bluuebunny/crossref_metadata_2025 huggingface dataset:
Intrinsic effective mobility extraction with extremely scaled gate dielectrics
Authors: Liu Zuoguang , Guo Dechao , Xiu Kai , Henson William Kirklen , Oldiges Philip J.
Published: July 2010

We propose a mobility extraction methodology for metal-oxide-semiconductor field effect transistors with extremely scaled equivalent oxide thickness (EOT) below 1 nm. In conventional split C-V method, extracted mobility shows strong dependence on drain bias. As EOT scales to the requirements of 22 nm node and beyond, the phenomenon becomes more pronounced and causes bigger errors in mobility determination. We studied the physical origin of the extracted mobility dependence on drain bias by technology computer aided design electrostatics modeling and electrical characterization. A methodology is proposed and verified for intrinsic effective mobility determination for devices with EOT down to 0.6 nm.
A phylogenetic study of subgenus Polypompholyx: a parallel radiation of Utricularia (Lentibulariaceae) throughout Australasia
Authors: Reut Markus S. , Jobson Richard W.
Published: July 2010

Phylogenetic relationships among 26 of the 37 recognised taxa of Utricularia subgenus Polypompholyx sensu Müller & Borsch were assessed by cladistic analysis of DNA sequences from the plastid rps16 intron. We also examined the placement of the recently described U. simmonsii (sect. Minutae), which was reported to share some morphological characters with subgenus Polypompholyx. We found strong jackknife support for a monophyletic subgenus Polypompholyx lineage; however, our strict consensus tree shows an unresolved relationship between the sections Polypompholyx and Pleiochasia. Within the section Pleiochasia, we found two supported clades, generally differing in a more northern or southern distribution. Despite high levels of morphological heterogeneity and convergence, we found some clade-specific character homogeneity within these two clades, particularly that of growth and bladder-trap form, and floral structure. Bladder-trap form corresponds most strongly with terrestrial v. aquatic habits. The evolution of filiform corolla appendages corresponds with floral colour, and is possibly associated with sexual mimicry, with those of the upper corolla arising twice independently. Furthermore, we found that U. monanthos and U. novae-zelandiae remain synonyms of U. dichotoma, and that U. simmonsii is not included in the subgenus Polypompholyx, but instead is allied with sections Stomoisia and Enskide of subgenus Bivalvaria.
Maternal dietary choline deficiency alters angiogenesis in fetal mouse hippocampus
Authors: Mehedint Mihai G. , Craciunescu Corneliu N. , Zeisel Steven H.
Published: July 2010

We examined whether maternal dietary choline modulates angiogenesis in fetal brain. Pregnant C57BL/6 mice were fed either a choline-deficient (CD), control (CT), or choline-supplemented diet (CS) from days 12 to 17 (E12-17) of pregnancy and then fetal brains were studied. In CD fetal hippocampus, proliferation of endothelial cells (EC) was decreased by 32% (p < 0.01 vs. CT or CS) while differentiated EC clusters (expressing factor VIII related antigen (RA)) increased by 25% (p < 0.01 vs. CT or CS). These changes were associated with > 25% decrease in the number of blood vessels in CD fetal hippocampus (p < 0.01 vs. CT and CS), with no change in total cross-sectional area of these blood vessels. Expression of genes for the angiogenic signals derived from both endothelial and neuronal progenitor cells (NPC) was increased in CD fetal hippocampus VEGF C (Vegfc), 2.0-fold,p < 0.01 vs. CT and angiopoietin 2 (Angpt2), 2.1-fold, (p < 0.01 vs. CT)). Similar increased expression was observed in NPC isolated from E14 fetal mouse brains and exposed to low (5 μM), CT (70 μM), or high choline (280 μM) media for 72 h (low choline caused a 9.7-fold increase in relative gene expression ofVegfc(p < 0.001 vs. CT and high) and a 3.4-fold increase in expression ofAngpt2, (p < 0.05 vs. CT and high). ANGPT2 protein was increased 42.2% (p < 0.01). Cytosine-phosphate-guanine dinucleotide islands in the proximity of the promoter areas ofVegfcandAngpt2were hypomethylated in low choline NPC compared to CT NPC (p < 0.01). We conclude that maternal dietary choline intake alters angiogenesis in the developing fetal hippocampus.
Topological optimization for designing patient-specific large craniofacial segmental bone replacements
Authors: Sutradhar Alok , Paulino Glaucio H. , Miller Michael J. , Nguyen Tam H.
Published: July 2010

Restoring normal function and appearance after massive facial injuries with bone loss is an important unsolved problem in surgery. An important limitation of the current methods is heuristic ad hoc design of bone replacements by the operating surgeon at the time of surgery. This problem might be addressed by incorporating a computational method known as topological optimization into routine surgical planning. We tested the feasibility of using a multiresolution three-dimensional topological optimization to design replacements for massive midface injuries with bone loss. The final solution to meet functional requirements may be shaped differently than the natural human bone but be optimized for functional needs sufficient to support full restoration using a combination of soft tissue repair and synthetic prosthetics. Topological optimization for designing facial bone tissue replacements might improve current clinical methods and provide essential enabling technology to translate generic bone tissue engineering methods into specific solutions for individual patients.
Learning-dependent plasticity with and without training in the human brain
Authors: Zhang Jiaxiang , Kourtzi Zoe
Published: July 2010

Long-term experience through development and evolution and shorter-term training in adulthood have both been suggested to contribute to the optimization of visual functions that mediate our ability to interpret complex scenes. However, the brain plasticity mechanisms that mediate the detection of objects in cluttered scenes remain largely unknown. Here, we combine behavioral and functional MRI (fMRI) measurements to investigate the human-brain mechanisms that mediate our ability to learn statistical regularities and detect targets in clutter. We show two different routes to visual learning in clutter with discrete brain plasticity signatures. Specifically, opportunistic learning of regularities typical in natural contours (i.e., collinearity) can occur simply through frequent exposure, generalize across untrained stimulus features, and shape processing in occipitotemporal regions implicated in the representation of global forms. In contrast, learning to integrate discontinuities (i.e., elements orthogonal to contour paths) requires task-specific training (bootstrap-based learning), is stimulus-dependent, and enhances processing in intraparietal regions implicated in attention-gated learning. We propose that long-term experience with statistical regularities may facilitate opportunistic learning of collinear contours, whereas learning to integrate discontinuities entails bootstrap-based training for the detection of contours in clutter. These findings provide insights in understanding how long-term experience and short-term training interact to shape the optimization of visual recognition processes.
Glutathione import in
Haemophilus influenzae
Rd is primed by the periplasmic heme-binding protein HbpA
Authors: Vergauwen Bjorn , Elegheert Jonathan , Dansercoer Ann , Devreese Bart , Savvides Savvas N.
Published: July 2010

Glutathione (GSH) is a vital intracellular cysteine-containing tripeptide across all kingdoms of life and assumes a plethora of cellular roles. Such pleiotropic behavior relies on a finely tuned spatiotemporal distribution of glutathione and its conjugates, which is not only controlled by synthesis and breakdown, but also by transport. Here, we show that import of glutathione in the obligate human pathogen
Haemophilus influenzae
, a glutathione auxotrophe, is mediated by the ATP-binding cassette (ABC)-like dipeptide transporter DppBCDF, which is primed for glutathione transport by a dedicated periplasmic-binding protein (PBP). We have identified the periplasmic lipoprotein HbpA, a protein hitherto implicated in heme acquisition, as the cognate PBP that specifically binds reduced (GSH) and oxidized glutathione (GSSG) forms of glutathione with physiologically relevant affinity, while it exhibits marginal binding to hemin. Dissection of the ligand preferences of HbpA showed that HbpA does not recognize bulky glutathione S conjugates or glutathione derivatives with C-terminal modifications, consistent with the need for selective import of useful forms of glutathione and the concomitant exclusion of potentially toxic glutathione adducts. Structural studies of the highly homologous HbpA from
Haemophilus parasuis
in complex with GSSG have revealed the structural basis of the proposed novel function for HbpA-like proteins, thus allowing a delineation of highly conserved structure-sequence fingerprints for the entire family of HbpA proteins. Taken together, our studies unmask the main physiological role of HbpA and establish a paradigm for glutathione import in bacteria. Accordingly, we propose a name change for HbpA to glutathione-binding protein A.
A cognitive scientific view on technical A cognitive scientific view on technical
Authors: Risku Hanna
Published: July 2010

This article provides a brief presentation of the development of some cognitive scientific views on technical communication and translation. I look in detail at one of the latest cognitive scientific trends, namelySituated and Embodied Cognition. According to this approach, humans are creative beings who are dependent on their physical and psychological circumstances. I provide a brief overview of the background to situated, embodied cognition, present some of its main concepts and conclude with a number of proposals about how findings in this field can be used to further develop research in Technical Communication and Translation Studies. In doing so, I argue that the new findings in cognitive science will necessarily change some of the common concepts and methodological traditions with regard to the actual text production process and competencies.
Highly efficient white light-emitting devices by direct excitation of phosphorescent guest molecules
Authors: Seo Yu-Seok , Moon Dae-Gyu
Published: July 2010

We have developed highly efficient white organic light-emitting devices using a multilayer emission structure consisting of a single host layer. The red phosphorescent, tris(2-phenyl-1-quinoline)iridium(III) [Ir(phq)3], and the blue phosphorescent, iridium(III)bis[(4,6-di-fluorophenyl)-pyridinato-N,C2′]picolinate (FIrpic), are doped into separate layers of N,N′-dicarbazolyl-3,5-benzene (mCP) host. The FIrpic and Ir(phq)3 guest molecules are directly excited by direct recombination on these molecules. A maximum external quantum efficiency of 20.3% and a current efficiency of 45.6 cd A−1 are achieved by optimizing charge balance, which is a major factor in achieving high efficiency in the mCP : FIrpic/mCP : Ir(phq)3 single host structure.
Temperature- and electrode-dependent leakage current behaviour of pulsed laser deposited Ba(Ti0.85Sn0.15)O3 thin films
Authors: Wang S J , Lai M O , Lu L
Published: July 2010

The leakage behaviour of Ba(Ti0.5Sn0.15)O3 (BTS) thin films deposited by pulsed laser deposition has been studied. Two kinds of materials, Pt and LaNiO3 (LNO), are used as bottom electrodes to investigate their influences on conduction mechanisms. It is found that the leakage of the BTS thin films is strongly related to the deposition temperature and electrode materials. For the Pt/BTS/LNO structure, the leakage current shows bulk-limited space-charge-limited current (SCLC) behaviour at a positive bias while interface-limited Fowler–Nordheim tunnelling at a negative bias. On the other hand, for the Pt/BTS/Pt structure, the leakage current shows a symmetric characteristic at both positive and negative biases. The conduction mechanism is controlled mainly by the bulk-limited SCLC and/or Poole–Frenkel emission, which is operative depending on the temperature and electric field.
OWL2Perl: creating Perl modules from OWL class definitions
Authors: Kawas Edward , Wilkinson Mark D.
Published: July 2010

Summary: Support for utilizing OWL ontologies in Perl is extremely limited, despite the growing importance of the Semantic Web in Healthcare and Life Sciences. Here, we present a Perl framework that generates Perl modules based on OWL Class definitions. These modules can then be used by other software applications to create resource description framework (RDF) data compliant with these OWL models.

Availability: OWL2Perl is available for download from CPAN, under the module name OWL2Perl. It is released under the new BSD license.

Contact:  edward.kawas@gmail.com; markw@illuminae.com
MetPA: a web-based metabolomics tool for pathway analysis and visualization
Authors: Xia Jianguo , Wishart David S.
Published: July 2010

Summary: MetPA (Metabolomics Pathway Analysis) is a user-friendly, web-based tool dedicated to the analysis and visualization of metabolomic data within the biological context of metabolic pathways. MetPA combines several advanced pathway enrichment analysis procedures along with the analysis of pathway topological characteristics to help identify the most relevant metabolic pathways involved in a given metabolomic study. The results are presented in a Google-map style network visualization system that supports intuitive and interactive data exploration through point-and-click, dragging and lossless zooming. Additional features include a comprehensive compound library for metabolite name conversion, automatic generation of analysis report, as well as the implementation of various univariate statistical procedures that can be accessed when users click on any metabolite node on a pathway map. MetPA currently enables analysis and visualization of 874 metabolic pathways, covering 11 common model organisms.

Availability: Freely available at http://metpa.metabolomics.ca

Contact:  david.wishart@ualberta.ca
Function annotation of the rice transcriptome at single-nucleotide resolution by RNA-seq
Authors: Lu Tingting , Lu Guojun , Fan Danlin , Zhu Chuanrang , Li Wei , Zhao Qiang , Feng Qi , Zhao Yan , Guo Yunli , Li Wenjun , Huang Xuehui , Han Bin
Published: July 2010

The functional complexity of the rice transcriptome is not yet fully elucidated, despite many studies having reported the use of DNA microarrays. Next-generation DNA sequencing technologies provide a powerful approach for mapping and quantifying the transcriptome, termed RNA sequencing (RNA-seq). In this study, we applied RNA-seq to globally sample transcripts of the cultivated rice Oryza sativa indica and japonica subspecies for resolving the whole-genome transcription profiles. We identified 15,708 novel transcriptional active regions (nTARs), of which 51.7% have no homolog to public protein data and >63% are putative single-exon transcripts, which are highly different from protein-coding genes (<20%). We found that ∼48% of rice genes show alternative splicing patterns, a percentage considerably higher than previous estimations. On the basis of the available rice gene models, 83.1% (46,472 genes) of the current rice gene models were validated by RNA-seq, and 6228 genes were identified to be extended at the 5′ and/or 3′ ends by at least 50 bp. Comparative transcriptome analysis demonstrated that 3464 genes exhibited differential expression patterns. The ratio of SNPs with nonsynonymous/synonymous mutations was nearly 1:1.06. In total, we interrogated and compared transcriptomes of the two rice subspecies to reveal the overall transcriptional landscape at maximal resolution.
TATA is a modular component of synthetic promoters
Authors: Mogno Ilaria , Vallania Francesco , Mitra Robi D. , Cohen Barak A.
Published: July 2010

The expression of most genes is regulated by multiple transcription factors. The interactions between transcription factors produce complex patterns of gene expression that are not always obvious from the arrangement of cis-regulatory elements in a promoter. One critical element of promoters is the TATA box, the docking site for the RNA polymerase holoenzyme. Using a synthetic promoter system coupled to a thermodynamic model of combinatorial regulation, we analyze the effects of different strength TATA boxes on various aspects of combinatorial cis-regulation. The thermodynamic model explains 75% of the variance in gene expression in synthetic promoter libraries with different strength TATA boxes, suggesting that many of the salient aspects of cis-regulation are captured by the model. Our results demonstrate that the effect of changing the TATA box on gene expression is the same for all synthetic promoters regardless of the arrangement of cis-regulatory sites we studied. Our analysis also showed that in our synthetic system the strength of the RNA polymerase–TATA interaction does not alter the combinatorial interactions between transcription factors, or between transcription factors and RNA polymerase. Finally, we show that although stronger TATA boxes increase expression in a predictable fashion, stronger TATA boxes have very little effect on noise in our synthetic promoters, regardless of the arrangement of cis-regulatory sites. Our results support a modular model of promoter function, where cis-regulatory elements can be mixed and matched (programmed) with outcomes on expression that are predictable based on the rules of simple protein–protein and protein–DNA interactions.
The validity of viral hepatitis and chronic liver disease diagnoses in Veterans Affairs administrative databases
Authors: KRAMER J. R. , DAVILA J. A. , MILLER E. D. , RICHARDSON P. , GIORDANO T. P. , EL‐SERAG H. B.
Published: July 2010

Background  The validity of International Classification of Diseases‐9 codes for liver disease has not been determined.

Aim  To examine the accuracy of International Classification of Diseases‐9 codes for cirrhosis with hepatitis C virus or alcoholic liver disease and HIV or hepatitis B virus coinfection with hepatitis C virus in Veterans Affairs data.

Methods  We conducted a retrospective study comparing the Veterans Affairs administrative data with abstracted data from the Michael E. DeBakey VA Medical Center’s medical records. We calculated the positive predictive value, negative predictive value, per cent agreement and kappa.

Results  For cirrhosis codes, the positive predictive value (probability that cirrhosis is present among those with a code) and negative predictive value (probability that cirrhosis is absent among those without a code) were 90% and 87% with 88% agreement and kappa = 0.70. For hepatitis C virus codes, the positive predictive value and negative predictive value were 93% and 92%, yielding 92% agreement and kappa = 0.78. For alcoholic liver disease codes, the positive predictive value and negative predictive value were 71% and 98%, with 89% agreement and kappa = 0.74. All parameters for HIV coinfection with hepatitis C virus were >89%; however, the codes for hepatitis B virus coinfection had a positive predictive value of 43–67%.

Conclusion  These diagnostic codes (except hepatitis B virus) in Veterans Affairs administrative data are highly predictive of the presence of these conditions in medical records and can be reliably used for research.
Modulation of salivation and heartburn in response to the site of acid infusion in the human oesophagus
Authors: Dutta S. K. , Agrawal K. , Mahmoud M. A.
Published: July 2010

Background  The pathogenesis of gastro‐oesophageal reflux disease includes increased acid reflux, reduced salivation and impaired peristalsis. This may depend upon the height of acid wave and magnitude of oesophageal mucosal exposure. Interestingly, the effect of site of acid infusion upon salivary secretion and heartburn has not been examined in any detail.

Aim  To examine whether acid infusion in the upper oesophagus may cause increased salivation and heartburn as compared with acid infusion in the lower oesophagus.

Methods  Twelve healthy male subjects (mean age 30) received infusions of HCl, citric acid and acetic acid at 10 and 20 cm above the lower oesophageal sphincter (LES) for fixed time periods. Parotid saliva collected periodically and heartburn severity scored using standardized scale. Standard statistical methods (paired t‐tests, analysis of variance) were used to determine the significance of results.

Results  Acid infusion in the upper oesophagus increased parotid flow rate as compared with that in the lower oesophagus (P < 0.05). Likewise, there was a significantly increased heartburn score at 20 cm as well as 10 cm above LES (P < 0.05) as compared with that in the stomach.

Conclusion  These data suggest a significant increase in salivation and heartburn in response to acid infusion in the upper vs. lower part of the oesophagus.
ORIGINAL ARTICLE: Risk of intravascular injection in transforaminal epidural injections
Authors: Nahm F. S. , Lee C. J. , Lee S. H. , Kim T. H. , Sim W. S. , Cho H. S. , Park S. Y. , Kim Y. C. , Lee S. C.
Published: July 2010

Transforaminal epidural injection is an effective method for treating spinal pain but can cause devastating complications that result from accidental vascular uptake of the injectate or a direct vascular injury. We prospectively evaluated the patient factors that might be associated with intravascular uptake during transforaminal epidural injections. A total of 2145 injections were performed on 1088 patients under contrast‐enhanced real‐time fluoroscopic guidance. The collected data included the patient’s age, sex, body mass index, diagnosis, injection level, side of injection, history of spinal surgery at the targeted level, and the number of injections at the targeted site. The overall incidence of intravascular injection was 10.5% (224/2145). The highest incidence was at the cervical level (28/136; 20.6%), followed by the sacral level (111/673; 16.5%), the thoracic level (23/280; 8.2%) and the lumbar level (64/1056; 6.1%). The difference was significant for the cervical and sacral level compared with the lumbar and thoracic levels (p < 0.001). Intravascular injection was not associated with the other patient characteristics studied.
Successful resuscitation following ropivacaine‐induced systemic toxicity in a neonate
Authors: Hübler M. , Gäbler R. , Ehm B. , Oertel R. , Gama de Abreu M. , Koch T.
Published: July 2010

A 5‐week‐old preterm infant was scheduled for inguinal hernia repair. Following induction of general anaesthesia, 10 mg.kg−1 ropivacaine was injected, accidently, into the caudal space. The infant developed cardiac depression with bradycardia (minimum heart rate 50 beats.min−1), elevated T waves and widening of QRS complexes. Resuscitation by means of external chest compression, intravenous adrenaline and fluid administration was successful. Ropivacaine serum concentrations were obtained at three time points yielding a peak level of 6 μg.ml−1 20 min after caudal injection.
ORIGINAL ARTICLE: Optimal effect‐site concentration of remifentanil for preventing cough during emergence from sevoflurane‐remifentanil anaesthesia*
Authors: Jun N. H. , Lee J. W. , Song J. W. , Koh J. C. , Park W. S. , Shim Y. H.
Published: July 2010

This randomised, double‐blinded, controlled trial was designed to identify the optimal dose of remifentanil for cough suppression without adverse effects during emergence from sevoflurane‐remifentanil anaesthesia for thyroidectomy. One hundred and four patients were randomly assigned to maintain target effect‐site concentrations of remifentanil at 0 (control group), 1.0 (remifentail 1 group), or 1.5 ng.ml−1 (remifentanil 1.5 group) during emergence. The incidence of coughing was lower in the remifentanil 1.5 group (31%) than in the control group (74%) or remifentanil 1 group (63%) (p = 0.0004). In addition, the severity of coughing during extubation was lower in the remifentanil 1.5 group (median (IQR [range]) 0 (0–1 [0–1]) than in the control group (1 (0–2 [0–3])) and remifentanil 1 group (1 (0–2 [0–3])) (p = 0.004). Haemodynamic changes were reduced, but emergence time and stay in the post‐anaesthesia care unit was prolonged in the remifentanil 1.5 group. Maintaining the remifentanil effect‐site concentration at 1.5 ng.ml−1 during emergence from sevoflurane‐remifentanil anaesthesia reduces the incidence and severity of coughing without serious adverse events and may provide haemodynamic stability in patients undergoing thyroidectomy. However, awakening may be delayed.
Emergency re‐admissions to hospital due to adverse drug reactions within 1 year of the index admission
Authors: Davies Emma C. , Green Christopher F. , Mottram David R. , Rowe Philip H. , Pirmohamed Munir
Published: July 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

ADRs in hospital patients are a significant burden, though how often ADRs cause re‐admission to hospital has not been well documented in the literature.

WHAT THIS STUDY ADDS

• One fifth of patients re‐admitted to hospital within 1 year of discharge from their index admission were re‐admitted due to an adverse drug reaction.

• Admission to a medical ward, elderly age and prescription of anti‐platelet agents or diuretics were identified as risk factors for re‐admission due to ADRs.

• Since up to 50% of these reactions were possibly avoidable, better methods of medication review in both hospital and primary care, in conjunction with a clinical review, are needed to enable improved prescribing practices that will be essential for improving the benefit‐harm balance of medicines.

AIM

The proportion of re‐admissions to hospital caused by ADRs is poorly documented in the UK. The aim of this study was to evaluate the impact of ADRs on re‐admission to hospital after a period as an inpatient.

METHODS

One thousand patients consecutively admitted to 12 wards were included. All subsequent admissions for this cohort within 1 year of discharge from the index admission were retrospectively reviewed.

RESULTS

Of the 1000 patients included, 403 (40.3%, 95% CI 39.1, 45.4%) were re‐admitted within 1 year. Complete data were available for 290 (70.2%) re‐admitted patients, with an ADR contributing to admission in 60 (20.8%, 95% CI 16.4, 25.6%) patients. Presence of an ADR in the index admission did not predict for an ADR‐related re‐admission (10.5% vs. 7.2%, P = 0.25), or re‐admission overall (47.2% vs. 41.2%, P = 0.15). The implicated drug was commenced in the index admission in 33/148 (22.3%) instances, with 37/148 (25%) commenced elsewhere since the index admission. Increasing age and an index admission in a medical ward were associated with a higher incidence of re‐admission ADR. The most frequent causative drugs were anti‐platelets and loop diuretics, with bleeding and renal impairment the most frequent ADRs. Over half (52/91, 57.1%) of the ADRs were judged to be definitely or possibly avoidable.

CONCLUSIONS

One fifth of patients re‐admitted to hospital within 1 year of discharge from their index admission are re‐admitted due to an ADR. Our data highlight drug and patient groups where interventions are needed to reduce the incidence of ADRs leading to re‐admission.
Corticosteroids therapy and peptic ulcer disease in nephrotic syndrome patients
Authors: Hsiang Kuo‐Wei , Ng Yee‐Yung , Lu Ching‐Liang , Chen Tseng‐Shing , Lin Hsiao‐Yi , Luo Jiing‐Chyuan , Wu Jia‐Min , Lin Han‐Chieh , Chang Full‐Young , Lee Shou‐Dong
Published: July 2010

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• Whether corticosteroid use induces peptic ulcer disease (PUD) remains uncertain.

• Helicobacter pylori infection in steroid users has not been well evaluated in the past.

WHAT THIS STUDY ADDS

• Prednisolone 60 mg daily for 3 months caused few endoscopic ulcers (1.6%) and no ulcer complications in 60 nephrotic patients, which was comparative with the controls, with an odds ratio of 0.5.

• Corticosteroid therapy did not to increase PUD in nephrotic syndrome patients. Further larger studies are needed to clarify the role of corticosteroid in PUD.

AIMS

Whether corticosteroids induce peptic ulcer disease (PUD) remains uncertain. The study evaluated and compared the occurrence of PUD between nephrotic patients receiving oral prednisolone therapy and nephritic patients without steroid therapy.

METHODS

The prospective case control study compared 60 nephrotic syndrome patients who received 60 mg daily prednisolone therapy for 3 months with 30 age‐and sex‐matched nephritic patients without steroid therapy. Each patient underwent endoscopic examination and tissue and blood sampling before and after the study. Examined parameters included Helicobacter pylori (H. pylori) infection, and gastric and serum prostaglandin (PG) E2 and thromboxane (TX) B2 concentrations. The primary endpoint was the occurrence of endoscopic peptic ulcers between the two groups, while the secondary end point was the occurrence of ulcer complications.

RESULTS

The two groups were comparable in sex, age, smoking habits, alcohol drinking, past history of PUD, H. pylori infection rate and serum creatinine. There were no differences in the occurrence of endoscopic peptic ulcers (1.6% vs. 3.3%) and ulcer complications (0% vs. 0%), pre‐therapy gastric PGE2, and pre‐ and post‐therapy gastric TXB2, serum PGE2 and serum TXB2 between the two groups. However, there was significantly lower post‐therapy gastric PGE2 concentrations in the prednisolone group.

CONCLUSIONS

Three‐month therapy with 60 mg daily prednisolone caused few endoscopic ulcers (1.6%) and no ulcer complications in nephrotic patients. Corticosteroids therapy did not increase PUD in nephrotic syndrome patients [odds ratio 0.492 with 95% confidence interval (CI) 0.03, 8.142, P= 0.620]. Further larger studies are needed to clarify the role of corticosteroids in PUD.
Expression and function of toll‐like receptors in multiple myeloma patients: toll‐like receptor ligands promote multiple myeloma cell growth and survival via activation of nuclear factor‐κB
Authors: Xu Yang , Zhao Yun , Huang Haiwen , Chen Guanghua , Wu Xiaojin , Wang Ying , Chang Weirong , Zhu Ziling , Feng Yufeng , Wu Depei
Published: July 2010

Toll like receptors (TLRs) are the major agents for innate immunity that recognize invading microbial products and regulate the growth of normal and malignant human B lymphocytes. Multiple myeloma (MM) is a clonal plasma cell malignancy, though the regulatory role of TLRs in MM plasma cells has been reported, the molecular mechanism remains unclear. We first compared the transcripts of TLR1 to TLR10 in MM patients and healthy donors and found that TLR2, ‐4 and ‐9 transcripts were higher in bone marrow mononuclear cells (BMMCs) from patients than those from donors; in addition the expression of TLR4 and TLR9 were higher in MM cells than normal cells as demonstrated by flow cytometric analyses. The ligands of these two TLRs were capable to promote the growth of MM cells and protect them from serum‐deprivation‐induced apoptosis but not normal plasma cells, which could be attenuated with anti‐IL6 neutralizing antibodies or blockage of NF‐κB activities. Further investigation demonstrated that these TLR ligands could trigger the nuclear translocation of NF‐κB p65 and the activated NF‐κB was sufficient to increase the expression of IL6 transcript in MM cells. These data suggested that activated NF‐κB signalling probably plays a crucial role for the ligands of TLR4 and TLR9 to promote the growth and survival of MM cells partially through IL6 autocrine.
research paper: Clinical use of unfractionated heparin therapy in children: time for change?
Authors: Newall Fiona , Ignjatovic Vera , Johnston Linda , Summerhayes Robyn , Lane Geoff , Cranswick Noel , Monagle Paul
Published: July 2010

Paediatric recommendations for unfractionated heparin (UFH) management are extrapolated from adult trials, a practice that may contribute to the inferior UFH‐related outcomes in children compared to adults. This is the first study to determine UFH concentration in a population of children and correlated UFH concentration with measures of UFH effect. Correlation coefficients between protamine titration (concentration) and activated partial thromboplastin time (APTT), anti‐ activated factor X (Xa) assay and thrombin clotting time (effect) were 0·59, 0·46 and 0·52 respectively. A protamine titration level of 0·2–0·4 iu/ml in children was not equivalent to an anti‐Xa assay of 0·35–0·7 iu/ml but to an anti‐Xa assay 0·17–0·85 iu/ml. In addition, use of the anti‐Xa or protamine titration assays to establish an APTT therapeutic range resulted in upper limits of APTT ranges exceeding 200 s. Existing methods for determining therapeutic ranges for UFH in adult populations do not produce equivalent ranges in children. As a result, paediatric clinical guidelines that state a therapeutic range for UFH can be determined using a protamine titration assay of 0·2–0·4 iu/ml or an anti‐Xa assay of 0·35–0·7 iu/ml are not based on appropriate evidence. There is an urgent need for change in our approach to the use of UFH in children.
A review of the evidence on the effectiveness of children's vision screening
Authors: Mathers M. , Keyes M. , Wright M.
Published: July 2010

Screening programmes enable health conditions to be identified so that effective interventions can be offered. The aim of this review was to determine: (1) the effectiveness of children's vision screening programmes; (2) at what age children should attend vision screening; and (3) what form vision screening programmes should take to be most effective. A literature review on the effectiveness of vision screening programmes in children aged 0–16 years was undertaken. Eligible studies/reviews were identified through clinical databases, hand searches and consultation with expert reviewers. The methodological quality of papers was rated using National Health and Medical Research Council (NHMRC) guidelines. Screening of children 18 months to 5 years, and subsequent early treatment, led to improved visual outcomes. The benefit was primarily through treatment of amblyopia, with improved visual acuity of the amblyopic eye. However, the overall quality of the evidence was low. The implication of improved visual acuity (e.g. any potential impact on quality of life) was not considered. Without consideration of ‘quality of life’ values, such as loss of vision in one eye or possibility of future bilateral vision loss, the cost‐effectiveness of screening is questionable. Screening and treating children with uncorrected refractive error can improve educational outcomes. Evidence suggested that screening occur in the preschool years. Orthoptists were favoured as screening personnel; however, nurses could achieve high sensitivity and specificity with appropriate training. Further research is required to assess the effectiveness of neonatal screening. Most studies suggested that children's vision screening was beneficial, although programme components varied widely (e.g. tests used, screening personnel and age at testing). Research is required to clearly define any improvements to quality of life and any related economic benefits resulting from childhood vision screening. The evidence could be used to guide optimization of existing programmes.
Perceived parenting and psychological well‐being in UK ethnic minority adolescents
Authors: Maynard M. J. , Harding S.
Published: July 2010

Background  Warm, caring parenting with appropriate supervision and control is considered to contribute to the best mental health outcomes for young people. The extent to which this view on ‘optimal’ parenting and health applies across ethnicities, warrants further attention. We examined associations between perceived parental care and parental control and psychological well‐being among ethnically diverse UK adolescents.

Methods  In 2003 a sample of 4349 pupils aged 11–13 years completed eight self‐reported parenting items. These items were used to derive the parental care and control scores. Higher score represents greater care and control, respectively. Psychological well‐being was based on total psychological difficulties score from Goodman's Strengths and Difficulties Questionnaire, increasing score corresponding to increasing difficulties.

Results  All minority pupils had lower mean care and higher mean control scores compared with Whites. In models stratified by ethnicity, increasing parental care was associated with lower psychological difficulties score (better mental health) and increasing parental control with higher psychological difficulties score within each ethnic group, compared with reference categories. The difference in psychological difficulties between the highest and lowest tertiles of parental care, adjusted for age, sex, family type and socio‐economic circumstances, was: White UK =−2.92 (95% confidence interval −3.72, −2.12); Black Caribbean =−2.08 (−2.94, −1.22); Nigerian/Ghanaian =−2.60 (−3.58, −1.62); Other African =−3.12 (−4.24, −2.01); Indian =−2.77 (−4.09, −1.45); Pakistani/ Bangladeshi =−3.15 (−4.27, −2.03). Between ethnic groups (i.e. in models including ethnicity), relatively better mental health of minority groups compared with Whites was apparent even in categories of low care and low autonomy. Adjusting for parenting scores, however, did not fully account for the protective effect of minority ethnicity.

Conclusions  Perceived quality of parenting is a correlate of psychological difficulties score for all ethnic groups despite differences in reporting. It is therefore likely that programmes supporting parenting will be effective regardless of ethnicity.
Indication for a role of regulatory T cells for the advent of influenza A (H1N1)-related pneumonia
Authors: Raftogiannis M , Antonopoulou A , Baziaka F , Spyridaki A , Koutoukas P , Tsaganos T , Savva A , Pistiki A , Georgitsi M , Giamarellos-Bourboulis E J
Published: July 2010

Regulatory T cells (Tregs) have an anti-inflammatory role. A former study in a limited number of patients found that absolute counts of Tregs increase when infection by the new influenza H1N1 virus is complicated with pneumonia. These results generate the question if H1N1-related pneumonia is associated with a state of hypo-inflammation. A total of 135 patients were enrolled with blood sampling within less than 24 h from diagnosis; 23 with flu-like syndrome; 69 with uncomplicated H1N1-infection; seven with bacterial pneumonia; and 36 with H1N1-related pneumonia. Tregs and CD14/HLA-DR co-expression were estimated by flow cytometry; concentrations of tumour necrosis factor-alpha (TNF-α), of interleukin (IL)-6 and of soluble triggering receptor expressed on myeloid cells-1 (sTREM-1) by an enzyme immunoassay; those of procalcitonin (PCT) by immuno-time-resolved amplified cryptate technology assay. Expression of human leucocyte antigen D-related (HLA-DR) on monocytes was similar between groups; absolute Treg counts were greater among patients with H1N1-related pneumonia than flu-like syndrome or H1N1-uncomplicated infection. Serum TNF-α of patients with bacterial pneumonia was greater than those of other groups, but IL-10 was similar between groups. Serum PCT was greater among patients with H1N1-related pneumonia and sTREM-1 among those with H1N1-related pneumonia. Regression analysis revealed that the most important factors related with the advent of pneumonia were the existence of underlying illnesses (P = 0·006) and of Tregs equal to or above 16 mm3 (P = 0·013). It is concluded that the advent of H1N1-related pneumonia is related to an early increase of the absolute Treg counts. This increase is probably not part of a hypo-inflammatory state of the host.
Tracing thymic output in older individuals
Authors: Mitchell W A , Lang P O , Aspinall R
Published: July 2010

As a result of age-associated thymic atrophy, T cell production declines with age. Some studies suggest that production undergoes an exponential decline starting at birth, while others consider the decline to be in a biphasic manner with a rapid reduction in output occurring before middle age followed by a phase in which output declines at a regular, albeit much slower, rate. Both approaches provide estimations of the time of termination of thymic output, but on the basis of limited amounts of data. We have analysed blood from more than 200 individuals between the ages of 58 and 104 years to determine changes in thymic output using signal-joint T cell receptor excision circles (sjTREC)/T cells as our measure. To reduce any potential geographical or nutritional bias we have obtained samples from five different European countries. Our results reveal that while the absolute number of T cells per microlitre of blood does not change significantly across the age range we tested, the values of sjTREC per microlitre show wide variation and reveal an age-associated decline in thymic output. In addition we show gender differences, with notably higher thymic output in females than males at each decade. More importantly, we noted a significant decline in sjTREC/T cell levels in those more than 90 years of age in both males and females. Our results provide information about the potential end-point for thymic output and suggest that sjTREC analysis may be a biomarker of effective ageing.
Autoimmune response and target autoantigens in Sjogren’s syndrome
Authors: Routsias John G. , Tzioufas Athanasios G.
Published: July 2010

Eur J Clin Invest 2010; 40 (11): 1026–1036

Background  Primary Sjogren’s syndrome (pSS) is characterized by the presence of autoantibodies targeting mainly the Ro/La ribonucleoprotein complex. It is now appreciated that the production of autoantibodies is an antigen‐driven immune response.

Design  In this review, candidate mechanisms for autoantigen presentation and perpetuation of the autoimmune response within the autoimmune tissue lesion of pSS are discussed.

Results  Several studies have shown that the epithelial cell in labial salivary glands of patients with Sjogren’s syndrome is activated, bearing characteristics of an antigen‐presenting cell, as suggested by inappropriate expression of class II HLA and co‐stimulatory molecules. Other studies have confirmed that in salivary glands, there is an increased autoantigen presentation via apoptotic blebs and bodies, exosomes and heat shock protein‐mediated cross‐priming. There is also an increased expression of interferon (IFN)‐induced genes, such as the autoantigen Ro52, which provide negative feedback regulation in inflammation. Ro60 and La autoantigens also appear to play a major role in the local autoimmune response in Sjogren’s syndrome. In this regard, La and Ro60 the messenger RNA (mRNA) expression is upregulated in the affected salivary glands with different isoforms of La autoantigen mRNA to be expressed in patients with pSS. At the protein level, La/SSB in pSS salivary glands is found to be post‐translationally modified.

Conclusions  Autoantigen alterations in a microenvironment of local inflammation with increased in situ apoptosis, Toll‐like receptor (TLR) signalling and antigen presentation may drive the autoimmune response and local autoantibody production in pSS.
C‐reactive protein evolution in obstructive sleep apnoea patients under CPAP therapy
Authors: Schiza Sophia E. , Mermigkis Charalampos , Panagiotis Panagou , Bouloukaki Izolde , Kallergis Eleftherios , Tzanakis Nikolaos , Tzortzaki Eleni , Vlachaki Eleni , Siafakas Nikolaos M.
Published: July 2010

Eur J Clin Invest 2010; 40 (11): 968–975

Background  C‐reactive protein (CRP) is recognized as a potential factor implicated in atherogenesis and associated cardiovascular morbidity. The aim of our study was to assess the CRP evolution during 1‐year follow‐up period in obstructive sleep apnoea (OSA) patients under CPAP treatment.

Methods  Five hundred and twenty‐eight patients with newly diagnosed moderate to severe OSA were included. CRP was assessed before CPAP initiation and at the 3rd, 6th and 12th month of the follow‐up period. Patients were divided into good and poor CPAP compliance groups.

Results  A significant reduction in CRP levels was observed after CPAP therapy (0·74 ± 0·62 mg dL−1 vs. 0·31 ± 0·29 mg dL−1, P < 0·001) in the whole patient group. The evolution of CRP values showed a gradual decrease at 3 months with a steep decline at 6 months, reaching a plateau after this time point. When the patients were divided into those with good and poor compliance with CPAP therapy, the above CRP evolution pattern was observed only in the former group.

Conclusion  Good CPAP compliance results in a significant CRP reduction. To achieve the best positive impact on cardiovascular morbidity and mortality, a time period of at least 6 months of CPAP use is required.
The vandalizing effects of irresponsible core sampling: a call for a new code of conduct
Authors: MacFadyen Colin
Published: July 2010

In 1989 the UK's Geologists' Association (GA) published the Code of Conduct for Rock Coring, a best practice guide to rock sampling by means of coring. The preparation of a code in the UK was required following acts of thoughtlessness by some researchers that permanently defaced outcrops ruining their photographic value. Despite the existence of the GA Code the vandalizing effects of irresponsible coring continue to this day and the cumulative effects are becoming increasingly apparent to even the most casual observers. As well as damaging exposures, irresponsible coring is tarnishing the reputation of geological science and there is concern that relations with landowners may be threatened by irresponsible coring, which may impact upon future sampling and research in the worst affected areas. Consequently, there is an urgent requirement for the reestablishment and promotion of a ‘Code of Conduct for Rock Coring’ based on the principles of the GA Code. To maximize awareness of the code and to ensure good practice guidance is not lost with the passage of time, its ethos could become enshrined in Earth science educational programmes. Just as importantly, adherence to the code could become an integral component of the standard ethical procedure conditions, attached to research funding for projects involving rock sampling.