bluuebunny/crossref_metadata_2025 huggingface dataset:
Earnings Management in the Spanish Hotel Industry
Authors: Esteban Laura Parte , Jesús Such Devesa María
Published: April 2011

An analysis of more than 1,990 Spanish hotel firms, large and small, over a period of five years found evidence that operating executives are not indifferent to earnings outcomes. As found in previous studies of other industries in other countries, the distribution of earnings outcomes shows a discontinuity near zero, such that one finds abnormally large numbers of observations for the interval immediately above zero and abnormally small numbers of observations immediately below zero. While the motivation of managers to avoid small losses remains open to speculation, it is clear that managers have at least some ability to manipulate profit and earnings figures. Although possible changes in stock values is one likely motivation for earnings manipulation, only two of the firms in this study are publicly traded (albeit their presence may skew results because of size). Explanations for this anomaly other than earnings manipulation do not seem to apply (such as company size or measurement error).
Prognostic significance of treatment response in CML in view of current recommendations for treatment and monitoring
Authors: von Bubnoff Nikolas
Published: April 2011

The use of small-molecule kinase inhibitors has redefined the management of cancer. Chronic myelogenous leukaemia (CML) has become the paradigm for targeted cancer treatment. Imatinib has become the gold standard in the treatment of CML with excellent and durable responses and minimal side effects. Molecular diagnostics constitute an integral part of the routine monitoring. Results of cytogenetic analysis and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) indicate suboptimal response or treatment failure and guide treatment. New Abl kinase inhibitors such as nilotinib or dasatinib are options after the failure of or intolerance to imatinib, and both are available for first-line treatment of newly diagnosed CML. This review focuses on the prognostic significance of achieving a response at specific time points in patients with CML treated with imatinib, nilotinib or dasatinib in view of available data and current treatment recommendations.
Salvage therapy for relapsed or refractory acute myeloid leukemia
Authors: Mangan James K. , Luger Selina M.
Published: April 2011

There are a significant number of patients diagnosed with acute leukemia who either fail to achieve remission or who relapse thereafter. Challenges in treating this patient population include accurately assessing prognosis of disease and whether remission can be achieved; assessing the ability of patients to tolerate aggressive salvage therapies; choosing a salvage therapy that is most likely to succeed; and identifying suitable patients for hematopoietic stem cell transplantation. Despite the development of a variety of new investigational therapies, relapsed or refractory acute myeloid leukemia remains a difficult clinical problem. Clinicians will need to consider all currently available approaches, including cytotoxic chemotherapy, targeted agents, and allogeneic stem cell transplantation, to optimize outcomes.
Merkel cell polyomavirus DNA sequences in the buffy coats of healthy blood donors
Authors: Pancaldi Cecilia , Corazzari Valentina , Maniero Stefania , Mazzoni Elisa , Comar Manola , Martini Fernanda , Tognon Mauro
Published: April 2011

Merkel cell polyomavirus (MCPyV), a DNA tumor virus, has been found to be associated with Merkel cell carcinoma and chronic lymphocytic leukemia. MCPyV sequences have also been detected in various normal tissues in tumor-affected patients. Immunologic studies have detected MCPyV antibodies in as many as 80% of healthy blood donors. This high seroprevalence suggests that MCPyV infection is widespread in humans. In our study, buffy coats, which were examined for MCPyV DNA Tag sequences, showed a prevalence of 22%. Viral DNA load was revealed in blood samples from 10 to 100 molecules/100 000 cells. DNA sequencing confirmed that polymerase chain reaction amplicons belong to the MCPyV strain, MKL-1. To interpret the putative role of MCPyV in chronic lymphocytic leukemia, we may infer that, during a long period of viral persistence in blood cells, this DNA tumor virus may generate mutants, which are able to participate as cofactors in the multistep process of cell transformation.
Protein O-fucosyltransferase 1 (Pofut1) regulates lymphoid and myeloid homeostasis through modulation of Notch receptor ligand interactions
Authors: Yao David , Huang Yuanshuai , Huang Xiaoran , Wang Weihuan , Yan Quanjian , Wei Lebing , Xin Wei , Gerson Stanton , Stanley Pamela , Lowe John B. , Zhou Lan
Published: April 2011

Notch signaling is essential for lymphocyte development and is also implicated in myelopoiesis. Notch receptors are modified by O-fucosylation catalyzed by protein O-fucosyltransferase 1 (Pofut1). Fringe enzymes add N-acetylglucosamine to O-fucose and modify Notch signaling by altering the sensitivity of Notch receptors to Notch ligands. To address physiologic functions in hematopoiesis of Notch modified by O-fucose glycans, we examined mice with inducible inactivation of Pofut1 using Mx-Cre. These mice exhibited a reduction in T lymphopoiesis and in the production of marginal-zone B cells, in addition to myeloid hyperplasia. Restoration of Notch1 signaling rescued T lymphopoiesis and the marrow myeloid hyperplasia. After marrow transfer, both cell-autonomous and environmental cues were found to contribute to lymphoid developmental defects and myeloid hyperplasia in Pofut1-deleted mice. Although Pofut1 deficiency slightly decreased cell surface expression of Notch1 and Notch2, it completely abrogated the binding of Notch receptors with Delta-like Notch ligands and suppressed downstream Notch target activation, indicating that O-fucose glycans are critical for efficient Notch-ligand binding that transduce Notch signals. The combined data support a key role for the O-fucose glycans generated by Pofut1 in Notch regulation of hematopoietic homeostasis through modulation of Notch-ligand interactions.
Impact of immune modulation with anti–T-cell antibodies on the outcome of reduced-intensity allogeneic hematopoietic stem cell transplantation for hematologic malignancies
Authors: Soiffer Robert J. , LeRademacher Jennifer , Ho Vincent , Kan Fangyu , Artz Andrew , Champlin Richard E. , Devine Steven , Isola Luis , Lazarus Hillard M. , Marks David I. , Porter David L. , Waller Edmund K. , Horowitz Mary M. , Eapen Mary
Published: April 2011

The success of reduced intensity conditioning (RIC) transplantation is largely dependent on alloimmune effects. It is critical to determine whether immune modulation with anti–T-cell antibody infusion abrogates the therapeutic benefits of transplantation. We examined 1676 adults undergoing RIC transplantation for hematologic malignancies. All patients received alkylating agent plus fludarabine; 792 received allografts from a human leukocyte antigen-matched sibling, 884 from a 7 or 8 of 8 HLA-matched unrelated donor. Using Cox regression, outcomes after in vivo T-cell depletion (n = 584 antithymocyte globulin [ATG]; n = 213 alemtuzumab) were compared with T cell– replete (n = 879) transplantation. Grade 2 to 4 acute GVHD was lower with alemtuzumab compared with ATG or T cell– replete regimens (19% vs 38% vs 40%, P < .0001) and chronic GVHD, lower with alemtuzumab, and ATG regimens compared with T-replete approaches (24% vs 40% vs 52%, P < .0001). However, relapse was more frequent with alemtuzumab and ATG compared with T cell–replete regimens (49%, 51%, and 38%, respectively, P < .001). Disease-free survival was lower with alemtuzumab and ATG compared with T cell–replete regimens (30%, 25%, and 39%, respectively, P < .001). Corresponding probabilities of overall survival were 50%, 38%, and 46% (P = .008). These data suggest adopting a cautious approach to routine use of in vivo T-cell depletion with RIC regimens.
Comparative analysis of mitochondrial genomes between a wheat K-type cytoplasmic male sterility (CMS) line and its maintainer line
Authors: Liu Huitao , Cui Peng , Zhan Kehui , Lin Qiang , Zhuo Guoyin , Guo Xiaoli , Ding Feng , Yang Wenlong , Liu Dongcheng , Hu Songnian , Yu Jun , Zhang Aimin
Published: April 2011

Background

Plant mitochondria, semiautonomous organelles that function as manufacturers of cellular ATP, have their own genome that has a slow rate of evolution and rapid rearrangement. Cytoplasmic male sterility (CMS), a common phenotype in higher plants, is closely associated with rearrangements in mitochondrial DNA (mtDNA), and is widely used to produce F1 hybrid seeds in a variety of valuable crop species. Novel chimeric genes deduced from mtDNA rearrangements causing CMS have been identified in several plants, such as rice, sunflower, pepper, and rapeseed, but there are very few reports about mtDNA rearrangements in wheat. In the present work, we describe the mitochondrial genome of a wheat K-type CMS line and compare it with its maintainer line.

Results

The complete mtDNA sequence of a wheat K-type (with cytoplasm of Aegilops kotschyi) CMS line, Ks3, was assembled into a master circle (MC) molecule of 647,559 bp and found to harbor 34 known protein-coding genes, three rRNAs (18 S, 26 S, and 5 S rRNAs), and 16 different tRNAs. Compared to our previously published sequence of a K-type maintainer line, Km3, we detected Ks3-specific mtDNA (> 100 bp, 11.38%) and repeats (> 100 bp, 29 units) as well as genes that are unique to each line: rpl5 was missing in Ks3 and trnH was absent from Km3. We also defined 32 single nucleotide polymorphisms (SNPs) in 13 protein-coding, albeit functionally irrelevant, genes, and predicted 22 unique ORFs in Ks3, representing potential candidates for K-type CMS. All these sequence variations are candidates for involvement in CMS. A comparative analysis of the mtDNA of several angiosperms, including those from Ks3, Km3, rice, maize, Arabidopsis thaliana, and rapeseed, showed that non-coding sequences of higher plants had mostly divergent multiple reorganizations during the mtDNA evolution of higher plants.

Conclusion

The complete mitochondrial genome of the wheat K-type CMS line Ks3 is very different from that of its maintainer line Km3, especially in non-coding sequences. Sequence rearrangement has produced novel chimeric ORFs, which may be candidate genes for CMS. Comparative analysis of several angiosperm mtDNAs indicated that non-coding sequences are the most frequently reorganized during mtDNA evolution in higher plants.
Molecular cloning and expression of bovine nucleoplasmin 2 (NPM2): a maternal effect gene regulated by miR-181a
Authors: Lingenfelter Brandon M , Tripurani Swamy K , Tejomurtula Jyothsna , Smith George W , Yao Jianbo
Published: April 2011

Background

Nucleoplasmin 2 (NPM2) is an oocyte-specific nuclear protein essential for nuclear and nucleolar organization and early embryonic development. The aims of this study were to clone the bovine NPM2 gene, determine its temporal expression during oocyte development and early embryogenesis, and evaluate the potential role of miRNA-181a in regulation of its expression.

Methods

A 329 bp cDNA fragment was amplified from bovine fetal ovary using primers designed based on the conserved regions of the human and mouse NPM2 cDNA sequences. RACE experiments were performed to obtain the 5' and 3' ends of the bovine NPM2 cDNA. Real time PCR and Western blot analysis were used to examine the expression of bovine NPM2 in oocytes and early embryos. Co-expression of bovine NPM2 and miRNA-181a in Hela cells was performed to determine if expression of bovine NPM2 is regulated by miRNA-181a.

Results

The bovine NPM2 cDNA is 851 bp in length encoding a protein of 200 amino acids. The protein contains the conserved bipartite nuclear localization sequence and shows 53% and 62% identity with mouse and human NPM2, respectively. Expression of bovine NPM2 mRNA is restricted to ovaries. NPM2 mRNA is abundant in GV and MII stage oocytes, decreases in early cleavage stage embryos, and barely detectable in morula and blastocyst stage embryos. Similarly, expression of NPM2 protein is high in oocytes and early embryos but extremely low in blastocysts. The abundance of NPM2 mRNA is significantly lower in oocytes isolated from persistent versus growing dominant follicles (P < 0.05). A miR-181a binding site in the 3'UTR of the NPM2 transcript was identified. Transfection experiments showed that bovine NPM2 protein expression is reduced in Hela cells expressing miR-181a compared to control cells without miR-181a, indicating that translation of NPM2 is repressed by miR-181a.

Conclusions

Our data suggest that expression of bovine NPM2 is temporally regulated during early embryogenesis and miR-181a may play a role in its regulation.
Nanoscale structural characterization of epitaxial graphene grown on off-axis 4H-SiC (0001)
Authors: Vecchio Carmelo , Sonde Sushant , Bongiorno Corrado , Rambach Martin , Yakimova Rositza , Raineri Vito , Giannazzo Filippo
Published: April 2011

In this work, we present a nanometer resolution structural characterization of epitaxial graphene (EG) layers grown on 4H-SiC (0001) 8° off-axis, by annealing in inert gas ambient (Ar) in a wide temperature range (Tgr from 1600 to 2000°C). For all the considered growth temperatures, few layers of graphene (FLG) conformally covering the 100 to 200-nm wide terraces of the SiC surface have been observed by high-resolution cross-sectional transmission electron microscopy (HR-XTEM). Tapping mode atomic force microscopy (t-AFM) showed the formation of wrinkles with approx. 1 to 2 nm height and 10 to 20 nm width in the FLG film, as a result of the release of the compressive strain, which builds up in FLG during the sample cooling due to the thermal expansion coefficients mismatch between graphene and SiC. While for EG grown on on-axis 4H-SiC an isotropic mesh-like network of wrinkles interconnected into nodes is commonly reported, in the present case of a vicinal SiC surface, wrinkles are preferentially oriented in the direction perpendicular to the step edges of the SiC terraces. For each Tgr, the number of graphene layers was determined on very small sample areas by HR-XTEM and, with high statistics and on several sample positions, by measuring the depth of selectively etched trenches in FLG by t-AFM. Both the density of wrinkles and the number of graphene layers are found to increase almost linearly as a function of the growth temperature in the considered temperature range.
ZnSe nanotrenches: formation mechanism and its role as a 1D template
Authors: Wang Gan , Lok Shu Kin , Sou Iam Keong
Published: April 2011

High-resolution transmission electron microscopy was used to characterize the microstructures of ZnSe nanotrenches induced by mobile Au-alloy droplets. The contact side interfaces between the AuZnδ alloy droplets and the ZnSe as well as the four side walls of the resulting <011>-oriented nanotrenches were found all belong to the {111} plane family, with the front and back walls being the {111}A planes while the other two side walls being the {111}B planes. These findings offer a deeper understanding on the formation mechanism of the nanotrenches. Pure Au nanodashes were formed upon further deposition of Au on the nanotrenches.

PACS: 61.46.Df, Structure of nanocrystals and nanoparticles. 81.16.Rf, Micro and nanoscale pattern formation. 68.37.Og, High resolution transmission electron microscopy.
A common set of developmental miRNAs are upregulated in Nicotiana benthamiana by diverse begomoviruses
Authors: Amin Imran , Patil Basavaprabhu L , Briddon Rob W , Mansoor Shahid , Fauquet Claude M
Published: April 2011

Background

Begomoviruses are single-stranded DNA viruses that cause economically important diseases of many crops throughout the world and induce symptoms in plants, including enations, leaf curling and stunting, that resemble developmental abnormalities. MicroRNAs (miRNAs) are small endogenous RNAs that are involved in a variety of activities, including plant development, signal transduction and protein degradation, as well as response to environmental stress, and pathogen invasion.

Results

The present study was aimed at understanding the deregulation of miRNAs upon begomovirus infection. Four distinct begomoviruses African cassava mosaic virus (ACMV), Cabbage leaf curl virus (CbLCuV), Tomato yellow leaf curl virus (TYLCV) and Cotton leaf curl Multan virus/Cotton leaf curl betasatellite (CLCuV/CLCuMB), were used in this study. Ten developmental miRNA were studied. N. benthamiana plants were inoculated with begomoviruses and their miRNA profiles were analysed by northern blotting using specific miRNA probes. The levels of most developmental miRNA were increased in N. benthamiana by TYLCV, CLCuMV/CLCuMB and CbLCuV infection with a common pattern despite their diverse genomic components. However, the increased levels of individual miRNAs differed for distinct begomoviruses, reflecting differences in severity of symptom phenotypes. Some of these miRNA were also common to ACMV infection.

Conclusions

Our results have shown a common pattern of miRNAs accumulation upon begomovirus infection. It was found that begomoviruses generally increase the accumulation of miRNA and thus result in the decreased translation of genes involved in the development of plants. Identification of common miRNAs that are deregulated upon begomovirus infection may provide novel targets for control strategies aimed at developing broad-spectrum resistance.
Analysis of codon usage and nucleotide composition bias in polioviruses
Authors: Zhang Jie , Wang Meng , Liu Wen-qian , Zhou Jian-hua , Chen Hao-tai , Ma Li-na , Ding Yao-zhong , Gu Yuan-xing , Liu Yong-sheng
Published: April 2011

Background

Poliovirus, the causative agent of poliomyelitis, is a human enterovirus and a member of the family of Picornaviridae and among the most rapidly evolving viruses known. Analysis of codon usage can reveal much about the molecular evolution of the viruses. However, little information about synonymous codon usage pattern of polioviruses genome has been acquired to date.

Methods

The relative synonymous codon usage (RSCU) values, effective number of codon (ENC) values, nucleotide contents and dinucleotides were investigated and a comparative analysis of codon usage pattern for open reading frames (ORFs) among 48 polioviruses isolates including 31 of genotype 1, 13 of genotype 2 and 4 of genotype 3.

Results

The result shows that the overall extent of codon usage bias in poliovirus samples is low (mean ENC = 53.754 > 40). The general correlation between base composition and codon usage bias suggests that mutational pressure rather than natural selection is the main factor that determines the codon usage bias in those polioviruses. Depending on the RSCU data, it was found that there was a significant variation in bias of codon usage among three genotypes. Geographic factor also has some effect on the codon usage pattern (exists in the genotype-1 of polioviruses). No significant effect in gene length or vaccine derived polioviruses (DVPVs), wild viruses and live attenuated virus was observed on the variations of synonymous codon usage in the virus genes. The relative abundance of dinucleotide (CpG) in the ORFs of polioviruses are far below expected values especially in DVPVs and attenuated virus of polioviruses genotype 1.

Conclusion

The information from this study may not only have theoretical value in understanding poliovirus evolution, especially for DVPVs genotype 1, but also have potential value for the development of poliovirus vaccines.
The role of human papillomavirus in the pathogenesis of head & neck squamous cell carcinoma: an overview
Authors: Pannone Giuseppe , Santoro Angela , Papagerakis Silvana , Lo Muzio Lorenzo , De Rosa Gaetano , Bufo Pantaleo
Published: April 2011

Cancer statistics report an increased incidence of OSCC and OPSCC around the world. Though improvements in screening and early diagnosis have dramatically reduced the incidence of this neoplasm in recent years, the 5-year-disease-free survival, is still poor, specially for oropharyngeal cancer, despite the great scientific and financial efforts. Recently, several papers showed that HPV may be involved at least in the pathogenesis of a subgroup of oral and cervical SCC, leading to distinct molecular characteristics compared with HPV-negative ones. Nevertheless, OPSCCs associated with HPV infection seem to show a better prognosis and affect younger patients (< 40 yrs.), especially females. Therefore, there is the need to properly assess oropharyngeal SCC subgroups: 1) not HPV associated/classic oral SCC: less responsive to anticancer drugs: needs novel post-surgical treatment; 2) HPV associated/oral SCC: needs several management options and suitable "target" therapy against the virus, and/or immune-stimulating therapy. Further issues are: 1) the disclosure of putative targets for more efficient molecular therapy, which may work as cervical cancer post-surgical treatment, in anticipation of the effects of "global prevention" performed by WHO anti-HPV vaccination programs; 2) careful identification of precancerous lesions in both sites; dysplasia is currently treated by excisional or ablative procedures, which don't consider the concept of field carcinogenesis. In fact, it is probable that near or far from an excised precancerous lesion new foci of cell transformation may exist, which are not yet macroscopically evident, but, if detected, would put the patient into a high risk subgroup.

Comparing findings reported in the recent literature, the data of this state of the art about HPV might add useful informations concerning oropharyngeal carcinogenesis. Moreover, our review would be useful in order to define novel perspectives of treatment choice for Head & Neck cancer patients, by combining well known chemotherapeutical drugs with new molecular "target" therapy.
The highly accurate anteriolateral portal for injecting the knee
Authors: Chavez-Chiang Colbert E , Sibbitt Wilmer L , Band Philip A , Chavez-Chiang Natalia R , DeLea Suzanne L , Bankhurst Arthur D
Published: April 2011

Background

The extended knee lateral midpatellar portal for intraarticular injection of the knee is accurate but is not practical for all patients. We hypothesized that a modified anteriolateral portal where the synovial membrane of the medial femoral condyle is the target would be highly accurate and effective for intraarticular injection of the knee.

Methods

83 subjects with non-effusive osteoarthritis of the knee were randomized to intraarticular injection using the modified anteriolateral bent knee versus the standard lateral midpatellar portal. After hydrodissection of the synovial membrane with lidocaine using a mechanical syringe (reciprocating procedure device), 80 mg of triamcinolone acetonide were injected into the knee with a 2.0-in (5.1-cm) 21-gauge needle. Baseline pain, procedural pain, and pain at outcome (2 weeks and 6 months) were determined with the 10 cm Visual Analogue Pain Score (VAS). The accuracy of needle placement was determined by sonographic imaging.

Results

The lateral midpatellar and anteriolateral portals resulted in equivalent clinical outcomes including procedural pain (VAS midpatellar: 4.6 ± 3.1 cm; anteriolateral: 4.8 ± 3.2 cm; p = 0.77), pain at outcome (VAS midpatellar: 2.6 ± 2.8 cm; anteriolateral: 1.7 ± 2.3 cm; p = 0.11), responders (midpatellar: 45%; anteriolateral: 56%; p = 0.33), duration of therapeutic effect (midpatellar: 3.9 ± 2.4 months; anteriolateral: 4.1 ± 2.2 months; p = 0.69), and time to next procedure (midpatellar: 7.3 ± 3.3 months; anteriolateral: 7.7 ± 3.7 months; p = 0.71). The anteriolateral portal was 97% accurate by real-time ultrasound imaging.

Conclusion

The modified anteriolateral bent knee portal is an effective, accurate, and equivalent alternative to the standard lateral midpatellar portal for intraarticular injection of the knee.

Trial Registration

ClinicalTrials.gov:NCT00651625
Management of cardiac fibrosis in diabetic rats; the role of peroxisome proliferator activated receptor gamma (PPAR-gamma) and calcium channel blockers (CCBs)
Authors: Mohamad Hoda E , Askar Mervat E , Hafez Mohamed M
Published: April 2011

Background

Diabetes mellitus (DM) and hypertension (HTN) are accused of being responsible for the development of the cardiac fibrosis due to severe cardiomyopathy.

Methods

Blood glucose (BG) test was carried out, lipid concentrations, tumor necrosis factor alpha (TNF-α), transforming growth factor beta (TGF-β), matrix metalloproteinase (MMP-2), collagen-I and collagen-III were measured in maleAlbinorats weighing 179-219 g. The rats were divided into five groups, kept on either control diet or high fat diet (HFD), and simultaneously treated with rosiglitazone (PPAR-gamma) only for one group with 3 mg/kg/day via oral route for 30 days, and with rosiglitazone and felodipine combination for another group with 3 mg/kg/day and 5 mg/kg/day, respectively via oral route for 30 days.

Results

Diabetic hypertensive (DH) rats which fed on a HFD, injected with streptozotocin (STZ) (i.p.) and obstruction for its right kidney was occurred develop hyperglycemia, hypertension, cardiac fibrosis, hypertriglyceridemia, hypercholesterolemia, increased TNF-α, increased TGF-β, decreased MMP-2, increased collagen-I and increased collagen-III, when compared to rats fed on control diet. Treating the DH rats with rosiglitazone only causes a significant decrease for BG levels by 52.79%, triglycerides (TGs) by 24.05%, total cholesterol (T-Chol) by 30.23%, low density lipoprotein cholesterol (LDL-C) by 40.53%, TNF-α by 20.81%, TGF-β by 46.54%, collagen-I by 48.11% and collagen-III by 53.85% but causes a significant increase for MMP-2 by 272.73%. Moreover, Treating the DH rats with rosiglitazone and felodipine combination causes a significant decrease for BG levels by 61.08%, blood pressure (BP) by 16.78%, TGs by 23.80%, T-Chol by 33.27%, LDL-C by 45.18%, TNF-α by 22.82%, TGF-β by 49.31%, collagen-I by 64.15% and collagen-III by 53.85% but causes a significant increase for MMP-2 by 290.91%. Rosiglitazone alone failed to decrease the BP in DH rats in the current dosage and duration.

Conclusion

Our results indicate that the co-existence of diabetes and hypertension could induce cardiomyopathy which could further result in cardiac fibrosis, and that combination treatment with rosiglitazone and felodipine has a great protective role against the metabolic abnormalities, meanwhile, the treatment with rosiglitazone alone has a protective role with a minimal effect against these abnormalities and has no effect on decreasing BP in these cases which may lead to coronary artery diseases (CADs) in future.
Clinical Management Factors Contribute to the Decision for Contralateral Prophylactic Mastectomy
Authors: King Tari A. , Sakr Rita , Patil Sujata , Gurevich Inga , Stempel Michelle , Sampson Michelle , Morrow Monica
Published: April 2011

Purpose

To determine whether increasing rates of contralateral prophylactic mastectomy (CPM) are due to recognition of risk factors for contralateral breast cancer (CBC) or treatment factors related to the index lesion.

Methods

From 1997 to 2005, 2,965 patients with stage 0 to III primary unilateral breast cancer underwent mastectomy at Memorial Sloan-Kettering Cancer Center. Patients who did and did not undergo CPM within 1 year of treatment for their index cancer were compared to identify independent predictors of CPM.

Results

The rate of CPM was 13.8% (n = 407), increasing from 6.7% in 1997 to 24.2% in 2005 (P < .0001). Patients with BRCA mutations or prior mantle radiation (n = 52) accounted for 13% of those having CPM. The rate of CPM by surgeon varied from 1% to 26%. Multivariate logistic regression adjusting for surgeon-identified white race (odds ratio [OR] = 3.3), immediate reconstruction (OR = 3.3), family history of breast cancer (OR = 2.9), magnetic resonance imaging (MRI) at diagnosis (OR = 2.8), age younger than 50 years (OR = 2.2), noninvasive histology (OR = 1.8), and prior attempt at breast conversation (OR = 1.7) to be independent predictors of CPM.

Conclusion

These data suggest that increasing use of CPM is not associated with increased recognition of patients at high risk for CBC. Treatment factors, such as immediate reconstruction, preoperative MRI, and unsuccessful attempts at breast conservation, are associated with increased rates of CPM. Efforts to optimize breast conservation, minimize unnecessary tests, and improve patient education about the low risk of CBC may help to curb this trend.
Randomized, Placebo-Controlled, Phase III Study of Oxaliplatin, Fluorouracil, and Leucovorin With or Without PTK787/ZK 222584 in Patients With Previously Treated Metastatic Colorectal Adenocarcinoma
Authors: Van Cutsem Eric , Bajetta Emilio , Valle Juan , Köhne Claus-Henning , Randolph Hecht J. , Moore Malcolm , Germond Colin , Berg William , Chen Bee-Lian , Jalava Tarja , Lebwohl David , Meinhardt Gerold , Laurent Dirk , Lin Edward
Published: April 2011

Purpose

Treatment options for patients with previously treated metastatic colorectal cancer (mCRC) are limited, and treatments with differing mechanisms of action are needed. PTK787/ZK 222584 (PTK/ZK) is a novel oral angiogenesis inhibitor with therapeutic potential for the treatment of solid tumors.

Methods

Patients (N = 855) were randomly assigned to treatment with PTK/ZK or placebo once daily in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4). Stratification factors included WHO performance status (PS; 0 v 1 to 2) and lactate dehydrogenase ([LDH] ≤ 1.5× the upper limit of normal [ULN] v > 1.5 × ULN). Treatment was given until disease progression or unacceptable toxicity. The primary end point was overall survival (OS); secondary end points included progression-free survival (PFS), safety, tolerability, and pharmacokinetics of PTK/ZK.

Results

No statistically significant differences were seen between the treatment groups for the overall comparison of OS. With PTK/ZK and placebo, respectively, median OS was 13.1 and 11.9 months (hazard ratio [HR], 1.00; 95% CI, 0.87 to 1.16; P = .957). Median PFS was longer with PTK/ZK than with placebo (5.6 and 4.2 months, respectively; HR, 0.83; 95% CI, 0.71 to 0.96; P = .013). An exploratory, post hoc analysis demonstrated improved PFS in patients with high LDH, regardless of WHO PS (HR, 0.63; 95% CI, 0.48 to 0.83; P < .001).

Conclusion

PTK/ZK in combination with FOLFOX4 did not improve OS of patients with pretreated mCRC but did improve PFS. The effect of PTK/ZK was more pronounced in patients with high LDH at baseline.
Developmental Programming of Energy Balance and Its Hypothalamic Regulation
Authors: Remmers Floor , Delemarre-van de Waal Henriette A.
Published: April 2011

Developmental programming is an important physiological process that allows different phenotypes to originate from a single genotype. Through plasticity in early life, the developing organism can adopt a phenotype (within the limits of its genetic background) that is best suited to its expected environment. In humans, together with the relative irreversibility of the phenomenon, the low predictive value of the fetal environment for later conditions in affluent countries makes it a potential contributor to the obesity epidemic of recent decades. Here, we review the current evidence for developmental programming of energy balance. For a proper understanding of the subject, knowledge about energy balance is indispensable. Therefore, we first present an overview of the major hypothalamic routes through which energy balance is regulated and their ontogeny. With this background, we then turn to the available evidence for programming of energy balance by the early nutritional environment, in both man and rodent models. A wealth of studies suggest that energy balance can indeed be permanently affected by the early-life environment. However, the direction of the effects of programming appears to vary considerably, both between and within different animal models. Because of these inconsistencies, a comprehensive picture is still elusive. More standardization between studies seems essential to reach veritable conclusions about the role of developmental programming in adult energy balance and obesity.
Synthesis and Characterization of Semiconducting Boron-doped Amorphous Carbon Materials Using an Organic Boron Compound as a Precursor
Authors: Inoue Yasunori , Kitano Masaaki , Nakajima Kiyotaka , Hara Michikazu
Published: April 2011

Boron-doped amorphous carbon was synthesized by polymerizing naphthalene and triphenylborane with subsequent heat treatment by spark plasma sintering. The boron-doped carbon material has negative Seebeck coefficient (−0.22 mV K−1), which indicates the carbon material functions as an n-type semiconductor.
Hole Transport of a Liquid-crystalline Phenylterthiophene Derivative Exhibiting the Nematic Phase at Ambient Temperature
Authors: Nuita Midori , Sakuda Junji , Hirai Yuki , Funahashi Masahiro , Kato Takashi
Published: April 2011

A liquid-crystalline phenylterthiophene derivative which exhibits a nematic phase at room temperature has been prepared. The hole mobility in the nematic phase at room temperature reaches 4 × 10−4 cm2 V−1 s−1. This value is two orders of magnitude larger than those of amorphous organic semiconductors and comparable to those in the smectic A or C phases of liquid-crystalline semiconductors.
Hyoid-laryngeal fractures in hanging: where was the knot in the noose?
Authors: Nikolić Slobodan , Živković Vladimir , Babić Dragan , Juković Fehim , Atanasijević Tatjana , Popović Vesna
Published: April 2011

The aims of this study were to determine the frequency of hyoid-laryngeal fractures in hanging in relation to the position of the ligature knot, to reconstruct the location of the ligature knot in cases of hanging when the furrow is not detectable on the skin, and to identify the possible mechanism of neck structure injuries. We report a retrospective autopsy study which included 557 cases of suicidal hanging: 413 men and 144 women, with an average age of 52.4 ± 17.8 years. In 57.3% of them, hyoid-laryngeal fractures were found (average age was 54.3 ± 16.5 years): 15.1% had only hyoid bone fracture, 26% had only thyroid cartilage fracture and 16.2% had both types of injury at the same time. Hyoid-laryngeal fractures were found more often in persons aged over 30 years. Hyoid bone fracture was a weak predictor of ligature knot position in our sample. Fracture frequencies of the thyroid cartilage show a statistically significant difference in relation to the ligature knot position among persons older than 30 years, which indicated the ipsilateral and posterior position of the knot. Absence or presence of any form of hyoid-laryngeal fracture indicated that knot position was anterior or posterior, respectively. The derived data would be useful for cases where the ligature has been removed from the body of the deceased shortly after hanging, where the noose is unavailable, and in cases where the ligature mark has faded such as with soft ligatures removed promptly or in decomposed bodies.
Evaluation of semen presumptive tests for use at crime scenes
Authors: Laffan Áine , Sawyer Ian , Quinones Ignacio , Daniel Barbara
Published: April 2011

The SERATEC® PSA Semiquant and RSID®-Semen tests are immunoassay kits that identify semen by detecting prostate-specific antigen (PSA) and semenogelin (Sg), respectively. Both kits were tested with semen, urine, blood, saliva, vaginal secretions and breast milk in order to determine their sensitivity and specificity. These results demonstrate that the SERATEC PSA kit is more sensitive than the RSID-Semen kit with a limit of detection of 200 ng/mL as opposed to 8.0 × 103ng/mL. The RSID-Semen kit gave no false-positives or -negatives compared with 2.9% false-negatives with the SERATEC PSA kit. Results from postcoital samples show the RSID-Semen kit to be more effective, indicating that this kit is more suitable for semen identification in the Haven Suites. As a more robust and cost-effective kit, the SERATEC PSA test is recommended for use at crime scenes. The ability to obtain DNA profiles from the buffer of both kits demonstrates the potential benefit of these kits in a rape investigation. The use of these kits at crime scenes would provide an invaluable contribution by prioritizing samples for subsequent analysis, thereby allowing greater efficiency with investigation times.
The responses of professional groups to the use of Section 136 of the Mental Health Act (1983, as amended by the 2007 Act) in Gloucestershire
Authors: Riley G , Laidlaw J , Pugh D , Freeman E
Published: April 2011

Background

Section 136 (S136) of the Mental Health Act (1983, as amended by the 2007 Act) empowers the police to detain those suspected of being mentally disordered in a public place and to convey them to a place of safety (POS) for further assessment. Gloucestershire has not had a specialist facility for S136 detentions and individuals were taken to the police cells or occasionally A&E departments for assessment.

Aims

This paper forms one part of three aspects under investigation. Two companion papers by the authors describe the use of S136 using anonymised audit data and the experiences of detainees. The objectives of this paper have been to assess the responses of the different professional groups involved in the process of S136.

Method

An anonymous postal questionnaire was distributed to eight groups of professionals who were identified as having the potential to be involved in part of the process of a S136 detention. Results were collated and analysed, and formed the basis for a series of follow-up focus groups within groups to explore themes that warranted further investigation.

Results

An overall response rate of 59% was achieved. Seventy-four per cent of participants thought that there should be an alternative POS to the police station. A&E was thought to be an unsuitable alternative POS, with a psychiatric hospital being the first choice for 58%.

Conclusions

There is a gap in the expectations of the different agencies involved in the S136 process, which have the potential to be divisive if interagency pathways and agreements are not in place.
Improved capillary electrophoresis determination of carbohydrate-deficient transferrin including on-line immunosubtraction
Authors: Pascali Jennifer P , Bortolotti Federica , Sorio Daniela , Ivanova Mariela , Palmbach Timothy M , Tagliaro Franco
Published: April 2011

The instrumental analysis of carbohydrate-deficient transferrin (CDT), a recognized marker of chronic alcohol abuse, is most commonly carried out by high-performance liquid chromatography (HPLC) or capillary zone electrophoresis (CZE). Between these two techniques, CZE shows higher efficiency and productivity, but is often reported to be inferior to HPLC in terms of selectivity, because of a less specific ultraviolet detection wavelength than HPLC. On these grounds, the present work was aimed at the development of an improved CZE method for CDT determination, including an on-line immunosubtraction step specifically aimed at enhancing the analytical specificity of CZE determination. The analytical conditions were as follows: uncoated fused silica capillary, 30 µm × 60 cm ( L = 50 cm to detector); running buffer, 100 mmol/L borate and 6 mmol/L DAB (1,4-diaminobutane), pH 8.3; voltage, 30 kV; temperature, 25°C; detection, 200 nm. Under the described CZE conditions, a baseline separation between all the CDT related peaks was achieved with good analytical performances in terms of both precision and accuracy. In order to achieve unequivocal recognition of the CDT peaks, an in-capillary immunosubtraction step was included by loading a plug of anti-human transferrin antibody solution after the sample plug. This analytical approach was applied successfully to recognize CDT peaks in the presence of potential interferences.
Air embolism: an unusual cause of delayed death following gunshot wound to the chest
Authors: Temlett Julia , Byard Roger W
Published: April 2011

A 29-year-old man was shot in the chest twice sustaining extensive contusion of the right lung. He was, however, clinically stable with no major vessel injury or significant blood loss. Unexpected cardiac arrest occurred hours after hospital admission due to left coronary artery air embolism. Lung parenchymal damage from the passage of two projectiles within the chest wall close to the pleural cavity had occurred, with disruption of the capillary–alveolar interface and passage of air into the pulmonary venous circulation. While tangential gunshot wounds to the chest wall may rarely cause air embolism, symptoms are usually immediate. The present case demonstrates, however, that death may occur unexpectedly some time after the initial trauma in an individual who is considered clinically stable.
Recent Publications on Medications and Pharmacy
Authors: Russett Flint
Published: April 2011

Hospital Pharmacy presents this feature to keep pharmacists abreast of new publications in the medical/pharmacy literature. Articles of interest regarding a broad scope of topics are abstracted monthly.
Musterstandardarbeitsanweisung Präanalytik/Exemplary standard operation procedure pre-examination/Arbeitsgruppe Richtwerte der Deutschen Vereinten Gesellschaft für Klinische Chemie und Laboratoriumsmedizin
Authors: Gurr Eberhard , Arzideh Farhad , Brandhorst Gunnar , Gröning Arndt , Haeckel Rainer , Hoff Torsten , Roggenbuck Lennart , Schumann Gerhard , Wolters Bernd , Wosniok Werner
Published: April 2011

DIN EN ISO 15189 und die Richtlinien der Bundesärztekammer zur Qualitätssicherung laboratoriumsmedizinischer Untersuchungen fordern die Regelung präanalytischer Variablen, um Ergebnisse so vergleichbar wie möglich zu machen. Die Arbeitsgruppe Richtwerte der Deutschen Vereinten Gesellschaft für Klinische Chemie und Laboratoriumsmedizin hat eine Musterstandardarbeitsanweisung entworfen, die an die lokalen Gegebenheiten angepasst werden kann. Die Anwendung dieser Standardarbeitsanweisung trägt zur Validität der bei der Überwachung von Referenzintervallen gewonnenen Ergebnisse bei.
Response of biochemical markers of bone turnover to oral glucose load in diseases that affect bone metabolism
Authors: Yavropoulou Maria P , Tomos Konstantinos , Tsekmekidou Xanthippi , Anastasiou Olympia , Zebekakis Pantelis , Karamouzis Michael , Gotzamani-Psarrakou Anna , Chassapopoulou Eleni , Chalkia Panagiota , Yovos John G
Published: April 2011

Objective

Postprandial suppression of bone resorption is considered one of the main contributors in the circadian rhythm of bone turnover markers. The aim of this study was to investigate this physiological response of bone tissue in diseases that affect bone metabolism.

Patients and methods

In this study, 118 patients (45 hypothyroid, 40 hyperthyroid, and 33 β-thalassemic patients) and 78 healthy individuals matched for age and body mass index were included. An oral glucose test (75 g glucose) was performed after overnight fasting. Serum levels of procollagen type-I N-terminal propeptide (P1NP), β-C-terminal telopeptide of type I collagen (β-CTX), and osteocalcin were assayed at 0, 60, and 120 min.

Results

Baseline values of bone turnover markers were significantly elevated in hyperthyroid and β-thalassemic patients but not in hypothyroid patients compared with the control group. After oral glucose, the levels of β-CTX but not P1NP or osteocalcin were significantly suppressed in all groups (mean change from baseline is 46.9% for β-CTX, 7.9% for P1NP, and 8% for osteocalcin). The percentage change from baseline for β-CTX was significantly augmented in hypothyroidism (52 vs 42%, P=0.009).

Conclusion

The preservation or even augmentation of postprandial suppression of bone resorption in diseases that affect bone metabolism through distinct pathogenetic mechanisms suggests the importance of this physiological response to nutrients for the general homeostasis and functional integrity of the skeleton.
Pediatric Drug-Trial Recruitment: Enticement Without Coercion
Authors: Tishler Carl L. , Reiss Natalie Staats
Published: April 2011

Despite federal initiatives to increase research and expand data about the effectiveness and safety of medications in children, data are still limited for this population. One of the most salient barriers to conducting pediatric clinical trials involves participant recruitment. In this article, we summarize recruitment challenges including a lack of research infrastructure, the need to properly define appropriate use of incentives and payments, and inconsistencies in the current use of payments and incentives. We also searched the Centerwatch.com and ClinicalTrials.gov databases for updated data on current practices in pediatric participant compensation/payment. We provide recommendations for tackling current barriers to recruiting and retaining children and families in clinical trials.
Regression of a Cardiac Rhabdomyoma in a Patient Receiving Everolimus
Authors: Tiberio Dana , Franz David N. , Phillips John R.
Published: April 2011

Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder that can affect every organ of the body, most commonly the brain, kidneys, heart, and lungs. The TSC mutation results in abnormal cellular proliferation and differentiation, which are responsible for hamartomatous lesions that affect the brain, kidney, heart, and lungs. mTOR (mammalian target of rapamycin) is a protein kinase that regulates the abnormal cellular proliferation and differentiation. Consequently, mTOR inhibitors are being studied to treat the subependymal giant-cell astrocytomas and renal angiomyolipomas that are commonly seen with TSC. We describe here the case of a patient with significant regression of a cardiac rhabdomyoma after receiving everolimus, an mTOR inhibitor. This finding suggests a possible novel therapy for patients with clinically significant cardiac rhabdomyomas.
Correlation between Deep-Level Defects and Current Collapses in AlGaN/GaN Hetero-Structures Probed by Steady-State Photo-Capacitance Spectroscopy
Authors: Nakano Yoshitaka , Irokawa Yoshihiro , Sumida Yasunobu , Yagi Shuichi , Kawai Hiroji
Published: April 2011

We have investigated a correlation between electronic deep levels and current collapses in AlGaN/GaN hetero-structures by capacitance-voltage and photo-capacitance spectroscopy techniques, using Schottky barrier diodes. Three specific deep levels located at ~2.07, ~2.80, ~3.23eV below the conduction band were found to be significantly enhanced for the severe current collapse. These levels probably originate in Ga vacancies and residual C impurities and are probably responsible for the current collapses of the AlGaN/GaN hetero-structures.