bluuebunny/crossref_metadata_2025 huggingface dataset:
Lymphotropic hepatitis C virus has an interferon‐resistant phenotype
Authors: Inokuchi M. , Ito T. , Nozawa H. , Miyashita M. , Morikawa K. , Uchikoshi M. , Shimozuma Y. , Arai J. , Shimazaki T. , Hiroishi K. , Imawari M.
Published: October 2011

Summary.  Hepatitis C virus (HCV) infects and associates with B cells, leading to abnormal B‐cell activation and development of lymphoproliferative and autoimmune disorders. This immune perturbation may in turn be associated with the resistance of HCV against the host immune system. The objective of this study was to analyse the effects of HCV infection of B cells on the efficacy of interferon (IFN)‐based therapy. The study enrolled 102 patients with chronic hepatitis C who were treated with pegylated IFN plus ribavirin. HCV RNA titres in B cells were compared in patients with rapid viral responder (RVR) vs non‐RVR, sustained viral responder (SVR) vs non‐SVR and null viral responder (NVR) vs VR. The levels of HCV RNA in B cells were significantly higher in non‐RVR, non‐SVR and NVR groups. Association between the therapy outcome and the positive B‐cell HCV RNA was also investigated in relation to other known viral and host factors. Multivariable analyses showed that the positive B‐cell HCV RNA and the minor single‐nucleotide polymorphism near the IL28B gene (rs8099917) were independent factors associated with NVR in patients infected with HCV genotype 1. When these two factors were combined, the sensitivity, specificity, positive and negative predictive values for NVR were 92.3%, 98.2%, 92.3% and 98.2%, respectively. Genotype 1 and the presence of one or no mutations in the IFN‐sensitivity determining region were associated with higher levels of B‐cell HCV RNA. B‐cell‐tropic HCV appears to have an IFN‐resistant phenotype. B‐cell HCV RNA positivity is a predictive factor for resistance to IFN‐based therapy.
Renal function in type 1 diabetics one year after successful pancreas transplantation
Authors: Chatzizacharias Nikolaos A. , Vaidya Anil , Sinha Sanjay , Smith Richard , Jones Gareth , Sharples Edward , Friend Peter J.
Published: October 2011

Chatzizacharias NA, Vaidya A, Sinha S, Smith R, Jones G, Sharples E, Friend PJ. Renal function in type 1 diabetics one year after successful pancreas transplantation. Clin Transplant 2011: 25: E509–E515. © 2011 John Wiley & Sons A/S.

Abstract:  The effect of pancreas transplantation on renal function remains a matter of debate. The purpose of this retrospective, single‐unit study is a preliminary analysis of renal function one yr after pancreas transplant (pancreas alone [PTA] or pancreas after kidney [PAK]). Fifty‐nine patients were included. Serum creatinine and estimated glomerular filtration rate (eGFR) levels were compared three, six, and 12 months post‐transplantation for the whole sample and separately for PTA and PAK and high (>45 mL/min/1.73 m2) and low (≤45 mL/min/1.73 m2) pre‐transplant eGFR subgroups. Overall, eGFR did not change significantly (p = 0.228) at the end of the first year post‐transplant, with patients of low initial eGFR presenting a more prominent trend toward stable or improved levels. In the PAK subgroup, eGFR was significantly improved (p = 0.035). High eGFR subgroup demonstrated no significant deterioration in renal function, while patients with low initial eGFR had significantly higher levels 3 (p = 0.012) and six months (p = 0.009) post‐transplant. Our study shows that renal function did not deteriorate significantly one yr after pancreas transplant (PTA or PAK), even in patients with substantial pre‐existing renal dysfunction. Evaluation at a wider scale and identification of risk factors for potential deterioration are challenges for future research.
Active chemical compounds of traditional Chinese medicine Herba Leonuri: implications for cardiovascular diseases
Authors: Liu Xin H , Pan Li L , Zhu Yi Z
Published: October 2011

1. Herba Leonuri, a traditional Chinese medicine, has a long history of development and application in China. In particular, Herba Leonuri has been widely used in the treatment of gynaecological and obstetric disorders for thousands of years. Recent studies have shown that Herba Leonuri has many different effects.

2. Herba Leonuri contains several active components, including alkaloids, flavonoids, diterpenes compounds and fatty acids. Recent studies have shown that these molecules exert beneficial effects in coronary artery disease and cerebral ischaemia. Thus, these molecules may become novel candidates for drug discovery and development.

3. The present review provides an overview of the chemical composition, with a focus on biological activity, of Herba Leonuri to stimulate new studies on traditional Chinese medicine.
Decreased anti‐hepatitis C virus titer and associated factors in chronic hepatitis C patients after sustained virological response: A prospective study
Authors: Kee Kwong‐Ming , Wang Jing‐Houng , Hung Chao‐Hung , Chen Chien‐Hung , Lee Chuang‐Mo , Chang Kuo‐Chin , Tseng Po‐Lin , Yen Yi‐Hao , Lin Chih‐Yun , Lu Sheng‐Nan
Published: October 2011

Background and Aim:  Long‐term trends of anti‐hepatitis C virus (HCV) antibody titer and their associated factors in patients with sustained virological response (SVR) were investigated.

Methods:  From May 1999 to July 2005, a total of 166 SVR consecutive patients (M/F: 86/80) were enrolled. Anti‐HCV titer, samples to cut‐off (S/CO) ratios, were measured with AxSYM HCV version 3.0. Their S/CO ratios were followed every 6 months after SVR and the patterns over time were identified by trajectory analyses. Changes of recombinant immunoblot assay (RIBA) pattern before treatment and end of follow‐up were compared (n = 64).

Results:  The mean duration of follow‐up was 4.7 ± 1.5 years (median 4.3; range 3–9 years). The rates of S/CO ratios decreased annually (P < 0.001). Two of them (1.2%) achieved seroreversion. Trajectory groups included lower pretreatment S/CO ratios (LAB, n = 83), rapid decrease (RD, n = 62) and slow decrease (SD, n = 21) groups. Comparing LAB to RD group, odds ratio (OR) of increased platelet count per 1 unit and interferon regimen was 1.12 (95% confidence interval [CI] 1.04–1.20) and 2.17 (95% CI 1.04–4.52) respectively. Comparing SD to LAB and RD groups, the OR of advanced fibrotic stage, using mild fibrotic stage as a reference, was 4.33 (95% CI 1.49–12.63). Reaction strength of all four RIBA bands decreased significantly at the end of follow‐up.

Conclusions:  Anti‐HCV titers decreased annually during long‐term follow‐up after SVR. Higher pretreatment platelet count, interferon regimen and mild fibrosis were associated with decreased anti‐HCV titers. However, only a few cases achieved seroreversion. All RIBA bands decreased significantly after long‐term follow‐up.
Clinical outcomes of radiofrequency ablation and surgical resection for small hepatocellular carcinoma: A meta‐analysis
Authors: Li Le , Zhang Jialin , Liu Xiaohua , Li Xiaohang , Jiao Baoping , Kang Tieli
Published: October 2011

Background and Aim:  To evaluate the evidence comparing radiofrequency ablation (RFA) and surgical resection (RES) on the treatment of hepatocellular carcinoma (HCC) using meta‐analytical techniques.

Methods:  Literature search was undertaken until March 2011 to identify comparative studies evaluating survival rates, recurrence rates, and complications. Pooled odds ratios (OR) and 95% confidence intervals (95% CI) were calculated with either the fixed or random effect model.

Results:  These studies included a total of 877 patients: 441 treated with RFA and 436 treated with RES. The overall survival was significantly higher in patients treated with RES than RFA at 1, 3 and 5 years (respectively: OR: 0.50, 95% CI: 0.29–0.86; OR: 0.51, 95% CI: 0.28–0.94; OR: 0.62, 95% CI: 0.45–0.84). In the RES group the 1, 3, and 5 years recurrence‐free survival rates were significantly higher than the RFA group (respectively: OR: 0.65, 95% CI: 0.44–0.97; OR: 0.65, 95% CI: 0.47–0.89; OR: 0.52, 95% CI: 0.35–0.77). RFA had a higher rate of local recurrence (OR: 4.08, 95% CI: 2.03–8.20). For tumors ≤ 3 cm RES was better than RFA in the 3‐year overall survival rates (OR: 0.38, 95% CI: 0.16–0.89).

Conclusions:  Surgical resection was superior to RFA in the treatment of HCC. However, the findings have to be carefully interpreted due to the lower level of evidence.
Large‐scale randomized clinical study on functional dyspepsia treatment with mosapride or teprenone: Japan Mosapride Mega‐Study (JMMS)
Authors: Hongo Michio , Harasawa Shigeru , Mine Tetsuya , Sasaki Iwao , Matsueda Kei , Kusano Motoyasu , Hanyu Nobuyoshi , Nakada Koji , Shibata Chikashi
Published: October 2011

Background and Aim:  Functional dyspepsia (FD) is a common condition seen in primary gastroenterology practice. The present study was conducted to compare the clinical effectiveness of mosapride and teprenone in patients with FD.

Methods:  Prospective clinical comparative study with random allocation of open labeled medications was performed as a multicenter trial in Japan. 1042 patients presenting symptoms of FD, either with gastric stasis (GSS) and/or epigastric pain (EPS), were enrolled. After initial endoscopic evaluation, medication either with mosapride 5 mg tid or teprenone 50 mg tid was started. Severity and frequency of GSS and EPS, health‐related quality of life (HR‐QOL) by the SF‐36 Japanese version, and patients' compliance to medication was evaluated.

Results:  Organic lesions were found in 90 patients (9%) in the 1027 patients examined by endoscopy. Among those without any specific lesions detected by endoscopy, gastrointestinal symptoms were resolved within one week after the endoscopy in 264 (28%) patients before initiating medication. 618 patients who remained symptomatic were randomized to medication either with mosapride (n = 311) or teprenone (n = 307). Two‐week treatment with mosapride significantly improved GSS and EPS, while teprenone tended to improve only GSS. Mosapride also improved HR‐QOL. 91% of patients treated with mosapride favored their medication, while only 52% of patients treated with teprenone favored their medication.

Conclusions:  Endoscopic evaluation at patients' presentation was effective to find active lesions and to improve FD symptoms. Mosapride was more favorably accepted than teprenone by the patients with sufficient safety and efficacy.
Analysis of aqueous humour proteins in patients with retinoblastoma
Authors: Hadjistilianou Theodora , Giglioni Stefania , Micheli Lavinia , Vannoni Daniela , Brogi Elena , Cevenini Gabriele , Cortelazzo Alessio , De Francesco Sonia , Menicacci Felice , Leoncini Roberto
Published: October 2011

Abstract

Background:  To investigate aqueous humour protein composition from retinoblastoma patients.

Design:  Prospective, hospital‐based study.

Participants:  Eighteen retinoblastoma patients (Reese–Ellsworth stage V or ABC classification group E RB) undergoing ocular enucleation, and 10 normal subjects undergoing cataract surgery. Five of 18 patients presented with associated secondary glaucoma whereas 13 had no secondary glaucoma; 5 of 13 patients with no secondary glaucoma received chemotherapeutical treatment with melphalan.

Methods:  Aqueous humour samples were collected by limbal paracentesis of the anterior chamber after ocular enucleation in patients and after the stab peripheral corneal incision in controls. Total protein concentration according to Bradford method and sodium dodecyl sulphate‐polyacrylamide gel electrophoresis of the samples were performed.

Main Outcome Measure:  Aqueous humour protein concentration.

Results:  Aqueous humour protein concentration was significantly higher in retinoblastoma patients than controls (P < 0.01); patients with secondary glaucoma presented the highest values (P < 0.05 vs. controls); patients treated with melphalan presented a significant decrease (P < 0.01) versus non‐treated; controls did not significantly differ from treated patients. Sodium dodecyl sulphate‐polyacrylamide gel electrophoresis pattern in retinoblastoma patients who did not receive any treatment was very different either from treated or from controls.

Conclusion:  This study represents a preliminary step towards a more accurate two dimensional electrophoresis (2DE) pattern, which will be combined with mass spectrometry analysis to clarify the potential role of specific proteins in tumour development and progression; although these results suggest that aqueous humour protein pattern in retinoblastoma is characteristic, several aspects of the study are still under investigation.
Types of smokers in a community sample of individuals with Type 2 diabetes: a latent class analysis
Authors: Gariepy G. , Malla A. , Wang J. , Messier L. , Strychar I. , Lesage A. , Schmitz N.
Published: October 2011

Diabet. Med. 29, 586–592 (2012)

Aims  Despite the detrimental effects of smoking on their health, a high number of adults with Type 2 diabetes continue to smoke. Identifying distinct types of smokers within this population could help tailor and target intervention programmes. This study examined whether smokers with Type 2 diabetes could be classified into different profiles based on smoking habits, socio‐economic characteristics and lifestyle factors.

Methods  A sample of adults with self‐reported diabetes was selected from random‐digit dialling. Analyses included 383 participants with Type 2 diabetes who were current smokers. Information related to smoking, socio‐economic status, health and lifestyle was collected by phone interview at baseline and 1 year later. Latent class analysis was used to identify subgroups of smokers.

Results  We uncovered three meaningful classes of smokers: class 1, long‐time smokers with long‐standing diabetes (n = 105); class 2, heavy smokers with deprived socio‐economic status, poor health and unhealthy lifestyle characteristics (n = 105); class 3, working and active smokers who were more recently diagnosed with diabetes (n = 173). Members of class 2 were significantly more likely to be disabled and depressed at baseline and 1 year later compared with other classes.

Conclusions  Different profiles of smokers exist among adults with Type 2 diabetes, each suggesting different cessation treatment needs. Distinguishing between these types of smokers may enable clinicians to tailor their approach to smoking cessation.
Effects of variations in duodenal glucose load on glycaemic, insulin, and incretin responses in type 2 diabetes
Authors: Ma J. , Pilichiewicz A. N. , Feinle‐Bisset C. , Wishart J. M. , Jones K. L. , Horowitz M. , Rayner C. K.
Published: October 2011

Diabet. Med. 29, 604–608 (2012)

Aims  Postprandial glucagon‐like peptide‐1 (GLP‐1) secretion and the ‘incretin effect’ have been reported to be deficient in Type 2 diabetes, but most studies have not controlled for variations in the rate of gastric emptying. We evaluated blood glucose, and plasma insulin, GLP‐1 and glucose‐dependent insulinotropic polypeptide (GIP) responses to intraduodenal glucose in Type 2 diabetes, and compared these with data from healthy controls.

Methods  Eight males with well‐controlled Type 2 diabetes, managed by diet alone, were studied on four occasions in single‐blind, randomized order. Blood glucose, and plasma insulin, GLP‐1, and GIP were measured during 120‐min intraduodenal glucose infusions at 1 kcal/min (G1), 2 kcal/min (G2) and 4 kcal/min (G4) or saline control.

Results  Type 2 patients had higher basal (P < 0.0005) and incremental (P < 0.0005) blood glucose responses to G2 and G4, when compared with healthy controls. In both groups, the stimulation of insulin and GLP‐1 by increasing glucose loads was not linear; responses to G1 and G2 were minimal, whereas responses to G4 were much greater (P < 0.005 for each) (incremental area under the GLP‐1 curve 224 ± 65, 756 ± 331 and 2807 ± 473 pmol/l.min, respectively, in Type 2 patients and 373 ± 231, 505 ± 161 and 1742 ± 456 pmol/l.min, respectively, in healthy controls). The GLP‐1 responses appeared comparable in the two groups. In both groups there was a load‐dependent increase in plasma GIP with no difference between them.

Conclusions  In patients with well‐controlled Type 2 diabetes, blood glucose, insulin and GLP‐1 responses are critically dependent on the small intestinal glucose load, and GLP‐1 responses are not deficient.
FINANCIAL EDUCATION AND BEHAVIORAL FINANCE: NEW INSIGHTS INTO THE ROLE OF INFORMATION IN FINANCIAL DECISIONS
Authors: García María José Roa
Published: October 2011

Recent empirical evidence based on surveys and experimental activities within the fields of behavioral finance and financial education has offered economists new empirically based insights into how individuals use information in making financial decisions. Specifically, the importance of information in financial decisions may be reduced or eliminated by psychological aspects of the individual, such as a state of overconfidence that is individual or shared with a group, or by the individual's limited ability to process complex and abundant information. This paper aims to complement this emerging body of literature by studying how individuals perceive and process information when making financial decisions. We review these contributions and suggest a number of broad guidelines that can provide a framework for future discussion of this topic within financial decision theory.
A New QEM for Parametrization of Raster Images
Authors: Yin Xuetao , Femiani John , Wonka Peter , Razdan Anshuman
Published: October 2011

We present an image processing method that converts a raster image to a simplical two‐complex which has only a small number of vertices (base mesh) plus a parametrization that maps each pixel in the original image to a combination of the barycentric coordinates of the triangle it is finally mapped into. Such a conversion of a raster image into a base mesh plus parametrization can be useful for many applications such as segmentation, image retargeting, multi‐resolution editing with arbitrary topologies, edge preserving smoothing, compression, etc. The goal of the algorithm is to produce a base mesh such that it has a small colour distortion as well as high shape fairness, and a parametrization that is globally continuous visually and numerically. Inspired by multi‐resolution adaptive parametrization of surfaces and quadric error metric, the algorithm converts pixels in the image to a dense triangle mesh and performs error‐bounded simplification jointly considering geometry and colour. The eliminated vertices are projected to an existing face. The implementation is iterative and stops when it reaches a prescribed error threshold. The algorithm is feature‐sensitive, i.e. salient feature edges in the images are preserved where possible and it takes colour into account thereby producing a better quality triangulation.
Structural Breaks and the Equilibrium Chinese Yuan/US Dollar Real Exchange Rate: A FEER Approach
Authors: You Kefei , Sarantis Nicholas
Published: October 2011

This paper examines the equilibrium Chinese yuan/US dollar (CNY/USD) real exchange rate within the framework of the fundamental equilibrium exchange rate (FEER) model. Endogenous structural breaks are allowed for in all cointegration relationships. Macroeconomic fundamentals that affect medium‐term savings and investment and hence, the sustainable current account, are also highlighted. A unique set of quarterly data for the post‐reform period (1982–2009) is constructed. This paper finds structural breaks in all trade and the sustainable current account equations. The misalignment rates show that the real exchange rate was overvalued in most years until 2003, followed by undervaluation during 2004–09. However, the average misalignment rates and revaluation required to correct this undervaluation are not as large as suggested by previous studies, with the undervaluation rate declining sharply in 2009. Further, misalignment rates are computed using a sustainable current account of 3%. The findings suggest such exogenous input leads to results biased towards larger undervaluation.
Another Look at the Underlying Cause of the End of the Bretton Woods System: International Price Differences Perspective
Authors: Fukumoto Yukio
Published: October 2011

In this study, the sustainability of the Bretton Woods system from the standpoint of purchasing power parity is discussed. The paper uses wholesale price indexes of the group of seven industrialized countries (G‐7) and examines when persistent price disparities among the countries occurred by applying the panel unit root tests. It is found that the price indexes of G‐7 countries began to diverge in the first half of the 1960s. Evidence from international price differences suggests that the price indexes may have signaled the breakdown of the Bretton Woods system before the inflation rate in the USA accelerated.
Monetary Integration in East Asia: Evidence from Real Effective Exchange Rates
Authors: Sun Wei , Simons Gerald
Published: October 2011

This paper investigates the feasibility of forming a monetary union in East Asia by examining the cointegration and causality of the real effective exchange rates of local currencies. A “pentagon” group of five countries is found—South Korea, the Philippines, Thailand, Indonesia, and Malaysia—which may have potential for success for further monetary integration. Singapore is loosely tied to this group. The Greater China area—China, Hong Kong and Taiwan—does not show any significant degree of integration either internally or externally. Neither a yen bloc nor a US dollar bloc is forming in East Asia.
Minimum Quality Standards and International Trade
Authors: Baltzer Kenneth
Published: October 2011

This paper investigates the impact of a non‐discriminating minimum quality standard (MQS) on trade and welfare when the market is characterized by imperfect competition and asymmetric information. A simple partial equilibrium model of an international Cournot duopoly is presented in which a domestic and a foreign firm are identical except that the foreign firm faces positive transport costs. Asymmetric information generates a market failure, which the government attempts to alleviate with a MQS. It is found that although firms face the exact same costs of compliance, they will generally prefer different levels of regulation. As a result, international trade disputes are likely to arise even when regulation is non‐discriminating.
How Elastic is East Asian Demand for Consumption Goods?
Authors: Thorbecke Willem
Published: October 2011

This paper investigates import demand in East Asia. Estimating exchange rate elasticities for countries in the region is difficult because many imports are used to produce goods for re‐export. An exchange rate appreciation that reduces East Asian exports will also reduce the demand for imported inputs that are used to produce exports. To correct for this bias this paper examines consumption imports, since these goods are intended primarily for the domestic market. Results from several specifications indicate that currency appreciations and increases in income in East Asian countries would significantly increase imports into the region.
Governing Climate Change: Towards a New Paradigm for Risk Regulation
Authors: Heyvaert Veerle
Published: October 2011

This article argues that the ascent of climate change on the EU regulatory agenda signals a new era of risk regulation and calls for the establishment of a new paradigm for risk regulation. Climate change is altering the EU's conception of environmental risks and its design of regulatory responses. In contrast to conventional risk regulation, climate change regulation must prioritise the risks of business‐as‐usual over the risks of change, must target systemic change instead of stability, and must favour the virtues of integration and orchestration over those of individualisation and compartmentalisation. There is an important role for risk regulation scholarship to analyse this shift and its consequences for regulation, such as the relocation of legitimacy needs and the emergence of new risks of regulatory failure. Such an enterprise would both reinvigorate risk regulation scholarship and offer a vital contribution to the European Union as it tackles the momentous challenge of climate change governance.
On Her Majesty's Commercial Service: Bribery, Public Officials and the UK Intelligence Services
Authors: Horder Jeremy
Published: October 2011

“To the instrumentality of commerce alone, the Brittanic Empire is most peculiarly indebted.”

This article sets into context and analyses the justification for committing bribery granted to the intelligence services by section 13 of the Bribery Act 2010. Particularly criticised is the extension of section 13 to include the intelligence services' statutory function of furthering ‘the economic well‐being’ of the UK. In a context in which there are high risks of corruption in forms of export business such as arms trading, it should not be acceptable that it is open to the intelligence services, if need be, to use bribery or related offences to further such business interests on behalf of the UK. More broadly, it is argued that the breadth of section 13 illustrates the moral ambivalence of the UK when it comes to bribery overseas. This is in spite of the strengthening of the law more generally through the Bribery Act 2010, in its application to overseas trade.
Distorting Vicarious Liability
Authors: Morgan Phillip
Published: October 2011

The note considers the decision of the Court of Appeal in Maga v The Trustees of the Birmingham Archdiocese of the Roman Catholic Church and analyses the application of the status based risk approach to vicarious liability in that case. It considers its application outside of the area of clerical sexual abuse, and also the role in vicarious liability of job conferred status which materially increases the risk of the commission of a tort, or helps to facilitate a tort.
UV absorption and scattering properties of inorganic‐based sunscreens
Authors: Egerton Terry A. , Tooley Ian R.
Published: October 2011

Synopsis

This article first introduces the concepts that underlie the calculations of scattering and absorption of light by small particles. Results of Mie theory calculations of light scattering and light absorption by 20, 50 and 100 nm TiO2 and ZnO particles are then presented. As the attenuation, or extinction, by these particles is the sum of the scattering and absorption, the attenuation can then be calculated for wavelengths over the UVA and UVB region. These theoretical results are then shown to be in reasonable agreement with experimental results for alkyl benzoate dispersions of three different types of TiO2 particle whose mean sizes range from 35 to 145 nm. Finally, the link between these measurements and the absorption curves of formulated dispersions of sunscreens are demonstrated and related to in vitro SPF and UVAPF measurements.
Acid treatment effects on the stable isotopic signatures of fossils
Authors: HELLAWELL JO , NICHOLAS CHRIS J.
Published: October 2011

Abstract:  Prior to geochemical analyses, fossil bones and teeth are often extracted from any surrounding lithified sediments using chemical techniques such as immersion in acid. As stable isotope analysis becomes more commonplace in palaeoecological investigations, it is important to consider what effects these chemical preparation techniques may have on any subsequent isotopic data and to constrain these effects as quantitatively as possible. This study aims to elucidate these effects, as it is vital that variability in a data set should not be introduced as a result of protocols used during sample preparation; in addition, it defines the most effective and viable method of carbonate removal for processing bulk fossil samples without causing alteration of their stable isotopic signatures. Various strengths of two weak acids commonly used during palaeontological preparation were tested to evaluate their effects on the δ15N and δ13Corg isotopic signatures of the vertebrae of a large Eocene fossil fish. Changes in the isotopic values occurred over time regardless of which acid was used, each causing a variable response in both δ15N and δ13Corg isotopic values. Without careful monitoring of the acidification process in a controlled environment, any resulting data could therefore confound interpretation. Based on these experiments, it is recommended that 2 m acetic acid be used for the pretreatment of fossils prior to the acquisition of N and C isotope data where carbonate removal is necessary.
Room with a rhinovirus? Blurring the boundaries between research and therapeutic space
Authors: Greenhough Beth
Published: October 2011

In the past, the Declaration of Helsinki insisted on a fundamental distinction between medical research (of no therapeutic benefit) and clinical research (carried out to gain insight into a patient’s condition and inform treatment). However, recent versions of the Helsinki Declaration no longer rehearse this distinction, instead recognising how experimental and clinical practices often and increasingly overlap. This paper argues that this same distinction might also be re‐thought within health geography and that much can be gained through exploring how spaces of health can be simultaneously research laboratory and therapeutic place. This is done in two key ways. Firstly, through an analysis of the Common Cold Unit, a medical research facility based near Salisbury in the UK that recruited volunteers by emphasising its qualities as a rather unusual holiday destination. Secondly, by a review of current work in human geography, medical sociology and anthropology that highlights the blending of research and clinical space. I conclude by considering some of the implications and challenges posed by the mixing of experimental and therapeutic space, with an emphasis on ethics, inequality and care.
Effect of bile duct ligation on bile acid composition in mouse serum and liver
Authors: Zhang Youcai , Hong Ji‐Young , Rockwell Cheryl E. , Copple Bryan L. , Jaeschke Hartmut , Klaassen Curtis D.
Published: October 2011

Background

Cholestatic liver diseases can be caused by genetic defects, drug toxicities, hepatobiliary malignancies or obstruction of the biliary tract. Cholestasis leads to accumulation of bile acids (BAs) in hepatocytes. Direct toxicity of BAs is currently the most accepted hypothesis for cholestatic liver injury. However, information on which bile acids are actually accumulating during cholestasis is limited.

Aim

To assess the BA composition in liver and serum after bile duct ligation (BDL) in male C57Bl/6 mice between 6 h and 14 days and evaluate toxicity of the most abundant BAs.

Results

Bile acid concentrations increased in liver (27‐fold) and serum (1400‐fold) within 6 h after surgery and remained elevated up to 14 days. BAs in livers of BDL mice became more hydrophilic than sham controls, mainly because of increased 6β‐hydroxylation and taurine conjugation. Among the eight unconjugated and 16 conjugated BAs identified in serum and liver, only taurocholic acid (TCA), β‐muricholic acid (βMCA) and TβMCA were substantially elevated representing >95% of these BAs over the entire time course. Although glycochenodeoxycholic acid and other conjugated BAs increased in BDL animals, the changes were several orders of magnitude lower compared with TCA, βMCA and TβMCA. A mixture of these BAs did not cause apoptosis or necrosis, but induced inflammatory gene expression in cultured murine hepatocytes.

Conclusion

The concentrations of cytotoxic BAs are insufficient to cause hepatocellular injury. In contrast, TCA, βMCA and TβMCA are able to induce pro‐inflammatory mediators in hepatocytes. Thus, BAs act as inflammagens and not as cytotoxic mediators after BDL in mice.
Circulating soluble urokinase plasminogen activator is elevated in patients with chronic liver disease, discriminates stage and aetiology of cirrhosis and predicts prognosis
Authors: Zimmermann Henning W. , Koch Alexander , Seidler Sebastian , Trautwein Christian , Tacke Frank
Published: October 2011

Background

Inflammation is a major factor for the progression of chronic liver diseases. Interactions between urokinase plasminogen activator (uPA) and its receptor (uPAR) have been functionally linked to hepatic inflammation and fibrosis in mice. High serum concentrations of soluble uPAR (suPAR) are suggested to reflect activated immune cells.

Aims

We evaluated suPAR serum levels as a diagnostic and prognostic biomarker in patients with chronic liver diseases.

Methods

Prospective, cross‐sectional cohort study of 159 patients with chronic liver diseases (61 without, 98 with established cirrhosis) and 43 healthy controls. Transplant‐free survival was monitored for up to 3 years.

Results

Soluble urokinase plasminogen activator serum concentrations were significantly elevated in patients with chronic liver diseases compared with controls. Cirrhotic patients displayed higher levels than non‐cirrhotics, closely depending on stage of fibrosis or cirrhosis. suPAR levels had high diagnostic power to identify established cirrhosis in chronic liver diseases. Circulating suPAR closely correlated with liver function, fibrosis markers, but also with systemic inflammation and renal function. A distinct suPAR elevation was noticed in patients with alcoholic aetiology of liver disease. suPAR identified alcoholic origin more precisely compared with classical indicators of alcoholism (mean corpuscular volume, gamma glutamyl transpeptidase). Strikingly, elevated suPAR levels were identified as a strong predictor of mortality or need for transplantation. suPAR levels >9 ng/ml indicated adverse prognosis (sensitivity: 70.7%, specificity: 77.8%, relative risk: 8.5; 95% confidence interval: 3.5–20.3).

Conclusions

Serum suPAR is a potential novel biomarker for the diagnosis of cirrhosis, identification of alcoholic origin and for determining prognosis in patients with chronic liver disease.
Lock‐and‐key structural isolation between sibling Drosophila species
Authors: KAMIMURA Yoshitaka , MITSUMOTO Hiroyuki
Published: October 2011

Drosophila santomea Lachaise & Harry, which is endemic to the African island of São Tomé, and its sibling D. yakuba Burla comprise a new model system of speciation. They are morphologically distinguishable only by slight differences in the male genitalia and body coloration. As a previously undescribed difference, the aedeagus of D. yakuba bears a pair of stout spines (the ventral branches of the basal processes (VB)), instead of the paired humps found in D. santomea. Here, we show that this difference works as a lock‐and‐key isolating mechanism between the siblings. During conspecific copulation, D. yakuba females receive the spines in a pair of pocket‐shaped structures, which are protected by hardened plates, in the genitalia. The females of D. santomea, which lack such pockets, are wounded by the spines of the VB when mated with D. yakuba males. This genital mismatching resulted in leakage of the ejaculate, making 80% of the matings infertile and causing a prolonged struggle to separate pairs glued together by the ejaculate.
Childhood Bullying: A Review of Constructs, Concepts, and Nursing Implications
Authors: Liu Jianghong , Graves Nicola
Published: October 2011

Bullying among children as a pervasive problem has been increasingly recognized as an important public health issue. However, while much attention has been given to understanding the impact of bullying on victims, it is equally important to examine predictors of bullying and potential outcomes for bullies themselves. The current literature on bullying lacks consensus on a utilizable definition of bullying in research, which can vary by theoretical framework. In an attempt to bridge the gaps in the literature, this article will provide a review of the state of the science on bullying among children, including the major theoretical constructs of bullying and their respective viewpoints on predictors and correlates of bullying. A secondary aim of this article is to summarize empirical evidence for predictors of bullying and victimization, which can provide strategies for intervention and prevention by public health nursing professionals. By calling attention to the variability in the bullying literature and the limitations of current evidence available, researchers can better address methodological gaps and effectively move toward developing studies to inform nursing treatment programs and enhance public health initiatives that reduce violence in school settings.
Effectiveness of Hand Hygiene Education in a Basic Nursing School Curricula
Authors: Kelcíkova Simona , Skodova Zuzana , Straka Stefan
Published: October 2011

Objectives

Although hand hygiene (HH) is the cheapest and simplest tool for the prevention of hospital‐acquired infections, poor HH compliance has been reported among health care professionals. A variety of factors influence the compliance with HH guidelines, the most important being the quality of the basic nursing education. The aims of this study were to analyze the effectiveness of the basic nursing education in relation to HH, and to explore the skills and attitudes toward HH among nursing students in praxis.

Design and Sample

A mixed‐method approach using a cross‐sectional survey combined with observation and curricular analysis was used. A total of 188 nursing students participated in the study.

Results

Content analysis revealed significant deficits in the quality of HH‐related information in basic nursing educational programs. Our results correlate directly with the reported insufficient levels of HH knowledge and the associated poor HH compliance by students during their training in clinical settings; as shown in observation and questionnaire‐based surveys.

Conclusions

The lack of compliance with HH standards among students lead to poor compliance among health care professionals in praxis. Consequently, the role of educational institutions in the prevention of hospital‐acquired infections is significant, if the effectiveness of HH education is to be improved.
Comparative study of peripheral neuropathy and nerve regeneration in NOD and ICR diabetic mice
Authors: Homs Judit , Ariza Lorena , Pagès Gemma , Verdú Enrique , Casals Laura , Udina Esther , Chillón Miguel , Bosch Assumpció , Navarro Xavier
Published: October 2011

The non‐obese diabetic (NOD) mouse was suggested as an adequate model for diabetic autonomic neuropathy. We evaluated sensory‐motor neuropathy and nerve regeneration following sciatic nerve crush in NOD males rendered diabetic by multiple low doses of streptozotocin, in comparison with similarly treated Institute for Cancer Research (ICR) mice, a widely used model for type I diabetes. Neurophysiological values for both strains showed a decline in motor and sensory nerve conduction velocity at 7 and 8 weeks after induction of diabetes in the intact hindlimb. However, amplitudes of compound muscle and sensory action potentials (CMAPs and CNAPs) were significantly reduced in NOD but not in ICR diabetic mice. Morphometrical analysis showed myelinated fiber loss in highly hyperglycemic NOD mice, but no significant changes in fiber size. There was a reduction of intraepidermal nerve fibers, more pronounced in NOD than in ICR diabetic mice. Interestingly, aldose reductase and poly(ADP‐ribose) polymerase (PARP) activities were increased already at 1 week of hyperglycemia, persisting until the end of the experiment in both strains. Muscle and nerve reinnervation was delayed in diabetic mice following sciatic nerve crush, being more marked in NOD mice. Thus, diabetes of mid‐duration induces more severe peripheral neuropathy and slower nerve regeneration in NOD than in ICR mice.
Evaluation of pre‐existing neuropathy and bortezomib retreatment as risk factors to develop severe neuropathy in a mouse model
Authors: Bruna Jordi , Alé Albert , Velasco Roser , Jaramillo Jessica , Navarro Xavier , Udina Esther
Published: October 2011

Pre‐existing neuropathy, a not uncommon feature in oncologic patients, is a potential but non‐confirmed risk factor to develop early or severe chemotherapy‐induced neuropathy. The main goal of this study is to evaluate the role of pre‐existing neuropathy induced by vincristine (VNC) or bortezomib (BTZ) as a risk factor to develop more severe BTZ‐induced neuropathy in a mouse model. VNC, at doses of 1 and 1.5 mg/kg given twice per week for 4 weeks, induced a moderate and severe sensory‐motor neuropathy, primarily axonal, with predominant involvement of myelinated sensory axons. The neuropathy induced by BTZ at dose of 1 mg/kg given twice per week for 6 weeks was a mild axonal sensory neuropathy involving myelinated and unmyelinated fibers. The neuropathy in mice previously treated and retreated with the same schedule of BTZ after 4 weeks of washout period was similar in profile and severity to the one observed after the first treatment. When basal neuropathy was classified as moderate (most of BTZ‐treated animals) or severe (all VNC‐treated animals and two BTZ‐treated animals), there was a more marked decline in sensory nerve function during BTZ retreatment in the group with basal severe neuropathy (−86%) than in the groups with basal mild (−57%) or without neuropathy (−52%; p < 0.001). Histopathological findings supported the functional results. Therefore, this study shows that the presence of a severe neuropathy previous to treatment with an antitumoral agent, such as BTZ, results in a more marked involvement of peripheral nerves.
Multifocal motor neuropathy is not associated with genetic variation in PTPN22, BANK1, Blk, FCGR2B, CD1A/E, and TAG‐1 genes
Authors: Vlam Lotte , Cats Elisabeth A. , Seelen Meinie , van Vught Paul W.J. , van den Berg Leonard H. , van der Pol W‐Ludo
Published: October 2011

The contribution of genetic heterogeneity to the pathogenesis of multifocal motor neuropathy (MMN) has not been elucidated. We investigated frequencies of single nucleotide polymorphisms (SNPs) in the candidate genes protein tyrosine phosphatase, non‐receptor type 22 (PTPN22), B‐cell scaffold protein with ankyrin repeats (BANK1), B lymphocyte kinase (Blk), and Fc gamma receptor class IIB (FCGR2B), which have been found to be associated with other autoimmune diseases, CD1A and CD1E, important for antigen presentation of glycolipids, and transient axonal glycoprotein 1 (TAG‐1), which is associated with responsiveness to intravenous immunoglobulin in patients with chronic inflammatory demyelinating polyneuropathy. SNP frequencies were determined by means of TaqMan SNP genotyping assay and direct sequencing of candidate genes in 92 Dutch patients with MMN and 1152 healthy controls. SNP frequencies did not differ between patients and controls (all p‐values >0.15) and disease characteristics were not associated with SNP genotypes. Our results suggest that allelic variation in these genes does not play a major role in determining MMN susceptibility.
Activity‐dependent conduction failure: molecular insights
Authors: Park Susanna B. , Lin Cindy S‐Y. , Burke David , Kiernan Matthew C.
Published: October 2011

Weakness and fatigue are commonly encountered symptoms in neurological disorders and significantly impair quality of life. In the case of motor axons, conduction block contributes to weakness and fatigue and may be associated with aberrant nerve activity including fasciculations and cramp. These symptoms result from dysfunction of the constituent channels and pumps of the axonal membrane. In critically conducting axons, impulse conduction can be impaired by the effects of activity or by other mechanisms that produce a significant shift in membrane potential. Conduction failure may be accentuated or relieved by maneuvers that manipulate the time course of the driving current, including the administration of agents that interfere with Na+ channel function. In patients with inflammatory neuropathies, normal activity may be sufficient to precipitate conduction failure at sites of impaired function in multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP). From a clinical perspective, these features are not assessed adequately by conventional neurophysiological techniques. As weakness and fatigue may only develop following activity or exertion, it is useful to assess the effects of impulse trains to determine the extent of conduction failure and the resulting symptoms in neurological patients. These techniques and the physiological mechanisms underlying the development of activity‐dependent hyperpolarization will be critically appraised in this review, with a focus on demyelinating neuropathies, MMN and the neurodegenerative disease, and amyotrophic lateral sclerosis (ALS).
Self‐Reported Alcohol Consumption and the Risk of Alcohol‐Related Problems: A Comparative Risk‐Curve Analysis of the 3 Baltic Countries, Sweden, and Italy
Authors: Landberg Jonas
Published: October 2011

Background:  Previous research has suggested a positive risk‐relationship between volume of consumption and adverse behavioral and social consequences of drinking. However, because the risk‐relationship may be modified by factors such as pattern of drinking, attributes of social drinking contexts, and drunken comportment, the shape of the risk‐function appear to be contingent upon the larger cultural context of drinking.

Methods:  In this article, I use graphical risk‐curve analyses and model estimations to assess how the risk of experiencing alcohol‐related problems is associated with self‐reported volume of alcohol consumption in the 3 Baltic countries (Estonia, Latvia, and Lithuania) as well as Sweden and Italy. The analysis utilized data from 2 general population surveys (including Sweden plus Italy and the Baltic countries, respectively) with approximately 1,000 respondents from each country.

Results:  The risk‐curves for the 3 Baltic countries and Sweden were fairly parallel and clearly steeper than that for Italy. In the logistic regression models, the country‐specific Baltic estimates were not entirely homogenous; for Estonia and Latvia, the estimates were similar to that for Sweden and significantly larger than that for Italy, whereas the estimate for Lithuania did not differ significantly from that for Italy. However, the negative binominal regression models suggested that increasing volume of consumption is associated with the risk of experiencing a larger number of different problems in all 3 Baltic countries and Sweden than in Italy. Overall, the result thus suggests that there is a significant relationship between volume of consumption and risk of experiencing alcohol‐related problems in all countries but that the relationship generally is stronger in the Baltic countries and Sweden than in Italy.

Conclusions:  The results were largely in line with the hypothesis of a European north to south gradient in the strength of the risk‐relationship, but also add that most Baltic countries may be placed alongside the Nordic countries in this context. Because only volume of consumption is considered, the results cannot be used to specify which factors and mechanisms that actually modify the shape of the risk‐function in each culture.
Product Development for the BoP: Insights on Concept and Prototype Development from University‐Based Student Projects in India
Authors: Viswanathan Madhubalan , Sridharan Srinivas
Published: October 2011

In recent years, market‐based approaches have been proposed for the base of the pyramid (BoP). However, the literature offers little theoretical or practical guidelines for innovative product development for what are radically new market contexts for most businesses in advanced economies. Considering that product development is a fundamental activity in a market economy, and that much BoP consumer welfare potentially arises from innovative and affordable goods and services that can solve critical life needs, this is a substantial gap in knowledge. This paper attempts to address this gap by using an analysis of 13 year‐long university projects on BoP‐focused concept and prototype development conducted between 2006 and 2010. An inventory of research propositions is developed that identifies factors necessary for effective product development for BoP markets. Implications for new product development research and practice are discussed.