , Rodriguez-Colon Sol , Bixler Edward O , Vgontzas Alexandros N , Williams Ronald W , Wu Rongling , Cascio Wayne E , Liao Duanping
Published: November 2010

Background

The mechanisms for the relationship between particulate air pollution and cardiac disease are not fully understood. Air pollution-induced myocardial ischemia is one of the potentially important mechanisms.

Methods

We investigate the acute effects and the time course of fine particulate pollution (PM2.5) on myocardium ischemic injury as assessed by ST-segment height in a community-based sample of 106 healthy non-smokers. Twenty-four hour beat-to-beat electrocardiogram (ECG) data were obtained using a high resolution 12-lead Holter ECG system. After visually identifying and removing all the artifacts and arrhythmic beats, we calculated beat-to-beat ST-height from ten leads (inferior leads II, III, and aVF; anterior leads V3 and V4; septal leads V1 and V2; lateral leads I, V5, and V6,). Individual-level 24-hour real-time PM2.5 concentration was obtained by a continuous personal PM2.5 monitor. We then calculated, on a 30-minute basis, the corresponding time-of-the-day specific average exposure to PM2.5 for each participant. Distributed lag models under a linear mixed-effects models framework were used to assess the regression coefficients between 30-minute PM2.5 and ST-height measures from each lead; i.e., one lag indicates a 30-minute separation between the exposure and outcome.

Results

The mean (SD) age was 56 (7.6) years, with 41% male and 74% white. The mean (SD) PM2.5 exposure was 14 (22) μg/m3. All inferior leads (II, III, and aVF) and two out of three lateral leads (I and V6), showed a significant association between higher PM2.5 levels and higher ST-height. Most of the adverse effects occurred within two hours after PM2.5 exposure. The multivariable adjusted regression coefficients β (95% CI) of the cumulative effect due to a 10 μg/m3 increase in Lag 0-4 PM2.5 on ST-I, II, III, aVF and ST-V6 were 0.29 (0.01-0.56) μV, 0.79 (0.20-1.39) μV, 0.52 (0.01-1.05) μV, 0.65 (0.11-1.19) μV, and 0.58 (0.07-1.09) μV, respectively, with all p < 0.05.

Conclusions

Increased PM2.5 concentration is associated with immediate increase in ST-segment height in inferior and lateral leads, generally within two hours. Such an acute effect of PM2.5 may contribute to increased potential for regional myocardial ischemic injury among healthy individuals.
ZNF217 confers resistance to the pro-apoptotic signals of paclitaxel and aberrant expression of Aurora-A in breast cancer cells
Authors: Thollet Aurélie , Vendrell Julie A , Payen Léa , Ghayad Sandra E , Ben Larbi Sabrina , Grisard Evelyne , Collins Colin , Villedieu Marie , Cohen Pascale A
Published: November 2010

Background

ZNF217 is a candidate oncogene located at 20q13, a chromosomal region frequently amplified in breast cancers. The precise mechanisms involved in ZNF217 pro-survival function are currently unknown, and utmost importance is given to deciphering the role of ZNF217 in cancer therapy response.

Results

We provide evidence that stable overexpression of ZNF217 in MDA-MB-231 breast cancer cells conferred resistance to paclitaxel, stimulated cell proliferationin vitroassociated with aberrant expression of several cyclins, and increased tumor growth in mouse xenograft models. Conversely, siRNA-mediated silencing of ZNF217 expression in MCF7 breast cancer cells, which possess high endogenous levels of ZNF217, led to decreased cell proliferation and increased sensitivity to paclitaxel. The paclitaxel resistance developed by ZNF217-overexpressing MDA-MB-231 cells was not mediated by the ABCB1/PgP transporter. However, ZNF217 was able to counteract the apoptotic signals mediated by paclitaxel as a consequence of alterations in the intrinsic apoptotic pathway through constitutive deregulation of the balance of Bcl-2 family proteins. Interestingly, ZNF217 expression levels were correlated with the oncogenic kinase Aurora-A expression levels, as ZNF217 overexpression led to increased expression of the Aurora-A protein, whereas ZNF217 silencing was associated with low Aurora-A expression levels. We showed that a potent Aurora-A kinase inhibitor was able to reverse paclitaxel resistance in the ZNF217-overexpressing cells.

Conclusion

Altogether, these data suggest that ZNF217 might play an important role in breast neoplastic progression and chemoresistance, and that Aurora-A might be involved in ZNF217-mediated effects.
The zipper mechanism in phagocytosis: energetic requirements and variability in phagocytic cup shape
Authors: Tollis Sylvain , Dart Anna E , Tzircotis George , Endres Robert G
Published: November 2010

Background

Phagocytosis is the fundamental cellular process by which eukaryotic cells bind and engulf particles by their cell membrane. Particle engulfment involves particle recognition by cell-surface receptors, signaling and remodeling of the actin cytoskeleton to guide the membrane around the particle in a zipper-like fashion. Despite the signaling complexity, phagocytosis also depends strongly on biophysical parameters, such as particle shape, and the need for actin-driven force generation remains poorly understood.

Results

Here, we propose a novel, three-dimensional and stochastic biophysical model of phagocytosis, and study the engulfment of particles of various sizes and shapes, including spiral and rod-shaped particles reminiscent of bacteria. Highly curved shapes are not taken up, in line with recent experimental results. Furthermore, we surprisingly find that even without actin-driven force generation, engulfment proceeds in a large regime of parameter values, albeit more slowly and with highly variable phagocytic cups. We experimentally confirm these predictions using fibroblasts, transfected with immunoreceptor FcγRIIa for engulfment of immunoglobulin G-opsonized particles. Specifically, we compare the wild-type receptor with a mutant receptor, unable to signal to the actin cytoskeleton. Based on the reconstruction of phagocytic cups from imaging data, we indeed show that cells are able to engulf small particles even without support from biological actin-driven processes.

Conclusions

This suggests that biochemical pathways render the evolutionary ancient process of phagocytic highly robust, allowing cells to engulf even very large particles. The particle-shape dependence of phagocytosis makes a systematic investigation of host-pathogen interactions and an efficient design of a vehicle for drug delivery possible.
CTCF regulates the local epigenetic state of ribosomal DNA repeats
Authors: van de Nobelen Suzanne , Rosa-Garrido Manuel , Leers Joerg , Heath Helen , Soochit Widia , Joosen Linda , Jonkers Iris , Demmers Jeroen , van der Reijden Michael , Torrano Verónica , Grosveld Frank , Delgado M Dolores , Renkawitz Rainer , Galjart Niels , Sleutels Frank
Published: November 2010

Background

CCCTC binding factor (CTCF) is a highly conserved zinc finger protein, which is involved in chromatin organization, local histone modifications, and RNA polymerase II-mediated gene transcription. CTCF may act by binding tightly to DNA and recruiting other proteins to mediate its various functions in the nucleus. To further explore the role of this essential factor, we used a mass spectrometry-based approach to screen for novel CTCF-interacting partners.

Results

Using biotinylated CTCF as bait, we identified upstream binding factor (UBF) and multiple other components of the RNA polymerase I complex as potential CTCF-interacting partners. Interestingly, CTCFL, the testis-specific paralog of CTCF, also binds UBF. The interaction between CTCF(L) and UBF is direct, and requires the zinc finger domain of CTCF(L) and the high mobility group (HMG)-box 1 and dimerization domain of UBF. Because UBF is involved in RNA polymerase I-mediated ribosomal (r)RNA transcription, we analyzed CTCF binding to the rDNA repeat. We found that CTCF bound to a site upstream of the rDNA spacer promoter and preferred non-methylated over methylated rDNA. DNA binding by CTCF in turn stimulated binding of UBF. Absence of CTCF in cultured cells resulted in decreased association of UBF with rDNA and in nucleolar fusion. Furthermore, lack of CTCF led to reduced binding of RNA polymerase I and variant histone H2A.Z near the rDNA spacer promoter, a loss of specific histone modifications, and diminished transcription of non-coding RNA from the spacer promoter.

Conclusions

UBF is the first common interaction partner of CTCF and CTCFL, suggesting a role for these proteins in chromatin organization of the rDNA repeats. We propose that CTCF affects RNA polymerase I-mediated events globally by controlling nucleolar number, and locally by regulating chromatin at the rDNA spacer promoter, similar to RNA polymerase II promoters. CTCF may load UBF onto rDNA, thereby forming part of a network that maintains rDNA genes poised for transcription.
Hepatitis C — feedback from the Consensus Conference on the Management of Acute Hepatitis C (AHC) in Paris, May 2010
Authors: Vogel M
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Fatal and non‐fatal AIDS and non‐AIDS events in HIV‐1 infected patients with high CD4 counts
Authors: Reekie J , Gatell J , Yust I , Bakowska E , Rachmanova A , Losso M , Krasnov M , Francioli P , Kowalska J , Mocroft A
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Maraviroc (MVC) increases CD4+ and CD8+ cells: long‐term data from the MVC clinical development program
Authors: Lazzarin A , Sierra‐Madero JG , Battegay M , Mukwaya G , Burnside R , Chapman D , McCracken J , Portsmouth S , Valluri S , Valdez H , Heera J
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Calibration and accuracy of the geno2pheno co‐receptor algorithm for predicting HIV tropism for single and triplicate measurements of V3 genotype
Authors: Swenson LC , Knapp D , Harrigan PR
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Comparing the effectiveness of efavirenz and nevirapine for first‐line antiretroviral treatment amongst an adult treatment cohort from South Africa
Authors: Bock P , Fatti G , Grimwood A
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Comparative efficacy and safety of regimens including ritonavir‐boosted lopinavir or nevirapine in antiretroviral‐naïve HIV‐1‐infected individuals
Authors: Pereira A , Lopes da Cruz JP , Carvalho C , Gonçalves C , Antunes F
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Raltegravir‐induced drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome: implications for clinical practice and patient safety
Authors: Perry MEO , Almaani N , Desai N , Fox J , Larbalestier N , Chilton D
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Antiretroviral regimen complexity as a predictor of adherence
Authors: Boyle C , Wilson A , Treacy G , Sheehan G , Lambert J , Meegan C , Mallon P
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Prevalence of HIV drug‐resistance mutations in HIV‐infected Mexican patients heavily experienced to antiretroviral therapy
Authors: Gaytán‐Martínez JE , Mata‐Marín JA , Gutierrez‐Escolano F , Pérez‐Saleme L , Treviño‐Pérez S , Vázquez‐Rosales JG , Matías‐Juan N , Díaz‐Ramos RD , Arias‐Flores R
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
HIV drug resistance in children with treatment failure to first‐line regimens in Ho Chi Minh City, Vietnam
Authors: Nhung VTT , Colby D , Khanh TH , Viet TT , Lu D , Thuy HT , An B , Giang LT
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Comparative evaluation of ARV therapy efficiency among patients at the Kiev regional AIDS center
Authors: Yurchenko YO , Stepchenkova T , Karnets KI , Martinenko MO
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Antiretroviral strategies for the treatment of pregnant HIV+ women and prevention of perinatal HIV transmission in Dodoma, Tanzania: AMANI Study
Authors: Liuzzi G , Vairo F , Chaula Z , Nguhuni B , Nicastri E , Bevilacqua N , Cannas A , Paglia MG , Ippolito G
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
A filter‐based cross‐sectional analysis of an HIV‐positive, HAART‐treated cohort in rural Burundi: pharmacokinetics, pharmacogenetics and viral load
Authors: Calcagno A , Milia MG , D'Avolio A , Ndayishimiyae P , Dusabimana P , Bonora S , Cusato J , Simiele M , Rostagno R , Siccardi M , Audagnotto S , Ghisetti V , Di Perri G
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Opportunistic infections (OIs) present in HIV‐seropositive patients: a study
Authors: Ramaiah K Ayodhya , Sudha Rani B , Anand R , Ramola S , Satish Babu P , Ramesh Babu R
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
No impact of IL28B polymorphisms on liver enzymes in patients coinfected with HIV and HCV
Authors: Fernández‐Montero JV , Martín‐Carbonero L , Barreiro P , Rallón NI , Benito JM , González‐Lahoz J , Soriano V
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Temporal trend of the first prescription of nevirapine: the ANRS CO3 Aquitaine Cohort, 1997‐2008
Authors: Bruyand M , Geffard S , Lawson‐Ayayi S , Dauchy F , Miremont‐Salamé G , Greib C , Farbos S , Morlat P , Dabis F
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Lopinavir to atazanavir or darunavir switch in HIV‐1‐infected patients with dyslipidemia: an observational study
Authors: Le Moal G , Beraud G , Prazuck T , Hocqueloux L , Dupuis A , Venisse N
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Low serum phosphate levels are related to increased cardiovascular risk in HIV‐1 infected patients
Authors: Grima P , Guido M , Chiavaroli R , Tundo P , Zizza A
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Hypertriglyceridemic waist identifies HIV+ men and women at increased cardiometabolic risk
Authors: Guaraldi G , Zona S , Orlando G , Carli F , Stentarelli C , Despres J , Ross R
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
The association between metabolic syndrome and the occurrence of nephrolithiasis in HIV‐infected patients
Authors: Dumitru IM , Rugina S , Sotila G , Dumitru E , Rugina CN
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
Prevalence of chronic renal failure stage 3 or more in HIV‐infected patients in Antwerp: an observational study
Authors: Colson AW , Florence E , Augustijn H , Verpooten GA , Lynen L , Gheuens E
Published: November 2010

7‐11 November 2010, Tenth International Congress on Drug Therapy in HIV Infection, Glasgow, UK
CXC chemokine receptor 4 expressed in T cells plays an important role in the development of collagen-induced arthritis
Authors: Chung Soo-Hyun , Seki Keisuke , Choi Byung-Il , Kimura Keiko B , Ito Akihiko , Fujikado Noriyuki , Saijo Shinobu , Iwakura Yoichiro
Published: November 2010

Introduction

Chemokines and their receptors are potential therapeutic targets in rheumatoid arthritis (RA). Among these, several studies suggested the involvement of CXC chemokine 4 (CXCR4) and its ligand CXC ligand 12 (SDF-1) in RA pathogenesis. However, the role of these molecules in T-cell function is not known completely because of embryonic lethality of Cxcr4- and Cxcl12-deficient mice. In this report, we generated T cell-specific Cxcr4-deficient mice and showed that the CXCR4 in T cells is important for the development of collagen-induced arthritis (CIA).

Methods

T cell-specific Cxcr4-deficient mice were generated by using the Cre-loxP system. Mice harboring loxP sites flanking exon 2 of the Cxcr4gene (Cxcr4
flox/flox
) were generated by homologous recombination and crossed with Cre transgenic mice expressing Cre recombinase under the control of Lck promoter (Cxcr4
+/+
/Lck-Cremice) to generate T cell-specific Cxcr4-deficient mice (Cxcr4
flox/flox
/Lck-Cre mice). CIA was induced by immunization with chicken type II collagen and Complete Freund's Adjuvant (CFA).

Results

The incidence, but not the severity, of CIA was significantly reduced in Cxcr4
flox/flox
/Lck-Cre mice compared with Cxcr4
+/+
/Lck-Cre mice. We found that the expression of CXCR4 was enhanced in activated T cells, and the migration of Cxcr4-deficient T cells toward SDF-1 was severely impaired. However, antibody production, cellular proliferative response, and cytokine production on treatment with type II collagen (IIC) were normal in these knockout mice, suggesting that CXCR4 is not involved in T-helper functions. Interestingly, the proportion of CXCR4-expressing T cells was much increased in affected joints compared with that in draining lymph nodes in CIA-induced mice, and distribution of Cxcr4
flox/flox
/Lck-Cre mouse-derived T cells into affected joints was suppressed compared with that in Cxcr4
+/+
/Lck-Cre T cells.

Conclusions

These results indicate that CXCR4 expression in T cells is important for the development of CIA, by recruiting activated T cells toward inflammatory sites, and suggest that CXCR4 is a good target for the treatment of RA in humans.
A genome-wide association scan on estrogen receptor-negative breast cancer
Authors: Li Jingmei , Humphreys Keith , Darabi Hatef , Rosin Gustaf , Hannelius Ulf , Heikkinen Tuomas , Aittomäki Kristiina , Blomqvist Carl , Pharoah Paul DP , Dunning Alison M , Ahmed Shahana , Hooning Maartje J , Hollestelle Antoinette , Oldenburg Rogier A , Alfredsson Lars , Palotie Aarno , Peltonen-Palotie Leena , Irwanto Astrid , Low Hui Qi , Teoh Garrett HK , Thalamuthu Anbupalam , Kere Juha , D'Amato Mauro , Easton Douglas F , Nevanlinna Heli , Liu Jianjun , Czene Kamila , Hall Per
Published: November 2010

Introduction

Breast cancer is a heterogeneous disease and may be characterized on the basis of whether estrogen receptors (ER) are expressed in the tumour cells. ER status of breast cancer is important clinically, and is used both as a prognostic indicator and treatment predictor. In this study, we focused on identifying genetic markers associated with ER-negative breast cancer risk.

Methods

We conducted a genome-wide association analysis of 285,984 single nucleotide polymorphisms (SNPs) genotyped in 617 ER-negative breast cancer cases and 4,583 controls. We also conducted a genome-wide pathway analysis on the discovery dataset using permutation-based tests on pre-defined pathways. The extent of shared polygenic variation between ER-negative and ER-positive breast cancers was assessed by relating risk scores, derived using ER-positive breast cancer samples, to disease state in independent, ER-negative breast cancer cases.

Results

Association with ER-negative breast cancer was not validated for any of the five most strongly associated SNPs followed up in independent studies (1,011 ER-negative breast cancer cases, 7,604 controls). However, an excess of smallP-values for SNPs with known regulatory functions in cancer-related pathways was found (globalP= 0.052). We found no evidence to suggest that ER-negative breast cancer shares a polygenic basis to disease with ER-positive breast cancer.

Conclusions

ER-negative breast cancer is a distinct breast cancer subtype that merits independent analyses. Given the clinical importance of this phenotype and the likelihood that genetic effect sizes are small, greater sample sizes and further studies are required to understand the etiology of ER-negative breast cancers.
Clinical aspects and cytokine response in severe H1N1 influenza A virus infection
Authors: Hagau Natalia , Slavcovici Adriana , Gonganau Daniel N , Oltean Simona , Dirzu Dan S , Brezoszki Erika S , Maxim Mihaela , Ciuce Constantin , Mlesnite Monica , Gavrus Rodica L , Laslo Carmen , Hagau Radu , Petrescu Magda , Studnicska Daniela M
Published: November 2010

Introduction

The immune responses in patients with novel A(H1N1) virus infection (nvA(H1N1)) are incompletely characterized. We investigated the profile of Th1 and Th17 mediators and interferon-inducible protein-10 (IP-10) in groups with severe and mild nvA(H1N1) disease and correlated them with clinical aspects.

Methods

Thirty-two patients hospitalized with confirmed nvA(H1N1) infection were enrolled in the study: 21 patients with nvA(H1N1)-acute respiratory distress syndrome (ARDS) and 11 patients with mild disease. One group of 20 patients with bacterial sepsis-ARDS and another group of 15 healthy volunteers were added to compare their cytokine levels with pandemic influenza groups. In the nvA(H1N1)-ARDS group, the serum cytokine samples were obtained on admission and 3 days later. The clinical aspects were recorded prospectively.

Results

In the nvA(H1N1)-ARDS group, obesity and lymphocytopenia were more common and IP-10, interleukin (IL)-12, IL-15, tumor necrosis factor (TNF)α, IL-6, IL-8 and IL-9 were significantly increased versus control. When comparing mild with severe nvA(H1N1) groups, IL-6, IL-8, IL-15 and TNFα were significantly higher in the severe group. In nonsurvivors versus survivors, IL-6 and IL-15 were increased on admission and remained higher 3 days later. A positive correlation of IL-6, IL-8 and IL-15 levels with C-reactive protein and with > 5-day interval between symptom onset and admission, and a negative correlation with the PaO2:FiO2 ratio, were found in nvA(H1N1) groups. In obese patients with influenza disease, a significant increased level of IL-8 was found. When comparing viral ARDS with bacterial ARDS, the level of IL-8, IL-17 and TNFα was significantly higher in bacterial ARDS and IL-12 was increased only in viral ARDS.

Conclusions

In our critically ill patients with novel influenza A(H1N1) virus infection, the hallmarks of the severity of disease were IL-6, IL-15, IL-8 and TNFα. These cytokines, except TNFα, had a positive correlation with the admission delay and C-reactive protein, and a negative correlation with the PaO2:FiO2 ratio. Obese patients with nvA(H1N1) disease have a significant level of IL-8. There are significant differences in the level of cytokines when comparing viral ARDS with bacterial ARDS.
Denosumab Compared With Zoledronic Acid for the Treatment of Bone Metastases in Patients With Advanced Breast Cancer: A Randomized, Double-Blind Study
Authors: Stopeck Alison T. , Lipton Allan , Body Jean-Jacques , Steger Guenther G. , Tonkin Katia , de Boer Richard H. , Lichinitser Mikhail , Fujiwara Yasuhiro , Yardley Denise A. , Viniegra María , Fan Michelle , Jiang Qi , Dansey Roger , Jun Susie , Braun Ada
Published: November 2010

Purpose

This randomized study compared denosumab, a fully human monoclonal antibody against receptor activator of nuclear factor κ B (RANK) ligand, with zoledronic acid in delaying or preventing skeletal-related events (SREs) in patients with breast cancer with bone metastases.

Patients and Methods

Patients were randomly assigned to receive either subcutaneous denosumab 120 mg and intravenous placebo (n = 1,026) or intravenous zoledronic acid 4 mg adjusted for creatinine clearance and subcutaneous placebo (n = 1,020) every 4 weeks. All patients were strongly recommended to take daily calcium and vitamin D supplements. The primary end point was time to first on-study SRE (defined as pathologic fracture, radiation or surgery to bone, or spinal cord compression).

Results

Denosumab was superior to zoledronic acid in delaying time to first on-study SRE (hazard ratio, 0.82; 95% CI, 0.71 to 0.95; P = .01 superiority) and time to first and subsequent (multiple) on-study SREs (rate ratio, 0.77; 95% CI, 0.66 to 0.89; P = .001). Reduction in bone turnover markers was greater with denosumab. Overall survival, disease progression, and rates of adverse events (AEs) and serious AEs were similar between groups. An excess of renal AEs and acute-phase reactions occurred with zoledronic acid; hypocalcemia occurred more frequently with denosumab. Osteonecrosis of the jaw occurred infrequently (2.0%, denosumab; 1.4%, zoledronic acid; P = .39).

Conclusion

Denosumab was superior to zoledronic acid in delaying or preventing SREs in patients with breast cancer metastatic to bone and was generally well tolerated. With the convenience of a subcutaneous injection and no requirement for renal monitoring, denosumab represents a potential treatment option for patients with bone metastases.
Multicenter, Randomized, Cross-Over Clinical Trial of Venlafaxine Versus Gabapentin for the Management of Hot Flashes in Breast Cancer Survivors
Authors: Bordeleau Louise , Pritchard Kathleen I. , Loprinzi Charles L. , Ennis Marguerite , Jugovic Olivera , Warr David , Haq Rashida , Goodwin Pamela J.
Published: November 2010

Purpose

Nonhormonal pharmacologic interventions are recommended for the treatment of hot flashes in breast cancer survivors. Antidepressants and gabapentin have been shown to be both effective and well tolerated; however, it is not clear which is preferred.

Patients and Methods

This was a group-sequential, open-label, randomized, cross-over trial of 4 weeks of venlafaxine (37.5 mg daily for 7 days followed by 75 mg daily for 21 days) versus gabapentin (300 mg once per day for 3 days, then 300 mg twice per day for 3 days, then 300 mg three times per day for 22 days), with patient preference as the primary outcome. Postmenopausal women with at least 14 bothersome hot flashes per week for the prior month were eligible. A 2-week baseline period and a 2-week tapering/washout time was used before the first and second treatment periods, respectively. Diaries were used to measure hot flashes and potential toxicities throughout the study. Participants completed a preference questionnaire at the end of the study. A predefined Pocock stopping rule was applied. Patient preference and hot flash and toxicity outcomes were compared between treatments.

Results

Sixty-six patients were randomly assigned, 56 of whom provided a preference (eight dropped out and two had no preference); 18 (32%) preferred gabapentin and 38 (68%) preferred venlafaxine (P = .01). Both agents reduced hot flash scores to a similar extent (66% reduction). Venlafaxine was associated with increased nausea, appetite loss, constipation, and reduced negative mood changes compared with gabapentin, whereas gabapentin was associated with increased dizziness and appetite compared with venlafaxine (all P < .05).

Conclusion

Breast cancer survivors prefer venlafaxine over gabapentin for treating hot flashes.
TP53 Mutation Is Frequently Associated With CTNNB1 Mutation or MYCN Amplification and Is Compatible With Long-Term Survival in Medulloblastoma
Authors: Pfaff Elke , Remke Marc , Sturm Dominik , Benner Axel , Witt Hendrik , Milde Till , von Bueren André O. , Wittmann Andrea , Schöttler Anna , Jorch Norbert , Graf Norbert , Kulozik Andreas E. , Witt Olaf , Scheurlen Wolfram , von Deimling Andreas , Rutkowski Stefan , Taylor Michael D. , Tabori Uri , Lichter Peter , Korshunov Andrey , Pfister Stefan M.
Published: November 2010

Purpose

The role of TP53 mutations in the tumorigenesis of sporadic medulloblastoma (MB) and the value of TP53 mutation status as a prognostic marker are not yet definitely elucidated. A recent report identified TP53 mutations in MB as an adverse prognostic marker. Hence, the current study was conducted to validate the prognostic role of TP53 mutation in MB and to understand its contribution to tumorigenesis.

Methods

A comprehensive genetic analysis of 310 MB samples was performed by screening for TP53 mutations and further relating the TP53 mutation status to p53 immunostaining, cytogenetic aberrations, and clinical variables.

Results

Mutation analysis of TP53 revealed mutations in 21 (6.8%) of 310 samples. Germline TP53 mutations were found in two patients with a history suggestive of a hereditary cancer syndrome. TP53 mutation status was not associated with unfavorable prognosis (P = .63) and was not linked to 17p allelic loss but was over-represented in the prognostically favorable WNT subgroup of MB as defined by CTNNB1 mutation (seven of 35 TP53-mutated tumors v 14 of 271 TP53 wild-type tumors; P = .005) and in tumors carrying high-level MYCN amplification (seven of 21 TP53-mutated tumors v 14 of 282 TP53 wild-type tumors; P = .001).

Conclusion

The contradictory results in the recent literature concerning the prognostic value of TP53 mutation might be explained by different frequencies of WNT MBs, different frequencies of patients with Li-Fraumeni syndrome, and different cumulative doses of alkylating drugs applied in these studies.
Jagged1 in the portal vein mesenchyme regulates intrahepatic bile duct development: insights into Alagille syndrome
Authors: Hofmann Jennifer J. , Zovein Ann C. , Koh Huilin , Radtke Freddy , Weinmaster Gerry , Iruela-Arispe M. Luisa
Published: November 2010

Mutations in the human Notch ligand jagged 1 (JAG1) result in a multi-system disorder called Alagille syndrome (AGS). AGS is chiefly characterized by a paucity of intrahepatic bile ducts (IHBD), but also includes cardiac, ocular, skeletal, craniofacial and renal defects. The disease penetration and severity of the affected organs can vary significantly and the molecular basis for this broad spectrum of pathology is unclear. Here, we report that Jag1 inactivation in the portal vein mesenchyme (PVM), but not in the endothelium of mice, leads to the hepatic defects associated with AGS. Loss of Jag1 expression in SM22α-positive cells of the PVM leads to defective bile duct development beyond the initial formation of the ductal plate. Cytokeratin 19-positive cells are detected surrounding the portal vein, yet they are unable to form biliary tubes, revealing an instructive role of the vasculature in liver development. These findings uncover the cellular basis for the defining feature of AGS, identify mesenchymal Jag1-dependent and -independent stages of duct development, and provide mechanistic information for the role of Jag1 in IHBD formation.
Vibration Characteristics of a Cracked Cantilever Beam under Free Vibration
Authors: Sutar Mihir Kumar , Pattnaik Sarojrani
Published: November 2010

The objective of this paper is to perform free vibration analysis of a cracked cantilever and to analyze the relation between the modal natural frequency with crack depth, modal natural frequency with crack location. Also the relation among the crack depth, crack location and natural frequency has been analyzed. Only single cracks at different depths and at different locations are evaluated. And the analysis reveals a relationship between crack depth and modal natural frequency. As we know when a structure suffers from damage its dynamic property can change and it was observed that cracks caused a stiffness reduction with an inherent reduction in modal natural frequencies. Consequently it leads to the change in the dynamic response of the beam. The analysis was performed using ALGOR software. Modal natural frequency was found to be decreasing with increases in crack depth. And the same was found to be increasing with increases in crack location from the fixed end.
Charlotte Waite's Fairy Project: Rethinking the fashion show
Authors: Tseëlon Efrat
Published: November 2010

Charlotte Waite's Fairy Project: Rethinking the fashion show, West Yorkshire, UK, 31 July to 7 August 2010
Predicting Language Outcomes at 4 Years of Age: Findings From Early Language in Victoria Study
Authors: Reilly Sheena , Wake Melissa , Ukoumunne Obioha C. , Bavin Edith , Prior Margot , Cini Eileen , Conway Laura , Eadie Patricia , Bretherton Lesley
Published: November 2010

OBJECTIVE:

To quantify the contributions of child, family, and environmental predictors to language ability at 4 years.

METHODS:

A longitudinal study was performed with a sample of 1910 infants recruited at 8 months in Melbourne, Australia. Predictors were child gender, prematurity, birth weight and order, multiple birth, socioeconomic status, maternal mental health, vocabulary, education, and age at child's birth, non–English-speaking background, and family history of speech/language difficulties. Outcomes were Clinical Evaluation of Language Fundamentals-Preschool, language scores, low language status (scores >1.25 SDs below the mean), and specific language impairment (SLI) (scores >1.25 SDs below the mean for children with normal nonverbal performance).

RESULTS:

A total of 1596 children provided outcome data. Twelve baseline predictors explained 18.9% and 20.9% of the variation in receptive and expressive scores, respectively, increasing to 23.6% and 30.4% with the addition of late talking status at age 2. A total of 20.6% of children (324 of 1573 children) met the criteria for low language status and 17.2% (251 of 1462 children) for SLI. Family history of speech/language problems and low maternal education levels and socioeconomic status predicted adverse language outcomes. The combined predictors discriminated only moderately between children with and without low language levels or SLIs (area under the curve: 0.72–0.76); this improved with the addition of late talking status (area under the curve: 0.78–0.84).

CONCLUSIONS:

Measures of social disadvantage helped explain more variation in outcomes at 4 years than at 2 years, but ability to predict low language status and SLI status remained limited.
Malnutrition and Helminth Infection Affect Performance of an Interferon γ–Release Assay
Authors: Thomas Tania A. , Mondal Dinesh , Noor Zannatun , Liu Lei , Alam Masud , Haque Rashidul , Banu Sayera , Sun Haiyan , Peterson Kristine M.
Published: November 2010

OBJECTIVE:

We sought to compare the tuberculin skin test (TST) to the QuantiFERON-TB Gold In-Tube assay (QFT-IT) and assess the effects of malnourishment and intestinal helminth infection on QFT-IT results.

METHODS:

In this population-based cross-sectional study from Dhaka, Bangladesh, we screened children for latent tuberculosis infection with the QFT-IT and TST. We assess the agreement between the TST and QFT-IT, risk factors associated with indeterminate QFT-IT results, and magnitude of interferon γ (IFN-γ) production.

RESULTS:

Three hundred and two children (aged 11–15.3 years) were enrolled, including 93 (30.8%) who were malnourished. Of 251 participants who provided stool samples, 117 (46.6%) were infected with Ascaris lumbricoides and/or Trichuris trichiura. TST results were positive (≥10 mm) for 101 (33.4%) children and negative for 201 (66.6%) children. QFT-IT results were positive for 107 (35.4%) children, negative for 121 (40.1%) children, and indeterminate for 74 (24.5%) children. Agreement between the tests was moderate (κ = 0.55 [95% confidence interval: 0.44–0.65]; P < .0001) when excluding indeterminate results. Children with indeterminate QFT-IT results were separately compared with children with positive and negative QFT-IT results; malnutrition (P = .0006 and .0003), and helminth infection (P = .05 and .02), and the statistical interaction between these 2 terms (P = .03 and .004) were associated with indeterminate results. Higher levels of IFN-γ in response to tuberculosis antigens were associated with positive TST results (P < .0001); lower levels were associated with malnutrition (P = .02).

CONCLUSIONS:

Malnutrition and helminth infections were associated with indeterminate QFT-IT results. Therefore, the presence of such conditions may limit the interpretability of QFT-IT results in children.
Observation of the peach fruit moth, Carposina sasakii, larvae in young apple fruit by dedicated micro-magnetic resonance imaging
Authors: Koizumi Mika , Ihara Fumio , Yaginuma Katsuhiko , Kano Hiromi , Haishi Tomoyuki
Published: November 2010

Infestation of young apple fruits by the larvae of the peach fruit moth, Carposina sasakii Matsumura (Lepidoptera: Carposinidae), was studied by a small dedicated micro-magnetic resonance imaging (MRI) apparatus using the three-dimensional (3D) gradient-echo method and the two-dimensional (2D) and 3D spin-echo methods. Changes from a young larva at 1.8 mm in length to a mature one ready to leave the fruit were observed in relation to the progression of infestation of the fruit tissues. The trace of larva intrusion was demonstrated by a series of sliced images in the 3D image data of an infested fruit, where it entered from outside the calyx, and migrated to near the vasculature around the carpel through the core. The small, dedicated MRI device was proven useful for ecological studies of the growth and movement of insect larvae in their food fruits. It can also be applied to detect the infestation of small fruits by insect larvae.
Comparison of Fallow Tillage Methods in the Intermediate Rainfall Inland Pacific Northwest
Authors: Riar Dilpreet S. , Ball Daniel A. , Yenish Joseph P. , Wuest Stewart B. , Corp Mary K.
Published: November 2010

Winter wheat (Triticum aestivum L.) is usually grown in the Pacific Northwest (PNW) intermediate rainfall zone following tilled or chemical summer fallow. Studies were conducted near Davenport, WA and Helix, OR over two fallow–winter wheat cycles to evaluate the efficacy of reduced or no‐tillage fallow compared to conventional fallow and compare the efficacy of herbicides applied using a light‐activated sensor‐controlled (LASC) applicator to broadcast applications. Six treatments included conventional primary tillage followed by rodweeding; sweep‐tillage followed by rodweeding, broadcast, or LASC herbicide application; and no‐tillage followed by broadcast or LASC herbicide application. Broadcast and LASC herbicide applications controlled weeds similarly in no‐tillage treatments. However, LASC applications used from 45 to 70% less herbicide than broadcast applications to attain similar weed control. No‐tillage or sweep‐tillage systems with herbicide application had from 15 to 30% greater surface residue cover than the conventional tillage system. Available soil moisture in both the root‐zone and seed‐zone soil profiles at time of planting was similar among tillage systems. There were no differences in wheat quality parameters across treatments. The conventional tillage system had similar wheat grain yield as sweep‐tillage systems followed by rodweed or broadcast herbicide application, but yields were up to 21% greater than sweep‐tillage with LASC applied herbicides and no‐tillage systems. Reduced tillage systems using sweep‐tillage and broadcast herbicide application could potentially replace more tillage intensive fallow systems in the PNW.