bluuebunny/crossref_metadata_2025 huggingface dataset:
IMPROVING THE EFFICIENCY OF THE BAYESIAN NETWORK RETRIEVAL MODEL BY REDUCING RELATIONSHIPS BETWEEN TERMS
Authors: DE CAMPOS LUIS M. , FERNÁNDEZ-LUNA JUAN M. , HUETE JUAN F.
Published: January 2004

The Bayesian Network Retrieval Model is able to represent the main (in)dependence relationships between the terms from a document collection by means of a specific type of Bayesian network, namely a polytree. However, although the learning and propagation algorithms designed for this topology are very efficient, in collections with a very large number of terms, these two tasks might be very time-consuming. This paper shows how by reducing the size of the polytree, which will only comprise one subset of terms which are selected according to their retrieval quality, the performance of the model is maintained, whereas the efforts needed to learn and later propagate in the model are considerably reduced. A method for selecting the best terms, based on their inverse document frequency and term discrimination value, is also presented.
INTELLIGENT KNOWLEDGE EXTRACTION FROM THE WEB
Authors: CARDEÑOSA JESÚS , TOVAR EDMUNDO
Published: January 2004

Many websites are in general poorly defined and its users are not able to find the information they need. That is the reason why many papers are addressed to propose techniques able to find the right information for a user. Most of these techniques focus on finding the required information in the whole Internet. Many times the owner of the website gives incomplete/imprecise information with low level of usefulness for the user. The re-structuring of the information is many times enough for detecting lacks of information, inconsistencies and imprecisions. However this work is normally very difficult without losing performances of the website. The authors have developed a novel application to exploit existing information in a website in a more profitable way restructuring the information without the intervention of the content provider. This paper describes the authors' experience during their participation in the European Commission ESPRIT 29158 FLEX Project.
'SWAHILI ENLIGHTENMENT'? EAST AFRICAN REFORMIST DISCOURSE AT THE TURNING POINT: THE EXAMPLE OF SHEIKH MUHAMMAD KASIM MAZRUI
Authors: Kresse Kai
Published: January 2004

This article discusses Sheikh Muhammad Kasim Mazrui, an influential yet largely ignored figure within East African Islamic reformism, which shifted from internal to external domination in the second half of the 20th century. His educational booklet 'Hukumu za sharia', written in Kiswahili, is analysed and contextualised. Advising local Muslims, by way of clear argument and reference to authoritative texts, on how to deal with controversial local practices from an Islamic point of view, it pushed for the development of self-reliance, and criticised dependence on Islamic clerics and dignitaries. The text itself displays the rational principles that the reformist movement relied on and propagated, while it also contains hints of a more dogmatic tone that was yet to dominate reformist discourse. Overall, the article establishes a wider comparison in discussing this African Islamic reformism as an 'enlightenment' movement. The focus hereby is on structure rather than substance, as Islamic reform is incompatible with secularism. Common features, however, can be seen in the emphasis on rationality and self-reliance of individual actors, as well as the internal dialectic of the movements, oscillating between liberation and dogmatism.
Interleukin-10 and tumor necrosis factor alpha region haplotypes predict transplant-related mortality after unrelated donor stem cell transplantation
Authors: Keen Leigh J. , DeFor Todd E. , Bidwell Jeffrey L. , Davies Stella M. , Bradley Benjamin A. , Hows Jill M.
Published: January 2004

Certain cytokine gene polymorphisms have been shown to correlate with outcome of human leukocyte antigen (HLA) identical sibling donor stem cell transplantation (SCT), but in unrelated donor SCT such information is scarce. We have studied the association between cytokine gene polymorphism and transplant-related mortality (TRM) in 182 unrelated SCTs performed at a single center. We found association of polymorphism in the tumor necrosis factor alpha (TNFα) and interleukin-10 (IL-10) gene and TRM. Both the TNFd4 allele and the TNFα -1031C alleles are associated with high risk for TRM. Statistical analysis showed that both polymorphisms were present on a single haplotype. This haplotype was associated with high risk of TRM when present in recipient or donor, 55% (43%-67%) compared with 21% (12%-30%) when absent from both (P < .01). A further allele associated with this haplotype, TNFa5, is also associated with increased risk of TRM. For IL-10, presence of the donor R2-G-C-C haplotype was associated with decreased risk of TRM, 61% (43%-79%) versus 34% (25%-43%), P = .01. In contrast, possession of the R3-G-C-C haplotype by the donor predicted reduced risk of TRM, 30% (19%-41%, 95% CI) versus 53% (40%-66%, 95% CI), P = .01. No independent associations of cytokine polymorphisms with acute graft-versus-host disease were shown. (Blood. 2004;103:3599-3602)
5′-Flanking region polymorphisms of CYP2C9 and their relationship to S-warfarin metabolism in white and Japanese patients
Authors: Takahashi Harumi , Ieiri Ichiro , Wilkinson Grant R. , Mayo Gail , Kashima Toshitaka , Kimura Sosuke , Otsubo Kenji , Echizen Hirotoshi
Published: January 2004

White and Japanese patients require different warfarin dosages to achieve therapeutic anticoagulation, but this can be only partly explained by genetic variability in the coding region of CYP2C9—a critical enzyme in the drug's metabolism. Accordingly, analysis of the -2.1-kb 5′-flanking region of CYP2C9 was undertaken in 22 white and 38 Japanese patients whose unbound oral clearance of S-warfarin had been previously determined. Thirteen single nucleotide polymorphisms (SNPs) were identified, some of which were in linkage disequilibrium with functionally defective coding region variants. Those 5′-flanking patterns linked with at least one CYP2C9*3 allele or CYP2C9*2/*3 were associated with reduced CYP2C9 activity and warfarin dose. Japanese patients possessing the wild-type promoter and coding sequences had significantly (P < .01) greater CYP2C9 activity than white patients with the corresponding genotype. In conclusion, either unidentified polymorphisms further upstream in the promoter region or environmental factor(s) account for the differences in the warfarin doses between whites and Japanese. (Blood. 2004;103: 3055-3057)
Hematopoietic-repopulating defects from STAT5-deficient bone marrow are not fully accounted for by loss of thrombopoietin responsiveness
Authors: Bradley Heath L. , Couldrey Christine , Bunting Kevin D.
Published: January 2004

Signal transducer and activator of transcription-5 (STAT5) plays an important role in repopulating activity of hematopoietic stem cells (HSCs). However, the relationship of STAT5 activation with early acting cytokine receptors is not well established. We have directly compared bone marrow (BM) from mice mutant for STAT5a and STAT5b (STAT5ab-/-) with that from mice lacking c-Mpl (c-Mpl-/-), the thrombopoietin receptor. Both STAT5 and c-Mpl deficiency only mildly affected committed myeloid progenitors assayed in vitro, but STAT5ab-/- BM showed lower Gr-1+ (4.4-fold), B220+ (23-fold), CD4+ (20-fold), and Ter119+ (17-fold) peripheral blood repopulating activity than c-Mpl-/- BM against wild-type competitor in long-term repopulating assays in vivo. Direct head-to-head competitions of STAT5ab-/- BM and c-Mpl-/- BM showed up to a 25-fold reduction in STAT5ab-/- contribution. Differences affecting reconstitution of primitive c-Kit+Lin-Sca-1+ multipotent progenitor (MPP)/HSC (1.8-fold) and c-Kit+Lin-Sca-1- oligopotent progenitor BM fractions (3.3-fold) were more modest. In serial transplantation experiments, STAT5ab-/- and c-Mpl-/- BM both failed to provide consistent engraftment in tertiary hosts and could not radioprotect lethally irradiated quaternary recipients. These results indicate substantial overlap in c-Mpl-STAT5 signaling defects at the MPP/HSC level but indicate that STAT5 is activated independent of c-Mpl to promote multilineage hematopoietic differentiation. (Blood. 2004;103:2965-2972)
Neutrophil PRV-1 expression across the chronic myeloproliferative disorders and in secondary or spurious polycythemia
Authors: Tefferi Ayalew , Lasho Terra L. , Wolanskyj Alexandra P. , Mesa Ruben A.
Published: January 2004

Recent studies have demonstrated neutrophil overexpression of the polycythemia rubra vera-1 (PRV-1) gene in polycythemia vera (PV) but not in secondary or spurious polycythemia (SP). To validate as well as expand upon this novel observation, we conducted a prospective study of 88 subjects: 30 with PV, 22 with SP, 14 with essential thrombocythemia (ET), 12 with myelofibrosis with myeloid metaplasia (MMM), and 10 controls. To minimize interstudy methodologic differences, we used a published real-time polymerase chain reaction (PCR)-based assay. The proportion of patients with increased neutrophil PRV-1 expression was 83% in PV, 21% in ET, 42% in MMM, 18% in SP, and 0% in controls. All 5 MMM patients with PRV-1 up-regulation had an antecedent history of PV. We conclude that neutrophil PRV-1 up-regulation is a characteristic feature of PV that may not be affected by fibrotic transformation. However, quantifying neutrophil PRV-1 mRNA, while complementary to other tests, is not in itself sufficient for the diagnosis of PV. (Blood. 2004;103:3547-3548)
Different airway inflammatory responses in asthmatic and healthy humans exposed to diesel
Authors: Stenfors N. , Nordenhäll C. , Salvi S.S. , Mudway I. , Söderberg M. , Blomberg A. , Helleday R. , Levin J-O. , Holgate S.T. , Kelly F.J. , Frew A.J. , Sandström T.
Published: January 2004

Particulate matter (PM) pollution adversely affects the airways, with asthmatic subjects thought to be especially sensitive. The authors hypothesised that exposure to diesel exhaust (DE), a major source of PM, would induce airway neutrophilia in healthy subjects, and that either these responses would be exaggerated in subjects with mild allergic asthma, or DE would exacerbate pre-existent allergic airways.

Healthy and mild asthmatic subjects were exposed for 2 h to ambient levels of DE (particles with a 50% cut-off aerodynamic diameter of 10 µm (PM10) 108 µg·m−3) and lung function and airway inflammation were assessed.

Both groups showed an increase in airway resistance of similar magnitude after DE exposure. Healthy subjects developed airway inflammation 6 h after DE exposure, with airways neutrophilia and lymphocytosis together with an increase in interleukin‐8 (IL‐8) protein in lavage fluid, increased IL‐8 messenger ribonucleic acid expression in the bronchial mucosa and upregulation of the endothelial adhesion molecules. In asthmatic subjects, DE exposure did not induce a neutrophilic response or exacerbate their pre-existing eosinophilic airway inflammation. Epithelial staining for the cytokine IL‐10 was increased after DE in the asthmatic group.

Differential effects on the airways of healthy subjects and asthmatics of particles with a 50% cut-off aerodynamic diameter of 10 µm at concentrations below current World Health Organisation air quality standards have been observed in this study. Further work is required to elucidate the significance of these differential responses.
Progressive damage on high resolution computed tomography despite stable lung function in cystic fibrosis
Authors: de Jong P.A. , Nakano Y. , Lequin M.H. , Mayo J.R , Woods R. , Paré P.D. , Tiddens H.A.W.M.
Published: January 2004

For effective clinical management of cystic fibrosis (CF) lung disease it is important to closely monitor the start and progression of lung damage. The aim of this study was to investigate the ability of high-resolution computed tomography (HRCT) scoring systems and pulmonary function tests (PFT) to detect changes in lung disease.

CF children (n=48) had two HRCT scans in combination with two PFT 2 yrs apart. Their scans were scored using five scoring systems (Castile, Brody, Helbich, Santamaria and Bhalla). “Sensitivity” was defined as the ability to detect disease progression.

In this group of children, HRCT scores worsened. PFT remained unchanged or improved. Of the HRCT parameters, mucous plugging and the severity, extent and peripheral extension of bronchiectasis worsened significantly. Relationships between changes in HRCT scores and PFT were weak. Substantial structural lung damage was evident in some children who had normal lung function.

These data show that high-resolution computed tomography is more sensitive than pulmonary function tests in the detection of early and progressive lung disease, and suggest that high-resolution computed tomography may be useful in the follow up of cystic fibrosis children and as an outcome measure in studies that aim to reduce lung damage.
Acute effects of inspiratory pressure support during exercise in patients with COPD
Authors: van 't Hul A. , Gosselink R. , Hollander P. , Postmus P. , Kwakkel G.
Published: January 2004

The aim of the present study was to evaluate the acute effects of inspiratory pressure support (IPS) of 5 cmH2O (IPS5) and 10 cmH2O (IPS10) on exercise endurance.

Forty-five patients with COPD (mean forced expiratory volume in one second (FEV1)=39±14% pred) performed three constant-load endurance tests on a cycle ergometer at 75% of maximal workload. One test was without IPS, one test with IPS5, and one with IPS10. No statistically significant difference was found in exercise endurance between tests without IPS and IPS5(4.2±2.6versus4.4±2.9 min).

In contrast, IPS10resulted in a statistically significant increase in endurance compared with exercise without IPS (6.3±6.7versus4.2±2.6 min), as well as compared with exercise with IPS5(6.3±6.7versus4.4±2.9 min). A wide scatter in individual responses to IPS was found, ranging from a deterioration of 1.6 min (−36%) to an improvement of 16.3 min (+445%). In only 15 patients, the increase in endurance exceeded the upper limit of the 95% confidence interval. Stepwise multiple regression analysis showed that maximal inspiratory pressure was the most important determinant of the increase in exercise endurance due to the application of IPS10.

It was concluded that in contrast to inspiratory pressure support of 5 cmH2O, the application of inspiratory pressure support of 10 cmH2O during exercise resulted in a statistically significant improvement in exercise endurance in patients with COPD compared with exercise without inspiratory pressure support. However, on an individual basis, large differences in responses were found. Inspiratory muscle weakness was revealed as a determinant of improvement in exercise endurance due to the application of inspiratory pressure support of 10 cmH2O, explaining only 24% of the variance in outcome.
Nuclear YB‐1 expression as a negative prognostic marker in nonsmall cell lung cancer
Authors: Gessner C. , Woischwill C. , Schumacher A. , Liebers U. , Kuhn H. , Stiehl P. , Jürchott K. , Royer H.D. , Witt C. , Wolff G.
Published: January 2004

The human Y‐box binding protein, YB‐1, is a multifunctional protein that regulates gene expression. Nuclear expression of YB‐1 has been associated with chemoresistance and poor prognosis of tumour patients.

Representative samples from autopsied material of primary tumours from 77 patients with NSCLC were investigated by immunohistochemistry for subcellular distribution of YB‐1 and p53, in order to evaluate the prognostic role of nuclear expression of YB‐1.

Cytoplasmic YB‐1 expression was found in all tumour samples, whereas nuclear expression was only observed in 48%. There was no correlation with histological classification, clinical parameters or tumour size, stage and metastasis status. However, patients with positive nuclear YB‐1 expression in tumours showed reduced survival times when compared with patients without nuclear expression. Including information about the histology and mutational status for p53 increased the prognostic value of nuclear YB‐1. Patients with nuclear YB‐1 expression and p53 mutations had the worst prognosis (median survival 3 months), while best outcome was found in patients with no nuclear YB‐1 and wildtype p53 (median survival 15 months).

This suggests that the combined analysis of both markers allows a better identification of subgroups with varying prognosis. Nuclear expression of Y‐box binding protien seems to be an independent prognostic marker.
The 6‐min walk distance: change over time and value as a predictor of survival in severe COPD
Authors: Pinto-Plata V.M. , Cote C. , Cabral H. , Taylor J. , Celli B.R.
Published: January 2004

The 6‐min walk distance (6MWD) is used to evaluate the functional capacity of patients with chronic obstructive pulmonary disease (COPD). The change in 6MWD over time and its correlation with changes in spirometry and survival are unclear.

Patients (n=198) with severe COPD and 41 age-matched controls were followed for 2 yrs, and anthropometrics, spirometry, 6MWD and comorbidities were measured.

The 6MWD decreased in the COPD group from 238±107 m to 218±112 m (−26±37 m·yr−1), and increased in the control group from 532±82 m to 549±86 m (12±25 m·yr−1). In both groups, there was a poor correlation with changes in forced expiratory volume in one second (FEV1). Nonsurvivors in the COPD group (42%) had a more pronounced change in the 6MWD (−40versus−22 m·yr−1) but a similar change in FEV1(118versus102 mL·yr−1). The 6MWD independently predicted survival, after accounting for age, body mass index, FEV1and comorbidities.

In severe chronic obstructive pulmonary disease, the 6‐min walk distance predicts mortality better than other traditional markers of disease severity. Its measurement is useful in the comprehensive evaluation of patients with severe disease.
Mechanical ventilation of healthy rats suppresses peripheral immune function
Authors: Vreugdenhil H.A. , Heijnen C.J. , Plötz F.B. , Zijlstra J. , Jansen N.J. , Haitsma J.J. , Lachmann B. , van Vught A.J.
Published: January 2004

This study was designed to investigate the possible effect of injurious mechanical ventilation on peripheral immune function of healthy rats. Three ventilation strategies were compared: 1) low peak inspiratory pressure (PIP)/positive end-expiratory pressure (PEEP); 2) high PIP/PEEP; and 3) high PIP/zero PEEP (ZEEP). As a reference group, healthy, nonventilated, sham-operated, anaesthetised rats were used.

After 4 h, rats were sacrificed and macrophage inflammatory protein (MIP)‐2 levels in lung and plasma were determined. Peripheral immune function was determined by measurement of splenic natural killer (NK) activity, mitogen-induced splenocyte proliferation andin vitrocytokine production. All immune measurements in the low PIP/PEEP group did not differ from the immune measurements in the reference group. High PIP strategies, irrespective of applied PEEP, enhanced MIP‐2 levels in lung and plasma.

NK cell activity, mitogen-induced splenocyte proliferation and MIP‐2 and interleukin (IL)‐10 production significantly decreased after high PIP/PEEP ventilation. In the high PIP/ZEEP‐ventilated group, the decrease in splenocyte proliferation, MIP‐2 and IL‐10 production and NK cell activity was more pronounced and interferon‐γ production was also significantly lower than in the low PIP/PEEP group.

These data show that high positive inspiratory pressure ventilation induces an inflammatory response in the lung, whereas at the same time the peripheral immune response is downregulated. Ventilator-induced peripheral immune suppression may contribute to poor outcome in acute respiratory distress syndrome patients.
Apoptosis and proliferation in lungs of ventilated and oxygen-treated preterm infants
Authors: May M. , Ströbel P. , Preisshofen T. , Seidenspinner S. , Marx A. , Speer C.P.
Published: January 2004

Apoptosis and proliferation and the effect of exogenous surfactant on these processes were investigated in the lungs of mechanically ventilated/oxygen-treated preterm infants with respiratory distress syndrome and stillborn foetuses.

Apoptotic and proliferation indices were determined in lung tissue sections from 27 ventilated/oxygen-treated preterm infants and 29 stillborn foetuses. The effect of exogenous surfactant on apoptosis and proliferation was studied in 16 ventilated preterm infants; 11 untreated infants served as control. Apoptotic and proliferating cells were identified by double labelling combining terminal deoxynucleotidyltransferase-mediated deoxyuridine triphosphate nick end-labelling or Ki‐67 with cell marker proteins. Pathways to cell death were explored by immunolabelling of cleaved caspases‐3, ‐8 and ‐9.

In the lungs of ventilated/oxygen-treated preterm infants, the numbers of apoptotic and proliferating cells increased significantly compared to the respective numbers in the lungs of stillborn foetuses. Apoptosis was detected in alveolar epithelial cells, whereas epithelial, endothelial and smooth muscle cells proliferated. Surfactant treatment reduced apoptosis induced by ventilation/oxygen-treatment; however, the decrease was not significant. Caspases‐8 and ‐9 do not contribute to ventilation-induced apoptosis, whereas caspase‐3 is involved.

In conclusion, ventilation/oxygen-treatment induces epithelial cell apoptosis and proliferation of epithelial, endothelial and smooth muscle cells in the lungs of preterm infants.
Dynamic dead space in face masks used with noninvasive ventilators: a lung model study
Authors: Saatci E. , Miller D.M. , Stell I.M. , Lee K.C. , Moxham J.
Published: January 2004

The aim of this study was to determine what the influence of different designs of face masks and different noninvasive ventilator modes would be upon total dynamic dead space.

Using a spontaneous breathing model, total dynamic dead space was measured when using 19 commercially available face masks and a range of ventilators in various ventilation modes.

Total dynamic dead space during spontaneous ventilation was increased above physiological dead space from 32% to 42% of tidal volume by using face masks. The use of noninvasive ventilation modes such as bilevel and continuous positive airway pressure, with continuous pressure throughout the expiratory phase, reduced total dynamic dead space to approach physiological dead space with most face masks. Pressure assist and pressure support ventilation decreased total dynamic dead space to a lesser degree, from 42% to 39% of tidal volume. Face masks with expiratory ports over the nasal bridge resulted in beneficial flow characteristics within the face mask and nasal cavity, so as to decrease total dynamic dead space to less than physiological dead space from 42% to 28.5% of tidal volume.

Exhaust ports over the nasal bridge in face masks effect important decreases in dynamic dead space provided positive pressure throughout the expiratory phase is used.
Prevalence of asthma and exhaled nitric oxide are increased in bleachery workers exposed to ozone
Authors: Olin A-C. , Andersson E. , Andersson M. , Granung G. , Hagberg S. , Torén K.
Published: January 2004

The aims of the present study were to determine whether exposure to high peaks of ozone resulted in an increased prevalence of asthma or respiratory symptoms among bleachery workers and whether nitric oxide (NO) was elevated in the exhaled air of these workers.

Bleachery workers (n=228) from three Swedish pulp mills who had been exposed to ozone, together with 63 unexposed control subjects, were investigated by means of spirometry, Phadiatop®, exhaled and nasal NO and answers to a questionnaire concerning respiratory symptoms and exposure. Exposure to an ozone peak that gave rise to respiratory symptoms was defined as a “gassing”.

Bleachery workers reporting four or more gassings involving ozone had an increased prevalence of adult-onset asthma, wheeze, and current asthma symptoms. They also had a higher median concentration of exhaled NO in comparison with those who reported no such gassings (19.2versus15.7 parts per billion). No such associations were found in respect of nasal NO.

The results from this study show that bleachery workers who have been repeatedly exposed to ozone gassings have an increased prevalence of adult-onset asthma. The results also indicate exhaled nitric oxide may be a marker of airway inflammation in bleachery workers who have been exposed to high peaks of ozone.
Childhood factors that predict asthma in young adulthood
Authors: Toelle B.G. , Xuan W. , Peat J.K. , Marks G.B.
Published: January 2004

Predicting adult asthma, using childhood characteristics, is important for advising on prognosis and, potentially, for secondary prevention. A novel use of multivariate likelihood ratios (LRs) to quantify prognosis is described here.

Of 718 subjects of a community-based cohort, 575 (80%) members were recruited at age 8–10 yrs and were re-assessed 15–17 yrs later. At baseline, information about symptoms, spirometry, histamine challenge and skin-prick tests were collected. At follow-up “asthma symptoms” were defined as wheeze, sleep disturbance from asthma or inhaled steroid use within the previous year. LRs were calculated for significant predictors of this outcome. Shinkage factors were applied to yield multivariate LRs.

Childhood characteristics that independently predicted asthma symptoms in adulthood were obstructive spirometry (adjusted (adj)LR 2.9, 95% confidence interval (CI) 1.3–6.5), airway hyperresponsiveness (adjLR 2.6, 95% CI 1.8–3.7), atopy (adjLR 2.0, 95% CI 1.5–2.7), recent wheeze (adjLR 1.9, 95% CI 1.5–2.5) and being female (adjLR 1.29, 95% CI 0.8–2.1). Children with all five characteristics had a cumulative LR of 36.9 for asthma symptoms in adulthood.

Most adults who had asthma symptoms did not have manifestations of asthma as children. However, the presence of obstructive spirometry, airway hyperresponsiveness and atopy in childhood identifies individuals with increased likelihood of having asthma in adulthood. Cumulative likelihood ratios are more valuable than odds ratios for quantifying risk in individuals and for identifying people with most to gain from preventive interventions.
New concepts of the pathogenesis of cystic fibrosis lung disease
Authors: Boucher R.C.
Published: January 2004

Although there has been impressive progress in the elucidation of the genetic and molecular basis of cystic fibrosis (CF), the pathogenesis of CF lung disease remains obscure. The elucidation of the pathogenesis of CF lung disease requires both a full description of normal innate airway defence and how absent function of the cystic fibrosis transmembrane regulator protein (CFTR) adversely perturbs this activity.

Recent data have linked the abnormal ion transport properties of CF airway epithelia to depleted airway surface liquid (ASL) volume, reflecting the combined defects of accelerated Na+transport and the failure to secrete Cl−. Depletion of a specific compartment of the ASL,i.e.the periciliary liquid (PCL), appears to abrogate both cilia-dependent and cough clearance.

Subsequent to PCL depletion, mucus adheres to airway surfaces and persistent mucin secretion generates the formation of “thickened” mucus plaques and plugs, which become the nidus for bacterial infection. The paucity of liquid in these plaques/plugs, and the hypoxia in this environment, appear to promote biofilm bacterial infection.

Therapeutic agents that restore airway surface liquid volume,i.e.blockers of Na+transport, initiators of Cl−transport and osmolytes, are reviewed, as are strategies that may be required to use volume-restoring agents safely in patients with cystic fibrosis.
Formoterol protects against platelet-activating factor-induced effects in asthma
Authors: Gabrijelcic J. , Casas A. , Rabinovich R.A. , Roca J. , Barberà J.A. , Chung K.F. , Rodríguez-Roisin R.
Published: January 2004

Platelet-activating factor (PAF) is an inflammatory mediator that provokes neutropaenia, bronchoconstriction and gas exchange defects due to exudation of bulk plasma within the airways. While the inhibitory effects of short-acting β2‐agonists on PAF‐induced disturbances have been consistently shown, those of long-acting β2‐agonists are less convincing.

To further explore the mechanisms involved in PAF challenge in asthma, 12 patients (forced expiratory volume in one second, 90±4% predicted) were investigated 2 h after inhaled formoterol (18 µg), in a double-blind, placebo-controlled, crossover design following PAF (18 µg) inhalation.

Compared with the placebo, at 5 min, premedication with formoterol reduced PAF-induced cough and dyspnoea, and attenuated increased respiratory system resistance (by 67%) and arterial deoxygenation (by 50%). Likewise, ventilation-perfusion (V′A/Q′) inequality improved, as reflected by the dispersion of pulmonary blood flow (by 63%) and an overall index ofV′A/Q′ heterogeneity (by 71%). In contrast, PAF-induced facial flushing, neutropaenia and subsequent rebound neutrophilia remained unchanged.

The improvement in gas exchange abnormalities shown after platelet-activating factor in patients with asthma pretreated with formoterol at the recommended clinical dose may reflect, in addition to its class effects, an anti-exudative effect of formoterol in the airways.
KL‐6 levels are elevated in plasma from patients with acute respiratory distress syndrome
Authors: Sato H. , Callister M.E.J. , Mumby S. , Quinlan G.J. , Welsh K.I. , duBois R.M. , Evans T.W.
Published: January 2004

The acute respiratory distress syndrome (ARDS) is an extreme form of lung injury characterised by disruption to the alveolar epithelium. KL‐6 is a mucin-like glycoprotein expressed on type II pneumocytes. Circulating levels of KL‐6 have diagnostic and prognostic significance in a number of interstitial lung diseases, and when elevated are thought to indicate disruption of the alveolar epithelial lining. In this study, the authors sought to determine whether plasma KL‐6 levels were elevated in patients with ARDS and whether these were associated with aetiology, disease severity, outcome or ventilatory strategy.

Plasma samples were collected from 28 patients with ARDS, nine ventilated controls of matched illness severity and 10 healthy individuals. KL‐6 concentrations were measured by enzyme-linked immunosorbent assay.

Patients with ARDS had higher plasma levels of KL‐6 (median 537 U·mL−1, interquartile range (IQR) 383–1,119), as compared to ventilated controls (median 255 U·mL−1, IQR 83–338) and normal individuals (median 215 U·mL−1, IQR 149–307). In patients with ARDS, plasma KL-6 levels were higher in nonsurvivors than survivors, and correlated positively with oxygenation index and negatively with arterial oxygen tension:inspiratory oxygen fraction ratio. There were also significant positive correlations with mean and peak airway pressures.

Elevated levels of plasma KL‐6 may provide a useful marker for acute respiratory distress syndrome in ventilated patients and have possible prognostic significance. Alveolar epithelial cell damage may be influenced by the nature of mechanical ventilatory support.
Dual tachykinin NK1/NK2antagonist DNK333 inhibits neurokinin A‐induced bronchoconstriction in asthma patients
Authors: Joos G.F. , Vincken W. , Louis R. , Schelfhout V.J. , Wang J.H. , Shaw M.J. , Cioppa G.D. , Pauwels R.A.
Published: January 2004

Inhalation of neurokinin A (NKA) causes bronchoconstriction in patients with asthma.In vitroboth tachykinin NK1and NK2receptors can mediate airway contraction. In this study the authors examined the effects of a single dose of the dual tachykinin NK1/NK2receptor antagonist, DNK333, on NKA‐induced bronchoconstriction in asthma.

A total of 19 male adults with mild asthma completed a randomised, double-blind, placebo-controlled, crossover trial. Increasing concentrations of NKA (3.3×10−9to 1.0×10−6 mol·mL−1) were inhaled at 1 and 10 h intervals after a single oral dosing with either DNK333 (100 mg) or a placebo.

It was observed that DNK333 did not affect baseline lung function but did protect against NKA‐induced bronchoconstriction in those patients. The mean log10provocative concentration causing a 20% fall in forced expiratory volume in one second for NKA was −5.6 log10mol·mL−1at 1 h after DNK333 treatment and −6.8 log10mol·mL−1after placebo. This was equivalent to a difference of 4.08 doubling doses, which decreased to a difference of 0.90 doubling doses 10 h after treatment.

The results shown in this report indicate that DNK333 blocks neurokinin A‐induced bronchoconstriction in patients with asthma.
Theophylline and acetazolamide reduce sleep-disordered breathing at high altitude
Authors: Fischer R. , Lang S.M. , Leitl M. , Thiere M. , Steiner U. , Huber R.M.
Published: January 2004

A randomised, double-blind, placebo-controlled study was conducted to evaluate the effects of theophylline and acetazolamide in the treatment of sleep-disordered breathing (SDB) after fast ascent to high altitude (3,454 m).

The study was conducted at a high-altitude research laboratory and included 30 healthy male volunteers. Study medication was either oral slow release theophylline (2×250 mg·day−1), oral acetazolamide (2×250 mg·day−1) or a matched placebo tablet. Polysomnographic measurements were performed during two consecutive nights, and acute mountain sickness, pulse rate, oxyhaemoglobin saturation and arterial blood gases were assessed three times a day.

Without active medication, the apnoea/hypopnoea index (AHI) was highly pathological (median 16.2·h−1, range 2–92). Both theophylline and acetazolamide normalised SDB (median AHI 2.5·h−1, range 0–11; 4.2·h−1, range 0–19, respectively) and reduced oxyhaemoglobin desaturations during sleep (median desaturation index placebo 41.5·h−1, range 6–114; acetazolamide 6.5·h−1, range 3–28; theophylline 8.5·h−1, range 3–32). Compared with the high amount of central apnoeas or hypopnoeas, the number of obstructive events during sleep was very low in all groups (<4·h−1). In contrast to theophylline, acetazolamide significantly improved basal oxyhaemoglobin saturation during sleep (86.2±1.7%versus81.0±3.0%).

The authors conclude that both oral slow release theophylline and acetazolamide are effective to normalise high-altitude sleep-disordered breathing.
Retinoic acid induces alveolar regeneration in the adult mouse lung
Authors: Hind M. , Maden M.
Published: January 2004

Recent data suggests that exogenous retinoic acid (RA) can induce alveolar regeneration in a mouse and a rat model of experimental emphysema and disrupted alveolar development. This may be because RA is required during normal alveolar development and the subsequent provision of RA reawakens the gene cascades used during development.

Here, additional evidence that RA is required during alveologenesis in the mouse is provided by showing that disulphiram disrupts this process. A further model of disrupted alveolar development using dexamethasone administered postnatally is then described, and it is further shown that RA administered to these adult mice restores the lung architecture to normal.

Alveolar regeneration with retinoic acid may therefore be an important novel therapeutic approach to the treatment of respiratory diseases characterised by a reduced gas-exchanging surface area, such as bronchopulmonary dysplasia and emphysema.
Travel Broadens the Mind
Authors: Campos Joseph J. , Anderson David I. , Barbu‐Roth Marianne A. , Hubbard Edward M. , Hertenstein Matthew J. , Witherington David
Published: January 2004

The onset of locomotion heralds one of the major life transitions in early development and involves a pervasive set of changes in perception, spatial cognition, and social and emotional development. Through a synthesis of published and hitherto unpublished findings, gathered from a number of converging research designs and methods, this article provides a comprehensive review and reanalysis of the consequences of self‐produced locomotor experience. Specifically, we focus on the role of locomotor experience in changes in social and emotional development, referential gestural communication, wariness of heights, the perception of self‐motion, distance perception, spatial search, and spatial coding strategies. Our analysis reveals new insights into the specific processes by which locomotor experience brings about psychological changes. We elaborate these processes and provide new predictions about previously unsuspected links between locomotor experience and psychological function. The research we describe is relevant to our broad understanding of the developmental process, particularly as it pertains to developmental transitions. Although acknowledging the role of genetically mediated developmental changes, our viewpoint is a transactional one in which a single acquisition, in this case the onset of locomotion, sets in motion a family of experiences and processes that in turn mobilize both broad‐based and context‐specific psychological reorganizations. We conclude that, in infancy, the onset of locomotor experience brings about widespread consequences, and after infancy, can be responsible for an enduring role in development by maintaining and updating existing skills.
Task‐to‐Task Vagal Regulation: Relations With Language and Play in 20‐Month‐Old Children
Authors: Suess Patricia E. , Bornstein Marc H.
Published: January 2004

In this article we report patterns of task‐to‐task vagal tone change across multiple language and play tasks as well as associations between these patterns of task‐to‐task vagal tone change and language and play performance in 20‐month‐old girls and boys. Although initially different in vagal tone suppression during solitary play, girls and boys exhibited similar group patterns of vagal reengagement during successive language and play tasks with their mothers and with an experimenter. In terms of individual differences, vagal suppression during solitary play and vagal reengagement during social interactive tasks predicted language and play performance. Gender differences emerged in patterns of predictive relations: Task‐to‐task vagal changes predicted primarily play performance in girls and language performance in boys. These findings expose the effects of social context on directional changes in task‐to‐task vagal tone and speak to the functional role of appropriate vagal regulation in young children's language and play performance.
Cortical Indexes of Saccade Planning in Infants
Authors: Richards John E.
Published: January 2004

This article briefly reviews the development of cortical involvement in saccadic eye movement in young infants. A distinction between reflexive and voluntary saccadic eye movements is made, and developmental changes in the neural systems controlling these eye movements are discussed. Cortical indexes of saccade planning in adults have been measured using scalp‐recorded, event‐related potential (ERP). The ERP may be useful in distinguishing reflexive and voluntary saccadic eye movements in infants. In the remainder of this Thematic Collection, 3 studies are introduced that used ERP measures to infer saccade planning in young infants, and 2 short articles comment on these studies.
Using Object Knowledge in Visual Tracking and Reaching
Authors: Berthier Neil E. , Bertenthal Bennett I. , Seaks Jill D. , Sylvia Monica R. , Johnson Renee L. , Clifton Rachel K.
Published: January 2004

Nine‐month‐old infants were presented with an engaging and challenging task of visually tracking and reaching for a rolling ball that disappeared and reappeared from behind an occluder. On some trials, the infant observed the experimenter place a barrier on the ball's track; the barrier remained partially visible above the occluder throughout the remainder of the trial. When the task involved only predictive tracking, infants' anticipatory gaze shifts were faster when no barrier was present. When the task involved both tracking and reaching, there were more reaches when no barrier was present. If the infant reached, the timing and extension of the reach and the accompanying gaze shift did not differ with regard to the barrier. Because catching the ball was quite difficult for these infants, task demands interfered with the integration of visual information and visuospatial reasoning about the barrier with the reaching action.
Individual Differences in Infants' Recognition of Briefly Presented Visual Stimuli
Authors: Frick Janet E. , Richards John E.
Published: January 2004

Infants' recognition memory has been shown to be related to individual differences in look duration and level of heart period variability. This study examined the effect of individual differences in these 2 measures on infants' recognition of briefly presented visual stimuli using a paired‐comparison recognition‐memory paradigm. A sample of 35 full‐term infants was studied longitudinally at 14, 20, and 26 weeks of age. Recognition memory for briefly presented stimuli was tested in 6 experimental conditions, with delays corresponding to different heart‐rate‐defined phases of attention. The 20‐and 26‐week‐old infants, and infants with high levels of heart period variability, generally showed more evidence of recognition memory for briefly presented visual stimuli. Greater evidence of recognition memory was observed when stimuli were presented during sustained attention. Infants with more mature baseline physiological responses show greater evidence of recognition memory, and stimulus and procedural factors may be more important for the study of individual differences in infant visual attention than has previously been suggested.
The Concept of Ecological Validity: What Are Its Limitations and Is It Bad to Be Invalid?
Authors: Lewkowicz David J.
Published: January 2004

The concept of ecological validity has played an important role in research on perceptual development. The limitations of this concept are discussed and illustrated with examples from research on the development of intersensory perception. By itself the concept of ecological validity fails to provide objective criteria for experimental design, but together with more traditional bottom‐up methodological approaches it can be used in a convergent operations manner to enrich our understanding of perceptual development.
Emotion Regulation Via Maternal Touch
Authors: Hertenstein Matthew J. , Campos Joseph J.
Published: January 2004

The study of emotion elicitation in the caregiver‐infant dyad has focused almost exclusively on the facial and vocal channels, whereas little attention has been given to the contribution of the tactile channel. This study was undertaken to investigate the effects of touch on infants' emotions. During the time that objects were presented to the dyad, mothers provided tactile stimulation to their 12‐month‐old infants by either (a) tensing their fingers around the infants' abdomen while abruptly inhaling, (b) relaxing their grip around the infants' abdomen, or (c) not providing additional tactile stimulation (control condition). The results revealed that infants in the first condition (a) touched the objects less and waited longer to touch the objects while displaying more negative emotional displays compared to infants in the control condition. However, no apparent differences were found between infants in the second condition (b) and the control condition. The results suggest that infants' emotions may be elicited by specific parameters of touch.
Mother‐Child Coregulation During Delay of Gratification at 30 Months
Authors: Putnam Samuel P. , Spritz Becky L. , Stifter Cynthia A.
Published: January 2004

Fifty‐eight 30‐month‐old children and their mothers were observed during a task in which the child was asked to refrain from touching an attractive toy. Child and maternal regulatory strategies were independently coded in 5‐sec intervals. Consistent with past research, the ability to refrain from touching the toy was associated with less time orienting to the forbidden object and more time focusing on other stimuli. Mothers of children who refrained from touching the toy were more likely to use distraction as a technique to assist in their children's regulation than were mothers of touchers, whereas mothers of children who transgressed used more nondistracting strategies than did mothers of nontouchers. Analysis of contingent behaviors suggested that mothers and children effectively coregulated behavior during this challenging situation, as children and mothers followed one another's lead in the allocation of attention away from the toy. These findings indicate the benefits of proactive, rather than reactive, parental strategies for assisting child delay of gratification.
Four‐Month Attentional Regulation and Its Prediction of Three‐Year Compliance
Authors: Hill Ashley L. , Braungart‐Rieker Julia M.
Published: January 2004

The extent to which 4‐month attentional regulation during an infant‐mother still‐face situation and 12‐month attachment security during the Strange Situation predicted rates of compliance and noncompliance during a cleanup task at 36 months was examined longitudinally in 70 infant‐mother dyads. Hierarchical multiple regression analyses indicated that infants who showed more attentional regulation during the still‐face situation with mothers later showed a higher rate of committed compliance and a lower rate of situational compliance during cleanup with mothers. Furthermore, lower levels of attentional regulation were later associated with higher rates of assertive behavior, but only for infants in an insecure attachment relationship.
Infants' Listening Preferences: Baby Talk or Happy Talk?
Authors: Singh Leher , Morgan James L. , Best Catherine T.
Published: January 2004

The most robust finding on infants' listening preferences has been widely characterized as a preference for baby talk (BT) over adult‐directed speech (ADS). Although prosodic modifications characteristic of BT also convey positive affect, differences in affect across BT and ADS speech registers have not been controlled in previous studies. This set of experiments sought to elucidate the basis for 6‐month‐olds' listening preference by independently manipulating affect and speech register. When affect was held constant, no preference for any speech register was observed. Moreover, when ADS stimuli presented more positive affect than BT stimuli, infants' preferences followed the positive affect. Higher and more variable pitch was neither necessary nor sufficient for determining infants' preferences, although pitch characteristics may modulate affect‐based preferences. The BT preference is thus attributable to a more general preference for speech that imparts relatively positive affect, a preference perhaps ascribable to a preexisting general‐purpose mechanism opportunistically exploited by language.
Emotion Regulation in Context: Situational Effects on Infant and Caregiver Behavior
Authors: Miller Alison L. , McDonough Susan C. , Rosenblum Katherine L. , Sameroff Arnold J.
Published: January 2004

Emotion regulation is an important developmental task of the early years of life. However, situational effects are rarely examined. In this study, we evaluated situational effects on 7‐month‐olds' and their mothers' emotional expression and interactive regulation behavior, individual differences across situations, and intercorrelations within situations. Mother‐infant dyads (N = 225) were observed interacting during episodes from play, teaching, and still‐face situations that varied along 2 developmentally salient dimensions: emotional challenge (low vs. high), and attentional focus (face‐to‐face vs. object). Attentional focus affected mothers' behavior, whereas both challenge and attentional focus affected infants. Associations between mother and infant behaviors varied in each situation. High‐challenge situations provided more consistent individual differences in infants and more negative behavior from mothers. Findings have implications for appropriate assessment of emotion regulation in infancy.