bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of Routine Pathology Review on Treatment for Node-Negative Breast Cancer
Authors: Kennecke Hagen F. , Speers Caroline H. , Ennis Catherine A. , Gelmon Karen , Olivotto Ivo A. , Hayes Malcolm
Published: May 2012

Purpose

Routine secondary pathology review influences diagnosis and treatment among patients diagnosed with breast cancer. The impact of review on patients with node-negative breast cancer and the nature of the pathology elements leading to management changes are not well described.

Methods

Patients with node-negative, invasive, or in situ breast cancer and evaluable nodes referred to the British Columbia Cancer Agency during two time periods between 2004 and 2007 were included. Pathologists with expertise in breast cancer reviewed the original reports and slides. Biomarker testing was not routinely repeated. Medical record review was conducted to determine whether original pathology was changed and whether recommended therapy was affected.

Results

Among 906 eligible patients, 405 (45%) received a pathology review. Univariate comparisons revealed that reviewed patients were younger (P < .001) and more likely to have close margins (P < .001), whereas other characteristics were similar. A total of 102 pathology changes were documented among 81 patients (20%). The most frequently changed elements were grade (40%) and lymphovascular (26%), nodal (15%), and margin (12%) status. These changes resulted in 27 treatment modifications among 25 patients (6%). Treatment changes were primarily related to nodal and margin status, and only two of 27 were related to measurement of tumor biology in women with estrogen receptor–positive, node-negative breast cancer.

Conclusion

Reported rates of change are significant and warrant routine secondary pathology review among patients with node-negative breast cancer or ductal carcinoma in situ before final treatment is recommended. Review remains relevant in the era of gene expression signatures to determine margin and nodal status.
Bevacizumab in Combination With Chemotherapy As First-Line Therapy in Advanced Gastric Cancer: A Biomarker Evaluation From the AVAGAST Randomized Phase III Trial
Authors: Van Cutsem Eric , de Haas Sanne , Kang Yoon-Koo , Ohtsu Atsushi , Tebbutt Niall C. , Ming Xu Jian , Peng Yong Wei , Langer Bernd , Delmar Paul , Scherer Stefan J. , Shah Manish A.
Published: May 2012

Purpose

The AVAGAST study showed that adding bevacizumab to chemotherapy in patients with advanced gastric cancer improves progression-free survival and tumor response rate but not overall survival. To examine the hypothesis that angiogenic markers may have predictive value for bevacizumab efficacy in gastric cancer, AVAGAST included a prospective, mandatory biomarker program.

Patients and Methods

Patients with previously untreated, locally advanced or metastatic gastric cancer were randomly assigned to bevacizumab (n = 387) or placebo (n = 387) in combination with chemotherapy. Blood and tumor tissue samples were collected at baseline. Prespecified biomarkers included plasma vascular endothelial growth factor-A (VEGF-A), protein expression of neuropilin-1, and VEGF receptors-1 and -2 (VEGFR-1 and VEGFR-2). Correlations between biomarkers and clinical outcomes were assessed by using a Cox proportional hazards model.

Results

Plasma was available from 712 patients (92%), and tumor samples were available from 727 patients (94%). Baseline plasma VEGF-A levels and tumor neuropilin-1 expression were identified as potential predictors of bevacizumab efficacy. Patients with high baseline plasma VEGF-A levels showed a trend toward improved overall survival (hazard ratio [HR], 0.72; 95% CI, 0.57 to 0.93) versus patients with low VEGF-A levels (HR, 1.01; 95% CI, 0.77 to 1.31; interaction P = .07). Patients with low baseline expression of neuropilin-1 also showed a trend toward improved overall survival (HR, 0.75; 95% CI, 0.59 to 0.97) versus patients with high neuropilin-1 expression (HR, 1.07; 95% CI, 0.81 to 1.40; interaction P = .06). For both biomarkers, subgroup analyses demonstrated significance only in patients from non-Asian regions.

Conclusion

Plasma VEGF-A and tumor neuropilin-1 are strong biomarker candidates for predicting clinical outcome in patients with advanced gastric cancer treated with bevacizumab.
Mechanism of PKA-Dependent and Lipid-Raft Independent Stimulation of Connexin43 Expression by Oxytoxin in Mouse Embryonic Stem Cells
Authors: Yun Seung Pil , Park Su Shin , Ryu Jung Min , Park Jae Hong , Kim Mi Ok , Lee Jang-Hern , Han Ho Jae
Published: May 2012

Previous studies shows that connexins appear very early during murine embryo development, the gap junctional intercellular communication found in the inner cell mass of early embryo is also maintained in embryonic stem cells (ESC), and expression of oxytocin receptor (OTR) is developmentally regulated at early embryonic development. However, effect of oxytocin (OT) on the regulation of the connexin43 (Cx43) and maintenance of undifferentiation is not fully understood in stem cells. Therefore, we investigated the effect of OT on Cx43 expression and related signaling cascades in mouse ESC. OT increased Cx43 expression that was inhibited by the OTR inhibitor atosiban. In experiments to examine whether the effect of OT depends on lipid rafts, caveolin-1 (cav-1), cav-2, and flotillin-2, but not OTR, were detected in lipid raft fractions. Also, colocalization of OTR, cav-1, and cav-2 was not detected. Moreover, the lipid raft disruptor methyl-β-cyclodextrin did not attenuate OT-induced Cx43 expression. In experiments to examine related signaling pathways, OT activated cAMP/protein kinase A (PKA) which was inhibited by adenylyl cyclase inhibitor SQ 22536 and PKA inhibitor PKI. OT increased nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) phosphorylation which was inhibited by PKI. OT also increased cAMP response element-binding (CREB)/CREB-binding protein (CBP) expression in the nucleus and induced the formation of CREB1/NF-κB/CBP complexes, which was blocked by the NF-κB-specific small interfering RNA, NF-κB inhibitors, SN50, and bay11–7082. Complex disruption by NF-κB inhibitors decreased OT-induced Cx43 expression. In conclusion, OT stimulates Cx43 expression through the NF-κB/CREB/CBP complex via the lipid raft-independent OTR-mediated cAMP/PKA in mouse ESC.
Wnt5a and Wnt11 are essential for second heart field progenitor development
Authors: Cohen Ethan David , Miller Mayumi F. , Wang Zichao , Moon Randall T. , Morrisey Edward E.
Published: May 2012

Wnt/β-catenin has a biphasic effect on cardiogenesis, promoting the induction of cardiac progenitors but later inhibiting their differentiation. Second heart field progenitors and expression of the second heart field transcription factor Islet1 are inhibited by the loss of β-catenin, indicating that Wnt/β-catenin signaling is necessary for second heart field development. However, expressing a constitutively active β-catenin with Islet1-Cre also inhibits endogenous Islet1 expression, reflecting the inhibitory effect of prolonged Wnt/β-catenin signaling on second heart field development. We show that two non-canonical Wnt ligands, Wnt5a and Wnt11, are co-required to regulate second heart field development in mice. Loss of Wnt5a and Wnt11 leads to a dramatic loss of second heart field progenitors in the developing heart. Importantly, this loss of Wnt5a and Wnt11 is accompanied by an increase in Wnt/β-catenin signaling, and ectopic Wnt5a/Wnt11 inhibits β-catenin signaling and promotes cardiac progenitor development in differentiating embryonic stem cells. These data show that Wnt5a and Wnt11 are essential regulators of the response of second heart field progenitors to Wnt/β-catenin signaling and that they act by restraining Wnt/β-catenin signaling during cardiac development.
Using Internet Data for Economic Research
Authors: Edelman Benjamin
Published: May 2012

The data used by economists can be broadly divided into two categories. First, structured datasets arise when a government agency, trade association, or company can justify the expense of assembling records. The Internet has transformed how economists interact with these datasets by lowering the cost of storing, updating, distributing, finding, and retrieving this information. Second, some economic researchers affirmatively collect data of interest. For researcher-collected data, the Internet opens exceptional possibilities both by increasing the amount of information available for researchers to gather and by lowering researchers' costs of collecting information. In this paper, I explore the Internet's new datasets, present methods for harnessing their wealth, and survey a sampling of the research questions these data help to answer. The first section of this paper discusses “scraping” the Internet for data—that is, collecting data on prices, quantities, and key characteristics that are already available on websites but not yet organized in a form useful for economic research. A second part of the paper considers online experiments, including experiments that the economic researcher observes but does not control (for example, when Amazon or eBay alters site design or bidding rules); and experiments in which a researcher participates in design, including those conducted in partnership with a company or website, and online versions of laboratory experiments. Finally, I discuss certain limits to this type of data collection, including both “terms of use” restrictions on websites and concerns about privacy and confidentiality.
The Rise of Middle Kingdoms: Emerging Economies in Global Trade
Authors: Hanson Gordon H
Published: May 2012

In this paper, I examine changes in international trade associated with the integration of low- and middle-income countries into the global economy. Led by China and India, the share of developing economies in global exports more than doubled between 1994 and 2008. One feature of new trade patterns is greater South-South trade. China and India have booming demand for imported raw materials, which they use to build cities and factories. Industrialization throughout the South has deepened global production networks, contributing to greater trade in intermediate inputs. A second feature of new trade patterns is the return of comparative advantage as a driver of global commerce. Growth in low- and middle-income nations makes specialization according to comparative advantage more important for the global composition of trade, as North-South and South-South commerce overtakes North-North flows. China's export specialization evolves rapidly over time, revealing a capacity to speed up product ladders. Most developing countries hyper-specialize in a handful of export products. The emergence of low- and middle-income countries in trade reveals significant gaps in knowledge about the deep empirical determinants of export specialization, the dynamics of specialization patterns, and why South-South and North-North trade differ.
I need to gain vascular access: ultrasound-guided techniques
Authors: Sloan John
Published: May 2012

Ultrasound has been used to assist line placement for many years, and it is known that ultrasound aids the placement of central and peripheral lines, both in terms of speed of access and reduction of complications. The indications for the use of ultrasound in vascular access vary. In central access, ultrasound should be used at all times unless time-critical intervention mandates otherwise, e.g. in cardiac arrest. In femoral access, it is a very useful adjunct and can be used for reliable, rapid large vein access. In peripheral access, it has a use when conventional access fails. In general terms ultrasound can be used to identify relevant anatomy prior to cannulation, or to guide the process of cannulation. This paper outlines the approaches available.
Investigating the value of a surveillance scan of the superficial femoral artery at one year post-bare metal stent insertion
Authors: Ralph R , Wolstenhulme S , Nicholls M
Published: May 2012

Introduction

Placing a bare metal stent within the superficial femoral artery (SFA) can prolong vessel patency when compared with balloon angioplasty alone. Subsequent in-stent re-stenosis does occur in some individuals. In our institution, a surveillance programme to identify and treat ‘clinically silent’ stenoses has been running for two years and the purpose of this study was to evaluate this programme.

Methods

Retrospective review of cases was performed making note of indication for stenting, initial clinical outcome and the results of follow-up diagnostic and interventional radiological procedures.

Results

In total, 41 patients were included in the study. The majority (76%) had a good clinical outcome maintained during the first year at which stage a surveillance ultrasound was performed. Sixteen of these showed no evidence of significant in-stent stenosis or occlusion. Eleven of the remainder had ‘clinically silent’ in-stent stenosis. Nine of these had successful in-stent angioplasty. Ten (24%) patients became symptomatic within the first year. Ultrasound in seven of these patients revealed two in-stent occlusions, one in-stent re-stenosis and four with no significant findings. One patient went straight to have angiography, revealing in-stent re-stenosis.

Conclusion

Our surveillance programme has successfully identified and treated clinically silent in-stent stenoses in 22% of patients with an SFA stent who may have progressed to symptomatic stenosis or occlusion. Our results highlight the importance of ultrasound surveillance following stent placement. Based on only one asymptomatic patient experiencing stent occlusion at one year, and symptomatic stent problems occurring anywhere from six to 193 days, we consider that one year surveillance is acceptable.
A rare case of liver lymphangioma
Authors: Edwards Hazel , Simkins Alexandra , Claxton Julie
Published: May 2012

Finding an unexpected large mass in the liver requires prompt careful investigation and management. Imaging plays a vital part in the patient's pathway but histological analysis remains the gold standard for accurate diagnosis and may prevent unnecessary surgical intervention. We report the incidental detection and subsequent management of a large intra-abdominal mass located directly adjacent to the left lobe of the liver. Imaging appearances were consistent with a necrotic metastasis or a fibrolamellar hepatocellular carcinoma (FLHCC), both of which carry a poor prognosis. However, tissue analysis from a core biopsy correlated with lymphangioma, thus affording conservative management. Both FLHCC and lymphangioma are rare tumours but the prognosis for these conditions is very different. We describe briefly the demographics and imaging features associated with each one.
The Learning Curve of IT Knowledge Workers in a Computing Call Center
Authors: Kim Youngsoo , Krishnan Ramayya , Argote Linda
Published: May 2012

We analyze learning and knowledge transfer in a computing call center. The information technology (IT) technical services provided by call centers are characterized by constant changes in relevant knowledge and a wide variety of support requests. Under this IT problem-solving context, we analyze the learning curve relationship between problem-solving experience and performance enhancement. Based on data collected from a university computing call center consisting of different types of consultants, our empirical findings indicate that (a) the learning effect—as measured by the reduction of average resolution time—occurs with experience, (b) knowledge transfer within a group occurs among lower-level consultants utilizing application-level knowledge (as opposed to technical-level knowledge), and (c) knowledge transfers across IT problem types. These estimates of learning and knowledge transfer contribute to the development of an empirically grounded understanding of IT knowledge workers' learning behavior. The results also have implications for operational decisions about the staffing and problem-solving strategy of call centers.
Underlying Consumer Heterogeneity in Markets for Subscription-Based IT Services with Network Effects
Authors: Niculescu Marius F. , Shin Hyoduk , Whang Seungjin
Published: May 2012

In this paper we explore the underlying consumer heterogeneity in competitive markets for subscription-based information technology services that exhibit network effects. Insights into consumer heterogeneity with respect to a given service are paramount in forecasting future subscriptions, understanding the impact of price and information dissemination on market penetration growth, and predicting the adoption path for complementary products that target the same customers as the original service. Employing a continuous-time utility model, we capture the behavior of a continuum of consumers who are differentiated by their intrinsic valuations from using the service. We study service subscription patterns under both perfect and imperfect information dissemination. In each case, we first specify the conditions under which consumer rational behavior supported by the utility model can explain a general observed adoption path, and if so, we explicitly derive the analytical closed-form expression for the consumer valuation distribution. We further explore the impact of awareness and distribution skewness on adoption. In particular, we highlight the practical forecasting importance of understanding the information dissemination process in the market as observed past adoption may be explained by several distinct awareness and heterogeneity scenarios that may lead to divergent adoption paths in the future. Moreover, we show that in the later part of the service lifecycle the subscription decision for new customers can be driven predominantly by information dissemination instead of further price markdowns. We also extend our results to time-varying consumer valuation scenarios. Furthermore, based on our framework, we advance a set of heuristic methods to be applied to discrete-time real industry data for estimation and forecasting purposes. In an empirical exercise, we apply our methodology to the Japanese mobile voice services market and provide relevant managerial insights from the analysis.
Young Adults' Contraceptive Knowledge, Norms and Attitudes: Associations with Risk Of Unintended Pregnancy
Authors: Frost Jennifer J. , Lindberg Laura Duberstein , Finer Lawrence B.
Published: May 2012

CONTEXT: Women aged 18–29 have higher rates of unintended pregnancy than any other age‐group. Information is needed to understand what characteristics are associated with risky contraceptive use practices among this population and to develop new strategies for reducing these women's risk of unintended pregnancy.

METHODS: Data related to unintended pregnancy risk were collected from a nationally representative sample of 1,800 unmarried women and men aged 18–29 surveyed by telephone in 2009. Among those at risk of unintended pregnancy, multiple logistic regression was used to assess associations between contraceptive knowledge, norms and attitudes and selected risky contraceptive behaviors.

RESULTS: More than half of young men and a quarter of young women received low scores on contraceptive knowledge, and six in 10 underestimated the effectiveness of oral contraceptives. Among women, for each correct response on a contraceptive knowledge scale, the odds of expecting to have unprotected sex in the next three months decreased by 9%, of currently using a hormonal or long‐acting reversible method increased by 17%, and of using no method decreased by 17%. Fear of side effects, norms and attitudes that favor nonmarital pregnancy or undervalue the importance of contraception, pregnancy ambivalence and mistrust of government's role in promoting contraception were also associated with one or more risky contraceptive use behaviors.

CONCLUSIONS: Programs to increase young adults’ knowledge about contraceptive methods and use are urgently needed. Given the demonstrated link between method knowledge and contraceptive behaviors, such programs may be useful in addressing risky behavior in this population.
STD and HIV Risk Factors Among U.S. Young Adults: Variations by Gender, Race, Ethnicity and Sexual Orientation
Authors: Mojola Sanyu A. , Everett Bethany
Published: May 2012

CONTEXT:

STDs, including HIV, disproportionately affect individuals who have multiple minority identities. Understanding differences in STD risk factors across racial, ethnic and sexual minority groups, as well as genders, is important for tailoring public health interventions.

METHODS:

Data from Waves 3 (2001–2002) and 4 (2007–2008) of the National Longitudinal Study of Adolescent Health were used to develop population‐based estimates of STD and HIV risk factors among 11,045 young adults (mean age, 29 at Wave 4), by gender, race and ethnicity, and sexual orientation (heterosexual, mixed‐oriented, gay). Regression analyses were conducted to examine associations between risk factors and young adults’ characteristics.

RESULTS:

Overall, sexual‐minority women in each racial or ethnic group had a higher prevalence of sexual risk behaviors—including a history of multiple partners, forced sex and incarceration—than their heterosexual counterparts. Mixed‐oriented women in each racial or ethnic group were more likely than heterosexual white women to have received an STD diagnosis (odds ratios, 1.8–6.4). Black men and sexual‐minority men also appeared to be at heightened risk. Gay men in all racial and ethnic groups were significantly more likely than heterosexual white men to report having received an STD diagnosis (2.3–8.3); compared with heterosexual white men, mixed‐oriented black men had the highest odds of having received such a diagnosis (15.2).

CONCLUSIONS:

Taking account of multiple minority identities should be an important part of future research and intervention efforts for STD and HIV prevention.
Response Surface Modeling and Optimization of Immobilized Candida antarctica Lipase-Catalyzed Production of Dicarboxylic Acid Ester
Authors: Chaibakhsh Naz , Abdul Rahman Mohd Basyaruddin , Basri Mahiran
Published: May 2012

Dicarboxylic acid esters are one of the important classes of synthetic lubricants which exhibit good oxidation and thermal stability, low volatility, shear stability, high viscosity index and low toxicity. In this work, enzymatic synthesis of dioleyl adipate ester was performed in batch mode with a stirred tank reactor (STR). Immobilized Candida antarctica lipase B was used as the biocatalyst for the esterification reaction. Response surface methodology (RSM) based on a four-factor-five-level central composite rotatable design (CCRD) was employed to model and analyze the reaction. The effects of all investigated parameters including amount of enzyme (1-10%w/w), temperature (35-75oC), time (30-480 min) and impeller speed (1-500 rpm) were significant (P<0.0001). All factors positively affected the yield with reaction time having the most significant effect. The highest obtained conversion yield was 96.2% under experimental conditions of 60.0oC, 323.7 min, amount of enzyme 6.0%w/w of the substrates and 500 rpm impeller speed. Verification experiments exhibited good correspondence between actual yields and the values predicted by the statistical model. The predictive model was successfully applied for optimization of upscale synthesis of adipate ester.
Optimization of Pumping Schedules Using the Genealogical Decision Tree Approach
Authors: Ikonen Enso , Selek István , Bene József
Published: May 2012

This paper examines the application of a particle filtering-based optimization technique, the genealogical decision trees (GDT), to a finite horizon pump scheduling problem in a water distribution network. The GDT approach for trajectory tracking is first introduced, and a modified algorithm for minimization of costs during pump sequence optimization is then presented. Several variants of the algorithm are suggested, using the extended end constraint and neutrality. The performance of the optimization in various algorithm and parameter settings is examined in extensive simulations. It was observed that both the extended end constraint and neutrality improved the performance, however the deviation between solutions within a population and between different runs remained uncomfortably large. Finally, a comparison with a number of alternative up-to-date optimization techniques is provided. It was observed that the performance of GDT was adequate, compared with the best available approaches.
Applying an FSK Based Transmission Scheme to Broadband Channels Using Frequency Domain Equalization
Authors: Georgi Dr. Sebastian , Peissig Prof. Dr. Jürgen
Published: May 2012

Equalization of broadband signals can be efficiently realized in frequency domain. One prominent example is the orthogonal frequency division multiplexing (OFDM) transmission technique. With the introduction of a cyclic prefix and a modulation onto orthogonal subcarriers the equalization can be performed in frequency domain with one tap only. However the extremely high peak to average power ratio of OFDM modulated transmit signals and the demand of linearity inside the signal transmission chain results in a poor energy efficiency at the power amplifier. This paper claims, that as long as a cyclic prefix exists, any receive signal can be equalized in frequency domain.

In this paper a transmission scheme with constant envelope is chosen for energy efficiency reasons. Therefore an FSK modulation and gaussian pulse shaping is used to create the transmit signal. Equalization at the receiver is done in frequency domain as known in OFDM. To simplify the equalization, a cyclic prefix is added to the transmit signal as well.

This transmission scheme is introduced and evaluated in terms of spectral efficiency and bit error rate (BER) performance in this paper. The comparison is done with a typical OFDM system. In particular the characteristics of a nonlinear power amplifier are considered. It will be shown, that signals with constant envelope such as FSK modulated signals can also make use of an OFDM like equalization procedure with comparable BER performance and spectral requirements.
Future Data Communication Architectures for Safety Critical Aircraft Cabin Systems
Authors: Berkhahn Sven-Olaf
Published: May 2012

The cabin of modern aircraft is subject to increasing demands for fast reconfiguration and hence flexibility. These demands require studies for new network architectures and technologies of the electronic cabin systems, which consider also weight and cost reductions as well as safety constraints.

Two major approaches are in consideration to reduce the complex and heavy wiring harness: the usage of a so called hybrid data bus technology, which enables the common usage of the same data bus for several electronic cabin systems with different safety and security requirements and the application of wireless data transfer technologies for electronic cabin systems.
10 Years of Car-2-X Communication – a Success Story?
Authors: Wischhof Lars , Ebner André
Published: May 2012

For more than ten years, car-2-x communication has been a major topic of research in the scientific community and an important development focus for the automotive industry. First, this article takes a retrospective look at the evolution of car-2-x and the two different communication paradigms: decentralized car-2-car communication and centralized cellular solutions. Afterwards, a comparison of their technical advantages and limitations is presented, respectively. The result shows that in order to implement safety-relevant applications, car-2-car communication has strong advantages compared to cellular technologies but requires high market penetration. However, its introduction solely for safety applications is difficult since the required penetration will not be achieved until several years after initial deployment. Therefore, car-2-car communication must provide a benefit to the customer, even in the phase of market introduction. For this purpose, the article outlines an approach called SODAD (Segment-Oriented Data Abstraction and Dissemination). It offers a possibility to introduce decentralized vehicular applications with early customer benefit, in order to enable safety applications based on car-2-car communication on a long term.
Assessment of the early signs of decay of Populus deltoides wafers exposed to Trametes versicolor by near infrared spectroscopy
Authors: Green Benny , Jones Paul David , Nicholas Darrel D. , Schimleck Laurence R. , Shmulsky Rubin , Dahlen Joseph
Published: May 2012

The use of near infrared (NIR) spectroscopy to predict levels of white-rot degradation in Populus deltoides (cottonwood) by Trametes versicolor over the couse of 1–8 days was investigated. NIR spectra were collected from cross-sectional faces following laboratory soil block decay tests. Spectra in the range of 1100–2400 nm were calibrated in terms of mass loss, compression strength and exposure period based on data of standard methods. The first and second derivatives of NIR spectra were also included into the calibration, which was done by partial least squares regression. The best calibrations with the strongest R2 values were obtained in terms of exposure period (R2 0.92, second derivative), mass loss (R2 0.89, first derivative) and compression strength (R2 0.51, second derivative). As far as the validation (prediction) statistics are concerned, the following data were obtained: exposure period (R2=0.71; RPDp 1.81, second derivative), mass loss prediction (R2=0.43; RPDp=0.67, first derivative) and compression strength R2=0.28; RPDp=1.14 (second derivative). The weak statistical data can be interpreted only in a way that the data are not robust and thus an early prediction of fungal attack by NIR spectroscopy is not yet reliable.
Impact of image analysis software on quantitation of 1D gel electrophoresis analysis/Einfluss der Bildanalysesoftware auf die Bewertung von 1D Gelelektrophoresen
Authors: Kahlenberg Franka , Sack Ulrich , Boldt Andreas
Published: May 2012

Background: Image analysis of 1D gel electrophoresis can be performed by numerous types of software. The results are used, e.g., to create reference data or for association with diseases. In this study, we analyzed statistical differences between two types of established image analysis software. The aim was to inform customers that different types of software may produce various results which may lead to different data interpretations.

Methods: Automated serum protein electrophoresis (albumin, α1-globulin, α2-globulin, β-globulin and γ-globulin) was performed with sera from 25 patients (randomized). Gel bands were quantitatively analyzed by TotalLab 120 (TL120), LabImage 1D (L340) and Phoresis (reference standard). Finally, the degree of deviation (vs. reference standard) of obtained data was investigated by statistical methods (Bland-Altman, Passing-Bablok, reliability).

Results: Passing-Bablok analysis: in L340 and TL120 linearity of test data vs. reference data was passed (p<0.01; L340: y=0.00+1.00x vs. TL120: y=–0.01+1.02x). Bland-Altman analysis: L340 exhibited a lower deviation and standard deviation to reference (mean: –1.5%; SD: 23.0% to –25.9%) vs. TL120 (mean: –8.2%; SD: 32.6% to –48.6%). Reliability: L340 (k=0.404; 95% CI=0.315–0.493) vs. TL120 (k=0.105; 95% CI=0.105–0.245). Detailed serum protein analysis revealed that most data (except α1-globulin) obtained by L340 were within 5% tolerance range, in contrast to data from TL120 (mean%±SEM%: albumin: 0.68±0.49 vs. 6.26±1.44; α1-globulin: –10.80±3.02 vs. –33.72±4.78; α2-globulin: –2.19±1.75 vs. –16.51±2.13; β-globulin: 0.99±1.67 vs. –9.84±2.78; γ-globulin: –1.44±1.73 vs. 5.00±5.67).

Conclusion: In this study, it was shown that 1D electrophoresis data varied in a wide range depending on the type of image software. Awareness of these facts and sensible choice of 1D electrophoresis image software may help avoid incorrect data analysis.
Autoantikörpernachweis mittels indirekter Immunfluoreszenz an HEp-2-Zellen1)/Autoantibody detection using indirect immunofluorescence on HEp-2 cells
Authors: Sack Ulrich , Conrad Karsten , Csernok Elena , Frank Ingrid , Hiepe Falk , Krieger Thorsten , Kromminga Arno , von Landenberg Philipp , Messer Gerald , Witte Torsten , Mierau Rudolf
Published: May 2012

Der Nachweis von Autoantikörpern ist ein wichtiger Bestandteil der Diagnostik und Verlaufskontrolle von Patienten mit Autoimmunerkrankungen. In der Labordiagnostik der Kollagenosen und der autoimmunen Lebererkrankungen spielt die indirekte Immunfluoreszenz an HEp-2-Zellen im Rahmen einer Stufendiagnostik eine zentrale Rolle. Trotz hoher Qualität der Diagnostik können die Befunde zwischen verschiedenen Labors jedoch wegen fehlender Standardisierung und subjektiver Faktoren zum Teil erheblich differieren. Die vorliegende Arbeit formuliert Empfehlungen für eine vereinheitlichte Bearbeitung und Interpretation des HEp-2-Zell-Testes zum Nachweis von nicht organspezifischen (v.a. antinukleären) Antikörpern. Dabei werden Anforderungen an die verwendeten Diagnostika, Hinweise für die Abarbeitung und Auswertung im Labor und Empfehlungen für die Interpretation gegeben. Für eine optimale Labordiagnostik sind neben einer aussagefähigen klinischen Verdachtsdiagnose und einem erfahrenen Labordiagnostiker folgende Eckpunkte zu empfehlen: Initiales Screening mittels indirekter Immunfluoreszenz an sorgfältig ausgewählten HEp2-Zellen, beginnend mit einer Serumverdünnung von 1:80 und Auswertung in einem lichtstarken Mikroskop, positive Befundung ab einem Titer von 1:160, laborinterne Qualitätssicherung und vereinheitlichte Befundung. Ziel ist die Verbesserung der Diagnostik und Betreuung von Patienten mit Autoimmunerkrankungen als zentrales Anliegen der „European Autoimmunity Standardization Initiative“ (EASI).
Birkenpollenassoziierte Sojaallergie: diagnostische Möglichkeiten und klinische Relevanz/Birch pollen associated soy allergy: possibilities in diagnostic and clinical relevance
Authors: Beyer Susanne , Sack Ulrich , Treudler Regina
Published: May 2012

Hintergrund: Birkenpollenallergiker leiden oft unter Nahrungsmittelallergien in Form eines oralen Allergiesyndroms beim Verzehr von Kern- und Steinobst. Diese Beschwerden beruhen auf einer immunologischen Kreuzreaktion zwischen Pollen- und Nahrungsmittelallergenen. In den letzten Jahren konnte gezeigt werden, dass auch proteinreiche Sojaprodukte von vielen Birkenpollenallergikern nicht vertragen werden können. Dabei sind zum Teil sehr schwere anaphylaktische Symptome beschrieben worden. Als Ursache dieser Soforttypreaktionen auf Soja wurde ein mit dem Hauptallergen der Birke, dem Bet v 1, kreuzreagierendes Sojaallergen mit dem Namen Gly m 4 identifiziert.

Methoden: Am Beispiel eines Kollektives von 73 Leipziger Birkenpollenallergikern mit begleitender Nahrungsmittelallergie werden Ergebnisse einer Patientenbefragung, eines Prick-zu-Prick-Tests mit Sojadrink, der Bestimmung von spezifischem IgE gegen Gly m 4 und des Basophilenstimulationstests mit Gly m 4 vorgestellt.

Ergebnisse und Schlussfolgerungen: Wir konnten zeigen, dass sich kommerziell erhältliche Prick-Test-Extrakte sowie die Bestimmung von spezifischem IgE gegen Sojabohnenmix/f14 nicht zur Diagnostik der pollenassoziierten Sojaallergie eignen. Deutlich häufiger kann durch einen Prick-zu-Prick-Test mit Sojadrink und die Bestimmung von spezifischem IgE gegen rGly m 4 eine Sojaensibilisierung nachgewiesen werden. So reagierten 79% (55/70) der eingeschlossenen Birkenpollenallergiker positiv im Prick-zu-Prick-Test mit Sojadrink und 89% (65/73) zeigten spezifisches IgE gegen rGly m 4 (CAP-Klasse>1). Obwohl nicht jede Sensibilisierung klinisch relevant zu sein scheint, konnte dennoch bei jedem dritten Patienten mit einer nachgewiesenen Sojasensibilisierung eine klinisch relevante Sojaallergie diagnostiziert werden.
Moderne Komplementanalytik Indikationen – Methodik – Perspektiven/Modern complement analysis: indications, methods and outlook
Authors: Tudoran Ruxandra , Kirschfink Michael
Published: May 2012

Das Komplementsystem ist eines der Schlüsselsysteme der angeborenen Immunität und der Homöostase. Eine überschießende Komplementaktivierung, aber auch das Fehlen einzelner Komplementkomponenten oder -regulatoren können lebensbedrohliche Zustände verursachen. Die zum Krankheitsverständnis notwendigen Grundlagen, Indikationen für eine Komplementdiagnostik, die Interpretation der Resultate sowie therapeutische Interventionsmöglichkeiten sollen in dieser Übersichtsarbeit detailliert dargestellt werden.
Ex ante Fairness in Criminal Law and Procedure
Authors: Chiao Vincent
Published: May 2012

In Furman v. Georgia, the United States Supreme Court announced that it would not tolerate a capital sentencing regime that imposed death sentences in a seriously arbitrary fashion. The question I ask in this paper is whether we should in fact object to arbitrariness in punishment. The answer I propose is that under plausibly adverse conditions, we might not object to arbitrary penal outcomes, because under those conditions a fair distribution of punishment would be one that equalizes chances across a class of similarly situated criminals. In particular, fairness may require no more than a rough equalization of ex ante chances under conditions of resource scarcity, an inability to rank claims reliably by comparative desert, and a pressing need for punishment to be imposed. I call this an ex ante theory of fairness.

The central virtue of ex ante fairness is that it is capable of reconciling parsimony in punishment with equity in its distribution, even when claims about who deserves what are deeply contested. Adopting an ex ante standard of fairness means that a concern for fair treatment of the guilty need not blind us to the realities of the severe resource constraints faced by American criminal justice, and vice versa.

After laying out the argument for ex ante fairness in general terms, I proceed to show how several prominent features of American criminal law and procedure—the Supreme Court’s capital jurisprudence, prosecutorial discretion, judicial sentencing discretion, and “strict” criminal liability—all exhibit an implicit commitment to an equalization of chances rather than of outcomes.
Effectiveness and Net Cost of Reminder/Recall for Adolescent Immunizations
Authors: Suh Christina A. , Saville Alison , Daley Matthew F. , Glazner Judith E. , Barrow Jennifer , Stokley Shannon , Dong Fran , Beaty Brenda , Dickinson L. Miriam , Kempe Allison
Published: May 2012

OBJECTIVE:

To assess the effectiveness of reminder/recall (R/R) for immunizing adolescents in private pediatric practices and to describe the associated costs and revenues.

METHODS:

We conducted a randomized controlled trial in 4 private pediatric practices in metropolitan Denver. In each practice, 400 adolescents aged 11 to 18 years who had not received 1 or more targeted vaccinations (tetanus-diphtheria-acellular pertussis, meningococcal conjugate, or first dose of human papillomavirus vaccine for female patients) were randomly selected and randomized to intervention (2 letters and 2 telephone calls) or control (usual care) groups. Primary outcomes were receipt of >1 targeted vaccines and receipt of all targeted vaccines 6 months postintervention. We calculated net additional revenue for each additional adolescent who received at least 1 targeted vaccine and for those who received all targeted vaccines.

RESULTS:

Eight hundred adolescents were randomized to the intervention and 800 to the control group. Baseline rates of having already received tetanus-diphtheria-acellular pertussis, meningococcal conjugate, and first dose of human papillomavirus vaccine before R/R ranged from 33% to 54%. Postintervention, the intervention group had significantly higher proportions of receipt of at least 1 targeted vaccine (47.1% vs 34.6%, P < .0001) and receipt of all targeted vaccines (36.2% vs 25.2%, P < .0001) compared with the control group. Three practices had positive net revenues from R/R; 1 showed net losses.

CONCLUSIONS:

R/R was successful at increasing immunization rates in adolescents and effect sizes were comparable to those in younger children. Practices conducting R/R may benefit financially if they can generate additional well-child care visits and keep supply costs low.
Reduction in Pediatric Identification Band Errors: A Quality Collaborative
Authors: Phillips Shannon Connor , Saysana Michele , Worley Sarah , Hain Paul D.
Published: May 2012

BACKGROUND AND OBJECTIVE:

Accurate and consistent placement of a patient identification (ID) band is used in health care to reduce errors associated with patient misidentification. Multiple safety organizations have devoted time and energy to improving patient ID, but no multicenter improvement collaboratives have shown scalability of previously successful interventions. We hoped to reduce by half the pediatric patient ID band error rate, defined as absent, illegible, or inaccurate ID band, across a quality improvement learning collaborative of hospitals in 1 year.

METHODS:

On the basis of a previously successful single-site intervention, we conducted a self-selected 6-site collaborative to reduce ID band errors in heterogeneous pediatric hospital settings. The collaborative had 3 phases: preparatory work and employee survey of current practice and barriers, data collection (ID band failure rate), and intervention driven by data and collaborative learning to accelerate change.

RESULTS:

The collaborative audited 11 377 patients for ID band errors between September 2009 and September 2010. The ID band failure rate decreased from 17% to 4.1% (77% relative reduction). Interventions including education of frontline staff regarding correct ID bands as a safety strategy; a change to softer ID bands, including “luggage tag” type ID bands for some patients; and partnering with families and patients through education were applied at all institutions.

CONCLUSIONS:

Over 13 months, a collaborative of pediatric institutions significantly reduced the ID band failure rate. This quality improvement learning collaborative demonstrates that safety improvements tested in a single institution can be disseminated to improve quality of care across large populations of children.
Cotransplantation of Allogeneic Mesenchymal and Hematopoietic Stem Cells in Children With Aplastic Anemia
Authors: Wang Hengxiang , Yan Hongmin , Wang Zhidong , Zhu Ling , Liu Jing , Guo Zikuan
Published: May 2012

We report here the preliminary results of allogeneic hematopoietic stem cell transplantation with mesenchymal stem cells (MSCs) for 6 cases of severe aplastic anemia. The patients ranged in age from 3 to 16 years, and the median time from diagnosis to transplantation was 32 months (range: 3–156 months). The conditioning regimens consisted of fludarabine, cyclophosphamide, and antithymocyte globulin with or without busulfan. Graft-versus-host disease (GvHD) was prevented by the administration of cyclosporine A, methotrexate, and mycophenolate mofetil, with or without anti-CD25 monoclonal antibody. The grafts were granulocyte colony–stimulating factor–mobilized bone marrow and peripheral blood from HLA antigen-haploidentical donors (3 cases) or peripheral blood only from unrelated HLA antigen-identical donors (3 cases). MSCs were intravenously injected at a median dose of 1.43 × 106/kg (range: 0.85–2.5 × 106/kg). The mean time for neutrophil and platelet recovery was 12.3 and 13.8 days, respectively. Acute GvHD grade I and II developed in 2 cases, and no chronic GvHD was documented. All patients were alive and transfusion independent at a median follow-up of 15 months (range: 6–29 months). Our report suggests that cotransplantation of allogeneic hematopoietic stem cells and MSCs might provide an opportunity for therapy for children with severe aplastic anemia.
Middle School Vaccination Requirements and Adolescent Vaccination Coverage
Authors: Bugenske Erin , Stokley Shannon , Kennedy Allison , Dorell Christina
Published: May 2012

OBJECTIVE:

To determine if middle school vaccination requirements are associated with higher coverage for adolescent vaccines.

METHODS:

School entry requirements for receipt of vaccination for school entry or education of parents for 3 vaccines recommended for adolescents: tetanus/diphtheria-containing (Td) or tetanus/diphtheria/acellular pertussis (TdaP), meningococcal conjugate (MenACWY), and human papillomavirus (HPV) vaccines in place for the 2008–2009 school year were reviewed for the 50 states and the District of Columbia. Vaccination coverage levels for adolescents 13 to 17 years of age by state requirement status and change in coverage from 2008 to 2009 were assessed by using the 2008–2009 National Immunization Survey-Teen.

RESULTS:

For the 2008–2009 school year, 32 states had requirements for Td/TdaP (14 specifically requiring TdaP) and none required education; 3 states required MenACWY vaccine and 10 others required education; and 1 state required HPV vaccine and 5 required education. Compared with states with no requirements, vaccination requirements were associated with significantly higher coverage for MenACWY (71% vs 53%, P < .001) and Td/TdaP (80% vs 70%, P < .001) vaccines. No association was found between education-only requirements and coverage levels for MenACWY and HPV vaccines. States with new 2008–2009 vaccination requirements (n = 6, P = .04) and states with preexisting vaccination requirements (n = 26, P = .02) for Td/TdaP experienced a significant increase in TdaP coverage over states with no requirements.

CONCLUSIONS:

Middle school vaccination requirements are associated with higher coverage for Td/TdaP and MenACWY vaccines, whereas education-only requirements do not appear to increase coverage levels for MenACWY or HPV vaccines. The impact on coverage should continue to be monitored as more states adopt requirements.
Developmental Outcome at 6.5 Years After Acidosis in Term Newborns: A Population-Based Study
Authors: Hafström Maria , Ehnberg Siv , Blad Sofia , Norén Håkan , Renman Cecilia , Rosén Karl Gustaf , Kjellmer Ingemar
Published: May 2012

OBJECTIVES:

Infants who develop encephalopathy after perinatal asphyxia have an increased risk of death and adverse neurologic outcome. Conflicting results exist concerning outcome in healthy infants with metabolic acidosis at birth. The aim of the current study was to evaluate whether metabolic acidosis at birth in term infants who appear healthy is associated with long-term developmental abnormalities.

METHODS:

From a population-based cohort (14 687 deliveries), 78 infants were prospectively identified as having metabolic acidosis (umbilical artery pH < 7.05 and base deficit in the extracellular fluid >12.0 mmol/L). Two matched controls per case were selected. The child health and school health care records were scrutinized for developmental abnormalities.

RESULTS:

Outcome measures at 6.5 years of age for 227 of 234 children (97%) were obtained. No differences were found concerning neurologic or behavioral problems in need of referral action or neurodevelopmental diagnosis in comparison of control children with acidotic children who had appeared healthy at birth, ie, had not required special neonatal care or had no signs of encephalopathy.

CONCLUSIONS:

Infants born with cord metabolic acidosis and who appear well do not have an increased risk for neurologic or behavioral problems in need of referral actions or special teaching approaches at the age of 6.5 years.