bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring the relationships between learning styles, online participation, learning achievement and course satisfaction: An empirical study of a blended learning course
Authors: Cheng Gary , Chau Juliana
Published: December 2014

The purpose of this study was twofold: first, to explore the relationship between students' learning styles and their online participation in a blended learning course, and second, to investigate the relationships of students' online participation with their learning achievement and with course satisfaction. A total of 78 undergraduate students from a general education course called Digital Citizenship took part in the study. All the participants were required to participate in four different types of online activity: information access, interactive learning, networked learning and materials development. The study used the method of partial least squares to explore the relationships between different constructs. The results indicate that students' learning styles were significantly related to online participation and that online participation in networked learning and materials development was significantly related to their learning achievement and course satisfaction. This study highlights not only the crucial role of learning styles in online participation but also the importance of individual constructivism and social interaction for effective online learning.
Age‐Associated White Matter Lesions: The MRC Cognitive Function and Ageing Study
Authors: Wharton Stephen B. , Simpson Julie E. , Brayne Carol , Ince Paul G.
Published: December 2014

Cerebral white matter lesions (WML) are common in the aging brain and are associated with dementia and depression. They are associated with vascular risk factors and small vessel disease, suggesting an ischemic origin, but recent pathology studies suggest a more complex pathogenesis. Studies using samples from the population‐representative Medical Research Council Cognitive Function and Ageing Study neuropathology cohort used post‐mortem magnetic resonance imaging to identify WML for further study. Expression of hypoxia‐related molecules and other injury and protective cellular pathways in candidate immunohistochemical and gene expression microarray studies support a role for hypoxia/ischemia. However, these approaches also suggest that immune activation, blood–brain barrier dysfunction, altered cell metabolic pathways and glial cell injury contribute to pathogenesis. These abnormalities are not confined to WML, but are also found in apparently normal white matter in brains with lesions, suggesting a field effect of white matter abnormality within which lesions arise. WML are an active pathology with a complex pathogenesis that may potentially offer a number of primary and secondary intervention targets.
Essential role of PU.1 in maintenance of mixed lineage leukemia‐associated leukemic stem cells
Authors: Aikawa Yukiko , Yamagata Kazutsune , Katsumoto Takuo , Shima Yutaka , Shino Mika , Stanley E. Richard , Cleary Michael L. , Akashi Koichi , Tenen Daniel G. , Kitabayashi Issay
Published: December 2014

Acute myeloid leukemia is a clonal malignant disorder derived from a small number of leukemic stem cells (LSCs). Rearrangements of the mixed lineage leukemia (MLL) gene are found in acute myeloid leukemia associated with poor prognosis. The upregulation of Hox genes is critical for LSC induction and maintenance, but is unlikely to support malignancy and the high LSC frequency observed in MLL leukemias. The present study shows that MLL fusion proteins interact with the transcription factor PU.1 to activate the transcription of CSF‐1R, which is critical for LSC activity. Acute myeloid leukemia is cured by either deletion of PU.1 or ablation of cells expressing CSF‐1R. Kinase inhibitors specific for CSF‐1R prolong survival time. These findings indicate that PU.1‐mediated upregulation of CSF‐1R is a critical effector of MLL leukemogenesis.
Novel roles of microglia
Authors: Nakanishi Hiroshi
Published: December 2014

Pío del Río Hortega, the father of the study of microglia, referred to microglia with highly branched fine processes in the healthy brain as “resting microglia,” because he thought these cells were quiescent. After brain injury, these resting microglia change their morphology into an activated type, which have phagocytic activity at the sites of neuronal damage and inflammation. At present, approximately 90 years after the discovery of microglia, microglia in the healthy brains of live animals are found to be very active using a two‐photon scanning laser microscope, and are much more active than any other cells in the brain. Beyond their role as brain‐resident macrophages, many lines of evidence have shown that microglia have essential roles in the maturation and maintenance of neuronal circuits in the developing and adult brain through both the elimination and formation of dendritic spines through their processes. Furthermore, the length and structural complexity of highly branched fine processes are regulated by the microglial intrinsic circadian clock. Dysfunction of the dendritic spines and disturbances of the circadian clock system are widely accepted characteristic abnormalities in neuropsychiatric disorders, including autism. Therefore, the growing understanding of the movement and functions of microglial processes might aid in the development of novel pharmacological interventions against neuropsychiatric disorders, which are associated with synapse loss and aberrant neuronal connectivity.
Adult onset distal and proximal myopathy with complete ophthalmoplegia associated with a novel de novo p.(Leu1877Pro) mutation in MYH2
Authors: Cabrera‐Serrano M. , Fabian V.A. , Boutilier J. , Wise C. , Faiz F. , Lamont P.J. , Laing N.G.
Published: December 2014

An MYH2 mutation p.(Glu706Lys) was originally described in a family with autosomal dominant inheritance, where the affected family members presented with multiple congenital contractures and ophthalmoplegia, progressing to a proximal myopathy in adulthood. Another patient with a dominant mutation p.(Leu1870Pro) was described, presenting as a congenital myopathy with ophthalmoplegia. Here, we present a patient with symptoms beginning at age 16 years, of prominent distal but also proximal weakness, bulbar involvement and ophthalmoplegia. Initially, clinically classified as oculopharyngodistal myopathy, the patient was found to carry a novel, de novo MYH2 mutation c.5630T>C p.(Leu1877Pro). This expands the phenotype of dominant MYH2 myopathies with the clinical phenotype overlapping the oculopharyngodistal myopathy spectrum.
A Survey on Data‐Driven Video Completion
Authors: Ilan S. , Shamir A.
Published: December 2014

Image completion techniques aim to complete selected regions of an image in a natural looking manner with little or no user interaction. Video Completion, the space–time equivalent of the image completion problem, inherits and extends both the difficulties and the solutions of the original 2D problem, but also imposes new ones—mainly temporal coherency and space complexity (videos contain significantly more information than images). Data‐driven approaches to completion have been established as a favoured choice, especially when large regions have to be filled. In this survey, we present the current state of the art in data‐driven video completion techniques. For unacquainted researchers, we aim to provide a broad yet easy to follow introduction to the subject (including an extensive review of the image completion foundations) and early guidance to the challenges ahead. For a versed reader, we offer a comprehensive review of the contemporary techniques, sectioned out by their approaches to key aspects of the problem.
Randomized controlled trial examining expectancy effects on the accuracy of weight measurement
Authors: Dutton G. R. , Fontaine K. R. , Alcorn A. S. , Dawson J. , Capers P. L. , Allison D. B.
Published: December 2014

Background

Researchers and participants' expectations can influence treatment response. Less is known about the effects of researchers' expectations on the accuracy of data collection in the context of a weight loss trial.

Methods

Student raters (N = 58; age = 20.1 ± 2.3 years) were recruited to weigh individuals who they thought were completing a 12‐month weight loss trial, although these ‘participants’ were actually standardized patients (SPs) playing these roles. Prior to data collection, student raters were provided information suggesting that the tested treatment had been effective. Each student rater received a list of 9–10 ‘participants’ to weigh. While the list identified each person as ‘treatment’ or ‘control’, this assignment was at random, which allowed us to examine the effects of non‐blinding and expectancy manipulation on weight measurement accuracy. We hypothesized that raters would record the weights of ‘treatment participants’ as lower than those of ‘control participants’.

Results

Contrary to our hypothesis, raters recorded weights that were 0.293 kg heavier when weighing ‘treatment’ vs. ‘control’ SPs, although this difference was not significant (P = 0.175).

Conclusions

This pilot study found no evidence that manipulating expectancies about treatment efficacy or not blinding raters biased measurements. Future work should examine other biases which may be created by not blinding research staff who implement weight loss trials as well as the participants in those trials.
Determinants of Scanpath Regularity in Reading
Authors: von der Malsburg Titus , Kliegl Reinhold , Vasishth Shravan
Published: December 2014

Scanpaths have played an important role in classic research on reading behavior. Nevertheless, they have largely been neglected in later research perhaps due to a lack of suitable analytical tools. Recently, von der Malsburg and Vasishth (2011) proposed a new measure for quantifying differences between scanpaths and demonstrated that this measure can recover effects that were missed with the traditional eyetracking measures. However, the sentences used in that study were difficult to process and scanpath effects accordingly strong. The purpose of the present study was to test the validity, sensitivity, and scope of applicability of the scanpath measure, using simple sentences that are typically read from left to right. We derived predictions for the regularity of scanpaths from the literature on oculomotor control, sentence processing, and cognitive aging and tested these predictions using the scanpath measure and a large database of eye movements. All predictions were confirmed: Sentences with short words and syntactically more difficult sentences elicited more irregular scanpaths. Also, older readers produced more irregular scanpaths than younger readers. In addition, we found an effect that was not reported earlier: Syntax had a smaller influence on the eye movements of older readers than on those of young readers. We discuss this interaction of syntactic parsing cost with age in terms of shifts in processing strategies and a decline of executive control as readers age. Overall, our results demonstrate the validity and sensitivity of the scanpath measure and thus establish it as a productive and versatile tool for reading research.
The safety of hand‐assisted laparoscopic living donor nephrectomy: The Ohio State University experience with 1500 cases
Authors: Rajab Amer , Pelletier Ronald P.
Published: December 2014

Hand‐assisted laparoscopic donor (HALD) nephrectomy has been performed at our institution since December 1999. Through May 2014, a total of 1500 HALD procedures have been performed. We have evaluated the outcomes of HALD. The HALD procedure consists of a hand‐port incision as well as two 12‐mm ports. Mean donor age was 40.8 ± 10.8 yr, BMI was 27.9 ± 5.0, there were 541 males, 1271 Caucasians, and the left kidney was removed in 1236 patients. All procedures were successfully completed. Four donors (0.27%) were converted to an open technique due to bleeding. Four donors required blood transfusions. 53 donors (3.5%) were readmitted in the first month post‐donation; almost half were due to gastrointestinal complaints. Six donors required reoperation; three for SBO and three for wound dehiscence. 27 patients (1.8%) developed incisional hernias. Seven donors (0.47%) developed bowel obstruction. All donors recovered well with a mean hospital stay after donation of 2.1 ± 0.3 d. All except one kidney were successfully implanted. Twenty‐one recipients (1.4%) experienced DGF. Ureter complications occurred in 17 (1.1%) recipients. Early graft loss occurred in 13 patients (0.9%). In conclusion, HALD is a safe procedure for the donor with good recipient outcomes.
The use of species–area relationships to partition the effects of hunting and deforestation on bird extirpations in a fragmented landscape
Authors: Sreekar Rachakonda , Huang Guohualing , Zhao Jiang‐Bo , Pasion Bonifacio O. , Yasuda Mika , Zhang Kai , Peabotuwage Indika , Wang Ximin , Quan Rui‐Chang , Ferry Slik J. W. , Corlett Richard T. , Goodale Eben , Harrison Rhett D.
Published: December 2014

Aim

Forest fragmentation is often accompanied by an increase in hunting intensity. Both factors are known drivers of species extirpations, but understanding of their independent effects is poor. Our goal was to partition the effects of hunting and fragmentation on bird species extirpations and to identify bird traits that make species more vulnerable to these two stressors.

Location

Menglun, Yunnan, SW China

Methods

We studied the landscape within 10 km radius of Menglun town, where forests have become highly fragmented by monoculture rubber plantations. We compiled data on birds recorded between 1954 and 1983 before forest loss and compared it with a checklist prepared between 2011 and 2014. We used countryside and matrix‐calibrated species–area models (SAMs) to estimate the observed slope of forest bird extirpations in Menglun and compared it with the slope expected in the absence of hunting. We also investigated six ecological traits to determine those that best explained bird extirpation probability (EP).

Results

We found that 34% of the bird fauna had been extirpated from the study landscape, and the estimated slopes of countryside and matrix‐calibrated SAMs for forest birds were around 1.4 and 1.7 times higher, respectively, than the 0.35 expected without hunting. Bird EP was strongly associated with size, and understorey insectivores that are known to be susceptible to fragmentation were less susceptible to hunting than frugivores. Given evidence of past and present hunting activity in the area, and the lack of support for alternative explanations, we suggest that hunting increased forest bird extirpations by around 1.3‐ to 1.6‐fold.

Conclusions

This study highlights the importance of using species–area relationships to separate area effects from the impacts of hunting. Our results suggest that hunting substantially increases species extirpations in tropical fragmented landscapes and conservation interventions that only target deforestation will therefore be inadequate.
Cognitive training in Parkinson's disease reduces cognitive decline in the long term
Authors: Petrelli A. , Kaesberg S. , Barbe M. T. , Timmermann L. , Rosen J. B. , Fink G. R. , Kessler J. , Kalbe E.
Published: December 2014

Background and purpose

Patients with Parkinson's disease (PD) are at high risk for cognitive dysfunction. Non‐pharmacological interventions have attracted increasing interest for enhancing PD patients' cognitive functions.

Methods

One‐year follow‐up data (T2) of a randomized controlled trial evaluating two 6‐week cognitive trainings – a structured (NEUROvitalis, NV) and an unstructured (mentally fit, MF) program − compared with a waiting list control group (CG) in non‐demented PD patients (Hoehn and Yahr I–III) are presented. Forty‐seven PD patients were examined at T2. Effects on overall cognitive functions (Mini‐Mental State Examination and DemTect) were compared between all groups with repeated measurement analyses of variance. A combined score of the percentage change value from baseline (T0) to T2 was calculated to identify patients who retained or improved their cognitive state (responders). The risk of developing mild cognitive impairment (MCI) was analyzed.

Results

Significant time × treatment effects on overall cognitive functions were found for both training groups, each compared separately to the CG (DemTect, P < 0.05). Nine patients (56.3%) of the NV group, seven (41.2%) of the MF group and three (21.4%) of the CG were responders. Comparing NV to CG the odds ratio was 4.7 [95% confidence interval (0.8; 33.3)], and comparing MF to CG it was 2.6 [95% confidence interval (0.4; 17.4)]. MCI risk for patients without prior MCI was 40.0% in CG, 18.2% in MF and 18.2% in NV. The odds ratio was 3 comparing NV to CG, MF to CG.

Discussion

This study gives evidence that cognitive training may be effective to prevent cognitive decline and onset of MCI in PD patients.
Spatial control of calcineurin in response to heat shock in fission yeast
Authors: Higa Mari , Kita Ayako , Hagihara Kanako , Kitai Yuki , Doi Akira , Nagasoko Rie , Satoh Ryosuke , Sugiura Reiko
Published: December 2014

In fission yeast, Ppb1, the Ca2+/calmodulin‐dependent protein phosphatase calcineurin regulates multiple biological processes, such as cytokinesis, Ca2+‐homeostasis, membrane trafficking and cell wall integrity. Calcineurin dephosphorylates the Prz1 transcription factor, leading to its nuclear translocation and gene expression under the control of CDRE (calcineurin‐dependent response element). Although the calcineurin‐mediated spatial control of downstream transcription factors has been intensively studied in many organisms, less is known about the spatial regulation of calcineurin on stresses. Here, we show that heat shock stimulates calcineurin‐dependent nuclear translocation of Prz1 and CDRE‐dependent gene expression. Notably, calcineurin exhibited a dramatic change in subcellular localization, translocating from diffuse cytoplasmic to dot‐like structures on heat shock. The calcineurin dots colocalized with Dcp2 or Pabp, the constituent of P‐bodies or stress granules, respectively, thus suggesting that calcineurin is a component of RNA granules under heat shock. Importantly, the calcineurin inhibitor FK506 markedly inhibited the accumulation of calcineurin granules, whereas the constitutively active calcineurin strongly accumulated in the granules on heat shock, suggesting that phosphatase activity is important for calcineurin localization. Notably, the depletion of calcineurin induced a rapid appearance of Nrd1‐ and Pabp‐positive RNA granules. The possible roles of calcineurin in response to heat shock will be discussed.
Assessment of repeatability of composition of perfumed waters by high‐performance liquid chromatography combined with numerical data analysis based on cluster analysis (HPLC UV/VIS – CA)
Authors: Ruzik L. , Obarski N. , Papierz A. , Mojski M.
Published: December 2014

Synopsis

High‐performance liquid chromatography (HPLC) with UV/VIS spectrophotometric detection combined with the chemometric method of cluster analysis (CA) was used for the assessment of repeatability of composition of nine types of perfumed waters. In addition, the chromatographic method of separating components of the perfume waters under analysis was subjected to an optimization procedure. The chromatograms thus obtained were used as sources of data for the chemometric method of cluster analysis (CA). The result was a classification of a set comprising 39 perfumed water samples with a similar composition at a specified level of probability (level of agglomeration). A comparison of the classification with the manufacturer's declarations reveals a good degree of consistency and demonstrates similarity between samples in different classes. A combination of the chromatographic method with cluster analysis (HPLC UV/VIS – CA) makes it possible to quickly assess the repeatability of composition of perfumed waters at selected levels of probability.
Living with antipsychotic medication side‐effects: The experience of Australian mental health consumers
Authors: Morrison Paul , Meehan Tom , Stomski Norman Jay
Published: December 2014

The present study explores people's experience of living with antipsychotic medication side‐effects. Qualitative data were gathered through semistructured interviews with 10 mental health consumers in a community care setting in Australia. The interview transcriptions were content analysed, and enhanced by combining manifest and latent content. Important contextual cues were identified through replaying the audio‐recordings. Several main themes emerged from the analysis, including the impact of side‐effects, attitudes to the use of medication and side‐effects, and coping strategies to manage medication side‐effects. Each participant reported between six and seven side‐effects on average, which were often pronounced and had a major disruptive impact on their lives. Of these effects, the most commonly mentioned was sedation, which the participants described as leaving them in a ‘zombie'‐like state. Most participants expressed an attitude of acceptance about the side‐effects. The participants' most common strategy to manage side‐effects was to change the dosage of the medication. Other common side‐effect management strategies involved using other medications to control side‐effects, and diverse self‐help techniques, the most common of which was relaxation/distraction techniques.
Fluidity in Sexual Identity, Unmeasured Heterogeneity, and the Earnings Effects of Sexual Orientation
Authors: Sabia Joseph J.
Published: December 2014

Using data drawn from the National Longitudinal Study of Adolescent Health, this study (1) examines the sensitivity of the estimated earnings penalty of sexual minority status to family‐level unobserved heterogeneity, and (2) explores whether the earnings effects of sexual orientation differ by the degree of fluidity in individuals' self‐reported sexual identity over time. Evidence from sibling pairs suggests that unobserved family heterogeneity is not an important source of bias in the estimated relationship between sexual orientation and young adult earnings. I find that gay males and bisexuals earn lower wages than their heterosexual counterparts, while lesbians earn wages that are not significantly different from heterosexual females. Finally, I examine the role of fluidity in sexual orientation over time and find that males who are longer‐term gay identifiers earn wages that are 26.4 percent lower than their consistently heterosexual‐identifying counterparts.
Labor‐Market Specialization within Same‐Sex and Difference‐Sex Couples
Authors: Jepsen Christopher , Jepsen Lisa K.
Published: December 2014

We use data from the 2000 decennial U.S. Census to compare differences in earnings, hours worked, and labor‐force participation between members of different household types, including same‐sex couples, different‐sex couples, and roommates. Both same‐sex and different‐sex couples exhibit some degree of household specialization, whereas roommates show little or no degree of specialization. Of all household types, married couples exhibit by far the highest degree of specialization with respect to labor‐market outcomes. With respect to differences in earnings and hours, gay male couples are more similar to married couples than lesbian or unmarried heterosexual couples are to married couples.
Testing for Discrimination against Lesbians of Different Marital Status: A Field Experiment
Authors: Weichselbaumer Doris
Published: December 2014

In this paper, I conduct a correspondence testing experiment to examine sexual orientation discrimination against lesbians in Germany. I sent applications from four fictional female characters in response to job advertisements in Munich and Berlin: a heterosexual single, a married heterosexual, a single lesbian, and a lesbian who is in a “same‐sex registered partnership.” While single lesbians and lesbians in a registered partnership are equally discriminated in comparison to the heterosexual women in the city of Munich, I found no discrimination based on sexual orientation in Berlin. Furthermore, for a subset of the data we can compare the effects of a randomized versus a paired testing approach, which suggests that under certain conditions, due to increased conspicuity, the paired testing approach may lead to biased results.
Increased syllable rate during aggressive singing in a bird with complex and fast song
Authors: Funghi Caterina , Cardoso Gonçalo C. , Mota Paulo G.
Published: December 2014

Sexual signals can comprise traits with multiple functions, and species with extreme phenotypes offer an opportunity to link function with signal evolution. This is the case in the serin Serinus serinus, a songbird with extremely fast syllable rate compared to related finches, and high sound frequency for its body size. Previous work on receiver responses showed that playback of artificially increased syllable rate is avoided and inhibits vocal responses, suggesting it is perceived as aggressive, while, on the contrary, higher sound frequency appears preferred by females. We tested whether senders also change these traits during aggressive singing, with a field playback experiment. Serin males responding aggressively by approaching the playback loudspeaker also increased syllable rate, while males responding less aggressively did not change syllable rate. Together with work on receiver responses, this suggests that aggressive signalling may have been an important selective pressure for the evolution of extremely fast syllable rate in this species. It is noteworthy that aggressive male serins still increase syllable rate, despite of their already elevated natural syllable rate. We found no changes in sound frequency when singing aggressively, which agrees with previous work that instead showed a female preference for high song frequency. We conclude that the evolution of extreme traits in serin song is best explained by multiple functions.
When Good News Is Not So Good: Economy‐wide Uncertainty and Stock Returns
Authors: Choi Hae mi
Published: December 2014

This paper shows that variation in economy‐wide uncertainty causes asymmetric stock price responses to firm earnings surprises. The uncertainty that attends bad earnings news that arrives during expansions with greater economy‐wide uncertainty occasions larger price declines. This is because news inconsistent with investors’ prior beliefs about the state of the economy increases uncertainty, which amplifies the negative cash flow effects contained in bad earnings news. Asymmetrically, the positive cash flow effect of good earnings news that arrives during recessions is offset by increased investor uncertainty, which results in relatively smaller price reactions to the good news. This is consistent with Veronesi's rational expectations equilibrium model, which shows that investors demand higher expected returns in the face of greater uncertainty.
Editorial: Process to progress? Investigative trials, mechanism and clinical science
Authors: Green Jonathan
Published: December 2014

In 2002 Helena Kraemer and colleagues published an important article on the analysis of clinical trials in mental health, which advocated a planned focus on mechanisms to investigate the processes behind treatment effects. Kraemer et al. considered not only new approaches to mediation analysis, but also a theoretical approach to factors, both pre‐treatment and during treatment, that might moderate this mediation. Trials should not just be about whether a treatment ‘worked’, but how it worked; with the results informing modification of the intervention for the next trial by discarding aspects that were not effective and reinforcing aspects that were – an iterative procedure towards greater effectiveness. Can we enjoy similar ambitions for complex interventions within mental health? It is not so long ago when the received wisdom within the clinical and much of the research community was that it was simply impossible in practice to mount randomised controlled trials relevant to the kind of psychosocial interventions we use in child and adolescent mental health (CAMHS). How different the situation is now, with burgeoning interest in a systematic evidence base for psychological treatment and the possibilities for unexpected advances (as well as unexpected harms). Nevertheless it is probably still fair to say that the systematic use of process and mechanism study within trials in our field is the exception rather than the rule. What are the possibilities and implications for our field?
The failure of gastroenterologists to apply intestinal ultrasound in inflammatory bowel disease in the Asia‐Pacific: A need for action
Authors: Asthana Anil Kumar , Friedman Antony B , Maconi Giovanni , Maaser Christian , Kucharzik Torsten , Watanabe Mamoru , Gibson Peter R
Published: December 2014

Intestinal ultrasound (IUS) is a cheap, noninvasive, risk‐free procedure that is significantly underutilized in the diagnosis and management of patients with inflammatory bowel disease (IBD) in the Asia‐Pacific region. More cost‐effective methods of monitoring disease activity are required in light of the increasing global burden of IBD (especially in Asia), the advent of personalized medicine, and the rising cost of healthcare. IUS is a prime example of a technique that meets these needs. Its common clinical applications include assessing the activity and complications of IBD. In continental Europe, countries such as Germany and Italy use this imaging tool as the standard of care and have integrated it into management protocols. There are formal training programs in these countries to train gastroenterologists in IUS, and it is used in an outpatient setting during patient consultations. Barriers to its use in the Asia‐Pacific region include lack of experience and research data, and there are few established centers with active training programs. These concerns can be addressed by investing more in IUS service provision and by increasing allocation of resources toward local research and training. Increased uptake of IUS will ultimately benefit patients with IBD.
Inhibiting reactions to emotional versus non‐emotional response cues in schizophrenia: Insights from a motor‐process paradigm
Authors: Patrick Regan E. , Christensen Bruce K. , Smolewska Kathy
Published: December 2014

Recent models of schizophrenia suggest deficient use of contextual response cues when confronted with countermanding emotional cues. It is important to clinically validate these models by testing patients diagnosed with schizophrenia on tasks with competing emotional and contextual response determinants. Control and schizophrenia groups completed a novel task that elicited motor responses consistent with, or in opposition to, pre‐potent emotional actions (i.e., approach vs. avoidance). An analogous non‐emotional task was also used to examine cue‐conflict impairment more generally. The groups demonstrated statistically equivalent performance decrements on incongruent versus congruent trials on both tasks. However, within the schizophrenia group, the incongruency effect was significantly greater in the emotional versus non‐emotional task. These data suggest that, while patients with schizophrenia were able to employ contextual response cues to override competing emotional responses, they were slower to resolve emotional versus non‐emotional response conflict. When patients were subdivided according to the presence or absence of disorganized symptoms, this effect was confined to patients with disorganized symptoms.
Strategic Obfuscation and Consumer Protection Policy
Authors: Gu Yiquan , Wenzel Tobias
Published: December 2014

This paper studies obfuscation decisions by firms. We show that more prominent firms are more likely to obfuscate. While prominent firms always choose maximum obfuscation, the obfuscation by less prominent firms depends on the degree of asymmetry in prominence and consumer protection policy. We evaluate the impact of a consumer protection policy that limits the scope of obfuscation. We show that such a policy may not be effective as less prominent firms may increase their obfuscation practice.
Capital Mobility—Resource Gains or Losses? How, When, and for Whom?
Authors: OGAWA HIKARU , OSHIRO JUN , SATO YASUHIRO
Published: December 2014

This paper investigates which of the two types of countries—resource‐rich or resource‐poor—gains from capital market integration and capital tax competition. We develop a framework involving vertical linkages through resource‐based inputs as well as international fiscal linkages between the two types of countries. Our analysis shows that capital market integration causes capital flows from resource‐poor to resource‐rich countries and improves global production efficiency. However, such gains accrue only to resource‐poor countries, and capital mobility might even negatively affect resource‐rich countries. Furthermore, we show that resource‐rich countries can exploit the gains when taxes on capital are available.
SHALE‐GAS POTENTIAL OF THE MID‐CARBONIFEROUS BOWLAND‐HODDER UNIT IN THE CLEVELAND BASIN (YORKSHIRE), CENTRAL BRITAIN
Authors: Słowakiewicz M. , Tucker Maurice E. , Vane C. H. , Harding R. , Collins A. , Pancost R. D.
Published: December 2014

The shale‐gas potential of mid‐Carboniferous mudrocks in the Bowland‐Hodder unit in the Cleveland Basin (Yorkshire, northern England) was investigated through the analysis of a cored section from the uppermost part of the unit in the Malton‐4 well using a multidisciplinary approach. Black shales are interbedded with bioturbated and bedded sandstones, representing basinal‐offshore to prodelta – delta‐front lithofacies. The total organic carbon (TOC) content of the shales ranges from 0.37 to 2.45 wt %. Rock‐Eval pyrolysis data indicate that the organic matter is mainly composed of Type III kerogen with an admixture of Type II kerogen. Tmax (436–454°C), 20S/(20S+20R) C29 sterane ratios, and vitrinite reflectance values indicate that organic matter is in the mid‐ to late‐ mature (oil) stage with respect to hydrocarbon generation. Sedimentological and geochemical redox proxies suggest that the black shales were deposited in periodically oxic‐dysoxic and anoxic bottom waters with episodic oxic conditions, explaining the relatively low TOC values. The Rock‐Eval parameters indicate that the analysed mudrocks have a limited shale‐gas potential. However, burial and thermal history modelling, and VRr data from other wells in the region, indicate that where they are more deeply‐buried, the Bowland‐Hodder shales will be within the gas window with VRr > 1.1 % at depths in excess of 2000 m. Therefore although no direct evidence for a high shale‐gas potential in the Cleveland Basin has been found, this cannot be precluded at greater depths especially if deeper horizons are more organic rich.
Size scaling of extracellular carbonic anhydrase activity in centric marine diatoms
Authors: Shen Chen , Hopkinson Brian M.
Published: December 2014

Many microalgae have a surface‐associated extracellular carbonic anhydrase (eCA) that converts HCO3− to CO2 for uptake and subsequent photosynthetic fixation. We investigated eCA activity and assessed its importance for photosynthetic CO2 supply in six centric diatom species spanning nearly the full range of cell sizes for centric diatoms (equivalent spherical radius 3–67 μm). Since larger cells are more susceptible to diffusion limitation, we hypothesized that eCA activity would increase with cell size as would its importance for CO2 supply. eCA activity did increase with cell size, increasing with cell radius by a size‐scaling exponent of 2.6 ± 0.3. The rapid increase in eCA activity with cell radius keeps the absolute CO2 concentration difference between bulk seawater and the cell surface very low (<~0.2 μM) allowing high rates of CO2 uptake even for large diatoms. Although inhibiting eCA did reduce photosynthesis in the diatoms, there was no overall relationship between the extent of inhibition of photosynthesis and cell size. The only indication that eCA may be more important for larger diatoms was that photosynthesis in the smallest diatoms (<4 μm radius) was only affected by eCA inhibition when CO2 concentrations were very low, while photosynthesis in some larger diatoms was affected even at typical seawater CO2 concentrations. eCA is ubiquitous in centric marine diatoms, in contrast to other taxa where its presence is irregularly distributed among different species, and plays an important role in supplying CO2 for photosynthesis across the size spectrum.
Reversibility of hepatitis B virus cirrhosis after therapy: who and why?
Authors: Bedossa Pierre
Published: December 2014

The end point of liver fibrosis in almost all chronic liver diseases including HBV chronic hepatitis is cirrhosis. Progression to cirrhosis is associated with annular deposition of fibrous tissue and vascular remodeling with a shift from a lobular to nodular organization. Although advanced liver fibrosis was previously thought to be irreversible, today there is compelling evidence that cirrhosis can be reversed if the underlying cause of liver injury is eliminated. Indeed, most clinical trials with antiviral therapy and histological follow‐up have shown that fibrosis can regress and that in some cases even cirrhosis can reverse following long‐term HBV‐DNA suppression, although the return to a fully normal liver is rarely observed and difficult to prove. Nevertheless, a marked percentage of cirrhosis will not reverse even after effective antiviral therapy. Generally cirrhosis is more likely to regress if it is recent, there is effective and long‐lasting viral suppression, an internal capacity to regenerate and no vascular thrombosis. HBV treatment in patients with cirrhosis is associated with an improved clinical outcome although there may still be a risk of hepatocellular carcinoma. Nevertheless it has not yet been determined if a favorable outcome depends on histological regression or whether the reversal of cirrhosis is merely a surrogate marker of viral suppression. The significance of the reversal of cirrhosis is still a subject of debate because neither the histological scoring systems nor non‐invasive markers to evaluate the reversal of cirrhosis have been validated.
Optimal therapy of genotype‐2 chronic hepatitis C: what's new?
Authors: Bourlière Marc , Benali Souad , Ansaldi Christelle , Le Folgoc Gaelle , Riso Aurelie , Lecomte Laurence
Published: December 2014

The standard of care (SOC) for the treatment of HCV genotype 2 (HCV‐2) was pegylated interferon alpha plus ribavirin (PEG‐IFN/RBV) at weight‐based doses for a response‐guided duration. The launches of sofosbuvir and daclatasvir in 2014 have resulted in new, better tolerated and shorter treatment. The combination of sofosbuvir and RBV for 12 weeks appears to be the new SOC in both European and American guidelines. The cost and therefore the access to this treatment remains a problem in many countries because of major economic constraints. For the few more difficult‐to‐treat patients, a combination of direct acting antivirals may be suitable and is being studied in ongoing trials. Because of rapidly changing treatment recommendations, the decision to treat HCV‐2 patients with currently approved drugs or to wait until a better option is available in the future, must be made according to the stage of fibrosis.
Optimal therapy of chronic hepatitis B: how do I treat my HBeAg‐negative patients?
Authors: Viganò Mauro , Invernizzi Federica , Lampertico Pietro
Published: December 2014

HBeAg negative chronic hepatitis B (CHB) is a frequent, progressive and difficult‐to‐cure phase of CHB. The end‐point of therapy is to persistently suppress viral replication to halt progression of liver disease. Two different treatment strategies are currently available: a short‐term course of pegylated interferon alpha (PEG‐IFN) or long‐term therapy with nucleot(s)ide analogues (NA), i.e. entecavir or tenofovir. Young patients with mild‐to‐moderate stages of liver disease can benefit from a 48‐week course of PEG‐IFN, while NA may be preferred in patients with more severe liver disease, in older patients, and in those who do not respond, are unwilling or have contraindications to PEG‐IFN. Nucleot(s)ide analogues provide persistent viral suppression and biochemical normalization in almost all patients, together with the regression of fibrosis and the prevention of decompensation, but the effect on hepatocellular carcinoma rates is limited. Thus, NAs have become the most popular treatment strategy worldwide but lifelong administration is associated with high cost, unknown safety and adherence issues and an unknown risk of drug‐resistance over time as well as limited rates of HBsAg seroclearance. On the other hand, PEG‐IFN treatment may achieve a SVR in nearly a quarter of patients ultimately leading to HBsAg loss in almost 30–50%. Interestingly, response rates to PEG‐IFN may further increase with more careful patient selection based on age, ALT and HBV DNA levels at baseline and by applying early on‐treatment stopping rules based on HBV DNA and HBsAg kinetics. The combination of NA and PEG‐IFN is not currently recommended but numerous studies are ongoing.
Optimal therapy for chronic hepatitis B: hepatitis B virus combination therapy?
Authors: Petersen Jorg , Dandri Maura
Published: December 2014

Currently available antiviral treatment for chronic hepatitis B can be divided into two classes of therapeutic agents: pegylated interferon alpha (PEG‐IFN) and nucleos(t)ide analogues (NAs). The major advantages of NAs are good tolerance and potent antiviral activity associated with high rates of on‐treatment response to therapy. The advantages of PEG‐IFN include a finite course of treatment, the absence of drug resistance, and an opportunity to obtain a durable post‐treatment response to therapy. The use of these two antiviral agents with different mechanisms of action in combination is theoretically an attractive approach for treatment, either simultaneously, as sequential combination therapy (add‐on), or even as an immediate switch from one agent to the other. Different NAs have also been combined in certain clinical situations. At present, several studies have confirmed certain virological advantages to combination therapies, but pivotal prospective studies demonstrating long‐term clinical benefit to patients are still missing. Therefore, combination treatment, especially with PEG‐IFN plus NAs, is not indicated and was not recommended by the European Association for the Study of the Liver Clinical Practice Guidelines written in 2012, while the guidelines for the use of combination NAs is limited to very few clinical situations.
Optimal therapy of HIV/HCV co‐infected patients with direct acting antivirals
Authors: Rockstroh Jürgen K.
Published: December 2014

The development of direct acting antivirals (DAAs) against the hepatitis C virus (HCV) has revolutionized treatment paradigms for HCV in HIV co‐infected subjects. In the era of DAAs, HIV/HCV co‐infected patients have the same cure rates of over 90% with interferon (IFN)‐free DAA combinations. Therefore, guidelines no longer separate mono‐ and co‐infected subjects. Indications for HCV therapy and DAA drug selection have become the same for all patients. The only special consideration in HIV/HCV co‐infected subjects is the need to check for drug–drug interactions between HIV and HCV drugs, especially HIV and HCV protease inhibitors which have a high risk of clinically significant drug interactions. Because of the faster progression of fibrosis and the higher risk of hepatic decompensation in co‐infected subjects, even with combination antiretroviral (ART) therapy, the availability of modern HCV treatments needs to be extended and HCV therapy should be discussed in all co‐infected patients.
An intrahepatic transcriptional signature of enhanced immune activity predicts response to peginterferon in chronic hepatitis B
Authors: Jansen Louis , de Niet Annikki , Makowska Zuzanna , Dill Michael T. , van Dort Karel A. , Terpstra Valeska , Bart Takkenberg R. , Janssen Harry L.A. , Heim Markus H. , Kootstra Neeltje A. , Reesink Hendrik W.
Published: December 2014

Background & Aims

Differences in intrahepatic gene expression patterns may be associated with therapy response in peginterferon‐treated chronic hepatitis B (CHB) patients.

Methods

We employed gene expression profiling in baseline liver biopsies of 40 CHB patients (19 HBeAg‐positive; 21 HBeAg‐negative) treated with peginterferon and adefovir for 48 weeks, and compared expression patterns of combined responders (HBeAg loss, HBV‐DNA <2000 IU/ml, alanine aminotransferase normalization after 1 year of treatment‐free follow‐up) with non‐responders. Genes identified by transcriptome analysis in 15 biopsies were confirmed in 25 additional biopsies by RT‐qPCR.

Results

Transcriptome analysis demonstrated significant differences in expression of 41 genes between responders and non‐responders. In responders, pathway analysis showed specific upregulation of genes related to the immune response, including chemotaxis and antigen processing and presentation. Genes upregulated in responders exhibited strongest similarity with a set of genes induced in livers of chimpanzees with acute Hepatitis B infection. Differential expression was confirmed for eight selected genes. A 2‐gene subset (HLA‐DPB1, SERPIN‐E1) was found to predict response most accurately. Incorporation of these genes in a multivariable model with HBeAg status, HBV genotype and baseline HBsAg level correctly classified 90% of all patients, in which HLA‐DPB1 and SERPIN‐E1 were independent predictors of response.

Conclusion

We identified an intrahepatic transcriptional signature associated with enhanced immune activation which predicts therapy response. These novel associations could lead to better understanding of responsiveness to peginterferon in CHB patients, and may assist in selecting possible responders to interferon‐based treatment.
Effect of pretransplant diabetes on short‐term outcomes after liver transplantation: A National cohort study
Authors: Hoehn Richard S. , Singhal Ashish , Wima Koffi , Sutton Jeffrey M. , Paterno Flavio , Steve Woodle E. , Hohmann Sam , Abbott Daniel E. , Shah Shimul A.
Published: December 2014

Background & Aims

We sought to analyse the effect of pretransplant diabetes on post‐operative outcomes and resource utilization following liver transplantation.

Methods

A retrospective cohort study was designed using a linkage between the University HealthSystem Consortium and Scientific Registry of Transplant Recipients databases. We identified 12 442 patients who underwent liver transplantation at 63 centres from 2007–2011 and separated cohorts of patients with diabetes (n = 2971; 24%) and without (n = 9471; 76%) at the time of transplant. We analysed transplant related outcomes and short‐term survival.

Results

Diabetic recipients were more likely to be male (70% vs 67%), non‐white (32% vs 26%), older (age ≥60; 41% vs 28%), and have a higher BMI (29 vs 27; P < 0.001). More diabetic patients were on haemodialysis (10% vs 7%), had cirrhosis caused by NASH (24% vs 9%; P < 0.001), and received liver allografts from older donors (≥ 60 years; 19% vs 15%) with a higher donor risk index (>1.49; 46% vs 42%; P < 0.001). Post‐transplant, diabetic recipients had longer hospital length of stay (10 vs 9 days), higher peri‐transplant mortality (5% vs 4%) and 30‐day readmission rates (41% vs 37%), were less often discharged to home (83% vs 87%; P < 0.05), and had inferior graft and patient survival. Liver transplant was more expensive for type 1 vs type 2 diabetics ($105 078 vs $100 624, P < 0.001). Poorly controlled diabetic recipients were less likely discharged home following transplant (75% vs 82%, P < 0.01).

Conclusions

This national study indicates that pretransplant diabetes is associated with inferior post‐operative outcomes and increased resource utilization after liver transplantation.