bluuebunny/crossref_metadata_2025 huggingface dataset:
Adaptation of the Human Factors Analysis and Classification System to Patient Safety Studies
Authors: Hoffman Ronald B. , Segal Cindy G. , Foster Julie A. , Rhoads Laura C.
Published: June 2013

Reliably analyzing and aggregating the gaps that lead to adverse outcomes in patient care has been difficult. We have modified and integrated the Human Factors Analysis and Classification System (HFACS) into the patient safety analyses of events at a large university cancer hospital environment to guide the development and implementation of interventions and to reduce medical errors. HFACS provides a systematic way to represent the qualitative findings of patient safety studies in a categorical database. Consistent application of this human factors tool and successive analyses of aggregated data from medical events offers healthcare organizations an objective guide for enhancements of safety risk identification and assessment systems.
Implementing Human Factors methods in the design of new clinical facilities
Authors: Bitan Yuval , Donchin Yoel
Published: June 2013

In spite of the vast literature demonstrating the safety benefits of having Human Factors engineers on board, only few medical organizations employ a Human Factors engineer as part of their staff. Following a safety training seminar, the hospital management decided to include a Human Factors engineer in the process of designing three new clinics in a 600 bed private hospital in Israel. Together with experts from other fields, our team of Human Factors engineers served as consultants for the interior designer during the initial stages of designing these new clinics. We found that adding the Human Factors aspects as part of the design phase might provide easy implementation of solutions that would improve the working environment with minimal budget. The implementation of this method improves both the patient and the caregiver experience and provide environment for safer treatments.
The Role of Monitor Technicians in Enhancing Alarm Response
Authors: Crandall Beth , Papautsky Elizabeth Lerner , Grome Anna , Dressman Kathy , Greenberg James , Geiser Maria
Published: June 2013

We report a study of monitor alarm response conducted in the newly designed Transitional Care Center (TCC) at Cincinnati Children’s Hospital Medical Center. A key component of the new TCC design has been the development and implementation of a Monitor Technician (MT) position. We examined the MT role from a human factors perspective, with particular focus on the MT’s coordination and communication with nurses (RNs) and respiratory therapists (RTs). We conducted observations and Cognitive Task Analysis interviews of MTs, RNs, and RTs. In this paper, we describe the value of the MT’s role and define the challenges associated with the MT’s responsibilities. MTs serve an important support function, but they face challenges in locating RNs/RTs to respond to alarms and at times, may be the only “eyes on” the patients, making training and preparation a critical aspect of the MT’s function. In response to findings, CCHMC has taken a number of steps to improve alarm and alert responses and provide further support to the MT’s role. The current study serves as a demonstration of the principles and methods that human factors can offer to healthcare organizations to support patient safety and quality of care.
Cognitive Factors Associated with Nurses’ Successful Detection of Sepsis Versus Failure to Rescue
Authors: Doig Alexa , Baraki Katie , Drews Frank
Published: June 2013

The objective of this study was to identify cognitive predictors of failure to rescue among acute care oncology nurses. Fifty-seven oncology nurses were video recorded as they monitored a patient developing a life threatening non-routine event in a high fidelity acute care hospital setting, in the case of this analysis– sepsis. Nurses who had higher levels of level 1 situation awareness (i.e., use limited data from the electronic health record and assessment findings) were more likely to detect sepsis and initiate an appropriate response. In the failure to rescue cases, the majority of errors occurred at the level of perception or level 1 situation awareness. Twenty percent of nurses who identified that the patient was septic, were not able to project the potential severity of the situation and apply appropriate interventions.
Reducing Unnecessary Sleep Disruption for Neonatal Patients
Authors: Rajaraman Swaroop , Ferris Thomas
Published: June 2013

This research addresses a major issue that is receiving growing attention in neonatal intensive care: the importance of uninterrupted sleep to promote healthy cognitive and physical development for NICU patients. This issue is addressed by targeting classic human factors problems with alarms in critical care environments. The focus of this research is in the intersection between alarm problems and problems related to unnecessary disruption of patients’ sleep. An observational study is currently underway at a major metropolitan hospital to document the relationship between alarms and sleep/wake state, highlighting characteristics of alarms and contexts when sleep is disrupted due to clinically insignificant/inactionable alarms and also when nurses’ response to the alarms leads to them intentionally waking the patients when it is unnecessary to do so. Methods for this work are discussed in detail, and preliminary anecdotal findings suggest that apnea and bradycardia are some of the more problematic alarms for unnecessary sleep disruption. Future research plans to address these and other problematic alarms are also discussed.
Patterns of missplicing due to somatic U2AF1 mutations in myeloid neoplasms
Authors: Przychodzen Bartlomiej , Jerez Andres , Guinta Kathryn , Sekeres Mikkael A. , Padgett Richard , Maciejewski Jaroslaw P. , Makishima Hideki
Published: June 2013

Key Points

Recurrent U2AF1 mutations are associated with missplicing in the specific genes. U2AF1 mutant protein might identify the specific sequence signals at the splice sites.
A capture-sequencing strategy identifies IRF8, EBF1, and APRIL as novel IGH fusion partners in B-cell lymphoma
Authors: Bouamar Hakim , Abbas Saman , Lin An-Ping , Wang Long , Jiang Daifeng , Holder Kenneth N. , Kinney Marsha C. , Hunicke-Smith Scott , Aguiar Ricardo C. T.
Published: June 2013

Key Points

Targeted capture/next-generation sequencing is a powerful tool for the diagnosis of known and discovery of new IGH fusions in DLBCL. IGH-mediated deregulation of IRF8 and EBF1 in DLBCL is characterized by induction of AID and BCL6, suppression of PRDM1, and antiapoptosis.
HASP server: a database and structural visualization platform for comparative models of influenza A hemagglutinin proteins
Authors: Ambroggio Xavier I , Dommer Jennifer , Gopalan Vivek , Dunham Eleca J , Taubenberger Jeffery K , Hurt Darrell E
Published: June 2013

Background

Influenza A viruses possess RNA genomes that mutate frequently in response to immune pressures. The mutations in the hemagglutinin genes are particularly significant, as the hemagglutinin proteins mediate attachment and fusion to host cells, thereby influencing viral pathogenicity and species specificity. Large-scale influenza A genome sequencing efforts have been ongoing to understand past epidemics and pandemics and anticipate future outbreaks. Sequencing efforts thus far have generated nearly 9,000 distinct hemagglutinin amino acid sequences.

Description

Comparative models for all publicly available influenza A hemagglutinin protein sequences (8,769 to date) were generated using the Rosetta modeling suite. The C-alpha root mean square deviations between a randomly chosen test set of models and their crystallographic templates were less than 2 Å, suggesting that the modeling protocols yielded high-quality results. The models were compiled into an online resource, the Hemagglutinin Structure Prediction (HASP) server. The HASP server was designed as a scientific tool for researchers to visualize hemagglutinin protein sequences of interest in a three-dimensional context. With a built-in molecular viewer, hemagglutinin models can be compared side-by-side and navigated by a corresponding sequence alignment. The models and alignments can be downloaded for offline use and further analysis.

Conclusions

The modeling protocols used in the HASP server scale well for large amounts of sequences and will keep pace with expanded sequencing efforts. The conservative approach to modeling and the intuitive search and visualization interfaces allow researchers to quickly analyze hemagglutinin sequences of interest in the context of the most highly related experimental structures, and allow them to directly compare hemagglutinin sequences to each other simultaneously in their two- and three-dimensional contexts. The models and methodology have shown utility in current research efforts and the ongoing aim of the HASP server is to continue to accelerate influenza A research and have a positive impact on global public health.
Haplotype association analysis of genes within the WNT signalling pathways in diabetic nephropathy
Authors: Kavanagh David H , Savage David A , Patterson Christopher C , McKnight Amy Jayne , Crean John K , Maxwell Alexander P , McKay Gareth J ,   the Warren 3/UK GoKinD Study Group
Published: June 2013

Background

Renal interstitial fibrosis and glomerular sclerosis are hallmarks of diabetic nephropathy (DN) and several studies have implicated members of the WNT pathways in these pathological processes. This study comprehensively examined common genetic variation within the WNT pathway for association with DN.

Methods

Genes within the WNT pathways were selected on the basis of nominal significance and consistent direction of effect in the GENIE meta-analysis dataset. Common SNPs and common haplotypes were examined within the selected WNT pathway genes in a white population with type 1 diabetes, discordant for DN (cases: n = 718; controls: n = 749). SNPs were genotyped using Sequenom or Taqman assays. Association analyses were performed using PLINK, to compare allele and haplotype frequencies in cases and controls. Correction for multiple testing was performed by either permutation testing or using false discovery rate.

Results

A logistic regression model including collection centre, duration of diabetes, and average HbA1c as covariates highlighted three SNPs inGSK3B(rs17810235, rs17471, rs334543), two inDAAM1(rs1253192, rs1252906) and one inNFAT5(rs17297207) as being significantly (P < 0.05) associated with DN, however these SNPs did not remain significant after correction for multiple testing. Logistic regression of haplotypes, with ESRD as the outcome, and pairwise interaction analyses did not yield any significant results after correction for multiple testing.

Conclusions

These results indicate that both common SNPs and common haplotypes of WNT pathway genes are not strongly associated with DN. However, this does not completely exclude these or the WNT pathways from association with DN, as unidentified rare genetic or copy number variants could still contribute towards the genetic architecture of DN.
Metabolic, hemodynamic and structural adjustments to low intensity exercise training in a metabolic syndrome model
Authors: Morvan Eduardo , Lima Nathalia Edviges Alves , Machi Jacqueline Freire , Mostarda Cristiano , De Angelis Kátia , Irigoyen Maria Cláudia , Wichi Rogério Brandão , Rodrigues Bruno , Maifrino Laura Beatriz Mesiano
Published: June 2013

Background

The increase in fructose consumption is paralleled by a higher incidence of metabolic syndrome, and consequently, cardiovascular disease mortality. We examined the effects of 8 weeks of low intensity exercise training (LET) on metabolic, hemodynamic, ventricular and vascular morphological changes induced by fructose drinking in male rats.

Methods

Male Wistar rats were divided into (n = 8 each) control (C), sedentary fructose (F) and ET fructose (FT) groups. Fructose-drinking rats received D-fructose (100 g/l). FT rats were assigned to a treadmill training protocol at low intensity (30% of maximal running speed) during 1 h/day, 5 days/week for 8 weeks. Measurements of triglyceride concentrations, white adipose tissue (WAT) and glycemia were carried out together with insulin tolerance test to evaluate metabolic profile. Arterial pressure (AP) signals were directly recorded. Baroreflex sensitivity (BS) was evaluated by the tachycardic and bradycardic responses. Right atria, left ventricle (LV) and ascending aorta were prepared to morphoquantitative analysis.

Results

LET reduced WAT (−37.7%), triglyceride levels (−33%), systolic AP (−6%), heart weight/body weight (−20.5%), LV (−36%) and aortic (−76%) collagen fibers, aortic intima-media thickness and circumferential wall tension in FT when compared to F rats. Additionally, FT group presented improve of BS, numerical density of atrial natriuretic peptide granules (+42%) and LV capillaries (+25%), as well as the number of elastic lamellae in aorta compared with F group.

Conclusions

Our data suggest that LET, a widely recommended practice, seems to be particularly effective for preventing metabolic, hemodynamic and morphological disorders triggered by MS.
Differential G protein subunit expression by prostate cancer cells and their interaction with CXCR5
Authors: El-Haibi Christelle P , Sharma Praveen , Singh Rajesh , Gupta Pranav , Taub Dennis D , Singh Shailesh , Lillard, Jr James W
Published: June 2013

Background

Prostate cancer (PCa) cell lines and tissues differentially express CXCR5, which positively correlate with PCa progression, and mediate PCa cell migration and invasion following interaction with CXCL13. However, the differential expression of G protein α, β, and γ subunits by PCa cell lines and the precise combination of these proteins with CXCR5 has not been elucidated.

Methods

We examined differences in G protein expression of normal prostate (RWPE-1) and PCa cell lines (LNCaP, C4-2B, and PC3) by western blot analysis. Further, we immunoprecipitated CXCR5 with different G protein subunits, and CXCR4, following CXCL13 stimulation. To investigate constitutive coupling of CXCR5 with CXCR4 and PAR-1 we performed invasion assay in PCa cells transfected with Gαq/i2 or Gα13 siRNA, following CXCL13 treatment. We also investigated Rac and RhoA activity by G-LISA activation assay in PCa cells following CXCL13/thrombin stimulation.

Result

Of the 22 G proteins studied, Gαi1-3, Gβ1-4, Gγ5, Gγ7, and Gγ10 were expressed by both normal and PCa cell lines. Gαs was moderately expressed in C4-2B and PC3 cell lines, Gαq/11 was only present in RWPE-1 and LNCaP cell lines, while Gα12 and Gα13 were expressed in C4-2B and PC3 cell lines. Gγ9 was expressed only in PCa cell lines. Gα16, Gβ5, Gγ1-4, and Gγ13 were not detected in any of the cell lines studied. Surprisingly, CXCR4 co-immunoprecipitated with CXCR5 in PCa cell lines irrespective of CXCL13 treatment. We also identified specific G protein isoforms coupled to CXCR5 in its resting and active states. Gαq/11/Gβ3/Gγ9 in LNCaP and Gαi2/Gβ3/Gγ9 in C4-2B and PC3 cell lines, were coupled to CXCR5 and disassociated following CXCL13 stimulation. Interestingly, Gα13 co-immunoprecipitated with CXCR5 in CXCL13-treated, but not in untreated PCa cell lines. Inhibition of Gαq/i2 significantly decreased the ability of cells to invade, whereas silencing Gα13 did not affect CXCL13-dependent cell invasion. Finally, CXCL13 treatment significantly increased Rac activity in Gαq/i2 dependent manner, but not RhoA activity, in PCa cell lines.

Conclusions

These findings offer insight into molecular mechanisms of PCa progression and can help to design some therapeutic strategies involving CXCR5 and/or CXCL13 blockade and specific G protein inhibition to abrogate PCa metastasis.
Boundary value problems for fractional differential equations with nonlocal boundary conditions
Authors: Yan Rian , Sun Shurong , Sun Ying , Han Zhenlai
Published: June 2013

In this paper, we establish some sufficient conditions for the existence of solutions to two classes of boundary value problems for fractional differential equations with nonlocal boundary conditions. Our goal is to establish some criteria of existence for the boundary problems with nonlocal boundary condition involving the Caputo fractional derivative, using Banach’s fixed point theorem and Schaefer’s fixed point theorem. Finally, we present four examples to show the importance of these results.

MSC:34A08, 34B10.
A new reporter mouse cytomegalovirus reveals maintained immediate-early gene expression but poor virus replication in cycling liver sinusoidal endothelial cells
Authors: Dag Franziska , Weingärtner Adrien , Butueva Milada , Conte Ianina , Holzki Julia , May Tobias , Adler Barbara , Wirth Dagmar , Cicin-Sain Luka
Published: June 2013

Background

The MCMV major immediate early promoter/enhancer (MIEP) is a bidirectional promoter that drives the expression of the three immediate early viral genes, namely ie1, ie2 and ie3. The regulation of their expression is intensively studied, but still incompletely understood.

Methods

We constructed a reporter MCMV, (MCMV-MIEPr) expressing YFP and tdTomato under the control of the MIEP as proxies of ie1 and ie2, respectively. Moreover, we generated a liver sinusoidal endothelial cell line (LSEC-uniLT) where cycling is dependent on doxycycline. We used these novel tools to study the kinetics of MIEP-driven gene expression in the context of infection and at the single cell level by flow cytometry and by live imaging of proliferating and G0-arrested cells.

Results

MCMV replicated to higher titers in G0-arrested LSEC, and cycling cells showed less cytopathic effect or YFP and tdTomato expression at 5 days post infection. In the first 24 h post infection, however, there was no difference in MIEP activity in cycling or G0-arrested cells, although we could observe different profiles of MIEP gene expression in different cell types, like LSECs, fibroblasts or macrophages. We monitored infected LSEC-uniLT in G0 by time lapse microscopy over five days and noticed that most cells survived infection for at least 96 h, arguing that quick lysis of infected cells could not account for the spread of the virus. Interestingly, we noticed a strong correlation between the ratio of median YFP and tdTomato expression and length of survival of infected cells.

Conclusion

By means of our newly developed genetic tools, we showed that the expression pattern of MCMV IE1 and IE2 genes differs between macrophages, endothelial cells and fibroblasts. Substantial and cell-cycle independent differences in the ie1 and ie2 transcription could also be observed within individual cells of the same population, and marked ie2 gene expression was associated with longer survival of the infected cells.
Exercise to preserve beta cell function in recent-onset type 1 diabetes mellitus (EXTOD) - a study protocol for a pilot randomized controlled trial
Authors: Lascar Nadia , Kennedy Amy , Jackson Nikki , Daley Amanda , Dowswell George , Thompson Dylan , Stokes Keith , Greenfield Sheila , Holder Roger , Andrews Rob , Narendran Parth
Published: June 2013

Background

Exercise has a beta cell preserving effect in patients with type 2 diabetes. This benefit of exercise has not been examined in type 1 diabetes. Significant beta cell function is present at the time of diagnosis of type 1 diabetes and therefore studies of beta cell preservation are ideally conducted immediately after diagnosis.

Many of the variables required to design and power such a study are currently unknown. The aim of EXTOD is to obtain the information required to design a formal study of exercise and beta cell preservation in newly diagnosed patients with type 1 diabetes.

Methods

Barriers to exercise will initially be assessed in a qualitative study of newly diagnosed patients. Then, sixty newly diagnosed adult type 1 diabetes patients will be randomized to either conventional treatment or exercise, stratified on beta cell function and fitness. The exercise group will be encouraged to increase their level of activity to a minimum of 150 minutes of moderate to vigorous intensity exercise per week, aiming for 240 minutes per week of exercise for 12 months. Beta cell function will be measured by meal-stimulated C peptide. Primary outcomes are recruitment, adherence to exercise, loss to follow-up, and exercise levels in the non-intervention arm (contamination). The secondary outcome of the study is rate of loss of beta cell function.

Discussion

The outcomes of the EXTOD study will help define the barriers, uptake and benefits of exercise in adults newly diagnosed with type 1 diabetes. This information will enable design of a formal study to assess the effect of exercise on beta cell preservation in newly diagnosed patients with type 1 diabetes.

Trial registration

Current controlled trials ISRCTN91388505
RETRACTED ARTICLE: Cervical type AB thymoma (Mixed) tumour diagnosis in a mynah as a model to study human: clinicohistological, immunohistochemical and cytohistopathological study
Authors: Khaki Fariba , Javanbakht Javad , Sasani Farhang , Gharagozlou Mohammad Javad , Bahrami Alimohammad , Moslemzadeh Hemmat , Sheikhzadeh Reza
Published: June 2013

Thymoma is a primary mediastinal neoplasm arising from or exhibiting differentiation towards thymic epithelial cells, typically with the presence of non-neoplastic lymphocytes. A 13-year-old male Mynah bird (acridotheres tristis) was presented for evaluation of a 2.3 × 1.5 × 1.0 cm mass in the left ventrolateral cervical region. The clinical signs, radiology, cytohistopathology and immunohistochimy findings related to the thymoma are presented. These findings indicated that the tumor was a type AB thymoma according to the World Health Organization (WHO) and veterinary classification. Thymomas are rarely reported in avian species and this is the first report in a Mynah bird.

Virtual slides

The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1159525819982779.
Interactions between Asaia, Plasmodium and Anopheles: new insights into mosquito symbiosis and implications in Malaria Symbiotic Control
Authors: Capone Aida , Ricci Irene , Damiani Claudia , Mosca Michela , Rossi Paolo , Scuppa Patrizia , Crotti Elena , Epis Sara , Angeletti Mauro , Valzano Matteo , Sacchi Luciano , Bandi Claudio , Daffonchio Daniele , Mandrioli Mauro , Favia Guido
Published: June 2013

Background

Malaria represents one of the most devastating infectious diseases. The lack of an effective vaccine and the emergence of drug resistance make necessary the development of new effective control methods. The recent identification of bacteria of the genus Asaia, associated with larvae and adults of malaria vectors, designates them as suitable candidates for malaria paratransgenic control.

To better characterize the interactions between Asaia, Plasmodium and the mosquito immune system we performed an integrated experimental approach.

Methods

Quantitative PCR analysis of the amount of native Asaia was performed on individual Anopheles stephensi specimens. Mosquito infection was carried out with the strain PbGFPCON and the number of parasites in the midgut was counted by fluorescent microscopy.

The colonisation of infected mosquitoes was achieved using GFP or DsRed tagged-Asaia strains.

Reverse transcriptase-PCR analysis, growth and phagocytosis tests were performed using An. stephensi and Drosophila melanogaster haemocyte cultures and DsRed tagged-Asaia and Escherichia coli strains.

Results

Using quantitative PCR we have quantified the relative amount of Asaia in infected and uninfected mosquitoes, showing that the parasite does not interfere with bacterial blooming. The correlation curves have confirmed the active replication of Asaia, while at the same time, the intense decrease of the parasite.

The ‘in vitro’ immunological studies have shown that Asaia induces the expression of antimicrobial peptides, however, the growth curves in conditioned medium as well as a phagocytosis test, indicated that the bacterium is not an immune-target.

Using fluorescent strains of Asaia and Plasmodium we defined their co-localisation in the mosquito midgut and salivary glands.

Conclusions

We have provided important information about the relationship of Asaia with both Plasmodium and Anophele s. First, physiological changes in the midgut following an infected or uninfected blood meal do not negatively affect the residing Asaia population that seems to benefit from this condition. Second, Asaia can act as an immune-modulator activating antimicrobial peptide expression and seems to be adapted to the host immune response. Last, the co-localization of Asaia and Plasmodium highlights the possibility of reducing vectorial competence using bacterial recombinant strains capable of releasing anti-parasite molecules.
Expression of germline markers in three species of amphioxus supports a preformation mechanism of germ cell development in cephalochordates
Authors: Zhang Qiu-Jin , Luo Yi-Jyun , Wu Hui-Ru , Chen Yen-Ta , Yu Jr-Kai
Published: June 2013

Background

In a previous study, we showed that the cephalochordate amphioxusBranchiostoma floridaehas localized maternal transcripts of conserved germ cell markersVasaandNanosin its early embryos. These results provided strong evidence to support a preformation mechanism for primordial germ cell (PGC) development inB. floridae.

Results

In this study, we further characterize the expression ofB. floridaehomologs ofPiwiandTudor, which play important roles in germline development in diverse metazoan animals. We show that maternal mRNA of one of the identifiedPiwi-like homologs,Bf-Piwil1, also colocalizes withVasain the vegetal germ plasm and has zygotic expression in both the putative PGCs and the tail bud, suggesting it may function in both germline and somatic stem cells. More interestingly, one Tudor family gene,Bf-Tdrd7, is only expressed maternally and colocalizes withVasain germ plasm, suggesting that it may function exclusively in germ cell specification. To evaluate the conservation of the preformation mechanism among amphioxus species, we further analyzeVasa,Nanos,Piwil1, andTdrd7expression in two Asian amphioxus species,B. belcheriandB. japonicum. Their maternal transcripts all localize in similar patterns to those seen inB. floridae. In addition, we labeled putative PGCs with Vasa antibody to trace their dynamic distribution in developing larvae.

Conclusions

We identify additional germ plasm components in amphioxus and demonstrate the molecular distinction between the putative germline stem cells and somatic stem cells. Moreover, our results suggest that preformation may be a conserved mechanism for PGC specification amongBranchiostomaspecies. Our Vasa antibody staining results suggest that after the late neurula stage, amphioxus PGCs probably proliferate with the tail bud cells during posterior elongation and are deposited near the forming myomere boundaries. Subsequently, these PGCs would concentrate at the ventral tip of the myoseptal walls to form the gonad anlagen.
Porphyromonas gingivalis and the pathogenesis of rheumatoid arthritis: analysis of various compartments including the synovial tissue
Authors: Totaro Michele Ciro , Cattani Paola , Ria Francesco , Tolusso Barbara , Gremese Elisa , Fedele Anna Laura , D'Onghia Sara , Marchetti Simona , Sante Gabriele Di , Canestri Silvia , Ferraccioli Gianfranco
Published: June 2013

Introduction

We evaluated the presence of Porphyromonas gingivalis (Pg) DNA in the synovial tissue through synovial biopsy and in other compartments of rheumatoid arthritis (RA) patients in comparison with patients affected by other arthritides. Possible links with clinical, immunologic and genetic features were assessed.

Methods

Peripheral blood (PB), sub-gingival dental plaque, synovial fluid (SF) and synovial tissue samples were collected from 69 patients with active knee arthritis (32 with RA and 37 with other arthritides, of which 14 had undifferentiated peripheral inflammatory arthritis - UPIA). Demographic, clinical, laboratory and immunological data were recorded. The presence of Pg DNA was evaluated through PCR. The HLA-DR haplotype was assessed for 45 patients with RA and UPIA.

Results

No differences arose in the positivity for Pg DNA in the sub-gingival plaque, PB and SF samples between RA and the cohort of other arthritides. Full PB samples showed a higher positivity for Pg DNA than plasma samples (11.8% vs. 1.5%, P = 0.04). Patients with RA showed a higher positivity for Pg DNA in the synovial tissue compared to controls (33.3% vs. 5.9%, P <0.01). UPIA and RA patients carrying the HLA DRB1*04 allele showed a higher positivity for Pg DNA in the synovial tissue compared to patients negative for the allele (57.1% vs. 16.7%, P = 0.04). RA patients positive for Pg DNA in the sub-gingival plaque had a lower disease duration and a higher peripheral blood leucocyte and neutrophil count. The presence of Pg DNA did not influence disease activity, disease disability or positivity for autoantibodies.

Conclusions

The presence of Pg DNA in the synovial tissue of RA patients suggests a pathogenic role of the bacterium. The higher positivity of Pg DNA in full peripheral blood and synovial tissue samples compared to plasma and synovial fluid suggests a possible intracellular localization of Pg, in particular in patients positive for HLA-DR4.
Endogenous sex steroids in premenopausal women and risk of breast cancer: the ORDET cohort
Authors: Schernhammer Eva S , Sperati Francesca , Razavi Pedram , Agnoli Claudia , Sieri Sabina , Berrino Franco , Krogh Vittorio , Abbagnato Carlo Alberto , Grioni Sara , Blandino Giovanni , Schunemann Holger J , Muti Paola
Published: June 2013

Introduction

Previous studies showed that higher testosterone levels are associated with greater risk of breast cancer in premenopausal women, but the literature is scant and inconsistent.

Methods

In a prospective nested case-control study of 104 premenopausal women with incident breast cancer and 225 matched controls, all characterized by regular menstrual cycles throughout their lifetime, we measured the concentration of estradiol, total and free testosterone (FT), progesterone, sex hormone-binding globulin (SHBG), follicle-stimulating hormone (FSH), and luteinizing hormone (LH) in blood samples collected on days 20 through 24 of their cycles.

Results

In logistic regression models, the multivariate odds ratios (ORs) of invasive breast cancer for women in the highest tertile of circulating FT compared with the lowest was 2.43 (95% confidence interval (95% CI), 1.15 to 5.10; Ptrend = 0.03), whereas for total testosterone, the association had the same direction but was not statistically significant (OR, 1.27; 95% CI, 0.62 to 2.61; Ptrend = 0.51). Endogenous progesterone was not statistically associated with breast cancer (OR, 1.16; 95% CI, 0.60 to 2.27; Ptrend = 0.75), nor were the other considered hormones.

Conclusions

Consistent with previous prospective studies in premenopausal women and our own earlier investigation, we observed that higher levels of FT are positively associated with breast cancer risk in women with regular menstrual cycles throughout their lifetimes. No evidence of risk was found associated with the other endogenous sex steroids.
Analyzing the soybean transcriptome during autoregulation of mycorrhization identifies the transcription factors GmNF-YA1a/b as positive regulators of arbuscular mycorrhization
Authors: Schaarschmidt Sara , Gresshoff Peter M , Hause Bettina
Published: June 2013

Background

Similarly to the legume-rhizobia symbiosis, the arbuscular mycorrhiza interaction is controlled by autoregulation representing a feedback inhibition involving the CLAVATA1-like receptor kinase NARK in shoots. However, little is known about signals and targets down-stream of NARK. To find NARK-related transcriptional changes in mycorrhizal soybean (Glycine max) plants, we analyzed wild-type and two nark mutant lines interacting with the arbuscular mycorrhiza fungus Rhizophagus irregularis.

Results

Affymetrix GeneChip analysis of non-inoculated and partially inoculated plants in a split-root system identified genes with potential regulation by arbuscular mycorrhiza or NARK. Most transcriptional changes occur locally during arbuscular mycorrhiza symbiosis and independently of NARK. RT-qPCR analysis verified nine genes as NARK-dependently regulated. Most of them have lower expression in roots or shoots of wild type compared to nark mutants, including genes encoding the receptor kinase GmSIK1, proteins with putative function as ornithine acetyl transferase, and a DEAD box RNA helicase. A predicted annexin named GmAnnx1a is differentially regulated by NARK and arbuscular mycorrhiza in distinct plant organs. Two putative CCAAT-binding transcription factor genes named GmNF-YA1a and GmNF-YA1b are down-regulated NARK-dependently in non-infected roots of mycorrhizal wild-type plants and functional gene analysis confirmed a positive role for these genes in the development of an arbuscular mycorrhiza symbiosis.

Conclusions

Our results indicate GmNF-YA1a/b as positive regulators in arbuscular mycorrhiza establishment, whose expression is down-regulated by NARK in the autoregulated root tissue thereby diminishing subsequent infections. Genes regulated independently of arbuscular mycorrhization by NARK support an additional function of NARK in symbioses-independent mechanisms.
Novel approach for simulating the elastic properties of porous rocks including the critical porosity phenomena
Authors: Markov Mikhail , Kazatchenko Elena , Mousatov Aleksandr , Pervago Evgeny
Published: June 2013

We tested an approach for calculating the effective elastic properties of rocks taking into account their critical porosity (the percolation threshold). The concept of critical porosity considers that when the porosity of a rock exceeds the critical value, the shear modulus of the rock tends to zero, making it lose its rigidity and the rock falls apart. The classical homogenization schemes do not describe the mechanical properties of a rock near the critical porosity. The approach proposed here is based on the generalized differential effective medium (GDEM) method. We introduce a model of porous elastic media composed of an elastic solid host containing ellipsoidal inclusions of two types. Inclusions of the first type (phase 1) represent pores, and inclusions of the second type (phase 2) contain elastic solid material described by the same elastic properties as the host (phase 0). In this model, with an increase in porosity, the concentration of the host decreased, and it tended to zero near the critical porosity. The model was used for simulation of rock elastic moduli. We compared the modeling results for elastic moduli and acoustic velocities with the experimental data and empirical petrophysical equations. The comparison showed that the GDEM model describes the elastic properties behavior in a wide range of porosity up to the critical value.
Prevalence and Predictors of the Short-Term Trajectory of Anxiety and Depression in the First Year After a Cancer Diagnosis: A Population-Based Longitudinal Study
Authors: Boyes Allison W. , Girgis Afaf , D'Este Catherine A. , Zucca Alison C. , Lecathelinais Christophe , Carey Mariko L.
Published: June 2013

Purpose

Few studies have examined psychological adjustment for cancer survivors in late treatment and early survivorship stages. Our study investigated the prevalence and short-term trajectories of anxiety, depression, and comorbid anxiety-depression among adult cancer survivors, and identified the individual, disease, health behavior, psychological, and social predictors of chronic and late psychological morbidity.

Methods

A heterogeneous sample of adult cancer survivors was recruited from two state-based cancer registries. A total of 1,154 survivors completed self-report questionnaires at 6 (Time 1) and 12 months (Time 2) postdiagnosis. Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale with cases identified by a subscale cutoff score ≥ 8. Logistic regression analyses identified Time 1 characteristics associated with anxiety and/or depression at Time 2.

Results

The point prevalence of anxiety (Time 1, 22%; Time 2, 21%), depression (13% at both timepoints) and comorbid anxiety-depression (9% at both timepoints) was similar at 6 and 12 months postdiagnosis. The most prevalent Time 1 to Time 2 trajectory was noncase for anxiety (70%), depression (82%), and comorbid anxiety-depression (87%). While psychological morbidity at Time 1 was the strongest predictor of psychological morbidity at Time 2, being diagnosed with lung cancer and health risk behaviors (smoking, insufficient physical activity) were also strong predictors.

Conclusion

Targeted psychological screening of vulnerable survivors and early intervention may prevent the onset and/or reduce the severity of psychological morbidity in early survivorship. Trials of risk reduction interventions targeting psychological functioning and health risk behaviors seem warranted.
Correlation Between Financial Relationships With Commercial Interests and Research Prominence at an Oncology Meeting
Authors: Moy Beverly , Bradbury Angela R. , Helft Paul R. , Egleston Brian L. , Sheikh-Salah Moktar , Peppercorn Jeffrey
Published: June 2013

Purpose

Little is known about the effects of financial relationships between biomedical researchers and industry (financial conflicts of interest [FCOIs]) on research prominence. We examined the prevalence of FCOIs in oncology and associations between FCOIs and research prominence among abstracts presented at American Society of Clinical Oncology (ASCO) annual meetings.

Methods

We analyzed 20,718 abstracts presented at ASCO meetings in 2006 and 2008 to 2011. Measures included the following: financial relationships, peer review score (PRS), and meeting placement prominence (descending order of prominence: plenary session, clinical science symposium, oral presentation, poster discussion, general posters, and publish only).

Results

Of 20,718 abstracts, 36% reported at least one author with an FCOI. The proportion of abstracts with any FCOI increased from 33% in 2006 to 38% in 2011 (P < .001). Abstracts with FCOIs had significantly higher meeting prominence compared with publish only and general poster abstracts. The odds ratios compared with general posters were 7.3 for plenary session, 2.2 for clinical science symposium, 1.9 for oral presentation, and 1.7 for poster discussion (P < .001). Abstracts with FCOIs had significantly better PRSs compared with those without FCOIs. For all abstracts, PRS was 2.76 (95% CI, 2.75 to 2.77) with FCOIs compared with 3.01 (95% CI, 3.001 to 3.02) without FCOIs (P < .001). Omitting publish-only abstracts, PRS was 2.62 (95% CI, 2.61 to 2.63) with FCOIs compared with 2.73 without FCOIs (95% CI, 2.71 to 2.73).

Conclusion

Abstracts with FCOIs had more prominent meeting placement and better PRSs. FCOIs were reported more frequently by year, suggesting an increasing influence of industry on cancer research, greater disclosure, or both.
Use of Allogeneic Hematopoietic Stem-Cell Transplantation Based on Minimal Residual Disease Response Improves Outcomes for Children With Relapsed Acute Lymphoblastic Leukemia in the Intermediate-Risk Group
Authors: Eckert Cornelia , Henze Günter , Seeger Karlheinz , Hagedorn Nikola , Mann Georg , Panzer-Grümayer Renate , Peters Christina , Klingebiel Thomas , Borkhardt Arndt , Schrappe Martin , Schrauder André , Escherich Gabriele , Sramkova Lucie , Niggli Felix , Hitzler Johann , von Stackelberg Arend
Published: June 2013

Purpose

In children with intermediate risk of relapse of acute lymphoblastic leukemia (ALL), it is essential to identify patients in need of treatment intensification. We hypothesized that the prognosis of patients with unsatisfactory reduction of minimal residual disease (MRD) can be improved by allogeneic hematopoietic stem-cell transplantation (HSCT).

Patients and Methods

In the Acute Lymphoblastic Leukemia–Relapse Study of the Berlin-Frankfurt-Münster Group (ALL-REZ BFM) 2002, patients with an MRD level of ≥ 10−3 (n = 99) at the end of induction therapy were allocated to HSCT, whereas those with an MRD level less than 10−3 (n = 109) continued to receive chemotherapy. MRD was quantified by real-time polymerase chain reaction for clone-specific T-cell receptor/immunoglobulin gene rearrangements.

Results

The probability of event-free survival for patients with MRD ≥ 10−3 was 64% ± 5% in ALL-REZ BFM 2002 compared with 18% ± 7% in the predecessor study ALL-REZ BFM P95/96 (P < .001). This was mainly achieved by reducing the cumulative incidence of subsequent relapse (CIR) at 8 years from 59% ± 9% to 27% ± 5% (P < .001). The favorable prognosis of patients with MRD less than 10−3 could be confirmed in those with a late combined or isolated bone marrow B-cell precursor (BCP) –ALL relapse (CIR, 20% ± 5%), whereas patients with an early combined BCP-ALL relapse had an unfavorable outcome (CIR, 63% ± 13%; P < .001).

Conclusion

Allogeneic HSCT markedly improved the prognosis of patients with intermediate risk of relapse of ALL and unsatisfactory MRD response. As a result, outcomes in this group approximated those of patients with favorable MRD response. Patients with early combined relapse require treatment intensification even in case of favorable MRD response, demonstrating the prognostic impact of time to relapse.
Chemotherapy-Induced Neuropathy and Its Association With Quality of Life Among 2- to 11-Year Colorectal Cancer Survivors: Results From the Population-Based PROFILES Registry
Authors: Mols Floortje , Beijers Tonneke , Lemmens Valery , van den Hurk Corina J. , Vreugdenhil Gerard , van de Poll-Franse Lonneke V.
Published: June 2013

Purpose

To gain insight into the prevalence and severity of chemotherapy-induced neuropathy and its influence on health-related quality of life (HRQOL) in a population-based sample of colorectal cancer (CRC) survivors 2 to 11 years after diagnosis.

Methods

All alive individuals diagnosed with CRC between 2000 and 2009 as registered by the Dutch population-based Eindhoven Cancer Registry were eligible for participation. Eighty-three percent (n = 1,643) of patients filled out the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ) C30 and the EORTC QLQ Chemotherapy-Induced Peripheral Neuropathy 20.

Results

The five neuropathy subscale–related symptoms that bothered patients with CRC the most during the past week were erectile problems (42% of men), trouble hearing (11%), trouble opening jars or bottles (11%), tingling toes/feet (10%), and trouble walking stairs or standing up (9%). Additionally, patients who received oxaliplatin more often reported tingling (29% v 8%; P = .001), numbness (17% v 5%; P = .005), and aching or burning pain (13% v 6%; P = .03) in toes/feet compared with those not treated with chemotherapy. They also more often reported tingling toes/feet (29% v 14%; P = .0127) compared with those treated with chemotherapy without oxaliplatin. Those with many neuropathy symptoms (eg, upper 10%) reported statistically significant and clinically relevant worse HRQOL scores on all EORTC QLQ-C30 subscales (all P < .01).

Conclusion

Two to 11 years after diagnosis of CRC, neuropathy-related symptoms are still reported, especially sensory symptoms in the lower extremities among those treated with oxaliplatin. Because neuropathy symptoms have a negative influence on HRQOL, these should be screened for and alleviated. Future studies should focus on prevention and relief of chemotherapy-induced neuropathy.
Increased postsynaptic density protein-95 expression in the frontal cortex of aged cognitively impaired rats
Authors: Preissmann Delphine , Leuba Geneviève , Savary Christine , Vernay André , Kraftsik Rudolf , Riederer IrèNe Monika , Schenk Françoise , Riederer Béat Michel , Savioz Armand
Published: June 2013

In the present work we studied synaptic protein concentrations in relation to behavioral performance. Long-Evans rats, aged 22-23 months, were classified for individual expression of place memory in the Morris water maze, in reference to young adults. Two main subgroups of aged rats were established: the Aged cognitively Unimpaired (AU) had search accuracy within the range (percent of time in training sector within mean+2 SEM) of young rats and the Aged cognitively Impaired (AI) rats had search accuracy below this range. Samples from the hippocampus and frontal cortex of all the AI, AU and young rats were analyzed for the expression of postsynaptic protein PSD-95 by Image J analysis of immunohistochemical data and by Western blots. PSD-95 expression was unchanged in the hippocampus, but, together with synaptophysin, was significantly increased in the frontal cortex of the AI rats. A significant correlation between individual accuracy (time spent in the training zone) and PSD-95 expression was observed in the aged group. No significant effect of age or PSD-95 expression was observed in the learning of a new position. All together, these data suggest that increased expression of PSD-95 in the frontal cortex of aged rats co-occurs with cognitive impairment that might be linked to functional alterations extending over frontal networks.
The Maximum Multiflow Problems with Bounded Fractionality
Authors: Hirai Hiroshi
Published: June 2013

We consider the weighted maximum multiflow problem with respect to a terminal weight. We show that if the dimension of the tight span associated with the weight is at most 2, then this problem has a 1/12-integral optimal multiflow for every Eulerian supply graph. This result solves a weighted generalization of Karzanov's conjecture for classifying commodity graphs with finite fractionality. In addition, our proof technique proves the existence of an integral or half-integrality optimal multiflow for a large class of multiflow maximization problems, and it gives a polynomial time algorithm.
Blow-up analysis of stationary two-valued functions
Authors: Bouafia Philippe
Published: June 2013

We consider two-valued real functions of two variables which are stationary with respect to both domain and range transformations. We prove their local Lipschitz continuity and use it to establish strong convergence in W1,2
to their unique blow-up at any point. The main theorem of this paper states that the branch set of any such function consists of finitely many real analytic curves meeting at nod points with equal angles. We also provide an example showing that stationarity with respect to domain transformations only does not imply continuity.
The Lao Động Party, Culture and the Campaign against “Modern Revisionism”
Authors: Grossheim Martin
Published: June 2013

The article tries to make a contribution to the reassessment of the Second Indochina War and of the significance of culture in the Democratic Republic of Vietnam before and during the conflict. By making use of as-yet untapped sources from the German Democratic Republic archives, DRV periodicals and interviews with Vietnamese informants, I highlight the cultural dimension of the campaign against modern revisionism in 1964, and thus present the Lao Động leadership as an actor on the cultural front of the Vietnam conflict. Moreover, I show that even after the beginning of the war an anti-revisionist undercurrent in cultural policy persisted and that the anti-revisionist campaign in 1964 was closely related to the Anti-Party Revisionist Affair in 1967. The article also sheds light on the impact of the Sino-Soviet conflict on North Vietnam.