bluuebunny/crossref_metadata_2025 huggingface dataset:
InGaAs HEMTs with T‐gate electrodes formed by multi‐layer SiCN molds
Authors: Yoshida Tomohiro , Kobayashi Kengo , Otsuji Taiichi , Suemitsu Tetsuya
Published: February 2013

We report a method to control the shape of T‐gates precisely by using multi‐layer SiCN molds. The SiCN molds consist of a series of SiCN thin films with gradually changed etching properties. The SiCN was deposited by plasma‐enhanced chemical vapor deposition using hexamethyldisilazane (HMDS) vapor. An optimized deposition condition of SiCN molds enables us to achieve more precisely control in the T‐gate shape such as the stem angle. The SiCN molds technique was applied to the fabrication of T‐gates in InGaAs high electron mobility transistors (HEMTs). Two types of HEMTs using the SiCN molds with different deposition conditions were fabricated. The detail analysis of the HEMTs indicates that the difference in the parasitic gate delay and gate resistance reflects the T‐gate shapes. (© 2013 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
A Biochemical and Cellular Approach to Explore the Antiproliferative and Prodifferentiative Activity of Aloe Arborescens Leaf Extract
Authors: Di Luccia Blanda , Manzo Nicola , Vivo Maria , Galano Eugenio , Amoresano Angela , Crescenzi Elvira , Pollice Alessandra , Tudisco Raffaella , Infascelli Federico , Calabrò Viola
Published: February 2013

Aloe arborescens Miller, belonging to the Aloe genus (Liliaceae family), is one of the main varieties of Aloe used worldwide. Although less characterized than the commonest Aloe vera, Aloe arborescens is known to be richer in beneficial phytotherapeutic, anticancer, and radio‐protective properties. It is commonly used as a pharmaceutical ingredient for its effect in burn treatment and ability to increase skin wound healing properties. However, very few studies have addressed the biological effects of Aloe at molecular level. The aim of the research is to provide evidences for the antiproliferative properties of Aloe arborescens crude leaf extract using an integrated proteomic and cellular biological approach. We analysed the composition of an Aloe arborescens leaf extract by gas chromatography‐mass spectrometry analysis. We found it rich in Aloe‐emodin, a hydroxylanthraquinone with known antitumoral activity and in several compounds with anti‐oxidant properties. Accordingly, we show that the Aloe extract has antiproliferative effects on several human transformed cell lines and exhibits prodifferentiative effects on both primary and immortalized human keratinocyte. Proteomic analysis of whole cell extracts revealed the presence of proteins with a strong antiproliferative and antimicrobial activity specifically induced in human keratinocytes by Aloe treatment supporting its application as a therapeutical agent. Copyright © 2013 John Wiley & Sons, Ltd.
Performance of numerical atom‐centered basis sets in the ground‐state correlated calculations of noncovalent interactions: Water and methane dimer cases
Authors: Zakharov Maxim
Published: February 2013

Numerical atom‐centered basis sets (orbitals) (NAO) are known for their compactness and rapid convergence in the Hartree–Fock and density‐functional theory (DFT) molecular electronic‐structure calculations. To date, not much is known about the performance of the numerical sets against the well‐studied Gaussian‐type bases in correlated calculations. In this study, one instance of NAO [Blum et al., The Fritz Haber Institute ab initio Molecular Simulations Package (FHI‐aims), 2009] was thoroughly examined in comparison to the correlation‐consistent basis sets in the ground‐state correlated calculations on the hydrogen‐bonded water and dispersion‐dominated methane dimers. It was shown that these NAO demonstrate improved, comparing to the unaugmented correlation‐consistent based, convergence of interaction energies in correlated calculations. However, the present version of NAO constructed in the DFT calculations on covalently‐bound diatomics exhibits enormous basis‐set superposition error (BSSE)—even with the largest bases. Moreover, these basis sets are essentially unable to capture diffuse character of the wave function, necessary for example, for the complete convergence of correlated interaction energies of the weakly‐bound complexes. The problem is usually treated by addition of the external Gaussian diffuse functions to the NAO part, what indeed allows to obtain accurate results. However, the operation increases BSSE with the resulting hybrid basis sets even further and breaks down the initial concept of NAO (i.e., improved compactness) due to the significant increase in their size. These findings clearly point at the need in the alternative strategies for the construction of sufficiently‐delocalized and BSSE‐balanced purely‐numerical bases adapted for correlated calculations, possible ones were outlined here. For comparison with the considered NAOs, a complementary study on the convergence properties of the correlation‐consistent basis sets, with a special emphasis on BSSE, was also performed. Some of its conclusions may represent independent interest. © 2013 Wiley Periodicals, Inc.
Coping with time and space in modelling malaria incidence: a comparison of survival and count regression models
Authors: Getachew Yehenew , Janssen Paul , Yewhalaw Delenasaw , Speybroeck Niko , Duchateau Luc
Published: February 2013

To study the effect of a mega hydropower dam in southwest Ethiopia on malaria incidence, we have set up a longitudinal study. To gain insight in temporal and spatial aspects, that is, in time (period  =  year–season combination) and location (village), we need models that account for these effects. The frailty model with periodwise constant baseline hazard (a constant value for each period) and a frailty term that models the clustering in villages provides an appropriate tool for the analysis of such incidence data. Count data can be obtained by aggregating for each period events at the village level. The mixed Poisson regression model can be used to model the count data. We show the similarities between the two models. The risk factor in both models is the distance to the dam, and we study the effect of the risk factor on malaria incidence. In the frailty model, each subject has its own risk factor, whereas in the Poisson regression model, we also need to average the risk factors of all subjects contributing to a particular count. The power loss caused by using village averaged distance instead of individual distance is studied and quantified. The loss in the malaria data example is rather small. In such a setting, it might be advantageous to use less labor‐intensive sampling schemes than the weekly individual follow‐up scheme used in this study; the proposed alternative sampling schemes might also avoid community fatigue, a typical problem in such research projects. Copyright © 2013 John Wiley & Sons, Ltd.
Analysis and testing of black‐box component‐based systems by inferring partial models
Authors: Shahbaz Muzammil , Groz Roland
Published: February 2013

From experience in component‐based software engineering, it is known that the integration of high‐quality components may not yield high‐quality software systems. It is difficult to evaluate all possible interactions between the components in the system to uncover inter‐component misfunctions. The problem is even harder when the components are used without source code, specifications or formal models. Such components are called black boxes in literature. This paper presents an iterative approach of combining model learning and testing techniques for the formal analysis of a system of black‐box components. In the approach, individual components in the system are learned as finite state machines that (partially) model the behavioural structure of the components. The learned models are then used to derive tests for refining the partial models and/or finding integration faults in the system. The approach has been applied on case studies that have produced encouraging results. Copyright © 2013 John Wiley & Sons, Ltd.
Association of sick building syndrome with neuropathy target esterase (NTE) activity in Japanese
Authors: Matsuzaka Yasunari , Ohkubo Tomoichi , Kikuti Yukie Y. , Mizutani Akiko , Tsuda Michio , Aoyama Yoshiko , Kakuta Kazuhiko , Oka Akira , Inoko Hidetoshi , Sakabe Kou , Ishikawa Satoshi , Kulski Jerzy K. , Kimura Minoru
Published: February 2013

Sick building syndrome (SBS) is a set of several clinically recognizable symptoms reported by occupants of a building without a clear cause. Neuropathy target esterase (NTE) is a membrane bound serine esterase and its reaction with organophosphates (OPs) can lead to OP‐induced delayed neuropathy (OPIDN) and nerve axon degeneration. The aim of our study was to determine whether there was a difference in NTE activity in the peripheral blood mononuclear cells (PBMCs) of Japanese patients with SBS and healthy controls and whether PNPLA6 (alias NTE) gene polymorphisms were associated with SBS. We found that the enzymatic activity of NTE was significantly higher (P < 0.0005) in SBS patients compared with controls. Moreover, population with an AA genotype of a single nucleotide polymorphism (SNP), rs480208, in intron 21 of the PNPLA6 gene strongly reduced the activity of NTE. Fifty‐eight SNP markers within the PNPLA6 gene were tested for association in a case–control study of 188 affected individuals and 401 age‐matched controls. Only one SNP, rs480208, was statistically different in genotype distribution (P = 0.005) and allele frequency (P = 0.006) between the cases and controls (uncorrected for testing multiple SNP sites), but these were not significant by multiple corrections. The findings of the association between the enzymatic activity of NTE and SBS in Japanese show for the first time that NTE activity might be involved with SBS. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1217–1226, 2014.
Effects of subchronic exposure to low‐dose volatile organic compounds on lung inflammation in mice
Authors: Wang Fan , Li Chonglei , Liu Wei , Jin Yihe , Guo Li
Published: February 2013

Inflammatory lung diseases are characterized by chronic inflammation and oxidant/antioxidant imbalance. Exposure to some kinds of volatile organic compounds (VOCs) leads to lung inflammation, oxidative stress, and immune modulation. However, it is suspected that sub‐chronic exposure to low‐dose VOCs mixture induces or aggravates lung inflammation. To clarify the effect of this exposure on lung inflammatory responses, 40 male Kunming mice were exposed in four similar static chambers, 0 (control) and three different doses of VOCs mixture (groups 1–3). The concentrations of VOCs mixture were as follows: formaldehyde, benzene, toluene, and xylene 0.10 + 0.11 + 0.20 + 0.20 mg/m3, 0.50 + 0.55 + 1.00 + 1.00 mg/m3, 1.00 + 1.10 + 2.00 + 2.00 mg/m3, respectively, which corresponded to 1, 5, and 10 times of indoor air quality standard in China. After 90 consecutive days of exposure (2 h/day), oxidative stress markers in lung, cellular infiltration and cytokines, chemokine, neurotrophin in bronchoalveolar lavage fluid (BALF), and immunoglobulin (Ig) in serum were examined. VOCs exposure could increase significantly reactive oxygen species (ROS) in lung, the levels of interleukin‐8 (IL‐8), IL‐4, eotaxin, nerve growth factor (NGF), and various types of leukocytes in BALF, IgE concentration in serum. In contrast, GSH to GSSG ratio and interferon‐gamma were significantly decreased following the VOCs exposure. These results indicate that the VOCs mixture‐induced inflammatory response is at least partly caused by release of the ROS and mediators from the activated eosinophils, neutrophils, alveolar macrophages and epithelial cells. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1089–1097, 2014.
Histological alterations in the structure of the testis in tench (Tinca tinca) after exposure to 17 alpha‐ethynylestradiol
Authors: Oropesa A. L. , Jiménez B. , Gil M. C. , Osswald J. , Fallola C. , Pula H. J. , Cuesta J. M. , Gómez L.
Published: February 2013

Environmental pollution with synthetic estrogens may pose a serious threat to reproduction of aquatic wildlife species. The current study describes the effects of 17α‐ethynylestradiol (EE2) on the structure of the testis in tench (Tinca tinca). Adult male tench were exposed to sublethal doses of EE2 (50, 100, and 500 μg/Kg t.w.) under semistatic conditions for a period of 30 days. The condition factor (CF), testicular somatic index (TSI), and histology (including a morphometric analysis) of the testis were examined. No consistent differences were observed in the CF of EE2‐exposed tench when compared with nonexposed fish. A significant decrease in TSI could only be observed at a 50 μg/Kg t.w. EE2 dose (p < 0.05) when compared with the control group. The histopathology of the testis was associated with loss of normal tubular structure with increased doses of exposure, decrease of tubule number, degeneration in Sertoli and Leydig cells, increase in necrotic testicular cells including formation of syncytia structures and, finally, a high incidence of fish with early primary oocytes at 100 and 500 μg/Kg t.w. EE2. These results indicate that long‐term exposure to EE2 may produce clear negative effects on testicular structure in tench. © 2013 Wiley Periodicals, Inc. Environ Toxicol 29: 1182–1192, 2014.
Generalised ladders and single-valued polylogs
Authors: Drummond J. M.
Published: February 2013

Abstract

We introduce and solve an infinite class of loop integrals which generalises the well-known ladder series. The integrals are described in terms of single-valued poly-logarithmic functions which satisfy certain differential equations. The combination of the differential equations and single-valued behaviour allow us to explicitly construct the poly-logarithms recursively. For this class of integrals the symbol may be read off from the integrand in a particularly simple way. We give an explicit formula for the simplest generalisation of the ladder series. We also relate the generalised ladder integrals to a class of vacuum diagrams which includes both the wheels and the zigzags.
Spinal stenosis frequent in children with multiple hereditary exostoses
Authors: Ashraf Ali , Larson A. Noelle , Ferski Gabriela , Mielke Cary H. , Wetjen Nicholas M. , Guidera Kenneth J.
Published: February 2013

Purpose

Children with multiple hereditary exostoses (MHE) have numerous osteochondromas, with the most prominent lesions typically over the appendicular skeleton. A recent report noted a high rate of intracanal lesions in this patient population and recommended preventative spinal screening with magnetic resonance imaging (MRI) or computed tomography (CT). We sought to evaluate the prevalence of spinal stenosis from intracanal osteochondromas at our pediatric orthopedic center in order to evaluate if routine screening is warranted.

Methods

All pediatric patients treated for MHE were retrospectively identified. Records were reviewed to determine demographics, previous orthopedic surgery, and indication and results of axial spine imaging (CT or MRI). Imaging studies were reviewed to evaluate the presence of intracanal and compressive spinal lesions.

Results

Between 1990 and 2011, axial imaging was performed in nine patients with MHE due to concerns of pain, weakness, and/or dizziness. These patients had moderate disease involvement, with a mean of 4.9 previous orthopedic surgeries to address skeletal osteochondromas. Two patients with MHE had cervical spinal stenosis secondary to intracanal osteochondromas. Both children successfully underwent spinal decompression. Thus, of our MHE population undergoing axial imaging, 22 % were noted to have intracanal lesions.

Conclusions

Our experience reveals a >20 % rate of compressive intracanal osteochondromas in MHE patients undergoing spinal imaging. These two patients represent 5 % of the MHE patients treated at our center. These lesions may be slow growing, and significant consequences can occur if not identified promptly. Thus, we confer that routine axial screening of the spinal canal may be warranted in these children.
Acute renal failure potentiates brain energy dysfunction elicited by methylmalonic acid
Authors: Schuck Patrícia F. , Januário Silvana B. , Simon Kellen R. , Scaini Giselli , Mafioleti Renato L. , Malgarin Fernanda , Pettenuzzo Leticia F. , Streck Emilio L. , Ferreira Gustavo C.
Published: February 2013

The influence of acute renal failure induced by gentamicin administration on the effects of MMA on mitochondrial respiratory chain complexes, citrate synthase, succinate dehydrogenase and creatine kinase activities in cerebral cortex and kidney of young rats were investigated. Animals received one intraperitoneal injection of saline or gentamicin (70 mg/kg). One hour after, the animals received three consecutive subcutaneous injections of MMA (1.67 μmol/g) or saline (11 h interval between injections) and 60 min after the last injection the animals were killed. Acute MMA administration decreased creatine kinase activity in both tissues and increased complexes I–III activity in cerebral cortex. Creatine kinase activity was also inhibited by gentamicin administration. Simultaneous administration of MMA and gentamicin increased the activities of citrate synthase in cerebral cortex and kidney and complexes II–III in cerebral cortex. The other enzyme activities in cerebral cortex and kidney of animals receiving MMA plus gentamicin did not significantly differ from those observed in animals receiving only MMA. Our present data is line with the hypothesis that MMA acts as a toxin in brain and kidney of rats and suggest that renal injury potentiates the toxicity of MMA on the Krebs cycle and respiratory chain in brain and peripheral tissues.
Optic Nerve Sheath Diameter and Acute Mountain Sickness
Authors: Keyes Linda E. , Paterson Ryan , Boatright Dowin , Browne Vaughn , Leadbetter Gig , Hackett Peter
Published: February 2013

Objective

Increased intracranial pressure (ICP) may contribute to acute mountain sickness (AMS). Measuring optic nerve sheath diameter (ONSD) by ultrasound (US) is a noninvasive technique to detect elevated ICP, and increased ONSD has been associated with AMS. We hypothesized that ONSD would increase with acute, rapid ascent to 4300 m and that increased ONSD would be associated with symptoms of AMS. We further hypothesized that treatment with oxygen at 4300 m would reduce symptoms and ONSD.

Methods

A cohort study was performed comparing US measurement of ONSD in healthy subjects at 1400 m and 18 hours after rapid ascent to 4300 m, both before and after oxygen treatment and between subjects with and without AMS (Lake Louise Score ≥3).

Results

Among 57 subjects, 29 (51%) experienced AMS after rapid ascent to 4300 m. In subjects without AMS, mean ONSD did not increase at 4300 m. In subjects with AMS, mean ONSD increased at 4300 m and was higher than in those without AMS. Treatment with oxygen lowered mean ONSD in subjects with AMS but not in those without AMS. Individual responses to altitude and oxygen varied greatly within groups, and the relationship between ONSD and AMS symptoms was weak.

Conclusions

In this controlled study, mean ONSD increased in subjects with AMS at high altitude. However, individual variation was high, and most ONSD values were below the clinical threshold for raised ICP. Observed differences were small, of questionable clinical importance, and within the range of precision of the US machine. Overall, our data do not support a role for increased ICP in mild to moderate AMS.
EpCAM proteolysis: new fragments with distinct functions?
Authors: Schnell Ulrike , Kuipers Jeroen , Giepmans Ben N. G.
Published: February 2013

EpCAM [epithelial cell adhesion molecule; CD326 (cluster of differentiation 326)] is highly expressed on epithelium-derived tumours and can play a role in cell proliferation. Recently, RIP (regulated intramembrane proteolysis) has been implicated as the trigger for EpCAM-mediated proliferative signalling. However, RIP does not explain all EpCAM-derived protein fragments. To shed light on how proteolytic cleavage is involved in EpCAM signalling, we characterized the protein biochemically using antibodies binding to three different EpCAM domains. Using a newly generated anti-EpCAM antibody, we find that EpCAM can be cleaved at multiple positions within its ectodomain in addition to described peptides, revealing that EpCAM is processed via distinct proteolytic pathways. Here, we report on four new peptides, but also discuss the previously described cleavage products to provide a comprehensive picture of EpCAM cleavage at multiple positions. The complex regulation of EpCAM might not only result in the absence of full-length EpCAM, but the newly formed EpCAM-derived proteins may have their own signalling properties.
Synthesis and Radiosynthesis of a Novel PET Fluorobenzyl Piperazine for Melanoma Tumour Imaging; [18F]MEL054
Authors: Taylor Stephen R. , Roberts Maxine P. , Wyatt Naomi A. , Pham Tien Q. , Stark Daniela , Bourdier Thomas , Roselt Peter , Katsifis Andrew , Greguric Ivan
Published: February 2013

2-{2-[4-(4-[18F]-Fluorobenzyl)piperazin-1-yl]-2-oxoethyl}isoindolin-1-one ([18F]MEL054), is a new potent indolinone-based melanin binder designed to target melanotic tumours. [18F]MEL054 was prepared by an automated two-step radiosynthesis, comprising of the preparation of 4-[18F]fluorobenzaldehyde from 4-formyl-N,N,N-trimethylanilinium triflate, followed by reductive alkylation with 2-(2-oxo-2-piperazin-1-ylethyl)isoindolin-1-one. 4-[18F]Fluorobenzaldehyde was prepared on a GE TRACERlab FXFN module in 68 ± 8 % radiochemical yield (RCY, non-decay corrected), purified by a Sep-Pak Plus C18 cartridge and eluted into the reactor of an in-house modified Nuclear Interface [18F]FDG synthesis module for the subsequent reductive alkylation reaction. HPLC purification produced [18F]MEL054 in a collected RCY of 34 ± 9 % (non-decay corrected), the total preparation time (including Sep-Pak Plus C18 and HPLC purification) did not exceed 105 min. The radiochemical purity of [18F]MEL054 was greater than 99 % with a specific radioactivity of 71–119 GBq μmol–1 and [18F]MEL054 remained stable in saline solution (>98 %) after 3 h.
Root distribution and demography in an avocado (Persea americana) orchard under groundcover management systems
Authors: Atucha Amaya , Merwin Ian A. , Brown Michael G. , Gardiazabal Francisco , Mena Francisco , Adriazola Cecilia , Goebel Marc , Bauerle Taryn
Published: February 2013

The effect of groundcover management systems on root demography and distribution of newly planted avocado (Persea americana Mill) trees was examined using minirhizotron techniques. We evaluated three groundcover systems: (1) bare soil (BS), pre- and post-emergence herbicides; (2) vegetation strip (VS), post-emergence herbicide applied in a 1-m wide strip centred on the tree row plus a groundcover mixture seeded between tree rows; and (3) complete groundcover (GC), covering the entire surface of the plots. Root production was higher in the non-bearing year (2009–10) than in the bearing year (2010–11). Trees in the BS plots had more roots of bigger diameter in the top 30 cm of soil and trees in VS and GC plots had more roots in the 30–60 cm depth and of smaller diameter. Lifespan of spring-born roots were 61 and 59% greater than those born during autumn and summer, respectively and soil depth and root diameter were positively correlated with root longevity. Lifespan of thinner roots (<0.2 mm) in the BS and VS plots were 49 and 33% greater than GC respectively. Avocado trees grown in contrasting condition compared with their native habitat show high morphological root plasticity, in response to resource and non-resource competition when grown in mixed stands.
Rangeland vegetation responses to traditional enclosure management in eastern Ethiopia
Authors: Haftay H. , Yayneshet T. , Animut G. , Treydte A. C.
Published: February 2013

Enclosures are widely used by pastoralists in East Africa. However, the response of herbaceous and woody vegetation to enclosures seasonally grazed by livestock remains poorly understood. This study investigated the effectiveness of traditional enclosures in improving herbaceous and woody vegetation in the Somali Regional State of eastern Ethiopia. Vegetation composition (species composition, diversity and richness) and structure (herbage mass, density and canopy cover) were measured inside and outside a set of enclosures. The enclosures contained higher numbers of desirable species than the adjacent open-access grazing areas. Woody species richness was higher in the open-access grazing areas than in the enclosures, which is attributed to the manual removal of most of the undesirable shrubs and trees in the enclosures by pastoralists. Herbage mass was 2642 and 843 kg of dry matter ha–1 in the enclosures and open-access communal grazing areas, respectively. Herbaceous species diversity was higher in the enclosures than in the open-access communal grazing areas (Shannon–Wiener index: 1.8 v. 1.4, respectively). The enclosures were richer in herb species than the open-access grazing areas (13.5 v. 6.8, respectively), but values for woody species were not significantly different. Overall, we found that establishment of enclosures and the short-term protection from grazing they allow is an option for realising positive vegetation changes that support the local pastoral economy in the semiarid rangelands of eastern Ethiopia.
Optimal patch application time in the evaluation of skin irritation
Authors: Kanto Hiromi , Washizaki Kumiko , Ito Masatoshi , Matsunaga Kayoko , Akamatsu Hirohiko , Kawai Keiichi , Katoh Norito , Natsuaki Masaru , Yoshimura Isao , Kojima Hajime , Okamoto Yuko , Okuda Minehiro , Kuwahara Hirofumi , Sugiyama Mariko , Kinoshita Shigemi , Mori Fukuyoshi
Published: February 2013

We investigated the optimum application for evaluating skin irritation response by using samples of irritants commonly used as additives in cosmetics and other common household products. We studied 47 volunteers (16 men and 31 women). We selected three types of surfactant, one moisturizer, one anti‐infective agent and one oil solution. Using Finn chambers on Scanpor tape, we performed the patch test. A total of 0.015 mL of each sample was applied to the Finn chamber. For liquids, circular filter paper was soaked in 0.015 mL of the sample. Samples were placed on the upper back of participants, and closed for 4, 24 or 48 h. A patch application time of 24 h is sufficient to detect primary skin irritation from irritants in cosmetics and other common household products. In addition, we found that skin irritation reactions were strongest at 24 h after patch removal and that the reaction tended to be weaker at 48 h after patch removal. Patch testing to evaluate irritants should be performed by means of a 24‐h patch test with a follow‐up reading at 24 h after patch removal. An application time of 24 h places less of a burden on patients than a 48‐h patch test.
Sentinel lymph node in Merkel cell carcinoma: To biopsy or not to biopsy?
Authors: Sattler Elke , Geimer Till , Sick Isabell , Flaig Michael J. , Ruzicka Thomas , Berking Carola , Kunte Christian
Published: February 2013

Sentinel lymph node biopsy (SLNB) is commonly recommended for patients with primary Merkel cell carcinoma (MCC). However, it is critically discussed whether survival rates improve by SLNB in MCC patients in general or in subgroups of higher risk (e.g. with primary tumor size >1 cm). The present study correlates clinical data, histology and lymph node status with follow‐up and survival data to see if subgroups can be identified for modification of the current recommendations. The medical records of 47 patients with histologically confirmed MCC treated between 1995 and 2010 at a German dermatosurgery department were reviewed. Nineteen patients with excision of the primary tumor and SLNB were compared to 28 patients with excision of the primary tumor but without SLNB. End‐points of this study were disease‐free survival (DFS) and overall survival (OS). In addition, clinical course was correlated with tumor size and size of safety margin. The group of patients who received SLNB showed a significant advantage in terms of OS (P < 0.05), but not in terms of DFS. Tumors of smaller size were associated with a significantly better DFS and a trend towards better OS. Comparing the groups with different safety margins (1–3 cm), no differences in DFS and OS could be found. Our data support the current recommendation for SLNB in all MCC patients and question the use of extensive safety margins in MCC surgery. Larger prospective multicenter studies with multivariate analysis are needed to confirm whether a prolonged OS is really due to the SLNB procedure or biased by other factors.
Comparison of clinical effects of psoriasis treatment regimens among calcipotriol alone, narrowband ultraviolet B phototherapy alone, combination of calcipotriol and narrowband ultraviolet B phototherapy once a week, and combination of calcipotriol and narrowband ultraviolet B phototherapy more than twice a week
Authors: Takahashi Hidetoshi , Tsuji Hitomi , Ishida‐Yamamoto Akemi , Iizuka Hajime
Published: February 2013

We compared the clinical efficacy of various psoriasis treatments among: (i) topical application of calcipotriol ointment twice daily (group I); (ii) topical application of calcipotriol ointment twice daily and narrowband ultraviolet B NB‐UVB phototherapy once a week (group II); (iii) topical application of heparinoid ointment twice daily and NB‐UVB phototherapy more than twice a week (group III); and (iv) topical application of calcipotriol ointment twice daily and NB‐UVB phototherapy more than twice a week (group IV). Ten patients were randomly selected for each group and treated by the indicated regimens for 12 weeks. All treatments were effective and significantly improved Psoriasis Area and Severity Index (PASI) scores, self‐administered PASI scores and visual analog scale scores of pruritus. Group IV showed most marked and rapid reduction in PASI and self‐PASI scores among the four regimens. Although the serum levels of interleukin (IL)‐17, IL‐20 and IL‐22 and psoriasis disability index were significantly decreased after the treatments, no significant difference was detected among the four groups. Our study indicates that combination of calcipotriol ointment plus NB‐UVB more than twice a week is superior to other treatment regimens, rapidly improving psoriasis lesions.
Impact of preterm birth and bronchopulmonary dysplasia on the developing lung: Long‐term consequences for respiratory health
Authors: O'Reilly Megan , Sozo Foula , Harding Richard
Published: February 2013

Preterm birth affects 8–10% of human pregnancies and is a major cause of long‐term disability. Individuals who are born very preterm, especially if they develop bronchopulmonary dysplasia (BPD), have an increased risk of impaired lung function in infancy, childhood and adulthood, as well as an increased risk of respiratory illness. Our aim is to briefly review current understanding of the basis for long‐term impairments in lung function and respiratory health following preterm birth and BPD.

Histopathology of the lungs of infants and children following preterm birth and BPD shows altered development of the lung parenchyma, conducting airways and pulmonary vasculature. Owing to improvements in the care of preterm infants, especially the use of exogenous surfactant and lower concentrations of administered oxygen, lung pathology following preterm birth and BPD is less severe than in the past.

Recent studies indicate that very preterm birth and BPD can lead to hyperplasia of airway smooth muscle, impaired alveolarization, pulmonary inflammation and an increase in pulmonary artery muscularization. Imaging of adult lungs suggests that the deficit in alveoli can persist into later life. Long‐term lung injury apparently relates to the use of mechanical ventilation and the use of supplemental oxygen in infancy.

Impaired lung function in later life is due to airway hyper‐reactivity and fewer alveoli, resulting in reductions in the surface area for gas exchange and physical support for bronchioles. Because the incidence of preterm birth is not declining, it will continue to be a major cause of respiratory ill‐health in adults.
Democratising Party Leadership Selection in Belgium: Motivations and Decision Makers
Authors: Wauters Bram
Published: February 2013

Political parties are increasingly adopting more inclusive procedures to select their party leader, most notably by introducing party primaries. This article tries to detect motives and decision makers for this introduction in Belgian parties. The literature on Westminster-style parties contends that party elites only reluctantly transfer more power from the parliamentary party group (PPG) to party members. They do so only when finding themselves in a weak position: after electoral defeat, when in opposition, when other parties are doing so or when the party is new. The situation in Belgium is different, as is demonstrated with quantitative and qualitative data. Mostly, the party elite was keen on introducing party primaries and took the initiative itself to carry them through. The mechanism at work, however, is the same as in Westminster parties: avoiding too much power for middle-level elites. Because of the different starting position (party delegates selecting the leader), the decision-making process looks completely different. We also argue that the results from Belgian parties might apply to consensus democracies in general.
Long‐Term Antihypertensive Effects of Aliskiren, a Direct Renin Inhibitor, in Chronic Hemodialysis Patients
Authors: Ishimitsu Toshihiko , Ohta Satoshi , Ohno Eri , Takahashi Toshiaki , Numabe Atsushi , Okamura Atsushi , Ohba Shuichi , Hashimoto Akiko , Matsuoka Hiroaki
Published: February 2013

The renin‐angiotensin‐aldosterone system is not necessarily suppressed in end‐stage renal disease patients undergoing dialysis. Of all the inhibitors of this system, the clinical efficacy of the renin inhibitor, aliskiren, has not been well demonstrated in dialysis patients. We evaluated the antihypertensive effect of aliskiren, administered as a single daily dose of 150 mg for 24 weeks, in 23 chronic hemodialysis patients (age 65 ± 12 years, 15 men and eight women) with blood pressure ≥140/90 mm Hg, and assessed the factors relating to blood pressure reduction. At 4 weeks, the average systolic blood pressure before the dialysis session was insignificantly reduced from 163 ± 10 mm Hg to 160 ± 15 mm Hg, while it was significantly lowered at 12 (154 ± 13 mm Hg) and 24 weeks (155 ± 10 mm Hg), although the pulse rate was not significantly altered. Serum K increased at 24 weeks from 4.9 ± 0.6 mEq/L to 5.2 ± 0.8 mEq/L. Only 10 out of 23 patients showed systolic blood pressure reduction by ≥10 mm Hg. Naturally, plasma renin immunoreactivity increased, while plasma renin activity, along with angiotensin II and aldosterone levels decreased. Basal levels of the components of the renin‐angiotensin‐aldosterone system were not significantly different in patients showing systolic blood pressure reduction by ≥10 mm Hg (n = 10) vs. those with <10 mm Hg changes (n = 13). The reduction in systolic blood pressure in all 23 patients taken as a whole correlated with changes in plasma renin activity (r = −0.432, P < 0.05) and angiotensin II (r = 0.467, P < 0.05). In chronic hemodialysis patients, aliskiren modestly lowers blood pressure over the long term, although the antihypertensive effect seems dependent on the changes, but not on the basal levels of plasma renin activity and angiotensin II.
Conceptual Framework for Holistic Dialysis Management Based on Key Performance Indicators
Authors: Liu Hu‐Chen , Itoh Kenji
Published: February 2013

This paper develops a theoretical framework of holistic hospital management based on performance indicators that can be applied to dialysis hospitals, clinics or departments in Japan. Selection of a key indicator set and its validity tests were performed primarily by a questionnaire survey to dialysis experts as well as their statements obtained through interviews. The expert questionnaire asked respondents to rate the degree of “usefulness” for each of 66 indicators on a three‐point scale (19 responses collected). Applying the theoretical framework, we selected a minimum set of key performance indicators for dialysis management that can be used in the Japanese context. The indicator set comprised 27 indicators and items that will be collected through three surveys: patient satisfaction, employee satisfaction, and safety culture. The indicators were confirmed by expert judgment from viewpoints of face, content and construct validity as well as their usefulness. This paper established a theoretical framework of performance measurement for holistic dialysis management from primary healthcare stakeholders’ perspectives. In this framework, performance indicators were largely divided into healthcare outcomes and performance shaping factors. Indicators of the former type may be applied for the detection of operational problems or weaknesses in a dialysis hospital, clinic or department, while latent causes of each problem can be more effectively addressed by the latter type of indicators in terms of process, structure and culture/climate within the organization.
Squamous cell carcinoma of the lung with simultaneous metastases to peritoneum and skeletal muscle
Authors: Song Sung Heon , Oh Yoon Jung , Kim Young Nam , Song Ha Hun , Ha Chang Won
Published: February 2013

Skeletal muscle and peritoneum are rare sites of metastases from lung cancer. We report a case of squamous cell lung cancer with concurrent metastases to skeletal muscle and peritoneum. A 71‐year‐old man was diagnosed with squamous cell carcinoma of the right lower lobe with metastasis to the right hilar lymph node at clinical stage T3N1M0. Because of poor performance status and comorbidity, he only received radiation therapy. Positron emission tomography‐computed tomography for mid‐assessment of response showed two abnormal hypermetabolic lesions in the peritoneum of the left upper quadrant area and the left thigh muscle. We performed a needle‐approach biopsy in each lesion and found both of the lesions were metastases from lung cancer. The patient died after two months.
Brain‐derived neurotrophic factor mediates the suppression of alcohol self‐administration by memantine
Authors: Jeanblanc Jérôme , Coune Fabien , Botia Béatrice , Naassila Mickaël
Published: February 2013

Brain‐derived neurotrophic factor (BDNF) within the striatum is part of a homeostatic pathway regulating alcohol consumption. Memantine, a non‐competitive antagonist of N‐methyl‐D‐aspartate receptors, induces expression of BDNF in several brain regions including the striatum. We hypothesized that memantine could decrease ethanol (EtOH) consumption via activation of the BNDF signalling pathway. Effects of memantine were evaluated in Long‐Evans rats self‐administering moderate or high amounts of EtOH 6, 30 and 54 hours after an acute injection (12.5 and 25 mg/kg). Motivation to consume alcohol was investigated through a progressive ratio paradigm. The possible role for BDNF in the memantine effect was tested by blockade of the TrkB receptor using the pharmacological agent K252a and by the BDNF scavenger TrkB‐Fc. Candidate genes expression was also assessed by polymerase chain reaction array 4 and 28 hours after memantine injection. We found that memantine decreased EtOH self‐administration and motivation to consume EtOH 6 and 30 hours post‐injection. In addition, we found that inhibition or blockade of the BDNF signalling pathway prevented the early, but not the delayed decrease in EtOH consumption induced by memantine. Finally, Bdnf expression was differentially regulated between the early and delayed timepoints. These results demonstrate that an acute injection of memantine specifically reduces EtOH self‐administration and motivation to consume EtOH for at least 30 hours. Moreover, we showed that BDNF was responsible for the early effect, but that the delayed effect was BDNF‐independent.
Cooperative pricing and scale efficiency: The case of Korean rice processing complexes
Authors: Yoo Chun‐Kwon , Buccola Steven , Gopinath Munisamy
Published: February 2013

Unlike most investor‐owned enterprises, cooperatives often have freedom to choose among a variety of firm objectives. Using 2002–2008 plant‐ and province‐level data, we ask in the present article which of several alternative maximands a Korean cooperative rice processing firm pursues. In contrast to earlier studies, farmer‐member supply functions are incorporated into the cooperative's optimization framework. We show that only large cooperative firms have operated at efficient scale, while small and medium‐sized ones have been scale‐inefficient. Because the latter operate where scale returns are increasing, mergers of small and medium‐sized cooperatives likely would be cost‐reducing and member‐return‐enhancing.
The aspirin cardiovascular/gastrointestinal risk calculator ‐ a tool to aid clinicians in practice
Authors: Lanas A. , Polo‐Tomás M. , Casado‐Arroyo R.
Published: February 2013

Background

Assessment of both GI and CV risks vs. the benefits of low‐dose aspirin for individual patients can be difficult in clinical practice.

Aim

To develop a tool to estimate CV and GI risks to facilitate the clinical decision‐making process.

Methods

We constructed risk‐ratio estimations and determined the incidence of CV events and upper GI complications according to the presence of different risk factors. For upper GI complications we assumed a baseline incidence of 1 case/1000‐persons‐year, a twofold increased risk with low‐dose aspirin, and estimated a 60% GI risk reduction with proton pump inhibitors (PPI) co‐therapy and a 60% risk reduction with H. pylori eradication in patients with a history of peptic ulcer.

Results

The calculator can be found at http://www.asariskcalculator.com. In patients with low CV risk the number of GI complications induced by low‐dose aspirin may be greater than the number of CV events prevented. In patients with high CV risk, low‐dose aspirin is recommended, but the number of GI complications induced may still overcome the CV events saved. The use of PPI reduces the number of complication events induced by low‐dose aspirin, but the number of CV events saved may still be offset by the number of GI complications induced in patients at very high GI risk.

Conclusions

There are many clinical situations where the number of potential upper GI complications induced by low‐dose aspirin may exceed the number of potentially prevented CV events. A risk calculator should guide physicians in choosing appropriate therapy and maximise the aspirin benefit.
Whole-body imaging of adoptively transferred T cells using magnetic resonance imaging, single photon emission computed tomography and positron emission tomography techniques, with a focus on regulatory T cells
Authors: Leech J M , Sharif-Paghaleh E , Maher J , Livieratos L , Lechler R I , Mullen G E , Lombardi G , Smyth L A
Published: February 2013

Cell-based therapies using natural or genetically modified regulatory T cells (Tregs) have shown significant promise as immune-based therapies. One of the main difficulties facing the further advancement of these therapies is that the fate and localization of adoptively transferred Tregs is largely unknown. The ability to dissect the migratory pathway of these cells in a non-invasive manner is of vital importance for the further development of in-vivo cell-based immunotherapies, as this technology allows the fate of the therapeutically administered cell to be imaged in real time. In this review we will provide an overview of the current clinical imaging techniques used to track T cells and Tregs  in vivo, including magnetic resonance imaging (MRI) and positron emission tomography (PET)/single photon emission computed tomography (SPECT). In addition, we will discuss how the finding of these studies can be used, in the context of transplantation, to define the most appropriate Treg subset required for cellular therapy.
An analysis of the relative risk for goitre in euthyroid patients with type 2 diabetes
Authors: Díez Juan J. , Iglesias Pedro
Published: February 2013

Aim

To assess the relative risk for goitre in a cohort of euthyroid patients with type 2 diabetes with special reference to the use of metformin and insulin therapy.

Patients and methods

Eight hundred euthyroid patients with type 2 diabetes (433 women, mean age 65·8 ± 12·5 years) and 671 euthyroid subjects without diabetes were retrospectively evaluated. There were 250 patients on metformin and 455 patients on insulin treatment.

Results

The gender‐, age‐, body mass index‐ and thyrotropin (TSH)‐adjusted relative risk for goitre occurring among diabetic patients relative to controls was 3·01 (1·61–5·64) (P < 0·01). This odds ratio was significant in females, patients with and without metformin therapy, patients without insulin therapy and without micro‐ and macrovascular complications of diabetes. However, male pateints, patients on insulin therapy or with micro‐ or macroangiopathy did not exhibit an increase in the risk of goitre. Patients on metformin therapy showed a significant increase in the risk of goitre only in the absence of insulin therapy. Multi‐adjusted logistic regression analysis showed that goitre was significantly related to gender, TSH and haemoglobin A1c levels. Metformin and insulin therapy were nonsignificant variables in this model.

Conclusion

This is the first survey analysing the relationship between the presence of palpable goitre and clinical parameters in a large cohort of patients with type 2 diabetes. Our data suggest a significant relationship between goitre and glycaemic control, but do not support the presence of independent and significant relationships between goitre and metformin or insulin treatment in euthyroid patients with type 2 diabetes.
Correlations with six‐month protocol biopsy findings in pediatric transplant recipients on low‐ and regular‐dose CNI regimens
Authors: Kanzelmeyer Nele K. , Ahlenstiel Thurid , Kreuzer Martin , Becker Jan U. , Pape Lars
Published: February 2013

Protocol biopsies (PB) are seldom performed after pediatric kidney transplantation (KTx), and factors influencing PB results have not previously been investigated. We performed PB in 79 children six months after KTx and evaluated the results using Banff 2007 criteria. Complications such as bleeding or infections were not detected. The influence of different variables on PB results was evaluated by covariance analysis. Children treated with a low‐dose calcineurin inhibitor (CNI) together with an mTOR inhibitor exhibited decreased subclinical rejection (0% vs. 19%, p = 0.001) and decreased interstitial fibrosis and tubular atrophy (IF/TA) (15% vs. 42%, p = 0.013) compared with patients treated with a conventional regimen consisting of normal‐dose CNI and mycophenolate mofetil. Children with IF/TA had a lower GFR four wk after Tx (83 ± 22 vs. 62 ± 20 mL/min/1.73 m2, p = 0.001). Cold ischemia time, living‐related donors, pre‐emptive KTx, and donor age did not influence PB results. Treatment with low‐dose CNI and mTOR inhibitor and high GFR directly after Tx are the main factors associated with less inflammation and fibrosis in PB and might therefore lead to better long‐term graft function.