bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perils and pitfalls of permutation tests for distinguishing the effects of neighbouring polymorphisms
Authors: Biernacka Joanna M. , Cordell Heather J. 
Published: July 2006

AbstractIn a small region several marker loci may be associated with a trait, either because they directly influence the trait or because they are in linkage disequilibrium (LD) with a causal variant. Having established a potentially causal effect at a primary variant, we may ask if any other variants in the region appear to further contribute to the trait, indicating that the additional variant is either causal or is in LD with another causal locus. Methods of approaching this problem using case‐parent trio data include the stepwise conditional logistic regression approach described by Cordell and Clayton ([2002] Am. J. Hum. Genet. 70:124–141), and a constrained‐permutation method recently proposed by Spijker et al. ([2005] Ann. Hum. Genet. 69:90–101). Through simulation we demonstrate that the procedure described by Spijker et al. [2005], as well as unconditional logistic regression with “affected family‐based controls” (AFBACs), can lead to inflated type 1 errors in situations when haplotypes are not inferable for all trios, whereas the conditional logistic regression approach gives correct significance levels. We propose an alternative to the permutation method of Spijker et al. [2005], which does not rely on haplotyping, and results in correct type 1 errors and potentially high power when assumptions of random mating, Hardy‐Weinberg Equilibrium, and multiplicative effects of disease alleles are satisfied. Genet. Epidemiol. 2006. © 2006 Wiley‐Liss, Inc.
Sentinel node detection in breast cancer using contrast‐enhanced sonography with 25% albumin—Initial clinical experience
Authors: Omoto Kiyoka , Hozumi Yasuo , Omoto Yawara , Taniguchi Nobuyuki , Itoh Kouichi , Fujii Yasutomo , Mizunuma Hirobumi , Nagai Hideo 
Published: July 2006

AbstractPurpose.To determine the clinical usefulness of a sentinel lymph node (SLN) identification technique using contrast‐enhanced sonography (CEUS) with 25% albumin.Methods.The subjects were 23 women with breast cancer. Each was injected subcutaneously with 5 ml of 25% albumin solution as a negative contrast agent directly superficial to the breast tumor. The area was massaged, and the inferior axillary hairline was examined continuously using gray‐scale sonography with a 7.5‐ or 10‐MHz transducer. Any contrast‐enhanced lymph node was considered a CEUS‐detected SLN, was differentiated from other level I and II nodes, and was resected and pathologically assessed.Results.In all 23 patients, 1 or 2 CEUS‐detected SLNs (mean, 1.3 SLNs) were identified. Their sizes ranged from 5 mm to 25 mm (mean, 11.3 mm), and their depths (from the skin surface) ranged from 5mm to 20 mm (mean, 12.6 mm). Pathologic examination revealed a metastasis in 5 of the 23 patients, all in CEUS‐detected SLNs.Conclusions.In a clinical study using CEUS with 25% albumin, contrast‐enhanced nodes were identified in all subjects. The pathologic findings suggested that any metastatic nodes observed were SLNs, indicating that this technique may represent a new modality for SLN identification. © 2006 Wiley Periodicals, Inc. J Clin Ultrasound 34:317–326, 2006
Possible role of scavenger receptor SRCL in the clearance of amyloid‐βin Alzheimer's disease
Authors: Nakamura Kenji , Ohya Wakana , Funakoshi Hiroshi , Sakaguchi Gaku , Kato Akira , Takeda Masatoshi , Kudo Takashi , Nakamura Toshikazu 
Published: July 2006

AbstractAccumulation of β‐amyloid protein (Aβ) in the brain is a hallmark of Alzheimer's disease (AD), and Aβ‐mediated pathogenesis could result from increased production of Aβ or insufficient Aβ clearance by microglia, astrocytes, or the vascular system. Cell‐surface receptors, such as scavenger receptors, might play a critical role in the binding and clearing of Aβ; however, the responsible receptors have yet to be identified. We show that scavenger receptor with C‐type lectin (SRCL), a member of the scavenger receptor family containing coiled‐coil, collagen‐like, and C‐type lectin/carbohydrate recognition domains, is expressed in cultured astrocytes and microglia. In contrast to the low expression of SRCL in the wild‐type mouse brain, in a double transgenic mouse model of AD (Tg‐APP/PS1), immunohistochemistry showed that SRCL was markedly induced in Aβ‐positive astrocytes and Aβ‐positive vascular/perivascular cells, which are associated closely with cerebral amyloid angiopathy. In patients with AD, the distribution of SRCL was similar to that seen in the Tg‐APP/PS1 temporal cortex. The presence of a large number of SRCL/Aβ double‐positive particles in the intracellular compartments of reactive astrocytes and vascular/perivascular cells in Tg‐APP/PS1 mice and AD patients suggests a role for SRCL in Aβ clearance. Moreover, CHO‐K1 cells transfected with SRCL isoforms were found to bind fibrillar Aβ1–42. These findings suggest that SRCL could be the receptor involved in the binding or clearing of Aβ by glial and vascular/perivascular cells in AD. © 2006 Wiley‐Liss, Inc.
Tetracycline‐inducible gene expression in nuclear transfer embryos derived from porcine fetal fibroblasts transformed with retrovirus vectors
Authors: Choi Bok Ryul , Koo Bon Chul , Ahn Kwang Sung , Kwon Mo Sun , Kim Jin‐Hoi , Cho Seong‐Keun , Kim Kyoung Mi , Kang Jee Hyun , Shim Hosup , Lee Hyuna , Uhm Sang Jun , Lee Hoon Taek , Kim Teoan 
Published: July 2006

AbstractA critical problem of transgenic livestock production is uncontrollable constitutive expression of the foreign gene, which usually results in serious physiological disturbances in transgenic animals. One of the best solutions for this problem may be use of controllable gene expression system. In this study, using retrovirus vectors designed to express the enhanced green fluorescent protein (EGFP) gene under the control of the tetracycline‐inducible promoter, we examined whether the expression of the transgene could be controllable in fibroblast cells and nuclear transfer (NT) embryos of porcine. Transformed fibroblast cells were cultured in medium supplemented with or without doxycycline (a tetracycline analog) for 48 hr, and the induction efficiency was measured by comparing EGFP gene expression using epifluorescence microscopy and Western and Northern blot analyses. After the addition of doxycycline, EGFP expression increased up to 17‐fold. The nuclei of transformed fibroblast cells were transferred into enucleated oocytes. Fluorescence emission data revealed strong EGFP gene expression in embryos cultured with doxycycline, but little or no expression in the absence of the antibiotic. Our results demonstrate the successful regulation of transgene expression in porcine nuclear transfer embryos, and support the application of an inducible expression system in transgenic pig production to solve the inherent problems of side‐effects due to constitutive expression of the transgene. Mol. Reprod. Dev. © 2006 Wiley‐Liss, Inc.
Ubiquitin ligase gene expression in healthy volunteers with 20‐day bedrest
Authors: Ogawa Takayuki , Furochi Harumi , Mameoka Mai , Hirasaka Katsuya , Onishi Yuko , Suzue Naoto , Oarada Motoko , Akamatsu Motoki , Akima Hiroshi , Fukunaga Tetsuo , Kishi Kyoichi , Yasui Natsuo , Ishidoh Kazumi , Fukuoka Hideoki , Nikawa Takeshi 
Published: July 2006

AbstractIn animal models, several ubiquitin ligases play an important role in skeletal muscle atrophy caused by unloading. In this study we examined protein ubiquitination and ubiquitin ligase gene expression in quadriceps femoris muscle from healthy volunteers after 20‐day bedrest to clarify ubiquitin‐dependent proteolysis in human muscles after unloading. During bedrest, thickness and cross‐sectional area of the quadriceps femoris muscle decreased significantly by 4.6% and 3.7%, respectively. Ubiquitinated proteins accumulated in these atrophied human muscles. A real‐time reverse transcription–polymerase chain reaction system showed that bedrest significantly upregulated expression of two ubiquitin ligase genes, Cbl‐b and atrogin‐1. We also performed DNA microarray analysis to examine comprehensive gene expression in the atrophied muscle. Bedrest mainly suppressed the expression of muscle genes associated with control of gene expression in skeletal muscle. Our results suggest that, in humans, Cbl‐b– or atrogin‐1–mediated ubiquitination plays an important role in unloading‐induced muscle atrophy, and that unloading stress may preferentially inhibit transcriptional responses in skeletal muscle. Muscle Nerve, 2006
An awkward threesome—donors, governments and non‐state providers of health in low income countries
Authors: Palmer Natasha 
Published: July 2006

AbstractBilateral and multilateral donors make frequent reference to collaboration with non‐state providers (NSPs) in the health sector, and the desirability of so‐called public private partnerships. Governments of many low‐income countries are also increasingly committed to this goal in their policy statements. This article presents a range of cases from six countries of how governments, donors and NSPs interact. It describes examples of what type of engagement is taking place between governments and NSPs, highlights some common themes and reflects on common motivations for collaboration and constraints to it. Examples are examined under the original study design headings of dialogue, regulation, facilitation and contracting. These categories were not easy to sustain. Much government support to NSPs was characterised by donor involvement, fostering a ‘pilot project’ style of approach. In other cases, it was not so much a case of governments pursuing a specific intervention to support or regulate NSPs, as NGOs taking an initiative to fill a gap in government provision. The article highlights the main gap in interaction with NSPs as a comprehensive framework for regulating services provided by small scale, for profit NSPs. This is a serious shortcoming given that they deliver the bulk of basic health care in most of the countries examined. Copyright © 2006 John Wiley & Sons, Ltd.
Engaged or divorced? Cross‐service findings on government relations with non‐state service‐providers
Authors: Batley Richard 
Published: July 2006

AbstractNon‐state provision (NSP) of basic services is an important substitute for government services in most developing countries. The international policy environment favours the idea that service levels could be improved if government and non‐state providers collaborated. This article examines the experience based on studies of basic education and healthcare, water and sanitation in six African and South Asian countries. It finds that, while policy is now generally in support of NSP, practice is more often unsupportive and relationships are surrounded by mistrust. The main providers of non‐state services—local entrepreneurs, individual practitioners, community organisations and small NGOs—are largely absent from any dialogue with government. They are exposed to forms of regulation that are largely repressive and effectively designed to protect established interests. Nevertheless, the article identifies positive examples of alternative forms of regulation that advance improved service standards, of facilitation by large NGOs acting in an intermediary role in support of local actors, and of replicable forms of collaboration between government and non‐state providers. Copyright © 2006 John Wiley & Sons, Ltd.
Plant safety and risk with temporary equipment
Authors: Cadwallader L.C. 
Published: July 2006

AbstractTemporary equipment may be brought onto a plant site for a variety of process needs. The risk profile of the facility is altered by use of such temporary equipment, but since the time durations of temporary equipment usage are generally small, usually fewer than 90 days per year, the risk increase is also small and is typically not modeled in a probabilistic risk assessment. This article describes some risk issues with temporary equipment in long‐term use, gives a case study of a temporary, diesel‐driven air compressor under extended use at the Idaho National Laboratory, and suggests the need to model temporary equipment in the facility risk assessment if the equipment is used more than a few months. © 2006 American Institute of Chemical Engineers Process Saf Prog, 2006
Assessing design instability in iterative (agile) object‐oriented projects
Authors: Olague Hector M. , Etzkorn Letha H. , Li Wei , Cox Glenn 
Published: July 2006

AbstractAssessing progress and stability in rapid, highly iterative and agile object‐oriented software development processes is difficult because program evolution appears somewhat disorderly. With agile software development methods, the expected time to reach software stability is obscured by the dynamic nature of the agile process itself. The System Design Instability (SDI) metric was developed to help analyze object‐oriented software evolution under these conditions. In this paper we examine a new version of SDI, called SDIe, based on the maximum entropy in a system. We believe our new measure is easier to calculate than the original version of SDI since it is based on data that are more commonly available than those used by SDI; also, SDIe gives a more accurate indication of software stability and maturity since it suffers less from data spikes. To validate the new metric, we use maintenance data from a commercial software project, developed using an agile process; these are the same data that were collected and analyzed in the original SDI study. In addition, we apply the refined SDI metric to the evolution of a well‐established, open‐source, iteratively‐developed software product. The results of our case study indicate our new SDIe metric is a viable measure of system design stability. Copyright © 2006 John Wiley & Sons, Ltd.
Serum HER2 levels are increased in patients with chronic heart failure
Authors: Perik Patrick J. , de Vries Elisabeth G.E. , Gietema Jourik A. , van der Graaf Winette T.A. , Smilde Tom D.J. , Sleijfer Dirk T. , van Veldhuisen Dirk J. 
Published: July 2006

AbstractBackgroundThe use of trastuzumab, an antibody against the human epidermal growth factor receptor 2 (HER2), in patients with HER2 positive metastatic breast cancer, is related to cardiotoxicity.AimsTo investigate whether serum HER2 is increased in heart failure patients and related to disease severity.MethodsSerum HER2, plasma tumor necrosis factor (TNF)‐α and its soluble (s) receptors (sTNF‐R1 and 2) were determined with ELISA in chronic heart failure patients and age and gender‐matched healthy controls.ResultsSerum HER2 was higher (P=0.013) in 50 heart failure patients (18 female; median age 57 (range 33–77) years), mean 12.1±S.D. 2.3 ng/mL, than in 15 controls, 10.4±2.6 ng/mL. Serum HER2 levels correlated inversely with left ventricular ejection fraction (P=0.037) and were highest among NYHA class III patients, followed by NYHA class II patients and controls (P=0.029, Kruskal–Wallis test). STNF‐R1 (P<.001) and sTNF‐R2 (P=0.015) were higher in patients than controls, and correlated positively with HER2 (P=0.027 and P=0.036, respectively).ConclusionsSerum HER2 levels are increased in chronic heart failure patients. Further research is necessary to determine whether HER2 plays a role in the pathophysiology of heart failure.
Flexible Interaction Model for Complex Interactions of Multiple Anesthetics
Authors: Fidler Matthew , Kern Steven E. 
Published: July 2006

Background
Minto et al. (Anesthesiology 2000) described a mathematical approach based on response surface methods for characterizing drug-drug interactions between several intravenous anesthetic drugs. To extend this effort, the authors developed a flexible interaction model based on the general Hill dose-response relation that includes a set of parameters that can be statistically assessed for interaction significance.

Methods
This new model was developed to identify pharmacologically meaningful interaction-related parameters and address mathematical limitations in previous models. The flexible interaction model and the model of Minto et al. were compared in their assessment of additivity using simulated sample data sets. The flexible interaction model was also compared with the Minto model in describing drug interactions using data from several other clinical studies of propofol, opioids, and benzodiazepines from Short et al. (Anesthesiology 2002) and Kern et al. (Anesthesiology 2004).

Results
The flexible interaction model was able to accurately classify an additive interaction based on the classic definition proposed by Loewe, with at most an 8% difference between the two surfaces. Also, the proposed model fit the clinical interaction data as well or slightly better than that of Minto et al.

Conclusions
The new model can accurately classify additive and synergistic drug interactions. It also can classify antagonistic interactions with biologically rational surfaces. This has been a problem for other interaction models in the past. The statistically assessable interaction parameters provide a quantitative manner to assess the interaction significance.
Effectiveness of interferon plus ribavirin combination in the treatment of naive patients with hepatitis C virus type 5. A French multicentre retrospective study
Authors: BONNY C. , FONTAINE H. , POYNARD T. , HÉZODE C. , LARREY D. , MARCELLIN P. , BOURLIÈRE M. , BRONOWICKI J. P. , MERLE P. , ZARSKI J. P. , SAPEY T. , GUILLEMARD C. , UGHETTO S. , HENQUELL C. , NICOLAS C. , ROCHE C. , RANDL K. , BOMMELAER G. , ABERGEL A. 
Published: July 2006

SummaryAimTo assess the rate of sustained virological response in naïve hepatitis C virus‐type 5 patients treated by standard interferon or percutaneous endoscopic gastrostomy‐interferon (peg‐interferon) and ribavirin combination for 48 weeks.Patients and methodsA total of 87 hepatitis C virus patients were included from 12 centres in France; 28 patients received interferon plus ribavirin and 59 were treated with peg‐interferon plus ribavirin.ResultsBaseline characteristics were: mean age 58 ± 11 years, sex ratio 1, 66% had metavir fibrosis score ≥F2, 21% were cirrhotics and 53% had pretherapeutic viral load ≥800 000 IU/mL. Sustained virological response was achieved in 64% and 58% of hepatitis C virus‐5 patients treated with interferon and peg‐interferon, respectively (NS). In adherent patients, sustained virological response was obtained in 75% of patients. Sustained virological response in hepatitis C virus‐5 patients (60%) was significantly higher than sustained virological response in hepatitis C virus‐1 patients (37%) (P = 0.0499) and not significantly different from sustained virological response in hepatitis C virus‐2–3 patients (63%) (P = 0.8098).ConclusionsCombination therapy is effective in 60% of hepatitis C virus‐5‐infected patients. Sustained virological response seems better in hepatitis C virus‐5 patients than in hepatitis C virus‐1 patients, and is similar to that of hepatitis C virus‐2–3 patients. More studies are needed to determine optimal duration of treatment in hepatitis C virus‐5 patients.
Effect of repeated capsaicin ingestion on intestinal chemosensation and mechanosensation
Authors: HAMMER J. 
Published: July 2006

SummaryBackgroundIngestion of capsaicin reduces symptoms in functional dyspepsia but induces upper abdominal symptoms initially.AimsTo evaluate the effects of one week of oral dosing with capsaicin on mechanonociception and chemonociception.MethodsHealthy subjects ingested capsules containing 0.5 mg capsaicin t.d.s (n = 8) or placebo (n = 5) for 7 days. Before (day 0) and after (day 8) capsule ingestion the jejunum was distended with a balloon and perfused with a capsaicin solution. A graded questionnaire evaluated distension‐ and capsaicin‐induced sensation, aggregate perception scores were calculated.ResultsInfusion of capsaicin induced sensations similar to distension. In subjects receiving capsaicin capsules, mean ± S.E.M. perception scores at 24 mL distension volumes were 4.7 ± 1.2 (day 0) and 3.2 ± 1.3 (day 8, N.S.). Distension with 40 mL induced perception scores of 10.3 ± 1.0 vs. 8.2 ± 1.0 (P < 0.05). During capsaicin perfusion, first sensation was reported after 13.2 ± 1.9 min (day 0) and 8.1 ± 0.8 min (day 8, N.S.), discomfort thresholds after 44.1 ± 6.0 and 31.2 ± 5.7 min (P < 0.05). In the placebo group, mechano‐ and chemonociception remained unaltered on days 0 and 8.ConclusionsOne week of ingestion of capsaicin sensitized chemonociceptors, while sensitivity of mechanonociceptors for distension decreased. Painful sensations during the first week of treatment with capsaicin can be attributed to a sensitizing effect of capsaicin on vanilloid receptors.
Peripheral blood stem cell yield in 400 normal donors mobilised with granulocyte colony‐stimulating factor (G‐CSF): impact of age, sex, donor weight and type of G‐CSF used
Authors: Ings Stuart J. , Balsa Carmen , Leverett David , Mackinnon Stephen , Linch David C. , Watts Michael J. 
Published: July 2006

SummaryMobilised peripheral blood is now the main source of stem cells collected from normal donors. We report our experience of mobilising and collecting 400 normal healthy donors using standardised procedures and techniques. Target recipient doses were reached with one aphaeresis in 63% of donors and with two aphaereses in 81% of donors. Approximately 2% of donors yielded such low progenitor values that they were termed ‘poor mobilisers’. There were minor effects of donor age, weight and sex and where possible, larger male donors under the age of 55 years should be selected. Two forms of granulocyte colony‐stimulating factor (G‐CSF) were used at the same dose and no significant difference was seen in the yield of CD34+ cells collected/l of blood processed. However, a greater number of granulocyte‐macrophage colony‐forming cells were harvested using lenograstim (glycosylated G‐CSF) compared with filgrastim (non‐glycosylated G‐CSF; P = 0·002). CD34+ cell yields were also measured halfway through the aphaeresis procedure. This was found to be highly predictive of final yield and facilitated distribution of the stem cell product to other centres. The observation that CD34+ yields did not decline in the second half compared with the first half of aphaeresis suggests that the circulating cell numbers are not static.
Negative effects of changing temperature on amphibian immunity under field conditions
Authors: RAFFEL T. R. , ROHR J. R. , KIESECKER J. M. , HUDSON P. J. 
Published: July 2006

Summary

Recent evidence of the important role of emerging diseases in amphibian population declines makes it increasingly important to understand how environmental changes affect amphibian immune systems.
Temperature‐dependent immunity may be particularly important to amphibian disease dynamics, especially in temperate regions. Changes in temperature are expected to cause deviations away from optimal levels of immunity until the immune system can respond.
To test whether temperature changes cause deviations from optimal immunity under natural conditions, we conducted a seasonal survey of adult Red‐Spotted Newts and measured basal levels of several immunological variables.
We then examined these findings in relation to: (1) the lag hypothesis, which predicts that changes in temperature‐dependent immune parameters lag behind short‐term temperature changes, and (2) the seasonal acclimation hypothesis, which predicts that immune cell production declines during long‐term temperature decreases until amphibians can fully acclimate to winter conditions.
Our results supported both hypotheses, showing a spring lag effect on lymphocyte levels and an even stronger seasonal acclimation effect on lymphocytes, neutrophils and eosinophils in the autumn. Our findings suggest that temperature variability causes increased susceptibility of amphibians to infection, and they have implications for the emergence of disease and the potential for climate change to exacerbate amphibian decline.