bluuebunny/crossref_metadata_2025 huggingface dataset:
NCCAM/NCI Phase 1 Study of Mistletoe Extract and Gemcitabine in Patients with Advanced Solid Tumors
Authors: Mansky Patrick J. , Wallerstedt Dawn B. , Sannes Timothy S. , Stagl Jamie , Johnson Laura Lee , Blackman Marc R. , Grem Jean L. , Swain Sandra M. , Monahan Brian P.
Published: October 2013

Purpose.European Mistletoe (Viscum albumL.) extracts (mistletoe) are commonly used for cancer treatment in Europe. This phase I study of gemcitabine (GEM) and mistletoe in advanced solid cancers (ASC) evaluated: (1) safety, toxicity, and maximum tolerated dose (MTD), (2) absolute neutrophil count (ANC) recovery, (3) formation of mistletoe lectin antibodies (ML ab), (4) cytokine plasma concentrations, (5) clinical response, and (6) pharmacokinetics of GEM.Methods.Design: increasing mistletoe and fixed GEM dose in stage I and increasing doses of GEM with a fixed dose of mistletoe in stage II. Dose limiting toxicities (DLT) were grade (G) 3 nonhematologic and G4 hematologic events; MTD was reached with 2 DLTs in one dosage level. Response in stage IV ASC was assessed with descriptive statistics. Statistical analyses examined clinical response/survival and ANC recovery.Results.DLTs were G4 neutropenia, G4 thrombocytopenia, G4 acute renal failure, and G3 cellulitis, attributed to mistletoe. GEM 1380 mg/m2and mistletoe 250 mg combined were the MTD. Of 44 patients, 24 developed nonneutropenic fever and flu-like syndrome. GEM pharmacokinetics were unaffected by mistletoe. All patients developed ML3 IgG antibodies. ANC showed a trend to increase between baseline and cycle 2 in stage I dose escalation. 6% of patients showed partial response, 42% stable disease. Median survival was 200 days. Compliance with mistletoe injections was high.Conclusion.GEM plus mistletoe is well tolerated. No botanical/drug interactions were observed. Clinical response is similar to GEM alone.
On the Stability of One‐Dimensional Wave Equation
Authors: Jung Soon-Mo
Published: October 2013

We prove the generalized Hyers‐Ulam stability of the one‐dimensional wave equation, utt = c2uxx, in a class of twice continuously differentiable functions.
Polymorphisms inPPARGenes (PPARD,PPARG, andPPARGC1A) and the Risk of Chronic Kidney Disease in Japanese: Cross-Sectional Data from the J-MICC Study
Authors: Hishida Asahi , Wakai Kenji , Naito Mariko , Tamura Takashi , Kawai Sayo , Hamajima Nobuyuki , Oze Isao , Imaizumi Takeshi , Turin Tanvir Chowdhury , Suzuki Sadao , Kheradmand Motahare , Mikami Haruo , Ohnaka Keizo , Watanabe Yoshiyuki , Arisawa Kokichi , Kubo Michiaki , Tanaka Hideo
Published: October 2013

Chronic kidney disease (CKD) is well known as a strong risk factor for both end stage renal disease and cardiovascular disease. To clarify the association of polymorphisms in thePPARgenes (PPARD,PPARG, andPPARGC1A) with the risk of CKD in Japanese, we examined this association among the Japanese subjects using the cross-sectional data of J-MICC (Japan Multi-Institutional Collaborative Cohort) Study. The subjects for this analysis were 3,285 men and women, aged 35–69 years, selected from J-MICC Study participants; genotyping was conducted by multiplex polymerase chain reaction-based Invader assay. The prevalence of CKD was determined for CKD stages 3–5 (defined as eGFR < 60 ml/min/1.73 m2). Participants with CKD accounted for 17.3% of the study population. When those withPPARDT-842CT/Twere defined as reference, those withPPARDT-842CT/CandC/Cdemonstrated the OR for CKD of 1.26 (95%CI 1.04–1.53) and 1.31 (95%CI 0.83–2.06), respectively. There were no significant associations between the polymorphisms in otherPPARgenes and the risk of CKD. The present study found a significantly increased risk of CKD in those with theCallele ofPPARDT-842C, which may suggest the possibility of personalized risk estimation of this life-limiting disease in the near future.
Solving Continuous Models with Dependent Uncertainty: A Computational Approach
Authors: Cortés J.-C. , Romero J.-V. , Roselló M.-D. , Santonja Francisco-J. , Villanueva Rafael-J.
Published: October 2013

This paper presents a computational study on a quasi-Galerkin projection-based method to deal with a class of systems of random ordinary differential equations (r.o.d.e.’s) which is assumed to depend on a finite number of random variables (r.v.’s). This class of systems of r.o.d.e.’s appears in different areas, particularly in epidemiology modelling. In contrast with the other available Galerkin-based techniques, such as the generalized Polynomial Chaos, the proposed method expands the solution directly in terms of the random inputs rather than auxiliary r.v.’s. Theoretically, Galerkin projection-based methods take advantage of orthogonality with the aim of simplifying the involved computations when solving r.o.d.e.’s, which means to compute both the solution and its main statistical functions such as the expectation and the standard deviation. This approach requires the previous determination of an orthonormal basis which, in practice, could become computationally burden and, as a consequence, could ruin the method. Motivated by this fact, we present a technique to deal with r.o.d.e.’s that avoids constructing an orthogonal basis and keeps computationally competitive even assuming statistical dependence among the random input parameters. Through a wide range of examples, including a classical epidemiologic model, we show the ability of the method to solve r.o.d.e.’s.
Clinical Implications of Girdin Protein Expression in Glioma
Authors: Zhao Liwei , Ma Shuyin , Liu Qing , Liang Peng
Published: October 2013

Objective. To investigate the expression status of Girdin in glioma and the relationship between Girdin expression and the biological behavior of glioma. Materials and methods. The expression status of Girdin in glioma from 560 cases was evaluated by RT‐PCR, Western Blot and immunohistochemistry. The relationship between Girdin expression and clinic‐pathological parameters as well as prognosis was also studied. Results. The expression of Girdin in high grade glioma was significantly higher than low grade glioma. After universal analysis, the expression of Girdin protein is closely related to KPS score, extent of resection, Ki67 and WHO grade, but it was not related to sex and age. Finally, extent of resection, Ki67 and WHO grade were indentified to be related to the Girdin protein expression in logistic regression. Interestingly, we found that the expression of Girdin is significantly related to the distant metastasis of glioma. After COX regression analysis, KPS score, Extent of resection, Ki67, WHO grade as well as Girdin were observed to be independent prognostic factors. Conclusions. Girdin is differential expressed in the glioma patients and closely related to the biological behavior of Glioma. Finally, Girdin was found to be a strong predictor for the post‐operative prognosis.
A Derivative of Chrysin Suppresses Two-Stage Skin Carcinogenesis by Inhibiting Mitogen- and Stress-Activated Kinase 1
Authors: Liu Haidan , Hwang Joonsung , Li Wei , Choi Tae Woong , Liu Kangdong , Huang Zunnan , Jang Jae-Hyuk , Thimmegowda N.R. , Lee Ki Won , Ryoo In-Ja , Ahn Jong-Seog , Bode Ann M. , Zhou Xinmin , Yang Yifeng , Erikson Raymond L. , Kim Bo-Yeon , Dong Zigang
Published: October 2013

Mitogen- and stress-activated kinase 1 (MSK1) is a nuclear serine/threonine protein kinase that acts downstream of both extracellular signal-regulated kinases and p38 mitogen-activated protein kinase in response to stress or mitogenic extracellular stimuli. Increasing evidence has shown that MSK1 is closely associated with malignant transformation and cancer development. MSK1 should be an effective target for cancer chemoprevention and chemotherapy. However, very few MSK1 inhibitors, especially natural compounds, have been reported. We used virtual screening of a natural products database and the active conformation of the C-terminal kinase domain of MSK1 (PDB id 3KN) as the receptor structure to identify chrysin and its derivative, compound 69407, as inhibitors of MSK1. Compared with chrysin, compound 69407 more strongly inhibited proliferation and 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced neoplastic transformation of JB6 P+ cells with lower cytotoxicity. Western blot data demonstrated that compound 69407 suppressed phosphorylation of the MSK1 downstream effector histone H3 in intact cells. Knocking down the expression of MSK1 effectively reduced the sensitivity of JB6 P+ cells to compound 69407. Moreover, topical treatment with compound 69407 before TPA application significantly reduced papilloma development in terms of number and size in a two-stage mouse skin carcinogenesis model. The reduction in papilloma development was accompanied by the inhibition of histone H3 phosphorylation at Ser10 in tumors extracted from mouse skin. The results indicated that compound 69407 exerts inhibitory effects on skin tumorigenesis by directly binding with MSK1 and attenuates the MSK1/histone H3 signaling pathway, which makes it an ideal chemopreventive agent against skin cancer. Cancer Prev Res; 7(1); 74–85. ©2013 AACR.
Effect of a Low-Fat Fish Oil Diet on Proinflammatory Eicosanoids and Cell-Cycle Progression Score in Men Undergoing Radical Prostatectomy
Authors: Galet Colette , Gollapudi Kiran , Stepanian Sevan , Byrd Joshua B. , Henning Susanne M. , Grogan Tristan , Elashoff David , Heber David , Said Jonathan , Cohen Pinchas , Aronson William J.
Published: October 2013

We previously reported that a 4- to 6-week low-fat fish oil (LFFO) diet did not affect serum insulin-like growth factor (IGF)-1 levels (primary outcome) but resulted in lower omega-6 to omega-3 fatty acid ratios in prostate tissue and lower prostate cancer proliferation (Ki67) as compared with a Western diet. In this post hoc analysis, the effect of the LFFO intervention on serum pro-inflammatory eicosanoids, leukotriene B4 (LTB4) and 15-S-hydroxyeicosatetraenoic acid [15(S)-HETE], and the cell-cycle progression (CCP) score were investigated. Serum fatty acids and eicosanoids were measured by gas chromatography and ELISA. CCP score was determined by quantitative real-time reverse transcriptase PCR (RT-PCR). Associations between serum eicosanoids, Ki67, and CCP score were evaluated using partial correlation analyses. BLT1 (LTB4 receptor) expression was determined in prostate cancer cell lines and prostatectomy specimens. Serum omega-6 fatty acids and 15(S)-HETE levels were significantly reduced, and serum omega-3 levels were increased in the LFFO group relative to the Western diet group, whereas there was no change in LTB4 levels. The CCP score was significantly lower in the LFFO compared with the Western diet group. The 15(S)-HETE change correlated with tissue Ki67 (R = 0.48; P < 0.01) but not with CCP score. The LTB4 change correlated with the CCP score (r = 0.4; P = 0.02) but not with Ki67. The LTB4 receptor BLT1 was detected in prostate cancer cell lines and human prostate cancer specimens. In conclusion, an LFFO diet resulted in decreased 15(S)-HETE levels and lower CCP score relative to a Western diet. Further studies are warranted to determine whether the LFFO diet antiproliferative effects are mediated through the LTB4/BLT1 and 15(S)-HETE pathways. Cancer Prev Res; 7(1); 97–104. ©2013 AACR.
Dyspnea and Reversibility of Antiplatelet Agents: Ticagrelor, Elinogrel, Cangrelor, and Beyond
Authors: Serebruany Victor L. , Sibbing Dirk , DiNicolantonio James J.
Published: October 2013

Context: Oral reversible platelet P2Y12 receptor inhibitors (ticagrelor and elinogrel) cause double-digit rates of dyspnea, while irreversible oral antiplatelet drugs (aspirin, ticlopidoine, clopidogrel, and prasugrel) or intravenous glycoprotein IIb/IIIa inhibitors (abciximab, eptifibatide, or tirofiban) do not increase the incidence of dyspnea in randomized trials. Dyspnea after oral reversible antiplatelet agents remains unexplained. A transfusion-related acute lung injury (TRALI) hypothesis has been proposed. The dyspnea risks after cangrelor, an intravenous reversible antiplatelet agent, are not well defined but may offer a universal mechanism linking TRALI, dyspnea, and reversible platelet inhibition. Objective: We analyzed safety data from recent head-to-head randomized trials with reversible antiplatelet agents (ticagrelor, elinogrel, and cangrelor) compared to irreversible (clopidogrel/placebo) comparators. Results: All three reversible antiplatelet agents cause excess dyspnea. In contrast to the high double-digit rates after oral ticagrelor or elinogrel, the dyspnea risks after intravenous cangrelor were smaller (<2%) but still consistently and significantly higher than in the corresponding control arms. Conclusions: The clinical utility of reversible antiplatelet strategies has been challenged. Despite a potential advantage of fewer bleeding events during heart surgery, reversible antiplatelet agents carry the risk of potential autoimmune reactions manifesting as dyspnea. Repeated binding and unbinding cycles, impaired platelet turnover, and lung sequestration or apoptosis of overloaded destructive platelets are among the potential mechanism(s) responsible for dyspnea after reversible antiplatelet agents.
Influence of Hypoxia, High Glucose, and Low Serum on the Growth Kinetics of Mesenchymal Stem Cells from Deciduous and Permanent Teeth
Authors: Kanafi Mohammad Mahboob , Ramesh Archana , Gupta Pawan Kumar , Bhonde Ramesh Ramchandra
Published: October 2013

The therapeutic potential of mesenchymal stromal cells depends on their ability to survive and proliferate under adverse in vivo scenarios in a particular disease. In most of the sites of injury, especially in diabetic wounds, there can be hypoxia, hyperglycemia, and ischemia, leading to a lack of nutrients. Hence, the aim of our present study was to investigate the influence of hypoxia, high glucose, and low serum concentrations on the growth kinetics and proliferative potential of human dental pulp stem cells from exfoliated deciduous teeth (SHED) and permanent teeth (DPSC). In this study we isolated two types of specialized stem cells from human dental pulp tissues, which were supposedly of neural crest origin, and cultured them in KO-DMEM medium supplemented with 10% fetal bovine serum (FBS). Both SHED and DPSC were characterized for standard CD surface markers, and their ability to differentiate into adipogenic and osteogenic lineages was tested. SHED and DPSC were exposed to either hypoxia or high glucose or low serum conditions, and their growth kinetics and differentiation potentials were compared with those of normal culture conditions. We found that SHED retained their phenotypic expression and differentiation potential under hypoxia, high-glucose, and low-serum conditions and exhibited a higher proliferation in terms of cell yield and a reduced doubling time compared to DPSC. Our findings clearly demonstrate for the first time that SHED are superior to DPSC as evidenced by their enhanced proliferation under adverse culture conditions.
Aberrant DNA Methylation in Breast Cancer Cells
Authors: Campoy Emanuel Martín , Laurito Sergio , Urrutia Guillermo , Branham María Teresita , Roqué María
Published: October 2013

The epigenome is regulated by a large number of macromolecular machines that are dynamically involved in various processes, including DNA methylation, histone modification and non-coding RNA signals, all of them working together to regulate the proper expression of the genome. Thus, in contrast with the genome, whose sequence is carefully conserved during cell life, the epigenome is highly dynamic. The epigenomic modifications are acquired during normal cell differentiation, replicated during mitosis and passed to daughter cells. A fundamental epigenetic attribute is that this plasticity occurs in response to environmental signals. It is therefore now accepted that the environment influences modifications in the cellular transcriptome through the epigenome. In developmental and evolutionary terms, the regulation of gene expression through epigenomic modifications is an advantageous shortcut and a highly conserved mechanism. However, it implies an increased risk for misregulation, as, for example, aberrant epigenomic modifications associate with the development of different human diseases, i.e. lupus, asthma, neurological diseases and cancer. Although epigenetic alterations in breast cancer have been deeply studied and discussed in the last decades, apparently contradictory results are yet often observed. Consequently, in this review, we will briefly discuss the latest findings of aberrant DNA methylation in breast tumorigenesis. Emphasis will be given to the discussion of the idea that different environments could explain paradoxical biological and pathobiological behaviors in individual patients and thus should be taken into consideration for the design and implementation of diagnosis, prognosis and predictive biomarkers.
Nuclear Factor of Activated T Cells Operates as Conductor of the Epigenetic Orchestra in Pancreatic Carcinogenesis
Authors: Hessmann Elisabeth , Ellenrieder Volker
Published: October 2013

Recent years have witnessed an explosive increase in our knowledge about the epigenetic features in human cancers. It became apparent that pancreatic cancer, additionally to its genetic background, is an epigenetic disease characterized by widespread alterations in DNA methylation, histone modification and recruitment of microRNAs. Although more and more in-depth research is performed and epigenetic modifications are shown in healthy and degenerated cells, we still lack insight into how epigenetic modifications are orchestrated during carcinogenesis. By introducing nuclear factor of activated T cell proteins and their impact on gene activation and silencing in pancreatic cancer, this review cites an example of how deregulated oncogenes modulate epigenetic alterations in epithelial cancers.
Noninvasive Prenatal Diagnosis Using Next-Generation Sequencing
Authors: Xu Liang , Shi Rui
Published: October 2013

Nowadays, prenatal diagnosis is necessary for pregnant women. For the parents who are expecting a child, the genetic test may provide the information whether they are carrying rare gene mutations and whether they are at risk of passing them onto their offspring. However, the ultimate determination of genetic diseases often requires invasive procedures such as amniocentesis and chorionic villus sampling, which may cause fetal miscarriage. A noninvasive type of prenatal diagnosis needs to be developed in clinical practice to dispel safety concerns. In this paper, we will review the technical advancement of using maternal circulating nucleic acids as the sample in noninvasive studies, and highlight the utilization of next-generation sequencing in the screening of genetic diseases.
Study on the Clinical Significance and Related Factors of Thirst and Xerostomia in Maintenance Hemodialysis Patients
Authors: Fan Wei-Feng , Zhang Qi , Luo Li-Hong , Niu Jian-Ying , Gu Yong
Published: October 2013

Aims: To analyse the clinical significance and related factors of thirst and xerostomia and to find methods to alleviate thirst and xerostomia in maintenance hemodialysis (MHD) patients. Methods: Forty-two MHD patients were included for observational study and eleven patients were enrolled for crossover trial. Thirst was assessed by 100-mm visual analog scales (VAS) and dialysis thirst inventory (DTI). Meanwhile, xerostomia was assessed by VAS and xerostomia inventory (XI). Depression, kidney disease quality of life (KDQOL), salivary flow rates and inter dialytic weight gain (IDWG) were measured. Data were analyzed by ANOVA and correlation coefficient was used to assess the correlations between continuous variables. The results of crossover trial were investigated by two-sample T-tests. Results: Strong positive correlations among DTI, VAS thirst score, XI and VAS xerostomia score were found (P=0.000). Daily IDWG was positively correlated with VAS thirst score (r=0.315, P=0.042) and DTI(r=0.391, P=0.010). UWS (unstimulated whole saliva) was negatively correlated with VAS xerostomia score (r=-0.308, P=0.048). Residual urine output was negatively correlated with DTI (r=-0.402, P=0.008), VAS xerostomia score (r=-0.461, P=0.002) and XI (r=-0.403, P=0.008). In the crossover trial, DTI, XI, IDWG2d, IDWG3d, VAS thirst and xerostomia score were significantly reduced by the use of chewing gum (P=0.000, 0.001, 0.009, 0.017, 0.038, 0.001). The VAS thirst score, DTI and IDWG3d were significantly reduced by receiveing straw (P=0.016, 0.003, 0.049). Conclusion: Thirst and xerostomia might affect the quality of life in MHD patients. Both chewing gum and straw could decrease thirst and IDWG.
Uremic Restless Legs Syndrome (RLS) and Sleep Quality in Patients With End-Stage Renal Disease on Hemodialysis: Potential Role of Homocysteine and Parathyroid Hormone
Authors: Gade Katrin , Blaschke Sabine , Rodenbeck Andrea , Becker Andreas , Anderson-Schmidt Heike , Cohrs Stefan
Published: October 2013

Background: The aetiology of uremic restless legs syndrome (RLS) remains unclear. Our research investigated whether an elevated plasma concentration of the excitatory amino acid homocysteine might be associated with RLS occurrence in patients with chronic renal insufficiency on hemodialysis. Methods: Total plasma homocysteine as well as creatinine, urea, folate, parathyroid hormone, hemoglobin, iron, ferritin, phosphate, calcium, magnesium, and albumin levels were compared between 26 RLS-affected (RLSpos) and 26 non-affected (RLSneg) patients on chronic hemodialysis. We further compared subjective sleep quality between RLSpos and RLSneg patients using the Pittsburgh-Sleep-Quality-Index and investigated possible relationships between laboratory parameters and sleep quality. Results: Taking individual albumin concentrations into account, a significant positive correlation between total plasma homocysteine and RLS occurrence was observed (r= 0.246; p=0.045). Sleep quality was significantly more reduced in RLSpos compared to RLSneg patients and RLS severity correlated positively with impairment of sleep quality. Bad sleep quality in all patients was associated with higher concentrations of parathyroid hormone. Conclusion: Our results suggest a possible aetiological role of homocysteine in uremic RLS. They confirm that uremic RLS is an important factor causing sleep impairment in patients on hemodialysis. Higher parathyroid hormone levels might also be associated with bad sleep quality in these patients.
Dialysis Dose and Intradialytic Hypotension: Results from the HEMO Study
Authors: Mc Causland Finnian R. , Brunelli Steven M. , Waikar Sushrut S.
Published: October 2013

Background: Intradialytic hypotension (IDH) is common and is associated with increased morbidity and mortality in chronic hemodialysis patients. A higher dialysis ‘dose' may generate transient intradialytic osmotic gradients, predisposing to intracellular fluid shifts and resulting in hypotension. Study Design: We performed a post hoc analysis of the HEMO study, a multicenter trial that randomized chronic hemodialysis patients to high versus standard Kt/V and higher versus lower membrane flux. In order to achieve dose targets, per protocol, adjustments were made in membrane efficiency, blood flow or dialysate flow before changing session length. Detailed hemodynamic and urea kinetic modeling data were abstracted from 1,825 individuals. The primary outcome was the occurrence of hypotensive events necessitating clinical intervention (saline infusion, lowering of ultrafiltration rate or reduced blood flow). Results: Intradialytic hypotensive events occurred more frequently in the higher-Kt/V group (18.3 vs. 16.8%; p < 0.001). Participants randomized to higher-target Kt/V had a greater adjusted risk of IDH than those randomized to standard Kt/V [odds ratio (OR) 1.12; 95% confidence interval (CI) 1.01-1.25]. Higher vs. lower dialyzer mass transfer-area coefficient for urea and rate of urea removal were associated with greater adjusted odds of IDH (OR 1.15; 95% CI 1.04-1.27 and OR 1.05; 95% CI 1.04-1.06 per mg/dl/h, respectively). Conclusions: Higher dialysis dose, at relatively constrained treatment times, may associate with an increased risk of IDH. These findings support the possibility that rapidity of intradialytic reductions in plasma osmolality may play an important role in mediating hemodynamic instability during dialysis.
Climate Forecasts for Corn Producer Decision Making
Authors: Takle Eugene S. , Anderson Christopher J. , Andresen Jeffrey , Angel James , Elmore Roger W. , Gramig Benjamin M. , Guinan Patrick , Hilberg Steven , Kluck Doug , Massey Raymond , Niyogi Dev , Schneider Jeanne M. , Shulski Martha D. , Todey Dennis , Widhalm Melissa
Published: October 2013

Corn is the most widely grown crop in the Americas, with annual production in the United States of approximately 332 million metric tons. Improved climate forecasts, together with climate-related decision tools for corn producers based on these improved forecasts, could substantially reduce uncertainty and increase profitability for corn producers. The purpose of this paper is to acquaint climate information developers, climate information users, and climate researchers with an overview of weather conditions throughout the year that affect corn production as well as forecast content and timing needed by producers. The authors provide a graphic depicting the climate-informed decision cycle, which they call the climate forecast–decision cycle calendar for corn.
An Objectively Determined Blocking Index and its Northern Hemisphere Climatology
Authors: Small David , Atallah Eyad , Gyakum John R.
Published: October 2013

A modified blocking index is defined based on vertically integrated potential vorticity. The application of this index identifies blocking activity over the Northern Hemisphere during all seasons. The index is developed by systematically identifying the magnitude and spatial scale that best characterizes persistent anticyclonic circulation anomalies in different seasons. By applying a systematic approach to the detection of blocking, the interannual, seasonal, and intraseasonal patterns of blocking frequency across the Northern Hemisphere are able to be characterized. The results are consistent with previous studies in finding that blocking is more frequent in the cold season months than in the warm season, although the results suggest that blocking occurs much more frequently in the summer and fall than many studies have previously reported. By examining blocking frequency monthly, interesting patterns of intraseasonal variability are found, especially over the central Pacific in August and the eastern Pacific in September and October, where blocking is nearly as frequent as in the winter. Possible explanations for this intraseasonal variability are discussed.
Using the Time-Lag Correlation Function of Dual-Aperture Scintillometer Measurements to Obtain the Crosswind
Authors: van Dinther Daniëlle , Hartogensis Oscar K.
Published: October 2013

In this study the crosswind (U⊥) is determined from the time-lag correlation function [r12(τ)] measured by a dual large-aperture scintillometer; U⊥ is defined as the wind component perpendicular to a path—in this case, the scintillometer path. A scintillometer obtains a path-averaged U⊥, which for some applications is an advantage compared to other wind measurement devices. Four methods were used to obtain U⊥: the peak method, the Briggs method, the zero-slope method, and the lookup table method. This last method is a new method introduced in this paper, which obtains U⊥ by comparing r12(τ) of a measurement to r12(τ) of a theoretical model. The U⊥ values obtained from the scintillometer were validated with sonic anemometer measurements. The best results were obtained by the zero-slope method for U⊥ < 2 m s−1 and by the lookup table method for U⊥ > 2 m s−1. The Briggs method also showed promising results, but it is not always able to obtain U⊥. The results showed that a high parallel wind component (>2.5 m s−1) on the scintillometer path can cause an overestimation of U⊥ mainly for low U⊥ values (<2 m s−1).
Naturalism and the Friends of Understanding
Authors: Cahill Kevin M.
Published: October 2013

Paul Roth claims that “interpretivists” in the philosophy of social sciences like Charles Taylor assume a positivist caricature of natural science to motivate their arguments against naturalism in the social sciences. Roth argues that not only is adopting the view of meaning relied upon by those he sometimes refers to as the “friends of understanding” unmotivated once the critique of positivism has been taken on board, he argues further that Quine has shown why this “meaning realism” is unavailable in principle. Roth bolsters his use of Quine against interpretivists by referring to Kripke’s reading of Wittgenstein on rule-following. But McDowell has shown how Kripke overlooks an alternative reading of those remarks, which provides “interpretivists” with arguments against mainstream naturalism and which makes no use of anything resembling “meaning realism.” This opening for interpretivists is actually already present in Roth’s discussion of the distinction between “thin” and “thick” description. This suggests how mainstream naturalism itself might be rethought to accommodate interpretivism.
Intraoperative Cone‐Beam Computed Tomography and Multi‐Slice Computed Tomography in Temporal Bone Imaging for Surgical Treatment
Authors: Erovic Boban M. , Chan Harley H. L. , Daly Michael J. , Pothier David D. , Yu Eugene , Coulson Chris , Lai Philip , Irish Jonathan C.
Published: October 2013

Objective

Conventional computed tomography (CT) imaging is the standard imaging technique for temporal bone diseases, whereas cone‐beam CT (CBCT) imaging is a very fast imaging tool with a significant less radiation dose compared with conventional CT. We hypothesize that a system for intraoperative cone‐beam CT provides comparable image quality to diagnostic CT for identifying temporal bone anatomical landmarks in cadaveric specimens.

Study Design

Cross‐sectional study.

Setting

University tertiary care facility.

Subjects and Methods

Twenty cadaveric temporal bones were affixed into a head phantom and scanned with both a prototype cone‐beam CT C‐arm and multislice helical CT. Imaging performance was evaluated by 3 otologic surgeons and 1 head and neck radiologist. Participants were presented images in a randomized order and completed landmark identification questionnaires covering 21 structures.

Results

CBCT and multislice CT have comparable performance in identifying temporal structures. Three otologic surgeons indicated that CBCT provided statistically equivalent performance for 19 of 21 landmarks, with CBCT superior to CT for the chorda tympani and inferior for the crura of the stapes. Subgroup analysis showed that CBCT performed superiorly for temporal bone structures compared with CT. The radiologist rated CBCT and CT as statistically equivalent for 18 of 21 landmarks, with CT superior to CBCT for the crura of stapes, chorda tympani, and sigmoid sinus.

Conclusion

CBCT provides comparable image quality to conventional CT for temporal bone anatomical sites in cadaveric specimens. Clinical applications of low‐dose CBCT imaging in surgical planning, intraoperative guidance, and postoperative assessment are promising but require further investigation.
Clinical impact of diastolic function after surgical ventricular restoration
Authors: Shimamoto Takeshi , Sakaguchi Genichi , Komiya Tatsuhiko
Published: October 2013

Objective

The impact of diastolic function on the clinical outcome of surgical ventricular restoration remains controversial.

Methods

71 patients undergoing surgical ventricular restoration between 1999 and 2012 were investigated. Perioperative echocardiographic parameters were compared, risk factors for deaths and cardiac events were analyzed, and actuarial freedom from death and cardiac events was computed.

Results

Preoperatively, the left ventricular end-systolic volume index was 77 ± 40 mL·m−2 and left ventricular ejection fraction was 33% ± 11%. Postoperatively, left ventricular systolic function was significantly improved (end-systolic volume index 49 ± 31 mL·m−2, ejection fraction 42.1% ± 11.7%) with a 33.8% ± 21.9% reduction in left ventricular end-systolic volume index. The transmitral filling deceleration time decreased from 198 ± 54 to 150 ± 46 ms, and the ratio of early peak filling velocities increased significantly postoperatively (from 16 ± 10 to 21 ± 17). Freedom from death and cardiac events at 5 years was 78% ± 5% and 64% ± 6%, respectively. Multivariate analyses revealed that age was a significant risk factor for all-cause death, postoperative transmitral inflow pattern for cardiac death, and preoperative mitral regurgitation and postoperative transmitral inflow pattern for cardiac events.

Conclusion

Despite its positive impact on systolic function, surgical ventricular restoration negatively affects postoperative diastolic function. Postoperative severe diastolic dysfunction may correlate with late mortality and cardiac events.
Role of renal biomarkers as predictors of acute kidney injury in cardiac surgery
Authors: Ghatanatti Ravi , Teli Anita , Tirkey Sundeep Sanjivan , Bhattacharya Subhankar , Sengupta Gautam , Mondal Ansuman
Published: October 2013

Cardiac surgery is unique in using cardiopulmonary bypass in various clinical scenarios. Injury of vital organs is unavoidable in the perioperative period. Acute kidney injury is a consequence of the systemic inflammatory response after bypass, emboli, ischemia, and low cardiac output states, reportedly occurring in 30%–40% of open heart surgeries. Acute kidney injury is associated with increased morbidity, mortality, and cost. Many preventive measures (off-pump procedures, decreased crossclamp time, pulsatile flow, adequate hydration) are taken in the perioperative period to avoid organ injury, but in vain. Traditionally, blood urea, serum creatinine, and creatinine clearance rate were applied for prediction of acute kidney injury. The recent emergence of biomarkers such as neutrophil gelatinase-associated lipocalin, cystatin C, liver-type fatty acid binding protein, interleukin-18, kidney injury molecule-1, and tetrahydrobiopterin have helped in detecting acute kidney injury long before the rise of serum creatinine. These biomarkers can also be used as tools for predicting therapeutic effects in acute kidney injury and for monitoring drug toxicity. This review consolidates the knowledge of biomarkers and their application in acute kidney injury management.
Ready or Not? How Citizens and Public Officials Perceive Risk and Preparedness
Authors: Donahue Amy K. , Eckel Catherine C. , Wilson Rick K.
Published: October 2013

The more prepared people are, the less harm they will suffer when disaster strikes. Yet anecdotal and empirical evidence shows that people overestimate their preparedness and are underprepared. While a robust literature has matured around hazards, risk, and vulnerability, and disaster policy, politics, and management, the literature about individual preparedness is much more limited and inconsistent. We know little about why people prepare (or why they do not), and what would make them prepare more. As a result, public managers are at a loss about how to design effective preparedness programs. In this paper, we survey the literature on preparedness to crystallize the gaps in our understanding of when and how citizens react to the threat of disaster. We then examine and compare the views of risk and preparedness held by individuals and government officials drawing on insights from a 4-year study that involved three national surveys and intensive studies in two communities. We use this analysis to address two questions: What do citizens think and do about risks and preparedness, and why? How do local government officials understand what citizens think and do about risks and preparedness?
Being Nonprofit-Like in a Market Economy
Authors: Sanders Matthew L.
Published: October 2013

Nonprofit organizations experience a tension between pursuing their social missions and meeting the demands of a market economy. This mission-market tension is an everyday, practical concern for nonprofit practitioners. Yet, scholars know very little about how nonprofit practitioners define and manage this tension. Drawing on contradiction-centered perspectives of organizing, data from an ethnographic study of a single U.S. nonprofit organization demonstrate that the mission-market tension was defined and managed by organizational members as both a contradictory and interconnected phenomenon. This framing was enabled by specific communication practices that supported a productive and generative relationship between these seemingly incompatible goals. Findings suggest that the mission-market tension is an inherent condition of nonprofit organizing and highlight the central role of communication in successfully managing mission and market concerns.
Critical realism and systematic dialectics: a reply to Andrew Brown
Authors: Fleetwood Steve
Published: October 2013

In ‘Approach with caution: critical realism in social research’, Andrew Brown sets out a series of criticisms of critical realism from the perspective of systematic dialectics. This current article is one critical realist’s reply to Brown.
Impact of implant size on cement filling in hip resurfacing arthroplasty
Authors: de Haan Roel , Buls Nico , Scheerlinck Thierry
Published: October 2013

Larger proportions of cement within femoral resurfacing implants might result in thermal bone necrosis. We postulate that smaller components are filled with proportionally more cement, causing an elevated failure rate. A total of 19 femoral heads were fitted with polymeric replicas of ReCap (Biomet) resurfacing components fixed with low-viscosity cement. Two specimens were used for each even size between 40 and 56 mm and one for size 58 mm. All specimens were imaged with computed tomography, and the cement thickness and bone density were analyzed. The average cement mantle thickness was 2.63 mm and was not correlated with the implant size. However, specimen with low bone density had thicker cement mantles regardless of size. The average filling index was 36.65% and was correlated to both implant size and bone density. Smaller implants and specimens with lower bone density contained proportionally more cement than larger implants. According to a linear regression model, bone density but not implant size influenced cement thickness. However, both implant size and bone density had a significant impact on the filling index. Large proportions of cement within the resurfacing head have the potential to generate thermal bone necrosis and implant failure. When considering hip resurfacing in patients with a small femoral head and/or osteoporotic bone, extra care should be taken to avoid thermal bone necrosis, and alternative cementing techniques or even cementless implants should be considered. This study should help delimiting the indications for hip resurfacing and to choose an optimal cementing technique taking implant size into account.
Hydrogen effects on low cycle fatigue of high strength steels
Authors: Mansilla G. , Hereñú S. , Brandaleze E.
Published: October 2013

Hydrogen absorption occurs during steelmaking processes and causes detriment on mechanical properties, such as plasticity, fatigue strength and tensile strength, among others. The main purpose of the present paper is to study the hydrogen effects on the low cycle fatigue behaviour of a high strength steel, resulphurised and microalloyed. Before the cyclic tests, samples are cathodically charged using a H2SO4 acid solution. In some samples, poisons are added. The flow stress evolution during cycling was studied by analysing the so called ‘back’ and ‘friction’ stresses derived from the hysteresis loops. Fatigued specimens were observed through scanning electron microscopy and transmission electron microscopy. Additionally, the metallographic technique known as ‘silver decoration’ allows evaluation of the hydrogen distribution in the structure by applying energy dispersive analysis. The higher stress levels and cyclic softening rates exhibited by hydrogen charged samples in comparison with uncharged ones are related with the friction stress behaviour. The hydrogen is found mainly associated with MnS inclusions.
Important scaffold function of the Janus kinase 2 uncovered by a novel mouse model harboring a Jak2 activation-loop mutation
Authors: Keil Eric , Finkenstädt David , Wufka Christian , Trilling Mirko , Liebfried Pia , Strobl Birgit , Müller Mathias , Pfeffer Klaus
Published: October 2013

Key Points

Jak2 activation-loop–defective mutation results in partial interferon γ signaling, but Jak2 mutant mice die due to abolished EpoR signaling. Jak2 scaffold function mediates IFNGR complex integrity, activity, and physiological Jak1 localization.
c-kit expression profile and regulatory factors during spermatogonial stem cell differentiation
Authors: Zhang Lei , Tang Jiangjing , Haines Christopher J , Feng Huai , Lai Liangxue , Teng Xiaoming , Han Yibing
Published: October 2013

Background

It has been proven that c-kit is crucial for proliferation, migration, survival and maturation of spermatogenic cells. A periodic expression of c-kit is observed from primordial germ cells (PGCs) to spermatogenetic stem cells (SSCs), However, the expression profile of c-kit during the entire spermatogenesis process is still unclear. This study aims to reveal and compare c-kit expression profiles in the SSCs before and after the anticipated differentiation, as well as to examine its relationship with retinoic acid (RA) stimulation.

Results

We have found that there are more than 4 transcripts of c-kit expressed in the cell lines and in the testes. The transcripts can be divided into short and long categories. The long transcripts include the full-length canonical c-kit transcript and the 3′ end short transcript. Short transcripts include the 3.4 kb short transcript and several truncated transcripts (1.9-3.2 kb). In addition, the 3.4 kb transcript (starting from intron 9 and covering exons 10 ~ 21) is discovered to be specifically expressed in the spermatogonia. The extracellular domain of Kit is obtained in the spermatogonia stage, but the intracellular domain (50 kDa) is constantly expressed in both SSCs and spermatogonia. The c-kit expression profiles in the testis and the spermatogonial stem cell lines vary after RA stimulation. The wave-like changes of the quantitative expression pattern of c-kit (increase initially and decrease afterwards) during the induction process are similar to that of the in vivo male germ cell development process.

Conclusions

There are dynamic transcription and translation changes of c-kit before and after SSCs’ anticipated differentiation and most importantly, RA is a significant upstream regulatory factor for c-kit expression.
Transcriptome analysis of chicken kidney tissues following coronavirus avian infectious bronchitis virus infection
Authors: Cong Feng , Liu Xiaoli , Han Zongxi , Shao Yuhao , Kong Xiangang , Liu Shengwang
Published: October 2013

Background

Infectious bronchitis virus (IBV), a prototype of theCoronaviridaefamily, is an economically important causative agent of infectious bronchitis in chickens and causes an acute and highly contagious upper respiratory tract infections that may lead to nephritis. However, the molecular antiviral mechanisms of chickens to IBV infection remain poorly understood. In this study, we conducted global gene expression profiling of chicken kidney tissue after nephropathogenic IBV infection to better understand the interactions between host and virus.

Results

IBV infection contributed to differential expression of 1777 genes, of which 876 were up-regulated and 901 down-regulated in the kidney compared to those of control chickens and 103 associated with immune and inflammatory responses may play important roles in the host defense response during IBV infection. Twelve of the altered immune-related genes were confirmed by real-time RT-PCR. Gene ontology category, KEGG pathway, and gene interaction networks (STRING analysis) were analyzed to identify relationships among differentially expressed genes involved in signal transduction, cell adhesion, immune responses, apoptosis regulation, positive regulation of the I-kappaB kinase/NF-kappaB cascade and response to cytokine stimulus. Most of these genes were related and formed a large network, in which IL6, STAT1, MYD88, IRF1 and NFKB2 were key genes.

Conclusions

Our results provided comprehensive knowledge regarding the host transcriptional response to IBV infection in chicken kidney tissues, thereby providing insight into IBV pathogenesis, particularly the involvement of innate immune pathway genes associated with IBV infection.
LPA, HGF, and EGF utilize distinct combinations of signaling pathways to promote migration and invasion of MDA-MB-231 breast carcinoma cells
Authors: Harrison Susan MW , Knifley Teresa , Chen Min , O’Connor Kathleen L
Published: October 2013

Background

Various pathways impinge on the actin-myosin pathway to facilitate cell migration and invasion including members of the Rho family of small GTPases and MAPK. However, the signaling components that are considered important for these processes vary substantially within the literature with certain pathways being favored. These distinctions in signaling pathways utilized are often attributed to differences in cell type or physiological conditions; however, these attributes have not been systematically assessed.

Methods

To address this question, we analyzed the migration and invasion of MDA-MB-231 breast carcinoma cell line in response to various stimuli including lysophosphatidic acid (LPA), hepatocyte growth factor (HGF) and epidermal growth factor (EGF) and determined the involvement of select signaling pathways that impact myosin light chain phosphorylation.

Results

LPA, a potent stimulator of the Rho-ROCK pathway, surprisingly did not require the Rho-ROCK pathway to stimulate migration but instead utilized Rac and MAPK. In contrast, LPA-stimulated invasion required Rho, Rac, and MAPK. Of these three major pathways, EGF-stimulated MDA-MB-231 migration and invasion required Rho; however, Rac was essential only for invasion and MAPK was dispensable for migration. HGF signaling, interestingly, utilized the same pathways for migration and invasion, requiring Rho but not Rac signaling. Notably, the dependency of HGF-stimulated migration and invasion as well as EGF-stimulated invasion on MAPK was subject to the inhibitors used. As expected, myosin light chain kinase (MLCK), a convergence point for MAPK and Rho family GTPase signaling, was required for all six conditions.

Conclusions

These observations suggest that, while multiple signaling pathways contribute to cancer cell motility, not all pathways operate under all conditions. Thus, our study highlights the plasticity of cancer cells to adapt to multiple migratory cues.