bluuebunny/crossref_metadata_2025 huggingface dataset:
Sleep Quality Perception in the Chronic Fatigue Syndrome: Correlations with Sleep Efficiency, Affective Symptoms and Intensity of Fatigue
Authors: Neu Daniel , Mairesse Olivier , Hoffmann Guy , Dris Amirouche , Lambrecht Luc J. , Linkowski Paul , Verbanck Paul , Le Bon Olivier
Published: November 2007

Background/Aims: One of the core symptoms of the chronic fatigue syndrome (CFS) is unrefreshing sleep and a subjective sensation of poor sleep quality. Whether this perception can be expressed, in a standardized questionnaire as the Pittsburgh Sleep Quality Index (PSQI), has to our knowledge never been documented in CFS. Furthermore, correlations of subjective fatigue, PSQI, affective symptoms and objective parameters such as sleep efficiency are poorly described in the literature. Methods: Using a cross-sectional paradigm, we studied subjective measures like PSQI, Fatigue Severity Scale scores and intensity of affective symptoms rated by the Hamilton Depression and Anxiety scales as well as objective sleep quality parameters measured by polysomnography of 28 ‘pure’ (no primary sleep and no psychiatric disorders) CFS patients compared to age- and gender-matched healthy controls. Results: The PSQI showed significantly poorer subjective sleep quality in CFS patients than in healthy controls. In contrast, objective sleep quality parameters, like the Sleep Efficiency Index (SEI) or the amount of slow-wave sleep did not differ significantly. Subjective sleep quality showed a correlation trend with severity of fatigue and was not correlated with the intensity of affective symptoms in CFS. Conclusion: Our findings indicate that a sleep quality misperception exists in CFS or that potential nocturnal neurophysiological disturbances involved in the nonrecovering sensation in CFS are not expressed by sleep variables such as the SEI or sleep stage distributions and proportions.
The Role of the TPH1 and TPH2 Genes for Nicotine Dependence: A Genetic Association Study in Two Different Age Cohorts
Authors: Reuter Martin , Hennig Juergen , Amelang Manfred , Montag Christian , Korkut Tatjana , Hueweler Anja , Stürmer Til
Published: November 2007

Based on pharmacological and genetic studies suggesting a role of the serotonergic system for nicotine dependence, two genetic variants, one on the tryptophan hydroxylase 1 (TPH1) and one on the TPH2 gene, were investigated. The TPH2 –703G/T promoter polymorphism was associated with smoking status and age of smoking onset in two independent Caucasian samples of different age cohorts. Sample 1 consisted of 3,602 subjects of a population-based cohort study of whom 95% were 40–65 years old, and sample 2 consisted of 723 subjects in the twenties. The TPH1 779A/C was only investigated in sample 2 where additional data with respect to the degree of nicotine dependence were assessed. Results yield support for previous findings of an association between the AA genotype of TPH1 779A/C and nicotine status and a tendency for a heterosis effect with respect to the degree of nicotine dependence. The TPH2 –703G/T was significantly associated with age of smoking onset in both samples. The interaction between the T allele and gender was significant in both samples. Carriers of the GG genotype started significantly earlier to smoke than carriers with a T allele. In the older cohort, age of onset was earlier in carriers of the GG genotype only in men, and in the younger cohort the GG genotype predisposes only women to start smoking earlier in life. This interaction could constitute a gene-by-environment interaction that is discussed on the background of previous studies relating the –703G/T polymorphism to anxiety, a personality dimension that has been shown to be a risk factor for nicotine dependence.
Neuropsychiatric Syndromes in Dementia
Authors: Aalten Pauline , Verhey Frans R.J. , Boziki Marina , Bullock Roger , Byrne Eleanor Jane , Camus Vincent , Caputo Miriam , Collins Debby , De Deyn Peter Paul , Elina Kazi , Frisoni Giovanni , Girtler Nicola , Holmes Clive , Hurt Catherine , Marriott Anna , Mecocci Patrizia , Nobili Flavio , Ousset Pierre Jean , Reynish Emma , Salmon Eric , Tsolaki Magda , Vellas Bruno , Robert Philippe H.
Published: November 2007

Background/Aims: The aim of this study was to identify neuropsychiatric subsyndromes of the Neuropsychiatric Inventory in a large sample of outpatients with Alzheimer’s disease (AD). Methods: Cross-sectional data of 2,354 patients with AD from 12 centres from the European Alzheimer’s Disease Consortium were collected. Principal component analysis was used for factor analysis. Results: The results showed the presence of 4 neuropsychiatric subsyndromes: hyperactivity, psychosis, affective symptoms and apathy. The subsyndrome apathy was the most common, occurring in almost 65% of the patients. Conclusion: This large study has provided additional robust evidence for the existence of neuropsychiatric subsyndromes in AD.
Analyses of postgraduate social work dissertations in Taiwan
Authors: Shek Daniel T.L. , Hua Lee Jun , Yan Tam Suet
Published: October 2007

English

This study was conducted to examine postgraduate theses in Taiwan. Results showed that most of the studies were qualitative researches and there were few studies adopting mixed-methods research approaches. There were few studies on social work methods; and the use of English references was not widespread.

French

Cette étude avait pour objectif d’examiner les thèses d’étudiants postgradués à Taiwan. Les résultats ont révé lé que: la majorité des recherches étaient de nature qualitative, quelques recherches ayant adopté une approche de modè les mixtes; peu de recherches ont été consacrées aux méthodes d’intervention en travail social; et les sources anglaises étaient rares.

Spanish

Este estudio se llevo a cabo para examinar las tesis de postgrado en Taiwán. Los resultados mostraron que: la mayoría de los estudios fueron investigaciones cualitativas y que solo hubo algunos estudios que adoptaron métodos mixtos de investigación; hubo solo algunos estudios en métodos de trabajo social; el uso de referencias en inglés no fue muy difundido.
Emerging practices of social work in the Dominican Republic
Authors: Parada Henry , Moffatt Ken , Duval Marisela
Published: October 2007

English

This study is based on consultation with governmental institutions working with women and children in the Dominican Republic and the Autonomous University of Santo Domingo, which is part of a six-year project funded by the Canadian International Development Agency. We report on some of the preliminary findings and the conceptualization of social work interventions within the Dominican Republic.

French

Cette étude s’inscrit dans le cadre d’un projet de six ans financé par l’Agence canadienne de développement international (ACDI) et elle s’appuie sur des consultations auprès d’institutions gouvernementales oeuvrant auprès des femmes et des enfants de la République dominicaine et de la Université Autonome de Santo Domingo. Elle fait état de quelques constats préliminaires et elle conceptualise l’intervention en travail social en République dominicaine.

Spanish

Este estudio se basa en la consulta de instituciones gubernamentales que trbajan con niños y mujeres en la República Dominicana y la Universidad Autónoma de Santo Domingo, la cual forma parte de un proyecto de seis años fundado por la IDA Canadiense. Nuestro reporte se basa en los hallazgos preliminares y la conceptualización de la intervención del trabajo social dentro de la República Dominicana.
Factors that influence workfare program participants
Authors: Kuen Kim Tae , Zurlo Karen A.
Published: October 2007

English

We empirically analyzed a representative workfare program in South Korea, the Self-Sufficiency Program (SSP), using multinomial logistic regression. Our findings demonstrated that family income sources, program participation length and health status are important factors affecting the self-sufficiency of program participants. Based on these results, we recommend improvements in the current SSP.

French

Nous avons fait l’analyse empirique d’un programme de sécurité du revenu de Corée du Sud, le Self-Sufficiency Program (programme d’autosuffisance), en utilisant le modè le de régression logistique multinomial. Les résultats indiquent que la provenance des revenus de la famille, la durée de participation au programme et l’état de santé sont d’importants facteurs qui ont un impact sur l’autosuffisance des participants au programme. À la lumière de ces résultats, nous suggérons des correctifs à apporter à l’actuel programme d’autosuffisance.

Spanish

Analizamos empíricamente un programa representativo de bienestar en el trabajo en Corea del Sur, el Self-Sufficiency Program (Programa de Autosuficiencia) (SSP), utilizando la regresión logística multinomial. Nuestros hallazgos demuestran que las fuentes de ingreso familiar, la duración del programa de participación, y el estatus de salud son factores importantes que afectan la auto-suficiencia de los participantes en el programa. Con base en los resultados, recomendamos el mejoramiento del actual SSP.
The Scriptural Basis of Jubilee, Part II: The Second Testament: At What Price?
Authors: Moloney Francis J.
Published: October 2007

A number of themes in the New Testament show that the early Church was influenced by the idea and practice of Jubilee, especially as it is found in Second and Third Isaiah. The following study is limited to reflection upon two themes: the explicit use of Jubilee texts at the beginning of the Gospel of Luke, and a Gospel understanding of our role as followers of the one who proclaimed the 'today' of Jubilee.
Language, Imagination, and the Status of the Human Embryo
Authors: Vincent Twomey D.
Published: October 2007

The use of language in moral and legal discourse on the status of the human embryo has itself developed into an important moral issue for both ethics and law. A related question, whose relevance is not limited to bioethics, is the role the imagination plays in moral reflection and decision making.
Contemplating God: YHWH and Being in the Theology of St Thomas Aquinas
Authors: Levering Matthew
Published: October 2007

Aquinas's treatise on God's essence, it is argued, contemplates Israel's God metaphysically. But Aquinas's purpose is a biblical one: encountering God through contemplating, with all available intellectual resources, God's names. Aquinas thus integrates his metaphysical reflection on the name 'I am Who am' into a rich account of YHWH, Moses, the Mosaic Law, and the relationship of Christians to the contemplative life enjoyed by Moses and sustained, against various forms of idolatry, by the Mosaic Law.
Bishop Daniel Cohalan of Cork on Republican Resistance and Hunger Strikes: A Theological Note
Authors: Corkery Pádraig
Published: October 2007

An analysis of the various responses of the Bishop of Cork to Republican resistance during the War of Independence reveals a fundamental shift between 1921 and 1923 in his moral analysis of violent resistance and the hunger strikes that formed part of it.
Eusebius on Some Constantinian Officials
Authors: Woods David
Published: October 2007

The role of the comes Acacius under Constantine is re-examined in detail. It is argued that it was as a comes consistorianus that he was present at the Council of Antioch in 327, and that it was he who presided at the festivities which accompanied the Dedication of the Church of the Holy Sepulchre in Jerusalem, September 335. Acacius, it is claimed, acted as Constantine's senior ecclesiastical adviser and troubleshooter from c.327, fulfilling duties of a type that had previously been performed by Bishop Ossius of Cordova.
The Jewish People and its Holy Scripture in the Christian Bible'
Authors: Wansbrough Henry
Published: October 2007

Earlier this year, the PontificaL Biblical Commission published the English translation of the document, The Jewish People and their Sacred Scriptures in the Christian Bible, the result of five years of research and deliberation. A member of the commission outlines the history of the document, and discusses its import.
Wrestling with Rahner on the Trinity1
Authors: Ormerod Neil
Published: October 2007

This article picks up on concerns recently expressed in this journal about Rahner's axiom relating the immanent and economic Trinity. While this axiom has become a theological commonplace, the present article raises concerns in relation to two areas: the blurring of the distinction between person and nature, and the place of the filioque in understanding the Trinity. UnderLying both these areas is a question of theological method, in particular the relationship between dogmatic and systematic questions.
A Contemporary Perspective on Atonement
Authors: Danaher James
Published: October 2007

The author reviews the development of the concept of atonement, and points out the strengths and weaknesses of the various stances. He points out that these theories are shaped by their respective cultures, and that our concept of atonement is affected by a myriad of other concepts that are philosophically loaded and culturally relative. Any contemporary theory must take this into account and ensure the base concepts are compatible with Christianity.
Approaching Theology with Newman
Authors: Madden Nicholas
Published: October 2007

As a possible alternative to the still dominant theological methodology based on a supposed scientific objectivity, the author explores Newman's approach to theology rooted in a subjective disposition which becomes the condition of the possibility of objective theological truth.
Herman Melville's Pierre : How Radical is the Critique of Christianity?
Authors: Cosgrove Brian
Published: October 2007

In the dark and problematic Pierre, the much lesser-known novel written after Moby-Dick, Melville provides a radical critique of Christian morality. Ironically, it is the untenable ideals fostered by Christianity that lead to Pierre's disillusionment and self-destruction. But if Christianity is subjected to such a critique, can the source of such moral beliefs — Christ himself - remain exempt from a related critical scrutiny? In any case, does not Pierre push to a further extreme the deep scepticism about a providential God the Father already evident in Moby-Dick?
Cuban Reform and Economic Opening
Authors: Mao Xianglin
Published: October 2007

Cuba's reform and economic opening have been crucial to its post—cold-war survival and the development of a uniquely Cuban socialism. The country has moved from a public-property system to a mixed economy and from a sugar mono-economy to a diversified economy while introducing and increasing foreign investment. The result has been steady increase in growth without the abandonment of socialist principles. Some problems remain to be resolved, however, if Cuba is to rise to prominence in the global order.
Lula's Development Council
Authors: Doctor Mahrukh
Published: October 2007

Brazil's recently created Council for Economic and Social Development was designed to enhance democratic governance and socioeconomic development via consultation and dialogue with civil society actors. In its first years of operation, it served to articulate the interests and preferences of political and economic elites, institutionalizing dialogue and in the process enhancing support for policy reform, improving governance, and driving forward democratization. Its substantive achievements were limited, however, by its bias in favor of business and the more developed South, its dependence on the executive, the government's minority status in Congress, and the lack of interest of political elites. As a result, the future of this neo-corporatist institution remains unclear.
Is the Soviet Collapse Dragging the United States Down?
Authors: Gandásegui Marco A.
Published: October 2007

The mix of old and new in the United States's role as world leader creates ambiguity and confusion. The United States is looking for ways to regain its lost economic punch and to consolidate its world hegemony. At present, however, with no true enemy on the horizon, it is being dragged down by the Soviet collapse. The twentieth century was a period of transition but not from capitalism to socialism. The nonmarket alternative or challenge represented by the Soviet Union gave capitalism the means to overcome many obstacles to its reproduction and raise profits to new levels. The United States occupied a privileged position in that process. However, the twenty-first century demands new solutions for capitalism's inherent contradictions, and as a result the United States is apparently still trying to invent a new Soviet Union.
`Disposable populations': the CSME, HIV and AIDS
Authors: Carr Robert , Lewis R. Anthony
Published: October 2007

The implementation of the Caribbean Single Market and Economy (CSME) will bring, among other things, the free movement of qualified labour, which political leaders hope will give the benefits of an economic bloc to the micro-economies of the region. There is, however, the question of whether the current status quo of unequal rights and the unequal distribution of benefits for various vulnerable groups will continue. This is particularly relevant as the epidemics of HIV and AIDS deepen in the region. This commentary argues for a critical analysis of the trends now emerging in the Caribbean Single Market that may reinforce the structural vulnerabilities that act as the drivers of these epidemics.
Scores on a Japanese-Language Version of the Learning Channel Preference Checklist
Authors: Isemonger Ian
Published: October 2007

The psychometric properties of scores derived from a Japanese version of the Learning Channel Preference Checklist (LCPC) are examined in this study. The LCPC is one of a line of instruments dedicated to measuring perceptual learning styles that emerged in the 1980s and 1990s out of earlier work and instrumentation in the 1970s. It is argued that the more recent line of instrumentation dedicated to perceptual learning styles emerged without awareness of significant earlier debate concerning the predictive power of perceptual constructs in learning outcome and their operational viability. This article re-engages this recent line of instrumentation in general, and the LCPC in particular, with the seemingly disregarded questions surrounding the viability of operationalizing perceptual constructs. The article also alerts practitioners to potential problems with instruments attempting to operationalize perceptual preference through self-report.
Valproic Acid—Induced Pancreatitis in Childhood Epilepsy: Case Series and Review
Authors: Sinclair D. Barry , Berg Marjorie , Breault Rene
Published: October 2007

In the past 6 years, 11 children on valproic acid have developed pancreatitis in our children's hospital. Valproic acid has been used as one of the primary anticonvulsants for generalized seizures in children for the past 25 years. A literature review reveals mostly singular reports of pancreatitis over the past decade. The charts of the 11 patients with valproic acid—induced pancreatitis were reviewed. Dosage, valproic acid serum levels, duration of therapy, and concomitant medications were examined. Families were contacted by telephone to determine the formulation (brand name vs generic) of valproic acid at the time of diagnosis. Six girls and five boys were studied. The ages ranged from 4 to 16 years. Eight of 11 children presented with an acute abdomen. Unexpectedly, three children presented with a flulike illness. Serum lipase values ranged from 341 to 5576 U/L (normal range < 190 U/L). The dose of valproic acid ranged from 20 to 50 mg/kg. Serum levels ranged from 334 to 884 μmol/L (therapeutic range 350—800 μmol/L). Six of the patients were on monotherapy. Seven children were on brand-name drugs. Four of the children had an abnormal neurologic syndromic diagnosis (West syndrome, Rett syndrome, Lowe syndrome, and Angelman's syndrome). Six of the children had a history of drug allergies with a skin rash. Valproic acid was reintroduced in one child and resulted in a second episode of pancreatitis. Resolution of symptoms usually took several weeks following discontinuation of the drug. No association was found with valproic acid dosage, type of preparation, serum levels, duration of therapy, or presence of concomitant medications. Pancreatitis is a severe adverse effect of valproic acid use in children. Dose, duration of treatment, serum valproic acid levels, generic preparation, and the presence of concomitant antiepileptic drugs do not appear to be risk factors. Children with known drug sensitivity might be at risk. Lipase levels at the time of an acute abdomen or a flulike illness in epileptic children taking valproic acid can reveal early stages of pancreatitis and are recommended. ( J Child Neurol 2004;19:498—502).
Influence of MECP2 Gene Mutation and X-Chromosome Inactivation on the Rett Syndrome Phenotype
Authors: Jong Hee Chae  , Hee Hwang  , Yong Seung Hwang  , Hee Jung Cheong  , Ki Joong Kim
Published: October 2007

To date, approximately 200 different mutations in the MECP2 gene have been identified. We analyzed the entire coding sequence of the MECP2 gene and the X-chromosome inactivation pattern in 42 sporadic cases of Rett syndrome. Of the 42 patients, 30 had pathogenic mutations, including 14 different mutations: 9 missense mutations, 4 nonsense mutations, and 1 frameshift mutation. One was a novel mutation (S134P). There was a tendency for patients who had a nonsense mutation in the transcriptional repression domain region to show earlier onset of regression and more severe language retardation than patients with a mutation in the methyl-CpG binding domain region. However, the parameters of clinical severity were variable among patients with the same type of mutation, depending on the pattern of X-chromosome inactivation. This study suggests that the X-chromosome inactivation pattern can modify the phenotype of Rett syndrome, which is primarily determined by the type and site of MECP2 gene mutation. ( J Child Neurol 2004;19:503—508).
Familial Hyperekplexia and Refractory Status Epilepticus: A New Autosomal Recessive Syndrome
Authors: Lerman-Sagie Tally , Watemberg Nathan , Vinkler Chana , Fishhof Judith , Leshinsky-Silver Esther , Lev Dorit
Published: October 2007

Hyperekplexia is a rare disorder characterized by an exaggerated startle response to noise and handling and by neonatal hypertonia. It is predominantly an autosomal dominant disease; however, atypical cases with additional variable manifestations have been reported. We report a hitherto undescribed association of hyperekplexia and refractory status epilepticus in two siblings. Both children were born after an uneventful pregnancy to healthy unrelated Ashkenazi Jews. Both had increased startle and tone from birth and later became hypotonic. A metabolic evaluation, including a muscle biopsy, was normal. At the age of 18 months and 12 months, respectively, they developed status epilepticus refractory to all treatment that culminated in death. An autopsy in the girl did not reveal any brain pathology. The unusual association of hyperekplexia and refractory status epilepticus in both children suggests that this is a new autosomal recessive syndrome, possibly a channelopathy affecting both the brain and the spinal cord. ( J Child Neurol 2004;19:522—525).
Broadcast News Diffusion in Crisis-Ridden Democracies
Authors: Cohen Yoel
Published: October 2007

Having covered many national crises in the past, Israel’s media structure appeared well suited to deal with the assassination of Prime Minister Itzhak Rabin. This study examines the social functions fulfilled by Israel’s broadcast media following the assassination. Three roles played by the media were examined. Drawing on survey data, television and radio were found to be important initial sources about the news of the assassination, and television was important for following subsequent events. They contributed to reintegrating the nation in the period afterwards. However, continuous coverage traumatized the population.
Being a Citizen Online
Authors: Scheufele Dietram A. , Nisbet Matthew C.
Published: October 2007

This study compares the impact of various types of traditional and Web-based forms of communication on political efficacy, knowledge, and participation. Findings suggest that the role of the Internet in promoting citizenship is limited. In fact, respondents who used the Web frequently for entertainment purposes were less likely to feel efficacious about their potential role in the democratic process and also knew less about facts relevant to current events. Regardless of the frequency with which people used the Internet for various informational or entertainment purposes, these analyses suggest that traditional mass media maintain a key role in promoting democratic citizenship.
Conceptualizing Work—Family Balance: Implications for Practice and Research
Authors: Grzywacz Joseph G. , Carlson Dawn S.
Published: November 2007

The problem and the solution. Systematic theorizing about work—family balance has not kept pace with interest, which undermines organizations' abilities to effectively monitor work—family balance and to use work—family balance strategically. The goal of this article is to develop a better conceptual understanding of work—family balance. Work—family balance is defined as accomplishment of role-related expectations that are negotiated and shared between an individual and his or her role-related partners in the work and family domains. This article elaborates on how this definition of work—family balance addresses limitations of previous conceptualizations and describes areas for human resource development research and implications for using work—family balance strategically in management practice.
Dual-Income Families in the New Millennium: Reconceptualizing Family Type
Authors: Duxbury Linda , Lyons Sean , Higgins Christopher
Published: November 2007

The problem and the solution. To assist employees in their pursuit of balance, human resource development practitioners must recognize that different family types face different challenges and require different approaches to promoting work—family balance. Early research in this area defined family type very simply: Both partners worked for pay outside the home or both partners had careers. Changes in the demographic profile of families and in the nature of work have rendered this typology obsolete. This article proposes a new, expanded conceptualization of family type that recognizes four family types: dual-career, dual-earner, new-traditional, and status-reversal.
Lessons From Work—Life Research for Developing Human Resources
Authors: MacDermid Shelley M. , Wittenborn Andrea K.
Published: November 2007

The problem and the solution. Human resource development (HRD) and work/life share several goals. Both are concerned with ensuring workers are effective and with the “business case” justifying their efforts within organizations. This article develops insights for HRD professionals by drawing on articles identified in the international competition for the Rosabeth Moss Kanter Award for Excellence in Work—Family Research. Specifically, work hours and work overload as well as gender and gender inequity are powerful influences on worker effectiveness. Several exemplary articles also generate important information for the business case for work/life. This article provides access to resources that can support HRD efforts in organizations.
Junctional adhesion molecule-A, JAM-A, is a novel cell-surface marker for long-term repopulating hematopoietic stem cells
Authors: Sugano Yasuyoshi , Takeuchi Masaki , Hirata Ayami , Matsushita Hirokazu , Kitamura Toshio , Tanaka Minoru , Miyajima Atsushi
Published: November 2007

Junctional adhesion molecule-A (JAM-A/JAM-1/F11R) is a cell adhesion molecule expressed in epithelial and endothelial cells, and also hematopoietic cells, such as leukocytes, platelets, and erythrocytes. Here, we show that JAM-A is expressed at a high level in the enriched hematopoietic stem cell (HSC) fraction; that is, CD34+c-Kit+ cells in embryonic day 11.5 (E11.5) aorta-gonod-mesonephros (AGM) and E11.5 fetal liver (FL), as well as c-Kit+Sca-1+Lineage− (KSL) cells in E14.5 FL, E18.5FL, and adult bone marrow (BM). Although the percentage of JAM-A+ cells in those tissues decreases during development, the expression in the HSC fraction is maintained throughout life. Colony-forming assays reveal that multilineage colony-forming activity in JAM-A+ cells is higher than that in JAM-A− cells in the enriched HSC fraction in all of those tissues. Transplantation assays show that long-term reconstituting HSC (LTR-HSC) activity is exclusively in the JAM-A+ population and is highly enriched in the JAM-A+ cells sorted directly from whole BM cells by anti–JAM-A antibody alone. Together, these results indicate that JAM-A is expressed on hematopoietic precursors in various hematopoietic tissues and is an excellent marker to isolate LTR-HSCs.
CD4+ T cells specific for glycoprotein B from cytomegalovirus exhibit extreme conservation of T-cell receptor usage between different individuals
Authors: Crompton Laura , Khan Naeem , Khanna Rajiv , Nayak Laxman , Moss Paul A. H.
Published: November 2007

Antigen-specific CD8+ cytotoxic T cells often demonstrate extreme conservation of T-cell receptor (TCR) usage between different individuals, but similar characteristics have not been documented for CD4+ T cells. CD4+ T cells predominantly have a helper immune role, but a cytotoxic CD4+ T-cell subset has been characterized, and we have studied the cytotoxic CD4+ T-cell response to a peptide from human cytomegalovirus glycoprotein B presented through HLA-DRB*0701. We show that this peptide elicits a cytotoxic CD4+ T-cell response that averages 3.6% of the total CD4+ T-cell repertoire of cytomegalovirus-seropositive donors. Moreover, CD4+ cytotoxic T-cell clones isolated from different individuals exhibit extensive conservation of TCR usage, which indicates strong T-cell clonal selection for peptide recognition. Remarkably, this TCR sequence was recently reported in more than 50% of cases of CD4+ T-cell large granular lymphocytosis. Immunodominance of cytotoxic CD4+ T cells thus parallels that of CD8+ subsets and suggests that cytotoxic effector function is critical to the development of T-cell clonal selection, possibly from immune competition secondary to lysis of antigen-presenting cells. In addition, these TCR sequences are highly homologous to those observed in HLA-DR7+ patients with CD4+ T-cell large granular lymphocytosis and implicate cytomegalovirus as a likely antigenic stimulus for this disorder.
Cytogenetic features of acute lymphoblastic and myeloid leukemias in pediatric patients with Down syndrome: an iBFM-SG study
Authors: Forestier Erik , Izraeli Shai , Beverloo Berna , Haas Oskar , Pession Andrea , Michalová Kyra , Stark Batia , Harrison Christine J. , Teigler-Schlegel Andrea , Johansson Bertil
Published: October 2007

Children with Down syndrome (DS) have a markedly increased risk of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). To identify chromosomal changes cooperating with +21 that may provide information on the pathogenesis of these leukemias, we analyzed 215 DS-ALLs and 189 DS-AMLs. Unlike previous smaller series, a significant proportion of DS-ALLs had the typical B-cell precursor ALL abnormalities high hyperdiploidy (HeH; 11%) and t(12;21)(p13;q22) (10%). The HeH DS-ALLs were characterized by gains of the same chromosomes as non–DS-HeH, suggesting the same etiology/pathogenesis. In addition, specific genetic subtypes of DS-ALL were suggested by the significant overrepresentation of cases with +X, t(8;14)(q11;q32), and del(9p). Unlike DS-ALL, the common translocations associated with non–DS-AML were rare in DS-AML, which instead were characterized by the frequent presence of dup(1q), del(6q), del(7p), dup(7q), +8, +11, del(16q), and +21. This series of DS leukemias—the largest to date—reveals that DS-ALL is a heterogeneous disorder that comprises both t(12;21) and HeH as well as DS-related abnormalities. Furthermore, this analysis confirms that DS-AML is a distinct entity, originating through other genetic pathways than do non–DS-AMLs, and suggests that unbalanced changes such as dup(1q), +8, and +21 are involved in the leukemogenic process.
Dermal fibroblasts derived from fetal and postnatal humans exhibit distinct responses to insulin like growth factors
Authors: Rolfe Kerstin J , Cambrey Alison D , Richardson Janette , Irvine Laurie M , Grobbelaar Adriaan O , Linge Claire
Published: November 2007

Background

It has been well established that human fetuses will heal cutaneous wounds with perfect regeneration. Insulin-like growth factors are pro-fibrotic fibroblast mitogens that have important roles in both adult wound healing and during development, although their relative contribution towards fetal wound healing is currently unknown. We have compared responses to IGF-I and -II in human dermal fibroblast strains derived from early gestational age fetal (<14 weeks) and developmentally mature postnatal skin to identify any differences that might relate to their respective wound healing responses of regeneration or fibrosis.

Results

We have established that the mitogenic response of fetal cells to both IGF-I and -II is much lower than that seen in postnatal dermal fibroblasts. Further, unlike postnatal cells, fetal cells fail to synthesise collagen in response to IGF-I, whereas they do increase synthesis in response to IGF-II. This apparent developmentally regulated difference in response to these related growth factors is also reflected in changes in the tyrosine phosphorylation pattern of a number of proteins. Postnatal cells exhibit a significant increase in phosphorylation of ERK 1 (p44) in response to IGF-I and conversely the p46 isoform of Shc on IGF-II stimulation. Fetal cells however only show a significant increase in an unidentified 100 kDa tyrosine-phosphorylated protein on stimulation with IGF-II.

Conclusion

Dermal fibroblasts exhibit different responses to the two forms of IGF depending on their developmental maturity. This may relate to the developmental transition in cutaneous wound healing from regeneration to fibrosis.
A cluster randomized controlled trial of a clinical pathway for hospital treatment of heart failure: study design and population
Authors: Panella Massimiliano , Marchisio Sara , Gardini Andrea , Di Stanislao Francesco
Published: November 2007

Background

The hospital treatment of heart failure frequently does not follow published guidelines, potentially contributing to the high morbidity, mortality and economic cost of this disorder. Consequently the development of clinical pathways has the potential to reduce the current variability in care, enhance guideline adherence, and improve outcomes for patients. Despite enthusiasm and diffusion, the widespread acceptance of clinical pathways remain questionable because very little prospective controlled data demonstrated their effectiveness. The Experimental Prospective Study on the Effectiveness and Efficiency of the Implementation of Clinical Pathways was designed in order to conduct a rigorous evaluation of clinical pathways in hospital treatment of acute heart failure. The primary objective of the trial was to evaluate the effectiveness of the implementation of clinical pathways for hospital treatment of heart failure in Italian hospitals.

Methods/design

Two-arm, cluster-randomized trial. 14 community hospitals were randomized either to arm 1 (clinical pathway: appropriate use of practice guidelines and supplies of drugs and ancillary services, new organization and procedures, patient education, etc.) or to arm 2 (no intervention, usual care). 424 patients sample (212 in each group), 80% of power at the 5% significance level (two-sided). The primary outcome measure is in-hospital mortality. We will also analyze the impact of the clinical pathways comparing the length and the appropriateness of the stay, the rate of unscheduled readmissions, the customers' satisfaction and the costs treating the patients with the pathways and with the current practice along all the observation period. The quality of the care will be assessed by monitoring the use of diagnostic and therapeutic procedures during hospital stay and by measuring key quality indicators at discharge.

Discussion

This paper examines the design of the evaluation of a complex intervention. Since clinical pathways are made up of various interconnecting parts we have chosen the cluster-randomized controlled trial because is widely accepted as the most reliable method of determining effectiveness when measuring cost-effectiveness in real practice.

Trial Registration

ClinicalTrials.gov ID [NCT00519038]
Natural variation in SAR11 marine bacterioplankton genomes inferred from metagenomic data
Authors: Wilhelm Larry J , Tripp H James , Givan Scott A , Smith Daniel P , Giovannoni Stephen J
Published: November 2007

Background

One objective of metagenomics is to reconstruct information about specific uncultured organisms from fragmentary environmental DNA sequences. We used the genome of an isolate of the marine alphaproteobacterium SAR11 ('Candidatus Pelagibacter ubique'; strain HTCC1062), obtained from the cold, productive Oregon coast, as a query sequence to study variation in SAR11 metagenome sequence data from the Sargasso Sea, a warm, oligotrophic ocean gyre.

Results

The average amino acid identity of SAR11 genes encoded by the metagenomic data to the query genome was only 71%, indicating significant evolutionary divergence between the coastal isolates and Sargasso Sea populations. However, an analysis of gene neighbors indicated that SAR11 genes in the Sargasso Sea metagenomic data match the gene order of the HTCC1062 genome in 96% of cases (> 85,000 observations), and that rearrangements are most frequent at predicted operon boundaries. There were no conserved examples of genes with known functions being found in the coastal isolates, but not the Sargasso Sea metagenomic data, or vice versa, suggesting that core regions of these diverse SAR11 genomes are relatively conserved in gene content. However, four hypervariable regions were observed, which may encode properties associated with variation in SAR11 ecotypes. The largest of these, HVR2, is a 48 kb region flanked by the sole 5S and 23S genes in the HTCC1062 genome, and mainly encodes genes that determine cell surface properties. A comparison of two closely related 'Candidatus Pelagibacter' genomes (HTCC1062 and HTCC1002) revealed a number of "gene indels" in core regions. Most of these were found to be polymorphic in the metagenomic data and showed evidence of purifying selection, suggesting that the same "polymorphic gene indels" are maintained in physically isolated SAR11 populations.

Conclusion

These findings suggest that natural selection has conserved many core features of SAR11 genomes across broad oceanic scales, but significant variation was found associated with four hypervariable genome regions. The data also led to the hypothesis that some gene insertions and deletions might be polymorphisms, similar to allelic polymorphisms.
Gene expression atlas of the mouse central nervous system: impact and interactions of age, energy intake and gender
Authors: Xu Xiangru , Zhan Ming , Duan Wenzhen , Prabhu Vinayakumar , Brenneman Randall , Wood William , Firman Jeff , Li Huai , Zhang Peisu , Ibe Carol , Zonderman Alan B , Longo Dan L , Poosala Suresh , Becker Kevin G , Mattson Mark P
Published: November 2007

Background

The structural and functional complexity of the mammalian central nervous system (CNS) is organized and modified by complicated molecular signaling processes that are poorly understood.

Results

We measured transcripts of 16,896 genes in 5 CNS regions from cohorts of young, middle-aged and old male and female mice that had been maintained on either a control diet or a low energy diet known to retard aging. Each CNS region (cerebral cortex, hippocampus, striatum, cerebellum and spinal cord) possessed its own unique transcriptome fingerprint that was independent of age, gender and energy intake. Less than 10% of genes were significantly affected by age, diet or gender, with most of these changes occurring between middle and old age. The transcriptome of the spinal cord was the most responsive to age, diet and gender, while the striatal transcriptome was the least responsive. Gender and energy restriction had particularly robust influences on the hippocampal transcriptome of middle-aged mice. Prominent functional groups of age- and energy-sensitive genes were those encoding proteins involved in DNA damage responses (Werner and telomere-associated proteins), mitochondrial and proteasome functions, cell fate determination (Wnt and Notch signaling) and synaptic vesicle trafficking.

Conclusion

Mouse CNS transcriptomes responded to age, energy intake and gender in a regionally distinctive manner. The systematic transcriptome dataset also provides a window into mechanisms of age-, diet- and sex-related CNS plasticity and vulnerability.
Cognitive–behavioural therapy for obsessive–compulsive disorder
Authors: Veale David
Published: October 2007

In the UK, the National Institute for Health and Clinical Excellence's guidelines on obsessive–compulsive disorder (OCD) recommend cognitive–behavioural therapy, including exposure and response prevention, as an effective treatment for the disorder. This article introduces a cognitive–behavioural model of the maintenance of symptoms in OCD. It discusses the process of engagement and how to develop a formulation to guide the strategies for overcoming the disorder.
Clinical effectiveness of treatments for anorexia nervosa in adolescents
Authors: Gowers Simon G. , Clark Andrew , Roberts Chris , Griffiths Alison , Edwards Vanessa , Bryan Claudine , Smethurst Nicola , Byford Sarah , Barrett Barbara
Published: October 2007

Background

Treatment guidelines identify few adequately powered trials to guide recommendations for anorexia nervosa.

Aims

To evaluate the effectiveness of three readily available National Health Service treatments for adolescents (aged 12–18 years) with anorexia nervosa.

Method

Multicentre randomised controlled trial of 167 young people comparing in-patient, specialist out-patient and general child and adolescent mental health service (CAMHS) treatment.

Results

Each group made considerable progress at 1 year, with further improvement by 2 years. Full recovery rates were poor (33% at 2 years, 27% still with anorexia nervosa). Adherence to in-patient treatment was only 50%. Neither in-patient nor specialist out-patient therapy demonstrated advantages over general CAMHS treatment by intention to treat, although some CAMHS out-patients were subsequently admitted on clinical grounds. In-patient treatment (randomised or after out-patient transfer) predicted poor outcomes.

Conclusions

First-line in-patient psychiatric treatment does not provide advantages over out-patient management. Out-patient treatment failures do very poorly on transfer to in-patient facilities.
Delays in mental health services and duration of untreated psychosis
Authors: Brunet Kat , Birchwood Max , Lester Helen , Thornhill Kate
Published: October 2007

AIMS AND METHOD

To dissect duration of untreated psychosis (DUP) into three components: help-seeking delay, referral delay and delay in mental health services, all mental health services in a defined geographical region were screened over a period of 1 year. All cases of first-episode psychosis without a primary mood disorder were identified (n=55).

RESULTS

The median delay within secondary services was over seven times the delay in the referral pathway. The mean delay in mental health services accounted for 35% of overall DUP.

CLINICAL IMPLICATIONS

Intervention is required in secondary as well as primary care services if DUP is to be reduced.
Extracellular Heat Shock Proteins in Cell Signaling and Immunity
Authors: CALDERWOOD STUART K. , MAMBULA SALAMATU S. , GRAY PHILLIP J.
Published: October 2007

Abstract:  Extracellular stress proteins including heat shock proteins (Hsps) and glucose‐regulated proteins (Grps) are emerging as important mediators of intercellular signaling and transport. Release of such proteins from cells is triggered by physical trauma and behavioral stress as well as exposure to immunological “danger signals.” Stress protein release occurs both through physiological secretion mechanisms and during cell death by necrosis. After release into the extracellular fluid, Hsp or Grp may then bind to the surfaces of adjacent cells and initiate signal transduction cascades as well as the transport of cargo molecules, such as antigenic peptides. In addition, Hsp60 and Hsp70 are able to enter the bloodstream and may possess the ability to act at distant sites in the body. Many of the effects of extracellular stress proteins are mediated through cell‐surface receptors. Such receptors include toll‐ like receptors (TLRs) 2 and 4, CD40, CD91, CCR5, and members of the scavenger receptor family, such as LOX‐1 and SREC‐1. The possession of a wide range of receptors for the Hsp and Grp family permits binding to a diverse range of cells and the performance of complex multicellular functions particularly in immune cells and neurons.
Long‐Term Acclimation of Plants to Elevated CO2and Its Interaction with Stresses
Authors: TUBA ZOLTÁN , LICHTENTHALER HARTMUT K.
Published: October 2007

Abstract: Rising atmospheric carbon dioxide (CO2) concentration and air temperature are of major concern when considering the possible effects of global climate change on vegetations. Although production has been found to increase in many cases, other experiments have also indicated increased hazards for plant growth because of the increased frequency of weather extremes, such as droughts, floods, and extreme temperatures. Thus at the same time elevated CO2and the extreme climatic events, intra‐ and interannual climatic variability alone can be foreseen as an indirect constraint, which separately influences significantly the carbon cycling in ecosystems, too. In the shorter term the effect of CO2is direct and is mediated by photosynthesis. In the longer term the effects of elevated CO2became more and more indirect and its effects are mediated by source‐sink interactions within plants, resources (nutrients, water), temperature, microbes, herbivores, and land‐use management practice. In fact, the plants can make use of their general stress coping mechanisms to avoid or compensate possible negative effects of elevated CO2. One has to consider that all the classical abiotic, biotic, and anthropogenic stressors are threatening plant growth and development also under elevated CO2, although at possibly different doses compared to ambient CO2concentrations. Therefore, the knowledge of the general stress coping, stress avoiding, and tolerance mechanisms is needed to understand the regulation of the plants' metabolism under normal and elevated CO2levels.