bluuebunny/crossref_metadata_2025 huggingface dataset:
Molecular characterization of commonly used cell lines for bone tumor research: A trans‐European EuroBoNet effort
Authors: Ottaviano Laura , Schaefer Karl‐Ludwig , Gajewski Melanie , Huckenbeck Wolfgang , Baldus Stefan , Rogel Uwe , Mackintosh Carlos , de Alava Enrique , Myklebost Ola , Kresse Stine H. , Meza‐Zepeda Leonardo A. , Serra Massimo , Cleton‐Jansen Anne‐Marie , Hogendoorn Pancras C. W. , Buerger Horst , Aigner Thomas , Gabbert Helmut E. , Poremba Christopher
Published: September 2009

Usage of cancer cell lines has repeatedly generated conflicting results provoked by differences among subclones or contamination with mycoplasm or other immortal mammalian cells. To overcome these limitations, we decided within the EuroBoNeT consortium to characterize a common set of cell lines including osteosarcomas (OS), Ewing sarcomas (ES), and chondrosarcomas (CS). DNA fingerprinting was used to guarantee the identity of all of the cell lines and to distinguish subclones of osteosarcoma cell line HOS. Screening for homozygous loss of 38 tumor suppressor genes by MLPA revealed deletion of CDKN2A as the most common event (15/36), strictly associated with absence of the CDKN2A (p16) protein. Ten cell lines showed missense mutations of the TP53 gene while another set of nine cell lines showed mutations resulting in truncation of the TP53 protein. Cells harboring missense mutations expressed high levels of nuclear TP53, while cell lines with nonsense mutations showed weak/absent staining for TP53. TP53wt cell lines usually expressed the protein in 2–10% of the cells. However, seven TP53wt osteosarcomas were negative for both mRNA and protein expression. Our analyses shed light on the correlation between immunohistochemical and genetic data for CDKN2A and TP53, and confirm the importance of these signaling pathways. The characterization of a substantial number of cell lines represents an important step to supply research groups with proven models for further advanced studies on tumor biology and may help to make results from different laboratories more comparable. © 2009 Wiley‐Liss, Inc.
Individual sensitivity to pain expectancy is related to differential activation of the hippocampus and amygdala
Authors: Ziv Michal , Tomer Rachel , Defrin Ruth , Hendler Talma
Published: September 2009

Anxiety arising during pain expectancy can modulate the subjective experience of pain. However, individuals differ in their sensitivity to pain expectancy. The amygdale and hippocampus were proposed to mediate the behavioral response to aversive stimuli. However, their differential role in mediating anxiety‐related individual differences is not clear. Using fMRI, we investigated brain activity during expectancy to cued or uncued thermal pain applied to the wrist. Following each stimulation participants rated the intensity of the painful experience. Activations in the amygdala and hippocampus were examined with respect to individual differences in harm avoidance (HA) personality trait, and individual sensitivity to expectancy, (i.e. response to cued vs. uncued painful stimuli). Only half of the subjects reported on cued pain as being more painful than uncued pain. In addition, we found a different activation profile for the amygdala and hippocampus during pain expectancy and experience. The amygdala was more active during expectancy and this activity was correlated with HA scores. The hippocampal activity was equally increased during both pain expectancy and experience, and correlated with the individual's sensitivity to expectancy. Our findings suggest that the amygdala supports an innate tendency to approach or avoid pain as reflected in HA trait, whereas the hippocampus mediates the effect of context possibly via appraisal of the stimulus value. Hum Brain Mapp, 2010. © 2009 Wiley‐Liss, Inc.
Laryngeal inflammatory myofibroblastic tumors: Different clinical appearance and histomorphologic presentation of one entity
Authors: Völker Hans‐Ullrich , Scheich Matthias , Zettl Andreas , Hagen Rudolf , Müller‐Hermelink Hans Konrad , Gattenlöhner Stefan
Published: September 2009

Background

Inflammatory myofibroblastic tumors (IMFTs) of the larynx are rare. We report the clinical presentation, histomorphology, and new molecular findings of 2 cases.

Methods

Paraffin‐embedded specimens were stained immunohistochemically (eg, vimentin, AE1/3, Alk‐1, smooth muscle [sm‐]actin, p53, Rb1, immunoglobulin G4 [IgG4]). Epstein–Barr virus–encoded RNA (EBER) in situ hybridization and HHV8–polymerase chain reaction (PCR) were done. Comparative genomic hybridization (CGH) was performed.

Results

Case 1 was that of a 56‐year‐old man with an infiltrating plasma‐cell–rich tumor (Alk‐1‐, sm‐actin+). Plasma cells were strongly positive for IgG4. CGH was unsuspicious. Case 2 was that of a 34‐year‐old woman with an exophytic tumor (Alk‐1+). CGH revealed losses on 13q14–22. The few plasma cells were negative for IgG4. The proliferation (Ki67) was low in both cases.

Conclusion

Different types of IMFTs may exist and could indicate different therapeutic strategies. Alk‐1‐positive cases with only scattered inflammatory cells could represent the neoplastic variant, whereas cases rich in plasma cells could be associated with IgG4 sclerosing diseases. © 2009 Wiley Periodicals, Inc. Head Neck, 2009
Dendritic cells pulsed with GST–EGFR fusion protein: Effect in antitumor immunity against head and neck squamous cell carcinoma
Authors: Yang Bei‐Bei , Jiang Hua , Chen Jia , Zhang Xing , Ye Jing‐Jia , Cao Jiang
Published: September 2009

Background

Overexpression of epidermal growth factor receptor (EGFR) is common in head and neck squamous cell carcinoma (HNSCC). Targeting EGFR is an effective approach to treat EGFR‐positive HNSCC. However, the clinical benefits of the present EGFR‐targeting agents are still limited in HNSCC patients.

Methods

Recombinant glutathione‐S‐transferase (GST)–EGFR fusion protein was produced and purified. Dendritic cells (DCs) of C3H mice were pulsed with fusion protein. Mice were challenged with HNSCC cells before or after vaccination with these DCs, and the cytotoxic T‐lymphocyte (CTL) response, interferon‐γ (IFN‐γ) secretion, tumor growth, and survival of mice were assessed.

Results

Significant in vitro and in vivo antitumor activities were observed for mice immunized with DCs pulsed with GST–EGFR fusion protein, compared with the control groups (p < .05).

Conclusion

The DCs pulsed with GST–EGFR fusion protein can provide not only preventive but also therapeutic antitumor activities against HNSCC in the animal model. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Nonparotid parapharyngeal oncocytoma: A case report and literature review
Authors: Barrese James L. , Lau Sean , Chen Bihong T. , Maghami Ellie
Published: September 2009

Oncocytoma is a rare, benign salivary neoplasm composed of mitochondria‐rich cells called oncocytes. Although oncocytoma usually occurs in the parotid glands, it has much less commonly been reported to occur in minor salivary gland tissues. Although there have been a few reported cases of oncocytomas being found in the parapharyngeal space, most if not all cases seem to be extensions of deep lobe parotid tumors. We present a case of a 73‐year‐old man with a previous history of prostate cancer that had the incidental finding of an 18F‐fluorodeoxyglucose (FDG) image of a highly avid parapharyngeal space lesion noted on a follow‐up positron emission tomography–computed tomography (PET/CT) scan. Excision of the mass, through a transcervical approach, demonstrated it to be an isolated oncocytoma of the parapharyngeal space, noncontiguous with the parotid gland. Based on our literature search, this may be the first such reported case. A brief review of the available literature examining the known body of knowledge regarding these neoplasms is presented. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
UltraCision harmonic scalpel versus clamp‐and‐tie total thyroidectomy: A clinical trial
Authors: Papavramidis Theodossis S. , Sapalidis Konstantinos , Michalopoulos Nick , Triantafillopoulou Konstantina , Gkoutzamanis George , Kesisoglou Isaak , Papavramidis Spiros T.
Published: September 2009

Background

Hemostasis is important in thyroid surgery to avoid complications. Our aim was to evaluate the effectiveness of the harmonic scalpel in patients undergoing total thyroidectomy.

Methods

In this study, 90 patients were randomized into group A (classic technique of tying and knots) and group B (harmonic scalpel). We recorded the following: age, sex, pathology, thyroid weight, hemostatic technique, duration of operation, change in calcemia (ΔCa), change in hematocrit (ΔHt), change in hemoglobin (ΔHgb), change in white blood cell count (ΔWBC), vocal motility, operative difficulty, postoperative vocal alteration, postoperative pain, complications, blood in the drains, operating time, mass of gland excised per minute, and hospitalization.

Results

Differences (p < .05) were observed concerning duration of surgery, operative difficulty, postoperative pain, hospitalization, ΔWBC, and quantity of gland removed per minute. No recurrent laryngeal nerve (RLN) palsies were observed.

Conclusions

Use of the Harmonic Scalpel in total thyroidectomy is more effective than the clamp‐and‐tie technique: the duration of surgery, intraoperative difficulty, postoperative pain, and hospitalization are reduced. Both techniques are equivalent concerning RLN injuries, postoperative vocal alterations, and blood loss. © 2009 Wiley Periodicals, Inc. Head Neck, 2010
Aging alters the expression of genes for neuroprotection and synaptic function following acute estradiol treatment
Authors: Aenlle Kristina K. , Foster Thomas C.
Published: September 2009

This study used microarray analysis to examine age‐related changes in gene expression 6 and 12 h following a single estradiol injection in ovariectomized mice. Estradiol‐responsive gene expression at the 6 h time point was reduced in aged (18 months) animals compared with young (4 months) and middle‐aged (MA, 12months) mice. Examination of gene clustering within biological and functional pathways indicated that young and MA mice exhibited increased expression of genes for cellular components of the synapse and decreased expression of genes related to oxidative phosphorylation and mitochondrial dysfunction. At the 12 h time point, estradiol‐responsive gene expression increased in aged animals and decreased in young and MA mice compared with the 6 h time point. Gene clustering analysis indicated that aged mice exhibited increased expression of genes for signaling pathways that are rapidly influenced by estradiol. The age differences in gene expression for rapid signaling pathways may relate to disparity in basal pathway activity and estradiol mediated activation of rapid signaling cascades. © 2009 Wiley‐Liss, Inc.
Effects of switching to long‐acting injectable risperidone from oral atypical antipsychotics on cognitive function in patients with schizophrenia
Authors: Kim Sung‐Wan , Shin Il‐Seon , Kim Jae‐Min , Lee Seung‐Hyun , Lee Yo‐Han , Yang Su‐Jin , Yoon Jin‐Sang
Published: September 2009

Objective

To investigate changes in cognitive function and clinical features following a switch from oral atypical antipsychotics (AAPs) to long‐acting injectable risperidone (LAIR) in patients with schizophrenia.

Methods

Thirty‐six patients with schizophrenia treated with oral AAPs participated in this open‐label, 26‐week study. Cognitive functions were measured at baseline and at 12 and 26 weeks. The secondary outcome measures included the Positive and Negative Syndrome Scale (PANSS), Social and Occupational Functioning Assessment Scale (SOFAS), Scale for Unawareness of Mental Disorder (SUMD), and measurements for extrapyramidal symptoms.

Results

Significant improvements in cognitive function were observed in the backward Digit Span Test, Verbal Learning Test, Wisconsin Card Sorting Test, correct responses on the Continuous Performance Test, and Trail Making Test part B following a switch to LAIR. Scores on the PANSS, SOFAS, SUMD, and the Simpson–Angus Rating Scale also improved significantly. Most improvements in neurocognitive function were not correlated with clinical measures. Weight gain and hyperprolactinemia were the most common adverse events.

Conclusions

Switching from oral AAPs to LAIR improved cognitive function including vigilance, verbal learning and memory, executive function, sustained attention, and visuomotor speed in patients with schizophrenia. It was also effective for improving psychotic symptoms, social functioning, and insight. Copyright © 2009 John Wiley & Sons, Ltd.
Effect of coastline configuration on precipitation distribution in coastal zones
Authors: Eris Ebru , Agiralioglu Necati
Published: September 2009

The effects of coastline, together with the other geographical and topographical factors such as longitude, latitude, elevation and distance from sea, on mean annual precipitation are investigated for the coastal area of the eastern Black Sea region. In this location, mountains run parallel to the sea coast. The coastline configuration is represented by a new variable, the coastline angle. A multiple linear regression (MLR) analysis is performed on mean annual precipitation recorded in coastal and inland gauges. In the study area, three variables—longitude, latitude and coastline angle—can explain 81% of the spatial variability of precipitation for the coastal gauges and 93% of that for the inland gauges. When the entire study area considered, without grouping the gauges, 80% of the spatial variability is explained by these variables. Copyright © 2009 John Wiley & Sons, Ltd.
Cigarette smoking, environmental tobacco smoke exposure and pancreatic cancer risk in the European Prospective Investigation into Cancer and Nutrition
Authors: Vrieling Alina , Bueno‐de‐Mesquita H. Bas , Boshuizen Hendriek C. , Michaud Dominique S. , Severinsen Marianne T. , Overvad Kim , Olsen Anja , Tjønneland Anne , Clavel‐Chapelon Françoise , Boutron‐Ruault Marie‐Christine , Kaaks Rudolf , Rohrmann Sabine , Boeing Heiner , Nöthlings Ute , Trichopoulou Antonia , Moutsiou Eftihia , Dilis Vardis , Palli Domenico , Krogh Vittorio , Panico Salvatore , Tumino Rosario , Vineis Paolo , van Gils Carla H. , Peeters Petra H.M. , Lund Eiliv , Gram Inger T. , Rodríguez Laudina , Agudo Antonio , Larrañaga Nerea , Sánchez María‐José , Navarro Carmen , Barricarte Aurelio , Manjer Jonas , Lindkvist Björn , Sund Malin , Ye Weimin , Bingham Sheila , Khaw Kay‐Tee , Roddam Andrew , Key Tim , Boffetta Paolo , Duell Eric J. , Jenab Mazda , Gallo Valentina , Riboli Elio
Published: September 2009

Cigarette smoking is an established risk factor for pancreatic cancer. However, prospective data for most European countries are lacking, and epidemiologic studies on exposure to environmental tobacco smoke (ETS) in relation to pancreatic cancer risk are scarce. We examined the association of cigarette smoking and exposure to ETS with pancreatic cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). This analysis was based on 465,910 participants, including 524 first incident pancreatic cancer cases diagnosed after a median follow‐up of 8.9 years. Estimates of risk were obtained by Cox proportional hazard models and adjusted for weight, height, and history of diabetes mellitus. An increased risk of pancreatic cancer was found for current cigarette smokers compared with never smokers (HR = 1.71, 95% CI = 1.36–2.15), and risk increased with greater intensity and pack‐years. Former cigarette smokers who quit for less than 5 years were at increased risk of pancreatic cancer (HR = 1.78, 95% CI = 1.23–2.56), but risk was comparable to never smokers after quitting for 5 years or more. Pancreatic cancer risk was increased among never smokers daily exposed to ETS (for many hours) during childhood (HR = 2.61, 95% CI = 0.96–7.10) and exposed to ETS at home and/or work (HR = 1.54, 95% CI = 1.00–2.39). These results suggest that both active cigarette smoking, as well as exposure to ETS, is associated with increased risk of pancreatic cancer and that risk is reduced to levels of never smokers within 5 years of quitting.
Contrast‐enhanced ultrasound with SonoVue: Differentiation between benign and malignant focal liver lesions in 317 patients
Authors: von Herbay Alexandra , Westendorff Julia , Gregor Michael
Published: September 2009

Purpose.

The aim of the study was to investigate the ability of contrast‐enhanced sonography (CEUS) with the contrast agent SonoVue to differentiate between benign and malignant focal liver lesions.

Methods.

In a prospective study, we examined 317 patients (204 males, 113 females, aged 59 ± 12 years) with focal liver lesions detected by B‐mode gray‐scale sonography. After intravenous injection of 1.2 mL SonoVue, the liver was examined continuously for 3 minutes using low‐MI sonography with contrast‐specific software. Final diagnosis was established by histopathology, CT, MRI, or HIDA‐scintigraphy.

Results.

Two hundred nine patients had malignant focal lesions, including 107 hepatocellular carcinomas, 70 metastases, 26 cholangiocellular carcinomas, and 6 other types of malignancy. One hundred eight patients had benign focal lesions, including 30 regenerative nodules, 30 hemangiomas, 13 cases of focal nodular hyperplasia, 12 abscesses, 8 cases of necrosis, 7 cases of focal steatosis areas, and 8 other benign lesions. Hypoenhancement or no enhancement in the late phase was found in 91% of the malignant lesions but in only 37% of the benign lesions (p < 0.001, sensitivity = 64%, specificity = 93%). Hyperenhancement in the late phase was found in 20% of the benign lesions but in none of the malignant lesions (p < 0.001, sensitivity = 21%, specificity = 100%). Hyperenhancement in the early phase with diffuse complete enhancement was found in 30% of the patients with malignant lesions but in only 2% of the patients with benign lesions (p < 0.001, sensitivity = 30%, specificity = 98%). CEUS had a sensitivity of 90%, a specificity of 99%, and an accuracy of 89% in the diagnosis of malignant liver lesions.

Conclusion.

CEUS is helpful in the differentiation between benign and malignant focal liver lesions. © 2009 Wiley Periodicals, Inc. J Clin Ultrasound, 2010
Retracted:Evidence for duplicated Hox genes in polyploid Cyprinidae fish of common carp, crucian carp and silver crucian carp
Authors: Yuan Jian , He Zhuzi , Yuan Xiangnan , Jiang Xiayun , Sun Xiaowen , Zou Shuming
Published: September 2009

Notice of Withdrawal: The following article from the Journal of Experimental Zoology Part B: Molecular and Developmental Evolution, “Evidence for duplicated Hox genes in polyploid Cyprinidae fish of common carp, crucian carp, and silver crucian carp” by Yuan J, He Z, Yuan X, Jiang X, Sun X, Zou S, published online on 29 Sept 2009 in Wiley InterScience (www.interscience.wiley.com), has been withdrawn from publication by agreement between the authors, the journal Editor‐in‐Chief, Gunter P. Wagner, and Wiley Periodicals, Inc.
Top heavy? Governance issues and policy decisions for the fair trade movement
Authors: Tallontire Anne
Published: September 2009

With the advent of mainstreaming, several different business models operate within the fair trade system. These differences are discussed in terms of how the value chain is governed, suggesting the need for a more nuanced understanding of fair trade in the mainstream. Institutional governance, that is, the structures and standards of fair trade, is also discussed. It is argued that if fair trade is to be more than just another consumer standard, it needs to address both value chain and institutional governance. Policy implications, especially with respect to fair trade institutions, particularly Fairtrade Labelling Organisations International, are set out. Copyright © 2009 John Wiley & Sons, Ltd.
Policy challenges for fair trade in Wales
Authors: Townley Jon
Published: September 2009

The Welsh Assembly Government is committed to encouraging the people of Wales to understand the benefits of Fair Trade. This policy briefing reflects on the importance of Fair Trade for the Welsh Assembly Government and challenges for the future. Copyright © 2009 John Wiley & Sons, Ltd.
Reduced size of the dendritic tree does not protect Purkinje cells from excitotoxic death
Authors: Gugger Olivia S. , Kapfhammer Josef P.
Published: October 2009

Purkinje cell loss by excitotoxic damage is a typical finding in many cerebellar diseases. One important aspect of this high sensitivity of Purkinje cells to excitotoxic death might be the enormous size of their dendritic tree, with a high load of excitatory glutamate receptors. We have studied whether reduction in the size of the dendritic tree might confer resistance against excitotoxic death to Purkinje cells. We have grown Purkinje cells in organotypic cerebellar slice cultures under chronic activation of metabotropic glutamate receptors or of protein kinase C. Both treatments strongly reduced dendritic tree size. After this treatment, cells were exposed to the glutamate receptor agonist AMPA, which has a strong excitotoxic effect on Purkinje cells. We found that Purkinje cells with small dendritic trees were as sensitive to AMPA exposure as untreated control cells with large dendritic trees. Immunostaining against vesicular glutamate transporter 1 revealed that the small dendritic trees were densely covered by glutamatergic terminals. Our results indicate that the expansion of the dendritic tree and the total number of AMPA receptors per neuron do not play a major role in determining the susceptibility of Purkinje cells to excitotoxic death. © 2009 Wiley‐Liss, Inc.
Influence of the Madden–Julian Oscillation on Indonesian rainfall variability in austral summer
Authors: Hidayat Rahmat , Kizu Shoichi
Published: September 2009

The impact of the Madden–Julian Oscillation (MJO) on Indonesian rainfall variability in austral summer is analysed by using the daily station rain gauge data and Tropical Rainfall Measuring Mission precipitation data for the periods of 1979 through 1990 and 1998 through 2006, respectively. Composite analysis of 21 and 16 MJO events identified in former respective periods shows that the rainfall variability over Indonesia is significantly affected by the phase of eastward‐propagating MJO. Excess rainfall is brought during ‘wet’ phase, when the convective activity reaches its maximum with enhanced low‐level wind convergence over the region. In addition, the impact of MJO tends to be more profound over the surrounding seas than over the large islands of this region. The positive rainfall anomaly over the eastern Indian Ocean and Java Sea during the wet phase is up to 5 mm/day (60% of the long‐term mean) as a pentad mean, while it is about 1–3 mm/day (10–30%) over Borneo and Java. Copyright © 2009 Royal Meteorological Society
A logistic regression approach for monthly rainfall forecasts in meteorological subdivisions of India based on DEMETER retrospective forecasts
Authors: Prasad K. , Dash S. K. , Mohanty U. C.
Published: September 2009

A multi‐predictor logistic regression model has been developed for probabilistic forecasts of domain average rainfall on monthly timescale for three study regions namely, India as a whole, and two homogeneous meteorological subdivisions of India, i.e. Orissa on the east coast and Gujarat on the west coast. The time series of the monthly total observed rainfall as the predictand variable was constructed from the gridded (1° × 1°) daily rainfall produced by India Meteorological Department, and those of the predictor data sets from 1‐month lead forecasts of several atmospheric and oceanic variables produced by the ‘Development of a European Multi‐model Ensemble system for seasonal to inTERannual prediction (DEMETER)’ project of European Centre for Medium‐Range Weather Forecasts (ECMWF). Multi‐model ensembles of nine‐member retrospective forecasts for the month of August generated by three constituent models of the DEMETER system, viz., ECMWF, United Kingdom Meteorological Office (UKMO) and Meteo France are used. The predictor variables (totally 36 in number) include direct model‐predicted total precipitation and its inter‐member standard deviation. A two‐stage procedure has been designed, where logistic regression is first computed for each individual variable and then for the variables ranked on the basis of Brier scores. The top‐ranked variables (up to four) are used for fitting the multiple logistic regression model in a stepwise manner. The fitted model provides estimates of probability of the value of an observation exceeding a specified quantile (such as median) of the statistical distribution of the predictand variable. The model shows good performance in capturing the extreme rainfall years and appears to perform better than the direct model forecasts of total precipitation in respect of such years. Copyright © 2009 Royal Meteorological Society
Interannual variability of precipitation distribution patterns in Southern Portugal
Authors: Mourato S. , Moreira M. , Corte‐Real J.
Published: September 2009

Southern Portugal is characterized by an irregular distribution of precipitation which is highly variable from year to year, requiring a clear ascertaining if the pattern of the precipitation is changing due to climate variability or climate change.

In this paper, the authors applied several statistical methods to annual and seasonal time series of precipitation during the period 1931–2006, in order to detect trends and evaluate the variability in the frequencies of occurrence of dry and wet periods and also to assess spatial distribution patterns.

The statistical methods include homogeneity tests, Mann–Kendall test, simple moving averages and cluster analysis. In spring, the authors detected a lack of homogeneity in the precipitation time series and a significant decreasing trend of precipitation was identified, by using simple moving averages and the Mann–Kendall test.

Cluster analyses also confirmed the results and identified significant trends in the interannual and spatial distributions of dry, normal and wet years. It is concluded that the annual precipitation regime in the North interior sector is becoming drier, as the winter and spring also become drier. The only season in which a precipitation increase is observed is at fall and near the sea, but even for that region springs are also becoming drier. Copyright © 2009 Royal Meteorological Society
Science versus myth: was there a connection between the Marmara Sea and Lake Sapanca?
Authors: Gürbüz Alper , Leroy Suzanne A. G.
Published: September 2009

The existence of an alternative strait between the Black and Marmara Seas, east of today's İstanbul Strait, on the route of İzmit Gulf–Lake Sapanca–Lower Sakarya Valley, was already claimed at the end of the 19th century and has also been considered in several recent studies. Firstly, in historical documents over the last 2500 years, some natural and artificial waterways between the Marmara Sea and Lake Sapanca have been reported. Secondly, according to the present geomorphological research between the İzmit Gulf and Lake Sapanca, the gutter‐like morphology, which was formed by the tectonics of the North Anatolian Fault in the centre of the plain, is suggested as a suitable geomorphic feature for a possible waterway between the gulf and the lake. Thirdly, the İzmit Plain that lies between the İzmit Gulf and Lake Sapanca is studied in this paper through its sedimentology. The facies associations of the basin‐fill deposits are examined here through the lithological descriptions and fossil assemblages in nine cores drilled in the plain. All these data suggest that the shoreline in the Quaternary did not lie much further landward from its current position, that the inner part of the plain was covered by a lagoon/coastal‐swamp environment and that a connection may have existed at an unknown time (perhaps for the last time during the Middle/Late Pleistocene) with perhaps only partial reuse during the last millennia in the course of catastrophic seismic movements and consecutive floods. Copyright © 2009 John Wiley & Sons, Ltd.
Assessment of a sheep animal model to optimise photodynamic therapy in the oesophagus
Authors: Glanzmann Thomas M. , Zellweger Matthieu P.E. , Borle François , Conde Ramiro , Radu Alexandre , Ballini Jean‐Pierre , Jaquet Yves , Pilloud Raphaëlle , van den Bergh Hubert , Monnier Philippe , Andrejevic‐Blant Snezana , Wagnières Georges A.
Published: September 2009

Background and Objectives

Precursor lesions of oesophagus adenocarcinoma constitute a clinical dilemma. Photodynamic therapy (PDT) is an effective treatment for this indication, but it is difficult to optimise without an appropriate animal model. For this reason, we assessed the sheep model for PDT in the oesophagus with the photosensitiser meta‐(tetra‐hydroxyphenyl) chlorin (mTHPC).

Materials and Methods

Twelve sheep underwent intravenous mTHPC injection, blood sampling and fluorescence measurements. mTHPC's pharmacokinetics was measured in vivo and in plasma by fluorescence spectroscopy. Biopsies of sheep oesophagus were compared to corresponding human tissue, and the mTHPC's biodistribution was studied under fluorescence microscopy. Finally, the sheep oesophageal mucosa was irradiated, 4 days after mTHPC's injection.

Results

Histologically, the sheep and human oesophagus were closely comparable, with the exception of additional fatty tissue in the sheep oesophagus. mTHPC's pharmacokinetics in sheep and human plasmas were similar, with a maximum of concentration in the sheep 10 hours after i.v. injection. mTHPC's pharmacokinetics in vivo reached its maximum after 30–50 hours, then decreased to background levels, as in humans under similar conditions. Two days after injection, mTHPC was mainly distributed in the lamina propria, followed by a penetration into the epithelium. The sheep and human tissue sensitivity to mTHPC PDT was similar.

Conclusion

In conclusion, this model showed many similarities with humans as to mTHPC's plasma and tissue pharmacokinetics, and for tissue PDT response, making it suitable to optimise oesophagus PDT. Lasers Surg. Med. 41:643–652, 2009. © 2009 Wiley‐Liss, Inc.
Risk factors for recurrence of autoimmune hepatitis after liver transplantation
Authors: Montano-Loza Aldo J. , Mason Andrew L. , Ma Mang , Bastiampillai Ravin J. , Bain Vincent G. , Tandon Puneeta
Published: September 2009

Autoimmune hepatitis has been reported to recur after liver transplantation. The aim of our study was to evaluate the risk factors associated with recurrence of autoimmune hepatitis. Forty-six patients that underwent liver transplantation because of end-stage liver disease secondary to autoimmune hepatitis were studied. Recurrence of autoimmune hepatitis was diagnosed in 11 of the 46 (24%) patients, and the overall 5-year probability of recurrence was 18%. By univariate Cox analysis, the features before liver transplantation associated with a higher risk of recurrence were concomitant autoimmune disease [hazard ratio (HR), 3.74; 95% confidence interval (CI), 1.05–13.36; P = 0.04], high aspartate aminotransferase (HR, 1.09; 95% CI, 1.03–1.14; P = 0.002), high alanine aminotransferase (HR, 1.09; 95% CI, 1.03–1.20; P = 0.003), and high immunoglobulin G (IgG; HR, 1.25; 95% CI, 1.11–1.41; P = 0.0003). Moreover, patients with recurrence had a higher frequency of moderate to severe inflammatory activity (HR, 5.3; 95% CI, 1.55–18.79; P = 0.008) and plasma cell infiltration in the liver explant (HR, 5.8; 95% CI, 1.52–22.43; P = 0.01). In the multivariate Cox analysis, only the presence of moderate to severe inflammation (HR, 6.9; 95% CI, 1.76–26.96; P = 0.006) and high IgG levels before liver transplantation (HR, 7.5; 95% CI, 1.45–38.45; P = 0.02) were independently associated with the risk of autoimmune hepatitis recurrence. In conclusion, patients with concomitant autoimmune disease, high aspartate aminotransferase, alanine aminotransferase, and IgG before the transplant, or moderate to severe inflammatory activity or plasma cell infiltration in the liver explant have a higher risk of recurrent disease. These findings suggest that recurrence of autoimmune hepatitis may reflect incomplete suppression of disease activity prior to liver transplantation. Liver Transpl 15:1254–1261, 2009. © 2009 AASLD.
Outcomes of liver transplantation for paracetamol (acetaminophen)-induced hepatic failure
Authors: Cooper Sheldon C. , Aldridge Roland C. , Shah Tahir , Webb Kerry , Nightingale Peter , Paris Sue , Gunson Bridget K. , Mutimer David J. , Neuberger James M.
Published: September 2009

Paracetamol (acetaminophen) hepatotoxicity, whether due to intentional overdose or therapeutic misadventure, is an indication for liver transplantation in selected cases. However, there is a concern that long-term outcomes may be compromised by associated psychopathology that may predispose patients to further episodes of self-harm or poor treatment adherence. We therefore undertook a retrospective analysis of patients transplanted for paracetamol-induced fulminant hepatic failure (FHF) to determine their long-term outcomes, psychiatric problems, and compliance and whether these issues could be predicted from pretransplant information. Records from patients undergoing liver transplantation for paracetamol-associated liver failure in this unit and 2 comparison groups (patients undergoing liver replacement for FHF from other causes and for chronic liver diseases) were examined. Of 60 patients transplanted for paracetamol-induced FHF between 1989 and 2007, 44 (73%) survived to discharge. Currently, 35 patients (58%) are surviving at an average of 9 years post-transplantation. The incidence of psychiatric disease (principally depression) and 30-day mortality were greatest in the paracetamol group, but for those who survived 30 days, there was no difference in long-term survival rates between the groups. Adherence to follow-up appointments and compliance with immunosuppression were lowest in the paracetamol overdose group. Poor adherence was not predicted by any identifiable premorbid psychiatric conditions. Two patients grafted for paracetamol FHF died from self-harm (1 from suicide and 1 from alcoholic liver disease after 5 years). This study suggests that, notwithstanding the shortage of donor liver grafts, transplantation is an appropriate therapy in selected patients, although close follow-up is indicated. Liver Transpl 15:1351–1357, 2009. © 2009 AASLD.
Liver transplantation cost in the model for end-stage liver disease era: Looking beyond the transplant admission
Authors: Buchanan Paula , Dzebisashvili Nino , Lentine Krista L. , Axelrod David A. , Schnitzler Mark A. , Salvalaggio Paolo R.
Published: September 2009

We examined the relationship between the total cost incurred by liver transplantation (LT) recipients and their Model for End-Stage Liver Disease (MELD) score at the time of transplant. We used a novel database linking billing claims from a large private payer with the Organ Procurement and Transplantation Network registry. Included were adults who underwent LT from March 2002 through August 2007 (n = 990). Claims within the year preceding and following transplantation were analyzed according to the recipient's calculated MELD score. Cost was the primary endpoint and was assessed by the length of stay and charges. Transplant admission charges represented approximately 50% of the total cost of LT. MELD was a significant cost driver for pretransplant, transplant, and total charges. A MELD score of 28 to 40 was associated with additional charges of $349,213 (P < 0.05) in comparison with a score of 15 to 20. Pretransplant and transplant admission charges were higher by $152,819 (P < 0.05) and $64,286 (P < 0.05), respectively, in this higher MELD group. No differences by MELD score were found for posttransplant charges. Those in the highest MELD group also experienced longer hospital stays both in the pretransplant period and at the time of LT but did not have higher rates of re-admissions. In conclusion, high-MELD patients incur significantly higher costs prior to and at the time of LT. Following LT, the MELD score is not a significant predictor of cost or re-admission. Liver Transpl 15:1270–1277, 2009. © 2009 AASLD.
A report of human herpesvirus 6–associated encephalitis in a solid organ transplant recipient and a review of previously published cases
Authors: Vinnard Christopher , Barton Todd , Jerud Elliot , Blumberg Emily
Published: September 2009

Human herpesvirus 6 (HHV-6) is a common pathogen among children, classically presenting as fever and rash that resolve without specific therapy (exanthem subitum or roseola infantum). Also identified as a pathogen in hematopoietic cell transplant and solid organ transplant (SOT) recipients, it has been recognized as a cause of limbic encephalitis, characterized by confusion and amnesia, with magnetic resonance imaging findings of T2 hyperintensity of the amygdala and hippocampus. We report a case of limbic encephalitis associated with HHV-6 infection in a liver transplant recipient, and we review previously reported cases of HHV-6 encephalitis in SOT recipients. Liver Transpl 15:1242–1246, 2009. © 2009 AASLD.
Liver transplantation for familial amyloidotic polyneuropathy: Impact on Swedish patients' survival
Authors: Okamoto Sadahisa , Wixner Jonas , Obayashi Konen , Ando Yukio , Ericzon Bo-Göran , Friman Styrbjörn , Uchino Makoto , Suhr Ole B.
Published: September 2009

Liver transplantation (LTx) for familial amyloidotic polyneuropathy (FAP) is an accepted treatment for this fatal disease. However, the long-term outcome with respect to that of nontransplanted patients has not been fully elucidated. The aim of this study was to compare the long-term survival of Swedish LTx FAP patients with that of historical controls, especially with respect to the age at onset of the disease and gender. In order to evaluate the outcome of LTx as a treatment for FAP, survival was calculated from the onset of disease. One hundred forty-one FAP patients, 108 transplanted and 33 not transplanted, were included in the study. Significantly increased survival was noted for LTx patients in comparison with controls. The outcome was especially favorable for those with an early onset of the disease (age at onset < 50 years) in comparison with early-onset controls (P < 0.001). In contrast, no significant difference for late-onset cases (≥50 years) was found. Transplanted late-onset females had significantly improved survival in comparison with transplanted late-onset males (P = 0.02). We were unable to find significant differences in survival between patients with long (≥7 years) or short (<7 years) disease duration at transplantation. The survival of male patients with late-onset disease appeared not to improve with LTx. LTx is an efficacious treatment for improving the survival of early-onset FAP patients. Further studies are needed to analyze the cause of the poorer outcome for late-onset male patients. Liver Transpl 15:1229–1235, 2009. © 2009 AASLD.
Acute liver failure at 26 weeks' gestation in a patient with sickle cell disease
Authors: Greenberg Mara , Daugherty Tami J. , Elihu Arvand , Sharaf Ravi , Concepcion Waldo , Druzin Maurice , Esquivel Carlos O.
Published: September 2009

Orthotopic liver transplantation (OLT) for acute liver failure (ALF) during pregnancy is an uncommon occurrence with variable outcomes. In pregnancy-related liver failure, prompt diagnosis and immediate delivery are essential for a reversal of the underlying process and for maternal and fetal survival. In rare cases, the reason for ALF during pregnancy is either unknown or irreversible, and thus OLT may be necessary. This case demonstrates the development of cryptogenic ALF during the 26th week of pregnancy in a woman with sickle cell disease. She underwent successful cesarean delivery of a healthy male fetus at 27 weeks with concurrent OLT. This report provides a literature review of OLT in pregnancy and examines the common causes of ALF in the pregnant patient. On the basis of the management and outcome of our case and the literature review, we present an algorithm for the suggested management of ALF in pregnancy. Liver Transpl 15:1236–1241, 2009. © 2009 AASLD.
Kinetics of host immune responses and cytomegalovirus resistance in a liver transplant patient
Authors: Schaffer Kirsten , Moran Julie , Duffy Margaret , McCormick Aiden P. , Hall William W. , Hassan Jaythoon
Published: September 2009

Among solid organ transplant (SOT) recipients, donor-seropositive/recipient-seronegative (D+/R−) cytomegalovirus (CMV) status is associated with the highest risk of ganciclovir-resistant CMV disease, which has been reported for patients receiving oral ganciclovir but not valganciclovir prophylaxis. We report a case of CMV breakthrough infection in a D+/R− liver transplant patient while he was receiving oral valganciclovir. Forty samples collected over 6 months were analyzed for the CMV viral load, lymphocyte counts, cytokine levels, and lymphocyte differentiation status. Genotypic resistance testing of the viral UL97 gene was performed when the patient failed to respond. CMV viremia occurred on day 50 post-transplant, and 5 samples taken between days 50 and 85 showed the wild-type UL97 genotype. The appearance of deletion 594-595 was observed from day 114 post-transplant. Viral loads declined when foscarnet was commenced and remained below 10,000 copies/mL when the lymphocyte count was greater than 1000/μL (P = 0.02). T cell responses revealed significant expansion of CD8+ terminal effector memory cells. CD4+ cells were largely populations of naïve and central memory cells. Circulating interleukin 10 (IL-10) levels correlated with the viral load (P < 0.0001). Seroconversion occurred on day 230. The CMV viral load in combination with lymphocyte counts and IL-10 may be a predictive marker for the risk of development of resistant CMV disease in D+/R− SOT patients. Liver Transpl 15:1199–1203, 2009. © 2009 AASLD.
Early noninvasive measurement of the indocyanine green plasma disappearance rate accurately predicts early graft dysfunction and mortality after deceased donor liver transplantation
Authors: Olmedilla Luis , Pérez-Peña José María , Ripoll Cristina , Garutti Ignacio , de Diego Roberto , Salcedo Magdalena , Jiménez Consuelo , Bañares Rafael
Published: September 2009

Early diagnosis of graft dysfunction in liver transplantation is essential for taking appropriate action. Indocyanine green clearance is closely related to liver function and can be measured noninvasively by spectrophotometry. The objectives of this study were to prospectively analyze the relationship between the indocyanine green plasma disappearance rate (ICGPDR) and early graft function after liver transplantation and to evaluate the role of ICGPDR in the prediction of severe graft dysfunction (SGD). One hundred seventy-two liver transplants from deceased donors were analyzed. Ten patients had SGD: 6 were retransplanted, and 4 died while waiting for a new graft. The plasma disappearance rate was measured 1 hour (PDRr60) and within the first 24 hours (PDR1) after reperfusion, and it was significantly lower in the SGD group. PDRr60 and PDR1 were excellent predictors of SGD. A threshold PDRr60 value of 10.8%/minute and a PDR1 value of 10%/minute accurately predicted SGD with areas under the receiver operating curve of 0.94 (95% confidence interval, 0.89-0.97) and 0.96 (95% confidence interval, 0.92-0.98), respectively. In addition, survival was significantly lower in patients with PDRr60 values below 10.8%/minute (53%, 47%, and 47% versus 95%, 94%, and 90% at 3, 6, and 12 months, respectively) and with PDR1 values below 10%/minute (62%, 62%, and 62% versus 94%, 92%, and 88%). In conclusion, very early noninvasive measurement of ICGPDR can accurately predict early severe graft dysfunction and mortality after liver transplantation. Liver Transpl 15:1247–1253, 2009. © 2009 AASLD.
Mesenchymal stem cells as immunomodulators after liver transplantation
Authors: Popp Felix C. , Renner Philipp , Eggenhofer Elke , Slowik Przemyslaw , Geissler Edward K. , Piso Pompiliu , Schlitt Hans J. , Dahlke Marc H.
Published: September 2009

Mesenchymal stem cells (MSCs) are promising candidate cells for immunomodulation therapy that are currently being tested in the preclinical and clinical setting. MSCs suppress the immune response in a variety of in vitro and disease models and may thus be of benefit for patients suffering from autoimmune disorders or transplant rejection. The mechanism by which MSCs modulate the immune response is still under thorough investigation, but it most likely involves expression of local factors such as indoleamine 2,3-dioxygenase, inducible nitric oxide synthase, and others as well as interactions with dendritic or antigen-presenting cells. Although MSCs have been evaluated in clinical phase I and II studies for graft-versus-host disease and heart, kidney, and bone disease, their introduction into solid organ transplantation is still eagerly awaited. In this short review, we summarize the current understanding of immunomodulation achieved by MSC therapies and introduce a possible outline for a clinical study that will use MSCs in the context of a calcineurin inhibitor–free induction protocol after liver transplantation. Liver Transpl 15:1192–1198, 2009. © 2009 AASLD.
Modelling apple tree bud burst time and frost risk in Iran
Authors: Farajzadeh Manuchehr , Rahimi Mohammad , Kamali Gholam Ali , Mavrommatis Theodoros
Published: September 2009

The bud burst phase of orchard trees is the most critical phase in relation to low temperature and frost since the most parts of the bud, especially the ovary, are very sensitive to low temperatures. Therefore, predicting the time of bud burst is important. If a model can predict the time of budding, it would be possible to protect buds from late spring frosts. In this study, the budding time of apple trees at two agrometeorological stations in northeast and northwest Iran was predicted by using a chilling and forcing model. Data for years 2002–2006 were used to calibrate the bud burst prediction model and respective information for the years 2007 and 2008 was used to validate it. For this purpose, five threshold temperatures (TC) and 11 chill requirements (CR) were used. Among 55 combinations of TC and CR, the combination with minimum Root Mean Square Error (RMSE) was selected for predicting bud burst of apple for each region. Meanwhile, the probability of last date of frost in spring was estimated by statistical distribution. By comparing the probability of frost occurrence with the date of predicted bud burst, the risk of frost damage on apple budding was estimated. Copyright © 2009 Royal Meteorological Society
Numerical simulation of a tornado over Ludhiana (India) using WRF‐NMM model
Authors: Litta A. J. , Mohanty U. C. , Bhan S. C.
Published: September 2009

A severe thunderstorm produced a tornado (F0 on the Fujita‐Pearson scale) close to Ludhiana airport (Punjab), northwest region of India (30.80°N, 76.05°E) on 15 August 2007. Relatively less damage occurred as it passed through the open fields, but there were minor injuries to some cattle and damage to property. In this paper, analysis of meteorological conditions that led to the tornado on 15 August 2007 at 1100 UTC in Ludhiana has been made. An attempt is also made to simulate this rare event using the Non‐hydrostatic Mesoscale Model (NMM) core of the Weather Research and Forecasting (WRF) system with a spatial resolution of 3 km for a period of 24 h, starting at 0000 UTC of 15 August 2007. The results are encouraging in terms of timing and location of occurrence of the event. The atmospheric settings as indicated by surface, upper air and radar echo studies are favourable for severe thunderstorm activity over Ludhiana. The simulated instability indices (lifted index, total totals index and CAPE) over Ludhiana during the tornado hour, which act as indicators of severe convective activity, have been found to be in good agreement with the actual analysis. The model‐simulated meteorological parameters, relative humidity, mean sea level pressure, rainfall, moisture convergence, pressure vertical velocity and surface wind speed, are favourable for tornado occurrence at 1100 UTC over Ludhiana, and agree reasonably well with the observations. Copyright © 2009 Royal Meteorological Society