bluuebunny/crossref_metadata_2025 huggingface dataset:
Defining a dose–response relationship for prostate external beam radiotherapy
Authors: Trada Yuvnik , Plank Ash , Martin Jarad
Published: December 2012

Introduction

We aimed to quantify a relationship between radiotherapy dose and freedom from biochemical failure (FFBF) in low‐ and intermediate‐risk prostate cancer. To reduce confounding we used data with a standardised end–point, mature follow‐up, low competing risk of metastatic failure, conventional fractionation and separate reporting for outcomes with hormonal therapy (HT).

Methods

A systematic review of the literature was carried out. Studies that reported the use of radiotherapy alone in 1.8–2 Gy fractions in low‐ and intermediate‐risk prostate cancer were included. The primary end–point was Phoenix definition 5‐year FFBF. A logistic regression was used to quantify the dose–response relationship.

Results

Data from eight studies with 3037 patients met the inclusion criteria. The data from 810 low‐risk patients and 2245 intermediate‐risk patients were analysed. A strong association between radiotherapy dose and FFBF was found in low‐ and intermediate‐risk patients managed with radiotherapy alone. In low‐risk patients not treated with HT the dose required to achieve 50% biochemical tumour control (TCD50) is 52.0 Gy and the slope of the dose–response curve at TCD50 (γ50) is 2.1%/Gy. At 78 Gy this represented a FFBF of 90.3%. In intermediate‐risk patients not treated with HT the TCD50 is 64.7 Gy and γ50 is 3.2%/Gy. At 78 Gy this translated into a FFBF of 84.3%. HT had a small effect for low‐risk patients and an inconsistent effect for intermediate‐risk men.

Conclusion

A strong association was found between radiation dose and biochemical outcome in both low‐ and intermediate‐risk patients. Standardised reporting of results from future studies will make future analyses more robust.
PET/CT mediastinal and liver FDG uptake: Effects of biological and procedural factors
Authors: Malladi Ashish , Viner Maya , Jackson Tatianie , Mercier Gustavo , Subramaniam Rathan M
Published: December 2012

Introduction

To establish the effects of biological and procedural factors on mediastinal and liver [18F]‐fluorodeoxyglucose (FDG) uptake in oncological FDG positron emission tomography/computed tomography (PET/CT).

Methods

This retrospective study included 557 patients who had a baseline FDG PET/CT scan in 2008 and 2009. Mediastinal and liver standardised uptake values mean normalised to lean body mass (SUVlbmmean) were measured in each patient. Univariate and multivariate regression models were established. Study population was then dichotomised into low and high body mass index (BMI) groups, and linear regression models were established for the effects of age, incubation period and blood glucose levels.

Results

BMI had the highest adjusted effect (standardised beta coefficient, b = 0.43) (P < 0.001) and partial correlation, adjusting for covariates included in the final model (r = 0.45; P < 0.001) on mediastinal FDG uptake. Partial correlations (r) were 0.22 for age, −0.17 for male gender, −0.25 for incubation period and 0.14 for blood glucose (P < 0.001). The linear regression models showed significant differences in mediastinal FDG uptake between the low and high BMI groups and the effects of age, incubation period and basal blood glucose levels (P < 0.001). Similar results were observed for liver FDG uptake except the partial correlation for incubation period was r = −0.09 (P = 0.02).

Conclusion

BMI has the highest effect and correlation on mediastinal and liver FDG uptake. FDG uptake time has a greater effect on mediastinal than liver SUVlbmmean.
Development of a prototype of the tele‐localisation system in radiotherapy using personal digital assistant via wireless communication
Authors: Wu Vincent Wing‐cheung , Tang Fuk‐hay , Cheung Wai‐kwan , Chan Kit‐chi
Published: December 2012

In localisation of radiotherapy treatment field, the oncologist is present at the simulator to approve treatment details produced by the therapist. Problems may arise if the oncologist is not available and the patient requires urgent treatment. The development of a tele‐localisation system is a potential solution, where the oncologist uses a personal digital assistant (PDA) to localise the treatment field on the image sent from the simulator through wireless communication and returns the information to the therapist after his or her approval. Our team developed the first tele‐localisation prototype, which consisted of a server workstation (simulator) for the administration of digital imaging and communication in medicine localisation images including viewing and communication with the PDA via a Wi‐Fi network; a PDA (oncologist's site) installed with the custom‐built programme that synchronises with the server workstation and performs treatment field editing. Trial tests on accuracy and speed of the prototype system were conducted on 30 subjects with the treatment regions covering the neck, skull, chest and pelvis. The average time required in performing the localisation using the PDA was less than 1.5 min, with the blocked field longer than the open field. The transmission speed of the four treatment regions was similar. The average physical distortion of the images was within 4.4% and the accuracy of field size indication was within 5.3%. Compared with the manual method, the tele‐localisation system presented with an average deviation of 5.5%. The prototype system fulfilled the planned objectives of tele‐localisation procedure with reasonable speed and accuracy.
Cold Code: the global initiative toDNAbarcode amphibians and nonavian reptiles
Authors: Murphy Robert W. , Crawford Andrew J. , Bauer Aaron M. , Che Jing , Donnellan Stephen C. , Fritz Uwe , Haddad Célio F.B. , Nagy Zoltán T. , Poyarkov Nikolay A. , Vences Miguel , Wang Wen‐zhi , Zhang Ya‐ping
Published: December 2012

DNA barcoding facilitates the identification of species and the estimation of biodiversity by using nucleotide sequences, usually from the mitochondrial genome. Most studies accomplish this task by using the gene encoding cytochrome oxidase subunit I (COI; EntrezCOX1). Within this barcoding framework, many taxonomic initiatives exist, such as those specializing in fishes, birds, mammals, and fungi. Other efforts center on regions, such as the Arctic, or on other topics, such as health.DNAbarcoding initiatives exist for all groups of vertebrates except for amphibians and nonavian reptiles. We announce the formation of Cold Code, the international initiative toDNAbarcode all species of these ‘cold‐blooded’ vertebrates. The project has a Steering Committee, Coordinators, and a home page. To facilitate Cold Code, the Kunming Institute of Zoology, Chinese Academy of Sciences will sequenceCOIfor the first 10 specimens of a species at no cost to the steward of the tissues.
Characterization of transcriptomes from sexual and asexual lineages of a New Zealand snail (Potamopyrgus antipodarum)
Authors: Wilton Peter R. , Sloan Daniel B. , Logsdon Jr John M. , Doddapaneni Harshavardhan , Neiman Maurine
Published: December 2012

Understanding the evolution and maintenance of sexual reproduction is one of the central challenges of evolutionary biology, yet we know very little about how sex influences molecular evolution. The New Zealand freshwater snail Potamopyrgus antipodarum is ideally suited to address this knowledge gap because obligately sexual individuals often coexist with multiple independently derived obligately asexual lineages. This unusual situation allows direct comparisons both between sexual and asexual P. antipodarum and across populations that differ in the relative frequency of sexual individuals. As such, P. antipodarum has received a great deal of attention as a model system for the maintenance of sex in nature and is also used as a model for environmental toxicology and biological invasions. Molecular genetic resources for P. antipodarum will thus be useful to investigators in a variety of biological fields. We used 454 sequencing of cDNA libraries to generate transcriptomes from two sexual and two asexual P. antipodarum lineages. A de novo assembly of 116.7 Mb of sequence reads produced 41 396 contigs, and sequence similarity‐based Gene Ontology annotations were obtained for 3740 contigs. We detected 408 315 SNP loci and 7315 microsatellite loci, which together represent the first genome‐scale resource available for P. antipodarum. Raw 454 read sequences, contig sequences, annotation data and polymorphism data are publicly available in a searchable online database and for download at http://www.biology.uiowa.edu/neiman/transcriptome.php.
Genomic resource development for shellfish of conservation concern
Authors: Timmins‐Schiffman Emma B. , Friedman Carolyn S. , Metzger Dave C. , White Samuel J. , Roberts Steven B.
Published: December 2012

Effective conservation of threatened species depends on the ability to assess organism physiology and population demography. To develop genomic resources to better understand the dynamics of two ecologically vulnerable species in the Pacific Northwest of the United States, larval transcriptomes were sequenced for the pinto abalone, Haliotis kamtschatkana kamtschatkana, and the Olympia oyster, Ostrea lurida. Based on comparative species analysis the Ostrea lurida transcriptome (41 136 contigs) is relatively complete. These transcriptomes represent the first significant contribution to genomic resources for both species. Genes are described based on biological function with particular attention to those associated with temperature change, oxidative stress and immune function. In addition, transcriptome‐derived genetic markers are provided. Together, these resources provide valuable tools for future studies aimed at conservation of Haliotis kamtschatkana kamtschatkana, Ostrea lurida and related species.
Lung cancer incidence and mortality in China, 2009
Authors: Chen Wanqing , Zheng Rongshou , Zhang Siwei , Zou Xiaonong , Zhao Ping , He Jie
Published: December 2012

Background

The National Central Cancer Registry (NCCR) is a governmental organization for cancer surveillance affiliated to the Bureau of Disease Control, Ministry of Health, in China. It annually collects cancer registration data from local registries and then analyzes and publishes the results to provide useful information for making anti‐cancer policy, program evaluation, and etiology research. At the end of 2012, the NCCR reported cancer statistics for 2009.

Methods

By mid 2012, 104 population‐based cancer registries reported cancer incidence and mortality data, including demographic information, for 2009, to the NCCR. After an evaluation procedure, a total of 72 registries’ data met the criteria, which was then compiled for analysis. Individual lung cancer cases were retrieved from the national database based on the International Classification of Diseases (ICD)‐10 topography code as “C33, C34,“ including cancers of the trachea and bronchus. The crude incidence and mortality rates of lung cancer were calculated by gender, age, and location (urban/rural). China's population in 1982 and Segi's population structures were used for age‐standardized rates.

Results

In cancer registration areas in 2009, lung cancer was the most common cancer in China and in urban areas, the second most common cancer in rural areas. It was the leading cause of cancer death both in males and females, urban and rural areas. The incidence and mortality rates of lung cancer were higher in males than those in females, and in urban areas than in rural areas. The age‐specific incidence and mortality rates showed that both rates were relatively low for those aged under 50 years, but dramatically increased and reached a peak in the age group of 80–84 years.

Conclusion

Lung cancer is the most common cancer in China and leading cause of cancer death. Primary and secondary prevention should be carried out in each group, such as tobacco control and early detection.
Localized biphasic type malignant mesothelioma arising in the peritoneum: Report of a case
Authors: Kohno Mikihiro , Maruyama Riichiroh , Kitagawa Dai , Sugimachi Keishi , Kinjo Mitsuru , Higashi Hidefumi
Published: December 2012

This report describes a rare case of localized malignant biphasic (mixed epithelioid and sarcomatoid) mesothelioma arising in the peritoneum. A 69‐year‐old male with a history of asbestos exposure, complaining of a painful mass in the left chest wall, was found via computed tomography (CT) to have a tumor in the left peritoneum. The resected tumor was histologically and immunohistochemically consistent with a malignant mesothelioma with mixed epithelioid and sarcomatoid type and no distant metastasis. The diagnosis of localized malignant biphasic mesothelioma arising in the peritoneum was appropriate because there was no evidence of any other primary tumor.
Prevention of post‐dural puncture headache in parturients: a systematic review and meta‐analysis
Authors: BRADBURY C. L. , SINGH S. I. , BADDER S. R. , WAKELY L. J. , JONES P. M.
Published: December 2012

Post‐dural puncture headaches (PDPHs) present an important clinical problem. We assessed methods to decrease accidental dural punctures (ADPs) and interventions to reduce PDPH following ADP. Multiple electronic databases were searched for randomised clinical trials (RCTs) of parturients having labour epidurals, in which the studied intervention could plausibly affect ADP or PDPH, and the incidence of at least one of these was recorded. Forty RCTs (n = 11,536 epidural insertions) were included, studying combined spinal–epidurals (CSEs), loss of resistance medium, prophylactic epidural blood patches, needle bevel orientation, ultrasound‐guided insertion, epidural morphine, Special Sprotte needles, acoustic‐guided insertion, administration of cosyntropin, and continuous spinal analgesia. The RCTs for CSE, loss of resistance medium, and prophylactic epidural blood patches were meta‐analysed. Five methods reduced PDPH: prophylactic epidural blood patch {four trials, median quality score = 2, risk difference = −0.48 [95% confidence interval (CI): −0.88 to −0.086]}, lateral positioning of the epidural needle bevel upon insertion (one trial, quality score = 1), Special Sprotte needles [one trial, quality score = 5, risk difference = −0.44 (95% CI: −0.67 to −0.21)], epidural morphine [one trial, quality score = 4, risk difference = −0.36 (95% CI −0.59 to −0.13)], and cosyntropin [one trial, quality score = 5, risk difference = −0.36 (95% CI −0.55 to −0.16)]. Several methods potentially reduce PDPH. Special Sprotte needles, epidural morphine, and cosyntropin are thus far each supported by a single, albeit good quality trial. Prophylactic blood patches are supported by three trials, but these had flawed methodology. Mostly, trials were of limited quality, and further well‐conducted, large studies are needed.
The gastrointestinal manifestations of telomere‐mediated disease
Authors: Jonassaint Naudia L. , Guo Nini , Califano Joseph A. , Montgomery Elizabeth A. , Armanios Mary
Published: December 2012

Defects in telomere maintenance genes cause pathological telomere shortening, and manifest in syndromes which have prominent phenotypes in tissues of high turnover: the skin and bone marrow. Because the gastrointestinal (GI) epithelium is highly proliferative, we sought to determine whether telomere syndromes cause GI disease, and to define its prevalence, spectrum, and natural history. We queried subjects in the Johns Hopkins Telomere Syndrome Registry for evidence of luminal GI disease. In sixteen percent of Registry subjects (6 of 38), there was a history of significant GI pathology, and 43 additional cases were identified in the literature. Esophageal stenosis, enteropathy, and enterocolitis were the recurrent findings. In the intestinal mucosa, there was striking villous atrophy, extensive apoptosis, and anaphase bridging pointing to regenerative defects in the epithelial compartment. GI disease was often the first and most severe manifestation of telomere disease in young children. These findings indicate that telomere dysfunction disrupts the epithelial integrity in the human GI tract manifesting in recognizable disease processes. A high index of suspicion should facilitate diagnosis and management.
Derivative (5;19)(p10;q10): A rare but recurrent whole‐arm translocation in acute myeloid leukemia
Authors: Manabe Masahiro , Takakuwa Teruhito , Nakano Hirofumi , Harada Naonori , Okamoto Shuichiro , Aoyama Yasutaka , Kumura Takeo , Ohta Tadanobu , Furukawa Yoshio , Matsuda Mitsuhiro , Mugitani Atsuko
Published: December 2012

A previous study of cases of myelodysplastic syndrome harboring der(5;19)(p10;q10) found that they displayed common characteristics including predominance in elderly men, dysplasia involving three hematopoietic lineages and CD7 expression in blasts. However, the whole‐arm translocation der(5;19)(p10;q10) has not been fully analyzed because of its rarity. In this study we used flow cytometry to evaluate the immunophenotype of two patients' bone marrow mononuclear cells. Both patients had involved der(5;19)(p10;q10) in their karyotype analyzed by standard G‐banding technique. Both patients had the CD7+ and CD41+ phenotype, and the CD41 positivity suggested that the myeloid neoplasms involving der(5;19)(p10;q10) were of megakaryoblastic origin. The der(5;19)(p10;q10) abnormality is associated with unique characteristics of the immunophenotype. We address the clinical, immunophenotypic and morphological aspects of hematological malignancy involving der(5;19)(p10;q10), along with a review of the literature.
Cutting‐Edge Report: TLR10 Plays a Role in Mediating Bacterial Peptidoglycan‐Induced Trophoblast Apoptosis
Authors: Mulla Melissa J. , Myrtolli Kledia , Tadesse Serkalem , Stanwood Nancy L. , Gariepy Aileen , Guller Seth , Norwitz Errol R. , Abrahams Vikki M.
Published: December 2012

Problem

There is a strong correlation between intrauterine bacterial infection and preterm labor. While inflammation is a common mechanism, certain pathogens may trigger placental apoptosis. TLR2 activation by gram‐positive bacterial peptidoglycan (PDG) induces first‐trimester trophoblast apoptosis and decreased IL‐6 secretion. This is dependent upon the presence of TLR1 and the absence of TLR6 and both TLR2 coreceptors. As TLR10 is also a TLR2 coreceptor, the objective of this study was to determine its expression and function in the trophoblast.

Method of study

First‐and third‐trimester human placental tissue and isolated trophoblast were evaluated for TLR10 expression. A first‐trimester human trophoblast cell line stably transfected with a TLR10 dominant negative (TLR10‐DN) or vector control was treated with or without PDG and analyzed for apoptosis and IL‐6.

Results

TLR10 was expressed by trophoblasts during the first and third trimesters of pregnancy. PDG‐induced trophoblast caspase‐3 activity was inhibited by the presence of the TLR10‐DN. The presence of the TLR10‐DN had no effect on PDG reduction in trophoblast IL‐6 secretion.

Conclusion

This study demonstrates that trophoblast TLR10 plays a role in promoting apoptosis triggered by gram‐positive bacterial components and suggests that TLR10 may regulate the balance between trophoblast survival and cell death.
Correlations between commonly used objective signs and symptoms for the diagnosis of dry eye disease: clinical implications
Authors: Sullivan Benjamin D. , Crews Leslie A. , Messmer Elisabeth M. , Foulks Gary N. , Nichols Kelly K. , Baenninger Philipp , Geerling Gerd , Figueiredo Francisco , Lemp Michael A.
Published: December 2012

Purpose:  To evaluate the relationship between signs and symptoms of dry eye disease (DED) in a clinic‐based population.

Methods:  In a retrospective analysis, clinical signs and symptoms were evaluated for 344 subjects (n = 82, normal; n = 263, dry eye), across 11 sites from the EU and United States. Pearson correlations between signs and symptoms (r2) and an independent components analysis (ICA) mixing matrix were derived from the data set. Similar analysis was performed on an independent data set from 200 subjects in a previous study in Munich, Germany.

Results:  No correlations above r2 = 0.17 were found between any signs and symptoms, except for corneal and conjunctival staining, which reported an r2 = 0.36. In the multisite study, the average r2 for osmolarity (0.07), tear breakup time (0.12), Schirmer test (0.09), corneal (0.16) and conjunctival staining (0.17), meibomian grading (0.11) and Ocular Surface Disease Index® (0.11) were consistently low. Among patients who showed evidence of DED by consensus of clinical signs, only 57% reported symptoms consistent with a diagnosis of DED. Similar results were observed in the Munich‐based study data set. Each component of the ICA mixing matrix exhibited minimal residual information.

Conclusions:  No consistent relationship was found between common signs and symptoms of DED. Each type of measurement provides distinct information about the condition of the ocular surface. These results also demonstrate that symptoms alone are insufficient for the diagnosis and management of DED and argue for a consensus of clinical signs that better reflect all aspects of the disease.
Unravelling the mechanism of action of NS9283, a positive allosteric modulator of (α4)3(β2)2 nicotinic ACh receptors
Authors: Grupe M , Jensen AA , Ahring PK , Christensen JK , Grunnet M
Published: December 2012

Background and Purpose

Strong implications in major neurological diseases make the neuronal α4β2 nicotinic ACh receptor (nAChR) a highly interesting drug target. In this study, we present a detailed electrophysiological characterization of NS9283, a potent positive allosteric modulator acting selectively at 3α:2β stoichiometry of α2* and α4* nAChRs.

Experimental Approach

The whole‐cell patch‐clamp technique equipped with an ultra‐fast drug application system was used to perform electrophysiological characterization of NS9283 modulatory actions on human α4β2 nAChRs stably expressed in HEK293 cells (HEK293‐hα4β2).

Key Results

NS9283 was demonstrated to increase the potency of ACh‐evoked currents in HEK293‐hα4β2 cells by left‐shifting the concentration–response curve ∼60‐fold. Interestingly, this modulation did not significantly alter maximal efficacy levels of ACh. Further, NS9283 did not affect the rate of desensitization of ACh‐evoked currents, was incapable of reactivating desensitized receptors and only moderately slowed recovery from desensitization. However, NS9283 strongly decreased the rate of deactivation kinetics and also modestly decreased the rate of activation. This resulted in a left‐shift of the ACh window current of (α4)3(β2)2 nAChRs in the presence of NS9283.

Conclusions and Implications

This study demonstrates that NS9283 increases responsiveness of human (α4)3(β2)2 nAChR to ACh with no change in maximum efficacy. We propose that this potentiation is due to a significant slowing of deactivation kinetics. In summary, the mechanism of action of NS9283 bears high resemblance to that of benzodiazepines at the GABAA receptor and to our knowledge, NS9283 constitutes the first nAChR compound of this class.
Polycystic ovary syndrome has no independent effect on vascular, inflammatory or thrombotic markers when matched for obesity
Authors: Kahal H. , Aburima A. , Ungvari T. , Rigby A. S. , Dawson A. J. , Coady A. M. , Vince R. V. , Ajjan R. A. , Kilpatrick E. S. , Naseem K. M. , Atkin S. L.
Published: December 2012

Introduction

Previous studies investigating cardiovascular (CV) risk in obese women with polycystic ovary syndrome (PCOS) have been potentially confounded by not adequately accounting for body weight.

Objective

To assess if PCOS increases CV risk independently in young obese women by examining carotid intima‐media wall thickness (cIMT) and platelet function.

Design

A case–control study comparing women with PCOS (n = 21) to age (32·8 ± 7·2 vs 33·5 ± 6·7 years), and weight (100·9 ± 16·7 vs 99·3 ± 14·7 kg)‐matched controls (n = 19). Platelet function was examined by flow cytometry, clot structure and fibrinolysis by turbidimetric assays and endothelial function by ELISA and post ischaemic reactive hyperaemia.

Results

The PCOS group had higher testosterone 1·2 ± 0·3 vs 0·9 ± 0·3 nmol/l (P = 0·01), HOMA‐IR 2·5 ± 1·7 vs 1·7 ± 1·0 (P = 0·08), impaired glucose regulation 33·3% vs 5·3% (P = 0·02), and urinary isoprostane 16·0 ± 4·4 vs 11·8 ± 7·1 ng/ml (P = 0·04) compared to controls. Mean cIMT 0·5 ± 0·05 vs 0·48 ± 0·06 mm (P = 0·36), and basal platelet surface expression (percentage of positive cells) of P‐selectin 0·52 ± 0·3 vs 0·43 ± 0·23 (P = 0·40) and fibrinogen binding 0·97 ± 0·4 vs 0·83 ± 0·3 (P = 0·48) did not significantly differ between the PCOS and control groups respectively. Furthermore, platelets sensitivity to stimulation with adenosine‐5′‐diphosphate or inhibition with prostacyclin, clot structure and fibrinolytic efficiency ex vivo, endothelial reactive hyperaemic index (RHI), inflammation (hsCRP) and adhesion markers (sE‐selectin, sP‐selectin, sVCAM‐1 and sICAM‐1) were not significantly different between the two groups.

Conclusions

PCOS appeared not to independently increase atherothrombotic risk when matched for obesity. It is likely that any excess CV risk in young obese women with PCOS can either be attributed to obesity or is not yet apparent at this early stage of the condition.
What Is Causing Extremely Elevated Amino Terminal Brain Natriuretic Peptide in Cancer Patients?
Authors: Popat Jesal , Rivero Abel , Pratap Pravin , Guglin Maya
Published: December 2012

High levels of B‐type natriuretic peptide in cancer patients are poorly studied. Previously published data suggest that they are not related to fluid overload and are encountered mostly in solid cancers. The authors investigated the distribution of amino terminal pro‐brain natriuretic peptide (NT‐proBNP) between hematologic and solid organ malignancies and the relationship of NT‐proBNP with volume status in oncologic patients. A total of 145 consecutive patients with at least one occurrence of NT‐proBNP exceeding the upper normal range 10‐fold were identified. The authors retrospectively reviewed their records including clinical, laboratory, and radiological data and echocardiograms. More than 70% of patients had hematologic malignancies. Patients with NT‐proBNP >50,000 pg/mL had only hematologic malignancies, primarily multiple myeloma. There was no association between M‐spike proteins and NT‐proBNP. About 80% of patients had signs of fluid overload. The magnitude of NT‐proBNP elevation was similar between those with and without heart failure or volume overload, as well as with solid cancers vs hematologic malignancies. Contrary to prior reports, it was found that very high NT‐proBNP in cancer patients is usually encountered in the context of fluid overload and most often in hematologic malignancies.
De novo malignancies in renal transplant recipients: experience at a single center with 1882 transplant patients over 39 yr
Authors: Apel Hendrik , Walschburger‐Zorn Karin , Häberle Lothar , Wach Sven , Engehausen Dirk G. , Wullich Bernd
Published: December 2012

Purpose

Cancers complicating organ allografts are a major cause of morbidity and mortality after renal transplantation. Different registries have described an overall three to eightfold increase in cancer risk compared with the general population. This retrospective study investigated the incidence and outcome of de novo malignancies following kidney transplantation in a single German kidney transplantation center.

Materials and Methods

Between 1966 and 2005, 1882 patients underwent kidney transplantation at the Erlangen–Nuremberg kidney transplantation center. The incidence and types of post‐transplant malignancies were retrospectively analyzed according to the patients' records and the database of the local cancer registry.

Results

We identified 257 malignancies in 231 patients, an overall incidence of 13.7%. The mean follow‐up time was 9.9 yr (range, 0.4–25.5 yr). The observed incidence data corresponded to a 12.1‐fold increase in the overall risk of developing a malignant nonskin tumor compared with the nontransplanted population. Urinary tract malignancies represented the most frequent malignancies among the nonskin tumors (32.1%), followed by gastrointestinal tract (30.7%) and gynecological (14%) cancers. When we considered the duration from renal transplantation to tumor detection and tumor‐specific survival, there was no difference between patients treated with or without a cyclosporine A‐based regimen.

Conclusions

In our study, the overall risk of developing a post‐transplant nonskin malignancy was 12.1‐fold higher compared with the age‐matched general population. Development of solid organ malignancies is one of the most frequent causes of morbidity and mortality in renal transplant recipients; thus, close tumor screening in patients after kidney transplantations is warranted.
Endoscopic therapy in the treatment of caustic esophageal stricture: A retrospective case series study
Authors: Zhang Cuiling , Zhou Xiaoying , Yu Lianzhen , Ding Jing , Shi Ruihua
Published: December 2012

Background

Endoscopic procedures, such as balloon/bougie dilation and stent implantation, have gained increasing potential as the treatment of corrosive esophageal stricture. The purpose of the present retrospective case series study was to assess clinical outcomes of endoscopic therapy of esophageal strictures after caustic injury.

Patients and Methods

Between January 2003 and December 2009, 13 admitted patients that developed esophageal stricture after caustic agent ingestion underwent endoscopic therapy at the First Affiliated Hospital of Nanjing Medical University. Data such as age, gender, caustic agents, site of burn, type of treatment, effectiveness and outcome of endoscopic therapy were recorded.

Results

The average follow up was 39 months with a range of 29–70 months. Successful endoscopic therapy was achieved in 12 of 13 patients (92%). Duration of stricture resolution was between 4 and 48 months (mean, 15 months). Among them, seven patients required dilations only, whereas the other five patients received both dilations and stent implantation. There were no severe complications in these patients.

Conclusions

These data suggest that endoscopic therapy is feasible, less invasive and effective for the management of caustic esophageal stricture. After repeat dilation and stenting, patients can achieve stricture resolution in approximately 15 months and avoid surgery.
Microparticle‐associated tissue factor activity in patients with pancreatic cancer: correlation with clinicopathological features
Authors: Thaler Johannes , Ay Cihan , Mackman Nigel , Metz‐Schimmerl Sylvia , Stift Judith , Kaider Alexandra , Müllauer Leonhard , Gnant Michael , Scheithauer Werner , Pabinger Ingrid
Published: December 2012

Background

Patients with pancreatic cancer have an unfavourable prognosis. A central role in pancreatic cancer progression has been suggested for tissue factor (TF), the main initiator of the blood coagulation cascade. We hypothesized that elevated levels of plasma microparticle (MP)‐associated TF activity might indicate the presence of poorly differentiated pancreatic cancer, disease dissemination and infiltration of peripancreatic vessels.

Methods

MP‐TF activity was measured in 73 pancreatic cancer patients and 22 healthy controls. Abdominal computerized tomography (CT) scans performed at study inclusion were investigated for probability of tumoural vascular invasion. In addition, intratumoural TF expression, D‐dimer and CA 19‐9 levels were determined.

Results

MP‐TF activity (pg/mL) was significantly higher in patients (median: 0·37 [range: 0·00–11·91]) than in controls (median: 0·05 [range: 0·00–0·76]; P < 0·001). When pancreatic cancer patients were compared with regard to stage and grade, significantly elevated levels of MP‐TF activity were only present in those with poorly differentiated metastatic nonresectable tumours (n = 11, median: 2·95 [range: 0·25–11·91]). In three patients with poorly differentiated tumours, a high probability of vascular invasion was found (MP‐TF activity in these cases: 2·95, 7·00 and 10·34). MP‐TF activity correlated strongly with CA 19‐9 (r = 0·60) and weakly with D‐dimer (r = 0·33) levels. Immunohistochemical staining for TF was positive in 14 of 15 resected tumours. MP‐TF activity was associated with an increased risk of mortality (HR: 1·8 per doubling in MP‐TF activity, [95% CI: 1·4–2·4, P < 0·001]).

Conclusion

MP‐TF activity might represent a biomarker for a poorly differentiated and invasive pancreatic cancer phenotype and poor survival.
Gaze is driven by an internal goal trajectory in a visuomotor task
Authors: Tramper J. J. , Lamont A. , Flanders M. , Gielen S.
Published: December 2012

When we make hand movements to visual targets, gaze usually leads hand position by a series of saccades to task‐relevant locations. Recent research suggests that the slow smooth pursuit eye movement system may interact with the saccadic system in complex tasks, suggesting that the smooth pursuit system can receive non‐retinal input. We hypothesise that a combination of saccades and smooth pursuit guides the hand movements towards a goal in a complex environment, using an internal representation of future trajectories as input to the visuomotor system. This would imply that smooth pursuit leads hand position, which is remarkable, as the general idea is that smooth pursuit is driven by retinal slip. To test this hypothesis, we designed a video‐game task in which human subjects used their thumbs to move two cursors to a common goal position while avoiding stationary obstacles. We found that gaze led the cursors by a series of saccades interleaved with ocular fixation or pursuit. Smooth pursuit was correlated with neither cursor position nor cursor velocity. We conclude that a combination of fast and slow eye movements, driven by an internal goal instead of a retinal goal, led the cursor movements, and that both saccades and pursuit are driven by an internal representation of future trajectories of the hand. The lead distance of gaze relative to the hand may reflect a compromise between exploring future hand (cursor) paths and verifying that the cursors move along the desired paths.
First report of chromosomes of the parasitoid wasp Trissolcus basalis (Wollaston) (Hymenoptera: Platygastridae: Telenominae)
Authors: Fusu Lucian , Bin Ferdinando , Popovici Ovidiu Alin
Published: December 2012

Here we present the first data on the chromosome complement of Trissolcus basalis gathered in conjunction with the ongoing whole genome sequencing efforts for this species. The cytogenetic investigation revealed a diploid karyotype with 20 chromosomes, comprising one pair of large metacentrics and nine pairs of acrocentrics that gradually decrease in length.
Breaking the Social–Non‐social Dichotomy: A Role for Reptiles in Vertebrate Social Behavior Research?
Authors: Doody J. Sean , Burghardt Gordon M. , Dinets Vladimir
Published: December 2012

Although social behavior in vertebrates spans a continuum from solitary to highly social, taxa are often dichotomized as either ‘social’ or ‘non‐social’. We argue that this social dichotomy is overly simplistic, neglects the diversity of vertebrate social systems, impedes our understanding of the evolution of social behavior, and perpetuates the erroneous belief that one group—the reptiles—is primarily ‘non‐social’. This perspective essay highlights the diversity and complexity of reptile social systems, briefly reviews reasons for their historical neglect in research, and indicates how reptiles can contribute to our understanding of the evolution of vertebrate social behavior. Although a robust review of social behavior across vertebrates is lacking, the repeated evolution of social systems in multiple independent lineages enables investigation of the factors that promote shifts in vertebrate social behavior and the paraphyly of reptiles reinforces the need to understand reptile social behavior.
A peptide derived from the C‐terminus of PB1 inhibits influenza virus replication by interfering with viral polymerase assembly
Authors: Li Chunfeng , Ba Qi , Wu Aiping , Zhang Hong , Deng Tao , Jiang Taijiao
Published: December 2012

Efficient assembly of the influenza virus RNA‐dependent RNA polymerase, a heterotrimeric complex formed by three subunits (PA, PB1 and PB2) is critical for virus replication and pathogenicity. Therefore, interfering with the assembly of the RNA‐dependent RNA polymerase complex could offer novel and effective anti‐influenza therapeutics. In the present study, we show that a short peptide derived from amino acids 731–757 of PB1 (PB1731–757) can disrupt the interaction between the C‐terminal part of PB1 (denoted as PB1c corresponding to PB1676–757) and the N‐terminal part of PB2 (denoted as PB2n corresponding to PB21–40). We further show that PB1731–757 is capable of inhibiting viral polymerase activity and viral replication. Interestingly, we find that PB1731–757 interacts with PB1c rather than PB2n. Furthermore, mutational analyses show that the hydrophobic sites of PB1c play an essential role in the PB1c–PB1731–757 interaction. The characterization of the inhibitory effect of PB1731–757 on viral polymerase activity and viral replication could offer a potential target for anti‐influenza drug development.

Structured digital abstract

PB2n physically interacts with PB1c by pull down (View interaction)

PB2n and PB1c physically interact by bimolecular fluorescence complementation (View interaction)

PB1 (731-757) physically interacts with PB1c by pull down (View interaction)

PB1 (731-757) and PB1c physically interact by bimolecular fluorescence complementation (View Interaction: 1, 2, 3, 4, 5)

[Structured digital abstract was added on 11 February 2013 after original online publication]
Ethical problems in geriatrics: Views of Turkish primary healthcare professionals
Authors: Kadıoğlu Funda Gülay , Can Rana , Nazik Sadık , Kadıoğlu Selim
Published: December 2012

Aim

Primary healthcare professionals frequently encounter ethical issues in the care of older adults. These issues might particularly appear in the context of “age discrimination”, “respect for autonomy”, “respect for privacy” and “decision‐making competency”. The aims of this study were to determine the frequency rates of various geriatric ethical problems and to evaluate the importance given to these problems in primary healthcare.

Methods

In order to evaluate the opinions, a questionnaire tool was formulated. The participants were asked to review the list of geriatric ethical issues, to state the frequency of encountering them and to identify the importance ratings for each issue. The sample consisted of 86 primary healthcare professionals (50 physicians and 36 nurses) aged between 24 and 50 years.

Results

Based on the results, the most frequently encountered ethical issues were on “decision‐making competency” and these issues respectively were “decision‐making with relatives instead of elder patients”, “not informing elders due to the lack of tolerance” and “not informing elders due to the lack of comprehending”. The most important geriatric ethical issues were “ignoring respect for privacy”, “ignoring patient's complaints” and “rejecting detailed examination or treatment because of age”.

Conclusion

Overall, the results show that the nurses and physicians in primary healthcare frequently encounter geriatric ethical problems related to the decision‐making process, which is a common issue for Turkey as a paternalistic society. The findings show that primary healthcare professionals are sensitive to geriatric ethical issues; however, this sensitivity does not prevent the emergence of these issues. Geriatr Gerontol Int 2012; 13: 1059–1068.
Association of spinal inclination with physical performance measures among community‐dwelling Japanese women aged 40 years and older
Authors: Abe Yasuyo , Aoyagi Kiyoshi , Tsurumoto Tadao , Chen Chih‐Yu , Kanagae Mitsuo , Mizukami Satoshi , Ye Zhaojia , Kusano Yosuke
Published: December 2012

Aim

Spinal inclination assesses spinal posture as a whole. However, the association between spinal inclination and physical performance has not yet been fully elucidated. Therefore, this study aimed to explore the association of spinal inclination with physical performance measures.

Methods

The participants were 107 Japanese women aged 40–84 years. Spinal posture was assessed as inclination to a perpendicular line by using a computer‐assisted device. Increased inclination value means forward inclination of the spine. Physical performance was measured by using the following methods: 6‐m walking time, chair stand time, functional reach, Timed Up & Go Test, and grip strength. Information on participants' comorbidities, osteoporosis, knee joint pain, back pain, falls in the previous year, regular exercise and usage of non‐steroidal anti‐inflammatory drugs (NSAIDs), was also collected.

Results

Pearson's correlation analysis showed significant associations between spinal inclination and all of the physical performance measures. Pearson's partial correlation analysis adjusted for age showed significant associations of increased inclination with poor physical functioning in 6‐m walking time, chair stand time, functional reach, and Timed Up & Go Test, but not in grip strength. Linear regression analysis adjusted for age, grip strength, number of comorbidities, osteoporosis, knee joint pain, back pain, falls in previous year, regular activity and taking NSAIDs showed that spinal inclination was associated with poor function in 6‐m walking time, chair stand time, functional reach and Timed Up & Go Test.

Conclusion

Forward spinal inclination was associated with impairment in various physical performance measures. Proper prevention and treatment of underlying disorders should be prompted. Geriatr Gerontol Int 2012; 13: 881–886.
Measuring illuminance and investigating methods for its quantification among elderly people living at home in Japan to study the relationship between illuminance and physical and mental health
Authors: Ichimori Akie , Tsukasaki Keiko , Koyama Emi
Published: December 2012

Aim

To measure illuminance in the home lives of elderly people to clarify the current state of affairs and concurrently investigate quantification methods for this purpose.

Methods

Illuminance and the physical and mental health of 24 elderly people living, with some assistance, in their homes in a prefecture in the Hokuriku region were studied over 3 days. Illuminance was quantified in accordance with the rotation of the earth, with day and night defined according to times of sunrise/sunset. Daytime mean illuminance and mean time exposed to seven levels of illuminance between 50 and 1000 lx during the day were calculated. Physical and mental health were assessed through interviews using the Instrumental Activities of Daily Living Scale, the Short‐Form 36‐Item Health Survey version 2, the Philadelphia Geriatric Center Morale Scale and the Geriatric Depression Scale‐Short Form. Analysis of the correlation between illuminance and scores on mental and physical health was carried out.

Results

The mean score for daytime illuminance was 687 lx. The mean time for daytime exposure to light above 400 lx was 59 min. A significant positive correlation was found between daytime mean illuminance, time exposed to light over 400 lx and life satisfaction. A significant negative correlation was found between time exposed to light over 400 lx and depression scores.

Conclusions

Findings uncovered for the first time the actual illumination experienced by frail elderly individuals living at home in Japan. The quantification of illuminance is important, because research has shown a relationship between mental health and illuminance exposure. Geriatr Gerontol Int 2013; 13: 798–806.
Cosmopolitan communities of climate risk: conceptual and empirical suggestions for a new research agenda
Authors: BECK ULRICH , BLOK ANDERS , TYFIELD DAVID , ZHANG JOY YUEYUE
Published: December 2012

Mitigating human‐induced climate change calls for a globalized change of consciousness and practice. These global challenges also demand a double transformation of the social sciences – first, from ‘methodological nationalism’ to ‘methodological cosmopolitanism’ and, second, an empirical reorientation towards ‘cosmopolitization’ as the social force of emerging cosmopolitan realities. One of these realities is the possible emergence, locally and globally, of ‘cosmopolitan communities of climate risk’ in response to a ‘world at risk’. A key research question for contemporary social science is thus: how and where are new cosmopolitan communities of climate risk being imagined and realized? In this article, we propose and explore a research agenda formulated around this key question. We both develop a theoretical perspective and provide short empirical illustrations of case studies regarding ongoing research in Europe and East Asia on such cosmopolitan climate risk communities.
Selective accumulation of platinum and formation of platinum–DNA adducts in hepatocellular carcinoma after transarterial chemoembolization with miriplatin
Authors: Yasui Kohichiroh , Takashima Hidetaka , Miyagawa Masami , Miyazawa Kazuhiro , Ochiai Toshiya , Mukaisho Ken‐ichi , Amaike Hisashi , Ueda Kazushige , Morikawa Junichiro , Otsuji Eigo , Yoshikawa Toshikazu
Published: December 2012

Aim

Miriplatin, a lipophilic platinum complex, is a novel intra‐arterial chemotherapeutic agent for hepatocellular carcinoma (HCC). Little is known about platinum–DNA adduct levels in human HCC after administration of platinum‐based drugs. We investigated whether miriplatin selectively accumulates and forms platinum–DNA adducts in human HCC tumors.

Methods

Using inductively coupled plasma mass spectrometry, we determined the platinum concentrations and platinum–DNA adduct levels in paired HCC tumors and non‐tumor liver tissues of four patients who received transcatheter arterial chemoembolization with miriplatin and subsequently underwent hepatic resection.

Results

The mean (± standard deviation) platinum concentrations were 730 ± 350 μg/g (range, 400–1100) in HCC tumors and 16 ± 9.2 μg/g (range, 9.2–29) in non‐tumor liver tissues. The concentrations were approximately 50‐fold higher in HCC tumors than in non‐tumor liver tissues. The mean platinum–DNA adduct levels were 54 ± 16 pg Pt/μg DNA (range, 37–69) in HCC tumors and 13 ± 13 pg Pt/μg DNA (range, 4.8–33) in non‐tumor liver tissues. The adduct levels were roughly 7.6‐fold higher in HCC tumors than in non‐tumor liver tissues. There were no significant correlations between platinum concentrations and platinum–DNA adduct levels in HCC tumors.

Conclusion

Our results quantitatively demonstrate that there is a selective accumulation of platinum and formation of platinum–DNA adducts in human HCC tumors after transarterial chemoembolization with miriplatin. No correlation was observed between platinum concentrations and platinum–DNA adduct levels.