bluuebunny/crossref_metadata_2025 huggingface dataset:
Using program evaluation to inform and improve the education of young English language learners in US schools
Authors: Llosa Lorena , Slayton Julie
Published: January 2009

The purpose of this paper is to discuss how program evaluation can be conducted and communicated in ways that meaningfully affect the education of English language learners (ELLs) in US schools. First, the paper describes the Waterford Early Reading Program Evaluation, a large-scale evaluation of a reading intervention implemented in schools with substantial populations of ELLs in a large urban school district in California. Second, using the Waterford evaluation as an example, this paper discusses the conditions necessary for conducting an evaluation that yields useful information about a program's implementation and effectiveness. The paper also highlights the importance of communicating those findings in a clear way so as to be meaningful to stakeholders and decision-makers in order to facilitate the goal of improving the education of young ELLs.
Late-stage refocusing of Irish-language programme evaluation: Maximizing the potential for productive debate and remediation
Authors: Harris John
Published: January 2009

The teaching and learning of Irish in primary school is both an important educational issue and central to the national language revitalization effort. The findings of Irish-language programme evaluations, therefore, are invariably scrutinized very closely by different sectors. This paper examines how the later stages of a major evaluation took account of challenging initial findings and anticipated likely misinterpretations of their implications. It documents how additional analyses, interpretative work, and careful reporting were used to provide a rich contextualization of the findings. In this way, the potential of the evaluation to generate productive debate and effective remedial action was maximized. The paper concludes with recommendations for how language program evaluators can guide the evaluation process in order to maximize contributions to critical decisions on language policy and educational practice.
Evaluation of teacher induction practices in a US university English language program: Towards useful evaluation
Authors: WeiWei Yang
Published: January 2009

This article reports on a formative and internal evaluation of teacher induction practices for newly hired teachers in a US university ESL program. By adopting a utilization-focused approach, evaluators produced a design that was articulated to the information needs of the evaluation users. The ensuing findings were then used to develop and improve program practices in specific and high-priority ways. This paper calls for attention to ways of enhancing the utility of evaluations within language education programs — and thereby enhancing the value of what language educators do — and it illustrates how a utilization-focused approach can help to ensure the actual uses and the utility of evaluation practices.
Becoming a teacher of English in Thailand
Authors: Hayes David
Published: January 2009

This paper explores the motivation and circumstances of a group of Thai teachers in government schools which influenced their becoming teachers of English. Through data derived from in-depth interviewing it seeks to privilege the perceptions of the informants and thus illuminate features of teachers' experience of their educational systems, in this particular case how they entered the teaching profession. The paper contends that the reasons why individuals who are non-native speakers decide to teach English as a foreign language has been little studied in the TESOL professional discourse, but that such research is crucial for any educational discipline, given that initial motivation and personal circumstances may have a significant impact upon future classroom practices and long-term commitment to teaching. The findings here suggest that individuals may choose to become members of their state teaching systems first and foremost and that their choice of subject to teach is a secondary consideration, simply arising from their own school performance in and aptitude for that particular subject.
The challenges of researching language teachers: What research manuals don't tell us
Authors: Hobbs Valerie , Kubanyiova Magdalena
Published: January 2009

Researching language teachers requires intensive involvement of both the researcher and the researched. Yet, the available methodological literature in the field often paints a blurred picture of the nature of such involvement and provides little advice on dealing with challenges inherent in this type of research. Our doctoral research projects aimed at exploring the impact of two different types of training courses on language teachers' beliefs and practices in two markedly different contexts: pre-service native-speaking ESL teachers in England and in-service non-native-speaking EFL teachers in Slovakia. And while almost all of the specific parameters of the two projects differed, the actual difficulties we experienced were strikingly similar. This paper therefore aims to extend the existing discussion of the problematics of conducting classroom-based research in the field of applied linguistics (e.g. Pica, 2005; Rossiter, 2001; Schachter & Gass, 1996; Spada, 2005) by discussing specific challenges of engaging busy language teachers in one's research, sustaining their commitment throughout the project and handling the physical and emotional strain of the researcher. By offering a set of solutions for each of these issues we hope to enable and encourage potential language teacher education researchers to embark on this demanding but immensely rewarding endeavour.
Exceptional bilingualism
Authors: Francis Norbert
Published: January 2009

New proposals for rethinking the concept of modularity have prompted researchers to increasingly consider the findings from outside their respective fields. A recent discussion by Marcus (2006) calls for such a multidisciplinary reflection. This paper reviews recent research from the field of bilingualism with a special focus on exceptional circumstances of learning and acquisition (deafness, language impairment, and literacy disorder). Findings from this work bear directly on the new approach to modularity that is being proposed. Both exceptionality and bilingualism allow for perspectives on cognitive architecture that may reveal how its components are structured and how they interact in a way that is not as easy to assess in typical language ability and monolingualism. The critical issues appear to be separability (autonomy) of neurophysiological systems, and whether or not cognitive structures are subserved by domain-specific or domain-general substrates. Resolving these questions will have important implications for the remediation of developmental disorders in language and literacy, and for a better understanding of the development of sign language and spoken language-based systems in deaf children.
Perceptions of Trained Leaders on Improving the Public Health Impact of Three Arthritis Foundation Programs
Authors: Brittain Danielle R. , Gyurcsik Nancy C.
Published: January 2009

The Arthritis Foundation (AF) offers effective community-based programs to help manage arthritis, including aquatic, exercise, and self-help programs. Trained leaders can facilitate the adoption, maintenance, and reach of these programs and thus the impact on public health. This study identifies reasons for becoming AF aquatic, exercise, and/or self-help program leaders, AF program reach, and adoption and maintenance challenges encountered by individuals after being trained. Researchers interviewed by telephone 72 participants who attended an AF leader training workshop. Participants reported various reasons for becoming program leaders (e.g., a wish to help others). AF programs were mainly adopted and maintained in urban communities and in fitness/ health clubs, medical centers, or senior centers. Aquatics programs were the most frequently offered, and all programs had low reach (with a mean number of participants of 14.41, 12.50, and 11.00 for aquatic programs, exercise programs, and self-help programs, respectively. Challenges to adopting and maintaining programs include the time of year (e.g., winter, holidays) and lack of a facility to offer the program.
Developing Methods to Compare Low-Education Community-Based and University-Based Survey Teams
Authors: Brugge Doug , Kapunan Patricia , Babcock-Dunning Lauren , Greenfield Matloff Robyn , Cagua-Koo Daniel , Okoroh Ekwutosi , Salas Fatima L. , Bradeen Laura , Woodin Mark
Published: January 2009

We compared the quality of low-education community-based survey teams to college educated graduate students. Our approach was to develop methods, conduct a pilot survey, and report lessons. Community and university teams conducted surveys from non-overlapping random samples of addresses at a public housing development in Boston, Massachusetts. The two types of teams make a similar number of attempts (122 and 124, respectively), and there was no statistically significant difference between the teams in terms of response rate or amount of missing data. Similarly, there was no statistically significant difference in refusal rate or in responses to questions in the survey. There was, however, evidence that the community teams used data tracking forms improperly. This study suggests that it is possible to study the relative quality of community and university-based teams in terms of data collection. The findings also suggest that the two types of teams may be roughly comparable.
Phonological Awareness and Word Recognition in Reading by Children With Autism
Authors: Smith Gabig Cheryl
Published: January 2009

This research examined phonological awareness (PA) and single word reading in 14 school-age children with autism and 10 age-matched, typically developing (TD) children between 5-7 years. Two measures of PA, an elision task (ELI) and a sound blending task (BLW), were given along with two measures of single word reading, word identification for real words (WID) and phonetic decoding of nonwords (WATTK). Group differences were found for performance on PA tasks but no group differences were found for WID or WATTK. All the children with autism scored within the average range on WID and WATTK, although a statistical bias was noted for WID. No relationship was found between PA and measures of word reading in children with autism. Children with autism have adequate ability in single word reading but below average PA. Word reading does not appear to be related to PA for some of the children with autism
The Impact of Postseason Restructuring on the Competitive Balance and Fan Demand in Major League Baseball
Authors: Young Hoon Lee
Published: January 2009

The author analyzed issues of playoff uncertainty (PU) by examining competitive balance and outcome uncertainty. Specifically, the author (a) developed an alternative measure of PU, (b) analyzed the relationship between PU and postseason structure in Major League Baseball (MLB), and (c) tested the PU of the outcome hypothesis using our PU measure. The results provide empirical evidence that postseason restructurings in 1969 and 1995 enhanced the PU significantly and had positive effects on fan demand for MLB. This implies that the league office can partly control PU by revising the league structure and thus increasing fan demand.
Shirking in Major League Baseball Revisited
Authors: Krautmann Anthony C. , Donley Thomas D.
Published: January 2009

A number of studies in sports economics looked at the shirking problem inherent in long-term contracts. Shirking is inferred if the player's actual performance falls below expected performance in the year following a newly signed long-term contract. In an attempt to shed light on these conflicting conclusions in the literature, we outline a novel approach for testing opportunistic behavior. We begin by running a standard test of shirking based upon a comparison of the player's expected to realized performance. We then introduce a new approach to analyzing shirking—one which is based on a comparison of a player's expected to realized Marginal Revenue Product. We find that tests for shirking are sensitive to the approach one uses in the analysis. In particular, when testing for opportunistic behavior using performance, we find no evidence of shirking. Yet when we conduct the test based on MRP, our tests suggest that players signing multi-year contracts create less value than they were expected to generate.
Contests, Grand Prizes, and the Hot Hand
Authors: McFall Todd A. , Knoeber Charles R. , Thurman Walter N.
Published: January 2009

Awarding a grand prize to the player who wins most often in a series of contests links the contests together and makes incentives in the current contest depend on past performance. A lucky player who wins early faces relatively stronger economic incentives to exert effort because of his early success. As a consequence, early winners are more likely to keep winning through the middle of the series. That is, a grand prize generates what looks like a hot hand. Indeed, this argument about economic incentives may help to rationalize the inconsistent evidence of a hot hand in sporting events. This article develops this argument and assesses it empirically using data from the Professional Golfers' Association Tour, before and after a grand prize, the season-ending Tour Championship, was introduced.
Determinants of Pay in the NHL
Authors: Vincent Claude , Eastman Byron
Published: January 2009

Using data from the pre-2004-2005 lockout period, we use quantile regression to estimate the earnings function of forwards and defensemen in the National Hockey League (NHL). We find that the explanatory power of Mincer's earnings equation is smaller for low-paid players than for high-paid stars. More importantly, we find significant differences in the returns to measures of performance and other variables across the conditional earnings distribution. Our estimation results suggest that the conditional expectation model used in previous studies misses some of the subtleties of the earnings determination process in professional hockey.
Pool Revenue Sharing, Team Investments, and Competitive Balance in Professional Sports A Theoretical Analysis
Authors: Chang Yang-Ming , Sanders Shane
Published: January 2009

Using a contest model of a professional sports league, we show that pool revenue sharing has a negative effect on total expenditure for player talent. There are ``moral hazard'' problems with lower revenue teams in that they may pocket the money they receive from the pool without increasing talent investments. Based on four alternative measures of competitive balance, we find that pool revenue sharing increases the variance of expected winning percentages for a match and thus reduces the degree of competition in the league. Policy recommendations that combine pool revenue sharing with the requirement of a minimum payroll on players are shown to be procompetitive.
Quetiapine Effective in Treatment of Inappropriate Sexual Behavior of Lewy Body Disease With Predominant Frontal Lobe Signs
Authors: Prakash Ravi , Pathak Amit , Munda Sanjay , Bagati Dhruv
Published: January 2009

Dementia of Lewy body disease is the second most common degenerative cause of dementia after Alzheimer's disease, among all the dementias. The core features are a progressive dementia, fluctuations in cognitive functions, visual hallucinations, and spontaneous parkinsonism. Rapid eye movement sleep behavior disorder, severe neuroleptic sensitivity, and low dopamine transporter uptake in basal ganglia are other suggestive features. Behavioral abnormalities are commonly present in the form of aggressive behavior, irritability, and disinhibited behaviors. These are mostly seen in the advanced stages of dementia. However, inappropriate sexual behavior is uncommonly seen in such cases. Three types of inappropriate sexual behaviors commonly found in cases of dementia are sex talks, sexual acts, and implied sexual acts. Such inappropriate sexual behaviors have not been described adequately in dementia of Lewy body disease. We report inappropriate sexual behaviors in a case of dementia of Lewy body disease, which improved rapidly after treatment with quetiapine.
Cell Proliferation Induction: Healing Chronic Wounds Through Low-Energy Pulsed Radiofrequency
Authors: Frykberg Robert , Tierney Edward , Tallis Arthur , Klotzbach Tosha
Published: January 2009

Chronic lower extremity wounds are a major source of morbidity and health care expenditure across the world. In the last decade, numerous advanced modalities have become available that can help expedite wound healing when standard wound care modalities are unsuccessful. In this case report, the authors present their early experience with one such modality that uses pulsed radiofrequency energy to initiate cell proliferation induction in chronic lower extremity wounds of different etiologies that had failed to respond to standard therapy.
Prolonged Mechanical Noise Restores Tactile Sense in Diabetic Neuropathic Patients
Authors: Cloutier Rachel , Horr Samuel , Niemi James B. , D'Andrea Susan , Lima Christina , Harry Jason D. , Veves Aristidis
Published: January 2009

Acute application of stochastic resonance (SR), defined as a subsensory level of mechanical noise presented directly to sensory neurons, improves the vibration and tactile perception in diabetic patients with mild to moderate neuropathy. This study examined the effect of 1 hour of continuous SR stimulation on sensory nerve function. Twenty diabetic patients were studied. The effect of stimulation was measured at 2 time points, at the beginning and after 60 minutes of continual SR stimulation. This effect was measured using the vibration perception threshold (VPT) at the big toe under 2 conditions: a null (no SR) condition and active SR, defined as mechanical noise below the subject's own threshold of perception. The measurements under null and active conditions were done randomly and the examiner was blinded regarding the type of condition. Immediately after SR application, the VPT with SR in null condition was similar to baseline (32.2 ± 13.1, P = nonsignificant) but was significantly lower during active SR (27.4 ± 11.9) compared with both baseline ( P = .018) and off position ( P = .045). The 60 minutes VPT with active SR (28.7 ± 11.1) reached significance comparing the baseline when one outlier was removed from the analysis ( P = .031). It may be concluded that SR for a continuous 60-minute period can sustain the VPT improvement in diabetic patients with moderate to severe neuropathy. These results permit the conclusion that there is no short-term adaptation to the stimulation signal. Long-term application of this technique, perhaps in the form of a continually vibrating shoe insert, or insole, may result in sustained improvement of nerve function.
Palmar Fixation of Dorsally Displaced Distal Radius Fractures Using Locking Plates with Smartlock Locking Screws
Authors: WONG T. C. , YEUNG C. C. , CHIU Y. , YEUNG S. H. , IP F. K.
Published: January 2009

We performed a prospective cohort study on a consecutive series of 35 unstable, dorsally displaced distal radius fractures, which were treated with palmar locking plates and SmartLock locking screws. There were 17 men and 18 women with a mean age of 44 years who were reviewed at a mean follow-up of 10 months. All the fractures healed at a mean time of 7 weeks. Radiographs did not show any change in alignment from the initial postoperative period until fracture union. The average Mayo wrist score was 90 after fracture union. One patient had an early loss of fracture reduction and one patient developed complex regional pain syndrome. There was no difference in the quality of life before and after surgery. Palmar plate fixation using SmartLock locking screws is effective and safe in stabilising unstable dorsally displaced distal radius fracture and produces good radiological and functional outcomes.
The Clinical Outcome of Scaphoid Fracture Malunion at 1 Year
Authors: FORWARD D. P. , SINGH H. P. , DAWSON S. , DAVIS T. R. C.
Published: January 2009

The aim of this study was to assess the effect of malunion of scaphoid fractures on the clinical outcome at 1 year. Forty-two consecutive patients with united scaphoid waist fractures which had been treated non-operatively underwent longitudinal CT scans to confirm union and assess malunion at 12 to 18 weeks after injury. A blind clinical assessment was made and the Patient Evaluation Measure (PEM) and DASH questionnaires were completed by all the patients 1 year after injury. The group consisted of 38 men and four women with a mean age of 31 years at the time of injury. Correlation analysis revealed no significant relationships between any of the outcome measures (range of motion, grip strength and PEM and DASH scores) and any of the three measures of malunion (height-to-length ratio, the dorsal cortical angle and the lateral intra-scaphoid angle).
The Lateral Digital Flap for Dupuytren’s Fasciectomy at the Proximal Interphalangeal Joint – a Study of 84 Consecutive Patients
Authors: ANWAR M. U. , AL GHAZAL S. K. , BOOME R. S.
Published: January 2009

Fasciectomy is the most common operation performed for Dupuytren’s disease. However, as the joint contracture increases, issues of skin deficiency following release become significant. For severe or recurrent disease dermafasciectomy is advised, but a digital transposition flap provides a viable alternative without the need for a skin graft for less-severe disease with moderate skin deficiency. A retrospective review identified 84 patients who had undergone this operation. The flap used was proximally based on the midlateral aspect of the finger allowing direct closure of the donor site. Ninety hands with 134 digits were operated on and 83% of the patients had a full correction. About 70% remained fully corrected at 1 year. All flaps were performed for proximal interphalangeal joint involvement. The mean pre-operative contracture was 34°, corrected postoperatively to 5°. The recurrence rate was 9%. Two percent of the patients had local infection but no flap necrosis was seen. A lateral digital transposition flap is a very stable operation for Dupuytren’s disease with moderate skin deficiency and our patients achieved favourable results when compared to other studies that used local flaps combined with skin graft.
Two Rare Cases of Association of Thumb Hypoplasia and Polydactyly of the Homolateral Foot
Authors: PHILANDRIANOS C. , SALAZARD B. , CASANOVA D.
Published: January 2009

This paper presents two cases of radial deficiency and thumb aplasia associated with polydactyly of the homolateral foot and a supernumerary toe resembling a thumb. To our knowledge, this association of malformations has not been described previously.
Four-Corner Arthrodesis Using the Quad Memory Staple
Authors: VAN AMERONGEN E. A. , SCHUURMAN A. H.
Published: January 2009

Range of motion, pain, consolidation and complications were evaluated for nine patients who underwent four-corner arthrodesis using the Quad Memory Staple (QMS) at a mean follow-up of 44 months. The mean pre-operative range of motion was 50° extension, 62° flexion, 9° radial deviation and 24° ulnar deviation. The postoperative range of motion was similar to previous studies at 32° extension, 31° flexion, 15° radial deviation and 20° ulnar deviation. The grip strength was 28 kg pre-operatively and 26 kg postoperatively. The mean pain score improved from 41 to 23 and the Disabilities of Arm, Shoulder, and Hand (DASH) score from 24 to 20. Non-union, haematoma and wound infection were not seen and eventually all four-corner fusions were consolidated. The main advantages of the QMS are its compressive property and the simple fixation technique. It gives good stability, enables early rehabilitation and avoids the risks of pin fixation methods.
An Ultrasonographic and Anatomical Study of Carpal Tunnel, with Special Emphasis on the Safe Zones in Percutaneous Release
Authors: CHERN T. -C. , JOU I. -M. , CHEN W. -C. , WU K. -C. , SHAO C. -J. , SHEN P. -C.
Published: January 2009

We examined 40 wrists of 12 embalmed and eight fresh cadavers and defined the relative position of the flexor retinaculum to the neurovascular structure, ultrasonographic markers and safe zones by ultrasonography and anatomical dissection. Both longitudinal and transverse ultrasonographic sections clearly depicted the flexor retinaculum, neurovascular bundles, median nerve, flexor tendons and bony boundaries of the underlying joints. Topographic measurement showed [i] good correlation between the actual extent of the flexor retinaculum and the ultrasonographically determined distance between bony landmarks in all hands, and [ii] the widths and lengths of well-defined safe zones. A comparison study confirmed the accuracy of ultrasonography. We conclude that these ultrasonographic landmarks can locate the flexor retinaculum and facilitate safe and complete carpal tunnel release with open or minimally invasive techniques.
Sagittal Rotational Malunions of the Distal Radius: The Role of Pure Derotational Osteotomy
Authors: PIÑAL F. DEL , GARCÍA-BERNAL F. J. , STUDER A. , REGALADO J. , AYALA H. , CAGIGAL L.
Published: January 2009

Sagittal rotational malunion after distal radius fractures was identified in eight patients by the presence of a “hinge” point on the volar cortex on the lateral radiograph, and the ulnar head being shorter than the anterior lip of the radius on the posterior–anterior radiograph. The surgical correction consisted of preplating the distal fragment with a volar locking plate before an osteotomy through the “hinge” point, and correcting the dorsal tilt of the distal fragment. Any dorsal defect was filled with cancellous bone graft from the olecranon. Pain, range of motion and grip all improved. Disabilities of arm, shoulder and hand score changed from 54 to six. Dorsal sagittal tilt improved by 26°, from −23°to +3°. Ulnar variance improved by 3 mm, from +1.5 to −1.5 mm, becoming identical to the opposite side. A pure derotational osteotomy corrected the apparent shortening of the radius and restored the volar tilt.
Symmetry of Sensory Loss in Developing Diabetic Sensory Polyneuropathy
Authors: Rader Andrew J. , Barry Timothy P.
Published: January 2009

The medical literature presents diabetic sensory polyneuropathy (DSPN) as an axonal length-dependent symmetric pathology producing a stocking-like pattern of anesthesia in the lower extremities. This has been based on anecdotal reports. Objective research has shown that damage may not occur in a purely length-dependent manner. A stocking distribution of sensory loss is atypical, and plantar sensory loss predominates. A single-blinded, age-matched, control/experimental study was performed of the symmetry of nerve damage in developing DSPN. Control (n = 46) and experimental (n = 83) subjects were examined. The patterns of sensory loss and the severity of axonal damage were evaluated. The right/left symmetry of pathology was recorded for each individual. Although there was not a stocking pattern of anesthesia found in developing DSPN, the pattern and severity of anesthesia were found to be generally symmetric. The severity of sensory impairment was symmetric at the dorsal foot (93%), lateral foot (95%), and plantar foot (69%). The most predominant site of sensory impairment was also symmetric (81%). This argues against a purely metabolic etiology for axonal damage. An anatomic component is implied. Further research will need to include examination of the unique physical characteristics of predominantly affected nerves.
Mesenchymal stem/progenitor cells promote the reconstitution of exogenous hematopoietic stem cells in Fancg−/− mice in vivo
Authors: Li Yan , Chen Shi , Yuan Jin , Yang Yanzhu , Li Jingling , Ma Jin , Wu Xiaohua , Freund Marcel , Pollok Karen , Hanenberg Helmut , Goebel W. Scott , Yang Feng-Chun
Published: January 2009

Fanconi anemia (FA) is a heterogeneous genetic disorder characterized by bone marrow failure and complex congenital anomalies. Although mutations in FA genes result in a characteristic phenotype in the hematopoietic stem/progenitor cells (HSPCs), little is known about the consequences of a nonfunctional FA pathway in other stem/progenitor cell compartments. Given the intense functional interactions between HSPCs and the mesenchymalmicroenvironment, we investigated the FA pathway on the cellular functions of murine mesenchymal stem/progenitor cells (MSPCs) and their interactions with HSPCs in vitro and in vivo. Here, we show that loss of the murine homologue of FANCG (Fancg) results in a defect in MSPC proliferation and in their ability to support the adhesion and engraftment of murine syngeneic HSPCs in vitro or in vivo. Transplantation of wild-type (WT) but not Fancg−/− MSPCs into the tibiae of Fancg−/− recipient mice enhances the HSPC engraftment kinetics, the BM cellularity, and the number of progenitors per tibia of WT HSPCs injected into lethally irradiated Fancg−/− recipients. Collectively, these data show that FA proteins are required in the BM microenvironment to maintain normal hematopoiesis and provide genetic and quantitative evidence that adoptive transfer of WT MSPCs enhances hematopoietic stem cell engraftment.
Inhibition of monocyte-derived inflammatory cytokines by IL-25 occurs via p38 Map kinase–dependent induction of Socs-3
Authors: Caruso Roberta , Stolfi Carmine , Sarra Massimiliano , Rizzo Angelamaria , Fantini Massimo C. , Pallone Francesco , MacDonald Thomas T. , Monteleone Giovanni
Published: January 2009

IL-25, a member of the IL-17 cytokine family, is known to enhance Th2-like responses associated with increased serum levels of IgE, IgG1, IgA, blood eosinophilia, and eosinophilic infiltrates in various tissues. However, IL-25 also abrogates inflammatory responses driven by Th17 cells. However, the cell types that respond to IL-25 and the mechanisms by which IL-25 differentially regulates immune reactions are not well explored. To identify potential targets of IL-25, we initially examined IL-25 receptor (IL-25R) in human peripheral blood cells. IL-25R was predominantly expressed by CD14+ cells. We next assessed the functional role of IL-25 in modulating the response of CD14+ cells to various inflammatory signals. CD14+ cells responded to IL-25 by down-regulating the synthesis of inflammatory cytokines induced by toll-like receptor (TLR) ligands and inflammatory cytokines. Inhibition of cytokine response by IL-25 occurred via a p38 Map kinase–driven Socs-3–dependent mechanism. In vivo, IL-25 inhibited monocyte-derived cytokines and protected against LPS-induced lethal endotoxemia in mice. These data indicate that IL-25 is a negative regulator of monocyte proinflammatory cytokine responses, which may have therapeutic implications.
First acute haemodynamic study of soluble guanylate cyclase stimulator riociguat in pulmonary hypertension
Authors: Grimminger F. , Weimann G. , Frey R. , Voswinckel R. , Thamm M. , Bölkow D. , Weissmann N. , Mück W. , Unger S. , Wensing G. , Schermuly R. T. , Ghofrani H.A.
Published: January 2009

Pulmonary hypertension (PH) is associated with impaired production of the vasodilator nitric oxide (NO). Riociguat (BAY 63-2521; Bayer Healthcare AG, Wuppertal, Germany) acts directly on soluble guanylate cyclase, stimulating the enzyme and increasing sensitivity to low NO levels. The present study evaluates riociguat safety, tolerability and efficacy in patients with moderate-to-severe PH (pulmonary arterial hypertension, distal chronic thromboembolic PH or PH with mild to moderate interstitial lung disease).

The optimal tolerated dose was identified by incremental dosing in four patients with PH; pharmacodynamic and pharmacokinetic parameters were assessed following single-dose administration (2.5 mg or 1 mg) in 10 and five patients with PH, respectively. All subjects (n = 19) were analysed for safety and tolerability.

Riociguat had a favourable safety profile at single doses ≤2.5 mg. It significantly improved pulmonary haemodynamic parameters and cardiac index in patients with PH in a dose-dependent manner, to a greater extent than inhaled NO. Although riociguat also had significant systemic effects and showed no pulmonary selectivity, mean systolic blood pressure remained >110 mmHg.

The present report is the first to describe the use of riociguat in patients with pulmonary hypertension. The drug was well-tolerated and superior to nitric oxide in efficacy and duration. Riociguat, therefore, has potential as a novel therapy for pulmonary hypertension and warrants further investigation.
Effect of sildenafil on acrolein-induced airway inflammation and mucus production in rats
Authors: Wang T. , Liu Y. , Chen L. , Wang X. , Hu X-R. , Feng Y-L. , Liu D-S. , Xu D. , Duan Y-P. , Lin J. , Ou X-M. , Wen F-Q.
Published: January 2009

Airway inflammation with mucus overproduction is a distinguishing pathophysiological feature of many chronic respiratory diseases. Phosphodiesterase (PDE) inhibitors have shown anti-inflammatory properties. In the present study, the effect of sildenafil, a potent inhibitor of PDE5 that selectively degrades cyclic guanosine 3′,5′-monophosphate (cGMP), on acrolein-induced inflammation and mucus production in rat airways was examined.

Rats were exposed to acrolein for 14 and 28 days. Sildenafil or distilled saline was administered intragastrically prior to acrolein exposure. Bronchoalveolar lavage fluid (BALF) was acquired for cell count and the detection of pro-inflammatory cytokine levels. Lung tissue was examined for cGMP content, nitric oxide (NO)-metabolite levels, histopathological lesion scores, goblet cell metaplasia and mucin production.

The results suggested that sildenafil pretreatment reversed the significant decline of cGMP content in rat lungs induced by acrolein exposure, and suppressed the increase of lung NO metabolites, the BALF leukocyte influx and pro-inflammatory cytokine release. Moreover, sildenafil pretreatment reduced acrolein-induced Muc5ac mucin synthesis at both mRNA and protein levels, and attenuated airway inflammation, as well as epithelial hyperplasia and metaplasia.

In conclusion, sildenafil could attenuate airway inflammation and mucus production in the rat model, possibly through the nitric oxide/cyclic guanosine 3′,5′-monophosphate pathway, and, thus, might have a therapeutic potential for chronic airway diseases.
High prevalence of vertebral deformities in COPD patients: relationship to disease severity
Authors: Kjensli A. , Falch J. A. , Ryg M. , Blenk T. , Armbrecht G. , Diep L. M. , Ellingsen I.
Published: January 2009

Bone mineral density decreases with advancing chronic obstructive pulmonary disease (COPD) severity, but it is not known whether this is reflected in higher fracture rates. The present authors wanted to compare the prevalence of vertebral deformities in COPD patients with those in a population-based reference group to determine whether the number of deformities was related to the severity of COPD and how far the use of oral corticosteroids (OCS) influenced the prevalence of deformities.

In the present cross-sectional study of 465 COPD patients and 462 controls, vertebral deformities were found in 31% of the COPD patients and 18% of the controls. In subjects who had never or sporadically used OCS, deformities were found in 29% of the COPD patients and 17% of the controls. In females, the average number of vertebral deformities was almost two-fold when COPD severity increased from Global Initiative of Chronic Obstructive Lung Disease stage II to III. In males, the use of OCS had a small but significant influence.

Prevalence of vertebral deformities was significantly higher in chronic obstructive pulmonary disease patients than in the controls. In females, the average number of deformities was related to chronic obstructive pulmonary disease severity even after adjustment for other known risk factors. The difference between patients and controls remained significant even in those who never or sporadically used oral corticosteroids.
Characterisation of severe obliterative bronchiolitis in rheumatoid arthritis
Authors: Devouassoux G. , Cottin V. , Lioté H. , Marchand E. , Frachon I. , Schuller A. , Béjui-Thivolet F. , Cordier J-F. ,   the Groupe d'Etudes et de Recherche sur les Maladies “Orphelines” Pulmonaires (GERM“O”P)
Published: January 2009

The characteristics of patients with rheumatoid arthritis (RA) who develop obliterative bronchiolitis characterised by severe airflow obstruction have been hitherto poorly investigated.

A retrospective study of 25 patients with RA and functional evidence of obliterative bronchiolitis (forced expiratory volume in one second (FEV1)/forced vital capacity (FVC) <50% and/or residual volume (RV)/total lung capacity (TLC) >140% predicted) was conducted.

Patients (mean±sdage 64±11 yrs) included 17 never-smokers and eight ex-smokers (10.5±5.4 pack-yrs). The diagnosis of RA preceded respiratory symptoms in 88% of cases. Dyspnoea on exertion was present in all patients and bronchorrhea in 44%. High-resolution computed tomography findings included: bronchial wall thickening (96%), bronchiectasis (40%), mosaic pattern (40%), centrilobular emphysema (56%), and reticular and/or ground-glass opacities (32%). Pulmonary function tests showed: FEV141±12% pred, FEV1/FVC 49±14%, FVC 70±20% pred, RV 148±68% pred and RV/TLC 142±34% pred. Lung biopsy, available in nine patients, demonstrated constrictive, follicular and mixed bronchiolitis. Patients were followed for 48.2±49 months. Treatment was poorly effective. Chronic respiratory failure occurred in 40% of patients, and four patients died.

Obliterative bronchiolitis associated with rheumatoid arthritis is a severe and under-recognised condition leading to respiratory failure and death in a high proportion of patients.
Abnormal mitochondrial function in locomotor and respiratory muscles of COPD patients
Authors: Puente-Maestu L. , Pérez-Parra J. , Godoy R. , Moreno N. , Tejedor A. , González-Aragoneses F. , Bravo J-L. , Villar Álvarez F. , Camaño S. , Agustí A.
Published: January 2009

Several cellular and molecular alterations have been described in skeletal and respiratory muscles of patients with chronic obstructive pulmonary disease (COPD), but information on potential abnormalities of mitochondrial function is scarce. The aim of the present study was to investigate mitochondrial function in the vastus lateralis (VL) and external intercostalis (EI) of COPD patients.

Biopsies from VL and EI were obtained during surgery for lung cancer in 13 patients with mild to moderate COPD (age 68±6 yrs, forced expiratory volume in one second (FEV1) 66±15% predicted) and 19 control subjects (age 67±9 yrs, FEV195±18% pred). State 3 and 4 mitochondrial oxygen consumption (V′O2,m), ATP synthesis, citrate synthase, cytochrome oxidase (COX) and complex I–III activities, as well as reactive oxygen species (ROS) production, were determined.

In COPD patients, in both muscles, COX activity (VL: COPD 3.0±0.8versuscontrol 2.0±0.8; EI: 3.7±1.6versus2.4±0.9 μmol·min−1·mg−1) and ROS production (VL: 1,643±290versus1,285±468; EI: 1,033±210versus848±288 arbitrary units) were increased, whereas state 3V′O2,mwas reduced (VL: 2.9±0.3versus3.6±0.4; EI: 3.6±0.3versus4.1±0.4 mmol·min−1·kg−1).

Skeletal muscle mitochondria of patients with chronic obstructive pulmonary disease show electron transport chain blockade and excessive production of reactive oxygen species. The concurrent involvement of both vastus lateralis and external intercostalis suggests a systemic (rather than a local) mechanism(s) already occurring in relatively early stages (Global Initiative for Chronic Obstructive Lung Disease stage II) of the disease.
Anti-inflammatory effects of salmeterol/fluticasone, tiotropium/fluticasone or tiotropium in COPD
Authors: Perng D-W. , Tao C-W. , Su K-C. , Tsai C-C. , Liu L-Y. , Lee Y-C.
Published: January 2009

The anti-inflammatory effects of salmeterol/fluticasone (SFP), tiotropium/fluticasone (Tio+FP) and tiotropium (Tio) alone were investigated on the inflammatory cells and mediators in sputum induced from chronic obstructive pulmonary disease patients.

Subjects were either newly diagnosed or had not taken any medication for 3 months prior to the study. Subjects (n = 99) were randomised (not double blinded) and received either SFP (100/1,000 μg daily), Tio+FP (18/1,000 μg daily) or Tio (18 μg daily) for 12 weeks. Induced sputum and serum C-reactive protein (CRP) were analysed prior to and at the end of treatment.

The results showed that treatment with SFP caused a significant reduction in interleukin (IL)-8 and matrix metalloprotease (MMP)-9 in induced sputum, compared with treatment with Tio alone. There were no treatment differences between the SFP and Tio+FP groups in decreasing IL-8 and MMP-9 levels. The reduction in IL-8 showed significant association with the reduction in MMP-9. All treatment groups failed to significantly reduce the numbers of total cells, neutrophils, macrophages and eosinophils in induced sputum; in addition, there were no treatment differences in terms of improvement of forced expiratory volume in one second, forced vital capacity, CRP or quality of life between the three groups.

The anti-inflammatory effects of salmeterol/fluticasone probably contribute to the clinical benefits seen in chronic obstructive pulmonary disease patients.
Asthma, airway inflammation and epithelial damage in swimmers and cold-air athletes
Authors: Bougault V. , Turmel J. , St-Laurent J. , Bertrand M. , Boulet L-P.
Published: January 2009

Endurance athletes show an increased prevalence of airway hyperresponsiveness. The aim of the present study was to evaluate the long-term effects of training on airway responsiveness, inflammation and epithelial damage in swimmers and cold-air athletes.

In total, 64 elite athletes (32 swimmers and 32 cold-air athletes), 32 mild asthmatic subjects and 32 healthy controls underwent allergy skin prick testing, methacholine challenge and induced sputum analysis.

Overall, 69% of swimmers and 28% of cold-air athletes had airway hyperresponsiveness. Sputum neutrophil count correlated with the number of training hours per week in both swimmers and cold-air athletes. Eosinophil counts were higher in swimmers than in healthy subjects, although they were lower than in asthmatic subjects, and correlated with airway hyperresponsiveness in swimmers only. The eosinophil count in cold-air athletes was similar to that in healthy subjects. Bronchial epithelial cell count was not correlated with airway hyperresponsiveness but was significantly increased in swimmers, compared with healthy and asthmatic controls.

In conclusion, the present authors observed significant airway inflammation only in competitive athletes with airway hyperresponsiveness. However, the majority of elite athletes showed evidence of bronchial epithelial damage that could possibly contribute to the development of airway hyperresponsiveness.
Haemosiderin-laden macrophages in the bronchoalveolar lavage fluid of patients with diffuse alveolar damage
Authors: Maldonado F. , Parambil J. G. , Yi E. S. , Decker P. A. , Ryu J. H.
Published: January 2009

Quantification of haemosiderin-laden macrophages in bronchoalveolar lavage fluid (BALF) has been used to diagnose diffuse alveolar haemorrhage (DAH) but has not been assessed in patients with diffuse alveolar damage (DAD).

The present study analysed BALF obtained from 21 patients with DAD diagnosed by surgical lung biopsy.

The median age of 21 patients with DAD was 68 yrs (range 18–79 yrs); 14 (67%) were male and 12 (57%) were immunocompromised. The median proportion of haemosiderin-laden macrophages in BALF was 5% (range 0–90%), but was ≥20% in seven (33%) patients, fulfilling the commonly used BALF criterion for DAH. There was a trend toward a positive correlation between the percentage of haemosiderin-laden macrophages in BALF and parenchymal haemorrhage assessed semiquantitatively by histopathological analysis. Patients with ≥20% haemosiderin-laden macrophages in BALF showed a significantly increased mortality rate (p = 0.047) compared to those with <20%.

In patients with an acute onset of diffuse lung infiltrates and respiratory distress, ≥20% haemosiderin-laden macrophages in BALF can occur with DAD, and is not necessarily diagnostic of DAH. The finding of ≥20% haemosiderin-laden macrophages in BALF is associated with a worse prognosis in patients with DAD.
Comparative airway response to high-versuslow-molecular weight agents in occupational asthma
Authors: Dufour M-H. , Lemière C. , Prince P. , Boulet L-P.
Published: January 2009

Airway responses to occupational agents in sensitised workers may vary clinically and physiologically. The patterns of change in airway responsiveness, type of response and fall in expiratory flows following laboratory exposure to high- or low-molecular weight agents (HMW and LMW agents, respectively) were compared in sensitised workers.

Data on workers who underwent specific inhalation challenges with occupational sensitisers (117 exposed to HMW agents and 130 to LMW agents) were collected from their medical charts.

Maximum falls in forced expiratory volume in one second (FEV1) were of similar magnitude for both types of agents. Compared with HMW agents, LMW agents induced more frequently late or dual responses and higher increases in airway responsiveness. After exposure to HMW agents, there was a mean±sdreduction in doubling concentrations of methacholine of 0.5±1.7 for early responses, compared with 2.8±1.2 and 1.4±2.0 for late and dual responses, respectively. Isolated early responses were more frequently found in females, smokers, workers with a higher % predicted FEV1and higher provocation concentration causing a 20% fall in FEV1, and in those with longer asthma duration.

Workers’ characteristics, as well as the type of agent they are sensitised to, may help to predict the type of response after specific inhalation challenge.
Effect of dexamethasone on acute respiratory distress syndrome induced by the H5N1 virus in mice
Authors: Xu T. , Qiao J. , Zhao L. , He G. , Li K. , Wang J. , Tian Y. , Wang H.
Published: January 2009

Glucocorticoids are widely used in the treatment of different inflammatory diseases. The present study was performed to investigate the effect of dexamethasone (DEX) on acute respiratory distress syndrome (ARDS) induced by the H5N1 viral infection in mice.

BALB/c mice, 6–8 weeks old, were divided into three groups with 80 mice in each. The infected group and the DEX-treated infected group were inoculated intranasally with 1×10250% mouse infectious dose of A/Chicken/Hebei/108/2002 (H5N1) viruses, with daily intraperitoneal injections of PBS, or 2.5 mg·kg−1DEX at days 3–14 post inoculation, respectively. The control group received noninfectious allantoic fluid and a daily intraperitoneal injection of PBS.

In H5N1-infected mice, DEX treatment did not improve the mortality (17 out of 20versus16 out of 20 deaths in the DEX-treated infected groupversusthe infected group), and did not alleviate clinical signs, including weight loss, decreased food intake and inactivity. There was no significant amelioration of the hypoxaemia and ARDS-associated pathological changes in DEX-treated infected mice, as assessed by blood gas analysis and histological score. Furthermore, DEX therapy did not inhibit inflammatory cellular infiltration and cytokine release (interleukin-6 and tumour necrosis factor-α) in bronchoalveolar lavage fluid induced by the H5N1 infection.

In conclusion, dexamethasone treatment (2.5 mg·kg−1) from days 3–14 post inoculation has no beneficial effect on acute respiratory distress syndrome caused by the H5N1 infection in mice.