bluuebunny/crossref_metadata_2025 huggingface dataset:
Caregiver burden among nocturnal home hemodialysis patients
Authors: Rioux Jean‐Philippe , Narayanan Ranjit , Chan Christopher T.
Published: February 2012

Recent studies have suggested improvements in quality of life (QOL) in patients on quotidian dialysis compared with conventional hemodialysis. Few studies have focused on the burden and QOL in caregivers of patients with end‐stage renal disease (ESRD) on nocturnal home hemodialysis (NHD). We aim to assess the caregivers’ burden, QOL, and depressive symptoms and to compare these parameters with their patients’ counterparts. Cross‐sectional surveys were sent to 61 prevalent NHD patients and their caregivers. Surveys assessed demographics, general self‐perceived health using the 12‐Item Short Form Health Survey (SF‐12) and the presence of depression using the Beck Depression Inventory. Subjective burden on caregivers was assessed by the Caregiver Burden scale and was compared with perceived burden by the patients. Thirty‐six patients and 31 caregivers completed the survey. The majority of caregivers were female (66%), spouse (81%) with no comorbid illness (72%). Their mean age was 51 ± 11 years. Patients were mostly male (64%) with a median ESRD vintage of 60 months (interquartile range [IQR], 18–136 months) and a mean age of 52 ± 10 years. Compared to caregivers, patients had lower perceived physical health score but had similar mental health score. Depression criteria were present in 47% of patients and 25% of caregivers. Total global burden perceived by either caregivers or patients is relatively low. Although there is a relatively low global burden perceived by caregivers and patients undergoing NHD, a significant proportion of both groups fulfilled criteria for depression. Further innovative approaches are needed to support caregivers and patients performing NHD to reduce the intrusion of caring for a chronic illness and the risk of developing depression.
Testing the Limits of Long‐Distance Learning: Learning Beyond a Three‐Segment Window
Authors: Finley Sara
Published: February 2012

Traditional flat‐structured bigram and trigram models of phonotactics are useful because they capture a large number of facts about phonological processes. Additionally, these models predict that local interactions should be easier to learn than long‐distance ones because long‐distance dependencies are difficult to capture with these models. Long‐distance phonotactic patterns have been observed by linguists in many languages, who have proposed different kinds of models, including feature‐based bigram and trigram models, as well as precedence models. Contrary to flat‐structured bigram and trigram models, these alternatives capture unbounded dependencies because at an abstract level of representation, the relevant elements are locally dependent, even if they are not adjacent at the observable level. Using an artificial grammar learning paradigm, we provide additional support for these alternative models of phonotactics. Participants in two experiments were exposed to a long‐distance consonant‐harmony pattern in which the first consonant of a five‐syllable word was [s] or [∫] (“sh”) and triggered a suffix that was either [‐su] or [‐∫u] depending on the sibilant quality of this first consonant. Participants learned this pattern, despite the large distance between the trigger and the target, suggesting that when participants learn long‐distance phonological patterns, that pattern is learned without specific reference to distance.
Musings About Beauty
Authors: Kintsch Walter
Published: February 2012

In this essay, I explore how cognitive science could illuminate the concept of beauty. Two results from the extensive literature on aesthetics guide my discussion. As the term “beauty” is overextended in general usage, I choose as my starting point the notion of “perfect form.” Aesthetic theorists are in reasonable agreement about the criteria for perfect form. What do these criteria imply for mental representations that are experienced as beautiful? Complexity theory can be used to specify constraints on mental representations abstractly formulated as vectors in a high‐dimensional space. A central feature of the proposed model is that perfect form depends both on features of the objects or events perceived and on the nature of the encoding strategies or model of the observer. A simple example illustrates the proposed calculations. A number of interesting implications that arise as a consequence of reformulating beauty in this way are noted.
Did the Chinese Have a Change of Heart?
Authors: Klein Esther , Klein Colin
Published: February 2012

In their “The Prevalence of Mind‐Body Dualism in Early China,” Slingerland and Chudek use a statistical analysis of the early Chinese corpus to argue for Weak Folk Dualism (WFD). We raise three methodological objections to their analysis. First, the change over time that they find is largely driven by genre. Second, the operationalization of WFD is potentially misleading. And, third, dating the texts they use is extremely controversial. We conclude with some positive remarks.
HTLV‐I‐Associated Myelopathy/Tropical Spastic Paraparesis: Semiautomatic Quantification of Spinal Cord Atrophy from 3‐Dimensional MR Images
Authors: Evangelou Iordanis E. , Massoud Raya , Jacobson Steven
Published: February 2012

BACKGROUND

Human T‐cell lymphotropic virus type I (HTLV‐I)‐associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a disabling neurological disorder characterized by inflammatory changes in the spinal cord. We used a semiautomatic technique to quantify spinal cord volume from 3‐dimensional MR images of patients with HAM/TSP.

METHODS

Five patients and 5 matched healthy volunteers (HVs) underwent MRI of the cervical and thoracic spinal cord at 1.5 T. Quantification of the spinal cord volume was obtained from 3‐dimensional MR images using a semiautomatic technique based on level sets. An unpaired t‐test was used to assess statistical significance.

RESULTS

Significant differences were found between mean spinal cord volume of HVs and HAM/TSP patients. The thoracic spinal cord volume was 14,050 ± 981 mm3 for HVs and 8,774 ± 2,218 mm3 for HAM/TSP patients (P = .0079), a reduction of 38%. The cervical spinal cord volume was 9,721 ± 797 mm3 for HVs and 6,589 ± 897 mm3 for HAM/TSP patients (P = .0079), a reduction of 32%. These results suggest that atrophy is evident throughout the spinal cord not routinely quantified.

CONCLUSIONS

Semiautomatic spinal cord volume quantification is a sensitive technique for quantifying the extent of spinal cord involvement in HAM/TSP.
The Unique Features of Traumatic Brain Injury in Children. Review of the Characteristics of the Pediatric Skull and Brain, Mechanisms of Trauma, Patterns of Injury, Complications, and their Imaging Findings—Part 2
Authors: Pinto Pedro S. , Meoded Avner , Poretti Andrea , Tekes Aylin , Huisman Thierry A. G. M.
Published: February 2012

Traumatic brain injury (TBI) is a major cause of morbidity and mortality in children. The unique biomechanical, hemodynamical, and functional characteristics of the developing brain and the age‐dependent variance in trauma mechanisms result in a wide range of age specific traumas and patterns of brain injuries. Detailed knowledge of the main primary and secondary pediatric injuries, which enhance sensitivity and specificity of diagnosis, will guide therapy and may give important information about the prognosis. In recent years, anatomical but also functional imaging methods have revolutionized neuroimaging of pediatric TBI. The purpose of this article is (1) to comprehensively review frequent primary and secondary brain injuries and (2) to give a short overview of two special types of pediatric TBI: birth related and nonaccidental injuries. J Neuroimaging 2012;22:e18–e41.
Vestibular regeneration – experimental models and clinical implications
Authors: Albu Silviu , Muresanu Dafin F.
Published: February 2012

Therapies aimed at the protection and/or regeneration of inner ear hair cells are of great interest, given the significant monetary and quality of life impact of balance disorders. Different viral vectors have been shown to transfect various cell types in the inner ear. The past decade has provided tremendous advances in the use of adenoviral vectors to achieve targeted treatment delivery. Several routes of delivery have been identified to introduce vectors into the inner ear while minimizing injury to surrounding structures. Recently, the transcription factor Atoh1 was determined to play a critical role in hair cell differentiation. Adenoviral‐mediated overexpression of Atoh1 in culture and in vivo has demonstrated the ability to regenerate vestibular hair cells by causing transdifferentiation of neighbouring epithelial‐supporting cells. Functional recovery of the vestibular system has also been documented following adenoviral‐induced Atoh1 overexpression. Experiments demonstrating gene transfer in human vestibular epithelial cells reveal that the human inner ear is a suitable target for gene therapy.
AL3810, a multi‐tyrosine kinase inhibitor, exhibits potent anti‐angiogenic and anti‐tumour activity via targeting VEGFR, FGFR and PDGFR
Authors: Zhou Yuanfeng , Chen Yi , Tong Linjiang , Xie Hua , Wen Weiwei , Zhang Jie , Xi Yong , Shen Yanyan , Geng Meiyu , Wang Yuanyuan , Jiang Hualiang , Luo Cheng , Lin Liping , Ding Jian
Published: February 2012

Angiogenesis plays an important role in neoplastic transformation and progression as well as in the metastasis process of most human cancers. Herein, we identified AL3810 as a novel and orally bioavailable small molecular inhibitor with potent inhibitory activity against multiple tyrosine kinases involved in the process of angiogenesis. We found that AL3810 substantially inhibited the autophosphorylation of VEGFR2, PDGFRβ and FGFR1 in endothelial cells. Moreover, AL3810 exhibited potent anti‐angiogenesis activity, manifested by significant inhibition of microvessel outgrowth of rat arterial ring and chickallantochorion membrane (CAM) in ex vivo angiogenesis models. Daily dosing of AL3810 has shown broad‐spectrum anti‐tumour activity in human kidney, pancreas, liver cancer xenograft models. Importantly, immunohistochemistry results demonstrated that the anti‐tumour activity of AL3810 was closely correlated with its anti‐angiogenesis activity, as demonstrated by a decreased microvessel area and reduced microvessel numbers in tumour tissues. The overall pharmacological profiles of AL3810 are superior to sorafenib. The clinical trials of AL3810 will soon be launched in China.
Genistein as a potential inducer of the anti‐atherogenic enzyme paraoxonase‐1: studies in cultured hepatocytes in vitro and in rat liver in vivo
Authors: Schrader Charlotte , Ernst Insa M. A. , Sinnecker Heike , Soukup Sebastian T. , Kulling Sabine E. , Rimbach Gerald
Published: February 2012

A number of cardioprotective effects, including the reduced oxidation of the low‐density lipoprotein (LDL) particles, have been attributed to dietary soy isoflavones. Paraoxonase 1 (PON1), an enzyme mainly synthesized in the liver, may exhibit anti‐atherogenic activity by protecting LDL from oxidation. Thus, dietary and pharmacological inducers of PON1 may decrease cardiovascular disease risk. Using a luciferase reporter gene assay we screened different flavonoids for their ability to induce PON1 in Huh7 hepatocytes in culture. Genistein was the most potent flavonoid with regard to its PON1‐inducing activity, followed by daidzein, luteolin, isorhamnetin and quercetin. Other flavonoids such as naringenin, cyanidin, malvidin and catechin showed only little or no PON1‐inducing activity. Genistein‐mediated PON1 transactivation was partly inhibited by the oestrogen‐receptor antagonist fulvestrant as well as by the aryl hydrocarbon receptor antagonist 7‐ketocholesterol. In contrast to genistein, the conjugated genistein metabolites genistein‐7‐glucuronide, genistein‐7‐sulfate and genistein‐7,4′‐disulfate were only weak inducers of PON1 transactivation. Accordingly, dietary genistein supplementation (2 g/kg diet over three weeks) in growing rats did not increase hepatic PON1 mRNA and protein levels as well as plasma PON1 activity. Thus, genistein may be a PON1 inducer in cultured hepatocytes in vitro, but not in rats in vivo.
Osteoinduction and survival of osteoblasts and bone‐marrow stromal cells in 3D biphasic calcium phosphate scaffolds under static and dynamic culture conditions
Authors: Rath Subha N. , Strobel Leonie A. , Arkudas Andreas , Beier Justus P. , Maier Anne‐Kathrin , Greil Peter , Horch Raymund E. , Kneser Ulrich
Published: February 2012

In many tissue engineering approaches, the basic difference between in vitro and in vivo conditions for cells within three‐dimensional (3D) constructs is the nutrition flow dynamics. To achieve comparable results in vitro, bioreactors are advised for improved cell survival, as they are able to provide a controlled flow through the scaffold. We hypothesize that a bioreactor would enhance long‐term differentiation conditions of osteogenic cells in 3D scaffolds. To achieve this either primary rat osteoblasts or bone marrow stromal cells (BMSC) were implanted on uniform‐sized biphasic calcium phosphate (BCP) scaffolds produced by a 3D printing method. Three types of culture conditions were applied: static culture without osteoinduction (Group A); static culture with osteoinduction (Group B); dynamic culture with osteoinduction (Group C). After 3 and 6 weeks, the scaffolds were analysed by alkaline phosphatase (ALP), dsDNA amount, SEM, fluorescent labelled live‐dead assay, and real‐time RT‐PCR in addition to weekly alamarBlue assays. With osteoinduction, increased ALP values and calcium deposition are observed; however, under static conditions, a significant decrease in the cell number on the biomaterial is observed. Interestingly, the bioreactor system not only reversed the decreased cell numbers but also increased their differentiation potential. We conclude from this study that a continuous flow bioreactor not only preserves the number of osteogenic cells but also keeps their differentiation ability in balance providing a suitable cell‐seeded scaffold product for applications in regenerative medicine.
Overexpression of mouse TTF‐2 gene causes cleft palate
Authors: Meng Tian , Shi Jia‐Yu , Wu Min , Wang Yan , Li Ling , Liu Yan , Zheng Qian , Huang Lei , Shi Bing
Published: February 2012

In humans, mutations of the gene encoding for thyroid transcription factor‐2 (TTF‐2 or FOXE1) result in Bamforth syndrome. Bamforth syndrome is characterized by agenesis, cleft palate, spiky hair and choanal atresia. TTF‐2 null mice (TTF‐2−/−) also exhibit cleft palate, suggesting its involvement in the palatogenesis. However, the molecular pathology and genetic regulation by TTF2 remain largely unknown. In the present study, the recombinant expression vector pBROAD3‐TTF‐2 containing the promoter of the mouse ROSA26 gene was created to form the structural gene of mouse TTF‐2 and was microinjected into the male pronuclei of fertilized ova. Sequence analysis confirmed that the TTF‐2 transgenic mouse model was established successfully. The transgenic mice displayed a phenotype of cleft palate. In addition, we found that TTF‐2 was highly expressed in the medial edge epithelium (MEE) from the embryonic day 12.5 (E12.5) to E14.5 in TTF‐2 transgenic mice. These observations suggest that overexpression of TTF‐2 during palatogenesis may contribute to formation of cleft palate.
Increased Twist expression in advanced stage of mycosis fungoides and Sézary syndrome
Authors: Goswami Meghali , Duvic Madeleine , Dougherty Alexis , Ni Xiao
Published: February 2012

Background: The mechanisms of tumor progression in mycosis fungoides (MF) and Sézary syndrome (SS) are poorly understood. Twist, a transcription factor, is thought to promote solid tumor progression by blocking p53 and inhibiting c‐myc‐induced apoptosis. Whether Twist expression is correlated to MF/SS stages remains unknown.

Methods: Twist, c‐myc and p53 proteins in 68 MF/SS lesions across all T stages were examined by immunohistochemistry, and mRNA levels in peripheral blood CD4+ T‐cells from SS patients were measured by real‐time quantitative polymerase chain reaction.

Results: Positive staining for Twist was found in 12.5% (2/16) of T1 and 33.3% (7/21) of T2 early stage patches/plaques compared to 50.0% (9/18) of T3 tumors and 84.6% (11/13) of T4 erythroderma. Most T4 erythroderma were positive for Twist in dermal lymphocytes, with the strongest staining. Positive staining for c‐myc was higher in T3/T4 lesions (29/31, 93.5%) than T1/T2 lesions (25/37, 67.6%, p < 0.05), with strongest staining in T3 tumors. Aberrant p53 expression was more common in T3/T4 lesions (8/31, 25.8%) than in T1/T2 lesions (2/37, 5.4%, p < 0.05). Twist mRNA was detected in all CD4+ T cells from SS patients but not in normal donors.

Conclusions: Increased Twist protein expression in advanced MF/SS lesions suggests that Twist expression may correlate with MF/SS stages.

Goswami M, Duvic M, Dougherty A, Ni X. Increased Twist expression in advanced stage of mycosis fungoides and Sézary syndrome.
Zinc gluconate is an agonist of peroxisome proliferator‐activated receptor‐α in the epidermis
Authors: Poiraud Carole , Quereux Gaëlle , Knol Anne‐Chantal , Allix Rémy , Khammari Amir , Dreno Brigitte
Published: February 2012

Abstract:  Peroxisome proliferator‐activated receptors‐α (PPARs‐α) are nuclear receptors with anti‐inflammatory properties. Zinc gluconate is efficient in the treatment of several inflammatory dermatoses. The aim of our work was to determine whether the modulation of PPAR‐α expression and activity could be one of the mechanisms of action of zinc gluconate anti‐inflammatory activity in inflammatory dermatoses. Thus, we used ex vivo skin explants incubated with lipopolysaccharide (LPS), a pro‐inflammatory molecule, with or without zinc gluconate. We evaluated PPAR‐α protein expression using immunohistochemistry, PPAR‐α DNA‐binding activity using an ELISA‐like technique, and PPAR‐α mRNA levels using quantitative PCR. On the one hand, we found that PPAR‐α epidermal protein expression was stimulated by LPS and that LPS suppressed PPAR‐α mRNA expression, without modifying its function. On the other hand, in inflammatory LPS‐stimulated explants, zinc gluconate significantly upregulated PPAR‐α function and mRNA expression level, without changing its epidermal protein expression. These results suggest that zinc gluconate may be a PPAR‐α agonist, which might play a role in the anti‐inflammatory activity of this molecule.
Age‐dependent change in behavioral feature in Rubinstein‐Taybi syndrome
Authors: Yagihashi Tatsuhiko , Kosaki Kenjiro , Okamoto Nobuhiko , Mizuno Seiji , Kurosawa Kenji , Takahashi Takao , Sato Yuji , Kosaki Rika
Published: February 2012

Rubinstein‐Taybi syndrome (RTS) is characterized by developmental delay, postnatal growth retardation, typical facial appearance, and broad thumbs and big toes. The behavioral phenotype of children with RTS has been described as friendly and having good social contacts; however, a short attention span and hyperactivity are sometimes present. Little attention has been paid to the behavioral aspects of adults with RTS. We conducted an observational study focusing on behavioral problems in adolescents and adults with RTS compared with children with RTS. A total of 63 patients with RTS and their caretakers answered self‐administered questionnaires regarding behavioral features including the Child Behavior Checklist (CBCL). High total CBCL scores were observed, and the mean score was beyond the clinical cut‐off point. After stratification into two groups according to age, the older group (≥14 years) displayed statistically significant higher scores for Anxious/Depression (P = 0.002) and Aggressive Behavior (P = 0.036) than the younger group (≤13 years). In analyses of single items, statistically significant differences between the younger group and the older group were found for ‘Nervous, high‐strung, or tense’ (31.3% vs 67.7%, P = 0.004) and ‘Too fearful or anxious’ (37.5% vs 64.5%, P = 0.032). Here, we showed that the specific behavioral phenotypes of RTS change during adolescence, with anxiety, mood instability, and aggressive behavior emerging as patients age. A clear need exists to follow‐up patients with RTS to catch the eventual emergence of psychiatric problems with age. If necessary, pharmacological treatment should be considered.
Contingency Management in Community Programs Treating Adolescent Substance Abuse: A Feasibility Study
Authors: Killeen Therese K. , McRae‐Clark Aimee L. , Waldrop Angela E. , Upadhyaya Himanshu , Brady Kathleen T.
Published: February 2012

PROBLEM:  Adolescent substance abuse remains a public health problem, and more effective treatment approaches are needed.

PURPOSE:  The study aims to determine the feasibility and preliminary effectiveness of implementing a cost‐effective contingency management (CM) intervention in community substance abuse treatment for adolescents with marijuana use disorders.

METHODS:  Thirty‐one adolescents with primary marijuana use disorder enrolled in a community treatment were randomized into either a prize‐based CM intervention contingent when submitting negative urine drug screens (UDS) or a noncontingent control group.

FINDINGS:  There were no significant group differences in percent negative UDS, sustained negative UDS, or retention in treatment.

CONCLUSIONS:  CM was difficult to integrate into community treatment programs and did not seem to be an effective adjunct to standard community substance abuse treatment for adolescents with marijuana use disorders. Modifying the CM procedure for adolescents, changing staff attitudes toward CM, and/or combining CM with other evidence‐based psychosocial treatment may improve outcomes.
Memory deficits for non‐amnestic mild cognitive impairment
Authors: Wang Bei , Guo Qihao , Zhao Qianhua , Hong Zhen
Published: February 2012

Non‐amnestic mild cognitive impairment (naMCI) is one of the clinical subtypes of mild cognitive impairment (MCI). However, the characteristics of memory deficits in naMCI as assessed by clinical neuropsychological evaluations are not clear. In this study, a battery of neuropsychological tests was administered to 122 cognitively normal controls (NC), 133 amnestic mild cognitive impairment (aMCI) patients, and 72 naMCI patients. The results showed that in individuals with naMCI, episodic memory, and other cognitive domains were impaired. The Prospective Memory Test (PMT) event‐based prospective memory (EBPM), the Symbol Digit Modalities Test (SDMT) Accidental Memory, Stick test (ST) visuoconstructional memory, and ST Working Memory were impaired, yet did not reach the level of aMCI. Semantic memory was affected to a degree comparable with aMCI. Some functions like Auditory Verbal Learning Test (AVLT) recognition, and Judgment of Confidence (JOC) were maintained, as well as PMT Time‐Based Prospective Memory (TBPM). This study verified that memory impairment among individuals with naMCI was mainly in memory functions mediated by the frontotemporal cortex.
The Psychology of Competitive Advantage: An Adjacent Possibility
Authors: Ployhart Robert E.
Published: February 2012

This article argues that the field of industrial–organizational (I–O) psychology should expand its focus from studying individual and small-group behavior to also studying how psychology contributes to organizational strategy and sustained competitive advantage. The field of strategy has recently sought to understand the microfoundations of competitive advantage, and I–O psychology brings much expertise to inform the study of such microfoundations. However, most I–O research pays little attention to strategic issues. In this article, I provide an introduction to strategic management, focusing primarily on the resource-based determinants of competitive advantage. I then discuss the potential benefits of I–O science and practice tackling important strategic issues yet also note the challenges and likely evolutions that will be necessary in our theory and research. The field of personnel selection is used as an illustration, but other areas of I–O are also considered.
Vanishing behaviors
Authors: Caro Tim , Sherman Paul W.
Published: February 2012

Unique patterns of animal behavior and life histories are not regarded as serious targets in making conservation and management decisions. Here we highlight the conceptual and practical conservation value of preserving such variations, review recent declines in behavioral diversity in wild populations, and encourage conservation biologists, animal behaviorists, and wildlife managers to document and protect behavioral diversity in the wild.
Patients for patient safety in China: A cross sectional study
Authors: Zhang Qiongwen , Li Yulin , Li Jing , Mao Xuanyue , Zhang Lijuan , Ying Qinghua , Wei Xin , Shang Lili , Zhang Mingming
Published: February 2012

Objectives: To investigate the baseline status of patients’ awareness, knowledge, and attitudes to patient safety in China, and to determine the factors that influence patients’ involvement in patient safety.

Methods: We conducted a cross sectional survey using questionnaires adapted from recent studies on patient safety from outside China. The items included medical errors, infection, medication safety, and other aspects of patient safety. The questionnaire included 17 items and 5 domains. The survey was conducted between Jan. 2009 and Dec. 2010 involving 1000 patients from ten grade‐A hospitals in seven provinces or cities in China. Most patients from the surgery departments completed the questionnaires voluntarily and anonymously. Five reviewers independently input the data into Microsoft Excel 2003, and the data were double‐checked. Data were analyzed using SPSS 15.0 software for differences in the perceptions and attitudes of patients toward patient safety among different genders, ages, and regions.

Results: We distributed 1000 questionnaires and collected 959 completed questionnaires (response rate: 96%). Among the respondents, 58% of patients did not know what medical error is. Sixty‐five percent of patients wanted disclosure of all medical errors. After errors occurred, 58% of patients wanted explanations of all possible harms that had resulted. Among 187 patients who had experienced medical errors, 83% of patients had sought appropriate legal action. About 52% of patients understood hospital infection, but 28% patients did not know that infections could occur in hospital. Seventy‐eight percent of patients thought that medical staff should wash their hands before examining patients. More than half of the patients (68%) were willing to remind the staff of hygiene if they saw unsanitary conditions in a health clinic. Only 14% of patients knew the side effects of medications that they took.

Conclusion: The majority of patients surveyed expressed willingness to contribute to patient safety, but their knowledge about patient safety practices was generally very limited.
Silencing thioredoxin induces liver cancer cell senescence under hypoxia
Authors: Zhang Ti , Liu Heping , Zhu Cihui , Briggs Katrina , Kang Ya'an , Fleming Jason A. , Curley Steven A.
Published: February 2012

Aim:  Although thioredoxin 1 (TXN) has pleiotropic cellular functions as a redox‐sensitive protein, very little is known about its role in tumor survival and growth under hypoxia. MHCC97H hepatocellular carcinoma cells have a high metastatic potential and high thioredoxin expression levels compared with their parent cell line, MHCC97. Thus, we used this cell line to explore the functional connections between TXN and hypoxia.

Methods:  MHCC97H cells were cultured under normoxia and hypoxia for specific periods after nucleofection with TXN siRNA or control siRNA. We assessed the β‐phenylethyl isothiocyanate (PEITC) sensitivity of the cells, cell proliferation, cell cycle and senescence, and DNA damage response by using 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) assays, colony formation assays, flow cytometry, β‐galactosidase staining, western blotting, and immunohistochemistry.

Results:  β‐phenylethyl isothiocyanate treatment shifted reduced TXN to oxidized TXN in MHCC97H cells. Although silencing of TXN via siRNA had no effect on the PEITC sensitivity of the cells, it suppressed cell proliferation and colony formation under both normoxia and hypoxia. Under hypoxia, silencing TXN did not induce apoptosis but induced DNA damage response and cellular senescence.

Conclusions:  High TXN levels in MHCC97H cells protect them from DNA damage and cellular senescence under hypoxia. Targeting TXN might enhance the chemotherapeutic effects of some DNA‐damaging agents against hepatocellular carcinoma.
Plasma free choline is a novel non‐invasive biomarker for early‐stage non‐alcoholic steatohepatitis: A multi‐center validation study
Authors: Imajo Kento , Fujita Koji , Yoneda Masato , Shinohara Yoshiyasu , Suzuki Kaori , Mawatari Hironori , Takahashi Junichiro , Nozaki Yuichi , Sumida Yoshio , Kirikoshi Hiroyuki , Saito Satoru , Nakamuta Makoto , Matsuhashi Nobuyuki , Wada Koichiro , Nakajima Atsushi
Published: February 2012

Aim:  Choline is a dietary component that is crucial for normal cellular function. Choline is predominantly absorbed from the small intestine and completely metabolized in the liver. We recently demonstrated that free choline (fCh) levels in blood reflect the level of phosphatidylcholine synthesis in the liver and is correlated with the onset of non‐alcoholic steatohepatitis (NASH). Our aim here was to validate the utility of this biomarker for NASH diagnosis.

Methods:  Our cohort consisted of 110 patients with biopsy proven non‐alcoholic fatty liver disease (NAFLD) from four centers across Japan and 25 age‐matched healthy controls. Plasma fCh levels were measured using high‐performance liquid chromatography.

Results:  Patients with diagnosed or borderline NASH had significantly increased plasma fCh levels when compared with control subjects, or patients not diagnosed with NASH. Interestingly, an association between plasma fCh levels and expression of microsomal triglyceride transfer protein, which catalyzes the transfer of triglyceride, was reflected in the markedly negative correlation between these two variables in patients with NAFLD. Moreover, the grade of liver steatosis and fibrosis stage increased with increasing plasma fCh levels (P < 0.05). The area under the receiver‐operating characteristic (ROC) curves for NASH, including borderline diagnosis, was 0.811. Additionally, the areas under the ROC for fibrosis stage were 0.816 for >stage 1, 0.805 for >stage 2, 0.809 for >stage 3 and 0.818 for >stage 4.

Conclusion:  Plasma fCh levels are closely related to the grade of liver steatosis and fibrosis, and predict NASH severity. Plasma fCh levels are therefore a potential diagnostic marker for early‐stage NASH in clinical practice.
Association of Ephrin receptor A3 gene polymorphism with susceptibility to chronic severe hepatitis B
Authors: Yang Hong , He Xing‐Xing , Song Qi‐Long , Chen Man , Li Jin , Wang Meng‐Yi , Yu Jin‐Ling , Yao Jin‐Jian , Liu Li‐Feng , Lin Ju‐Sheng
Published: February 2012

Aim:  Previous research has suggested that Ephrin receptor A3 (EphA3) plays signaling roles in the processes of inflammation by regulating lymphocyte migration and proliferation. In this study, we investigated whether the EphA3 gene polymorphism was associated with disease progression of chronic hepatitis B virus (HBV) infection.

Methods:  The EphA3 variant rs9310117 was genotyped in 1245 unrelated Han Chinese HBV carriers including 800 cases and 445 controls. χ2 test was used to examine the difference in allele frequencies and genotype distributions between groups. The association between the polymorphism and disease progression of HBV infection was conducted by unconditional logistic regression analysis.

Results:  Statistical analysis revealed that the genetic variant was significantly associated with the occurrence of chronic severe hepatitis B (CSHB). We observed that subjects bearing at least one T allele (C/T or T/T genotype) had a decreased susceptibility to chronic severe hepatitis B compared with those bearing C/C genotype (P = 0.003, odds ratio = 0.560; 95% confidence interval, 0.381–0.824, recessive model). Genotype C/T had also been confirmed to protect subjects from suffering chronic severe hepatitis B (P = 0.001, odds ratio = 0.498; 95% confidence interval, 0.330–0.752, additive model).

Conclusion:  Our results suggest that the genetic alteration at EphA3 locus plays a role in the occurrence of chronic severe hepatitis B.
Labor Unions and Management’s Incentive to Signal a Negative Outlook*
Authors: Bova Francesco
Published: February 2012

Evidence suggests that the negotiated wage for a unionized employee group is an increasing function of the firm’s prior profitability. As a result, managers may have an incentive to strategically signal a negative outlook to their unionized workers in order to improve the firm’s bargaining position. I assess the strategy of missing mean consensus analysts’ earnings estimates as a way for managers to signal a negative outlook to their unionized employees. I find that unionized firms are more likely to miss estimates than their nonunionized counterparts. Additionally, this propensity to miss estimates is increasing in both the firm’s percentage of unionized employees and multiunionism, but is unaffected by the timing of the signal relative to contract renewal. Finally, the increased propensity to miss estimates appears to be driven by both differences in expectations management and earnings management across the two groups. Specifically, managers of unionized firms take less action than their nonunionized counterparts to guide forecasts downward when estimates are too high, and they take more action to deflate earnings when expectations are too low. Taken together, the findings suggest that managers do seek to project a negative outlook to their unions, and that this tendency is increasing in the union’s negotiation strength.
Experimental Soybean Meal Intoxication in Cattle
Authors: Raboisson D. , Ferrières A. , Nicot M.C. , Enjalbert F. , Schelcher F.
Published: February 2012

Background

Cattle are commonly fed soybean meal (SBM) and accidental intoxication sometimes occurs.

Objectives

To describe the biologic and clinical features of SBM intoxication.

Animals

Four steers with ruminal cannula.

Methods

Controlled experimental trial. SBM was administered once at 1 and 2% of body weight (BW) via cannula at 2‐month intervals.

Results

This study showed a 2‐phase pathogenic course for 2% BW SBM intoxication. The 1st phase (until 10 hours post‐administration) is restricted to ruminal modification with volatile fatty acid overproduction and moderate ruminal ammonia concentration. In the 2nd phase (12–22 hours post‐administration), ruminal pH returned to initial values and marked ammonia accumulation occurred in blood, inducing severe metabolic alkalosis with hyperglycemia, hyperinsulinemia, and delayed aciduria (30–40 hours post‐administration). Among the clinical signs, nervous signs were only observed during the period with increased plasma ammonia concentration. At 1% BW, ruminal and blood modifications were less pronounced than at 2% BW, and clinical signs were not observed.

Conclusions and Clinical Relevance

Ammonia accumulation in blood during the second phase is the consequence of continued ammonia production, decreased carbohydrate fermentation, and overwhelming of hepatic detoxifying capacity. Because ammonia accumulation is associated with the clinical signs, treatment of SBM intoxication could be similar to treatment of urea intoxication, including rumenotomy, oral administration of cold water and vinegar, and measurement of ruminal pH.
Patient-specific factors relating to medication adherence in a post-percutaneous coronary intervention cohort
Authors: Rushworth Gordon F , Cunningham Scot , Mort Alasdai , Rudd Ia , Leslie Stephen J
Published: February 2012

Objective

To explore the association between medication adherence and qualitatively characterised patient-specific themes relating to medication adherence in patients following percutaneous coronary intervention (PCI).

Methods

Data-collection questionnaires and qualitative topic guides were piloted in two patients. A validated questionnaire generated an adherence score for a convenience sample of 20 patients within 7 days of PCI. Semi-structured qualitative interviews were subsequently carried out with all patients to explore patient-specific themes relating to measured medication adherence.

Key findings

Fourteen out of 20 patients (70%) had scores indicative of good adherence. Key factors associated with good adherence included having a good relationship with the doctor, having an understanding of the condition, knowledge of the indications and consequences of non-adherence, perceived health benefits and medications eliciting tangible symptom control. There were misconceptions of concern regarding adverse drug reactions and the importance of aspirin, both of which had a negative effect on adherence. The role of the community pharmacist was sometimes, although not always, misunderstood.

Conclusion

This study suggests there is an association between patients' beliefs, knowledge, understanding and misconceptions about medication and their adherence in a post-PCI cohort. To optimise medication adherence it is vital for prescribers to remain patient-focused and cognisant of patient-specific themes relating to medication adherence.
Using Bayes’ theorem in behavioural crime linking of serial homicide
Authors: Salo Benny , Sirén Jukka , Corander Jukka , Zappalà Angelo , Bosco Dario , Mokros Andreas , Santtila Pekka
Published: February 2012

Purpose. The study extends research by Santtila et al. (2008) by investigating the effectiveness of linking cases of serial homicide using behavioural patterns of offenders, analysed through Bayesian reasoning. The study also investigates the informative value of individual behavioural variables in the linking process.

Methods. Offender behaviour was coded from official documents relating to 116 solved homicide cases belonging to 19 separate series. The basis of the linkage analyses was 92 behaviours coded as present or absent in the case based on investigator observations on the crime scene. We developed a Bayesian method for linking crime cases and judged its accuracy using cross‐validation. We explored the information added by individual behavioural variables, first, by testing if the variable represented purely noise with respect to classification, and second, by excluding variables from the original model, one by one, by choosing the behaviour that had the smallest effect on classification accuracy.

Results. The model achieved a classification accuracy of 83.6% whereas chance expectancy was 5.3%. In simulated scenarios of only one and two known cases in a series, the accuracy was 59.0 and 69.2%, respectively. No behavioural variable represented pure noise but the same level of accuracy was achieved by analysing a set of 15, as analysing all 92 variables.

Conclusion. The study illustrates the utility of analysing individual behavioural variables through Bayesian reasoning for crime linking. Feasible applied use of the approach is illustrated by the effectiveness of analysing a small set of carefully chosen variables.
On the Manifold Property of the Set of Singularities of Kinematic Mappings: Genericity Conditions
Authors: Müller Andreas
Published: February 2012

Whether the singularities of a kinematic mapping constitute smoothmanifolds is an important question with significance to mechanism design and robot control. It is thus obvious to ask if this is generically so. In a preceding paper, two kinematically meaningful genericity concepts have been introduced. In this paper, geometric conditions for the manifold property of families of kinematic mappings are addressed, and a sufficient condition is presented. This condition involves the joint screws and screws representing feasible link geometries specific to a class of kinematic mappings. It admits to establish genericity of the manifold property for given classes of kinematic mappings. This is a step forward to prove that singularities of kinematic mappings form generically smooth manifolds. As an example it is shown that the singularities of 3-DOF forward kinematic mappings form generically smooth manifolds. Restricting this condition to a particular geometry allows to check whether singularities of a given kinematic mapping form smooth manifolds.
A General Degree of Freedom Formula for Parallel Mechanisms and Multiloop Spatial Mechanisms
Authors: Yang Ting-Li , Sun Dong-Jin
Published: February 2012

Based on the position and orientation characteristic (POC) set and the POC equations for serial mechanisms and parallel mechanisms proposed by authors, this paper presents a novel general degree of freedom (DOF) formula which is totally different from approaches based on the screw theory and the displacement group. It can be used to determine the full-cycle DOF of parallel mechanisms (PMs) and multiloop spatial mechanisms using symbolic “union” and “intersection” operations for POC sets. These operations involve only several rules and only simple mathematical tools (vector algebra, theory of sets, etc.) are used. Furthermore, criteria for determination of the inactive joints and selection of the actuating joints are proposed. The presented approach is illustrated with several examples.
Founder Effects Persist Despite Adaptive Differentiation: A Field Experiment with Lizards
Authors: Kolbe Jason J. , Leal Manuel , Schoener Thomas W. , Spiller David A. , Losos Jonathan B.
Published: February 2012

Random and Directed

Natural selection drives populations to adapt to new environments; the raw material or “founder effects” provided by the first colonizing individuals can thus have a formative influence on the population's future.

Kolbe
et al.

(p.
1086
, published online 2 February; see the cover) tested the relative contributions of selection and founder effects in Bahamian lizards. Founders were taken from an island covered in forest: These lizards had long hindlimbs for sprinting across the broad expanses of tree trunks. Long-limbed lizards were introduced to seven smaller islands covered in scrub that, before hurricane Frances in 2004 swept them away, had been populated by lizards with short hindlimbs better suited for navigating a twiggy habitat. After several generations, all the new lizard populations had adapted to their new habitats by evolving shorter hindlimbs but they also retained other morphological and genetic signatures from their founding ancestors. Thus, evolution occurs by a combination of arbitrary events, as well as those shaped by selection.
Pollinator-Mediated Selection on Flower Color Allele Drives Reinforcement
Authors: Hopkins Robin , Rausher Mark D.
Published: February 2012

The Constant Pollinator

In ecology, reinforcement is the process by which species prevent hybridization and maintain species boundaries, but the underlying genetic mechanisms are unclear.
Hopkins and Rausher
(p.
1090
, published online 2 February) examined reinforcement between two species of a wild flowering plant called
Phlox
that show incomplete hybrid sterility. Down-regulation of a flavonoid gene produces red flowers and operates in concert with a color intensity locus to adjust flower color and tone. A distinct geography of flower color has emerged in which it appears that dark coloration causes less hybridization between the species because the butterfly pollinators tend to favor light-blue flower color variants. If pollinators visit flowers with similar phenotypes more frequently than flowers with dissimilar phenotypes, this will decrease gene flow between the unlike flowers.
Extremely Long-Lived Nuclear Pore Proteins in the Rat Brain
Authors: Savas Jeffrey N. , Toyama Brandon H. , Xu Tao , Yates John R. , Hetzer Martin W.
Published: February 2012

Individual components of rat brain nuclear pores can be almost as old as the animal itself.
Field-Effect Tunneling Transistor Based on Vertical Graphene Heterostructures
Authors: Britnell L. , Gorbachev R. V. , Jalil R. , Belle B. D. , Schedin F. , Mishchenko A. , Georgiou T. , Katsnelson M. I. , Eaves L. , Morozov S. V. , Peres N. M. R. , Leist J. , Geim A. K. , Novoselov K. S. , Ponomarenko L. A.
Published: February 2012

Tunnel Barriers for Graphene Transistors

Transistor operation for integrated circuits not only requires that the gate material has high-charge carrier mobility, but that there is also an effective way of creating a barrier to current flow so that the device can be switched off and not waste power. Graphene offers high carrier mobility, but the shape of its conduction and valence bands enables electron tunneling and makes it difficult to achieve low currents in an “off” state.

Britnell
et al.

(p.
947
, published online 2 February) have fabricated field-effect transistors in which a thin tunneling barrier created from a layered material—either hexagonal boron nitride or molybdenum disulfide—is sandwiched between graphene sheets. These devices exhibit on-off switching ratios of ≈50 and ≈10,000, respectively, at room temperature.
Why do disilanes fail to fluoresce?
Authors: MacLeod Matthew K. , Michl Josef
Published: February 2012

In contrast to longer peralkylated oligosilanes, many of which fluoresce efficiently, disilanes and trisilanes exhibit no detectable fluorescence even at low temperatures. This is especially striking in the case of disilanes, whose S1-S0 transition is quite strongly allowed, and which must have very efficient electronic excited state deactivation mechanisms. To identify them, we examine the lowest excited singlet state potential energy surface S1 of Si2Me6 with TDDFT (B3LYP/TZVP, PBE0/TZVP and BHLYP/TZVP) and ab initio (RICC2/TZVP and RIADC(2)/TZVP) methods and identify several shallow minima and nearby funnels. Relaxed excited state structures show strong valence rehybridization relative to the ground state, allowing optimal accomodation of the simultaneous presence of a negative and a positive charge in their Lewis structures. Efficient decay pathways and relations to longer oligosilanes are discussed.
Can management regulate the population size of wild reindeer (Rangifer tarandus) through harvest?
Authors: Strand O. , Nilsen E.B. , Solberg E.J. , Linnell J.C.D.
Published: February 2012

We analyzed a 51-year time series of harvest data from a small population of wild mountain reindeer ( Rangifer tarandus (L., 1758)) in southern Norway and examined the relative role of biological and management related processes as drivers of its population dynamics. The population is monitored annually to obtain information on population size and structure, and since 1980, managers have attempted to stabilize the population at about 1.1 reindeer/km2. The harvest increased at a higher rate than the population size and was thus probably sufficient to not only limit but also regulate population size. Phase plot analyses showed that the population has varied around a density attractor of about 1.0 reindeer/km2since 1980 and is therefore close to the targeted population size of 1.1 reindeer/km2. However, the annual harvest explained only 49% of the variation in population growth rate (λ) in a linear regression model, despite relatively low variation in population productivity (proportion of calves). Between 1999 and 2006, the population in Forolhogna declined by almost 50% before recovering to its previous size. We suggest that both imprecise population estimates and high harvest effectiveness at reduced population densities contributed to this decline. As such, this study points to some of the obstacles managers are facing when trying to stabilize productive ungulate populations even when they live in closed populations and in stable, predator-free environments.