bluuebunny/crossref_metadata_2025 huggingface dataset:
AQUINAS AND THE OBLIGATIONS OF MERCY
Authors: Floyd Shawn
Published: August 2009

Contemporary philosophers often construe mercy as a supererogatory notion or a matter of punitive leniency. Yet it is false that no merciful actions are obligatory. Further, it is questionable whether mercy is really about punitive leniency, either exclusively or primarily. As an alternative to these accounts, I consider the view offered by St. Thomas Aquinas. He rejects the claim that we are never obligated to be merciful. Also, his view of mercy is not restricted to legal contexts. For him, mercy's scope is considerably broader, as it concerns a wide range of needs and hardships to which human beings are vulnerable. Such a view, I submit, affords a kind of normative depth lacking in many contemporary accounts. Unlike those views that construe mercy as either a supererogatory or legal concept, Aquinas's account illuminates mercy's obligatory nature and encourages us to make mercy a more salient fixture of our moral lives.
Sensitivity to Violations of Gender Agreement in Native and Nonnative Spanish: An Eye‐Movement Investigation
Authors: Keating Gregory D.
Published: August 2009

This article reports the results of an eye‐tracking experiment that investigated the effects of structural distance on readers' sensitivity to violations of Spanish gender agreement during online sentence comprehension. The study tracked the eye movements of native Spanish speakers and English‐speaking learners of Spanish as they read sentences that contained nouns modified by postnominal adjectives located in three syntactic domains: (a) in the DP, (b) in the VP, or (c) in a subordinate clause. In half of the sentences in each condition, adjectives agreed with the noun in gender, and in half, they did not. The results indicate that gender agreement is acquirable in adulthood, contra the failed functional features hypothesis, and that the distance that separates nouns and adjectives affects the detection of gender anomalies in the second language. The findings support Clahsen and Felser's (2006a) shallow structure hypothesis, as it pertains to morphological processing.
The Effects of Instruction on Linguistic Development in Spanish Heritage Language Speakers
Authors: Potowski Kim , Jegerski Jill , Morgan‐Short Kara
Published: August 2009

The current study compared the effects of two second language (L2) instruction types—processing instruction (VanPatten, 2004) and traditional output‐based instruction—on the development of the Spanish past subjunctive among U.S. Spanish heritage language speakers and traditional L2 learners. After exposure to instruction, both the heritage learners and the L2 learners showed significant improvement on interpretation and production tasks. Only the L2 learners showed significant improvement for grammaticality judgments. Overall, the L2 learners outperformed the heritage learners. The results suggest that heritage speakers' language development may differ from that of L2 learners, although they also suggest that heritage speakers can benefit from focused grammar instruction.
EFNS guideline on the drug treatment of migraine – revised report of an EFNS task force
Authors: Evers S. , Áfra J. , Frese A. , Goadsby P. J. , Linde M. , May A. , Sándor P. S.
Published: August 2009

Background:  Migraine is one of the most frequent disabling neurological conditions with a major impact on the patients’ quality of life.

Objectives:  To give evidence‐based or expert recommendations for the different drug treatment procedures in the particular migraine syndromes based on a literature search and the consensus of an expert panel.

Methods:  All available medical reference systems were screened for the range of clinical studies on migraine with and without aura and on migraine‐like syndromes. The findings in these studies were evaluated according to the recommendations of the European Federation of Neurological Societies (EFNS) resulting in level A, B, or C recommendations and good practice points.

Recommendations:  For the acute treatment of migraine attacks, oral non‐steroidal antiinflammatory drug (NSAID) and triptans are recommended. The administration should follow the concept of stratified treatment. Before intake of NSAID and triptans, oral metoclopramide or domperidone is recommended. In very severe attacks, intravenous acetylsalicylic acid or subcutaneous sumatriptan are drugs of first choice. Status migrainosus can be treated by cortoicosteroids, although this is not universally held to be helpful, or dihydroergotamine. For the prophylaxis of migraine, betablockers (propranolol and metoprolol) flunarizine, valproic acid, and topiramate are drugs of first choice. Drugs of second choice for migraine prophylaxis include amitriptyline, naproxen, petasites, and bisoprolol.
Proposals for New Standardized General Diagnostic Criteria for the Secondary Headaches
Authors: Olesen J , Steiner T , Bousser M-G , Diener H-C , Dodick D , First MB , Goadsby PJ , Göbel H , Lainez MJA , Lipton RB , Nappi G , Sakai F , Schoenen J , Silberstein SD
Published: August 2009

Headache classification is a dynamic process through clinical testing and re-testing of current and proposed criteria. After publication of the second edition of the International Classification of Headache Disorders (ICHD-II), need arose for revisions in the classification of medication overuse headache and chronic migraine. These changes made apparent a further need for broader revisions to the standard formulation of diagnostic criteria for the secondary headaches. Currently, the fourth criterion makes impossible the definitive diagnosis of a secondary headache until the underlying cause has resolved or been cured or greatly ameliorated by therapy, at which time the headache may no longer be present. Given that the main purpose of diagnostic criteria is to enable a diagnosis at the onset of a disease in order to guide treatment, this is unhelpful in clinical practice. In the present paper we propose maintaining a standard approach to the secondary headaches using a set of four criteria A, B, C and D, but we construct these so that the requirement for resolution or successful treatment is removed. The proposal for general diagnostic criteria for the secondary headaches will be entered into the internet-based version of the appendix of ICHD-II. During 2009 the Classification Committee will apply the general criteria to all the specific types of secondary headaches. These, and other changes, will be included in a revision of the entire classification entitled ICHD-IIR, expected to be published in 2010. ICHD-IIR will be printed and posted on the website and will be the official classification of the International Headache Society. Unfortunately, it will be necessary to translate ICHD-IIR into the many languages of the world, but the good news is that no major changes to the headache classification are then foreseen for the next 10 years. Until the printing of ICHD-IIR, the printed ICHD-II criteria remain in place for all other purposes. We issue a plea to the headache community to use and study these proposed general criteria for the secondary headaches in order to provide more evidence for their utility—before their incorporation in the main body of the classification.
Role of the oestrogen receptor (ESR1 PvuII and ESR1 325 C→G) and progesterone receptor (PROGINS) polymorphisms in genetic susceptibility to migraine in a North Indian population
Authors: Joshi G , Pradhan S , Mittal B
Published: August 2009

We aimed to explore the single-locus, haplotype and epistasis patterns and the contribution of oestrogen receptor [ESR1 PvuII (rs2234693), ESR1 325 C→G (rs1801132)] and progesterone receptor [PROGINS (rs1042838)] polymorphisms in genetic susceptibility to migraine by analysing 613 subjects consisting of 217 migraine patients, 217 healthy controls (HC) and 179 patients with tension-type headache (TTH). Entire data were analysed by taking the Bonferroni corrected P-value into account. We found significant association of TT genotype [odds ratio (OR) 3.458, confidence interval (CI) 1.757, 6.806; P = 0.0003] and T allele (OR 1.729, CI 1.309, 2.284; P = 0.0001) of ESR1 PvuII single nucleotide polymorphism with migraine when compared with HC. Significant association was seen only in female migraine patients at both genotype ( P = 0.002; OR 3.834, CI 1.625, 9.043) and allele level ( P = 0.002; OR 1.721, CI 1.228, 2.413). Moreover, higher risk was limited to migraine with aura (MA) (in case of TT genotype, P = 0.002; OR 4.377, CI 1.703, 1.246; in case of T allele, P = 0.001; OR 1.888, CI 1.305, 2.735) rather than migraine without aura (MoA) ( P-value of TT genotype = 0.003; OR 3.082, CI 1.465, 6.483; P-value T allele = 0.002; OR 1.630, CI 1.188, 2.236). In case of a recessive model, risk was seen with migraine patients ( P = 0.0003; OR 2.514, CI 1.635, 3.867), MA ( P = 0.0001; OR 3.583, CI 1.858, 6.909) and MoA patients ( P = 0.002; OR 2.125, CI 1.304, 3.464) when compared with HC. No risk was observed when TTH patients were compared with HC. No significance of ESR 325 G→C polymorphism was seen in any of the models under study. Significant differences in genotypic ( P = 0.0001) and allelic frequency ( P = 0.0002) were seen in case of PROGINS polymorphism when migraine patients were compared with HC, showing a protective effect (for A1A2 genotype, OR 0.292, CI 0.155, 0.549; for A2 allele, OR 0.320, CI 0.174, 0.589). Moreover, significance was seen only in case of female migraine patients at genotype ( P = 0.002; OR 0.344, CI 0.176, 0.684) as well as allele levels ( P = 0.004; OR 0.379, CI 0.198, 0.727) in case of PROGINS polymorphism. ESR1 PvuII TT*ESR1 325 C→G CG genotype, PROGINS A1A2*ESR1 325 C→G CG genotype and ESR1 PvuII CT*PROGINS A1A2 interacted significantly, but significance was lost after Bonferroni correction. In conclusion, ESR1 PvuII polymorphism is a significant risk factor for migraine particularly in women and MA patients, but ESR 325 C→G polymorphism is not associated with migraine susceptibility. PROGINS polymorphism seems to play a protective role in genetic susceptibility to migraine in the North Indian population.
MTHFR 677C→T and ACE D/I polymorphisms and migraine attack frequency in women
Authors: Schürks M , Zee RYL , Buring JE , Kurth T
Published: August 2009

Data on the association of the MTHFR 677C→T and ACE D/I polymorphisms with migraine severity, measured by attack frequency, are scarce. We performed an association study among 24 961 women participating in the Women's Health Study. Migraine, aura status and attack frequency were self-reported. Multinomial logistic regression was used to investigate the genotype–migraine association. Among the 3186 migraineurs with complete genotype and attack frequency data, 1270 reported migraine with aura (MA) (attack frequency 76 ≥ weekly; 219 monthly; 123 every other month; 852 fewer than six times/year) and 1916 migraine without aura (MoA) (attack frequency: 85 ≥ weekly; 414 monthly; 208 every other month; 1209 fewer than six times/year). The MTHFR 677TT genotype was associated with a reduced risk for MA, which only appeared for attacks fewer than six times/year (age-adjusted odds ratio 0.78; 95% confidence interval 0.61, 0.99). We did not find a specific pattern of association of the ACE D/I polymorphism with attack frequency for MA or MoA.
Is the Value Spread a Good Predictor of Stock Returns? UK Evidence
Authors: Michou Maria
Published: August 2009

Abstract:  This paper explores the predictive ability of the value spread in the UK. I replicate the US analysis of Liu and Zhang (2007) using UK data. In addition, I extend their work by exploring the predictive ability of the book‐to‐market, market‐to‐book and value spread on other size and value investment strategies, namely: large‐caps only; small‐caps minus large‐caps (SML); value stocks only; growth stocks only; value stocks minus growth stocks (VMG) and a market portfolio that includes all stocks. The results are consistent with Liu and Zhang (2007) on the value spread. The value spread shows no predictive power for portfolio returns. Therefore, I show that the predictive power of book‐to‐market and market‐to‐book spreads depend on the portfolio formation strategies and the relative proportion of small‐cap, large‐cap, value and growth stocks in the portfolio.
A meta‐analysis of parasite virulence in nestling birds
Authors: Møller A. P. , Arriero E. , Lobato E. , Merino S.
Published: August 2009

Parasitism is a common cause of host mortality, but little is known about the ecological factors affecting parasite virulence (the rate of mortality among infected hosts). We reviewed 117 field estimates of parasite‐induced nestling mortality in birds, showing that there was significant consistency in mortality among host and parasite taxa. Virulence increased towards the tropics in analyses of both species‐specific data and phylogenetic analyses. We found evidence of greater parasite prevalence being associated with reduced virulence. Furthermore, bird species breeding in open nest sites suffered from greater parasite‐induced mortality than hole‐nesting species. By contrast, parasite specialization and generation time of parasites relative to that of hosts explained little variation in virulence. Likewise, there were little or no significant effects of host genetic variability, host sociality, host migration, host insular distribution or host survival on parasite virulence. These findings suggest that parasite‐induced nestling mortality in birds is mainly determined by geographical location and to a smaller extent nest site and prevalence.
The effects of valence and arousal on the neural activity leading to subsequent memory
Authors: Mickley Steinmetz Katherine R. , Kensinger Elizabeth A.
Published: August 2009

This study examined how valence and arousal affect the processes linked to subsequent memory for emotional information. While undergoing an fMRI scan, participants viewed neutral pictures and emotional pictures varying by valence and arousal. After the scan, participants performed a recognition test. Subsequent memory for negative or high arousal information was associated with occipital and temporal activity, whereas memory for positive or low arousal information was associated with frontal activity. Regression analyses confirmed that for negative or high arousal items, temporal lobe activity was the strongest predictor of later memory whereas for positive or low arousal items, frontal activity corresponded most strongly with later memory. These results suggest that the types of encoding processes relating to memory (e.g., sensory vs. elaborative processing) can differ based on the affective qualities of emotional information.
Early life stress and psychiatric disorder modulate cortical responses to affective stimuli
Authors: Weber Katja , Miller Gregory A. , Schupp Harald T. , Borgelt Jens , Awiszus Barbara , Popov Tzvetan , Elbert Thomas , Rockstroh Brigitte
Published: August 2009

Altered affective processing has been proposed as mediating between early life stress (ELS) and subsequent psychopathology. The present study examined whether ELS influences affective cortical processing differently in psychiatric patients and healthy subjects. The number of stressful experiences before onset of puberty was assessed in 50 inpatients with diagnoses of Major Depressive Disorder, schizophrenia, drug addiction, or Borderline Personality Disorder and in 20 healthy comparison subjects. Subjects monitored pleasant, neutral, and unpleasant pictures during magnetoencephalographic recording. Suppression of right‐posterior activity 160–210 ms after stimulus onset was associated with certain diagnoses and high ELS. Results confirmed specific contributions of ELS versus adult stress, comorbid posttraumatic stress disorder, or depression.
On the differentiation of N2 components in an appetitive choice task: Evidence for the revised Reinforcement Sensitivity Theory
Authors: Leue Anja , Chavanon Mira‐Lynn , Wacker Jan , Stemmler Gerhard
Published: August 2009

Task‐ and personality‐related modulations of the N2 were probed within the framework of the revised Reinforcement Sensitivity Theory (RST). Using an appetitive choice task, we investigated 58 students with extreme scores on the behavioral inhibition system and behavioral approach system (BIS/BAS) scales. The baseline‐to‐peak N2 amplitude was sensitive to the strength of decision conflict and demonstrated RST‐related personality differences. In addition to the baseline N2 amplitude, temporal PCA results suggested two N2 components accounting for a laterality effect and capturing different N2 patterns for BIS/BAS groups with increasing conflict level. Evidence for RST‐related personality differences was obtained for baseline‐to‐peak N2 and tPCA components in the present task. The results support the RST prediction that BAS sensitivity modulates conflict processing and confirm the cognitive–motivational conflict concept of RST.
ERP correlates of online monitoring of auditory feedback during vocalization
Authors: Hawco Colin S. , Jones Jeffery A. , Ferretti Todd R. , Keough Dwayne
Published: August 2009

When speakers hear the fundamental frequency (F0) of their voice altered, they shift their F0 in the direction opposite the perturbation. The current study used ERPs to examine sensory processing of short feedback perturbations during an ongoing utterance. In one session, participants produced a vowel at an F0 of their own choosing. In another session, participants matched the F0 of a cue voice. An F0 perturbation of 0, 25, 50, 100, or 200 cents was introduced for 100 ms. A mismatch negativity (MMN) was observed. Differences between sessions were only found for 200‐cent perturbations. Reduced compensation when speakers experienced the 200‐cent perturbations suggests that this larger perturbation was perceived as externally generated. The presence of an MMN, and no earlier (N100) response suggests that the underlying sensory process used to identify and compensate for errors in mid‐utterance may differ from feedback monitoring at utterance onset.
‘Home comes first’: housing and homemaking in Finnish civic educational films during 1945–1969
Authors: Lammi Minna
Published: August 2009

This article focuses on how the ideals of housing and homemaking were presented in post‐war civic educational films in Finland. The films chosen for the article pertain to housing on a wide scope. The analysis shows that the ideals of good homes appeared to be remarkably consistent in the Finnish educational short films. The most important objective was to guide citizens towards careful household management and saving. Through rationalizing home economics, consumers were able to buy their own home. The ideal housewife had a positive attitude towards technology and rational household management. While the short films instructed people towards temperate and sensible consumption, they also created space for ordinary people to envision new opportunities for consumption.
Trompe l'œil: architects, consumers, and the need to rediscover technical function for ecologically sustainable housing
Authors: Gabe Jeremy , Vale Robert , Vale Brenda
Published: August 2009

One challenge facing the need for ecologically sustainable housing is that it must cope with change over time. However, the flexibility required for housing to cope with change needs to be limited, as frequent change may offset the economy of resource use provided by durable housing stock. We describe two distinctly different but crucial aspects of housing services – social and technical functions – and briefly discuss how consumers and architects, who influence what consumers value in housing, have shifted design practices away from technical function and towards enhancement and growth of social function. Specifically, psychological obsolescence, which began in consumer products, is now emerging in housing, potentially accelerating demand for change as a result of fashion trends (an approach to the social function of identity expression) in housing. Four potential approaches to inspire consumer recognition of technical function in pursuit of ecologically sustainable housing are briefly discussed. These include promoting a ‘green’ fashion trend and three approaches that aim to restore the balance between social and technical function within housing design: regulatory tools, internalization of unaccounted costs, and incentives to move consumers from assumed to explicit recognition of technical function. Because they address the core problem of missing technical function, not just the increased demand for social functions, only these latter three approaches, possibly in combination, appear likely to contribute to a paradigm of ecologically sustainable housing.
Discovering the variables that influence new home‐buyer service satisfaction
Authors: Nahmens Isabelina , Ikuma Laura H.
Published: August 2009

While home builders traditionally think of customer service in terms of upgrades and mortgage options, home buyers are thought to view the quality of service on a much broader basis. Previous research has identified five dimensions of service quality: appearance, reliability, timeliness, knowledge, and empathy. Home‐buyer satisfaction with service quality is then the result of home builders providing services that are perceived as meeting or exceeding buyer expectations. Although much research has been done regarding home‐buyer satisfaction with service quality, there is still a gap between builders' and home buyers' perception of the quality of service. Builders need to identify and understand home‐buyer needs in order to constantly improve service quality. This paper describes an exploratory study that focused on customer satisfaction with service quality. The objective of this study was to assess the correlations between various factors on home‐buyer expectations and their perceptions of service quality. Demographics considered in this study included age, gender and household income, while transaction characteristics included purchase price, number of occupants and house size. Characteristics such as higher income, higher purchase price, and larger house size appeared to value dimensions such as reliability most highly. Characteristics such as lower income, lower purchase price and smaller house size appeared to value dimensions such as empathy and appearance most highly. Gender, age and household size did not have significant associations with expectations or relative importance, but age and household size were associated with actual perceptions of service dimensions. Understanding the influence of these variables on customer satisfaction with service quality can positively impact home builders through improved reputation and increased local referrals.
The information needs of prospective homebuyers: an exploratory study of apartment purchases in Finland
Authors: Savolainen Reijo
Published: August 2009

Ultimately, the search for housing depends on information about the housing market and individual apartments for sale. The housing search process gives rise to diverse information needs. Their nature is elaborated in an exploratory study drawing on interviews conducted with 16 Finnish homebuyers in 2008. The data were analysed by means of qualitative content analysis. The constant comparative approach was utilized to capture the nuances of information needs experienced at three major phases of the housing search process. At the phase of orientation to the housing market and identifying vacancies, the information needs covered a broad area including the supply of relevant apartments in preferred districts and the realistic funding opportunities. The temporal frame within which these needs were experienced was fairly broad. At the phase of assessing vacancies, the information needs became more specific and the temporal frame narrower, since the needs primarily dealt with concrete issues such as the renovation requirements of the apartment. Finally, at the phase of bid formation, information needs were mainly related to the determination of the proper price level and the optimal timing of the price bid.
Furnishing the salon: symbolic ethnicity and performative practices in Moroccan‐Dutch domestic interiors
Authors: Dibbits Hester
Published: August 2009

Confronted with traditional‐looking Moroccan furniture in a house where Moroccan migrants or their descendants live, one may interpret this furniture as an ethnic symbol, underlining the Moroccan, North African or Arabic background of the owners. Analysing interviews and discussions on the Internet, this article shows that the furniture has many other significances as well. It not only functions as an ethnic symbol, but also signals affluence and fashionability, and it appeals in different, often emotional ways to the senses of those who experience the furniture by sitting on it while eating, drinking and talking. Apparently the traditional‐looking Moroccan furniture has the capacity to transport people to other worlds. For those who spent their childhood in Morocco, these are often worlds that are part of their embodied memory, while for those who grew up outside Morocco, these are more often worlds that are primarily imagined and appropriated through aesthetic images in glossy magazines and coffee‐table books. In both cases however, traditional‐looking Moroccan furniture appear to respond to an emotional longing for the (re‐)creation of experiences of conviviality. Especially in interviews with first‐generation Moroccan migrants, this emotional longing resonates more strongly than the wish to make a statement about ethnic belonging.
The development of 3‐D visualization technology: the potential impact on interior design and its consumers
Authors: Lee Seunghae
Published: August 2009

Three‐dimensional visualization has developed and improved significantly over the last several decades and resulted in consumers' having multidimensional, multi‐sensory experiences with a wide range of products and services. It has affected the built environment and its related businesses. Designers create 3‐D images and walk‐through animations to communicate with their clients more clearly, starting from the early stage of the design process. The interior–design‐related material manufacturers and retailers have enhanced their online stores with 3‐D visualization features to improve their interactivity and provide user‐friendly interfaces for product information search and purchase planning. Because of the continuing widespread interest in 3‐D visualization and the amount of its applications in the interior design field, a review of this area was a necessity to suggest the future research direction for the development of 3‐D visualization in interior design. This paper sought to demonstrate the status of the development of 3‐D visualization and its impact on the interior design field and its consumers while highlighting an area where future research is a potentially considerable benefit in developing 3‐D visualization in interior design.
Implicit Employment Contracts: The Limits of Management Reputation for Promoting Firm Productivity
Authors: HALES JEFFREY , WILLIAMSON MICHAEL G.
Published: August 2009

Implicit employment contracts are a common way to motivate firm productivity but also require that employees trust management to be fair when allocating postproduction firm resources between employees and owners. We use an experiment to study the problem of motivating firm productivity, which depends on levels of owner investment and employee productive effort, when managers have an incentive to favor the owner's interests over those of the employee. Drawing on research in psychology and behavioral economics, we argue that reputation concerns can more effectively promote firm productivity when manager compensation is relatively insensitive to how much the owner is allocated after production occurs. Consistent with our predictions, we find that reputation concerns lead to greater firm productivity and higher payoffs for all firm members, but only when manager pay is relatively insensitive to the owner's ex post allocation. In addition to offering testable empirical implications, our theory and results are important because they can help explain why executive compensation is, in practice, surprisingly insensitive to owner returns.
An Analysis of the Key Factors Influencing Farmer’s Choice of Crop, Kibamba Ward, Tanzania
Authors: Greig Laura
Published: August 2009

The need for further research into indigenous knowledge, in the context of agrarian development strategies, led to this investigation of one aspect of local knowedge; that of crop choice. Through the use of point score analysis, research was conducted in the Kibamba Ward located in the peri‐urban zone of Dar es Salaam, Tanzania. The main aims were to investigate the key factors underlying farmers’ choice of crop as well as to assess the differences in the decision‐making process between commercial and subsistence farmers. Vegetable cultivation was observed as the main practice, influenced particularly by the physical environment, the availability of machinery as well as certain economic factors. A significant difference in decision making among subsistence and commercial farmers was found. Subsistence farmers placed greater emphasis on the taste of the crop, whereas commercial farmers were predictably more influenced by the market. In addition, this study highlights several practical areas of concern regarding water resources, basic machinery and the lack of formal extension provision in the area. Although the complexity of crop choice is portrayed, a need for future research in different geographical contexts is noted.
A Cell‐Free Collagen Type I Device for the Treatment of Focal Cartilage Defects
Authors: Gavenis Karsten , Schmidt‐Rohlfing Bernhard , Andereya Stefan , Mumme Torsten , Schneider Ulrich , Mueller‐Rath Ralf
Published: August 2009

The purpose of this study was to evaluate the potential value of a cell‐free collagen type I gel plug for the treatment of focal cartilage defects. Cellular migration and proliferation was addressed in vitro, and the formation of repair tissue in a nude mouse‐based defect model. A cell‐free plug made of collagen type I was placed in the center of an incubation plate. Surrounding space was filled with a collagen type I gel (Arthro Kinetics, Esslingen, Germany) seeded with 2 × 105 human articular chondrocytes/mL gel. After cultivation for up to 6 weeks in vitro, samples were subject to histological and immunohistochemical staining and gene expression analysis. Subsequently, chondral defects of human osteochondral blocks were treated with the plug, and specimens were cultivated subcutaneously in nude mice for 6 weeks. The repair tissue was evaluated macroscopically, and collagen type II production was investigated immunohistochemically. In vitro, morphology of immigrated cells did not show any differences, as did collagen type II gene expression. After 4 weeks, the plug was homogeneously inhabited. After 6 weeks of cultivation in nude mice, collagen gel plug treatment led to a macroscopically excellent repair tissue. Histological staining revealed a tight bonding, and the collagen gel plug started to be remodeled. We conclude that the novel collagen gel plug device offers an environment favorable for the migration of articular chondrocytes and leads to a good‐quality repair tissue in the nude mouse model. The arthroscopic transplantation of a collagen gel plug may be one option in the treatment of focal cartilage defects.
Highly Permeable Genipin‐Cross‐linked Gelatin Conduits Enhance Peripheral Nerve Regeneration
Authors: Chang Ju‐Ying , Ho Tin‐Yun , Lee Han‐Chung , Lai Yen‐Liang , Lu Ming‐Chin , Yao Chun‐Hsu , Chen Yueh‐Sheng
Published: August 2009

Here we have evaluated peripheral nerve regeneration with a porous biodegradable nerve conduit (PGGC), which was made from genipin‐cross‐linked gelatin. To examine the effect of pores, nonporous genipin‐cross‐linked gelatin conduit (GGC) was considered as the control. Both the PGGC and the GGC were dark blue in appearance with a concentric and round lumina. The PGGC featured an outer surface with pores of variable size homogeneously traversing, and a partially fenestrated inner surface connected by an open trabecular meshwork. The GGC had a rough outer surface whereas its inner lumen was smooth. Both PGGCs and GGCs had similar hydrophilicity on condition of the same material and cross‐linking degree. The porosity of PGGCs and GGCs was 90.8 ± 0.9% and 24.3 ± 2.9%, respectively. The maximum tensile force of the GGCs (0.12 ± 0.06 kN) exceeded that of the PGGCs (0.03 ± 0.01 kN), but the PGGCs had a higher swelling ratio than GGCs at 0.5, 1, 3, 6, 12, 24, 48, 60, 72, and 84 h after soaking in deionized water. Cytotoxic testing revealed the soaking solutions of both of the tube composites would not produce cytotoxicity to cocultured Schwann cells. After subcutaneous implantation on the dorsal side of the rat, the PGGC was degraded completely after 12 weeks of implantation whereas a thin tissue capsule was formed encapsulating the partially degraded GGC. Biodegradability of both of the tube groups and their effectiveness as a guidance channel were examined as they were used to repair a 10 mm gap in the rat sciatic nerve. As a result, fragmentation of the GGC was still seen after 12 weeks of implantation, yet the PGGC had been completely degraded. Histological observation showed that numerous myelinated axons had crossed over the gap region in the PGGCs after 8 weeks of implantation despite only few myelinated axons and unmyelinated axons mostly surrounded by Schwann cells seen in the GGCs. In addition, the regenerated nerves in the PGGCs presented a significantly higher nerve conductive velocity than those in the GGCs (P < 0.05). Thus, the PGGCs can not only offer effective aids for regenerating nerves but also accelerate favorable nerve functional recovery compared with the GGCs.
Effect of glucocorticoid receptor gene polymorphisms in Guillain‐Barré syndrome
Authors: Dekker Marieke J. H. J. , Van Den Akker Erica L. T. , Koper Jan Willem , Manenschijn Laura , Geleijns Karin , Ruts Liselotte , Van Rijs Wouter , Tio‐Gillen Anne P. , Van Doorn Pieter A. , Lamberts Steven W. J. , Jacobs Bart C.
Published: August 2009

Guillain‐Barré syndrome (GBS) is a postinfectious immune‐mediated polyneuroradiculopathy in which host factors influence disease susceptibility and clinical course. Single‐nucleotide polymorphisms (SNPs) in the glucocorticoid receptor (GR) gene influence the sensitivity to glucocorticoids and are related to both microbial colonization and susceptibility to develop auto‐immune disease. This genetic variation may therefore also influence the chance to develop GBS. In this study, we genotyped 318 GBS patients and 210 control subjects for five known SNPs in the GR gene. We could distinguish six different GR haplotypes of which two carried the BclI polymorphism: haplotype 1, which consists of the minor allele of BclI in combination with the common variant of TthIIII and haplotype 2, which carries the minor allele of BclI as well as the minor allele of TthIIII. The GR haplotypes were not related to susceptibility to develop GBS. Carriers of haplotype 2 had more frequently preceding diarrhea, serum antibodies to GM1 and GD1a, and more severe muscle weakness at entry. Haplotype 1 carriers had a significantly better prognosis. In conclusion, GR haplotypes are not a susceptibility factor for GBS. However, haplotypes carrying the minor allele of the BclI polymorphism were related to the phenotype and outcome of GBS.
Autologous peripheral blood stem cell transplantation for chronic acquired demyelinating neuropathy
Authors: Mahdi‐Rogers Mohamed , Kazmi Majid , Ferner Rosalie , Hughes Richard A. C. , Renaud Susanne , Steck Andreas J. , Fuhr Peter , Halter Jörg , Gratwohl Alois , Tyndall Alan
Published: August 2009

Six patients with chronic acquired demyelinating neuropathy (CADP) were treated with autologous peripheral blood stem cell transplantation (PBSCT). Two with polyneuropathy, organomegaly, endocrinopathy, M‐protein, and skin changes (POEMS) syndrome improved–improvement was sustained in one but relapsed and required repeat transplant in the other. Two of the three with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and one with an IgM paraprotein and antibodies to nerve improved–of the responders, one relapsed after 18 months and the other was in remission after 6 months. Four developed neutropenic septicemia and pneumonia. The role of PBSCT in CADP refractory to other treatment deserves further investigation but the serious adverse events and lack of sustained response in some patients emphasize the need for caution.
Mutational analysis of GJB1, MPZ, PMP22, EGR2, and LITAF/SIMPLE in Serbian Charcot‐Marie‐Tooth patients
Authors: Keckarevic‐Markovic Milica , Milic‐Rasic Vedrana , Mladenovic Jelena , Dackovic Jelena , Kecmanovic Miljana , Keckarevic Dusan , Savic‐Pavicevic Dusanka , Romac Stanka
Published: August 2009

We report the results of mutational analysis in the following genes: GJB1, MPZ, PMP22, EGR2, and LITAF/SIMPLE in 57 Charcot‐Marie‐Tooth (CMT) patients of Serbian origin without the PMP22 duplication. We found 10 different mutations in 14 CMT patients: 6 mutations in GJB1, 3 in MPZ, and 1 in PMP22. Five of six GJB1 mutations are reported for the first time, and the most frequent one appears to be a founder mutation in the Serbian population. No mutations were found in EGR2 or LITAF. Thus, GJB1 mutation analysis should be done in patients without the PMP22 duplication and male‐to‐male transmission of CMT.
Phrenic nerve diabetic neuropathy in rats: unmyelinated fibers morphometry
Authors: Fazan Valéria Paula S. , Rodrigues Filho Omar A. , Jordão Caroline E. R. , Moore Kenneth C.
Published: August 2009

We have demonstrated that phrenic nerves' large myelinated fibers in streptozotocin (STZ)‐induced diabetic rats show axonal atrophy, which is reversed by insulin treatment. However, studies on structural abnormalities of the small myelinated and the unmyelinated fibers in the STZ‐model of neuropathy are limited. Also, structural changes in the endoneural vasculature are not clearly described in this model and require detailed study. We have undertaken morphometric studies of the phrenic nerve in insulin‐treated and untreated STZ‐diabetic rats and non‐diabetic control animals over a 12‐week period. The presence of neuropathy was assessed by means of transmission electron microscopy, and morphometry of the unmyelinated fibers was performed. The most striking finding was the morphological evidence of small myelinated fiber neuropathy due to the STZ injection, which was not protected or reversed by conventional insulin treatment. This neuropathy was clearly associated with severe damage of the endoneural vessels present on both STZ groups, besides the insulin treatment. The STZ‐diabetes model is widely used to investigate experimental diabetic neuropathies, but few studies have performed a detailed assessment of either unmyelinated fibers or capillary morphology in this animal model. The present study adds useful information for further investigations on the ultrastructural basis of nerve function in diabetes.
Effects of Prenatal Alcohol Exposure on Brain Activation During an Arithmetic Task: An fMRI Study
Authors: Santhanam Priya , Li Zhihao , Hu Xiaoping , Lynch Mary Ellen , Coles Claire D.
Published: August 2009

Background:  While behavioral studies have established that prenatal alcohol exposure (PAE) can result in diminished arithmetic processing capability, the underlying neural correlates of this deficit are still unclear. The aim of the present study was to use functional magnetic resonance imaging to determine the effect of PAE on neuronal activation during a subtraction task.

Methods:  Participants were young adults from a low socio‐economic status population who were identified prenatally; the sample consisted of healthy unexposed controls (n = 17) and PAE who were subdivided based on the presence (n = 19) or absence of physical dysmorphic signs (n = 18). Multiple regression analysis was used to determine extent of activation and percent signal change during arithmetic processing, using a letter‐matching task as the baseline. Region of interest analysis of activation was performed in the native space and normalized for each individual to compensate for the considerable variability in head size observed in the alcohol‐exposed population.

Results:  An exposure‐dependent response was observed in task performance and neuronal activation. Dysmorphic PAE individuals showed significantly lower task‐related performance and activation in regions known to be associated with arithmetic processing, including left superior and right inferior parietal regions and medial frontal gyrus, while the nondysmorphic PAE group was generally intermediate but not significantly different from the control group in task performance and activation.

Conclusions:  Results indicate that there is a range of effects of PAE on arithmetic processing and that the severity of this deficit may be dependent on degree of impairment demonstrated by the exposed individual. Evidence of physical dysmorphia may be indicative of functional damage to regions associated with arithmetic calculation, resulting in markedly impaired neuronal recruitment.
Differential Effects of Chronic Ethanol Consumption and Withdrawal on Homer/Glutamate Receptor Expression in Subregions of the Accumbens and Amygdala of P Rats
Authors: Obara Ilona , Bell Richard L. , Goulding Scott P. , Reyes Cindy M. , Larson Lindsay A. , Ary Alexis W. , Truitt William A. , Szumlinski Karen K.
Published: August 2009

Background: Homer proteins are constituents of scaffolding complexes that regulate the trafficking and function of central Group1 metabotropic glutamate receptors (mGluRs) andN‐methyl‐d‐aspartate (NMDA) receptors. Research supports the involvement of these proteins in ethanol‐induced neuroplasticity in mouse. In this study, we examined the effects of short versus long‐term withdrawal from chronic ethanol consumption on Homer and glutamate receptor protein expression within striatal and amygdala subregions of selectively bred, alcohol‐preferring P rats.

Methods: For 6 months, male P rats had concurrent access to 15% and 30% ethanol solutions under intermittent (IA: 4 d/wk) or continuous (CA: 7 d/wk) access conditions in their home cage. Rats were killed 24 hours (short withdrawal: SW) or 4 weeks (long withdrawal: LW) after termination of ethanol access, subregions of interest were micropunched and tissue processed for detection of Group1 mGluRs, NR2 subunits of the NMDA receptor and Homer protein expression.

Results: Within the nucleus accumbens (NAC), limited changes in NR2a and NR2b expression were detected in the shell (NACsh), whereas substantial changes were observed for Homer2a/b, mGluRs as well as NR2a and NR2b subunits in the core (NACc). Within the amygdala, no changes were detected in the basolateral subregion, whereas substantial changes, many paralleling those observed in the NACc, were detected in the central nucleus (CeA) subregion. In addition, most of the changes observed in the CeA, but not NACc, were present in both SW and LW rats.

Conclusions: Overall, these subregion specific, ethanol‐induced increases in mGluR/Homer2/NR2 expression within the NAC and amygdala suggest changes in glutamatergic plasticity had taken place. This may be a result of learning and subsequent memory formation of ethanol’s rewarding effects in these brain structures, which may, in part, mediate the chronic relapsing nature of alcohol abuse.
Suppression of Heavy Drinking and Alcohol Seeking by a Selective ALDH‐2 Inhibitor
Authors: Arolfo Maria P. , Overstreet David H. , Yao Lina , Fan Peidong , Lawrence Andrew J. , Tao Guoxin , Keung Wing‐Ming , Vallee Bert L. , Olive M. Foster , Gass Justin T. , Rubin Emanuel , Anni Helen , Hodge Clyde W. , Besheer Joyce , Zablocki Jeff , Leung Kwan , Blackburn Brent K. , Lange Louis G. , Diamond Ivan
Published: August 2009

Background: Inherited human aldehyde dehydrogenase 2 (ALDH‐2) deficiency reduces the risk for alcoholism. Kudzu plants and extracts have been used for 1,000 years in traditional Chinese medicine to treat alcoholism. Kudzu contains daidzin, which inhibits ALDH‐2 and suppresses heavy drinking in rodents. Decreased drinking due to ALDH‐2 inhibition is attributed to aversive properties of acetaldehyde accumulated during alcohol consumption. However, daidzin can reduce drinking in some rodents without necessarily increasing acetaldehyde. Therefore, a selective ALDH‐2 inhibitor might affect other metabolic factors involved in regulating drinking.

Methods: Aldehyde dehydrogenase 2 inhibitors were synthesized based on the co‐crystal structure of ALDH‐2 and daidzin. We tested the efficacy of a highly selective reversible ALDH‐2 inhibitor, CVT‐10216, in models of moderate and high alcohol drinking rats. We studied 2‐bottle choice and deprivation‐induced drinking paradigms in Fawn Hooded (FH) rats, operant self‐administration in Long Evans (LE), FH, and inbred P (iP) rats and in cue‐induced reinstatement in iP rats. We also assayed blood acetaldehyde levels as well as dopamine (DA) release in the nucleus accumbens (NAc) and tested possible rewarding/aversive effects of the inhibitor in a conditioned place preference (CPP) paradigm.

Results: CVT‐10216 increases acetaldehyde after alcohol gavage and inhibits 2‐bottle choice alcohol intake in heavy drinking rodents, including deprivation‐induced drinking. Moreover, CVT‐10216 also prevents operant self‐administration and eliminates cue‐induced reinstatement of alcohol seeking even when alcohol is not available (i.e., no acetaldehyde). Alcohol stimulates DA release in the NAc, which is thought to contribute to increased drinking and relapse in alcoholism. CVT‐10216 prevents alcohol‐induced increases in NAc DA without changing basal levels. CVT‐10216 does not show rewarding or aversive properties in the CPP paradigm at therapeutic doses.

Conclusion: Our findings suggest that selective reversible ALDH‐2 inhibitors may have therapeutic potential to reduce excessive drinking and to suppress relapse in abstinent alcoholics.
Longitudinal Studies of Binary Response Data Following Case–Control and Stratified Case–Control Sampling: Design and Analysis
Authors: Schildcrout Jonathan S. , Rathouz Paul J.
Published: August 2009

SummaryWe discuss design and analysis of longitudinal studies after case–control sampling, wherein interest is in the relationship between a longitudinal binary response that is related to the sampling (case–control) variable, and a set of covariates. We propose a semiparametric modeling framework based on a marginal longitudinal binary response model and an ancillary model for subjects' case–control status. In this approach, the analyst must posit the population prevalence of being a case, which is then used to compute an offset term in the ancillary model. Parameter estimates from this model are used to compute offsets for the longitudinal response model. Examining the impact of population prevalence and ancillary model misspecification, we show that time‐invariant covariate parameter estimates, other than the intercept, are reasonably robust, but intercept and time‐varying covariate parameter estimates can be sensitive to such misspecification. We study design and analysis issues impacting study efficiency, namely: choice of sampling variable and the strength of its relationship to the response, sample stratification, choice of working covariance weighting, and degree of flexibility of the ancillary model. The research is motivated by a longitudinal study following case–control sampling of the time course of attention deficit hyperactivity disorder (ADHD) symptoms.