bluuebunny/crossref_metadata_2025 huggingface dataset:
Internationalization of University Curricula in Japan: Major Policies and Practice Since the 1980s
Authors: Huang Futao
Published: April 2006

This article begins by discussing the context and major policies as well as the rationales related to internationalization of the university curricula in Japan. It then touches on internationalization of the curricula in Japanese higher education institutions at home and on development of cross-border curricula that are both imported into Japan and provided in higher education institutions abroad. The article concludes by arguing that internationalization of the university curricula in Japan has changed to the extent that it no longer plays the minor and unimportant role in attracting and hosting international students that used to be expected in the early 1980s. Currently internationalization of the university curricula in Japan is not confined merely to the development of language education for both international students and Japanese students at home but also involves a variety of cross-border educational initiatives.
Biases in Ratings of Disruptive Behavior in Children
Authors: Hartung Cynthia M. , Van Pelt Jill C. , Armendariz Monica L. , Knight Laura A.
Published: April 2006

Objective: Behavior disorders are more prevalent among boys than girls, but the etiology of this difference is unclear. Studies have not tested for sex bias in ratings as a contributing factor to the differential sex prevalence rates. However, there are several studies showing “negative halo effects” in ratings of boys (i.e., the presence of one type of behavior artificially inflating ratings of another behavior). These findings have only been extended to girls in one recent study. The current study is designed to test for sex difference in (a) ratings of boys and girls who exhibit the same degree of disruptive behavior and (b) negative halo effects. Method: Two hundred and thirty-nine college students participated. Sex differences in ratings are not found. Nonetheless, bidirectional negative halo effects are found for boys and girls (i.e., the presence of oppositionality artificially increased ratings of inattention and hyperactivity; the presence of inattention and hyperactivity artificially increased oppositionality).
Psychometric Properties of the Chinese Version of the Conners’ Parent and Teacher Rating Scales-Revised: Short Form
Authors: Gau Susan Shur-Fen , Soong Wei-Tsuen , Chiu Yen-Nan , Tsai Wen-Che
Published: April 2006

Objective: This article examines the psychometric properties of the Chinese version of the Conners’ Parent and Teacher Rating Scales-Revised: Short Forms (CPRS-R:S-C and CTRS-R:S-C) in a representative sample of 2,584 first to ninth graders in Taipei and 479 clinical participants (274 with ADHD). Method: The instruments include the CPRS-R:S-C, CTRS-R:S-C, and the Chinese version of the Swanson, Kotkin, Atkins, M-Flynn, and Pelham Scale. Results: Results show satisfactory factor structure, test-retest reliability, internal consistency, and convergent validity for all the subscales of the CTRS-R:S-C and CPRS-R:S-C. They clearly distinguish clinical participants with ADHD from those without. Conclusion: Our findings suggest that the CPRS-R:S-C and CTRS-R:S-C are reliable and valid instruments for measuring inattention and hyperactivity in both clinical and community settings in the Chinese population in Taipei.
ADHD Characteristics in Canadian Aboriginal Children
Authors: Baydala Lola , Sherman Jody , Rasmussen Carmen , Wikman Erik , Janzen Henry
Published: April 2006

Objective: The authors examine how many Aboriginal children attending two reservation-based elementary schools in Northern Alberta, Canada, would demonstrate symptoms associated with ADHD using standardized parent and teacher questionnaires. Method: Seventy-five Aboriginal children in Grades 1 through 4 are tested. Seventeen of the 75 (22.7%) Aboriginal children demonstrated a match on parent and teacher forms, with T-scores greater than 1.5 standard deviations from the mean on the Conners’ ADHD Index, Diagnostic and Statistical Manual of Mental Disorders (4th ed.; DSM-IV) Hyperactive/Impulsive Index, DSM-IV Inattentive Index, and/or DSM-IV Total Combined T-score. Results: The number of Aboriginal children found to have symptoms associated with ADHD is significantly higher than expected based on prevalence rates in the general population. Conclusion: These findings suggest either a high prevalence of ADHD in Aboriginal children or unique learning and behavioral patterns in Aboriginal children that may erroneously lead to a diagnosis of ADHD if screening questionnaires are used.
A Comparison of Preferred Treatment Outcomes Between Children With ADHD and Their Parents
Authors: Traywick Tracey B. , Lamson Angela L. , Diamond John M. , Carawan Sandra
Published: April 2006

Objective: The newest guidelines for the treatment of ADHD call for the formation of an individualized treatment plan based on collaboration. Because the process of collaboration requires the communication of desired outcomes, the authors’ goal is to examine the preferred outcomes of treatment for ADHD for children and parents. Method: A preferred outcomes questionnaire is used to gather data. A listing of the outcomes in ranked order is generated for each group. Spearman’s rho is used to generate comparative data. Results: Our results indicate a significant correlation between the preferred outcomes of the children and the parents. There is one outlier regarding the use of medication. Conclusion: The existence of the single outlier concerning the use of medication may infer that an assessment of the child’s feelings regarding a medication regimen is therapeutically indicated.
Constitutive activation of Akt contributes to the pathogenesis and survival of mantle cell lymphoma
Authors: Rudelius Martina , Pittaluga Stefania , Nishizuka Satoshi , Pham Trinh H.-T. , Fend Falko , Jaffe Elaine S. , Quintanilla-Martinez Leticia , Raffeld Mark
Published: April 2006

To determine whether the PI3K/Akt signaling pathway is involved in the pathogenesis of mantle cell lymphoma (MCL), we investigated the phosphorylation status of Akt and multiple downstream targets in primary MCL cases and cell lines. Akt was phosphorylated in 12 of 12 aggressive blastoid MCL variants and in 4 of 4 MCL cell lines. In contrast, phosphorylated Akt was present in only 5 of 16 typical MCL, 3 at comparable levels to the blastoid cases, and 2 at low levels. The presence of p-Akt was accompanied by the phosphorylation of p27kip1, FRKHL-1, MDM2, Bad, mTOR, and p70S6K. Inhibition of the PI3K/Akt pathway in the MCL cell lines abrogated or reduced the phosphorylation of Akt, p27kip1, FRKHL-1, MDM2, Bad, mTOR, GSK-3β, IκB, and led to cell-cycle arrest and apoptosis. Six MCL cases (5 with activated Akt and 1 with inactive Akt) and 3 of 4 cell lines showed loss of PTEN expression. PIK3CA mutations were not detected. We conclude that constitutive activation of the PI3K/Akt pathway contributes to the pathogenesis of MCL and preferentially occurs in blastoid variants. One possible mechanism of activation is loss of PTEN expression. These data suggest that PI3K/Akt inhibitors may be effective in the treatment of Akt-activated MCL.
Increased oxidative stress in asymptomatic current chronic smokers and GOLD stage 0 COPD
Authors: Rytilä Paula , Rehn Tiina , Ilumets Helen , Rouhos Annamari , Sovijärvi Anssi , Myllärniemi Marjukka , Kinnula Vuokko L
Published: April 2006

Background

Chronic obstructive pulmonary disease (COPD) is associated with increased oxidative and nitrosative stress. The aim of our study was to assess the importance of these factors in the airways of healthy smokers and symptomatic smokers without airway obstruction, i.e. individuals with GOLD stage 0 COPD.

Methods

Exhaled NO (FENO) and induced sputum samples were collected from 22 current smokers (13 healthy smokers without any respiratory symptoms and 9 with symptoms i.e. stage 0 COPD) and 22 healthy age-matched non-smokers (11 never smokers and 11 ex-smokers). Sputum cell differential counts, and expressions of inducible nitric oxide synthase (iNOS), myeloperoxidase (MPO), nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE) were analysed from cytospins by immunocytochemistry. Eosinophil cationic protein (ECP) and lactoferrin were measured from sputum supernatants by ELISA.

Results

FENO was significantly decreased in smokers, mean (SD) 11.0 (6.7) ppb, compared to non-smokers, 22.9 (10.0), p < 0.0001. Induced sputum showed increased levels of neutrophils (p = 0.01) and elevated numbers of iNOS (p = 0.004), MPO (p = 0.003), nitrotyrosine (p = 0.003), and 4-HNE (p = 0.03) positive cells in smokers when compared to non-smokers. Sputum lactoferrin levels were also higher in smokers than in non-smokers (p = 0.02). Furthermore, we noted four negative correlations between FENO and 1) total neutrophils (r = -0.367, p = 0.02), 2) positive cells for iNOS (r = -0.503, p = 0.005), 3) MPO (r = -0.547, p = 0.008), and 4) nitrotyrosine (r = -0.424, p = 0.03). However, no major differences were found between never smokers and ex-smokers or between healthy smokers and stage 0 COPD patients.

Conclusion

Our results clearly indicate that several markers of oxidative/nitrosative stress are increased in current cigarette smokers compared to non-smokers and no major differences can be observed in these biomarkers between non-symptomatic smokers and subjects with GOLD stage 0 COPD.
Histological staining methods preparatory to laser capture microdissection significantly affect the integrity of the cellular RNA
Authors: Wang Hongyang , Owens James D , Shih Joanna H , Li Ming-Chung , Bonner Robert F , Mushinski J Frederic
Published: April 2006

Background

Gene expression profiling by microarray analysis of cells enriched by laser capture microdissection (LCM) faces several technical challenges. Frozen sections yield higher quality RNA than paraffin-imbedded sections, but even with frozen sections, the staining methods used for histological identification of cells of interest could still damage the mRNA in the cells. To study the contribution of staining methods to degradation of results from gene expression profiling of LCM samples, we subjected pellets of the mouse plasma cell tumor cell line TEPC 1165 to direct RNA extraction and to parallel frozen sectioning for LCM and subsequent RNA extraction. We used microarray hybridization analysis to compare gene expression profiles of RNA from cell pellets with gene expression profiles of RNA from frozen sections that had been stained with hematoxylin and eosin (H&E), Nissl Stain (NS), and for immunofluorescence (IF) as well as with the plasma cell-revealing methyl green pyronin (MGP) stain. All RNAs were amplified with two rounds of T7-based in vitro transcription and analyzed by two-color expression analysis on 10-K cDNA microarrays.

Results

The MGP-stained samples showed the least introduction of mRNA loss, followed by H&E and immunofluorescence. Nissl staining was significantly more detrimental to gene expression profiles, presumably owing to an aqueous step in which RNA may have been damaged by endogenous or exogenous RNAases.

Conclusion

RNA damage can occur during the staining steps preparatory to laser capture microdissection, with the consequence of loss of representation of certain genes in microarray hybridization analysis. Inclusion of RNAase inhibitor in aqueous staining solutions appears to be important in protecting RNA from loss of gene transcripts.
Phylogenomic analysis of the GIY-YIG nuclease superfamily
Authors: Dunin-Horkawicz Stanislaw , Feder Marcin , Bujnicki Janusz M
Published: April 2006

Background

The GIY-YIG domain was initially identified in homing endonucleases and later in other selfish mobile genetic elements (including restriction enzymes and non-LTR retrotransposons) and in enzymes involved in DNA repair and recombination. However, to date no systematic search for novel members of the GIY-YIG superfamily or comparative analysis of these enzymes has been reported.

Results

We carried out database searches to identify all members of known GIY-YIG nuclease families. Multiple sequence alignments together with predicted secondary structures of identified families were represented as Hidden Markov Models (HMM) and compared by the HHsearch method to the uncharacterized protein families gathered in the COG, KOG, and PFAM databases. This analysis allowed for extending the GIY-YIG superfamily to include members of COG3680 and a number of proteins not classified in COGs and to predict that these proteins may function as nucleases, potentially involved in DNA recombination and/or repair. Finally, all old and new members of the GIY-YIG superfamily were compared and analyzed to infer the phylogenetic tree.

Conclusion

An evolutionary classification of the GIY-YIG superfamily is presented for the very first time, along with the structural annotation of all (sub)families. It provides a comprehensive picture of sequence-structure-function relationships in this superfamily of nucleases, which will help to design experiments to study the mechanism of action of known members (especially the uncharacterized ones) and will facilitate the prediction of function for the newly discovered ones.
Eight previously unidentified mutations found in the OA1ocular albinism gene
Authors: Mayeur Hélène , Roche Olivier , Vêtu Christelle , Jaliffa Carolina , Marchant Dominique , Dollfus Hélène , Bonneau Dominique , Munier Francis L , Schorderet Daniel F , Levin Alex V , Héon Elise , Sutherland Joanne , Lacombe Didier , Said Edith , Mezer Eedy , Kaplan Josseline , Dufier Jean-Louis , Marsac Cécile , Menasche Maurice , Abitbol Marc
Published: April 2006

Background

Ocular albinism type 1 (OA1) is an X-linked ocular disorder characterized by a severe reduction in visual acuity, nystagmus, hypopigmentation of the retinal pigmented epithelium, foveal hypoplasia, macromelanosomes in pigmented skin and eye cells, and misrouting of the optical tracts. This disease is primarily caused by mutations in the OA1 gene.

Methods

The ophthalmologic phenotype of the patients and their family members was characterized. We screened for mutations in the OA1 gene by direct sequencing of the nine PCR-amplified exons, and for genomic deletions by PCR-amplification of large DNA fragments.

Results

We sequenced the nine exons of the OA1 gene in 72 individuals and found ten different mutations in seven unrelated families and three sporadic cases. The ten mutations include an amino acid substitution and a premature stop codon previously reported by our team, and eight previously unidentified mutations: three amino acid substitutions, a duplication, a deletion, an insertion and two splice-site mutations. The use of a novel Taq polymerase enabled us to amplify large genomic fragments covering the OA1 gene. and to detect very likely six distinct large deletions. Furthermore, we were able to confirm that there was no deletion in twenty one patients where no mutation had been found.

Conclusion

The identified mutations affect highly conserved amino acids, cause frameshifts or alternative splicing, thus affecting folding of the OA1 G protein coupled receptor, interactions of OA1 with its G protein and/or binding with its ligand.
Insomnia in school-age children with Asperger syndrome or high-functioning autism
Authors: Allik Hiie , Larsson Jan-Olov , Smedje Hans
Published: April 2006

Background

Asperger syndrome (AS) and high-functioning autism (HFA) are pervasive developmental disorders (PDD) in individuals of normal intelligence. Childhood AS/HFA is considered to be often associated with disturbed sleep, in particular with difficulties initiating and/or maintaining sleep (insomnia). However, studies about the topic are still scarce. The present study investigated childhood AS/HFA regarding a wide range of parent reported sleep-wake behaviour, with a particular focus on insomnia.

Methods

Thirty-two 8–12 yr old children with AS/HFA were compared with 32 age and gender matched typically developing children regarding sleep and associated behavioural characteristics. Several aspects of sleep-wake behaviour including insomnia were surveyed using a structured paediatric sleep questionnaire in which parents reported their children's sleep patterns for the previous six months. Recent sleep patterns were monitored by use of a one-week sleep diary and actigraphy. Behavioural characteristics were surveyed by use of information gleaned from parent and teacher-ratings in the High-Functioning Autism Spectrum Screening Questionnaire, and in the Strengths and Difficulties Questionnaire.

Results

Parent-reported difficulties initiating sleep and daytime sleepiness were more common in children with AS/HFA than in controls, and 10/32 children with AS/HFA (31.2%) but none of the controls fulfilled our definition of paediatric insomnia. The parent-reported insomnia corresponded to the findings obtained by actigraphy. Children with insomnia had also more parent-reported autistic and emotional symptoms, and more teacher-reported emotional and hyperactivity symptoms than those children without insomnia.

Conclusion

Parental reports indicate that in childhood AS/HFA insomnia is a common and distressing symptom which is frequently associated with coexistent behaviour problems. Identification and treatment of sleep problems need to be a routine part of the treatment plan for children with AS/HFA.
Pontiac fever: an operational definition for epidemiological studies
Authors: Tossa Paul , Deloge-Abarkan Magali , Zmirou-Navier Denis , Hartemann Philippe , Mathieu Laurence
Published: April 2006

Background

Pontiac fever is usually described in epidemic settings. Detection of Pontiac fever is a marker of an environmental contamination byLegionellaand should thereby call for prevention measures in order to prevent outbreak of Legionnaire's disease. The objective of this study is to propose an operational definition of Pontiac fever that is amenable to epidemiological surveillance and investigation in a non epidemic setting.

Methods

A population of 560 elderly subjects residing in 25 nursing homes was followed during 4 months in order to assess the daily incidence of symptoms associated, in the literature, with Pontiac fever. The water and aerosol of one to 8 showers by nursing home were characterized combining conventional bacterial culture ofLegionellaand the Fluorescence In Situ Hybridization (FISH) technique that used oligonucleotides probes specific forLegionellaceae. A definition of Pontiac fever was devised based on clinical symptoms described in epidemic investigations and on their timing after the exposure event. The association between incidence of Pontiac fever and shower contamination levels was evaluated to test the relevance of this definition.

Results

The proposed definition of Pontiac fever associated the following criteria: occurrence of at least one symptom among headache, myalgia, fever and shivers, possibly associated with other 'minor' symptoms, within three days after a shower contaminated byLegionella, during a maximum of 8 days (minimum 2 days). 23 such cases occurred during the study (incidence rate: 0.125 cases per person-year [95% CI: 0.122–0.127]). A concentration ofLegionellain water equal to or greater than 104.L-1(FISH method) was associated with a significant increase of incidence of Pontiac fever (p = 0.04).

Conclusion

Once validated in other settings, the proposed definition of Pontiac fever might be used to develop epidemiological surveillance and help draw attention on sources ofLegionella.
Primary histologic diagnosis using automated whole slide imaging: a validation study
Authors: Gilbertson John R , Ho Jonhan , Anthony Leslie , Jukic Drazen M , Yagi Yukako , Parwani Anil V
Published: April 2006

Background

Only prototypes 5 years ago, high-speed, automated whole slide imaging (WSI) systems (also called digital slide systems, virtual microscopes or wide field imagers) are becoming increasingly capable and robust. Modern devices can capture a slide in 5 minutes at spatial sampling periods of less than 0.5 micron/pixel. The capacity to rapidly digitize large numbers of slides should eventually have a profound, positive impact on pathology. It is important, however, that pathologists validate these systems during development, not only to identify their limitations but to guide their evolution.

Methods

Three pathologists fully signed out 25 cases representing 31 parts. The laboratory information system was used to simulate real-world sign-out conditions including entering a full diagnostic field and comment (when appropriate) and ordering special stains and recuts. For each case, discrepancies between diagnoses were documented by committee and a "consensus" report was formed and then compared with the microscope-based, sign-out report from the clinical archive.

Results

In 17 of 25 cases there were no discrepancies between the individual study pathologist reports. In 8 of the remaining cases, there were 12 discrepancies, including 3 in which image quality could be at least partially implicated. When the WSI consensus diagnoses were compared with the original sign-out diagnoses, no significant discrepancies were found. Full text of the pathologist reports, the WSI consensus diagnoses, and the original sign-out diagnoses are available as an attachment to this publication.

Conclusion

The results indicated that the image information contained in current whole slide images is sufficient for pathologists to make reliable diagnostic decisions and compose complex diagnostic reports. This is a very positive result; however, this does not mean that WSI is as good as a microscope. Virtually every slide had focal areas in which image quality (focus and dynamic range) was less than perfect. In some cases, there was evidence of over-compression and regions made "soft" by less than perfect focus. We expect systems will continue to get better, image quality and speed will continue to improve, but that further validation studies will be needed to guide development of this promising technology.
Efficacy and safety of non-invasive ventilation in the treatment of acute cardiogenic pulmonary edema – a systematic review and meta-analysis
Authors: Winck João C , Azevedo Luís F , Costa-Pereira Altamiro , Antonelli Massimo , Wyatt Jeremy C
Published: April 2006

Introduction

Continuous positive airway pressure ventilation (CPAP) and non-invasive positive pressure ventilation (NPPV) are accepted treatments in acute cardiogenic pulmonary edema (ACPE). However, it remains unclear whether NPPV is better than CPAP in reducing the need for endotracheal intubation (NETI) rates, mortality and other adverse events. Our aim was to review the evidence about the efficacy and safety of these two methods in ACPE management.

Methods

We conducted a systematic review and meta-analysis of randomized controlled trials on the effect of CPAP and/or NIPV in the treatment of ACPE, considering the outcomes NETI, mortality and incidence of acute myocardial infarction (AMI). We searched six electronic databases up to May 2005 without language restrictions, reviewed references of relevant articles, hand searched conference proceedings and contacted experts.

Results

Of 790 articles identified, 17 were included. In a pooled analysis, 10 studies of CPAP compared to standard medical therapy (SMT) showed a significant 22% absolute risk reduction (ARR) in NETI (95% confidence interval (CI), -34% to -10%) and 13% in mortality (95%CI, -22% to -5%). Six studies of NPPV compared to SMT showed an 18% ARR in NETI (95%CI, -32% to -4%) and 7% in mortality (95%CI, -14% to 0%). Seven studies of NPPV compared to CPAP showed a non-significant 3% ARR in NETI (95%CI, -4% to 9%) and 2% in mortality (95%CI, -6% to 10%). None of these methods increased AMI risk. In a subgroup analysis, NPPV did not lead to better outcomes than CPAP in studies including more hypercapnic patients.

Conclusion

Robust evidence now supports the use of CPAP and NPPV in ACPE. Both techniques decrease NETI and mortality compared to SMT and none shows increased AMI risk. CPAP should be considered a first line intervention as NPPV did not show a better efficacy, even in patients with more severe conditions, and CPAP is cheaper and easier to implement in clinical practice.
Prevalence and correlates of personality disorder in Great Britain
Authors: Coid Jeremy , Yang Min , Tyrer Peter , Roberts Amanda , Ullrich Simone
Published: April 2006

Background

Epidemiological data on personality disorders, comorbidity and associated use of services are essential for health service policy.

Aims

To measure the prevalence and correlates of personality disorder in a representative community sample.

Method

The Structured Clinical Interview for DSM-IV Axis II disorders was used to measure personality disorder in 626 persons aged 16-74 years in households in England, Scotland and Wales, in atwo-phase survey.

Results

The weighted prevalence of personality disorder was 4.4% (95% CI 2.9-6.7). Rates were highest among men, separated and unemployed participants in urban locations. High use of healthcare services was confounded by comorbid mental disorder and substance misuse. Cluster B disorders were associated with early institutional care and criminality.

Conclusions

Personality disorder is common in the community especially in urban areas. Services are normally restricted to symptomatic, help-seeking individuals, but a vulnerable group with cluster B disorders can be identified early are in care during childhood and enter the criminal justice system when young. This suggests the need for preventive interventions at the public mental health level.
Military deployment to the Gulf War as a risk factor for psychiatric illness among US troops
Authors: Fiedler Nancy , Ozakinci Gozde , Hallman William , Wartenberg Daniel , Brewer Noel T. , Barrett Drue H. , Kipen Howard M.
Published: April 2006

Background

Several studies document an excess of psychiatric symptoms among veterans of the 1991 Gulf War. However, little is known about the prevalence of psychiatric disorders in those who were deployed to that conflict.

Aims

To compare the 12-month prevalence and associated risk factors for DSM Axis I psychiatric diagnoses between random samples of Gulf War-deployed veterans and veterans of the same era notdeployed to the Persian Gulf (era veterans).

Method

Interview data from 967 Gulf War veterans and 784 era veterans were examined to determine current health status, medical conditions, symptoms and Axis I psychiatric disorders. Logistic regression models evaluated risk factors for psychiatric disorder.

Results

Gulf War veterans had a significantly higher prevalence of psychiatric diagnoses, with twice the prevalence of anxiety disorders and depression. Lower rank, female gender and divorced or single marital status were significant independent predictors of psychiatric disorder.

Conclusions

Deployment to the Gulf War is associated with a range of mental health outcomes more than 10 years after deployment.
Lifetime and 12-month prevalence of mental disorders in the Nigerian Survey of Mental Health and Well-Being
Authors: Gureje Oye , Lasebikan Victor O. , Kola Lola , Makanjuola Victor A.
Published: April 2006

Background

Large-scale community studies of the prevalence of mental disorders using standardised assessment tools are rare in sub-Saharan Africa.

Aims

To conduct such a study.

Method

Multistage stratified clustered sampling of households in the Yoruba-speaking parts of Nigeria. Face-to-face interviews used the World Mental Health version of the Composite International Diagnostic Interview (WMH-CIDI).

Results

Of the 4984 people interviewed (response rate 79.9%), 12.1% had a lifetime rate of at least one DSM–IV disorder and 5.8% had 12-month disorders. Anxiety disorders were the most common (5.7% lifetime, 4.1% 12-month rates) but virtually no generalised anxiety or post-traumatic stress disorder were identified. Of the 23% who had seriously disabling disorders, only about 8% had received treatment in the preceding 12 months. Treatment was mostly provided by general medical practitioners; only a few were treated by alternative practitioners such as traditional healers.

Conclusions

The observed low rates seem to reflect demographic and ascertainment factors. There was a large burden of unmet need for care among people with serious disorders.
Views of child psychiatrists on physical contact with patients
Authors: Blower Aileen , Lander Roddy , Crawford Anna , Elliot Ruth , McNulty Clare , Holmes Christopher , Srireddy Pavan , Mulcahy Michelle , Minnis Helen
Published: April 2006

The appropriateness and therapeutic value of physical contact with children is under increasing scrutiny. We conducted a postal questionnaire and telephone survey of consultant child and adolescent psychiatrists within Great Britain to investigate attitudes of specialists towards physical contact with their patients in different clinical contexts. Here we report that psychiatrists tend to restrict physical contact to the minimum essential for patient comfort or safety. Decision-making about contact is primarily influenced by professional experience and training. This conservative approach to physical contact with patients has implications for clinical practice and requires to be better informed by evidence.
Antidepressant therapy and C-reactive protein levels
Authors: O'Brien Sinead M. , Scott Lucinda V. , Dinan Timothy G.
Published: April 2006

Background

Major depression is associated with activation of the inflammatory response.

Aims

To examine C-reactive protein levels in depression and to determine the impact of selective serotonin reuptake inhibitor (SSRI) therapy.

Method

Atwo-part study. In study 1, which used a between-subjects design, C-reactive protein was measured in 32 patients (20 currently depressed, 12 euthymic) with a history of DSM–IV major depression, all of whom were treated with an SSRI, and in a healthy comparison group (n=20). Study 2 employed a within-subject design: C-reactive protein was measured in 20 patients with major depression both before and after SSRI treatment.

Results

In study 1, C-reactive protein levels did not differ between the group with depressive disorder (either currently depressed or euthymic) treated with SSRIs and the healthy group. In study 2 the protein levels dropped significantly following treatment with antidepressant medication.

Conclusions

Following SSRI treatment for major depression there is a significant drop in C-reactive protein concentrations whether or not the depression resolves. These findings indicate that antidepressants induce an anti-inflammatory response independent of antidepressant action.
Aggressive behaviour in an acute general adult psychiatric unit
Authors: El-Badri Selim M. , Mellsop Graham
Published: April 2006

Aims and Method

The study aimed to identify the correlates of aggressive behaviour in an adult acute psychiatric ward. Over a period of 9 months, all incidents of verbal and physical aggressive behaviour exhibited by in-patients were routinely assessed using the Overt Aggression Scale.

Results

Of the 535 patients admitted during the study period, 80 (15%) were involved in a total of 124 aggressive incidents. Of these 80, 44 (55%) had a history of previous violence and 54 (68%) had a history of substance misuse. The majority of events occurred early in the hospital stay and in most cases aggression was against staff. There were significant differences between aggressive and non-aggressive patients in terms of gender and ethnicity, with the lowest rate occurring in European females.

Clinical Implications

These results reinforce clinical impressions, and empirical evidence, and allow risk assessment to be performed with greater confidence. The relevance of ethnicity (or more likely culture) highlights the difficulties of a ‘one size fits all’ approach to risk assessment.
Prognosis and Management of Patients With Node-Negative Invasive Breast Carcinoma That Is 1 cm or Smaller in Size (stage 1; T1a,bN0M0): A Review of the Literature
Authors: Hanrahan Emer O. , Valero Vicente , Gonzalez-Angulo Ana M. , Hortobagyi Gabriel N.
Published: April 2006

Purpose

Mammographic screening has led to an increase in the number of small, node-negative breast cancers being diagnosed. Node-negative breast cancers that are ≤ 1 cm are stage T1a,bN0M0. Controversy surrounds the prognosis of these patients with locoregional therapy only and the need for adjuvant systemic therapy.

Methods

We performed a comprehensive review of the literature describing outcome and prognostic factors in stage T1a,bN0M0 breast cancer. We also reviewed current guidelines for systemic therapy in these patients.

Results

Early studies reported 10-year relapse-free survival (RFS) rates higher than 90% without adjuvant systemic therapy, but some more recent data suggest inferior outcomes. High tumor grade is the most consistent factor associated with poor prognosis. Other adverse prognostic factors are younger age, lymphovascular invasion (LVI), high Ki-67, and larger tumors within the T1a,b subgroup. Patients with high-grade tumors and/or LVI may have 10-year RFS rates of less than 75% in the absence of systemic therapy. The prognostic significance of hormone receptor status is unclear. Current guidelines for the systemic management of early-stage breast cancer differ when applied to stage T1a,bN0M0, reflecting the controversial nature of the issue.

Conclusion

Adjuvant systemic therapy is advisable for most patients with stage T1a,bN0M0 breast cancer who have grade 3 tumors and/or LVI. Other T1a,bN0M0 cases should be considered for systemic therapy based on clinicopathologic factors with known prognostic significance and assessment of the risk-benefit ratio. More reliable tools are needed to assess the prognosis of patients with stage T1a,bN0M0 breast cancer and their potential to benefit from specific therapeutic agents.
Patient-Controlled Methylphenidate for Cancer Fatigue: A Double-Blind, Randomized, Placebo-Controlled Trial
Authors: Bruera Eduardo , Valero Vicente , Driver Larry , Shen Loren , Willey Jie , Zhang Tao , Palmer J. Lynn
Published: April 2006

Purpose

To evaluate the effectiveness of patient-controlled methylphenidate as compared with placebo in cancer patients with fatigue, as measured by the Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F).

Patients and Methods

Patients with a fatigue score of at least 4 on a scale of 0 to 10 (0 = no fatigue, 10 = worst possible fatigue) and hemoglobin level of at least 10 g/dL were included. Patients were randomly assigned to receive 5 mg methylphenidate or placebo every 2 hours as needed (maximum of four capsules a day), for 7 days. Patients completed a daily diary including study drug record and fatigue intensity. A research nurse telephoned patients daily to assess toxicity and fatigue level. All patients were offered open-label methylphenidate for 4 weeks. FACIT-F and the Edmonton Symptom Assessment System (ESAS) were assessed at baseline, and days 8, 15, and 36. The FACIT-F fatigue subscore on day 8 was considered the primary end point.

Results

Of 112 patients randomly assigned, 52 patients in the methylphenidate and 53 in the placebo group were assessable for analysis. Fatigue intensity improved significantly on day 8 in both the methylphenidate and placebo groups. However, there was no significant difference in fatigue improvement by FACIT-F (P = .31) or ESAS (P = .14) between groups. In open-label phase, fatigue intensity maintained low as compared with baseline. No significant toxicities were observed.

Conclusion

Both methylphenidate and placebo resulted in significant symptom improvement. Methylphenidate was not significantly superior to placebo after 1 week of treatment. Longer study duration is justified. The role of daily telephone calls from a research nurse should be explored as a palliative care intervention.
Changes in Neurologic Function Tests May Predict Neurotoxicity Caused by Ixabepilone
Authors: Lee James J. , Low Jennifer A. , Croarkin Earllaine , Parks Rebecca , Berman Arlene W. , Mannan Nitin , Steinberg Seth M. , Swain Sandra M.
Published: April 2006

Purpose

To investigate baseline factors and neurologic function tests (NFTs) that may predict the development of grade 2 or higher peripheral neuropathy (PN) after treatment with ixabepilone, an epothilone microtubule-stabilizing agent with antitumor activity.

Patients and Methods

Advanced breast cancer patients were treated with ixabepilone (6 mg/m2) for 5 consecutive days every 3 weeks in a phase II clinical trial. Physical examinations, questionnaires, nerve conduction studies, and NFTs, including the Jebsen Test of Hand Function (JTH) and the Grooved Pegboard Test (GPT), were performed at baseline and during subsequent cycles.

Results

Forty-seven patients assessable for PN received a median of five cycles of therapy (range, one to 22 cycles). Nine of these patients developed grade 2 PN, and two developed grade 3 PN, with a median time to onset of 144 days (range, 6 to 189 days). Among these 11 patients, PN resolved in eight patients, with a median of 15 days (range, 6 to 346 days) after onset, but PN did not resolve in three patients during follow-ups at 76, 361, and 746 days after onset. GPT and changes of JTH scores at onset of PN were significantly different between patients with and without PN at comparable follow-up times (P = .006 and P = .002, respectively). Changes in GPT and JTH scores over the first two cycles were often associated with the development of PN by exploratory actuarial analysis.

Conclusion

Serious ixabepilone-induced neuropathy was relatively rare on the treatment schedule used. NFTs, such as JTH and GPT, may have utility for predicting PN, but further testing is needed.
Randomized Phase III Trial Comparing Irinotecan/Cisplatin With Etoposide/Cisplatin in Patients With Previously Untreated Extensive-Stage Disease Small-Cell Lung Cancer
Authors: Hanna Nasser , Bunn Paul A. , Langer Corey , Einhorn Lawrence , Guthrie Troy , Beck Thaddeus , Ansari Rafat , Ellis Peter , Byrne Michael , Morrison Mark , Hariharan Subramanian , Wang Benjamin , Sandler Alan
Published: April 2006

Purpose

Etoposide and cisplatin (EP) has been a standard treatment for extensive-disease small-cell lung cancer (SCLC). An earlier phase III trial reported improved survival for patients receiving irinotecan plus cisplatin (IP) versus EP. Our trial was designed to determine if a modified weekly regimen of IP would provide superior survival with less toxicity than EP.

Patients and Methods

The primary objective was to compare overall survival in extensive-disease SCLC patients randomly assigned to receive IP (n = 221) or EP (n = 110). Patients were randomly assigned in 2:1 ratio to cisplatin 30 mg/m2 intravenously (IV) + irinotecan 65 mg/m2 IV on days 1 and 8 every 21 days, or cisplatin 60 mg/m2 IV on day 1, and etoposide 120 mg/m2 IV on days 1 to 3 every 21 days for at least four cycles, until progressive disease, or until intolerable toxicity resulted.

Results

Selected grade 3/4 toxicities for IP/EP were: neutropenia (36.2% v 86.5%; P < .01), febrile neutropenia (3.7% v 10.4%; P = .06), anemia (4.8% v 11.5%; P = .02), thrombocytopenia (4.3% v 19.2%; P < .01), vomiting (12.5% v 3.8%; P = .04), and diarrhea (21.3% v 0%; P < .01). There was no significant difference in response rates (48% v 43.6%), median time to progression (4.1 v 4.6 months), or overall survival (median survival time, 9.3 months v 10.2 months; P = .74).

Conclusion

Treatment with this dose and schedule of IP did not result in improved survival when compared with EP. Fewer patients receiving IP had grade 3/4 anemia, thrombocytopenia, neutropenia, and febrile neutropenia compared with patients receiving EP, but more had grade 3/4 diarrhea and vomiting.
Maturational Constraints on Language Learning
Authors: Newport Elissa L.
Published: April 2006

This paper suggests that there are constraints on learning required to explain the acquisition of language, in particular, maturational constraints. First, empirical evidence for this claim is reviewed. The evidence from several studies of both first and second language acquisition suggests that normal language learning occurs only when exposure to the language begins early in life. With exposure beginning later in life, asymptotic performance in the language declines: the effects over age of first exposure are approximately linear through childhood, with a flattening of the function in adulthood. These outcomes argue that some type of constraints ensuring successful language learning exist early in life, and weaken with increasing maturation. Second, two hypotheses are considered as to the nature of these maturational changes. One hypothesis is that constraints on learning particular to language acquisition undergo maturational decay. A second hypothesis, which is considered in more detail, suggests that language learning abilities decline because of the expansion of nonlinguistic cognitive abilities.
Constraints Children Place on Word Meanings
Authors: Markman Ellen M.
Published: April 2006

This paper views lexical acquisition as a problem of induction: Children must figure out the meaning of a given term, given the large number of possible meanings any term could have. If children had to consider, evaluate, and rule out an unlimited number of hypotheses about each word in order to figure out its meaning, learning word meanings would be hopeless. Children must, therefore, be limited in the kinds of hypotheses they consider as possible word meanings. This paper considers three possible constraints on word meanings: (1) The whole object assumption which leads children to interpret novel terms as labels for objects—not parts, substances, or other properties of objects: (2) The taxonomic assumption which leads children to consider labels as referring to objects of like kind, rather than to objects that are thematically related: and (3) The mutual exclusivity assumption which leads children to expect each object to have only one label. Some of the evidence for these constraints is reviewed.
Constraints on Constraints: Surveying the Epigenetic Landscape
Authors: Keil Frank C.
Published: April 2006

It is now relatively commonplace to advocate the need for some sorts of constraints on learning and knowledge acquisition. The critical issues to cognitive science concern the sorts of constraints that are able to best model various phenomena of learning and development. Four types of constraints on learning are proposed to be used as an interpretative framework within which to: 1. Better understand the nature of current research: 2. Allow the exploration of alternative models of learning related phenomena, and 3. See more clearly needs for further research. Superficially similar learning phenomena can be modeled by very different configurations of underlying constraints with strong implications for the sorts of representational states that are involved. Each of the five papers in this issue (Brown, Gelman, Markman, Newport, and Spelke) is considered in terms of the configuration of constraints after which each author intends to model their phenomena and in terms of alternate configurations. The papers are construed as illustrating a diverse set of models of how constraints might guide learning, and while the evidence generally favors the configurations suggested by the authors, in each case alternative models are possible and motivate quite specific future research questions.

More broadly, it is suggested that asking detailed questions about the sorts of Constraints types that could potentially model complex cases of natural knowledge acquisition helps motivate fundamental questions about learning and the nature of knowledge and that the five papers in this issue are superb examples of how adopting this kind of perspective has been fruitful research orientation.
The Notion of Dynamic Unit: Conceptual Developments in Cognitive Science
Authors: Mandelblit Nili , Zachar Oron
Published: April 2006

We suggest a common ground for alternative proposals In different domains of cognitive science which have previously seemed to have little in common. The underlying common theme is associated with a redefinition of the basic unit of analysis in each domain of thought. Our framework suggests a definition of unity which is based not on inherent properties of the elements constituting the unit, but rather on dynamic patterns of correlation across the elements. We introduce a set of features that characterize the new dynamic units, and distinguish them from traditional units of analysis. A conceptual connection is made with the identification of elementary units in modern physics theories, as well as with concepts and structures in the study of complex dynamical systems and connectionism. The paper analyses the evolution of the concept of unit in different domains of thought in cognitive science, and examines the proposed framework of “dynamic unity” with regard to various theoretical problems within each domain. The particular cognitive science issues discussed in the paper include: (1) the binding problem in the brain; (2) the mental unit of conceptual organization; (3) defining ‘wordhood’ in linguistics; and (4) identifying the unit of cognition in the natural environment.
Motor protein KIFC5A interacts with Nubp1 and Nubp2, and is implicated in the regulation of centrosome duplication
Authors: Christodoulou Andri , Lederer Carsten W. , Surrey Thomas , Vernos Isabelle , Santama Niovi
Published: April 2006

Inhibition of motor protein activity has been linked with defects in the formation of poles in the spindle of dividing cells. However, the molecular mechanisms underlying the functional relationship between motor activity and centrosome dynamics have remained uncharacterised. Here, we characterise KIFC5A, a mouse kinesin-like protein that is highly expressed in dividing cells and tissues, and is subject to developmental and cell-type-specific regulation. KIFC5A is a minus-end-directed, microtubule-dependent motor that produces velocities of up to 1.26 μm minute-1 in gliding assays and possesses microtubule bundling activity. It is nuclear in interphase, localises to the centre of the two microtubule asters at the beginning of mitosis, and to spindle microtubules in later mitotic phases. Overexpression of KIFC5A in mouse cells causes the formation of aberrant, non-separated microtubule asters and mitotic arrest in a prometaphase-like state. KIFC5A knockdown partly rescues the phenotype caused by inhibition of plus-end-directed motor Eg5 by monastrol on the mitotic spindle, indicating that it is involved in the balance of forces determining bipolar spindle assembly and integrity. Silencing of KIFC5A also results in centrosome amplification detectable throughout the cell cycle. Supernumerary centrosomes arise primarily as a result of reduplication and partly as a result of cytokinesis defects. They contain duplicated centrioles and have the ability to organise microtubule asters, resulting in the formation of multipolar spindles. We show that KIFC5A interacts with nucleotide-binding proteins 1 and 2 (Nubp1 and Nubp2), which have extensive sequence similarity to prokaryotic division-site-determining protein MinD. Nubp1 and Nubp2 also interact with each other. Knockdown of Nubp1 or double knockdown of Nubp1 and Nubp2 (Nubp1&Nubp2) both phenocopy the KIFC5A silencing effect. These results implicate KIFC5A and the Nubp proteins in a common regulatory pathway involved in the control of centrosome duplication in mammalian cells.
Pair-Selective Coupling of Alkynes with Alkenes on Zirconocene Complex
Authors: Takahashi Tamotsu , Xi Zhenfeng , Rousset Christophe J , Suzuki Noriyuki
Published: April 2006

When ethylene and alkynes such as 4-octyne and diphenylacetylene were treated with Cp2ZrBu2 highly pair selective coupling products were formed in high yields. Similarly, styrene or trimethylvinylsilane also afforded cross coupling products with alkynes on zirconocene complex.
A Novel Antimicrobial Substance in Etiolated Seedlings of Adlay
Authors: Ishiguro Yukio , Okamoto Kenji , Ojima Fumihiro , Sonoda Youji
Published: April 2006

A novel antimicrobial substance was isolated from the extract of etiolated seedlings of Adlay (Coix lachryma-jobi L. var. ma-yuen Stapf). This substance showed antimicrobial activity against bacteria, but no activity against yeast and fungi.