bluuebunny/crossref_metadata_2025 huggingface dataset:
Post‐marketing observational study on 5% intravenous immunoglobulin therapy in patients with secondary immunodeficiency and recurrent serious bacterial infections
Authors: Günther Georg , Dreger Bettina
Published: April 2013

Secondary hypogammaglobulinemia is one of the factors responsible for the increased susceptibility to infection in patients with chronic lymphocytic leukemia (CLL). This study assessed the therapeutic results, concomitant medication and tolerance of administering 5% intravenous immunoglobulin, secondary immunodeficiency and recurrent serious bacterial infections. A single center, post‐marketing, observational clinical study was performed on 10 patients with a variety of hematological malignancies (CLL, follicular non‐Hodgkin lymphoma, IgM‐secreting immunocytoma, IgA plasmacytoma and myelodysplastic syndrome/non‐Hodgkin lymphoma) who had been infused with IVIG from June 1994 to May 2009. The clinical benefit of IVIG was assessed by comparing the incidence of bacterial infections before and after starting this therapy. Plasma immunoglobulin concentrations and relevant hematological variables were recorded. For safety assessment, adverse events were monitored. The standard IVIG dosage was approximately 0.35 g/kg body weight every 3–4 weeks. Most patients had normal IgG trough values of >600 mg/dL during the IVIG treatment period. The rate of bacterial infections was reduced from 2.4 per patient in the 3 months before IVIG to 0.7 (0–1.5) per patient per year during IVIG treatment. All patients received concomitant medication, mainly anticancer and anti‐anemia therapy (100%). No serious adverse events related to IVIG were observed. The frequency of at least one minor adverse reaction was 1.44% (8/556 infusions). In conclusion, the investigated IVIG preparation was well tolerated and clinically beneficial in reducing the long term rate of serious bacterial infections in patients receiving concomitant treatment for malignant diseases.
Who needs an artificial pancreas? (怎样的患者需要一个人工胰腺？)
Authors: Winikoff Janet , Drexler Andrew
Published: April 2013

The development of a closed‐loop “artificial pancreas” would be a welcome advance for both endocrinologists and diabetic patients struggling to attain near normal glycemic control. While great strides in automatically controlling blood sugar in the fasting, sedentary state have been made through complex mathematical modeling, management of blood sugar excursions due to food and exercise have been more problematic. An artificial pancreas is not feasible at this time because of limitations inherent in the currently available technology.
Recent advances in urologic laparoscopic surgeries: laparoendoscopic single‐site surgery, natural orifice transluminal endoscopic surgery, robotics and navigation
Authors: Matsuda Tadashi
Published: April 2013

Laparoscopic surgery was developed at the end of the 1980s and has been utilized in almost all urologic surgical procedures. It offers the benefits of less invasiveness and earlier recovery than open surgery. The introduction of laparoendoscopic single‐site surgery has offered reduced pain and improved cosmetic satisfaction to patients. Scarless nephrectomy has been realized with transvaginal natural orifice transluminal endoscopic surgery in women. The development of surgical robots has decreased the technical difficulty of complicated procedures, shortened the learning curve, and improved perioperative outcomes relative to laparoscopic surgery. Surgical navigation using real‐time sonography, augmented reality, fluorescence, or radioisotope images will improve the quality of these surgeries.
The Effect of Fenofibrate on Lymphocyte Release of Proinflammatory Cytokines and Systemic Inflammation in Simvastatin‐Treated Patients with Atherosclerosis and Early Glucose Metabolism Disturbances
Authors: Krysiak Robert , Gdula‐Dymek Anna , Okopien Boguslaw
Published: April 2013

This study was designed to investigate whether fibrates produce lymphocyte‐suppressing and systemic anti‐inflammatory effects in statin‐treated pre‐diabetic patients. The study included 47 atherosclerotic patients with the concomitant presence of impaired fasting glucose and impaired glucose tolerance already receiving simvastatin treatment (40 mg daily) who were allocated to one of two groups treated for 90 days with, respectively, fenofibrate (200 mg daily) or placebo. Plasma lipids, glucose homoeostasis markers, plasma high‐sensitivity C‐reactive protein as well as lymphocyte release of pro‐inflammatory cytokines were determined on the allocation day and after 90 days of therapy. Compared with placebo, fenofibrate reduced lymphocyte release of interleukin‐2, interferon‐γ and tumour necrosis factor‐α, which was accompanied by a reduction in plasma C‐reactive protein levels. The results obtained indicate that fenofibrate inhibits lymphocyte secretory function and reduces low‐grade inflammation in patients with both impaired fasting glucose and impaired glucose tolerance. Our findings suggest that the combined treatment with simvastatin and fenofibrate may be a better treatment option than simvastatin alone in this group of patients, particularly in those who are at high risk for cardiovascular events.
Evaluation of the In Vivo Anti‐Inflammatory and Analgesic Activity of a Highly Water‐Soluble Aspirin Conjugate
Authors: Jacob James N. , Badyal Dinesh K. , Bala Suman
Published: April 2013

Glucose‐aspirin (GA) was synthesized by conjugating aspirin (ASA) to the 3‐carbon of glucose to produce a stable water‐soluble aspirin derivative. The in vivo activities were compared with those of aspirin. The mouse tail flick assay showed that at 120 min., both aspirin and GA showed the maximum possible effect, and the higher dose (200 mg/kg) generally had less of an effect than the lower dose (100 mg/kg). Per cent inhibition of paw oedema was 63% and 69% for ASA and GA at 100 mg/kg, respectively. In the tail immersion test, the increase in reaction time was significantly greater with GA as compared to aspirin (100 mg/kg) at 60 min. In conclusion, there was significant anti‐inflammatory and analgesic activity for GA at the doses studied under the experimental conditions.
The Effect of Genistein on the Content and Activity of α‐ and β‐Secretase and Protein Kinase C in Aβ‐Injured Hippocampal Neurons
Authors: Liao Weiliang , Jin Guifang , Zhao Meishun , Yang Hong
Published: April 2013

Genistein (Gen), a derivative of soy isoflavone aglycone, has been shown to exert significant protective effect on Aβ‐induced neurotoxicity and neuroinjury. However, its underlying mechanism remains elusive. The objective was to investigate the inhibitory effect of Gen on Aβ‐induced neurotoxicity and to elucidate the underlying mechanism. Primary rat hippocampal neurons were pre‐treated with Gen for 2 hr followed by incubation with Aβ 25–35 for an additional 24 hr. The cell viability was assessed by MTT assay. The content and activity of α‐, β‐secretase and protein kinase C (PKC) were measured, and the antagonistic effect of PKC inhibitor Myr was also analysed to clarify the molecular mechanism of Gen inhibition of Aβ‐induced toxicity to hippocampal neurons. The results showed that pre‐treatment with Gen significantly increased the cell viability and presented the best effect at the final concentration of 0.375 µg/mL. Gen increases the activity of α‐secretase but down‐regulates the β‐secretase activity. It also enhances the expression and activity of PKC. Myr, a PKC inhibitor, partially blocks the activation effect of Gen. Gen exerts protective effect on Aβ‐induced neurotoxicity via activating the PKC signalling pathway, which further regulates the activities of α‐ and β‐secretase and thereby inhibits the formation and toxicity of Aβ.
Bayesian Inference for Two‐Phase Studies with Categorical Covariates
Authors: Ross Michelle , Wakefield Jon
Published: April 2013

In this article, we consider two‐phase sampling in the situation in which all covariates are categorical. Two‐phase designs are appealing from an efficiency perspective since they allow sampling to be concentrated in informative cells. A number of likelihood‐based methods have been developed for the analysis of two‐phase data, but we describe a Bayesian approach which has previously been unavailable. The methods are first compared with existing approaches via a simulation study, and are then applied to data collected on Wilms tumor. The benefits of a Bayesian approach include relaxation of the reliance on asymptotic inference, particularly in sparse data situations, and the potential to model data with complex dependencies, for example, via the introduction of random effects. The sparse data situation is illustrated via a simulated example.
Joint High‐Dimensional Bayesian Variable and Covariance Selection with an Application to eQTL Analysis
Authors: Bhadra Anindya , Mallick Bani K.
Published: April 2013

We describe a Bayesian technique to (a) perform a sparse joint selection of significant predictor variables and significant inverse covariance matrix elements of the response variables in a high‐dimensional linear Gaussian sparse seemingly unrelated regression (SSUR) setting and (b) perform an association analysis between the high‐dimensional sets of predictors and responses in such a setting. To search the high‐dimensional model space, where both the number of predictors and the number of possibly correlated responses can be larger than the sample size, we demonstrate that a marginalization‐based collapsed Gibbs sampler, in combination with spike and slab type of priors, offers a computationally feasible and efficient solution. As an example, we apply our method to an expression quantitative trait loci (eQTL) analysis on publicly available single nucleotide polymorphism (SNP) and gene expression data for humans where the primary interest lies in finding the significant associations between the sets of SNPs and possibly correlated genetic transcripts. Our method also allows for inference on the sparse interaction network of the transcripts (response variables) after accounting for the effect of the SNPs (predictor variables). We exploit properties of Gaussian graphical models to make statements concerning conditional independence of the responses. Our method compares favorably to existing Bayesian approaches developed for this purpose.
Maternal hypothyroxinemia and effects on cognitive functioning in childhood: how and why?
Authors: Henrichs Jens , Ghassabian Akhgar , Peeters Robin P. , Tiemeier Henning
Published: April 2013

Exposure to maternal hypothyroxinemia during pregnancy, which is characterized by low free T4 but normal thyroid‐stimulating hormone (TSH) levels, can negatively affect the foetus. This review provides an overview of present findings concerning the association between maternal hypothyroxinemia during pregnancy and childhood cognitive functioning. Possible causes of maternal hypothyroxinemia and potential mechanisms underlying this association are also discussed. Clinical and epidemiological studies suggest that maternal hypothyroxinemia in the first half of pregnancy but not later in pregnancy impairs cognitive development in infancy and childhood. Animal models confirm that the first half of pregnancy may constitute a sensitive period in which maternal hypothyroxinemia alters neurogenesis and causes neuronal migration errors in the developing foetal brain. However, observational studies in humans cannot demonstrate causality of the association between hypothyroxinemia and neurodevelopment. In the only completed randomized trial of antenatal thyroid screening and subsequent levothyroxine treatment of mild maternal subclinical thyroid dysfunction, including hypothyroxinemia, the interventions did not affect offspring intelligence quotient (IQ). More randomized trials are needed investigating whether screening for hypothyroxinemia and its treatment earlier in the first trimester of pregnancy can improve child cognitive functioning or prevent neurodevelopmental changes. Long‐term observational studies should identify molecular, neuroanatomical and neurophysiological factors involved in the association between maternal hypothyroxinemia and offspring cognitive functioning. Information on such mechanisms can be used for the development of innovative prevention and intervention studies that address maternal hypothyroxinemia and its potential consequences.
Cement‐associated peri‐implantitis: a retrospective clinical observational study of fixed implant‐supported restorations using a methacrylate cement
Authors: Korsch Michael , Obst Ursula , Walther Winfried
Published: April 2013

Background

Cement‐retained fixed implant‐supported restorations involve the risk of excess cement, which can associate peri‐implantitis. In connection with routine therapy using a methacrylate cement (Premier Implant Cement, Premier® Dental Products Company, Plymouth Meeting, PA, USA) to retain fixed implant‐supported restorations, complications, that is, inflammations, were developed in some cases. After removing the suprastructure and the abutment, residual excessive cement was found. For this reason, all implant‐supported restorations that had been fixed with this type of methacrylate cement were reevaluated and retreated.

Methods

In a retrospective clinical observational study including 71 patients with 126 implants, the findings made during retreatment were documented. In all cases, the suprastructure and the abutment were removed. For recementation, Temp Bond (Kerr Sybron Dental Specialities, Washington, D.C., USA) was used. If an inflammation had developed, a follow‐up appointment was scheduled 3–4 weeks later.

Results

In 59.5% of the implants, cement residues were identified. Bleeding on probing was diagnosed at 80% of the implants with excess cement and suppuration at 21.3% of the implants. After removal of the excess cement and recementation with Temp Bond, a 76.9% reduction in bleeding on probing was found at follow‐up. Suppuration was not found around any of the implants at follow‐up.

Conclusion

Excess cement left in the implant–mucosal interface caused bleeding on probing in most cases and suppuration in some. The removal of excess cement after cementation should be given high priority. In this retrospective observational study, an unusually high number of implants with excess cement after cementation was found with the methacrylate cement applied in the study.
Non‐organ donors' attitudes toward incentives
Authors: Tumin Makmor , Noh Abdillah , Chong Chin‐Sieng , Lim Soo‐Kun , Abdullah Nawi , Ng Kok‐Peng
Published: April 2013

Malaysians indicating that they did not intend to become organ donors upon their death were surveyed regarding interest in non‐fungible financial incentives to be granted to surviving family members. Among the 730 (56% of the total sample of 1311) indicating unwillingness to be donors, 29.6% (216/730) subsequently indicated that they would be willing donors if the government introduced policies that, upon their death, “rewarded your (their) family with incentives for your (their) deeds.” Among the 69% (504/730) who insisted that they would not become organ donor even with incentive, nearly 80% (404/501) of them were able to identify relevant incentives they thought should be provided by the state to those who make organ donations upon death. The majority of both groups preferred the state provide medical benefits to a surviving family member, suggesting this may be an attractive policy option for the state to raise the deceased organ donation pool.
Assessing the non‐motor symptoms of Parkinson's disease: MDS‐UPDRS and NMS Scale
Authors: Martinez‐Martin P. , Chaudhuri K. R. , Rojo‐Abuin J. M. , Rodriguez‐Blazquez C. , Alvarez‐Sanchez M. , Arakaki T. , Bergareche‐Yarza A. , Chade A. , Garretto N. , Gershanik O. , Kurtis M. M. , Martinez‐Castrillo J. C. , Mendoza‐Rodriguez A. , Moore H. P. , Rodriguez‐Violante M. , Singer C. , Tilley B. C. , Huang J. , Stebbins G. T. , Goetz C. G.
Published: April 2013

Background and purpose

Although Parkinson's disease (PD) is characterized by typical motor manifestations, non‐motor symptoms (NMS) are an outstanding part of the disease. At present, several specific instruments for assessment of NMS are available. The objective of our study was to determine the performance of the Movement Disorder Society‐Unified Parkinson's Disease Rating Scale (MDS‐UPDRS): Part I – Non‐Motor Aspects of Experiences of Daily Living (nM‐EDL) compared with the Non‐Motor Symptoms Scale (NMSS).

Methods

To this purpose, 434 consecutive patients with PD were included in an international, observational, cross‐sectional study. The association between scores of both scales was determined by the Spearman rank correlation coefficient. Equations for transformation of total score of a scale to the other were constructed from weighted regression models and both, transformed and observed score, contrasted by means of the Lin's Concordance Correlation Coefficient (LCCC) and Bland–Altman plot.

Results

As a whole, the prevalence of the NMS according to each scale was quite similar, and most of the correlations between their corresponding components were high (rS > 0.60). The total score correlation of the MDS‐UPDRS Part I with the NMSS was high (rS = 0.81). Concerning the transformed scores, estimated scores only partially approach the observed ones (sharing about 60–64% of the variance) because residual variance increased with increasing magnitudes of the scores, i.e. the most severe patients (Bland–Altman plot; LCCC < 0.60 for severe patients).

Conclusions

(i) MDS‐UPDRS Part I (nM‐EDL) and NMSS showed a strong convergent validity; (ii) however, transformed scores using the equations from weighted regression models showed that for patients with the most severe NMS they are not concordant.
A myogenic precursor cell that could contribute to regeneration in zebrafish and its similarity to the satellite cell
Authors: Siegel Ashley L. , Gurevich David B. , Currie Peter D.
Published: April 2013

The cellular basis for mammalian muscle regeneration has been an area of intense investigation over recent decades. The consensus is that a specialized self‐renewing stem cell, termed the satellite cell, plays a major role during the process of regeneration in amniotes. How broadly this mechanism is deployed within the vertebrate phylogeny remains an open question. A lack of information on the role of cells analogous to the satellite cell in other vertebrate systems is even more unexpected given the fact that satellite cells were first designated in frogs. An intriguing aspect of this debate is that a number of amphibia and many fish species exhibit epimorphic regenerative processes in specific tissues, whereby regeneration occurs by the dedifferentiation of the damaged tissue, without deploying specialized stem cell populations analogous to satellite cells. Hence, it is feasible that a cellular process completely distinct from that deployed during mammalian muscle regeneration could operate in species capable of epimorphic regeneration. In this minireview, we examine the evidence for the broad phylogenetic distribution of satellite cells. We conclude that, in the vertebrates examined so far, epimorphosis does not appear to be deployed during muscle regeneration, and that analogous cells expressing similar marker genes to satellite cells appear to be deployed during the regenerative process. However, the functional definition of these cells as self‐renewing muscle stem cells remains a final hurdle to the definition of the satellite cell as a generic vertebrate cell type.
Common biological networks underlie genetic risk for alcoholism in African‐ and European‐American populations
Authors: Kos M. Z. , Yan J. , Dick D. M. , Agrawal A. , Bucholz K. K. , Rice J. P. , Johnson E. O. , Schuckit M. , Kuperman S. , Kramer J. , Goate A. M. , Tischfield J. A. , Foroud T. , Nurnberger J. , Hesselbrock V. , Porjesz B. , Bierut L. J. , Edenberg H. J. , Almasy L.
Published: April 2013

Alcohol dependence (AD) is a heritable substance addiction with adverse physical and psychological consequences, representing a major health and economic burden on societies worldwide. Genes thus far implicated via linkage, candidate gene and genome‐wide association studies (GWAS) account for only a small fraction of its overall risk, with effects varying across ethnic groups. Here we investigate the genetic architecture of alcoholism and report on the extent to which common, genome‐wide SNPs collectively account for risk of AD in two US populations, African‐Americans (AAs) and European‐Americans (EAs). Analyzing GWAS data for two independent case–control sample sets, we compute polymarker scores that are significantly associated with alcoholism (P = 1.64 × 10–3 and 2.08 × 10–4 for EAs and AAs, respectively), reflecting the small individual effects of thousands of variants derived from patterns of allelic architecture that are population specific. Simulations show that disease models based on rare and uncommon causal variants (MAF < 0.05) best fit the observed distribution of polymarker signals. When scoring bins were annotated for gene location and examined for constituent biological networks, gene enrichment is observed for several cellular processes and functions in both EA and AA populations, transcending their underlying allelic differences. Our results reveal key insights into the complex etiology of AD, raising the possibility of an important role for rare and uncommon variants, and identify polygenic mechanisms that encompass a spectrum of disease liability, with some, such as chloride transporters and glycine metabolism genes, displaying subtle, modifying effects that are likely to escape detection in most GWAS designs.
Authigenic iron oxide proxies for marine zinc over geological time and implications for eukaryotic metallome evolution
Authors: Robbins L. J. , Lalonde S. V. , Saito M. A. , Planavsky N. J. , Mloszewska A. M. , Pecoits E. , Scott C. , Dupont C. L. , Kappler A. , Konhauser K. O.
Published: April 2013

Here, we explore enrichments in paleomarine Zn as recorded by authigenic iron oxides including Precambrian iron formations, ironstones, and Phanerozoic hydrothermal exhalites. This compilation of new and literature‐based iron formation analyses track dissolved Zn abundances and constrain the magnitude of the marine reservoir over geological time. Overall, the iron formation record is characterized by a fairly static range in Zn/Fe ratios throughout the Precambrian, consistent with the shale record (Scottet al., 2013, Nature Geoscience,6, 125–128). When hypothetical partitioning scenarios are applied to this record, paleomarine Zn concentrations within about an order of magnitude of modern are indicated. We couple this examination with new chemical speciation models to interpret the iron formation record. We present two scenarios: first, under all but the most sulfidic conditions and with Zn‐binding organic ligand concentrations similar to modern oceans, the amount of bioavailable Zn remained relatively unchanged through time. Late proliferation of Zn in eukaryotic metallomes has previously been linked to marine Zn biolimitation, but under this scenario the expansion in eukaryotic Zn metallomes may be better linked to biologically intrinsic evolutionary factors. In this case, zinc‘s geochemical and biological evolution may be decoupled and viewed as a function of increasing need for genome regulation and diversification of Zn‐binding transcription factors. In the second scenario, we consider Archean organic ligand complexation in such excess that it may render Zn bioavailability low. However, this is dependent on Zn–organic ligand complexes not being bioavailable, which remains unclear. In this case, although bioavailability may be low, sphalerite precipitation is prevented, thereby maintaining a constant Zn inventory throughout both ferruginous and euxinic conditions. These results provide new perspectives and constraints on potential couplings between the trajectory of biological and marine geochemical coevolution.
Advances in the treatment of inherited coagulation disorders
Authors: Escobar M. A.
Published: April 2013

Inherited coagulation disorders constitute a broad spectrum of coagulation factor deficiencies that include X‐linked factor (F)VIII or FIX deficiency that causes haemophilia, and autosomal recessive disorders producing heterogeneous deficiencies in fibrinogen (FI), prothrombin (FII), FV, FVII, FX, FXI, FXIII and combined FV+FVIII. Significant advances in treatments for patients with congenital haemophilia A (FVIII deficiency) and B (FIX deficiency) over the last two decades have resulted from improvements in the production, availability and patient access to factor replacement products. Translation of advances in biotechnology, namely recombinant protein technology, targeted protein modifications to improve function and potentially reduce immunogenicity, and advanced formulations to optimize bioavailability and sustain activity offer promisingly new treatments for haemophilia as well as recessively inherited bleeding disorders in patients who otherwise have few therapeutic options. Though a theoretical risk remains for blood‐borne viral infections with pooled plasma‐derived products, this concern has diminished with breakthroughs in purification and viral inactivation methods. Development of inhibitory antibodies is still the most daunting problem for patients with inherited bleeding disorders, complicating treatment approaches to control and prevent bleeding, and posing risks for allergic and anaphylactic reactions in susceptible patients. The objectives of this review are to (i) highlight emerging advances in hemostatic therapies that are bioengineered to improve pharmacokinetic properties and bioavailability, sustain functional activity, and possibly eliminate immunogenicity of recombinant factor proteins; and (ii) present an overview of key clinical trials of novel factor products currently in the development pipeline.
Inhibitors in haemophilia B: the Italian experience
Authors: Castaman G. , Bonetti E. , Messina M. , Morfini M. , Rocino A. , Scaraggi F. A. , Tagariello G. ,   Italian Association of Hemophilia Centers
Published: April 2013

The prevalence of inhibitors in haemophilia B is significantly lower than that of patients with haemophilia A. However, the peculiar occurrence of allergic reactions associated with the onset of inhibitor in haemophilia B (HB) may render immune tolerance a risky procedure. We have carried out a detailed survey among all the Italian Hemophilia Centers to analyse all the patients with HB and inhibitors. A total of eight patients were reported among 282 living patients (2.8%) with severe factor IX (FIX) deficiency (FIX < 1 U dL−1). In addition, two deceased patients were also identified. Six patients carried nonsense mutations while in four partial or complete gene deletions were detected. Three patients (one deceased) had history of allergic/anaphylactic reaction upon substitutive treatment, which in one case was recurrent and resolved after switching to plasma derived FIX. Immune tolerance was adopted in five patients and in four complete response was achieved while in the remaining it was partial. No nephrotic syndrome was observed. Our data confirm that inhibitors in HB occur in patients with null mutations or complete/partial gene deletion. Immune tolerance can be achieved also in HB patients, without allergic reactions or nephrotic syndrome upon replacement therapy.
Efficacy of Two Levofloxacin‐Containing Second‐Line Therapies for Helicobacter pylori: A Pilot Study
Authors: Calhan Turan , Kahraman Resul , Sahin Abdurrahman , Senates Ebubekir , Doganay Hamdi Levent , Kanat Evren , Ozdil Kamil , Sokmen Hacı Mehmet
Published: April 2013

Background

An ideal second‐line therapeutic regimen for the treatment of patients who do not respond to standard triple therapy is currently being investigated. In this study, we aimed to investigate the efficacy of two levofloxacin‐containing second‐line therapies for Helicobacter pylori (H. pylori).

Materials and Methods

One hundred and forty eight consecutive H. pylori ‐positive patients who did not respond to the standard triple therapy (77 female, 71 male) were enrolled in the study. The patients were randomized consecutively to two‐second‐line therapy groups; 73 to the levofloxacin‐containing sequential (LCS) and 75 to the levofloxacin‐containing quadruple (LCQ) therapy group. The LCS therapy group received pantoprazole 40 mg and amoxicillin 1,000 mg twice daily for 5 days followed by pantoprazole 40 mg twice daily and metronidazole 500 mg three times daily and levofloxacin 500 mg one time daily for 7 days. The LCQ therapy group received pantoprazole 40 mg twice daily, tetracycline 500 mg four times daily, bismuth subcitrate 300 mg four times daily and levofloxacin 500 mg one time daily for 10 days. H. pylori eradication was confirmed by stool antigen testing at least 6 weeks after cessation of therapy. Side‐effects and compliance were assessed by a questionnaire.

Results

Intention‐to‐treat cure rates were: 82.2% (95%CI; 73–91) and 90.6% (95%CI; 79–95) in the LCS and LCQ therapy, respectively. Per protocol cure rates were: 85.7% (95%CI; 75–92) and 93.1% (95%CI; 85–98) in the LCS and LCQ therapy, respectively. No statistically significant difference was found between two groups (p = .1). No differences in compliance or adverse effects were demonstrated between two groups.

Conclusions

This prospective trial demonstrates that both levofloxacin‐containing sequential therapy and levofloxacin‐containing quadruple therapy regimens have higher H. pylori eradication rates and are well tolerated. The levofloxacin‐containing quadruple therapy is likely the best treatment option for a second‐line therapy, at least in the Turkish population.
Open‐labeled randomized controlled trial to compare diuretic therapy with recombinant human serum albumin and diuretic therapy for therapeutic treatment of ascites in patients with advanced liver cirrhosis: An exploratory trial
Authors: Nakamura Toru , Sata Michio , Suzuki Kazuyuki , Moriwaki Hisataka , Fukui Hiroshi , Fujiyama Shigetoshi , Imawari Michio
Published: April 2013

Aim

There have been only a few trials demonstrating additional effects of human serum albumin (HSA) on diuretic therapy in patients with cirrhotic ascites. We aimed to evaluate the safety and efficacy of recombinant HSA, KD‐294, treatment in patients with cirrhotic ascites.

Methods

The inclusion criteria were patients 20–75 years of age, with cirrhotic ascites and a serum albumin concentration of less than 3.0 g/dL. Eighty‐five patients were registered and 71 patients underwent randomization. Enrolled patients received oral spironolactone at 50 mg/day and i.v. furosemide at 20 mg/day in addition to low‐sodium diet. They were divided randomly into a KD‐294 treatment group (n = 35) or non‐treatment control group (n = 36). Patients in the KD‐294 group received KD‐294 at 25 g/day for up to 5 days and those in the control group continued the diuretic therapy. They were followed up for 5 weeks.

Results

KD‐294 was well tolerated. A correlation between the increases in serum albumin and decreases in bodyweight was not shown. However, changes of plasma renin concentration (PRC) showed a significant decrease in the KD‐294 group compared with the control group. As a result of this exploratory analysis, patients with high PRC showed a significant correlation between increases in serum albumin and decreases in bodyweight.

Conclusion

The present data do not show efficacy in all patients with cirrhotic ascites, however, they suggest that additional effects of HSA on diuretic therapy are expected in high PRC patients.
The accuracy of references in PhD theses: a case study
Authors: Azadeh Fereydoon , Vaez Reyhaneh
Published: April 2013

Background

Inaccurate references and citations cause confusion, distrust in the accuracy of a report, waste of time and unnecessary financial charges for libraries, information centres and researchers.

Objectives

The aim of the study was to establish the accuracy of article references in PhD theses from the Tehran and Tabriz Universities of Medical Sciences and their compliance with the Vancouver style.

Methods

We analysed 357 article references in the Tehran and 347 in the Tabriz. Six bibliographic elements were assessed: authors' names, article title, journal title, publication year, volume and page range. Referencing errors were divided into major and minor.

Results

Sixty two percent of references in the Tehran and 53% of those in the Tabriz were erroneous. In total, 164 references in the Tehran and 136 in the Tabriz were complete without error. Of 357 reference articles in the Tehran, 34 (9.8%) were in complete accordance with the Vancouver style, compared with none in the Tabriz. Accuracy of referencing did not differ significantly between the two groups, but compliance with the Vancouver style was significantly better in the Tehran.

Conclusions

The accuracy of referencing was not satisfactory in both groups, and students need to gain adequate instruction in appropriate referencing methods.
Paucity of synaptophysin‐expressing cells in Barrett's mucosa
Authors: Rubio Carlos A , Kaufeldt Ann
Published: April 2013

Aims

To assess synaptophysin expression in columnar‐lined oesophageal mucosa showing either goblet cells, known as intestinal metaplasia, or with accompanying oxyntic glands or pyloric glands.

Methods and results

Of 159 biopsies, 53 were oesophageal (19 had intestinal metaplasia, 13 oxyntic glands, and 21 pyloric glands), 77 gastric (12 had goblet cells and 27 no goblet cells) and 29 duodenal. Synaptophysin‐positive goblet cells were found in all biopsies from the normal duodenum, in 53% of the oesophageal biopsies showing intestinal metaplasia, but only in 8% of gastric biopsies showing intestinal metaplasia. Synaptophysin‐positive Paneth cells occurred in all duodenal biopsies, and in nine of the gastric biopsies showing intestinal metaplasia, but in only one of the oesophageal biopsies showing intestinal metaplasia. A continuous synaptophysin‐positive neck cell zone was found in all biopsies from the normal antrum, but in none of the oesophageal biopsies with pyloric glands or with chronic antritis.

Conclusions

The paucity or absence of synaptophysin‐positive cells in all three phenotypes of Barrett's mucosa might mirror a sequela of chronic inflammation caused by the particular pathogenic bacteria present in the immediate oesophageal microenvironment.
Impact of MET expression on outcome in BRAFV600E/K advanced melanoma
Authors: Jubb Adrian M , Ribas Antoni , Sosman Jeffrey A , McArthur Grant A , Yan Yibing , Rost Sandra , Zhao Sherry , Koeppen Hartmut
Published: April 2013

Aims

Preclinical data suggest that signalling through the HGF–MET pathway may confer resistance to BRAF inhibition in BRAFV600E/K melanoma. Therefore, blockade of HGF–MET signalling might be a valid therapeutic strategy, in combination with BRAF inhibition, in BRAFV600E/K melanoma. The aim of this study was to investigate the clinical relevance of these observations by evaluating the survival impact of MET expression in patients with BRAFV600E/K advanced melanoma treated with vemurafenib.

Methods and results

Formalin‐fixed tissue blocks were obtained of tumours from patients enrolled in the BRIM2 (n = 59) and BRIM3 (n = 150) trials of vemurafenib in advanced BRAFV600E/K melanoma. Immunohistochemistry for MET (SP44 rabbit monoclonal antibody) was performed with a highly validated assay and clinically validated scoring system. Pretreatment MET expression was frequent at the ≥1 + cutoff (BRIM3, 31%; BRIM2, 49%), but relatively infrequent at the ≥2 + cutoff (BRIM3, 9%; BRIM2, 19%). Retrospective subset analyses showed that, irrespective of the cutoff used or the treatment arm, MET expression did not show prognostic significance, in terms of objective response rate, progression‐free survival, or overall survival.

Conclusions

MET is expressed in a proportion of BRAFV600E/K advanced melanomas. Further analyses on appropriately powered subsets are needed to determine the prognostic and predictive significance of MET in vemurafenib‐treated melanoma.
Electrochemical induced dissolution of fragments of nickel–titanium endodontic files and their removal from simulated root canals
Authors: Aboud L. R. L. , Ormiga F. , Gomes J. A. C. P.
Published: April 2013

Aim

To improve the dissolution process of NiTi endodontic rotary files aiming at fragment removal and the recovery of the original path of the root canal during a clinically acceptable period of time.

Methodology

Anodic polarization curves and redox curves were obtained to determine the conditions necessary for the dissolution of endodontic files. Anodic polarization of K3 files was performed, and analysis of variance (P < 0.05) was used to compare different test times in relation to weight loss, length loss and electrical charge generated in each solution. The polarization of fragments in simulated root canals was undertaken to evaluate the dissolution process. After the tests, a size 10 K‐file was used to verify the possibility to bypass the fragment. The total electrical charge of each test was obtained from the corresponding graph area. Radiographic analysis of the simulated canals was used before and after the tests to verify fragment dissolution.

Results

The weight loss values, the length loss values and the total values of electrical charge in each period of time were significantly higher (P < 0.05) in the tests using the selected solution compared with the solution previously proposed. A progressive consumption of the K3 file tip was observed up to 30 min. The anodic polarization of file fragments in simulated root canals for 60 min resulted in their partial dissolution and enabled the recovery of the original canal pathway with size 10 K‐files.

Conclusions

Increasing fluoride concentration resulted in greater active dissolution of NiTi files. The dissolution of fractured files in simulated root canals enabled the recovery of its original path during a clinically acceptable period of time.
Additional Evidence on the Relationship between an Internal Audit Function and External Audit Fees in Australia
Authors: Singh Harjinder , Woodliff David , Sultana Nigar , Newby Rick
Published: April 2013

Studies examining the relationship between a firm's internal audit (IA) function and its audit fees have produced mixed results with suggestions of possible model mis‐specification in these studies. Our analysis reveals that differences in significance for IA with audit fees is driven by the choice of variables proxying for firm size and other firm characteristics, suggesting that prior results are entangled with model specification issues. Specifically, when the sales variable is used as a measure of firm size, IA is insignificant (in explaining variations in audit fees) but subsequently becomes significant when assets and employees are used. To overcome the conflicting results, subsequent factor analysis supported a positive relationship between IA and audit fees. The most significant implication from this study is that previously reported relationships involving audit fees may be the outcome of the model adopted rather than the underlying relationship between the variable of interest and audit fees
A method for fuzzy group decision making based on induced aggregation operators and Euclidean distance
Authors: Su Weihua , Peng Wuzhen , Zeng Shouzhen , Peng Bo , Pan Tiejun
Published: April 2013

In this paper, we present the fuzzy‐induced Euclidean ordered weighted averaging distance (FIEOWAD) operator. It is an extension of the ordered weighted averaging (OWA) operator that uses the main characteristics of the induced OWA (IOWA), the Euclidean distance and uncertain information represented by fuzzy numbers. The main advantage of this operator is that it is able to consider complex attitudinal characters of the decision maker by using order‐inducing variables in the aggregation of the Euclidean distance. Moreover, it is able to deal with uncertain environments where the information is very imprecise and can be assessed with fuzzy numbers. We study some of its main properties and particular cases such as the fuzzy maximum distance, fuzzy minimum distance, fuzzy‐normalized Euclidean distance (FNED), fuzzy‐weighted Euclidean distance (FWED), and fuzzy Euclidean ordered weighted averaging distance (FEOWAD) operator. Finally, we present an application of the operator to a group decision‐making problem concerning the selection of strategies.
Analysing trade‐offs in container loading: combining load plan construction heuristics with agent‐based simulation
Authors: Mustafee Navonil , Bischoff Eberhard E.
Published: April 2013

In this paper we describe two operations research techniques, cutting and packing optimisation (CPO) and simulation, and present a multi‐methodology approach for analysing the trade‐offs between loading efficiency and various important practical considerations in relation to the cargo, such as its stability, fragility or possible cross‐contamination between different types of items over time. The feasibility of this approach is demonstrated by considering a situation where the items to be loaded have differing degrees of perishability and where badly deteriorated items can affect those in their immediate vicinity (e.g. through the spread of mould). Our approach uses the output of the CPO algorithms to create agents that simulate the spread of mould through proximity‐based interactions between the agents. The results show the trade‐offs involved in container utilisation and the propagation of mould, without evidence of any correlation between them. The contribution of this research is the methodology and the feasibility study.
Genetics of sexual compatibility and resistance to benzimidazole and dicarboximide fungicides in isolates of Botryotinia fuckeliana (Botrytis cinerea) from nine countries
Authors: FARETRA F. , POLLASTRO S.
Published: April 2013

Field isolates and laboratory mutants of Botryotinia fuckeliana (Botrytis cinerea) from nine different countries were crossed with reference strains of known mating type, to determine the genetic bases of differences in sexual fertility and in resistance to benzimidazole and dicarboximide fungicides. Most isolates were heterothallic, and carried the MAT1‐1 or MAT1‐2 mating‐type allele. A few isolates were fertile with strains of opposite mating types, due to the presence of both mating‐type alleles in heterokaryotic mycelia. The MAT1‐1 and MAT1‐2 alleles were fairly evenly distributed among the field isolates from most countries. Seventy‐six isolates displayed resistance to benzimidazole and/or dicarboximide fungicides due to mutant alleles of the Mbc1 and/or Daf1 genes. Unlike wild‐type and low‐resistant isolates, those carrying the high‐resistance Mbc/HR alleles were sensitive to N‐phenylcarbamates. With one exception, isolates carrying the high‐resistance Daf/HR alleles were hypersensitive to media of high osmolarity. Heterokaryons containing Daf/HR alleles together with sensitive Daf/S or low‐resistance Daf/LR alleles in separate nuclei combined high resistance to dicarboximides with relative tolerance of media with high osmolarity.
Virus Inactivation by Solvent/Detergent Treatment and the Manufacture of SD‐Plasma
Authors: Horowitz B. , Lazo A. , Grossberg H. , Page G. , Lippin A. , Swan G.
Published: April 2013

Solvent/Detergent (SD) is an extraordinarily effective means for eliminating enveloped viruses from plasma and plasma products [1]. The safety margin suggested by the rapid and complete kill of enveloped viruses observed in the laboratory has been confirmed repeatedly by groups worldwide and by thirteen years of routine clinical use encompassing an estimated 35 million doses of a wide variety of products. Throughout this time, there has not been a single documented case of enveloped virus transmission by an SD‐treated product. This record of safety spawned the development of SD‐treated plasma as a substitute for fresh frozen plasma (FFP) [2] and has encouraged the adoption of SD for the treatment of non‐blood products such as monoclonal antibodies and those derived from recombinant DNA procedures [3]. This review summarizes the use of SD treatment, including its use in combination with other viral elimination procedures, and also summarizes Vitex's initial experience in the manufacture of SD‐Plasma, recently licensed by the U.S. FDA.
Hemovigilance: Clinical Tolerance of Solvent‐Detergent Treated Plasma
Authors: Baudoux E. , Margraff U. , Coenen A. , Jacobs X. , Strivay M. , Lungu C. , Sondag‐Thull D.
Published: April 2013

Objective: This study was conducted to assess retrospectively the clinical tolerance of SD treated plasma and to compare it to other labile blood products (red blood cell and platelet concentrates). Method: Adverse events (AEs) related to the use of blood products at the Blood Transfusion Center (BTC) are routinely collected through a formalised system of hemovigilance. All AEs reported are entered into a safety data base which was used for the study. All AEs reported during a one‐year period to the BTC were retrospectively re‐assessed and descriptive statistics calculated. Results: 5064 units of SD treated plasma were transfused to 894 recipients during the study period at the occasion of 1553 transfusions. No AE associated to SD treatment plasma was reported during that period. In contrast, during the same period, 485 AEs associated with the use of red blood cell concentrates (RBCC) were reported in 251 patients at the occasion of 262 transfusions. 2.1% (251/11748) of the patients transfused with RBCC experienced one or more AEs. The incidence of AEs per unit transfused was 1.3% (485/37332), and 2.4% (485/20460) of RBCC transfusions were associated with one or more AEs. 142 AEs associated with the use of platelet concentrate (PC) were observed in 69 patients at the occasion of 73 transfusions. 4.2% (69/1645) of patients transfused with PC experienced one or more AEs. The incidence of AEs per unit transfused was 1.1% (142/12772), and 2.8% (142/5034) of PC transfusions were associated with one or more AEs. All reported AEs were classified and non serious. The most frequently observed AEs were fever, chills and rashes which accounted for roughly 64% of all reported AEs. Conclusion: As for the overall clinical tolerance of red cell and platelet concentrates, the results of this study are in complete agreement with the published literature. The study also confirms the extremely good tolerability of SD treated plasma in comparison with other labile blood products.
Recentering Southeast Asian Cities
Authors: Goh Daniel P.S. , Bunnell Tim
Published: April 2013

For nearly two decades now, scholars have been heralding the arrival of new urbanisms. One debate in rapidly urbanizing Southeast Asia concerns the convergence of Western and Asian urban processes, and the riposte that interaction between globalizing processes and the historical momentum of local and regional forces make for complex Asian urbanisms. In recent years, attention has been drawn to the impact of decentralization, with consequences for the reorganization of the developmental state and the growing importance of private capital and urban social movements in driving urban processes and politics. This symposium offers the fresh lens of ‘recentering’ to discuss the urbanisms emerging from decentralization and the triangulating state–capital–social movement politics of the new urbanisms. Drawing on recent discussions of Manuel Castells' (1983) The City and the Grassroots, we seek to expand the conception of urban activism not just by considering non‐Western cases in the newly democratizing states of Southeast Asia, but also by considering cities as co‐agents of activism. We see the recentering of Southeast Asian cities as referring to political actions that take the city not only as site and repository, but also reflexively as identity in itself to be fought with, for and over.