bluuebunny/crossref_metadata_2025 huggingface dataset:
Insulin-like growth factor-I receptor blockade by a specific tyrosine kinase inhibitor for human gastrointestinal carcinomas
Authors: Piao Wenhua , Wang Yu , Adachi Yasushi , Yamamoto Hiroyuki , Li Rong , Imsumran Arisa , Li Hua , Maehata Tadateru , Li Masanori , Arimura Yoshiaki , Lee Choon-Taek , Shinomura Yasuhisa , Carbone David P. , Imai Kohzoh
Published: June 2008

Insulin-like growth factor-I receptor (IGF-IR) signaling is required for carcinogenicity and proliferation of gastrointestinal (GI) cancers. In this study, we sought to evaluate the effect of a new tyrosine kinase inhibitor of IGF-IR, NVP-AEW541, on the signal transduction and the progression of GI carcinomas. We assessed the effect of NVP-AEW541 on signal transduction, proliferation, survival, and migration in four GI cancer cells: colorectal adenocarcinoma HT29, pancreatic adenocarcinoma BxPC3, esophageal squamous cell carcinoma TE1, and hepatoma PLC/PRF/5. The effects of NVP-AEW541 alone and with chemotherapy were studied in vitro and in nude mouse xenografts. We also analyzed the effects of NVP-AEW541 on insulin signals and hybrid receptor formation between IGF-IR and insulin receptor. NVP-AEW541 blocked autophosphorylation of IGF-IR and both Akt and extracellular signal-regulated kinase activation by IGF but not by insulin. NVP-AEW541 suppressed proliferation and tumorigenicity in vitro in a dose-dependent manner in all cell lines. The drug inhibited tumor as a single agent and, when combined with stressors, up-regulated apoptosis in a dose-dependent fashion and inhibited mobility. NVP-AEW541 augmented the effects of chemotherapy on in vitro growth and induction of apoptosis. Moreover, the combination of NVP-AEW541 and chemotherapy was highly effective against tumors in mice. This compound did not influence hybrid receptor formation. Thus, NVP-AEW541 may have significant therapeutic utility in human GI carcinomas both alone and in combination with chemotherapy. [Mol Cancer Ther 2008;7(6):1483–93]
A novel triple-regulated oncolytic adenovirus carrying p53 gene exerts potent antitumor efficacy on common human solid cancers
Authors: Wang Xinghua , Su Changqing , Cao Hui , Li Kui , Chen Jie , Jiang Lixin , Zhang Qi , Wu Xiaobing , Jia Xiaoyuan , Liu Yongjing , Wang Weiguo , Liu Xinyuan , Wu Mengchao , Qian Qijun
Published: June 2008

Conditionally replicating adenoviruses (CRAd) can replicate specifically in cancer cells and lyse them. The CRAds were widely used in the preclinical and clinical studies of cancer therapy. We hypothesize that more precisely regulated replication of CRAds may further improve the vector safety profile and enhance its antitumor efficacy. Here, a triple-regulated CRAd carrying p53 gene expression cassette, SG600-p53, was engineered. In SG600-p53, the E1a gene with a deletion of 24 nucleotides within CR2 region is controlled under the human telomerase reverse transcriptase (hTERT) promoter, the E1b gene expression is directed by the hypoxia response element (HRE), whereas the p53 gene is controlled by the cytomegalovirus promoter. The precise triple-regulation endows SG600-p53 with enhanced antitumor potential and improved safety profile. The tumor-selective replication of this virus and its antitumor efficacy were characterized in several tumor cell lines in vitro and in xenograft models of human non-small cell lung cancer in nude mice. With the selective replication and oncolysis, it was found by ELISA assay that SG600-p53 expressed p53 efficiently in cancer cells. In NCI-H1299 tumor xenograft models, SG600-p53 displayed a tumor-selective killing capacity. At a dose of 2 × 109 plaque-forming units, SG600-p53 could completely inhibit the tumor growth and more effective than replication-defective Ad-p53. Histopathologic examination revealed that SG600-p53 administration resulted in cancer cell apoptosis. We concluded that the triple-regulated SG600-p53, as a more potent and safer antitumor therapeutic, could provide a new strategy for cancer biotherapy. [Mol Cancer Ther 2008;7(6):1598–603]
Bortezomib induces apoptosis via Bim and Bik up-regulation and synergizes with cisplatin in the killing of head and neck squamous cell carcinoma cells
Authors: Li Changyou , Li Rongxiu , Grandis Jennifer R. , Johnson Daniel E.
Published: June 2008

Head and neck squamous cell carcinomas (HNSCC) are characterized by resistance to chemotherapy and overexpression of antiapoptotic Bcl-2 family members, including Bcl-XL and Bcl-2. Molecular targeting of Bcl-XL and/or Bcl-2 in HNSCC cells has been shown to promote apoptosis signaling and to sensitize cells to chemotherapy drugs, including cisplatin, which is commonly used in the treatment of HNSCC. We report that induction of HNSCC apoptosis by the proteasome inhibitor bortezomib is accompanied by up-regulation of the proapoptotic proteins Bik and Bim, natural cellular inhibitors of Bcl-XL and Bcl-2. Additionally, bortezomib treatment of HNSCC cells caused up-regulation of antiapoptotic Mcl-1L. Inhibition of Bik or Bim up-regulation using small interfering RNA markedly attenuated bortezomib-induced cell death. By contrast, small interfering RNA–mediated inhibition of Mcl-1L expression resulted in enhanced killing by bortezomib. Further investigation showed that the combination of bortezomib and cisplatin led to synergistic killing of HNSCC cells, with calculated combination indexes well below 1.0. Taken together, these results delineate a novel mechanism of HNSCC killing by bortezomib that involves up-regulation of Bik and Bik. Moreover, our findings suggest that the combination of bortezomib plus cisplatin, or bortezomib plus an inhibitor of Mcl-1L, may have therapeutic value in the treatment of HNSCC. [Mol Cancer Ther 2008;7(6):1647–55]
STAT3 inhibition in prostate and pancreatic cancer lines by STAT3 binding sequence oligonucleotides: differential activity between 5′ and 3′ ends
Authors: Lewis H. Dan , Winter Ashley , Murphy Thomas F. , Tripathi Snehlata , Pandey Virendra N. , Barton Beverly E.
Published: June 2008

Signal transducers and activators of transcription (STAT) were originally discovered as components of signal transduction pathways. Persistent aberrant activation of STAT3 is a feature of many malignancies including prostate cancer and pancreatic cancer. One consequence of persistently activated STAT3 in malignant cells is that they depend on it for survival; thus, STAT3 is an excellent molecular target for therapy. Previously, we reported that single-stranded oligonucleotides containing consensus STAT3 binding sequences (13410 and 13411) were more effective for inducing apoptosis in prostate cancer cells than antisense STAT3 oligonucleotides. Control oligonucleotides (scrambled sequences) had no effect. Here, we report that authentic STAT3 binding sequences, identified from published literature, were more effective for inducing apoptosis in prostate cancer cells and pancreatic cancer cells than was oligonucleotide 13410. Moreover, the authentic STAT3 binding sequences showed differing efficacies in the malignant cell lines depending on whether the canonical STAT3 binding sequence was truncated at the 5′ or the 3′ end. Finally, expression of one STAT3-regulated gene was decreased following treatment, suggesting that STAT3 may regulate the same set of genes in the two types of cancer. We conclude that truncating the 5′ end left intact enough of the canonical STAT3 binding site for effective hybridization to the genome, whereas truncation of the 3′ end, which is outside the canonical binding site, may have affected binding of required cofactors essential for STAT3 activity, thereby reducing the capacity of this modified oligonucleotide to induce apoptosis. Additional experiments to answer this hypothesis are under way. [Mol Cancer Ther 2008;7(6):1543–50]
Neural Correlates of Stereotype Application
Authors: Mitchell Jason P. , Ames Daniel L. , Jenkins Adrianna C. , Banaji Mahzarin R.
Published: June 2008

Recent research has focused on the disparate mechanisms that support the human ability to “mentalize” about the thoughts and feelings of others. One such process may rely on precompiled, semantic beliefs about the characteristics common to members of a social group, that is, on stereotypes; for example, judging that a woman may be more likely than a man to have certain interests or opinions. In the current study, we identified a pattern of neural activity associated with the use of stereotypes to judge another person's psychological characteristics. During fMRI scanning, participants mentalized about the likely responses of a female and male target to a series of questions, some of which were related to gender stereotypes (e.g., “enjoys shopping for new clothes”). Trials on which participants applied a stereotype were segregated from those on which participants avoided stereotype use. The BOLD response in an extensive region of the right frontal cortex differentiated stereotype-applied from -unapplied trials. Moreover, this neural difference was correlated with a behavioral index of gender associations—the Implicit Association Test—administered after scanning. Results suggest that stereotype application may draw on cognitive processes that more generally subserve semantic knowledge about categories.
Hemisphere-specific Episodic Memory Networks in the Human Brain: A Correlation Study between Intracarotid Amobarbital Test and [18F]FDG-PET
Authors: Akanuma Nozomi , Reed Laurence J. , Marsden Paul K. , Jarosz Jozeph , Adachi Naoto , Hallett William A. , Alarcón Gonzalo , Morris Robin G. , Koutroumanidis Michael
Published: June 2008

The purpose of the present study was to explore the brain regions involved in human episodic memory by correlating unilateral memory performance estimated by the intracarotid amobarbital test (IAT) and interictal cerebral metabolism measured by [18F]fluorodeoxyglucose positron emission tomography ([18F]FDG-PET). Using this method, regional alterations of cerebral metabolism associated with epilepsy pathophysiology are used to predict hemisphere-specific episodic memory function, hence, investigate the differential distribution of memory in each hemisphere. Sixty-two patients with unilateral temporal lobe epilepsy (35 left and 27 right) were studied using [18F]FDG-PET with complementary voxel-based statistical parametric mapping (SPM) and region-of-interest (ROI) methods of analysis. Positive regression was analyzed in SPM with a series of different thresholds (p = .001, .01 or .05) with a correction to 100 voxels. IAT memory performance in which left hemisphere was tested by right-sided injection of amobarbital correlated with [18F]FDG uptake in left lateral and medial temporal regions, and in the left ventrolateral frontal cortex. Right IAT memory performance correlated with [18F]FDG uptake in the right inferior parietal lobule, right dorsolateral frontal cortex, right precentral gyrus, and caudal portion of the right anterior cingulate cortex. ROI analysis corroborated these results. Analyses carried out separately in patients with left (n = 50) and nonleft (n = 12) dominance for language showed that in the nonleft dominant group, right IAT scores correlated with right fronto-temporal regions, whereas left total memory scores correlated with left lateral and medial temporal regions. The findings indicate that (i) episodic memory is subserved by more widespread cortical regions beyond the core mesiotemporal lobe memory structures; (ii) there are different networks functional in the two hemispheres; and (iii) areas involved in memory may be different between patients with left and nonleft dominance for language, particularly in the right hemisphere.
The Attentional Blink Reveals Serial Working Memory Encoding: Evidence from Virtual and Human Event-related Potentials
Authors: Craston Patrick , Wyble Brad , Chennu Srivas , Bowman Howard
Published: June 2008

Observers often miss a second target (T2) if it follows an identified first target item (T1) within half a second in rapid serial visual presentation (RSVP), a finding termed the attentional blink. If two targets are presented in immediate succession, however, accuracy is excellent (Lag 1 sparing). The resource sharing hypothesis proposes a dynamic distribution of resources over a time span of up to 600 msec during the attentional blink. In contrast, the ST2 model argues that working memory encoding is serial during the attentional blink and that, due to joint consolidation, Lag 1 is the only case where resources are shared. Experiment 1 investigates the P3 ERP component evoked by targets in RSVP. The results suggest that, in this context, P3 amplitude is an indication of bottom–up strength rather than a measure of cognitive resource allocation. Experiment 2, employing a two-target paradigm, suggests that T1 consolidation is not affected by the presentation of T2 during the attentional blink. However, if targets are presented in immediate succession (Lag 1 sparing), they are jointly encoded into working memory. We use the ST2 model's neural network implementation, which replicates a range of behavioral results related to the attentional blink, to generate “virtual ERPs” by summing across activation traces. We compare virtual to human ERPs and show how the results suggest a serial nature of working memory encoding as implied by the ST2 model.
Retrieval from Episodic Memory: Neural Mechanisms of Interference Resolution
Authors: Wimber Maria , Rutschmann Roland Marcus , Greenlee Mark W. , Bäuml Karl-Heinz
Published: June 2008

Selectively retrieving a target memory among related memories requires some degree of inhibitory control over interfering and competing memories, a process assumed to be supported by inhibitory mechanisms. Evidence from behavioral studies suggests that such inhibitory control can lead to subsequent forgetting of the interfering information, a finding called retrieval-induced forgetting [Anderson, M. C., Bjork, R. A., & Bjork, E. L. Remembering can cause forgetting: Retrieval dynamics in long-term memory. Journal of Experimental Psychology: Learning, Memory & Cognition, 20, 1063–1087, 1994]. In the present functional magnetic resonance imaging study, we investigated the neural processes underlying retrieval-induced forgetting and, in particular, examined the extent to which these processes are retrieval (i.e., selection) specific. Participants actively retrieved a subset of previously studied material (selection condition), or were re-exposed to the same material for relearning (nonselection condition). Replicating prior behavioral work, selective retrieval caused significant forgetting of the nonretrieved items on a delayed recall test, relative to the re-exposure condition. Selective retrieval was associated with increased BOLD responses in the posterior temporal and parietal association cortices, in the bilateral hippocampus, and in the dorsolateral prefrontal cortex. Medial and lateral prefrontal areas showed a strong negative linear relationship between selection-related neural activity and subsequent forgetting of competitors. These findings suggest reduced demands on inhibitory control processes when interference is successfully resolved during early selective retrieval from episodic memory.
Cerebral White Matter Integrity Mediates Adult Age Differences in Cognitive Performance
Authors: Madden David J. , Spaniol Julia , Costello Matthew C. , Bucur Barbara , White Leonard E. , Cabeza Roberto , Davis Simon W. , Dennis Nancy A. , Provenzale James M. , Huettel Scott A.
Published: June 2008

Previous research has established that age-related decline occurs in measures of cerebral white matter integrity, but the role of this decline in age-related cognitive changes is not clear. To conclude that white matter integrity has a mediating (causal) contribution, it is necessary to demonstrate that statistical control of the white matter–cognition relation reduces the magnitude of age–cognition relation. In this research, we tested the mediating role of white matter integrity, in the context of a task-switching paradigm involving word categorization. Participants were 20 healthy, community-dwelling older adults (60–85 years), and 20 younger adults (18–27 years). From diffusion tensor imaging tractography, we obtained fractional anisotropy (FA) as an index of white matter integrity in the genu and splenium of the corpus callosum and the superior longitudinal fasciculus (SLF). Mean FA values exhibited age-related decline consistent with a decrease in white matter integrity. From a model of reaction time distributions, we obtained independent estimates of the decisional and nondecisional (perceptual–motor) components of task performance. Age-related decline was evident in both components. Critically, age differences in task performance were mediated by FA in two regions: the central portion of the genu, and splenium–parietal fibers in the right hemisphere. This relation held only for the decisional component and was not evident in the nondecisional component. This result is the first demonstration that the integrity of specific white matter tracts is a mediator of age-related changes in cognitive performance.
Grapheme–Color Synesthesia Influences Overt Visual Attention
Authors: Carriere Jonathan S. A. , Eaton Daniel , Reynolds Michael G. , Dixon Mike J. , Smilek Daniel
Published: June 2008

For individuals with grapheme–color synesthesia, achromatic letters and digits elicit vivid perceptual experiences of color. We report two experiments that evaluate whether synesthesia influences overt visual attention. In these experiments, two grapheme–color synesthetes viewed colored letters while their eye movements were monitored. Letters were presented in colors that were either congruent or incongruent with the synesthetes' colors. Eye tracking analysis showed that synesthetes exhibited a color congruity bias—a propensity to fixate congruently colored letters more often and for longer durations than incongruently colored letters—in a naturalistic free-viewing task. In a more structured visual search task, this congruity bias caused synesthetes to rapidly fixate and identify congruently colored target letters, but led to problems in identifying incongruently colored target letters. The results are discussed in terms of their implications for perception in synesthesia.
The Case of Pretense: Observing Actions and Inferring Goals
Authors: Schubotz Ricarda I. , von Cramon D. Yves
Published: June 2008

When we observe an action, we know almost immediately what goal is pursued by the actor. Strikingly, this applies also to pretend action (pantomime), which provides relevant information about the manipulation itself but not about the manipulated objects. The present fMRI study addressed the issue of goal inference from pretend action as compared with real action. We found differences as well as commonalities for the brain correlates of inferring goals from both types of action. They differed with regard to the weights of the underlying action observation network, indicating the exploitation of object information in the case of real actions and manipulation information in the case of pretense. However, goal inferences from manipulation information resulted in a common network for both real and pretend action. Interestingly, this latter network also comprised areas that are not identified by action observation and that might be due to the processing of scene gist and to the evaluation of fit of putative action goals. These findings suggest that observation of pretense emphasizes the requirement to internally simulate the observed act but rule out fundamental differences of how observers cope with real and pretend action.
Predicting Burnout and Career Choice Satisfaction in Counseling Psychology Graduate Students
Authors: Kovach Clark Heddy , Murdock Nancy L. , Koetting Kristin
Published: June 2008

Counseling psychology doctoral students ( N = 284) from 53 training programs throughout the United States anonymously completed online measures of burnout, career choice satisfaction, global stress, role conflict, social support (from family/friends, advisors, other students) and psychological sense of community (SOC) in the doctoral program. Two hierarchical multiple regressions were performed to test hypotheses that social support would buffer the effects of stress on burnout and career choice satisfaction. For burnout, neither social support nor SOC significantly moderated the effects of stress on burnout; however, global stress, advisor support, and SOC were significant predictors. For career choice satisfaction, SOC was a significant single predictor and moderated the effects of global stress. Under low stress, career choice satisfaction increased as SOC increased. Under high stress, these moderating effects seemed to disappear.
Black Football Players on a Predominantly White College Campus: Psychosocial and Emotional Realities of the Black College Athlete Experience
Authors: Melendez Mickey C.
Published: June 2008

Black student-athletes have been the focus of study regarding academic and psychosocial adjustment to college since the 1960s. Although recent literature generally reports higher graduation rates for Black student-athletes compared to their nonathlete peers, little attention has been given to their psychosocial experiences on predominantly White college campuses. The current study explored the social experiences of a small group of Black football players attending a predominantly White university in the northeastern United States. A qualitative “grounded theory” methodology was employed for data collection and analysis and a coding system was created centered on the main areas of team, campus, and city experiences. Findings revealed that the Black players felt isolated, rejected, and mistrustful of their Black and White classmates and teammates. They also felt unfairly judged by their coaches and campus community. Other team, campus, and city issues were revealed, all of which negatively influenced these players' emotional and educational experiences. Implications for recruitment, retention, and educational policy are discussed.
Race, Parental Socioeconomic Status, and Computer Use Time Outside of School Among Young American Children, 1997 to 2003
Authors: Ono Hiromi , Tsai Hsin-Jen
Published: June 2008

This article investigates the role that parental socioeconomic status plays in forming the racial gap in home computer use among young school-age children. Descriptive statistics from time diary data of 6- to 11-year-olds in the Panel Study of Income Dynamics, Child Development Supplement, reveal that Black American children spend substantially fewer minutes on the computer than do non-Hispanic White children; however, the racial gap in percentage terms has narrowed between 1997 and 2003. Multivariate analyses indicate that the extent to which parental socioeconomic status explains the racial gap declined between 1997 and 2003—in 2003, less than 10% of the gap is explained by family income and household head's education. The pattern of decline is not observed when analyzing the racial gap in reading time. As home computer ownership approaches saturation, the racial gap in computer use time may increasingly reflect the underlying racial boundaries rather than parental status differentials.
Is it time to revisit the role of psychedelic drugs in enhancing human creativity?
Authors: Sessa B.
Published: June 2008

Human creativity is difficult to define and measure, but it is undoubtedly an important cognitive process. This makes it an interesting challenge for modern neuroscientific exploration — especially given the current interest in developing cognitive enhancers for commercial and clinical uses. There are similarities between the typical traits of creative people and the subjective psychological characteristics of the psychedelic (hallucinogenic) drug experience. This phenomenon was studied in a number of small trials and case studies in the 1960s. Results were inconclusive, and the quality of these studies — by modern research standards — was merely anecdotal. Nevertheless, with today's current renaissance in psychedelic drug research and the growing interest in cognitive enhancing drugs, now may be the time to re-visit these studies with contemporary research methods.
Effects of acute alcohol consumption and alcohol expectancy on processing of perceptual cues of emotional expression
Authors: Craig LC , Attwood AS , Benton CP , Penton-Voak IS , Munafò MR
Published: June 2008

Abstract

We recently demonstrated that alcohol elicits a difference between men and women in perceptual threshold for facial expressions of sadness. However, this study did not include a manipulation of alcohol expectancy. Therefore, we sought to determine whether these effects may be due to the expectation of having consumed alcohol. Male and female participants ( n = 100) were randomised using a balanced-placebo design to receive either an alcoholic or a non-alcoholic drink and to be told that this was alcoholic or non-alcoholic. Participants completed a psychophysical task which presented male and female faces expressing angry, happy, and sad emotions. Analysis of threshold data indicated a significant two-way interaction of drink × target emotion, reflecting a higher threshold for the detection of sad facial expressions of emotion, compared with angry or happy expressions, in the alcohol condition compared with the placebo condition. We did not observe any evidence of sex differences in these effects. Our data indicate that alcohol modifies the perceptual threshold for facial expressions of sadness. Unlike our previous report, we did not observe evidence of sex differences in these effects. Most importantly, we did not observe any evidence that these effects were due to expectancy effects associated with alcohol consumption.
Chronic exposure to low levels of aluminum alters cerebral cell signaling in response to acute MPTP administration
Authors: Li H , Campbell A , Ali SF , Cong P , Bondy SC
Published: June 2008

Two-month-old male B/6C3F1 mice were treated for 10 weeks with 100 μM aluminum lactate (Al) in drinking water. This dose of Al did not alter body weight, and there was no evidence of systemic toxicity. The degree of phosphorylation of several kinases which lead to transcription factor activation (reflecting the extent of their activation) was studied. The proportion of extracellular signal-regulated kinase (ERK) that was activated was depressed in cortex but not in the hippocampus following treatment but c-Jun N-terminal kinase (JNK), p38, IκB phosphorylation was unaltered in either tissue. Treatment of mice with 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) alone produced no significant changes in the degree of activation of any transcription factor studied. When MPTP dosing had been preceded by extended exposure to low levels of Al in drinking water, ERK activation was profoundly depressed in cortex and hippocampus, whereas JNK in hippocampus and IκB in cortex were greatly elevated. These changes consequent to exposure to both Al and MPTP were accompanied by an increase in NF-κB in both regions, whereas AP-1 was elevated in the hippocampus alone. Neither agent alone modulated AP-1 or NF-κB. Thus a synergistic interaction occurred between the toxicants. This interaction tended to promote the functioning of a kinase largely associated with inflammation and to depress that of ERK, which is associated with maintenance of cell survival. It is concluded that exposure to levels of Al with no evident toxicity can worsen the response to an acute challenge with MPTP. Al treatment alone was able to increase striatal 3,4-dihydroxyphenylacetic acid levels, suggesting an elevation of the rate of dopamine turnover in the striatum. However, no interaction in alteration of monoamine levels was found between Al and MPTP.
The Role of Personal Attributes in African American Roll-Call Voting Behavior in Congress
Authors: Rocca Michael S. , Sanchez Gabriel R. , Nikora Ron
Published: June 2008

In this research note, the authors explore the extent to which personal attributes influence voting behavior for African American members of Congress. The authors test the relationship between legislators' personal attributes and Poole and Rosenthal's DW-NOMINATE scores for black members of the 101st to 108th Congresses. The results suggest that personal attributes matter. They increase the explained variance in the models, and factors such as generational cohort, religion, and military experience are statistically significant. These results suggest that while descriptive members of Congress share much in common, they should not be interpreted as monolithic with respect to congressional voting.
Commentary on “The Economics of Specialty Hospitals”
Authors: Devers Kelly J.
Published: June 2008

There are two major aims of this commentary on “The Economics of Specialty Hospitals” by Schneider and colleagues (this issue). The first aim is to identify and discuss the policy, market, and organizational context in which physician-owned specialty hospitals have emerged and now exist in the United States. This context is critical for understanding aspects of the economic model and the potential advantages and disadvantages of physician-owned specialty (or limited-service) hospitals relative to general (or full-service) hospitals now and over time. The second aim is to discuss the six specific elements of the model (i.e., consumer demand, procedural operating margins, clinical efficiencies, procedural economies of scale, economies or diseconomies of scope, and competencies and learning). Specifically, to raise some key questions and to point to other ideas and empirical evidence that suggest that in practice, physician-owned specialty hospitals may not have all the advantages that the economic theory described seems to imply.
Effect of relapses over early progression of disability in multiple sclerosis patients treated with beta-interferon
Authors: Bosca I , Coret F , Valero C , Pascual AM , Magraner MJ , Landete L , Casanova B
Published: June 2008

Observational study designed to explore the effect of demographical variables and number of relapses over the disability progression in the two first years of beta-interferon treatment for multiple sclerosis. One hundred and sixty two patients treated with beta-interferon for at least two years were included, 70.9% females, mean age 33.4 years, mean disease duration 75.1 months, mean EDSS 2.4, previous year relapse rate 1.3. Main end-point was defined as a sustained EDSS increase (1.5 if previous EDSS 0-2.0; 1.0 if previous EDSS 2.5-4.0; 0.5 if previous EDSS 4.5 or higher). 62.3% of patients presented one or more relapses and 32.7% patients reached sustained disability increase. The univariate and multivariate Cox regression analysis only showed statistical significance for the relapses in the two first years after the treatment (HR 1 relapse: 3.4, p = 0.05; HR ≥ 2 relapses: 4.3, p < 0.001). The Kaplan-Meier survival analysis showed a higher probability of EDSS progression for patients with one relapse (log rank 10.9, p = 0.02) and with ≥ 2 relapses (log rank 17.7, p < 0.001), with no differences between them ( p = 0.38). In conclusion, patients with one or more relapses in the first two years of interferon treatment developed an earlier sustained progression of the disability.
Fatal neurogenic pulmonary edema in a patient with progressive multiple sclerosis
Authors: Bramow S , Faber-Rod JC , Jacobsen C , Kutzelnigg A , Patrikios P , Sorensen PS , Lassmann H , Laursen H
Published: June 2008

We report a case of fatal neurogenic pulmonary edema in progressive multiple sclerosis (MS). The patient had one isolated relapse-like episode. Six years later progressive disease began, lasting 5 years until unexpected death during sleep. Medico-legal autopsy revealed pulmonary edema and neuropathological examination showed infiltrations with lymphocytes and microglia in the respiratory centers of the medulla. More classical demyelinated lesions were found in the white matter of spinal cord and in the gray matter of the brain along with disseminated perivascular lymphocytic infiltrates. Medullary inflammation in progressive MS may result in sudden fatal respiratory failure.
Intervention Psychometrics
Authors: Decker Scott L.
Published: June 2008

This article reviews issues involved with using norm-referenced measures within an intervention validity model. Methodological examination of intervention validity has become more important as intervention methodologies have become part of federal legislation. However, current practice and federal guidelines often implicitly portray a dichotomy between individualized norm-referenced testing and intervention methodologies. This dichotomy is reified in the literature for various reasons. Consequently, it is not clear how information from individualized norm-referenced measures can be used within a treatment or intervention context. This article briefly addresses the perceived dichotomy between traditional psychoeducational assessment and behaviorally oriented assessments and discusses the importance of a multidimensional view of intervention that integrates multiple sources of information to guide intervention planning, implementation, and monitoring. Some practical applications of a hypothesis-testing model that integrates multiple sources of data with intervention-focused practices are used to integrate various assessment strategies for intervention purposes.
The medaka novel immune-type receptor (NITR) gene clusters reveal an extraordinary degree of divergence in variable domains
Authors: Desai Salil , Heffelfinger Amy K , Orcutt Timothy M , Litman Gary W , Yoder Jeffrey A
Published: June 2008

Background

Novel immune-type receptor (NITR) genes are members of diversified multigene families that are found in bony fish and encode type I transmembrane proteins containing one or two extracellular immunoglobulin (Ig) domains. The majority of NITRs can be classified as inhibitory receptors that possess cytoplasmic immunoreceptor tyrosine-based inhibition motifs (ITIMs). A much smaller number of NITRs can be classified as activating receptors by the lack of cytoplasmic ITIMs and presence of a positively charged residue within their transmembrane domain, which permits partnering with an activating adaptor protein.

Results

Forty-four NITR genes in medaka (Oryzias latipes) are located in three gene clusters on chromosomes 10, 18 and 21 and can be organized into 24 families including inhibitory and activating forms. The particularly large dataset acquired in medaka makes direct comparison possible to another complete dataset acquired in zebrafish in which NITRs are localized in two clusters on different chromosomes. The two largest medaka NITR gene clusters share conserved synteny with the two zebrafish NITR gene clusters. Shared synteny between NITRs and CD8A/CD8B is limited but consistent with a potential common ancestry.

Conclusion

Comprehensive phylogenetic analyses between the complete datasets of NITRs from medaka and zebrafish indicate multiple species-specific expansions of different families of NITRs. The patterns of sequence variation among gene family members are consistent with recent birth-and-death events. Similar effects have been observed with mammalian immunoglobulin (Ig), T cell antigen receptor (TCR) and killer cell immunoglobulin-like receptor (KIR) genes. NITRs likely diverged along an independent pathway from that of the somatically rearranging antigen binding receptors but have undergone parallel evolution of V family diversity.
Transcriptional analysis of Mycobacterium fortuitum cultures upon hydrogen peroxide treatment using the novel standard rrn A-P1
Authors: Núñez María Carmen , Menéndez María Carmen , Rebollo María José , García María J
Published: June 2008

Background

The ability of an intracellular pathogen to establish infection depends on the capacity of the organism to survive and replicate inside the host.Mycobacterium fortuitumis a bacteria that contains genes involved in the detoxification of the oxygen reactive species such as those produced by the host during the infection. In this work, we investigate the effects of hydrogen peroxide on the transcription and expression of these genes by developing a real time quantitative PCR technique (qRT-PCR) using the ribosomal promoter region (rrnA-P1) as reference product for quantification of the mRNA levels.

Results

M. fortuitumcultures were treated with different hydrogen peroxide concentrations (0.02 to 20 mM) during several periods of time (30 to 120 minutes). The activity of the enzymes KatGII and SodA, and the transcription of corresponding genes were evaluated. The transcriptional regulatorfurAII gene was also studied.

The ribosomal promoter regionrrnA-P1 was validated as referential product under the stress conditions checked by qRT-PCR.

Minor changes were observed under the conditions tested except when bacteria were incubated in the presence of 20 mM hydrogen peroxide. Under those conditions, the levels of transcription of the three genes under study increased at 30 minutes of treatment. The viability of the bacteria was not influenced under the conditions tested.

Conclusion

In this work, we have quantified transcriptional responses to stress suggesting that, the opportunistic pathogenM. fortuitumis more resistant and differs in behaviour in the presence of hydrogen peroxide, when compared to the major pathogenMycobacterium tuberculosisand the saprophyteMycobacterium smegmatis. Besides, we demonstrate the mycobacterial non-coding regionrrnA-P1 to be a suitable reference product in the analysis of qRT-PCR transcriptional data ofM. fortuitum.
Fonsecaea pedrosoiinfection induces differential modulation of costimulatory molecules and cytokines in monocytes from patients with severe and mild forms of chromoblastomycosis
Authors: Sousa Maria Glória Teixeira , Azevedo Conceição de Maria Pedrozo e Silva , Nascimento Rosana Cicera , Ghosn Eliver Eid Bou , Santiago Karla Leticia , Noal Vanessa , Bomfim Gisele Facholi , Marques Sirlei Garcia , Gonçalves Azizedite Guedes , Santos Daniel Wagner de Castro Lima , Almeida Sandro Rogerio
Published: June 2008

The host defense mechanism in chromoblastomycosis has not been thoroughly investigated. It has been suggested that cell-mediated immunity in patients with long-standing chromoblastomycosis is somehow impaired. As a result, these individuals became unable to develop an efficient immune reaction. Many studies have shown that monocyte-derived macrophages exhibit critical activities in immunity to microorganisms. Moreover, the ability of cells from the monocytic lineage to process and present antigens, to produce cytokines, and to provide costimulatory signals confirms their pivotal role in the initiation of specific immune responses. In the present study, it was observed that monocytes from patients with a severe form of disease had a higher production of IL-10 and a lower expression of HLA-DR and costimulatory molecules when stimulated with specific antigen or LPS. Immune modulation with recombinant IL-12 or anti-IL-10 can restore the antigen-specific Th1-type immune response in chromoblastomycosis patients by up-regulating HLA-DR and costimulatory molecules in monocytes. Therefore, our data show that monocytes from patients with different clinical forms of chromoblastomycosis present distinct phenotypic and functional profiles. This observation suggests possible mechanisms that control the T cell response and influence their role in the development of pathology.
An NGA Model for the Average Horizontal Component of Peak Ground Motion and Response Spectra
Authors: Chiou BrianS-J. , Youngs Robert R.
Published: June 2008

We present a model for estimating horizontal ground motion amplitudes caused by shallow crustal earthquakes occurring in active tectonic environments. The model provides predictive relationships for the orientation-independent average horizontal component of ground motions. Relationships are provided for peak acceleration, peak velocity, and 5-percent damped pseudo-spectral acceleration for spectral periods of 0.01 to 10 seconds. The model represents an update of the relationships developed by Sadigh et. al. (1997) and incorporates improved magnitude and distance scaling forms as well as hanging-wall effects. Site effects are represented by smooth functions of average shear wave velocity of the upper 30 m ( VS30) and sediment depth. The new model predicts median ground motion that is similar to Sadigh et. al. (1997) at short spectral period, but lower ground motions at longer periods. The new model produces slightly lower ground motions in the distance range of 10 to 50 km and larger ground motions at larger distances. The aleatory variability in ground motion amplitude was found to depend upon earthquake magnitude and on the degree of nonlinear soil response, For large magnitude earthquakes, the aleatory variability is larger than found by Sadigh et. al. (1997).
Summary of the Abrahamson & Silva NGA Ground-Motion Relations
Authors: Abrahamson Norman , Silva Walter
Published: June 2008

Empirical ground-motion models for the rotation-independent average horizontal component from shallow crustal earthquakes are derived using the PEER NGA database. The model is applicable to magnitudes 5–8.5, distances 0–200 km, and spectral periods of 0–10 sec. In place of generic site categories (soil and rock), the site is parameterized by average shear-wave velocity in the top 30 m ( VS30) and the depth to engineering rock (depth to VS=1000 m/s). In addition to magnitude and style-of-faulting, the source term is also dependent on the depth to top-of-rupture: for the same magnitude and rupture distance, buried ruptures lead to larger short-period ground motions than surface ruptures. The hanging-wall effect is included with an improved model that varies smoothly as a function of the source properties (M, dip, depth), and the site location. The standard deviation is magnitude dependent with smaller magnitudes leading to larger standard deviations. The short-period standard deviation model for soil sites is also distant-dependent due to nonlinear site response, with smaller standard deviations at short distances.
Nonlinear Site Amplification Factors for Constraining the NGA Models
Authors: Walling Melanie , Silva Walter , Abrahamson Norman
Published: June 2008

Amplification factors computed from the equivalent-linear method using the program RASCALS are used to develop constraints on the nonlinear soil response for possible use by the NGA ground-motion model developers. The site response computations covered site conditions with average VS30 values ranging from 160 to 900 m/s, soil depths from 15 to 914 m, and peak accelerations of the input rock motion ( VS30=1100 m/s) between 0.01 g and 1.5 g. Four sets of nonlinear properties of the soils are used: EPRI, Peninsular Range, Imperial Valley, and Bay Mud. The first two soil models are used for VS30≥270 m/s and the later two are used for VS30≤190 m/s. Simple parametric models of the nonlinear amplification factors that are functions of the PGA on rock and VS30 are developed for the EPRI and Peninsula models.
Creating New Landscapes and Ecosystems
Authors: Johnson E.A. , Miyanishi K.
Published: June 2008

Extraction of oil from the Alberta Oil Sands through surface mining involves the removal of the overburden and oil sand to a depth of up to 100 m and over extremely large areas. While the operation of the bitumen processing plants has serious environmental impacts on downstream habitats, this article focuses on the reclamation of areas from which the oil sands have been removed, processed, and returned. This reclamation following closure of the mines will entail the complete re‐creation of landforms and ecosystems at a landscape scale, with the goal of producing suitable habitats for plants, animals, and people. Such projects will require a reasonable understanding of the geophysical and ecological processes that operate at a wide range of scales. Some information is provided on the climate, hydrology, vegetation, and land use (past and current) of the Oil Sands area, situated within the Boreal Plain ecozone, to provide a framework for discussion of issues to be addressed in, and proposed guidelines for, such large‐scale reclamation. Although none of the mines has yet closed, numerous consultant reports have been produced with recommendations for various aspects of such reclamation projects (e.g., wetland hydrology, vegetation, wildlife habitat). The scientific basis of such reports is found to vary with respect to depth of understanding of the relevant processes.
Ocean Acidification and Its Potential Effects on Marine Ecosystems
Authors: Guinotte John M. , Fabry Victoria J.
Published: June 2008

Ocean acidification is rapidly changing the carbonate system of the world oceans. Past mass extinction events have been linked to ocean acidification, and the current rate of change in seawater chemistry is unprecedented. Evidence suggests that these changes will have significant consequences for marine taxa, particularly those that build skeletons, shells, and tests of biogenic calcium carbonate. Potential changes in species distributions and abundances could propagate through multiple trophic levels of marine food webs, though research into the long‐term ecosystem impacts of ocean acidification is in its infancy. This review attempts to provide a general synthesis of known and/or hypothesized biological and ecosystem responses to increasing ocean acidification. Marine taxa covered in this review include tropical reef‐building corals, cold‐water corals, crustose coralline algae, Halimeda, benthic mollusks, echinoderms, coccolithophores, foraminifera, pteropods, seagrasses, jellyfishes, and fishes. The risk of irreversible ecosystem changes due to ocean acidification should enlighten the ongoing CO2 emissions debate and make it clear that the human dependence on fossil fuels must end quickly. Political will and significant large‐scale investment in clean‐energy technologies are essential if we are to avoid the most damaging effects of human‐induced climate change, including ocean acidification.
Understanding, Managing, and Minimizing Urban Impacts on Surface Water Nitrogen Loading
Authors: Bernhardt Emily S. , Band Lawrence E. , Walsh Christopher J. , Berke Philip E.
Published: June 2008

The concentration of materials and energy within cities is an inevitable consequence of dense populations and their per capita requirements for food, fiber, and fuel. As the world population becomes increasingly urban over the coming decades, urban areas will dramatically affect the distribution of nutrients across the face of the planet. In many cities, technological developments and urban planning have been effective at reducing the amount of waste nitrogen that is ultimately exported to downstream surface waters, largely through investments in sanitary sewer infrastructure and wastewater treatment. There are, however, still large cities throughout the developed world that have failed to take advantage of these obvious innovations to reduce their impact on downstream ecosystems. In addition, very few cities have adequately addressed the problems of diffuse nitrogen pollution, instead city infrastructure is often designed to route this N directly into downstream ecosystems. In the developing world, many of these problems are more acute, as rapidly growing urban populations exceed the capacity of limited municipal infrastructure. Reducing urban N pollution of groundwaters and surface waters both locally and globally can only be achieved through cultural and political adaptation in addition to technological innovations. In this review, we will focus on the implications of an increasingly urban world population on local, regional, and global nitrogen cycles and propose a variety of approaches for minimizing and mitigating the impacts of urban N concentration.