bluuebunny/crossref_metadata_2025 huggingface dataset:
First steps in experimental cancer evolution
Authors: Taylor Tiffany B. , Johnson Louise J. , Jackson Robert W. , Brockhurst Michael A. , Dash Philip R.
Published: January 2013

Evolutionary processes play a central role in the development, progression and response to treatment of cancers. The current challenge facing researchers is to harness evolutionary theory to further our understanding of the clinical progression of cancers. Central to this endeavour will be the development of experimental systems and approaches by which theories of cancer evolution can be effectively tested. We argue here that the experimental evolution approach – whereby evolution is observed in real time and which has typically employed microorganisms – can be usefully applied to cancer. This approach allows us to disentangle the ecological causes of natural selection, identify the genetic basis of evolutionary changes and determine their repeatability. Cell cultures used in cancer research share many of the desirable traits that make microorganisms ideal for studying evolution. As such, experimental cancer evolution is feasible and likely to give great insight into the selective pressures driving the evolution of clinically destructive cancer traits. We highlight three areas of evolutionary theory with importance to cancer biology that are amenable to experimental evolution: drug resistance, social evolution and resource competition. Understanding the diversity, persistence and evolution of cancers is vital for treatment and drug development, and an experimental evolution approach could provide strategic directions and focus for future research.
Use of General Purpose Graphics Processing Units with MODFLOW
Authors: Hughes Joseph D. , White Jeremy T.
Published: January 2013

To evaluate the use of general‐purpose graphics processing units (GPGPUs) to improve the performance of MODFLOW, an unstructured preconditioned conjugate gradient (UPCG) solver has been developed. The UPCG solver uses a compressed sparse row storage scheme and includes Jacobi, zero fill‐in incomplete, and modified‐incomplete lower‐upper (LU) factorization, and generalized least‐squares polynomial preconditioners. The UPCG solver also includes options for sequential and parallel solution on the central processing unit (CPU) using OpenMP. For simulations utilizing the GPGPU, all basic linear algebra operations are performed on the GPGPU; memory copies between the central processing unit CPU and GPCPU occur prior to the first iteration of the UPCG solver and after satisfying head and flow criteria or exceeding a maximum number of iterations. The efficiency of the UPCG solver for GPGPU and CPU solutions is benchmarked using simulations of a synthetic, heterogeneous unconfined aquifer with tens of thousands to millions of active grid cells. Testing indicates GPGPU speedups on the order of 2 to 8, relative to the standard MODFLOW preconditioned conjugate gradient (PCG) solver, can be achieved when (1) memory copies between the CPU and GPGPU are optimized, (2) the percentage of time performing memory copies between the CPU and GPGPU is small relative to the calculation time, (3) high‐performance GPGPU cards are utilized, and (4) CPU‐GPGPU combinations are used to execute sequential operations that are difficult to parallelize. Furthermore, UPCG solver testing indicates GPGPU speedups exceed parallel CPU speedups achieved using OpenMP on multicore CPUs for preconditioners that can be easily parallelized.
Perihepatic lymph node enlargement is a negative predictor for sustained responses to pegylated interferon‐α and ribavirin therapy for Japanese patients infected with hepatitis C virus genotype 1
Authors: Hikita Hiromi , Enooku Kenichiro , Satoh Yumiko , Yoshida Haruhiko , Nakagawa Hayato , Masuzaki Ryota , Tateishi Ryosuke , Soroida Yoko , Sato Mamiko , Suzuki Atsushi , Gotoh Hiroaki , Iwai Tomomi , Yokota Hiromitsu , Koike Kazuhiko , Yatomi Yutaka , Ikeda Hitoshi
Published: January 2013

Aim

 Although perihepatic lymph node enlargement (PLNE) is reportedly associated with the negative outcome of interferon therapy for chronic hepatitis C, there were limitations in that the results were obtained in patients with various genotypes, viral loads and treatment regimens. We aimed to precisely clarify the significance of PLNE in interferon therapy for chronic hepatitis C.

Methods

 Between December 2004 and June 2005, 112 patients with hepatitis C virus (HCV) genotype 1 and HCV RNA of more than 100 KIU/mL were enrolled, who underwent pegylated interferon‐α plus ribavirin therapy thereafter. PLNE was defined as a perihepatic lymph node of more than 1 cm in the longest axis by ultrasonography.

Results

 The sustained virological response (SVR) rate was lower in patients with PLNE (4/22, 18.2%) than in those without (37/90, 41.1%; P = 0.045) and viral load decline was smaller in patients with PLNE than in those without (P = 0.028). The proportion of PLNE positive patients was the smallest in the SVR group (P = 0.033) among the patient groups divided by the treatment outcome. PLNE was retained as a negative predictor for SVR by multivariate logistic regression analysis (P = 0.012). Furthermore, PLNE was not significantly associated with the mutations at HCV core protein and at interferon sensitivity‐determining region, or interleukin‐28B polymorphism in 45 patients with HCV genotype 1, enrolled between December 2011 and March 2012.

Conclusion

 PLNE is a negative predictor for SVR in patients with HCV genotype 1 and HCV RNA of more than 100 KIU/mL treated with pegylated interferon‐α plus ribavirin, independent of other known predictors for SVR.
Establishment of reference interval for immature platelet fraction
Authors: Ko Y. J. , Kim H. , Hur M. , Choi S. G. , Moon H.‐W. , Yun Y.‐M. , Hong S. N.
Published: January 2013

Introduction

Immature platelet fraction (IPF) is a parameter for reticulated platelets. A high percentage IPF (%‐IPF) is indicative of consumptive or recovering thrombocytopenic disorders in contrast to a low %‐IPF seen in aplastic states. Absolute IPF (A‐IPF) specifically reflects the number of immature platelets in circulation. This study aimed to establish reliable reference intervals for %‐IPF and A‐IPF.

Methods

Except outliers, platelet counts and IPF were determined in 2152 healthy individuals (1252 men and 900 women) and 133 umbilical cord blood from healthy full‐term neonates using XE‐2100 hematology analyzer (Sysmex, Kobe, Japan). The reference intervals for %‐IPF and A‐IPF were defined using nonparametrical percentile methods according to the Clinical and Laboratory Standard Institute (CLSI) guideline.

Results

Platelets,%‐IPF, and A‐IPF all showed nonparametrical distributions. In total individuals, the reference intervals for %‐IPF and A‐IPF were 0.5–3.3% (0.5–3.1% in men; 0.5–3.4% in women) and 1.25–7.02 × 109/L (1.30–6.80 × 109/L in men; 1.21–7.15 × 109/L in women), respectively. The reference intervals for %‐IPF and A‐IPF in umbilical cord blood were 0.7–3.8% and 1.93–9.7 × 109/L, respectively.

Conclusions

This study provides the reference interval for IPF, including %‐IPF and A‐IPF, according to the CLSI guideline. These results could be used as fundamental data for clinical use as well as future researches.
The Achilles' heel of scale service design in social security administration: The case of the United Kingdom's Universal Credit
Authors: Seddon John , O'Donovan Brendan
Published: January 2013

This article takes a critical view of the United Kingdom government's design for the delivery of the Universal Credit (UC) benefit reforms. It is argued that the UC is destined to fail because of the policy's extension into specifying the means (“digital by default”) of delivery for such services. The authors argue that an unseen but ubiquitous set of “scale” management assumptions has been allowed to infiltrate the means by which the government intends to enact its headline policy objective to “make work pay”. Following Seddon's “Vanguard Method”, a practical example of how a better service was designed in a local authority housing benefits service is then examined. Results from this service include being able to deal with up to 50 per cent more demand, with fewer resources, in half the official target time. Finally, the article will conclude with a call for more evidence‐based policy.
The health care system of the People's Republic of China: Between privatization and public health care
Authors: Liu Dongmei , Darimont Barbara
Published: January 2013

Chinese health care policy has undergone numerous reforms in recent years that have often led to new challenges, inciting the need for further reform. The most recent reforms attempt to find a middle path between public health care provision and commercial private insurance. In this way, China is following in the footsteps of countries that initially increased the role of privatization in the 1990s and at the beginning of the 21st century, but are now gearing towards public health care. However, this process of constant reform has led to a lack of transparency in the functioning of the health care system, provoking a loss in public trust. There remains an important degree of uncertainty about the future direction of developments in China. Nonetheless, a dual financing approach to health care using tax finance and social insurance might yet crystallize, offering a potential model to inform developments in other countries.
The View From the Looking Glass: How Are Narcissistic Individuals Perceived by Others?
Authors: Malkin Mallory L. , Zeigler‐Hill Virgil , Barry Christopher T. , Southard Ashton C.
Published: January 2013

Previous studies have found that narcissistic individuals are often viewed negatively by those who know them well. The present study sought to extend these previous findings by examining whether normal and pathological aspects of narcissism were associated with perceiver ratings of narcissistic characteristics and aggression. This was accomplished by having each of our undergraduate participants (288 targets) recruit friends or family members to complete ratings of the target who recruited them (1,296 perceivers). Results revealed that perceived entitlement was strongly associated with perceived aggression. Further, self‐reported levels of pathological narcissism moderated these results such that vulnerable narcissism exacerbated the association between perceived entitlement and aggression, whereas grandiose narcissism mitigated the association. The discussion will focus on the implications of these results for understanding the various features of narcissism.
The role of oral language in ­underpinning the text generation ­difficulties in children with specific ­language impairment
Authors: Dockrell Julie E. , Connelly Vincent
Published: January 2013

Children with specific language impairments (SLI) have difficulties in producing written text. It was hypothesised that the constraints on writing in children with SLI were similar to typically developing younger children with the same level of vocabulary knowledge. Twenty‐three children with SLI (aged 10:5) were matched with 23 children for chronological age (CA) and 23 children for vocabulary levels (VC). Children with SLI performed significantly below their CA peers but not their VC peers on all aspects of writing including spelling. Regression analyses indicated that written text measures of spelling errors and oral language measures of vocabulary were significant predictors of writing products for both the children with SLI and their VC peers. This highlights the importance of oral and written language for the quality of children's written text and indicates that the writing of children with SLI was commensurate with their vocabulary and spelling levels. The results point to the role of both phonological and non‐phonological processes in written text production in struggling writers.
Effects of community structure on the species–area relationship in China's forests
Authors: Qiao Xiujuan , Tang Zhiyao , Wang Shaopeng , Liu Yining , Fang Jingyun
Published: January 2013

The species–area relationship (SAR) is the oldest and most frequently documented law in ecology. In a community, the SAR is regulated by the abiotic environment and biotic interactions and depends on the individual–spatial distribution of species (ISD) and the species–abundance distribution (SAD). In this study, we explored the effects of aggregation of ISDs and unevenness of SADs on SARs in forests of China by comparing the empirical and simulated SARs of 32 nested plots distributed along an extensive latitudinal gradient. Both aggregation and unevenness affected the shape of SARs significantly: ISDs accounted for 12.6 ± 4.0% of the incremental increase in species richness with area, and SADs accounted for 18.7 ± 3.8 and 23.5 ± 3.9% under the broken‐stick model and even abundance model, respectively. Effects of both aggregation and unevenness decreased as temperature increased, suggesting that individuals of a species were spatially more aggregated than random, and the individuals among species were more discrepant from the null distribution (broken‐stick model and even abundance model in this study), in the cold than in the warm areas. Taken together, our results demonstrate that ISDs and SADs within communities can shape SARs, but these effects vary along latitudinal gradients, and are likely mediated by temperature.
Clinical behaviour and long‐term therapeutic response in orofacial granulomatosis patients treated with intralesional triamcinolone acetonide injections alone or in combination with topical pimecrolimus 1%
Authors: Mignogna Michele D. , Pollio Annamaria , Leuci Stefania , Ruoppo Elvira , Fortuna Giulio
Published: January 2013

Background:  Orofacial granulomatosis (OFG) is a relapsing inflammatory disorder of unknown aetiology and non‐standardized treatment protocols. The aim of this study was to assess the clinical behaviour and long‐term therapeutic response in OFG patients treated with intralesional triamcinolone acetonide (TA) injections alone or in combination with topical pimecrolimus 1%, as adjuvant, in those patients partially responders to TA.

Methods:  We analysed data from 19 OFG patients followed‐up for 7 years. Demographic characteristics, clinical behaviour and long‐term therapeutic response were investigated.

Results:  Eleven (57.9%) OFG patients treated with intralesional TA injections therapy reached first complete clinical remission in a mean time of 10 ± 2.2 (95% CI, 8.5–11.5) weeks, while eight (42.1%) patients, partially responders to intralesional TA injections, were treated with TA injections plus topical pimecrolimus 1%, as adjuvant, achieving complete clinical remission in a mean time of 29.8 ± 7.8 (95% CI, 23.2–36.3) weeks. Relapses occurred in four TA responder patients with a disease‐free time of 35.8 ± 8.7 (95% CI, 21.9–46.4) weeks and in five patients treated with TA and topical pimecrolimus 1% with a disease‐free time of 55.8 ± 18.5 (95% CI, 32.8–78.8) weeks. Patients were followed‐up for a mean time of 56.3 ± 18.2 (95% CI, 47.6–65.1) months. At last control, all 19 patients were in complete clinical remission.

Conclusion:  These preliminary data suggest that intralesional TA injections still represent a mainstay in the treatment of OFG. It is unclear the role of topical pimecrolimus, as adjuvant, in leading OFG patients, partly responders to intralesional TA injections, to a complete clinical remission.
The extra‐large light‐gas gun of the Fraunhofer EMI: Applications for impact cratering research
Authors: LEXOW B. , WICKERT M. , THOMA K. , SCHÄFER F. , POELCHAU M. H. , KENKMANN T.
Published: January 2013

Abstract– The extra‐large light‐gas gun (XLLGG) at the Fraunhofer Ernst‐Mach‐Institut (EMI, Efringen‐Kirchen, Germany) is a two‐stage light‐gas gun that can accelerate projectile masses of up to 100 g up to velocities of 6 km s−1. The accelerator’s set‐up allows various combinations of pump and launch tubes for applications in different fields of hypervelocity impact research. In the framework of the MEMIN (Multidisciplinary Experimental and Modeling Impact Research Network) program, the XLLGG is used for mesoscale cratering experiments with projectiles made of steel and of iron meteorites, and targets consisting of sandstone and other rocks. The craters produced with this equipment reach a diameter of up to 40 cm, a size unique in laboratory cratering research. With the implementation of neural networks, the acceleration process is being optimized, currently yielding peak velocities of 7.8 km s−1 for a 100 g projectile. Here, we summarize technical aspects of the XLLGG.
Male courtship preferences demonstrate discrimination against allopatric colour morphs in a cichlid fish
Authors: Zoppoth P. , Koblmüller S. , Sefc K. M.
Published: January 2013

Whether premating isolation is achieved by male‐specific, female‐specific or sex‐independent assortative preferences often depends on the underlying evolutionary processes. Here we test mate preferences of males presented with females of different allopatric colour variants of the cichlid fish Tropheus sp., a Lake Tanganyika endemic with rich geographical colour pattern variation, in which the strength of sexual isolation varies between populations. We conducted two‐way mate choice experiments to compare behaviour of males of a red‐bodied morph (population Moliro) towards females from their own population with behaviour towards females from four allopatric populations at different stages of phylogenetic and phenotypic divergence. Males courted same‐population females significantly more intensely than females of other populations, and reduced their heteromorphic courtship efforts both with increasing genetic and increasing phenotypic distinctness of the females. In particular, females of a closely related red‐bodied population received significantly more courtship than either genetically distinct, similarly coloured females (‘Kirschfleck’ morph) or genetically related, differently coloured females (‘yellow‐blotch’ morph), both of which were courted similarly. Genetically and phenotypically distinct females (Tropheus polli) were not courted at all. Consistent with previous female‐choice experiments, female courtship activity also decreased with increasing genetic distance from the males’ population. Given successful experimental and natural introgression between colour morphs and the pervasive allopatry of related variants, we consider it unlikely that assortative preferences of both sexes were driven by direct selection during periods of secondary contact or, in turn, drove colour pattern differentiation in allopatry. Rather, we suggest that sexual isolation evolved as by‐product of allopatric divergence.
Non‐alcoholic fatty liver disease as an independent manifestation of the metabolic syndrome: Results of a US national survey in three ethnic groups
Authors: Smits Mark M , Ioannou George N , Boyko Edward J , Utzschneider Kristina M
Published: January 2013

Background and Aim

The metabolic syndrome (MetS) and each of its components are strongly associated with non‐alcoholic fatty liver disease (NAFLD). This has led many investigators to suggest that NAFLD is an independent component of the MetS. We formally tested this hypothesis using confirmatory factor analysis, which allows comparison of different models, with or without including NAFLD as a component of the MetS.

Methods

We analyzed data from 3846 subjects of the Third National Health and Nutrition Examination Survey (1988–1994). NAFLD was defined by increased liver fat measured by ultrasonography.

Results

MetS by Adult Treatment Panel III criteria was present in 20.5%, and 30.2% had NAFLD, defined as mild, moderate, or severe ultrasonographic steatosis. Using confirmatory factor analysis, a basic model representing the MetS using its currently accepted components (glucose, waist, triglyceride/high‐density lipoprotein ratio, and mean arterial pressure) showed excellent goodness‐of‐fit statistics. Addition of NAFLD to the model as a fifth independent variable decreased model fit, suggesting that NAFLD is not an additional independent component of the MetS. Analysis by ethnicity showed that addition of NAFLD decreased model fit in Whites but resulted in minor improvements in non‐Hispanic Blacks and Mexican Americans.

Conclusions

The MetS is strongly associated with NAFLD. However, we found no evidence that NAFLD is an independent component or manifestation of the MetS. Interestingly, ethnic differences might be important in this relationship and require further study.
Striatal CB1 and D2 receptors regulate expression of each other, CRIP1A and delta opioid systems
Authors: Blume Lawrence C. , Bass Caroline E. , Childers Steven R. , Dalton George D. , Roberts David C. S. , Richardson Jasmine M. , Xiao Ruoyu , Selley Dana E. , Howlett Allyn C.
Published: January 2013

Although biochemical and physiological evidence suggests a strong interaction between striatal CB1 cannabinoid (CB1R) and D2 dopamine (D2R) receptors, the mechanisms are poorly understood. We targeted medium spiny neurons of the indirect pathway using shRNA to knockdown either CB1R or D2R. Chronic reduction in either receptor resulted in deficits in gene and protein expression for the alternative receptor and concomitantly increased expression of the cannabinoid receptor interacting protein 1a (CRIP1a), suggesting a novel role for CRIP1a in dopaminergic systems. Both CB1R and D2R knockdown reduced striatal dopaminergic‐stimulated [35S]GTPγS binding, and D2R knockdown reduced pallidal WIN55212‐2‐stimulated [35S]GTPγS binding. Decreased D2R and CB1R activity was associated with decreased striatal phosphoERK. A decrease in mRNA for opioid peptide precursors pDYN and pENK accompanied knockdown of CB1Rs or D2Rs, and over‐expression of CRIP1a. Down‐regulation in opioid peptide mRNAs was followed in time by increased DOR1 but not MOR1 expression, leading to increased [D‐Pen2, D‐Pen5]‐enkephalin‐stimulated [35S]GTPγS binding in the striatum. We conclude that mechanisms intrinsic to striatal medium spiny neurons or extrinsic via the indirect pathway adjust for changes in CB1R or D2R levels by modifying the expression and signaling capabilities of the alternative receptor as well as CRIP1a and the DELTA opioid system.
How to optimize HCV therapy in genotype 1 patients: predictors of response
Authors: Petta Salvatore , Craxì Antonio
Published: January 2013

The advent of triple therapy (TT) with first‐generation protease inhibitors boceprevir (BOC) and telaprevir (TVR) in addition to pegylated interferon and ribavirin (PEG‐IFN/RBV) has resulted in a significant improvement in the sustained virological response (SVR) rate and potentially in life years gained compared to dual therapy (DT), when treating naïve or treatment‐experienced patients with genotype 1 (G1) chronic hepatitis C (CHC). This benefit is partly offset by the increased complexity of treatment, and the increased costs and risks of therapy, making it necessary to optimize the indications for TT. Naïve patients with mild fibrosis and the IL28B CC polymorphism and/or with a rapid virological response (RVR) to DT can still benefit from DT, while TT is preferable in all others. Phase 3 trials have clearly shown that a 1 log10 decrease in HCVRNA after 4 weeks of DT associated with a favourable IL28B genotype and a low stage of fibrosis, and a pattern of previous response to DT in treatment‐experienced patients are the strongest predictors of an SVR to TT. Moreover, an extended rapid virological response (eRVR) is associated with an SVR rate >90%, so that the overall duration of treatment can be shortened in a high proportion of patients. Further efforts to optimize the current TT regimens both by increasing efficacy and improving tolerance are still needed. Most important, in the future, treatment can probably be personalized based on data from post‐marketing surveillance of TT providing information about patient groups that were underrepresented in phase 3 studies such as those with cirrhosis.
How to optimize HCV therapy in genotype 2 patients
Authors: Grassi Eleonora , Aghemo Alessio
Published: January 2013

Hepatitis C Virus (HCV) Genotype 2 accounts for 10% of the patients with chronic HCV worldwide. The current standard of care (SOC) in these patients is 24 weeks of Pegylated Interferon (PEG‐IFN) plus Ribavirin (RBV), with sustained virological response rates (SVR) of 80–90%. However, there are subgroups of patients with HCV‐2, such as those with advanced fibrosis/cirrhosis, in whom SVR rates are still suboptimal, and highly responsive groups in whom SVR rates reach 95%. Treatment optimization is necessary to maximize efficacy in the former group and reduce treatment‐related side effects in the latter. Unfortunately, any attempt to modify the duration or dosing of the SOC according to baseline factors has been disappointing and should not be continued at present. On the other hand on‐treatment HCV RNA kinetics are fundamental for individualized treatment regimens because achieving negative HCV RNA at week 4 (rapid virological response, RVR) is the key factor when the duration of PEG‐IFN/RBV is tailored in HCV‐2 patients. Several studies have shown that treatment can be shortened to 16 weeks in HCV‐2 patients with a RVR, without increasing the risk of post‐treatment relapse, thus increasing tolerance to treatment while reducing healthcare costs. On the other hand, patients who do not achieve a RVR correspond to a population of difficult‐to‐cure HCV‐2 patients who need alternative treatment strategies which are not yet available.
Impact of therapy on the outcome of chronic hepatitis B
Authors: Liaw Yun‐Fan
Published: January 2013

Chronic hepatitis B virus (HBV) infection is a dynamic state in which HBV replication is the key driving force of disease progression, resulting in the development of hepatic decompensation, cirrhosis and hepatocellular carcinoma (HCC). The primary aim of therapy is to eliminate or suppress HBV to reduce the activity of hepatitis thus reducing the risk of or slowing the progression of liver disease. Treatment with nucleos(t)ide analogues (Nuc) may result in rapid suppression of HBV replication with normalization of serum transaminases and restore liver function thus increasing survival in patients with hepatic decompensation. The long‐term benefits of a finite course of interferon α (IFN) therapy include a sustained and cumulative response, as well as a reduction in the progression of fibrosis and in the development of cirrhosis and/or HCC. Long‐term Nuc therapy may also result in histological improvement or reversal of advanced fibrosis and reduction in disease progression including the development of HCC. Hepatitis B surface antigen (HBsAg) seroclearance, a status close to a “cure”, may also occur in patients with a sustained or maintained viral response, especially in those with IFN‐based therapy. Pegylated IFN (PEG‐IFN) and newer Nucs may have even better long‐term outcomes because of improved efficacy and/or a low risk of drug resistance. However, treatment outcomes are still far from satisfactory. The development of more effective and safe but affordable anti‐HBV agents/strategies is needed to further improve outcomes.
New therapeutic strategies in HCV: second‐generation protease inhibitors
Authors: Clark Virginia C. , Peter Joy A. , Nelson David R.
Published: January 2013

Telaprevir and boceprevir are the first direct‐acting antiviral agents approved for use in HCV treatment and represent a significant advance in HCV therapy. However, these first‐generation drugs also have significant limitations related to thrice‐daily dosing, clinically challenging side‐effect profiles, low barriers to resistance and a lack of pan‐genotype activity. A second wave of protease inhibitors are in phase II and III trials and promise to provide a drug regimen with a better dosing schedule and improved tolerance. These second‐wave protease inhibitors will probably be approved in combination with PEG‐IFN and Ribavirin (RBV), as well as future all‐oral regimens. The true second‐generation protease inhibitors are in earlier stages of development and efficacy data are anxiously awaited as they may provide pan‐genotypic antiviral activity and a high genetic barrier to resistance.
Best strategies for global HCV eradication
Authors: Hagan Liesl M. , Schinazi Raymond F.
Published: January 2013

Worldwide eradication of hepatitis C virus (HCV) is possible through a combination of prevention education, universal clinical and targeted community screening, effective linkage to care and treatment with promising new direct‐acting antiviral drug regimens. Universal screening should be offered in all healthcare visits, and parallel community screening efforts should prioritize high‐prevalence, high‐transmission populations including injection drug users, prison inmates and those with HIV/HCV co‐infection. Increasing awareness of HCV infection through screening, improving treatment uptake and cure rates by providing linkage to care and more effective treatment, and ultimately combining education efforts with vaccination campaigns to prevent transmission and reinfection can slow and eventually stop the ‘silent epidemic’.
Optimal management of chronic hepatitis B patients with treatment failure and antiviral drug resistance
Authors: Zoulim Fabien , Locarnini Stephen
Published: January 2013

The management of treatment failure in patients with chronic hepatitis B, remains a clinical concern. Incomplete viral suppression and the emergence of drug resistance are key determinants of treatment failure. The correct choice of a potent first‐line therapy to achieve sustained long‐term suppression of viral replication provides the best chance of preventing treatment failure and drug resistance. Clinical studies have demonstrated that drugs with a high barrier to resistance have significantly lower rates of resistance compared with those with a low barrier to resistance. Management of treatment failure requires precise clinical and virological monitoring as well as early treatment intervention with appropriate noncross‐resistant antivirals. Long‐term surveillance of treatment efficacy and possible emergence of drug resistance is necessary in patients who have been sequentially treated with multiple antivirals. The identification of novel treatment targets remains a major research goal to improve the efficacy of current antiviral therapy through combination therapy regimens.
Treatment of HBV related cirrhosis
Authors: van Bömmel Florian , Berg Thomas
Published: January 2013

Until very recently, hepatitis B virus (HBV)‐associated cirrhosis was often regarded as an irreversible condition. It is associated with strongly increased mortality and a high risk of the development of hepatocellular carcinoma (HCC). Indeed, the incidence of HCC per 100 person years was shown to be 2–3.7 in patients with cirrhosis compared with only 0.3–0.6 in patients with active hepatitis B without cirrhosis and 0.02–0.2 in asymptomatic carriers. Liver transplantation was considered to be the only medical intervention, which could resolve this condition and which could improve the general condition of these patients. However, it is now becoming increasingly evident that long‐term suppression of viral replication allows the regenerative potential of the liver to reverse even high grade liver fibrosis. For the management of HBV‐related cirrhosis, it is therefore important to provide effective treatment and to identify and avoid risk factors for the development of cirrhosis and hepatic decompensation.
Treatment of HBeAg positive chronic hepatitis B: interferon or nucleoside analogues
Authors: Dusheiko Geoffrey
Published: January 2013

Interferon alpha has restricted efficacy in as much as only a proportion of patients show a response. However, in appropriately selected HBeAg‐positive and HBeAg‐negative patients, sustained suppression of viral replication can be achieved, and HBeAg or even HBsAg seroconversion can be attained. Thus, finite course of interferon alpha can be successful, and offer an advantage to patient. Interferon (IFN) remains a benchmark therapy for chronic hepatitis B. The main advantages of IFN‐α over nucleoside analogues are the absence of resistance and the possibility of immune‐mediated clearance of hepatitis B. Unfortunately, side effects preclude the use of interferon alpha in substantial proportions of patients, and prolonged maintenance therapy to suppress hepatitis B virus (HBV) is not feasible. Nucleoside analogues are given by mouth, once per day, and the safety, potency and efficacy have improved and facilitated treatment. However, maintenance of long‐term suppression is required for the majority of patients. In general, treatment of chronic hepatitis B should target patients with active disease and viral replication, preferably before the signs and symptoms of cirrhosis or significant injury has occurred. Current EASL guidelines suggest that treatment be based on the evaluation of three criteria: Serum aminotransferase levels, serum HBV DNA levels and histological grade and stage. Many questions remain unanswered on the optimal treatment of patients with chronic hepatitis B with a nucleoside vs interferon alpha. Both forms of treatment have benefits and the choice should be selected and tailored. Stopping or futility rules can be implemented in patients who fail interferon. Recent data suggest the safety and efficacy of nucleoside analogues in the third trimester of pregnancy to reduce the risk of transmission from mothers to their children.
Application of nondestructive testing methods to study the damage zone underneath impact craters of MEMIN laboratory experiments
Authors: MOSER Dorothee , POELCHAU Michael H. , STARK Florian , GROSSE Christian
Published: January 2013

Abstract– Within the framework of the Multidisciplinary Experimental and Modeling Impact Research Network (MEMIN) research group, the damage zones underneath two experimentally produced impact craters in sandstone targets were investigated using several nondestructive testing (NDT) methods. The 20 × 20 × 20 cm sandstones were impacted by steel projectiles with a radius of 1.25 mm at approximately 5 km s−1, resulting in craters with approximately 6 cm diameter and approximately 1 cm depth. Ultrasound (US) tomography and vibrational analysis were applied before and after the impact experiments to characterize the damage zone, and micro‐computer tomography (μ‐CT) measurements were performed to visualize subsurface fractures. The newly obtained experimental data can help to quantify the extent of the damage zone, which extends to about 8 cm depth in the target. The impacted sandstone shows a local p‐wave reduction of 18% below the crater floor, and a general reduction in elastic moduli by between approximately 9 and approximately 18%, depending on the type of elastic modulus. The results contribute to a better empirical and theoretical understanding of hypervelocity events and simulations of cratering processes.
Phylogeography of the widespread African puff adder (Bitis arietans) reveals multiple Pleistocene refugia in southern Africa
Authors: Barlow Axel , Baker Karis , Hendry Catriona R. , Peppin Lindsay , Phelps Tony , Tolley Krystal A. , Wüster Catharine E. , Wüster Wolfgang
Published: January 2013

Evidence from numerous Pan‐African savannah mammals indicates that open‐habitat refugia existed in Africa during the Pleistocene, isolated by expanding tropical forests during warm and humid interglacial periods. However, comparative data from other taxonomic groups are currently lacking. We present a phylogeographic investigation of the African puff adder (Bitis arietans), a snake that occurs in open‐habitat formations throughout sub‐Saharan Africa. Multiple parapatric mitochondrial clades occur across the current distribution of B. arietans, including a widespread southern African clade that is subdivided into four separate clades. We investigated the historical processes responsible for generating these phylogeographic patterns in southern Africa using species distribution modelling and genetic approaches. Our results show that interior regions of South Africa became largely inhospitable for B. arietans during glacial maxima, whereas coastal and more northerly areas remained habitable. This corresponds well with the locations of refugia inferred from mitochondrial data using a continuous phylogeographic diffusion model. Analysis of data from five anonymous nuclear loci revealed broadly similar patterns to mtDNA. Secondary admixture was detected between previously isolated refugial populations. In some cases, this is limited to individuals occurring near mitochondrial clade contact zones, but in other cases, more extensive admixture is evident. Overall, our study reveals a complex history of refugial isolation and secondary expansion for puff adders and a mosaic of isolated refugia in southern Africa. We also identify key differences between the processes that drove isolation in B. arietans and those hypothesized for sympatric savannah mammals.
Comparison of the 308‐nm excimer laser with the 308‐nm excimer lamp in the treatment of vitiligo – a randomized bilateral comparison study
Authors: Shi Qiong , Li Kai , Fu Jun , Wang Yanchun , Ma Cuiling , Li Qiang , Li Chunying , Gao Tianwen
Published: January 2013

Background

Vitiligo is an acquired pigment disorder characterized by areas of depigmented skin resulting from the loss of epidermal melanocytes. Recently, several investigations have documented the benefits of excimer phototherapy (e.g., using the 308‐nm excimer laser or the 308‐nm excimer lamp) for the treatment of vitiligo.

Aim

To compare the effectiveness of the 308‐nm excimer laser with the 308‐nm excimer lamp in the treatment of vitiligo patients.

Methods

This intervention study was designed as a randomized self‐control trial. Fourteen subjects with 48 symmetrical vitiligo lesions were enrolled in this study. One lesion was treated with the 308‐nm excimer laser, and its counterpart was treated with the 308‐nm excimer lamp. Lesions were treated three times a week with the same dose on both sides for a total of 20 sessions.

Results

All of the patients completed the study, and 48 lesions were treated. The two treatments exhibited similar results in terms of repigmentation.

Conclusions

The 308‐nm excimer lamp and the 308‐nm excimer laser exhibited similar efficacies in treating vitiligo.
Cryopreservation of Zona‐Free Cloned Buffalo (Bubalus Bubalis) Embryos: Slow Freezing vs Open‐Pulled Straw Vitrification
Authors: Sirisha K , Selokar NL , Saini M , Palta P , Manik RS , Chauhan MS , Singla SK
Published: January 2013

Contents

This study was carried out to compare the post‐thaw cryosurvival rate and the level of apoptosis in vitro produced zona‐free cloned buffalo blastocysts subjected to slow freezing or vitrification in open‐pulled straws (OPS). Zona‐free cloned embryos produced by handmade cloning were divided into two groups and were cryopreserved either by slow freezing or by vitrification in OPS. Cryosurvival of blastocysts was determined by their re‐expansion rate following post‐thaw culture for 22–24 h. The post‐thaw re‐expansion rate was significantly (p < 0.05) higher following vitrification in OPS (71.2 ± 2.3%) compared with that after slow freezing (41.6 ± 4.8%). For examining embryo quality, the level of apoptosis in day 8 frozen‐thawed blastocysts was determined by TUNEL staining. The total cell number was not significantly different among the control non‐cryopreserved cloned embryos (422.6 ± 67.8) and those cryopreserved by slow freezing (376.4 ± 29.3) or vitrification in OPS (422.8 ± 36.2). However, the apoptotic index, which was similar for embryos subjected to slow freezing (14.8 ± 2.0) or OPS vitrification (13.3 ± 1.8), was significantly (p < 0.05) higher than that for the control non‐cryopreserved cloned embryos (3.4 ± 0.6). In conclusion, the results of this study demonstrate that vitrification in OPS is better than slow freezing for the cryopreservation of zona‐free cloned buffalo blastocysts because it offers a much higher cryosurvival rate.
Experiencing malevolent voices is associated with attentional dysfunction in psychotic patients
Authors: KRÅKVIK BODIL , STILES TORE , HUGDAHL KENNETH
Published: January 2013

Inattention in people with schizophrenia is common. However, there has been little research on the association between inattention and auditory hallucinations. The aim of the study was to investigate how inattention is affected by beliefs about voices as benevolent and malevolent and perceived control of voices. A total of 31 patients who experienced auditory hallucinations and who met the criteria for schizophrenia or other psychosis completed the attention subscale of the Scale for the Assessment of Negative Symptoms (SANS) and the Connors’ Continuous Performance Test II (CCPT‐II). The revised Beliefs About Voices Questionnaire (BAVQ‐R) was used to assess malevolent and benevolent beliefs about voices, and severity of auditory hallucinations (the Psychotic Symptom Rating Scales; PSYRATS) was used to assess perceived control of voices and frequency of voices. Levels of depression (the Beck Depression Inventory; BDI), anxiety (the Beck Anxiety Inventory; BAI), severity of overall psychiatric symptoms (the Brief Psychiatric Rating Scale; BPRS), and severity of negative symptoms (SANS) were assessed to control for their potential confounding effects. The relations between the variables were explored with correlations and multiple hierarchical regression analyses. The results indicated that more malevolent, but not more benevolent, beliefs about voices predicted lower levels of attention, independently of general psychiatric symptoms and various other psychotic symptoms such as frequency of and perceived control of voices. These findings suggest an important relationship between malevolent beliefs about voices and levels of inattention. The possible impact of changing beliefs about voices to improve attentional functioning is discussed.
Occupational Change and Mobility Among Employed and Unemployed Job Seekers
Authors: Longhi Simonetta , Taylor Mark
Published: January 2013

We use data from the Labour Force Survey to show that employed and unemployed job seekers in Great Britain originate from different occupations and find jobs in different occupations. We find substantial differences in occupational mobility between job seekers: employed job seekers are most likely to move to occupations paying higher average wages relative to their previous occupation, while unemployed job seekers are most likely to move to lower paying occupations. Employed and unemployed job seekers exhibit different patterns of occupational mobility and, therefore, do not accept the same types of jobs.
English for Bible and Theology: Understanding and Communicating Theology Across Cultural and Linguistic Barriers
Authors: Pierson Cheri , Bankston Will
Published: January 2013

This article introducesEnglish forBible and Theology (EBT), an inherently interdisciplinary field that mergesEnglish language learning with the content of biblical and theological studies in a context that is, by nature, cross‐cultural. Within this collaboration there exists the possibility not only to enable theological study, but also to enhance it through a focus on personal meaning and its communication, both of which are foundational to the communicative language classroom. That is,EBTseeks both to aid students worldwide in attaining the specialized language and cultural proficiency necessary to accessEnglish theological resources and to provide a community in which students can connect theological content to their lives. It is this second aim that providesEBTits relevance across a range of theological contexts, as nativeEnglish‐speaking students likewise stand to benefit from the application ofEBT's principles.
From Classroom to Controversy: Conflict in the Teaching of Religion
Authors: Neal Lynn S.
Published: January 2013

What happens when a class assignment becomes a source of controversy? How do we respond? What do we learn? By describing the controversy surrounding an assignment on religion and representation, this article examines conflict's productive role in teaching about New Religious Movements (NRMs) and religion. It suggests that we consider how our personal and institutional dispositions toward conflict influence our pedagogies. Moreover, it urges us to consider how teaching conflicts within and/or between disciplines can enhance our learning objectives and stimulate students' ability to think critically.
Financial Integration in East Asia: An Empirical Investigation
Authors: Lee Hyun‐Hoon , Huh Hyeon‐Seung , Park Donghyun
Published: January 2013

The central objective of this paper is to empirically evaluate the degree of linkages among East Asian equity and bond markets. Using data from the IMF’s Coordinated Portfolio Investment Survey (CPIS), we find that intra‐East Asian financial asset holdings of four East Asian countries – Japan, Korea, Hong Kong and Singapore – are larger than the levels predicted by the financial gravity model. However, our analysis suggests that this result is likely to be driven by intra‐regional trade linkages and reflect those linkages. Therefore, the salient implication for regional policymakers is that they should continue to promote intra‐regional financial integration. This paper also aims to analyse the impact of three different types of country‐specific risks – political, economic and financial risks – on investment from the four countries. This analysis yields a clear positive relationship between destination‐country risk, in particular political risk, and capital inflows.
Restrictive orbital myofibroblastic sarcoma in a cat – Cross‐sectional imaging (MRI&CT) appearance, treatment, and outcome
Authors: Thomasy Sara M. , Cissell Derek D. , Arzi Boaz , Vilches‐Moure Jose G. , Lo Winnie Y. , Wisner Erik R. , Dubielzig Richard R. , Maggs David J.
Published: January 2013

A 16‐year‐old spayed female cat was evaluated for lagophthalmos and chronic exposure keratitis in both eyes. Ophthalmic examination revealed upper and lower eyelid entropion of the left eye (OS) and markedly decreased retropulsion, restricted eye movement, marked episcleral congestion, and severe keratitis of both eyes (OU). Magnetic resonance imaging of both orbits revealed extensive, irregular, contrast‐enhancing tissue without evidence of osteolysis considered compatible with diffuse inflammatory tissue. Feline herpesvirusDNAwas not detected in conjunctival samples. Partial temporary tarsorrhaphies were placedOU, and the cat was treated with topically administered erythromycin ointmentOU, orally administered famciclovir and prednisolone, and sublingually administered buprenorphine. Little improvement was noted after 2 weeks. Six weeks after initial presentation, a left exenteration was performed and histopathology was consistent with idiopathic sclerosing orbital pseudotumor (ISOP). Ten weeks after initial presentation, the patient represented for weight loss and jaw pain. Computed tomography demonstrated disease progression in the right orbit and the patient was euthanized. Histopathology of the decalcified skull revealed an aggressive and highly infiltrative mass involving the right orbit with extension to the maxilla, hard palate, nasal cavity and gingiva most consistent with feline restrictive orbital myofibroblastic sarcoma (FROMS). Clinical data from this patient support the reclassification ofISOPasFROMS.MRIandCTmay provide supportive evidence forFROMS, but histopathology is necessary for definitive diagnosis. Aggressive and early surgical treatment, including bilateral exenteration, with adjunctive radiotherapy and/or chemotherapy should be considered for patients withFROMS.