bluuebunny/crossref_metadata_2025 huggingface dataset:
A proof of concept study for the integration of robot therapy with physiotherapy in the treatment of stroke patients
Authors: Casadio Maura , Giannoni Psiche , Morasso Pietro , Sanguineti Vittorio
Published: February 2009

Objective: To carry out a proof of concept study for integrating robot therapy with physiotherapy in the treatment of stroke patients.

Design: A simple and `gentle' paradigm of robot—patient interaction was designed in order to foster the re-emergence of smooth, active control patterns in coordinated shoulder/elbow reaching movements. A haptic robot was programmed according to a strategy of minimal, progressively reduced assistance, with a double representation of targets: (i) visual (circles on a screen) and (ii) haptic (robot-generated force fields). The protocol included trials with and without vision, in order to emphasize the role of proprioceptive feedback. The training paradigm included 10 sessions and more than 5000 movements.

Subjects: Ten chronic, hemiparetic subjects; four controls provided reference values for the performance measurements.

Outcome measures: Four performance indicators (derived from the analysis of the reaching trajectories); clinical/functional measures (Fugl-Meyer and Ashworth scales).

Results: After robot therapy reaching movements became faster and smoother. The performance in the no-vision trials was at least as good as in the vision trials. The Fugl-Meyer arm scores also increased significantly and remained approximately constant at follow-up; the Ashworth scores did not change.

Conclusion: In spite of its simplicity, a limited number of `gentle' robot therapy sessions appear to be beneficial, even for severely impaired patients, although no firm conclusion can be drawn at this point. However, the study provides support material for the careful design of controlled clinical trials and for a better integration with physiotherapy.
The effect of walking mobility on the measurement of physical activity using accelerometry in multiple sclerosis
Authors: Snook Erin M , Motl Robert W , Gliottoni Rachael C
Published: February 2009

Objective: To examine whether accelerometry provides a measure of physical activity, walking ability or both in a sample of individuals with multiple sclerosis. The secondary purpose was to examine the validity of physical activity measures in people with multiple sclerosis who have ambulatory impairments.

Participants: Forty-two individuals with multiple sclerosis without ambulatory impairment (Expanded Disability Status Scale (EDSS) score ≤ 4.5) and 32 individuals with multiple sclerosis with ambulatory impairment (EDSS ≥5.0).

Method: Participants completed the Multiple Sclerosis Walking Scale-12 and Performance Scales, wore an accelerometer for seven days, and completed the Godin Leisure-Time Exercise Questionnaire and short-form of the International Physical Activity Questionnaire.

Results: There were significant differences between groups on scores from the five measures. There were large correlations between the accelerometer counts with scores from both the self-report measures of physical activity and the self-report measures of walking mobility in the overall sample. There were large correlations between scores from both measures of physical activity in the overall sample and the subsample with ambulatory impairment.

Conclusion: Our data suggest that accelerometers are measuring both physical activity and walking mobility in individuals with multiple sclerosis, whereas self-report measures are measuring physical activity in individuals with multiple sclerosis, including those with ambulatory impairment.
Attributions for Problem Behavior as Described by Turkish Teachers of Special Education
Authors: Erbas Dilek , Turan Yasemin , Aslan Yesim Gulec , Dunlap Glen
Published: February 2009

The purpose of this survey study was to determine Turkish teachers’ attributions of problem behaviors. The participants’ (special education teachers) attributions of problem behaviors varied with some teachers showing agreement with a behavioral perspective while others attributed the occurrence of problem behaviors to other factors (e.g., poor parenting, God, the child’s disability). Teachers’ educational area of specialty and training on behavioral interventions were associated with their beliefs about problem behaviors. Results are discussed in the context of current literature and directions for future researches are suggested.
From Drafter to Engineer, Doctor to Nurse
Authors: Packard Becky Wai-Ling , Babineau Maureen E.
Published: February 2009

This article explored career compromise as negotiated by working-class adults pursuing science-related careers. Using a multiple case study method, we focused on eight individuals who participated in an interview about their career choices and then were followed longitudinally for 2 years. All participants were first-generation college students from working-class families and, at the start of the study, were enrolled at a community college. The results highlight key factors that influenced initial compromises including time and financial constraints, family obligations, and lacking requisite skills. In addition, renegotiations of initial career compromises were sparked by plateaus at work, role models, wanting more money, and having limited time. An extended window of time and financial resources were critical for sustained college pursuit 2 years later. Implications for career development initiatives are discussed.
Relationship of Advisory Mentoring to MBA Career Maturity
Authors: Melien Wu  , Chang Chen-Chieh
Published: February 2009

This study investigates the influences of gender and work experiences on career maturity, as well as the relationship between advisory mentoring and career maturity. Analytical results from 528 full-time MBA students are summarized as follows: (a) gender exerts significant differences in advisory mentoring functions (instrumental and career-related functions) but not in career maturity, (b) work experience is significantly related to planfulness, (c) psychosocial function is a strong predictor of planfulness and independence, whereas career-related function is a strong predictor of both information gathering and involvement. The results are interpreted and implications discussed in terms of advisory mentoring behavior and career counseling of MBA education.
Constructivist Career Development as a Paradigm of Empowerment for At-Risk Culturally Diverse College Students
Authors: Grier-Reed Tabitha L. , Skaar Nicole R. , Conkel-Ziebell Julia L.
Published: February 2009

Although constructivist career theory is routinely discussed in the literature, links between theory and practice in education are lacking. The current study focused on the potential of a constructivist curriculum to empower at-risk culturally diverse college students by increasing career self-efficacy and reducing dysfunctional career thoughts. Using a pre/post-test design, 75 under-prepared undergraduates who were enrolled in six sections of a constructivist career course at a large Midwestern university completed the Career Decision Self-Efficacy Scale Short-Form (CDSE-SF) and the Career Thoughts Inventory (CTI). The sample was 45% students of color and 55% White. Multivariate analysis of variance with follow-up univariate analyses revealed significantly higher CDSE-SF scores and significantly lower CTI scores. These results suggest that a constructivist career development course may be a viable educational vehicle for empowering at-risk culturally diverse college students by increasing career self-efficacy and decreasing self-defeating thoughts, particularly thoughts associated with decision-making confusion and commitment anxiety.
The Relationship Among Work Possible Selves, Socioeconomic Position, and the Psychological Well-Being of Individuals in Early Adulthood
Authors: Pisarik Christopher T. , Shoffner Marie F.
Published: February 2009

This study examines the relationships among work possible selves, socioeconomic position, gender, and psychological well-being. Participants were college students in early adulthood (N = 201), aged 20 to 35. Work possible selves, a construct based on the theory of possible selves, were examined. The results showed relationships between expectations for the future self in work (expected work possible selves) and socioeconomic position. Results also showed that individuals who report larger discrepancies between hoped-for and expected work possible selves reported lower psychological well-being in terms of satisfaction with life.
Librarians' attitudes towards marketing library services
Authors: Aharony Noa
Published: February 2009

This research set out to explore the attitudes of school, academic and public librarians towards marketing libraries. The main question that was examined is whether personality characteristics such as empowerment, extroversion and resistance to change influence librarians' attitudes towards the marketing of libraries. One hundred and fifty-six participants took part in this study. The research tools included: a personal details questionnaire, extroversion/ introversion questionnaire, attitudes towards marketing a library questionnaire, a resistance to change questionnaire and an empowerment questionnaire. The most important finding of this research was the positive correlation between personal characteristics: empowerment, extroversion and resistance to change and attitudes towards marketing libraries. The results of the current research emphasize the idea that librarians of all branches should be exposed to marketing concepts in order to maintain their central position as information providers despite — and within — the new technologies.
Legal Issues in End-of-life Care: Perspectives from Saudi Arabia and United States
Authors: Babgi Amani
Published: February 2009

Aim: This paper provides different perspectives on end-of-life legal issues in Saudi Arabia, and contrasts those perspectives with current legal practice in the United States. Background: Islamic law governs end-of-life legal issues in Saudi Arabia which applies to end-of-life legal issues. There is a specific legal terminology, derived from the Qura'an, that is used to settle conflicts in end-of-life care. This contrasts with the United States which has a secular system of law that informs end-of-life issues. Data Sources: extent literature review of Muslim medical ethics; review of Shari'a law and review of US law and legal cases was used to provide both perspectives regarding end-of-life issues. Discussion: Commonalities and differences regarding end-of-life issues were highlighted in depth. Conclusions: There are many differences, and some commonalities between the laws practiced in both countries which help explain medical and nursing practice at the end of life.
Neurotrophic Modulation of Motor Neuron Development
Authors: Gould Thomas W. , Enomoto Hideki
Published: February 2009

Neurotrophic factors (NTFs) are a pleiotropic group of secreted growth factors that regulate multiple aspects of neuronal development, including the regressive event of cell death. Skeletal muscleinnervating lower motoneurons (MNs) of the brain stem and spinal cord comprise one population of central neurons in which programmed cell death (PCD) during embryogenesis has been actively investigated, as much for reasons of technical facility as clinical relevance. The precise identity of NTF-dependent MNs has remained unclear, with most studies simply reporting losses or gains across the entire spinal cord or individual brain-stem nuclei. However, MNs are grouped into highly heterogenous populations based on transcriptional identity, target innervation, and physiological function. Therefore, recent work has focused on the effects of NTF overexpression or deletion on the survival of these MN subpopulations. Together with the recent progress attained in the generation of conditional mutant mice, in which the function of an NTF or its receptor can be eliminated specifically in MNs, these recent studies have begun to define the differential trophic requirements for MN subpopulations during PCD. The intent of this review is to summarize these recent findings and to discuss their significance with respect to neurotrophic theory.
Neurotrophic Support and Oxidative Stress: Converging Effects in the Normal and Diseased Nervous System
Authors: Gardiner John , Barton Deborah , Overall Robyn , Marc Jan
Published: February 2009

Oxidative stress and loss of neurotrophic support play major roles in the development of various diseases of the central and peripheral nervous systems. In disorders of the central nervous system such as Alzheimer's, Parkinson's, and Huntington's diseases, oxidative stress appears inextricably linked to the loss of neurotrophic support. A similar situation is seen in the peripheral nervous system in diseases of olfaction, hearing, and vision. Neurotrophic factors act to up-regulate antioxidant enzymes and promote the expression of antioxidant proteins. On the other hand, oxidative stress can cause down-regulation of neurotrophic factors. We propose that normal functioning of the nervous systems involves a positive feedback loop between antioxidant processes and neurotrophic support. Breakdown of this feedback loop in disease states leads to increased oxidative stress and reduced neurotrophic support.
Psychometric Properties of the Marlowe-Crowne Social Desirability Scale With Adult Male Sexual Offenders
Authors: Tatman Anthony W. , Swogger Marc T. , Love Keisha , Cook Michelle D.
Published: February 2009

This research project investigates the factor structure, reliability, and validity of the Marlowe-Crowne Social Desirability Scale (MCSDS) when used with a sample of convicted, adult male sexual offenders. Results confirm the two-factor structure (Denial and Attribution) originally proposed by the authors (Study 1, n = 247). Results also reveal that the full-scale MCSDS has strong internal consistency estimates (Study 1), discriminant and convergent validity (Study 2, n = 91), and test-retest reliability over a 3-week period (Study 3, n = 74). Information is provided to aid evaluators' interpretation of MCSDS full-scale and factor scores when used with male adult sexual offenders.
An Evil King `Thing', Rising, Falling and Multiplying in Trucker Culture
Authors: Sköld David
Published: February 2009

Paraphrasing Slavoj Žižek (1991: 65), the paper proposes that: `The Scania Truck does not exist': it is nothing but `the symptom of passionate users', its power of fascination masks the void of its nonexistence'. Along the same line of reasoning, it argues, again paraphrasing Žižek, that `the customized Scania truck is becoming the sinthome of its user'. (c.f. Žižek, 1991: 137). The paper does so by digging into a customizing discourse found in trucker media; by describing some of the customizing endeavours of Lennart Källström, a passionate truck owner, haulier and waste management entrepreneur; and by describing the rise and fall of a customizing King, and the Evil which befalls him in this process. The main purpose of the paper is to explore the workings and the effects of a circular movement of desire, fantasy and ideology at play in truck design development. As is already evident, Žižek is the main support in this endeavour.
Informed Consent: The Making of a Ubiquitous Rule in Medical Practice
Authors: Hoeyer Klaus
Published: February 2009

During the past few decades the rule of informed consent has thoroughly changed everyday decision-making in the healthcare sector. This paper explores the dissemination of informed consent from the perspective of organizational fashion studies. It is argued that this approach can be employed to stimulate renewed reflections on what informed consent procedures do as well as when and how such procedures become endorsed by various organizational actors. A history of the agencies involved in formulating the consent requirement is presented and related to the implications of this new emphasis on the autonomous choice of patients and research participants.
Security Studies and Organization Studies: Parallels and Possibilities
Authors: Grey Christopher
Published: February 2009

This note provides an outline of the field of security studies, drawing comparison between it and that of organization studies. It is noted that whilst having many parallels, the two fields exist almost entirely in isolation from each other. The potential overlaps between the fields offer opportunities to extend the range of each and to contribute to the renewal of organization studies.
Supporting nurse decision making in primary care: exploring use of and attitude to decision tools
Authors: Randell Rebecca , Mitchell Natasha , Thompson Carl , McCaughan Dorothy , Dowding Dawn
Published: February 2009

Nurses are increasingly working more autonomously in extended roles, yet we know little about the nature of the decisions they make. Decisions vary in terms of complexity, ambiguity and presentation, and the nature of the decision task impacts on the process of decision making, such as the likelihood of using a decision tool. Thus, knowledge about the nature of nursing decisions is essential for development of effective decision tools. This article presents an analysis of 410 nurse—patient consultations and interviews with 76 primary care nurses, and explores the nature of the decisions that primary care nurses make and the impact of that on their use of and attitudes towards decision tools.
Managing the β-cell with GLP-1 in type 2 diabetes
Authors: Gallwitz Baptist
Published: February 2009

The clinical course of type 2 diabetes mellitus is characterised by a progressive decline in β -cell mass. The changing β-cell mass reflects a shifting balance between β-cell neogenesis, islet neogenesis and β-cell apoptosis. In persons with diabetes, administration of exogenous glucagon-like peptide-1 (GLP-1) improves glucose sensitivity and insulin synthesis and may help increase β cell mass. As the effects of GLP-1 on the β cell are becoming better understood at both the molecular and cellular levels, it has become possible to develop therapies with the potential to harness and sustain the positive effects of endogenous GLP-1 in patients with type 2 diabetes. Data from in vitro, preclinical and phase II studies show promising results with GLP-1 analogues in improving β-cell function in patients with type 2 diabetes. For example, in vitro models have shown the GLP-1 analogue liraglutide inhibits β-cell apoptosis in isolated neonatal rat islets. In vitro, animal models demonstrate increasing β-cell mass with liraglutide administration. Results from a recently completed phase II clinical trial with liraglutide in patients with type 2 diabetes demonstrate that daily treatment markedly improves β -cell function as shown by an increased first-phase insulin response and secretory capacity and a decreased proinsulin:insulin ratio. Now, phase III trials continue to bear out the potential for liraglutide for treatment of patients with type 2 diabetes.Br J Diabetes Vasc Dis 2008;8 (Suppl 2): S19-S25
Cortical Excitability in Chronic Stroke and Modulation by Training: A TMS Study
Authors: Blicher Jakob Udby , Jakobsen Johannes , Andersen Grethe , Nielsen Jørgen Feldbæk
Published: February 2009

Background. A possible role for GABA in regulating cortical plasticity after stroke has been proposed. Objective. To investigate changes in intracortical inhibitory and facilitatory circuits in the affected hemisphere more than 6 months after stroke, as well as modulation of excitability by a single training session. Methods. A total of 22 patients >6 months after stroke were compared to age- and gender-matched healthy participants. Cortical excitability was assessed by transcranial magnetic stimulation (TMS), including paired-pulse stimulation, before and up to 30 minutes after a single 15-minute session of 1 Hz thumb abduction-adduction movements. Results. At baseline, TMS showed decreased intracortical inhibition in the affected hemisphere of patients ( P = .004) compared to healthy participants. After training a short-lasting decline in motor evoked potentials was observed in both patients ( P = .002) and healthy participants ( P = .06). Moreover, in healthy participants, inhibitory activity decreased up to 30 minutes after training whereas no significant change was seen in the patients. Conclusions. The findings indicate that inhibitory intracortical circuits are less active after stroke, and no change in inhibitory activity is evident after a single training session. This may indicate that intracortical disinhibition is beneficial during recovery and that an impaired capacity for modulation remains in the chronic stage of stroke.
Empowerment or Prescription? Workforce Remodelling at the National and School Level
Authors: Hammersley-Fletcher Linda , Adnett Nick
Published: February 2009

Workforce Remodelling in England implemented between 2003 and 2005 has been presented by the `New Labour' government as a means of enhancing the development of teachers and promoting rising educational attainments. While the processes that schools were to follow to achieve the desired `fundamental alteration in mindset' were prescribed, the outcomes of this process were less so. Conceptually therefore this initiative could potentially be viewed as having more in common with policies seeking to empower schools, rather than the performance management ethos of the dominant market-based approach to reforming English state schooling. This tension created within national policy is reflected in the research reported below which demonstrates that while in some schools Workforce Remodelling has largely taken the form of a centralized reallocation of tasks along lines favoured by the government, in others a more delegated style of leadership has encouraged and enabled redefinitions of roles and opened up fundamental debates about current practice. We find that both intended and unintended outcomes were shaped by the processes adopted in schools to respond to the remodelling agenda.
Behaviour of Turkish Elementary School Principals in the Change Process
Authors: Gokçe Feyyat
Published: February 2009

Technological and economic changes affect societies, and consequently bring about change in education. Elementary school principals in Turkey spend considerable time and effort managing change in their schools. This study contributes to the better management of Turkish elementary schools by determining the behavior of elementary school principals in the process of change. Data were gathered through interviews of 80 elementary school principals and 280 elementary school teachers in the Cappadocian city of Nevşehir. School principals and teachers considered their own behaviour in the process of change as `generally' sufficient. However, a significant difference was found between the opinions of teachers and school principals. Teachers expect principals to show more effective behaviour in the change process. The results of the study suggest that eliminating handicaps caused by sex discrimination when selecting and appointing school administrators, giving administrators postgraduate education and applying an education program based on approaches that internalize improvement would contribute to more effective school management.
`I Don't Want to Be a School Head'
Authors: Oplatka Izhar , Tamir Vered
Published: February 2009

In light of feminist scholars who have called for challenging the epistemology of existing theories and concepts in social sciences and recreating an innovative knowledge in which women are the focus, the current study aimed at tracing the career stories of 25 Israeli female deputy heads who explicitly do not aspire to headship. These deputies hold a stance that is in sharp contrast with widespread beliefs on career aspiration and advancement, albeit that they are considered to be competent candidates for headship. The female deputies' stories revealed that they construct a clear and sharp distinction between the deputy's role and that of the school head. Whereas the former is perceived to be challenging and less complicated, leaving them sufficient space to establish informal, warm relationships with staff and students, the latter is portrayed as stressful, formal and essentially administrative-oriented. This distinction corroborates the dichotomy of masculine versus feminine leadership, and provides insight into new conceptions of headship and deputy headship in the era of marketization and accountability. Practical and empirical implications are suggested.
Working the Interface
Authors: Kubiak Chris
Published: February 2009

The establishment of school-based learning networks is one of the more significant recent changes in the way that professional learning and organizational change have been conceptualized. This article argues that network development requires facilitation and conceptualizes this work as brokerage, a concept highlighting the tensions of working as an `inside—outsider'. Using interviews, observations of meetings, document analysis and case studies, an understanding of the practices of a group of National College of School Leadership network facilitators employed to support network development was developed. Facilitators saw themselves as facilitating the learning of network members and fostering accountability. Positioned at the boundary of the network, connected to many other groups, the success of their attempts to access and establish a legitimate role in their networks varied from group to group. As such, some facilitators experienced their work as disorienting. `Communities of brokerage practice' served as buffer zones between networks and their employing organization—a space to not only reflect upon and build an understanding of brokerage work but to evolve and develop the practice itself. Recommendations for organizations supporting a similar role are made.
Tension deformation mechanism and fracture characteristics of high nitrogen steel 6Cr21Mn10MoVNbN at 25–800°C
Authors: Zhu Y. Z. , Zhu Z. , Yin Z. M. , Xiang Z. D.
Published: February 2009

The tensile deformation behaviour and the fracture mechanism of 6Cr21Mn10MoVNbN alloy were studied in the range between 25–800°C using thermal simulator, hardness tester, optical microscopy, scanning electronic microscopy attached with energy dispersive spectroscopy and transmission electronic microscopy. Elongation of the steel was found to decrease as temperature increases, which was due to the growth of the coarse nitrides and carbides and the precipitation of Cr2N at grain boundaries. It was also found that the fracture behaviour and deformation mechanism differed at different temperatures. At a low temperature, such as 225°C, the steel showed features of transgranular fracture and the deformation mechanism of the steel was dislocation slip and deformation twinning. At a high temperature, such as 800°C, the steel demonstrated characteristics of intergranular failure and the major deformation mechanism of the steel was dislocation slip and rotation of grains.
Research on plastic deformation behaviour and conditions for stepped hole ring rolling
Authors: Hua L. , Qian D.-S. , Pan L.-B.
Published: February 2009

Stepped hole ring rolling is an advanced forming technique, in which ring is formed by rolling under the action of ring rolling mill. Boundary and contact conditions of stepped hole ring rolling are different from that of rectangular section ring, and there are active deformation and passive deformation in rolling process. Then, the plastic deformation behaviour of stepped hole ring rolling is more complicated than that of rectangular section ring, various rolling defects are easy to be formed, and the rolling stability and forming quality are hard to be ensured. In this paper, three-dimensional finite element (FE) model for plastic penetration of stepped hole ring rolling is firstly established under the ABAQUS software environment. Through FE simulation, the expanding rules of plastic zone in the plastic penetration process of stepped hole ring rolling are revealed, and four kinds of plastic deformation behaviour existing in stepped hole ring rolling and their conditions are studied. The rolling conditions for stepped hole ring blank are determined at last, and their validity are testified by experiments of stepped hole ring rolling.
Advanced vanadium alloyed steel for heavy product applications
Authors: Capdevila C. , García-Mateo C. , Chao J. , Caballero F. G.
Published: February 2009

The present paper deals with a new vanadium and nitrogen alloyed steel for heavy products applications, which offer improved toughness and strength properties as compare with a commercial heavy product steel. A strong structural refinement, by introducing acicular ferrite microstructure, combined with an optimum cooling process can be utilised to develop tough, high strength thick products.
A controlled trial of 6-weeks' treatment with a novel inhaled phosphodiesterase type-4 inhibitor in COPD
Authors: Vestbo J. , Tan L. , Atkinson G. , Ward J.
Published: February 2009

Anti-inflammatory drugs are lacking in chronic obstructive pulmonary disease (COPD) and inhibitors of the phosphodiesterase type-4 (PDE4) enzyme have been suggested to be an interesting class of drugs to treat inflammation in COPD. The present authors report the findings of a phase II trial of a novel inhaled PDE4 inhibitor.

Three doses, 0.1, 0.4 and 1.0 mgb.i.d., of the compound UK-500,001 were tested in a double-blind, placebo-controlled, 6-week trial in 209 patients with moderate-to-severe COPD. The primary efficacy parameter was trough forced expiratory volume in one second after 6 weeks of treatment, and secondary end-points included other lung function end-points and symptom scores assessed at 2-week intervals. The present study was stopped following a planned interim analysis for futility.

No effect on the primary efficacy parameter, other measures of lung function or symptom scores was observed at any dose of UK-500,001 after 6 weeks of treatment. However, after the first 2 weeks of treatment, an improvement in a number of outcome measures in the 1.0 mgb.i.d.dose group was observed compared with placebo. The drug was well tolerated, although PDE4 inhibitor-related side-effects were observed, especially in the highest dose group.

The findings of the present study question the role of inhaled phosphodiesterase type-4 inhibitors in chronic obstructive pulmonary disease.
Suberoylanilide hydroxamic acid: a potential epigenetic therapeutic agent for lung fibrosis?
Authors: Wang Z. , Chen C. , Finger S. N. , d/o Kwajah M.M S. , Jung M. , Schwarz H. , Swanson N. , Lareu R. R. , Raghunath M.
Published: February 2009

Pulmonary fibrosis represents a fatal stage of interstitial lung diseases of known and idiopathic aetiology. No effective therapy is currently available. Based on an indication-discovery approach we present novelin vitroevidence that the histone deacetylases inhibitor suberoylanilide hydroxamic acid (SAHA), an FDA approved anti-cancer drug, has antifibrotic and anti-inflammatory potential.

Human lung fibroblasts (fetal, adult and idiopathic adult pulmonary fibrosis) were treated with transforming growth factor (TGF)-β1 with or without SAHA. Collagen deposition, α-smooth muscle actin (α-SMA) expression, matrix metalloproteinase (MMP)1 activity, tissue inhibitor of MMP (TIMP)1 production, apoptosis and cell proliferation were assessed. Pro-inflammatory cytokines relevant to pulmonary fibrosis were assayed in SAHA-treated human peripheral blood mononuclear cells (PBMC) and its subpopulations.

SAHA abrogated TGF-β1 effects on all the fibroblast lines by preventing their transdifferentiation into α-SMA positive myofibroblasts and increased collagen deposition without inducing apoptosis. However, MMP1 activity and TIMP1 production was modulated without a clear fibrolytic effect. SAHA also inhibited serum-induced proliferation of the fibroblast lines and caused hyperacetylation of α-tubulin and histone. Cytokine secretion was inhibited from PBMC and lymphocytes at nonapoptotic concentrations.

Taken together, these data demonstrate combined antifibrotic and anti-inflammatory properties of SAHA, suggesting its therapeutic potential for pulmonary fibrosis.
Feedback dose alteration significantly affects probability of pathogen eradication in nosocomial pneumonia
Authors: Scaglione F. , Esposito S. , Leone S. , Lucini V. , Pannacci M. , Ma L. , Drusano G. L.
Published: February 2009

Nosocomial pneumonia (NP) is associated with considerable morbidity and mortality. Data have shown that inadequate initial antibiotic therapy is a major risk for infection-attributed mortality. The aim of the present study was to measure antibiotic concentration and minimum inhibitory concentration (MIC) in infected hospitalised patients early in therapy, in order to determine whether dose alterations, in those with low drug concentrations, could affect outcomes.

Only patients treated with aminoglycosides, fluoroquinolones, and β-lactams were evaluated. MICs were determined using standard National Committee for Clinical Laboratory Standards procedures. Antibiotics were assayed using validated high-performance liquid chromatographic methods. Pharmacokinetic/pharmacodynamic markers adopted were: aminoglycoside peak/MIC ratio ≥8 mg·L−1; fluoroquinolone peak/MIC ≥10 mg·L−1; β-lactam peak/MIC ≥4 mg·L−1and time that plasma levels remain above the MIC ≥70%.

638 patients with NP were included in the study. In 205 patients, both drug concentration and isolate MIC were available, while in other patients, used as controls, one or both parameters were lacking. For clinical outcome, the Acute Physiology and Chronic Health Evaluation II score (p<0.0001), the presence of combination therapy (p = 0.0014) and whether both MIC and drug concentration(s) were measured (p = 0.0002) significantly affected the probability of a good outcome. For microbiological outcome, the MIC for the β-lactams (≤2 mg·L−1; p<0.0001) and whether the second drug was a fluoroquinolone or aminoglycoside (fluoroquinolones were better than aminoglycosides; p = 0.0177), as well as whether both MIC and drug concentration(s) were measured (p = 0.02), affected the probability of eradication.

Measurement of drug concentrations and determination of pathogen MIC values with subsequent dose alteration significantly improves the probability of good clinical outcome and pathogen eradication in NP.
Impact of influenza vaccination on mortality risk among the elderly
Authors: Groenwold R. H. H. , Hoes A. W. , Hak E.
Published: February 2009

Estimates of influenza vaccine effectiveness have mostly been derived from nonrandomised studies and therefore are potentially confounded. The aim of the current study was to estimate influenza vaccine effectiveness in preventing mortality among the elderly, taking both measured and unmeasured confounding into account.

Information on patients aged ≥65 yrs from the computerised Utrecht General Practitioner database on eight influenza epidemic periods and summer periods was pooled to estimate influenza vaccine effectiveness in preventing mortality. Summer periods (during which no effect of vaccination was expected) were used as a reference to control for unmeasured confounding in epidemic periods.

After adjustment for measured confounders using multivariable regression analysis, propensity score matching and propensity score regression analysis, influenza vaccination reduced mortality risk (odds ratios (ORs) 0.58 (95% confidence interval (CI) 0.46–0.72), 0.56 (95% CI 0.44–0.71) and 0.56 (95% CI 0.45–0.69), respectively). After additional adjustment for unmeasured confounding (as observed during summer periods), the association between influenza vaccination and mortality risk decreased (OR 0.69 (95% CI 0.52–0.92)).

We conclude that after state-of-the-art adjustment for typical confounders such as age, sex and comorbidity status, unmeasured confounding still biased estimates of influenza vaccine effectiveness. After taking unmeasured confounding into account, influenza vaccination is still associated with substantial reduction in mortality risk.
A comparison on effects of normalisations in the detection of differentially expressed genes
Authors: Chiogna Monica , Massa Maria Sofia , Risso Davide , Romualdi Chiara
Published: February 2009

Background

Various normalisation techniques have been developed in the context of microarray analysis to try to correct expression measurements for experimental bias and random fluctuations. Major techniques include: total intensity normalisation; intensity dependent normalisation; and variance stabilising normalisation. The aim of this paper is to discuss the impact of normalisation techniques for two-channel array technology on the process of identification of differentially expressed genes.

Results

Through three precise simulation plans, we quantify the impact of normalisations: (a) on the sensitivity and specificity of a specified test statistic for the identification of deregulated genes, (b) on the gene ranking induced by the statistic.

Conclusion

Although we found a limited difference of sensitivities and specificities for the test after each normalisation, the study highlights a strong impact in terms of gene ranking agreement, resulting in different levels of agreement between competing normalisations. However, we show that the combination of two normalisations, such as glog and lowess, that handle different aspects of microarray data, is able to outperform other individual techniques.
Rapid glycation with D-ribose induces globular amyloid-like aggregations of BSA with high cytotoxicity to SH-SY5Y cells
Authors: Wei Yan , Chen Lan , Chen Ji , Ge Lin , He Rong Qiao
Published: February 2009

Background

D-ribose in cells and human serum participates in glycation of proteins resulting in advanced glycation end products (AGEs) that affect cell metabolism and induce cell death. However, the mechanism by which D-ribose-glycated proteins induce cell death is still unclear.

Results

Here, we incubated D-ribose with bovine serum albumin (BSA) and observed changes in the intensity of fluorescence at 410 nm and 425 nm to monitor the formation of D-ribose-glycated BSA. Comparing glycation of BSA with xylose (a control for furanose), glucose and fructose (controls for pyranose), the rate of glycation with D-ribose was the most rapid. Protein intrinsic fluorescence (335 nm), Nitroblue tetrazolium (NBT) assays and Western blotting with anti-AGEs showed that glycation of BSA incubated with D-ribose occurred faster than for the other reducing sugars. Protein intrinsic fluorescence showed marked conformational changes when BSA was incubated with D-ribose. Importantly, observations with atomic force microscopy showed that D-ribose-glycated BSA appeared in globular polymers. Furthermore, a fluorescent assay with Thioflavin T (ThT) showed a remarkable increase in fluorescence at 485 nm in the presence of D-ribose-glycated BSA. However, ThT fluorescence did not show the same marked increase in the presence of xylose or glucose. This suggests that glycation with D-ribose induced BSA to aggregate into globular amyloid-like deposits. As observed by Hoechst 33258 staining, 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and cell counting kit-8 (CCK-8) assay, lactate dehydrogenase (LDH) activity assay, flow cytometry using Annexin V and Propidium Iodide staining and reactive oxygen species (ROS) measurements, the amyloid-like aggregation of glycated BSA induced apoptosis in the neurotypic cell line SH-SY5Y.

Conclusion

Glycation with D-ribose induces BSA to misfold rapidly and form globular amyloid-like aggregations which play an important role in cytotoxicity to neural cells.
Mismatch oligonucleotides in human and yeast: guidelines for probe design on tiling microarrays
Authors: Seringhaus Michael , Rozowsky Joel , Royce Thomas , Nagalakshmi Ugrappa , Jee Justin , Snyder Michael , Gerstein Mark
Published: February 2009

Background

Mismatched oligonucleotides are widely used on microarrays to differentiate specific from nonspecific hybridization. While many experiments rely on such oligos, the hybridization behavior of various degrees of mismatch (MM) structure has not been extensively studied. Here, we present the results of two large-scale microarray experiments on S. cerevisiae and H. sapiens genomic DNA, to explore MM oligonucleotide behavior with real sample mixtures under tiling-array conditions.

Results

We examined all possible nucleotide substitutions at the central position of 36-nucleotide probes, and found that nonspecific binding by MM oligos depends upon the individual nucleotide substitutions they incorporate: C→A, C→G and T→A (yielding purine-purine mispairs) are most disruptive, whereas A→X were least disruptive. We also quantify a marked GC skew effect: substitutions raising probe GC content exhibit higher intensity (and vice versa). This skew is small in highly-expressed regions (± 0.5% of total intensity range) and large (± 2% or more) elsewhere. Multiple mismatches per oligo are largely additive in effect: each MM added in a distributed fashion causes an additional 21% intensity drop relative to PM, three-fold more disruptive than adding adjacent mispairs (7% drop per MM).

Conclusion

We investigate several parameters for oligonucleotide design, including the effects of each central nucleotide substitution on array signal intensity and of multiple MM per oligo. To avoid GC skew, individual substitutions should not alter probe GC content. RNA sample mixture complexity may increase the amount of nonspecific hybridization, magnify GC skew and boost the intensity of MM oligos at all levels.
The effect of the dual Src/Abl kinase inhibitor AZD0530 on Philadelphia positive leukaemia cell lines
Authors: Gwanmesia Patricia Mambou , Romanski Annette , Schwarz Kerstin , Bacic Biserka , Ruthardt Martin , Ottmann Oliver G
Published: February 2009

Background

Imatinib mesylate, a selective inhibitor of Abl tyrosine kinase, is efficacious in treating chronic myeloid leukaemia (CML) and Ph+ acute lymphoblastic leukaemia (ALL). However, most advanced-phase CML and Ph+ ALL patients relapse on Imatinib therapy. Several mechanisms of refractoriness have been reported, including the activation of the Src-family kinases (SFK). Here, we investigated the biological effect of the new specific dual Src/Abl kinase inhibitor AZD0530 on Ph+ leukaemic cells.

Methods

Cell lines used included BV173 (CML in myeloid blast crisis), SEM t(4;11), Ba/F3 (IL-3 dependent murine pro B), p185Bcr-Abl infected Ba/F3 cells, p185Bcr-Abl mutant infected Ba/F3 cells, SupB15 (Ph+ ALL) and Imatinib resistant SupB15 (RTSupB15) (Ph+ ALL) cells. Cells were exposed to AZD0530 and Imatinib. Cell proliferation, apoptosis, survival and signalling pathways were assessed by dye exclusion, flow cytometry and Western blotting respectively.

Results

AZD0530 specifically inhibited the growth of, and induced apoptosis in CML and Ph+ ALL cells in a dose dependent manner, but showed only marginal effects on Ph- ALL cells. Resistance to Imatinib due to the mutation Y253F in p185Bcr-Abl was overcome by AZD0530. Combination of AZD0530 and Imatinib showed an additive inhibitory effect on the proliferation of CML BV173 cells but not on Ph+ ALL SupB15 cells. An ongoing transphosphorylation was demonstrated between SFKs and Bcr-Abl. AZD0530 significantly down-regulated the activation of survival signalling pathways in Ph+ cells, resistant or sensitive to Imatinib, with the exception of the RTSupB15.

Conclusion

Our results indicate that AZD0530 targets both Src and Bcr-Abl kinase activity and reduces the leukaemic maintenance by Bcr-Abl.
The incidence of interstitial lung disease 1995–2005: a Danish nationwide population-based study
Authors: Kornum Jette B , Christensen Steffen , Grijota Miriam , Pedersen Lars , Wogelius Pia , Beiderbeck Annette , Sørensen Henrik Toft
Published: February 2009

Background

Current data on incidence of interstitial lung diseases (ILDs) are sparse and concerns about an increasing trend have been raised. We examined incidence rates (IRs) of ILDs and changes in IRs between 1995 and 2005.

Methods

All persons with a first-time hospital discharge or outpatient diagnosis of ILD were identified through the Danish National Registry of Patients, which covers all Danish hospitals. Crude and age-standardised IRs were computed for ILD overall, as well as stratified by ILD subcategories.

Results

A total of 21,765 patients with ILD were identified. Between 1995 and 1998 the overall standardised IR of ILD decreased from 27.14 (95% CI 25.82–28.46) per 100,000 person-years to 19.36 (95% CI 18.26–20.46) per 100,000 person-years. After 1998 the IR increased considerably, peaking at 34.34 (95% CI 32.84–35.85) per 100,000 person-years in 2002. Subsequently there was a slight decrease. The highest IR was observed in the non-specific category "Respiratory disorders in diseases classified elsewhere". By ILD subcategory, the greatest average increase during the study period was observed in "Respiratory disorders in diseases classified elsewhere".

Conclusion

The incidence rate of ILD in Denmark increased during the study period, most pronounced for ILDs associated with systemic diseases.
Estimation of thickness and velocity changes of injected carbon dioxide layers from prestack time-lapse seismic data
Authors: Ghaderi Amir , Landrø Martin
Published: February 2009

In this study, we bring together the two main categories of time-lapse seismic analysis — amplitude analysis and time-shift analysis — to estimate simultaneously the changes in thickness and velocity of a 4D seismic anomaly. The methodology is applied to time-lapse seismic monitoring of carbon dioxide [Formula: see text] storage at Sleipner field, Norway, that shows significant 4D effects. The 4D anomalies resulting from [Formula: see text] injection appear as a multilayer reflection pattern within the relatively shallow Utsira Sand. This multireflective appearance within the sand layer is interpreted as [Formula: see text] layers trapped below thin shale layers. Because most of the [Formula: see text] layers are believed to be thin [Formula: see text], the interference between top and base of these layers needs to be taken into account in 4D seismic analysis. By studying the reflected event from a horizon below the Utsira Sand, we estimate 4D traveltime shifts caused by the presence of the [Formula: see text] layer above thishorizon. We then combine these traveltime shifts with measured amplitude changes for the top and base of the [Formula: see text] layer to estimate velocity and thickness changes for the thin [Formula: see text] layer. In 1999, after three years of injection, the most likely velocity change was around [Formula: see text] and the thickness of the [Formula: see text] layer was around [Formula: see text]. In 2001, the corresponding velocity change and thickness estimates were [Formula: see text] and [Formula: see text], respectively. Finally, in 2002, the most likely velocity change was [Formula: see text] and the thickness of the [Formula: see text] layer was [Formula: see text]. It is not straightforward to apply this method to a stack of [Formula: see text] layers because 4D time shifts below the Utsira Sand only provide information about the average time shift for all layers. The amplitude information for each individual [Formula: see text] layer cannot be resolved without knowing the velocity change within each layer. However, our result from a single [Formula: see text] layer may be used to constrain the velocity changes for the multilayer [Formula: see text] case.