bluuebunny/crossref_metadata_2025 huggingface dataset:
Identification of Complex Order-distributions
Authors: Adams J.L. , Hartley T.T. , Lorenzo C.F.
Published: September 2008

This article discusses the identification of fractional systems using the concepts of complex order distribution. Based on the ability to define systems using complex order-distributions, it is shown that system identification in the frequency domain using a least-squares approach can be performed. A mesh is created to cover an area in the complex-order plane. The weighting of each block in the order-plane is selected to minimize the square-error between the frequency response of the system and the identified system. The identified systems have real time responses. Four examples, including both pure real-order systems and pure complex-order systems, are presented to demonstrate the utility of the identification method.
Application of a Sigma-point Kalman-filter for the Online Estimation of Fractional Order Impedance Models for Solid Oxide Fuel Cells
Authors: Haschka Markus , Weickert Thomas , Krebs Volker
Published: September 2008

To operate a solid oxide fuel cell (SOFC) safely and efficiently, it is necessary to monitor the values of characteristic model parameters of the cell impedance. This paper addresses the problem to compute online estimates of model parameters for SOFCs, whose impedance is represented by a fractional (non-integer) order impedance model. The fractional model of the impedance is approximated through serial connection of a finite number of RC-elements. Assuming that the time-dependent model parameters of the impedance are treated as state-variables of an augmented state vector, the linearity is lost, and the application of the classical linear Kalman filter for state estimation is not longer possible. The so-called sigma-point Kalman filter is therefore used to solve the online estimation problem for nonlinear system dynamics. The feasibility and quality of this online identification approach is outlined using simulated data with additional noise.
Fractional Central Differences and Derivatives
Authors: Ortigueira Manuel Duarte
Published: September 2008

Fractional central differences and derivatives are studied in this article. These are generalisations to real orders of the ordinary positive (even and odd) integer order differences and derivatives, and also coincide with the well known Riesz potentials. The coherence of these definitions is studied by applying the definitions to functions with Fourier transformable functions. Some properties of these derivatives are presented and particular cases studied.
Using Rn-222 to Manage the Air Quality of Air Conditioned Buildings in Hong Kong
Authors: Chan Daniel W.T. , Wong C.S. , Tung Thomas C.W.
Published: September 2008

This paper proposes a pragmatic methodology to manage the air quality of an air conditioned building as well as optimizing energy consumption during venting. Radon-222 (Rn-222) is used as a tracer to quantify the specific production rates and resultant losses of pollutants for which the information is important in indoor air quality management. A term, indoor pollutant inventory, is introduced for easy handling of various indoor pollutants. The specific production rate (Φj) of pollutant-j is the production rate of a pollutant normalized by the control volume of sampled room. The resultant loss (L j)RL of pollutant-j is defined as the sum of its natural decay (λj), reaction loss (Rj), and ventilation loss (q/v). Rn-222 and total volatile organic compounds are used to verify the methodology. In the verification tests, the air conditioned system of an office was scheduled to shut down overnight and return to supply mode in the next morning. The build-up and decay of the pollutants were measured and used to quantify (Φj) and (Lj)RL. The values of (Φj) and (Lj)RL obtained from the pollutants at two different modes mutually agreed with each other. The mean specific production rates of Rn-222 and TVOC were 20.7 Bq·m -3·h-1 and 2.0 mg·m-3·h-1 respectively, while the lump sum of chemical and natural losses of these pollutants were 0.0076 h-1 and 0.0226h-1, respectively. Concentrations of the pollutants at various air change rates were also simulated in the study.
Exposure to Environmental Tobacco Smoke at Work, at Home, and During Leisure Time: Personal Exposure Measurements by Diffusive Sampling of Airborne 3-Ethenylpyridine
Authors: Vainiotalo Sinikka , Patja Kristiina , Laatikainen Tiina , Kuusimäki Leea , Peltonen Kimmo , Vartiainen Erkki
Published: September 2008

Environmental tobacco smoke (ETS) is associated with an increased risk of several diseases. In 2002, the ETS exposure level was studied in a Finnish cross-sectional population sample with a sub-sample of currently working nonsmokers. In all, 123 nonsmokers (25—64 years) reporting at least 1 h of daily exposure to ETS participated in personal exposure measurements. Two 3 M organic vapor monitors, one for work and one for free time, were given to each participant. A 5-day sampling of breathing zone air was based on the passive monitoring of 3-ethenylpyridine (3-EP), a vapor-phase compound specific to tobacco smoke. The 3-EP concentrations ranged from <0.01 to 30 μg·m-3 (n=221), with low exposures as the most frequent. More than half (55%) of the study group was exposed both at work and during free time. The geometric mean concentration for 3-EP at home and during leisure time was 0.07 μg·m-3 (mean sampling time 74 h) and during working hours 0.30 μg·m-3 (mean sampling time 32 h). The study showed that despite the restrictions concerning indoor smoking at work, the ETS exposure seemed to be higher at work than at home or during leisure time. The average exposure levels were similar for men and women.
Policy Influence of Formaldehyde Exposure Risk in Air-conditioned Office Environment
Authors: Mui K.W. , Wong L.T. , Hui P.S.
Published: September 2008

Long-term measurement of indoor air quality (IAQ) over a general community could be a good approach to evaluate the influence of policy on pollutant exposure levels. However, this approach requires considerable measurement efforts and in many circumstances an updated data set will not be available. Formaldehyde is an indoor pollutant that presents a health hazard to building occupants in the long term. It is widely associated with common building materials and products. An IAQ policy for Hong Kong offices was initiated in 1997 to improve the indoor environment and occupants' health. A Bayesian risk analysis was used to evaluate the unbiased estimators of the exposure risk profiles, with the regional IAQ assessment results for offices in 1996, 1998—2001, 2004—2005. The results showed that the expected loss of life expectancy due to the life-time exposure to the airborne toxic substance formaldehyde for the air-conditioned offices of Hong Kong decreased from 0.45 day to 0.22 day, probably due to the implementation of the IAQ policy. The study is a useful reference for controlling the life-time exposure of formaldehyde in air-conditioned offices.
Prevalence of Plastic Additives in Indoor Air related to Newly Diagnosed Asthma
Authors: Villberg K. , Mussalo-Rauhamaa H. , Haahtela T. , Saarela K.
Published: September 2008

This paper presents a correlation between the certain plastic additives and newly diagnosed asthma. We studied this association by measuring the plastic additives in the indoor air of the homes of presenting patients at the Skin and Allergy hospitals, including old and new, clinically diagnosed cases of asthma and controls. A total of 465 people filled in a questionnaire that probed, for example, health complaints, illnesses, and perceived conditions of their home environment. Asthma was diagnosed in 19 patients, and had earlier been found in 31 people. Compounds commonly used in plastic flooring manufacture were found to be more prevalent and in higher concentrations in the homes of subjects having newly diagnosed asthma. When the indoor air concentration of one plastic additive (2,2,4-trimethyl-1, 3-pentanediol di-isobutyrate) was 10 μg/m 3 or greater (in Toluene equivalent), the age and sex adjusted odds ratio of having new asthma was 2.844, 95% CI 1.035—7.813.
Survey of Airborne Bacterial Genus at a University Campus
Authors: Chan Daniel W.T. , Leung Polly H.M. , Tam Cinnie S.Y. , Jones A.P.
Published: September 2008

Indoor airborne bacterial concentrations were measured at different locations in a university campus in Hong Kong where there was a Mechanical Ventilation and Air-conditioning (MVAC) system. Total bacterial counts were enumerated for both indoor and outdoor areas at specific time intervals. Information on temperature, relative humidity, number of occupants, and carbon dioxide levels were recorded simultaneously. Those parameters were correlated with total bacterial counts and each identifiable genus. Although, the number of genera for Gram-negative bacteria was higher than Gram-positive bacteria, the most abundant airborne genera found were Gram-positive bacteria especially Micrococcus and Staphylococcus. The indoor-to-outdoor ratios for the two predominant Gram-positive genera were greater than one, indicating that the source of the bacteria was indoors. There was a correlation between total bacterial counts with temperature, but the correlation was not significant. Pseudomonas had a correlation with relative humidity, but the correlation was not significant. The study also found that the total bacterial counts and a few genera including Staphylococcus and Pseudomonas, had a strong correlation with ventilation.
Social Work and Spirituality in a Secular Society
Authors: Crisp Beth R.
Published: September 2008

• Summary: In an increasingly secular era which finds only a small minority of the population regularly participating in organized religion, there is emerging interest in how spirituality can be incorporated into social work practice. This article proposes one way in which this might occur in `deliberately secular' nations such as Australia.

• Findings: A framework in which spirituality is considered to be an aspect of lived experience is proposed. Dimensions of life which can be incorporated into such a framework include life rituals, creativity, social action, and sense of place.

• Applications : Conceptualizing spirituality in a way which does not use specifically religious language or concepts, may enable discussion of spiritual issues to be incorporated into social work practice when either practitioners or service users have or no religious background or affiliation or no shared religious background.
African Social Services in Peril
Authors: Laird Siobhan E.
Published: September 2008

• Summary: Using Ghana as an illustrative case study, this article examines the ideology and intentions which underpin the Poverty Reduction Strategy Paper required for approval by the IMF and World Bank to qualify for debt relief under the Highly Indebted Poor Countries initiative. This article critically examines the functions assigned to governmental and non-governmental agencies within the social sector generally and the Department of Social Welfare specifically. Conditions at the Department of Social Welfare are explored through data gathered from semi-structured interviews with frontline social workers. These document the day-to-day realities of social work practice in Ghana and the relationship of the Department of Social Welfare with the non-governmental sector in the delivery of welfare services.

• Findings: Social workers at the Department of Social Welfare report chronic under-funding which undermines even the most rudimentary activities. They also describe difficulties in holding NGOs to account due to the lack of logistical support and the inability to enforce compliance with statutory requirements.

• Applications : Across the sub-Saharan region are government departments responsible for the delivery of social services and operating within the social policy frameworks created by the Poverty Reduction Strategy Papers required for debt relief. Evidence produced by this case study has implications for similar sub-Saharan countries implementing a social policy based on the neoliberal precepts if the New Policy Agenda.
Emerging Practices in Leadership Development
Authors: Ardichvili Alexandre , Manderscheid Steven V.
Published: September 2008

The problem and the solution .This article reviews recent novel contributions to leadership development theory and practice. It provides definitions and a brief overview of leadership and leadership development, and a summary of a number of seminal and contemporary leadership theories that serve as a foundation for leadership development practice today. In addition, the article discusses emerging new directions and approaches in leadership development. Last, this introduction provides a brief overview of each of the articles in this issue of emerging practices in leadership development.
Using Multisource Feedback to Develop Leaders: Applying Theory and Research to Improve Practice
Authors: Hezlett Sarah A.
Published: September 2008

The problem and the solution . Empirical research suggests that, on average, the changes made by leaders after receiving multisource feedback (MSF) are positive, but fairly small. Four sets of explanations for these results are analyzed in this article: potential limitations in the design of previous studies on MSF, the psychometric characteristics of MSF instruments, flaws in implementing MSF systems, and theory-based explanations of development following receipt of feedback. Models of development, feedback, and MSF suggest that it is unrealistic to expect MSF to lead to development for all leaders. Implications for practice and research are discussed. MSF can help many leaders develop, but only when associated development programs are correctly designed and implemented.
The Developmental Relationships of Women Leaders in Career Transition: Implications for Leader Development
Authors: Gibson Sharon K.
Published: September 2008

The problem and the solution. Developmental relationships are distinct in that they serve as a source of leader development that spans organizational boundaries. These relationships are potentially more critical for women leaders due to their limited access to informal networks in the organizational context.This article explores the alignment between the essential attributes that emerged from women leaders' descriptions of their developmental relationships during career transition and the functions of developmental relationships identified as important for leader development. The analysis indicated that developmental relationships provide similar functions for women leaders during career transition as they do for leader development, supporting the notion that developmental relationships during career transition serve as an ongoing vehicle for leader development. However, three predominantly intraorganizational leader development functions were not consistently evident in these women's descriptions. Additionally, there was increased emphasis on the support element of developmental relationships during career transition. Implications for HRD practice and research are proposed.
Avoiding verification bias in screening test evaluation in resource poor settings: a case study from Zimbabwe
Authors: Gaffikin Lynne , McGrath John , Arbyn Marc , Blumenthal Paul D
Published: September 2008

Background Verification bias occurs when the percentage of subjects receiving disease verification differs according to the test result. Statistical adjustment yields unbiased sensitivity and specificity under a missing at random (MAR) assumption.

Purpose To use an example from an international study to show how the assumptions needed for unbiased statistical adjustment for verification bias can be undermined by conditions on the ground, and that accuracy of estimates is also compromised by too low a sampling fraction of subjects who test negative.

Methods A study in Zimbabwe assessed the accuracy of a screening test for cervical cancer screening, visual inspection with acetic acid (VIA). The study was conducted in two phases, Phase I, where only 10% of subjects with negative tests received verification, and Phase II, in which nearly all subjects were verified. Unadjusted, simple- and covariate-adjusted estimates were compared to investigate factors affecting differences. Bootstrap simulations were used to illustrate the effect of varying test negative sampling fractions.

Results Phase I unadjusted sensitivity and specificity were 0.66 (0.61—0.70) and 0.34 (0.31—0.36), respectively. Simple-weighted adjusted estimators accounting only for VIA status were 0.20 (0.17—0.23) and 0.80 (0.78—0.81), respectively, suggesting the test to be useless. It was found that verification (colposcopy) capacity in-country had been exceeded, and that random selection of test negative patients for colposcopy had been compromised. Phase II estimates of sensitivity and specificity were 0.77 and 0.64, respectively. With 9% disease prevalence, a VIA test-negative sampling fraction >50% was necessary for the confidence intervals for sensitivity to have more than a 90% probability of including the true value. Limitations Phase I statistical adjustment was not made for MAR deviations unexplained by the two auxiliary factors, Pap results and STD history. Adjustment was not possible for other unmeasured co-factors.

Conclusions While there are standard formulae for correcting for verification bias, these will be biased if the MAR assumption is not met, which can occur through the actions of study personnel or subjects. Design of such studies in low resource environments needs to either require 100% verification, or employ procedures ensuring that the sample of test negatives who receive verification is indeed random. In addition, required test negative sampling fractions need to incorporate information on both disease prevalence and overall sample size. Clinical Trials 2008; 5: 496—503. http://ctj.sagepub.com
Recruitment of a racially and ethnically diverse sample into a physical activity efficacy trial
Authors: Frierson Georita M , Williams David M , Dunsiger Shira , Lewis Beth A , Whiteley Jessica A , Albrecht Anna E , Jakicic John M , Horowitz Santina M , Marcus Bess H
Published: September 2008

Background Healthy People 2010 underscores the relevance of eliminating health disparities. Thus, it is paramount to create interventions that promote health for all individuals.

Purpose This study examined differences in rates of and reasons for ineligibility among non-Hispanic blacks and whites in a randomized controlled physical activity intervention study.

Methods Participants (1245 adults) responded to community advertising for the research study. Eligibility at the four pre-randomization assessment sessions was determined by self-reported medical information, resting EKG, 7-Day Physical Activity Recall, fitness test and Stage of Change. We used t-tests to examine the rates of eligibility among participant subgroups.

Results Blacks had higher rates of overall ineligibility (86.9%) than whites (75.1%; p < 0.01) and were more likely to be ineligible due to lack of interest or no-show at a pre-randomization appointment (35.4% vs. 24.3%; p < 0.01). Blacks were more likely to be ineligible for medical reasons after the telephone screen (16.3% vs. 7.8%; p = 0.01).

Limitations This study did not use a random sampling of potential participants from each of the racial/ethnic groups and thus, there is the potential for selection bias.

Conclusions Blacks were more likely to choose not to enroll in the study due to a lack of interest, but had similar rates of overall medical ineligibility to whites. This highlights the importance of strategies that enhance interest among blacks, who initially respond to recruitment advertising. Clinical Trials 2008; 5: 504—516. http://ctj.sagepub.com
Design considerations and rationale of a multi-center trial to sustain weight loss: the weight loss maintenance trial
Authors: Brantley Phillip , Appel Lawrence , Hollis Jack , Stevens Victor , Ard Jamy , Champagne Catherine , Elmer Patricia , Harsha David , Myers Valerie , Proschan Michael , William Vollmer , Svetkey Laura
Published: September 2008

Background The Weight Loss Maintenance Trial (WLM) is a multi-center, randomized, controlled trial that compares the effects of two 30-month maintenance interventions, i.e., Personal Contact (PC) and Interactive Technology (IT) to a self-directed usual care control group (SD), in overweight or obese individuals who are at high risk for cardiovascular disease.

Purpose This paper provides an overview of the design and methods, and design considerations and lessons learned from this trial.

Methods All participants received a 6-month behavioral weight loss program consisting of weekly group sessions. Participants who lost 4 kg were randomized to one of three conditions (PC, IT, or SD). The PC condition provided monthly contacts with an interventionist primarily via telephone and quarterly face-to-face visits. The IT condition provided frequent, individualized contact through a tailored, website system. Both the PC and IT maintenance programs encouraged the DASH dietary pattern and employed theory-based behavioral techniques to promote maintenance.

Results Design considerations included choice of study population, frequency and type of intervention visits, and choice of primary outcome. Overweight or obese persons with CVD risk factors were studied. The pros and cons of studying this population while excluding others are presented. We studied intervention contact strategies that made fewer demands on participant time and travel, while providing frequent opportunities for interaction. The primary outcome variable for the trial was change in weight from randomization to end of follow-up (30 months). Limitations Limits to generalizability are discussed. Individuals in need of weight loss strategies may have been excluded due to barriers associated with internet use. Other participants may have been excluded secondary to a comorbid condition.

Conclusions This paper highlights the design and methods of WLM and informs readers of discussions of critical issues and lessons learned from the trial. Clinical Trials 2008; 5: 546—556. http://ctj.sagepub.com
Chitosan membrane in separation applications
Authors: Xu D. , Hein S. , Wang K.
Published: September 2008

Membrane separation technology, owing to its low energy consumption, operational simplicity, ease of control and scale-up, has gained increasing interest. The rapid development requires highly selective membranes with high through rates and chemical/mechanical stability. Chitosan, a relatively inert biomaterial with film forming ability, has been rapidly recognised for its potential in separation and purification technology in recent decades. Because of its hydrophilicity, cationicity, biocompatibility, ease of modification, remarkable affinity to dyes, metals and proteins, chitosan membranes have become a promising candidate for several applications. In the present review, the pervaporation of azeotropic mixtures and protein purification and separation of gaseous mixtures using chitosan membranes are discussed. The general overview of the preparation of different chitosan membranes, its capabilities in the separation of various solvents, gases and biomacromolecules are presented. Finally, the opportunities, challenges and perspectives in these areas are discussed.
Review of stent coating strategies: Clinical insights
Authors: Sydow-Plum G. , Tabrizian M.
Published: September 2008

Despite advances in stent design, expansion techniques and anti-thrombotic agents to improve pharmacological control of subacute thrombosis (SAT) and to reduce to 2 the occlusive thrombosis rates, a significant risk of mortality associated with thrombotic vascular occlusion due to the adhesion of blood constituents remains a problem for patients with more complex lesions. The adhesion process is greatly governed by the surface characteristics, mainly the surface chemical composition, surface morphology, presence of charge, surface wettability and surface roughness. Surface chemical inertness (reduced interaction with chemicals and biological components) subsequently became the primary criteria which guided the development of non thrombotic stents as well as other blood-contacting materials. A number of strategies have been adopted in an effort to coat the stent with or without the use of a drug delivery system, to overcome the thrombus formation, to minimize the stent occlusion and to improve the overall hemocompatibility of the device. This paper aims at reviewing the clinical outcomes of main non-pharmaceutical stent coating procedures and their clinical outcomes. New stents which combine the anti-thrombotic coating with the drug delivery ability, such as radioactive stents, degradable stents and some new challenging trends which are mostly at research and development stage for stent surface coatings are also introduced.
Review of laser based biomimetic and bioactive Ca–P coatings
Authors: Paital S. R. , Dahotre N. B.
Published: September 2008

Human bone is typically a hierarchical organisation at different length scales ranging from nanoscale to mesoscale. Synthetic biomaterials mimicking this structural aspect of the bone and thereby facilitating structure and function of damaged or dysfunctional tissues is the current trend in designing of biomaterials. Under such trend artificial biomaterials with biocompatible surface coatings and engineered three-dimensional features ranging from nanoscale to mesosclae to support cells and tissue growth is becoming a reality. In light of this, the present review provides a description of laser induced coating techniques, one of several methods of design and synthesis of biosurfaces. Especially, the laser induced coating technique to produce a bioactive and biomimetic calcium phosphate (Ca–P) based ceramic coating on Ti based alloys is the focus of present discussion. The two common coating methodologies namely, the pulsed laser deposition and direct melting using a pulsed and continuous wave laser are the subject of discussion. The formation of multiscale features, microstructures and phase evolution due to such coatings are discussed. Finally, the concept of laser based interference patterning as a future tool to explore these kinds of coatings is highlighted. Attempts are also made to demonstrate the effectiveness of these coatings in bioenvironment.
Molecular biology of bcr-abl1–positive chronic myeloid leukemia
Authors: Quintás-Cardama Alfonso , Cortes Jorge
Published: September 2008

Chronic myeloid leukemia (CML) has been regarded as the paradigmatic example of a malignancy defined by a unique molecular event, the BCR-ABL1 oncogene. Decades of research zeroing in on the role of BCR-ABL1 kinase in the pathogenesis of CML have culminated in the development of highly efficacious therapeutics that, like imatinib mesylate, target the oncogenic kinase activity of BCR-ABL1. In recent years, most research efforts in CML have been devoted to developing novel tyrosine kinase inhibitors (TKIs) as well as to elucidating the mechanisms of resistance to imatinib and other TKIs. Nonetheless, primordial aspects of the pathogenesis of CML, such as the mechanisms responsible for the transition from chronic phase to blast crisis, the causes of genomic instability and faulty DNA repair, the phenomenon of stem cell quiescence, the role of tumor suppressors in TKI resistance and CML progression, or the cross-talk between BCR-ABL1 and other oncogenic signaling pathways, still remain poorly understood. Herein, we synthesize the most relevant and current knowledge on such areas of the pathogenesis of CML.
Elevated growth differentiation factor 15 expression in patients with congenital dyserythropoietic anemia type I
Authors: Tamary Hannah , Shalev Hanna , Perez-Avraham Galit , Zoldan Meira , Levi Itai , Swinkels Dorine W. , Tanno Toshihiko , Miller Jeffery L.
Published: September 2008

Congenital dyserythropoietic anemia (CDA) is a rare group of red blood cell disorders characterized by ineffective erythropoiesis and increased iron absorption. To determine whether growth differentation factor 15 (GDF15) hyper-expression is associated with the ineffective erythropoiesis and iron-loading complications of CDA type I (CDA I), GDF15 levels and other markers of erythropoiesis and iron overload were studied in blood from 17 CDA I patients. Significantly higher levels of GDF15 were detected among the CDA I patients (10 239 ± 3049 pg/mL) compared with healthy volunteers (269 ± 238 pg/mL). In addition, GDF15 correlated significantly with several erythropoietic and iron parameters including Hepcidin-25, Ferritin, and Hepcidin-25/Ferritin ratios. These novel results suggest that CDA I patients express very high levels of serum GDF15, and that GDF15 contributes to the inappropriate suppression of hepcidin with subsequent secondary hemochromatosis.
A dichotomy in bronchiolitis obliterans syndrome after lung transplantation revealed by azithromycin therapy
Authors: Vanaudenaerde B. M. , Meyts I. , Vos R. , Geudens N. , De Wever W. , Verbeken E. K. , Van Raemdonck D. E. , Dupont L. J. , Verleden G. M.
Published: September 2008

Bronchiolitis obliterans syndrome (BOS) is the most important cause of late mortality following lung transplantation, resulting in major morbidity and a huge burden on healthcare resources. Treatment options are limited, resulting in a mere stabilisation of the lung function decline. Recent introduction of the macrolide antibiotic azithromycin raised new hope after demonstrating lung function improvement in subsets of patients.

The present study aimed to provide an overview of the clinical effects on azithromycin in the setting of BOS after lung transplantation, with special emphasis on the anti-inflammatory actions. Moreover, the authors proposed a new frame of thinking centred on a dichotomy in the pathogenesis and clinical phenotype of BOS. Subsets of BOS patients were identified who do or do not respond to azithromycin (regarding forced expiratory volume in one second (FEV1), bronchoalveolar lavage (BAL) neutrophilia/interleukin-8). These observations have shed new light on the current belief that BOS represents a homogenous clinical entity in which the neutrophil is the main culprit.

Recent clinical observations, supported by research findings, have revealed a dichotomy in the clinical spectrum of BOS with neutrophilic (partially) reversible allograft dysfunction (responding to azithromycin) and fibroproliferative BOS (not responding to azithromycin). This concept is reinforced by unique data obtained in BOS patients, consisting of histology specimens, physical and radiological examination, FEV1and BAL examination.

The acceptance of this dichotomy can improve understanding of the heterogeneous pathological condition that constitutes bronchiolitis obliterans syndrome, thus encouraging a more accurate diagnosis and, ultimately, better tailored treatment for each bronchiolitis obliterans syndrome patient.
Antigen stimulation of peripheral blood mononuclear cells from Mycobacterium bovis infected cattle yields evidence for a novel gene expression program
Authors: Meade Kieran G , Gormley Eamonn , O'Farrelly Cliona , Park Stephen D , Costello Eamon , Keane Joseph , Zhao Yingdong , MacHugh David E
Published: September 2008

Background

Bovine tuberculosis (BTB) caused by Mycobacterium bovis continues to cause substantial losses to global agriculture and has significant repercussions for human health. The advent of high throughput genomics has facilitated large scale gene expression analyses that present a novel opportunity for revealing the molecular mechanisms underlying mycobacterial infection. Using this approach, we have previously shown that innate immune genes in peripheral blood mononuclear cells (PBMC) from BTB-infected animals are repressed in vivo in the absence of exogenous antigen stimulation. In the present study, we hypothesized that the PBMC from BTB-infected cattle would display a distinct gene expression program resulting from exposure to M. bovis. A functional genomics approach was used to examine the immune response of BTB-infected (n = 6) and healthy control (n = 6) cattle to stimulation with bovine tuberculin (purified protein derivative – PPD-b) in vitro. PBMC were harvested before, and at 3 h and 12 h post in vitro stimulation with bovine tuberculin. Gene expression changes were catalogued within each group using a reference hybridization design and a targeted immunospecific cDNA microarray platform (BOTL-5) with 4,800 spot features representing 1,391 genes.

Results

250 gene spot features were significantly differentially expressed in BTB-infected animals at 3 h post-stimulation contrasting with only 88 gene spot features in the non-infected control animals (P ≤ 0.05). At 12 h post-stimulation, 56 and 80 gene spot features were differentially expressed in both groups respectively. The results provided evidence of a proinflammatory gene expression profile in PBMC from BTB-infected animals in response to antigen stimulation. Furthermore, a common panel of eighteen genes, including transcription factors were significantly expressed in opposite directions in both groups. Real-time quantitative reverse transcription PCR (qRT-PCR) demonstrated that many innate immune genes, including components of the TLR pathway and cytokines were differentially expressed in BTB-infected (n = 8) versus control animals (n = 8) after stimulation with bovine tuberculin.

Conclusion

The PBMC from BTB-infected animals exhibit different transcriptional profiles compared with PBMC from healthy control animals in response to M. bovis antigen stimulation, providing evidence of a novel gene expression program due to M. bovis exposure.
CXCR4 expression in papillary thyroid carcinoma: induction by nitric oxide and correlation with lymph node metastasis
Authors: Yasuoka Hironao , Kodama Rieko , Hirokawa Mitsuyoshi , Takamura Yuuki , Miyauchi Akira , Sanke Tokio , Nakamura Yasushi
Published: September 2008

Background

Metastasis to regional lymph nodes is a common step in the progression of cancer. Recent evidence suggests that tumor production of CXCR4 promotes lymph node metastasis. Nitric oxide (NO) may also increase metastatic ability in human cancers.

Methods

Nitrite/nitrate levels and functional CXCR4 expression were assessed in K1 and B-CPAP papillary thyroid carcinoma (PTC) cells after induction and/or inhibition of NO synthesis. CXCR4 expression was also analyzed in primary human PTC. The relationship between nitrotyrosine levels, which are a biomarker for peroxynitrate formation from NO in vivo, CXCR4 expression, and lymph node status was also analyzed.

Results

Production of nitrite/nitrate and functional CXCR4 expression in both cell lines was increased by treatment with the NO donor DETA NONOate. The NOS inhibitor L-NAME eliminated this increase. Positive CXCR4 immunostaining was observed in 60.7% (34/56) of PTCs. CXCR4 expression was significantly correlated with nitrotyrosine levels and lymph node metastasis in human PTC.

Conclusion

Our data indicate that NO stimulates CXCR4 expression in vitro. Formation of the NO biomarker nitrotyrosine was also correlated with CXCR4 expression and lymph node metastasis in human PTC. NO may induce lymph node metastasis via CXCR4 induction in papillary thyroid carcinoma.
The relationship between depressive symptoms, health service consumption, and prognosis after acute myocardial infarction: a prospective cohort study
Authors: Kurdyak Paul A , Gnam William H , Goering Paula , Chong Alice , Alter David A
Published: September 2008

Background

The use of cardiovascular health services is greater among patients with depressive symptoms than among patients without. However, the extent to which such associations between depressive symptoms and health service utilization are attributable to variations in comorbidity and prognostic disease severity is unknown. This paper explores the relationship between depressive symptoms, health service cardiovascular consumption, and prognosis following acute myocardial infarction (AMI).

Methods

The study design was a prospective cohort study with follow-up telephone interviews of 1,941 patients 30 days following AMI discharged from 53 hospitals across Ontario, Canada between December 1999 and February, 2003. Outcome measures were post discharge use of cardiac and non-cardiac health care services. The service utilization outcomes were adjusted for age, sex, income, comorbidity, two validated measures of prognosis (cardiac functional capacity and risk adjustment severity index), cardiac procedures (CABG or PTCA) and drugs prescribed at discharge.

Results

Depressive symptoms were associated with a 24% (Adjusted RR:1.24; 95% CI:1.19–1.30, P < 0.001), 9% (Adjusted RR:1.09; 95% CI:1.02–1.16, P = 0.007) and 43% (Adjusted RR: 1.43; 95% CI:1.34–1.52, P < 0.001) increase in total, cardiac, and non-cardiac hospitalization days post-AMI respectively, after adjusting for baseline patient and hospital characteristics. Depressive-associated increases in cardiac health service consumption were significantly more pronounced among patients of lower than higher cardiac risk severity. Depressive symptoms were not associated with increased mortality after adjusting for baseline patient characteristics.

Conclusion

Depressive symptoms are associated with significantly higher cardiac and non-cardiac health service consumption following AMI despite adjustments for comorbidity and prognostic severity. The disproportionately higher cardiac health service consumption among lower-risk AMI depressive patients may suggest that health seeking behaviors are mediated by psychosocial factors more so than by objective measures of cardiovascular risk or necessity.
A genome-wide association study for late-onset Alzheimer's disease using DNA pooling
Authors: Abraham Richard , Moskvina Valentina , Sims Rebecca , Hollingworth Paul , Morgan Angharad , Georgieva Lyudmila , Dowzell Kimberley , Cichon Sven , Hillmer Axel M , O'Donovan Michael C , Williams Julie , Owen Michael J , Kirov George
Published: September 2008

Background

Late-onset Alzheimer's disease (LOAD) is an age related neurodegenerative disease with a high prevalence that places major demands on healthcare resources in societies with increasingly aged populations. The only extensively replicable genetic risk factor for LOAD is the apolipoprotein E gene. In order to identify additional genetic risk loci we have conducted a genome-wide association (GWA) study in a large LOAD case – control sample, reducing costs through the use of DNA pooling.

Methods

DNA samples were collected from 1,082 individuals with LOAD and 1,239 control subjects. Age at onset ranged from 60 to 95 and Controls were matched for age (mean = 76.53 years, SD = 33), gender and ethnicity. Equimolar amounts of each DNA sample were added to either a case or control pool. The pools were genotyped using Illumina HumanHap300 and Illumina Sentrix HumanHap240S arrays testing 561,494 SNPs. 114 of our best hit SNPs from the pooling data were identified and then individually genotyped in the case – control sample used to construct the pools.

Results

Highly significant association with LOAD was observed at the APOE locus confirming the validity of the pooled genotyping approach.

For 109 SNPs outside the APOE locus, we obtained uncorrected p-values ≤ 0.05 for 74 after individual genotyping. To further test these associations, we added control data from 1400 subjects from the 1958 Birth Cohort with the evidence for association increasing to 3.4 × 10-6 for our strongest finding, rs727153.

rs727153 lies 13 kb from the start of transcription of lecithin retinol acyltransferase (phosphatidylcholine – retinol O-acyltransferase, LRAT). Five of seven tag SNPs chosen to cover LRAT showed significant association with LOAD with a SNP in intron 2 of LRAT, showing greatest evidence of association (rs201825, p-value = 6.1 × 10-7).

Conclusion

We have validated the pooling method for GWA studies by both identifying the APOE locus and by observing a strong enrichment for significantly associated SNPs. We provide evidence for LRAT as a novel candidate gene for LOAD. LRAT plays a prominent role in the Vitamin A cascade, a system that has been previously implicated in LOAD.
Induction- and conditioning-protocol dependent involvement of NR2B-containing NMDA receptors in synaptic potentiation and contextual fear memory in the hippocampal CA1 region of rats
Authors: Zhang Xue-Han , Wu Long-Jun , Gong Bo , Ren Ming , Li Bao-Ming , Zhuo Min
Published: September 2008

Long-term potentiation (LTP) in the hippocampal CA1 region requires the activation of N-methyl-D-aspartate receptors (NMDARs). Studies using genetic and pharmacological approaches have reported inconsistent results of the requirement of NR2B-containing NMDARs in LTP in the CA1 region. Pharmacological studies showed that NR2B-containing NMDARs are not required for LTP, while genetic studies reported that over-expression of NR2B-NMDARs enhances LTP and hippocampus-dependent memory. Here, we provide evidence showing that the functional role of NR2B-NMDARs in hippocampal LTP and memory depends on LTP-inducing and behavior-conditioning protocols. Inhibition of NR2B-NMDARs with the NR2B selective antagonist ifenprodil or Ro25-6981 suppressed LTP induced by spike-timing protocol, with no impact on LTP induced by pairing protocol or two-train high-frequency stimulation (HFS) protocol. Inhibition of NR2B-NMDARs did not affect the late phase LTP induced by four-train HFS. Ca2+imaging showed that there was difference in kinetics of intracellular Ca2+signals induced by spiking-timing and pairing protocols. Pre-training intra-CA1 infusion of ifenprodil or Ro25-6981 impaired the contextual fear memory induced by five CS-US pairings, with no effect on the memory induced by one CS-US pairing.
Association of thyroid function with arterial pressure in normotensive and hypertensive euthyroid individuals: A cross-sectional study
Authors: Saltiki Katerina , Voidonikola Paraskevi , Stamatelopoulos Kimon , Mantzou Emily , Papamichael Christos , Alevizaki Maria
Published: September 2008

Background

Overt hypothyroidism has been associated with arterial hypertension and increased arterial stiffness. Results in euthyroid individuals have been conflicting. We investigated associations of thyroid function with systolic (SAP) and diastolic (DAP) arterial pressure in euthyroid subjects.

Methods

311 euthyroid individuals (185 women, mean age 43.9 ± 9) without a history of diabetes attending a preventive medicine program were examined. Subjects receiving thyroxine (10.6%) were excluded; 19.3% had hypertension, 43% had a family history for hypertension. TSH, fT4, thyroid autoantibodies, insulin, glucose were measured. The "fT4.TSH product", which has been suggested as a T4 resistance-index, was calculated.

Results

TSH range was 0.1–8, median 1.4 mU/L, fT4 range was 11.5–25.2 pmol/L, median 17.4. TSH and the "fT4.TSH product" were positively associated with DAP (p < 0.03, for both associations). In the subgroup of individuals with TSH levels 0.36–2.5 mU/L, both TSH and the "fT4.TSH product" were positively correlated with SAP (r = +0.133 p = 0.044, r = +0.152 p = 0.026) and DAP (r = +0.243 p < 0.001, r = +0.252 p < 0.001 respectively); in multivariate analysis the "fT4.TSH product" was a significant predictor of DAP independently of HOMA-IR and BMI (p < 0.001). Similar associations were found when only the non-hypertensive subjects were analysed (p = 0.004). Hypertensive patients had higher TSH levels (p = 0.02) and belonged more frequently to the subgroup with TSH > 2 mU/L (35.3% vs 21.3%, p = 0.045).

Conclusion

In euthyroid individuals the association of thyroid function with diastolic arterial pressure remains significant even when a stricter "normal range" for TSH levels is considered. The "freeT4.TSH" product appears to be an even stronger predictor of DAP, independently of HOMA insulin resistance index and obesity.
Presentation and course of brain metastases from breast cancer in a paranoid-schizophrenic patient: A case report
Authors: Dalhaug Astrid , Pawinski Adam , Norum Jan , Nieder Carsten
Published: September 2008

Case presentation

This is an unusual case where a 49-year old female patient with known schizophrenia, paranoid type and a history of early-stage breast cancer, which was treated more than 6 years earlier, attempted suicide. Computed tomography and magnetic resonance imaging after this incident revealed the presence of multiple brain metastases as the first symptomatic site of recurrent cancer. Further staging lead to the diagnosis of lung, hilar and mediastinal lymph node metastases and histology confirmed estrogen receptor-positive metastatic cancer. Treatment consisted of whole-brain radiotherapy and letrozole. Twenty-one months later, the patient is in continued partial remission.
Psychiatric outcomes 10 years after treatment with antidepressants or anxiolytics
Authors: Colman Ian , Croudace Tim J. , Wadsworth Michael E. J. , Kuh Diana , Jones Peter B.
Published: September 2008

Background

Antidepressants and anxiolytics have demonstrated short-term efficacy; however, little is known about the long-term effectiveness of these drugs.

Aims

To investigate long-term psychiatric outcomes following antidepressant and/or anxiolytic use during an episode of mental disorder in mid-life.

Method

Members of the 1946 British birth cohort were assessed for symptoms of depression and anxiety at age 43. Among 157 with mental disorder, those using antidepressants and/or anxiolytics were compared with those not using medications on psychiatric outcomes at age 53.

Results

Use of antidepressants or anxiolytics was associated with a lower prevalence of mental disorder at age 53 (odds ratio (OR)=0.3, 95% CI 0.1–1.0) after adjustment for eight variables in a propensity-for-treatment analysis. Only 24% of those being treated with medications at age 43 were still using them at 53.

Conclusions

Use of antidepressants or anxiolytics during an episode of mental disorder may have long-term beneficial effects on mental health. This may be because of a demonstrated willingness to seek help rather than long-term maintenance therapy.
Extrapyramidal side-effects of antipsychotics in a randomised
trial
Authors: Miller Del D. , Caroff Stanley N. , Davis Sonia M. , Rosenheck Robert A. , McEvoy Joseph P. , Saltz Bruce L. , Riggio Silvana , Chakos Miranda H. , Swartz Marvin S. , Keefe Richard S.E. , Stroup T. Scott , Lieberman Jeffrey A. ,   for the Clinical Antipsychotic Trials of Intervention Effectiveness
                           (CATIE) Investigators
Published: September 2008

Background

There are claims that second-generation antipsychotics produce fewer
extrapyramidal side-effects (EPS) compared with first-generation
drugs.

Aims

To compare the incidence of treatment-emergent EPS between
second-generation antipsychotics and perphenazine in people with
schizophrenia.

Method

Incidence analyses integrated data from standardised rating scales and
documented use of concomitant medication or treatment discontinuation for
EPS events. Mixed model analyses of change in rating scales from baseline
were also conducted.

Results

There were no significant differences in incidence or change in rating
scales for parkinsonism, dystonia, akathisia or tardive dyskinesia when
comparing second-generation antipsychotics with perphenazine or comparing
between second-generation antipsychotics. Secondary analyses revealed
greater rates of concomitant antiparkinsonism medication among
individuals on risperidone and lower rates among individuals on
quetiapine, and lower rates of discontinuation because of parkinsonism
among people on quetiapine and ziprasidone. There was a trend for a
greater likelihood of concomitant medication for akathisia among
individuals on risperidone and perphenazine.

Conclusions

The incidence of treatment-emergent EPS and change in EPS ratings
indicated that there are no significant differences between
second-generation antipsychotics and perphenazine or between
second-generation antipsychotics in people with schizophrenia.