bluuebunny/crossref_metadata_2025 huggingface dataset:
Interactive exploration of movement data: A case study of geovisual analytics for fishing vessel analysis
Authors: Enguehard René A , Hoeber Orland , Devillers Rodolphe
Published: August 2012

The analysis of large movement datasets is a challenging task, because of their size and spatial complexity. This paper presents an interactive geovisual analytics approach named Hybrid Spatio-Temporal Filtering that integrates filtering of multiple movement characteristics, geovisual representations of the data, and multiple coordinated views to enable analysts to focus on movement patterns that are of interest. In particular, we propose a novel technique that combines the fractal dimension and velocity of movement paths to filter out uninteresting records through an iterative signature-building process. In order to allow analysts to explore the data at different scales of the movement path length, fractal dimension estimation is performed using an adjustable moving window technique. These tools are provided in conjunction with a probability-based zonal incursion tool to visually represent when the movement nears areas of interest. The outcome is a geovisual analytics system that allows analysts to specify a hybrid filter consisting of the desired movement path complexity, the length of the paths to consider, and the velocity range that represents specific types of behaviors. This filtering of the data supports analysts in identifying movement paths that match their specified interests, resulting in a reduction in the amount of data shown to the analyst. The utility of the approach was validated through field trials, wherein fisheries enforcement officers analyzed and explored fishing vessel movement data using the prototype system. The participants responded positively to the features of the system and the support it provided for their data analysis activities. The combination of fractal dimension, velocity, and temporal filtering helped them to effectively identify subsets of data that conformed to particular behavioral patterns of interest.
On Playing Cowboys and Indians
Authors: Pelias Ronald J.
Published: August 2012

This article traces my childhood experience of playing with cowboy and Indian toy figures. I argue that such playing was both productive and problematic for developing an ethical sense of the other. Layered between my accounts are the words of Michael Yellow Bird, who offers an alternative point of view, one that establishes how such playing might be read from the perspective of Indigenous people.
“Cowboys and Indians”
Authors: Hao Richie Neil
Published: August 2012

A sorority and fraternity at the University of Denver recently held a “Cowboys and Indians” theme party. Reflecting from this event, I examine how it has shaped my students’ attitudes toward dominant constructions of Native Americans through writing responses and class discussions to Ward Churchill’s (2010) “Crimes Against Humanity,” which questions and challenges U.S. sports teams’ and media’s use of Native American names and symbols. I critique my students’ writings and class discussions, and incorporate pedagogical practices to interrupt problematic Native American identity constructions as moments of pedagogical intervention.
Gene–Environment Interaction in Alzheimer’s Disease
Authors: Singh Neeraj Kumar , Chhillar Neelam , Banerjee B. D. , Bala Kiran , Mukherjee Ajit Kumar , Mustafa M. D. , Mitrabasu
Published: August 2012

Objectives:

The aim was to examine the gene environment (GxE) interaction with reference to APO E genotypes, serum lipids and organochlorine pesticides (OCPs) as one of the factors in the etiology of Alzheimer’s disease (AD).

Methods:

A case control study was used to examine, APOE HhaI polymorphism by polymerase chain reaction (PCR)/PCRrestriction fragment length polymorphism method, serum lipids by autoanalyser and OCPs by gas chromatography (GC).

Results:

APOE ∊4 allele frequency was significantly high (p=0.000, OR=5.73, CI=2.68-12.50) in AD as compared to controls. The serum cholesterol, β- hexachlorocyclohexane and dieldrin are risk factors for AD independent of the APOE ∊4 risk allele, recording an odds ratio of 1.16, 11.38 and 10.45 respectively.

Conclusion:

GxE interactions exist with APOE ∊4 allele status that need to be considered for the study design and analysis of such data in future studies of AD.
A New Measure of Caregiver Burden in Alzheimer’s Disease
Authors: Erder M. Haim , Wilcox Teresa K. , Chen Wen-Hung , O’Quinn Sean , Setyawan Juliana , Saxton Judith
Published: August 2012

Objective:

To validate the Caregiver-Perceived Burden Questionnaire (CPBQ) and report its psychometric properties.

Methods:

The CPBQ was administered to caregivers of patients with moderate-to-severe AD in a double-blind randomized trial comparing extended-release memantine to placebo (n = 676). Measurement properties were analyzed using factor analysis, classical test theory, and Rasch analysis.

Results:

Two subscales were identified: the Caregivers’ Assessment of the Patient (CAP) and the Caregivers’ Assessment of Themselves (CAT). The reliability was .89 (CAP) and .83 (CAT). The CAP scores were significantly correlated ( r > .3) with scores from the Severe Impairment Battery (SIB) and the Neuropsychiatric Inventory (NPI). The CAT scores were significantly correlated with NPI scores. The CAT discriminated among patients by clinician-rated severity and significantly differentiated between responders and nonresponders.

Conclusion:

The CPBQ appears to be a reliable, valid, and responsive measure that enables linking caregiver’s perceptions about burden and patient function in patients with moderate-to-severe AD.
Nutritional and Global Indexes of Progression in Dementia
Authors: Coin Alessandra , Bolzetta Francesco , Rui Marina De , Veronese Nicola , Granziera Serena , Girardi Agostino , Manzato Enzo , Sergi Giuseppe
Published: August 2012

Background:

To assess the influence of body mass index (BMI) on the progression of dementia.

Methods:

Sixty elderly outpatients with untreated dementia followed for 12 months. All patients underwent clinical, cognitive, functional, and nutritional assessment at the baseline and after 12 months. Patients were divided into 2 groups by baseline BMI (< or ≥25 kg/m2).

Results:

Participants with a baseline BMI ≥25 kg/m2 had significantly higher Mini-Mental State Examination (MMSE) scores (21 ± 5.1 vs 15.9 ± 5.5; P < .001), while clinical dementia rating (CDR) and multidimensional prognostic index (MPI) scores were similar in the 2 groups. After 12 months, the MMSE score decreased significantly in both groups compared to the baseline, while the CDR and MPI scores increased significantly for patients with a baseline BMI <25 kg/m2.

Conclusion:

A BMI cutoff of 25 kg/m2 could be useful for identifying frail patients with dementia who will experience a more rapid global impairment, which could be assessed adequately using multidimensional evaluation tools.
Bilateral Non-Superselective Embolization With Particles Under Transient Occlusion of the Internal Carotid Artery in the Management of Juvenile Nasopharyngeal Angiofibroma
Authors: Santos-Franco J. A. , Lee A. , Campos-Navarro L. A. , Tenorio-Sánchez J. , Zenteno M. , Osorio-Alvarado A. R.
Published: August 2012

Summary. Juvenile nasopharyngeal angiofibroma (JNA) is a rare histologically benign tumor, highly vascularized, with usually aggressive behavior, and can extend from the nasal cavity to neighboring structures. We present the case of a 14-year-old male harboring a JNA, presenting with an active severe and persistent epistaxis. Two previous surgical attempts of removal were unsuccessful, because of profuse intraoperative bleeding. Angiography showed a highly vascularized neoplasm with multiple branches arising from both internal carotid arteries, with absence of branches from the external carotid due to previous surgical ligation. Direct puncture tumor embolization was not possible because removal of nasal packing triggered major hemorrhage. The only option for embolization was a technique of non-superselective embolization with particles under transient occlusion of the internal carotid artery. The procedure was performed uneventfully from either side, the tumor was subsequently removed, and the patient had no recurrence 2 years after the initial treatment.
Long-Term Follow-Up of Patients After Carotid Stenting With or Without Distal Protective Device in a Single Tertiary Medical Center
Authors: Kimiagar Itzhak , Gur Alexander Y. , Auriel Eitan , Peer Amir , Sacagiu Tzvika , Bass Arie
Published: August 2012

Objective: To evaluate the immediate and long-term clinical outcomes after carotid artery stenting (CAS) with and without protection devices (PDs), compared with carotid endarterectomy (CEA). Methods: A total of 116 patients with symptomatic carotid stenosis underwent CAS; 56 patients (48.3%) underwent CAS-PD; and 137 patients underwent CEA. Results: There were more ipsilateral transient ischemic attacks (TIAs) in the CEA group than in CAS-PD and CAS + PD (4 [3%] vs 1 [1.6%] and 0 respectively, P = 0.02). In the CAS-PD group there were more vertebrobasilar TIAs, ipsi- and contralateral strokes, myocardial infarctions, and death rates in the 30-day postprocedural period. After 8-year follow-up, there were 18 (30%) death cases in the CAS-PD group, 10 death cases (17%) in the CAS + PD patients, and 15 death cases (11%) in the CEA group of patients ( P = .02). Conclusion: Our data show that CAS + PD was associated with lower rate of vascular complications and mortality compared with CAS-PD and CEA.
Effect of l-arginine on intestinal mucosal immune barrier function in weaned pigs after Escherichia coli LPS challenge
Authors: Zhu HL , Liu YL , Xie XL , Huang JJ , Hou YQ
Published: August 2012

The effects of l-arginine (Arg) supplementation on intestinal mucosal immune barrier function in weaned pigs after Escherichia coli LPS challenge were evaluated. Twenty-four weaned pigs were allotted to four treatments including: (i) non-challenged control; (ii) LPS-challenged control; (iii) LPS + 0.5% Arg; and (iv) LPS + 1.0% Arg. On d 16, pigs in the LPS, LPS + 0.5% Arg and LPS + 1.0% Arg groups were challenged by injection with 100 µg/kg of body mass LPS, whereas the control group were given sterile saline. At 48 h post-challenge, all pigs were sacrificed for evaluation of small intestinal morphology and mucosal immune barrier function. In the jejunum and ileum, LPS caused villous atrophy and intestinal morphology disruption, whereas 0.5% or 1.0% Arg supplementation mitigated villus atrophy and intestinal morphology impairment caused by LPS challenge. Arg (0.5%) supplementation increased the numbers of IgA-secreting cells, CD8+ and CD4+ T cells in the ileum ( P < 0.05). Arg supplementation prevented the elevation of mast cell numbers induced by LPS challenge ( P < 0.05). Dietary supplementation of Arg caused a decreased lymphocyte apoptosis of Peyer’s patches in pigs challenged by LPS ( P < 0.05). These results indicated that Arg supplementation protects and enhances intestinal mucosal immune barrier function and maintains intestinal integrity in weaned pigs after E. coli LPS challenge.
A therapeutic approach to hyperglycaemia in the setting of acute myocardial infarction: spotlight on glucagon-like peptide 1
Authors: Egom Emmanuel Eroume A
Published: August 2012

Patients with acute myocardial infarction (AMI) frequently have abnormalities of glucose metabolism and insulin resistance, both of which are associated with a poor outcome. Glucagon-like peptide 1 (GLP-1) is a naturally occurring incretin with both insulinotropic and insulinomimetic properties which not only controls glucose levels but also has potential beneficial actions on the ischaemic and failing heart. In this review we highlight the underlying pathophysiological mechanisms for the development of hyperglycaemia in AMI, speculate on the potential relationship between GLP-1 and sphingosine-1-phosphate, and review the literature on the role of GLP-1 as an important approach to treating hyperglycaemia in the setting of AMI.
Neurological Complications of Transplantation
Authors: Pruitt Amy A. , Graus Francesc , Rosenfeld Myrna R.
Published: August 2012

Hematopoietic cell transplantation (HCT) is the preferred treatment for an expanding range of neoplastic and nonmalignant conditions. Increasing numbers of solid organ transplantations (SOTs) add an additional population of immunosuppressed patients with multiple potential neurological problems. While the spectrum of neurological complications varies with conditioning procedure and hematopoietic cell or solid organ source, major neurological complications occur with all transplantation procedures. This 2 part review emphasizes a practical consultative approach to central and peripheral nervous system problems related to HCT or SOT with clinical and neuroimaging examples from the authors’ institutional experience with the following conditions: the diversity of manifestations of common infections such as varicella zoster virus, Aspergillus, and progressive multifocal leukoencephalopathy (PML), drug therapy-related complications, stroke mechanisms, the spectrum of graft versus host disease (GVHD), and neurologically important syndromes of immune reconstitution inflammatory syndrome (IRIS), posterior reversible encephalopathy syndrome (PRES), and posttransplantation lymphoproliferative disorder (PTLD). These complications preferentially occur at specific intervals after HCT and SOT, and neurological consultants must recognize an extensive spectrum of syndromes in order to effect timely diagnosis and expedite appropriate treatment.
BET bromodomain inhibition targets both c-Myc and IL7R in high-risk acute lymphoblastic leukemia
Authors: Ott Christopher J. , Kopp Nadja , Bird Liat , Paranal Ronald M. , Qi Jun , Bowman Teresa , Rodig Scott J. , Kung Andrew L. , Bradner James E. , Weinstock David M.
Published: August 2012

We investigated the therapeutic potential of JQ1, an inhibitor of the BET class of human bromodomain proteins, in B-cell acute lymphoblastic leukemia (B-ALL). We show that JQ1 potently reduces the viability of B-ALL cell lines with high-risk cytogenetics. Among the most sensitive were lines with rearrangements of CRLF2, which is overexpressed in ∼ 10% of B-ALL. CRLF2 heterodimerizes with the IL7 receptor (IL7R) and signals through JAK2, JAK1, and STAT5 to drive proliferation and suppress apoptosis. As previously observed, JQ1 induced the down-regulation of MYC transcription, the loss of BRD4 at the MYC promoter, and the reduced expression of c-Myc target genes. Strikingly, JQ1 also down-regulated IL7R transcription, depleted BRD4 from the IL7R promoter, and reduced JAK2 and STAT5 phosphorylation. Genome-wide expression profiling demonstrated a restricted effect of JQ1 on transcription, with MYC and IL7R being among the most down-regulated genes. Indeed, IL7R was the only cytokine receptor in CRLF2-rearranged B-ALL cells significantly down-regulated by JQ1 treatment. In mice xenografted with primary human CRLF2-rearranged B-ALL, JQ1 suppressed c-Myc expression and STAT5 phosphorylation and significantly prolonged survival. Thus, bromodomain inhibition is a promising therapeutic strategy for B-ALL as well as other conditions dependent on IL7R signaling.
Specific lipid mediator signatures of human phagocytes: microparticles stimulate macrophage efferocytosis and pro-resolving mediators
Authors: Dalli Jesmond , Serhan Charles N.
Published: August 2012

Phagocytes orchestrate acute inflammation and host defense. Here we carried out lipid mediator (LM) metabololipidomics profiling distinct phagocytes: neutrophils (PMN), apoptotic PMN, and macrophages. Efferocytosis increased specialized pro-resolving mediator (SPM) biosynthesis, including Resolvin D1 (RvD1), RvD2, and RvE2, which were further elevated by PMN microparticles. Apoptotic PMN gave elevated prostaglandin E2, lipoxin B4 and RvE2, whereas zymosan-stimulated PMN showed predominantly leukotriene B4 and 20-OH-leukotriene B4, as well as lipoxin marker 5,15-diHETE. Using deuterium-labeled precursors (d8-arachidonic acid, d5-eicosapentaenoic acid, and d5-docosahexaenoic acid), we found that apoptotic PMN and microparticles contributed to SPM biosynthesis during efferocytosis. M2 macrophages produced SPM including maresin-1 (299 ± 8 vs 45 ± 6 pg/2.5 × 105 cells; P < .01) and lower amounts of leukotriene B4 and prostaglandin than M1. Apoptotic PMN uptake by both macrophage subtypes led to modulation of their LM profiles. Leukotriene B4 was down-regulated in M2 (668 ± 81 vs 351 ± 39 pg/2.5 × 105 cells; P < .01), whereas SPM including lipoxin A4 (977 ± 173 vs 675 ± 167 pg/2.5 × 105 cells; P < .05) were increased. Conversely, uptake of apoptotic PMN by M2 macrophages reduced (∼ 25%) overall LM. Together, these results establish LM signature profiles of human phagocytes and related subpopulations. Moreover, they provide evidence for microparticle regulation of specific endogenous LM during defined stages of the acute inflammatory process and their dynamic changes in human primary phagocytes.
Reawakening fetal hemoglobin: prospects for new therapies for the β-globin disorders
Authors: Bauer Daniel E. , Kamran Sophia C. , Orkin Stuart H.
Published: August 2012

The level of fetal hemoglobin (HbF) modifies the severity of the common β-globin disorders. Knowledge of the normal mechanisms that repress HbF in the adult stage has remained limited until recently despite nearly 3 decades of molecular investigation, in part because of imperfect model systems. Recent studies have provided new insights into the developmental regulation of globin genes and identified specific transcription factors and epigenetic regulators responsible for physiologic silencing of HbF. Most prominent among these regulators is BCL11A, a transcriptional repressor that inhibits adult-stage HbF expression. KLF1 and c-Myb are additional critical HbF-regulating erythroid transcription factors more broadly involved in erythroid gene expression programs. Chromatin modifiers, including histone deacetylases and DNA methyltransferases, also play key roles in orchestrating appropriate globin gene expression. Taken together, these discoveries present novel therapeutic targets for further consideration. Although substantial hurdles remain, opportunities are now rich for the rational design of HbF inducers.
Differences between asthmatics and nonasthmatics hospitalised with influenza A infection
Authors: Myles Puja , Nguyen-Van-Tam Jonathan S. , Semple Malcolm G. , Brett Stephen J. , Bannister Barbara , Read Robert C. , Taylor Bruce L. , McMenamin Jim , Enstone Joanne E. , Nicholson Karl G. , Openshaw Peter J. , Lim Wei Shen
Published: August 2012

Asthmatics hospitalised because of influenza A infection are less likely to require intensive care or die compared with nonasthmatics. The reasons for this are unknown.

We performed a retrospective analysis of data on 1520 patients admitted to 75 UK hospitals with confirmed influenza A/H1N1 2009 infection. A multivariable model was used to investigate reasons for the association between asthma and severe outcomes (intensive care unit support or death).

Asthmatics were less likely than nonasthmatics to have severe outcome (11.2%versus19.8%, unadjusted OR 0.51, 95% CI 0.36–0.72) despite a greater proportion requiring oxygen on admission (36.4%versus26%, unadjusted OR 1.63) and similar rates of pneumonia (17.1%versus16.6%, unadjusted OR 1.04). The results of multivariable logistic regression suggest the association of asthma with outcome (adjusted OR 0.62, 95% CI 0.36–1.05; p=0.075) are explained by pre-admission inhaled corticosteroid use (adjusted OR 0.34, 95% CI 0.18–0.66) and earlier admission (≤4 days from symptom onset) (adjusted OR 0.60, 95% CI 0.38–0.94). In asthmatics, systemic corticosteroids were associated with a decreased likelihood of severe outcomes (adjusted OR 0.36, 95% CI 0.18–0.72).

Corticosteroid use and earlier hospital admission explained the association of asthma with less severe outcomes in hospitalised patients.
Sleep in children with asthma: results of the PIAMA study
Authors: van Maanen Annette , Wijga Alet H. , Gehring Ulrike , Postma Dirkje S. , Smit Henriëtte A. , Oort Frans J. , Rodenburg Roos , Meijer Anne Marie
Published: August 2012

Children with asthma are thought to have impaired sleep quality and quantity. In this study, we investigated which of the many sleep aspects are associated with asthma.

Our sample consisted of 2529 children (aged 11 years) who participated in the Prevention and Incidence of Asthma and Mite Allergy (PIAMA) birth cohort study. Parents reported about asthma symptoms (wheezing, dyspnoea, prescription of inhaled corticosteroids and asthma diagnosis) and children reported about different aspects of sleep (bedtime, rise time, sleep quality and daytime sleepiness/tiredness). Results were analysed with (logistic) regression analysis.

Children with frequent asthma symptoms significantly more often reported that they felt sleepy or tired during the day (34.4% experienced daytime sleepiness/tiredness at least once a week) than children without asthma symptoms (22.2%) and children with infrequent asthma symptoms (21.9%). This association was not confounded by sex, age of the child, parental educational level or smoking inside the house; the effect was also not modified by sex. There were no associations between asthma and bedtime, time spent in bed or sleep quality.

Children with frequent asthma symptoms experienced daytime sleepiness/tiredness more often than children with infrequent or no asthma symptoms. Otherwise, children with asthma did not differ much from children without asthma with regard to sleep.
Rapid diagnosis of primary ciliary dyskinesia: cell culture and soft computing analysis
Authors: Pifferi Massimo , Bush Andrew , Montemurro Francesca , Pioggia Giovanni , Piras Martina , Tartarisco Gennaro , Di Cicco Maria , Chinellato Iolanda , Cangiotti Angela M. , Boner Attilio L.
Published: August 2012

Diagnosis of primary ciliary dyskinesia (PCD) sometimes requires repeated nasal brushing to exclude secondary ciliary alterations. Our aim was to evaluate whether the use of a new method of nasal epithelial cell culture can speed PCD diagnosis in doubtful cases and to identify which are the most informative parameters by means of a multilayer artificial neural network (ANN).

A cross-sectional study was performed in patients with suspected PCD. All patients underwent nasal brushing for ciliary motion analysis, ultrastructural assessment and evaluation of ciliary function after ciliogenesis in culture by ANN.

151 subjects were studied. A diagnostic suspension cell culture was obtained in 117 nasal brushings. A diagnosis of PCD was made in 36 subjects (29 of whom were children). In nine out of the 36 patients the diagnosis was made only after a second brushing, because of equivocal results of both tests at first examination. In each of these subjects diagnosis of PCD was confirmed by cell culture results.

Cell culture in suspension evaluated by means of ANN allows the separation of PCD from secondary ciliary dyskinesia patients after only 5 days of culture and allows diagnosis to be reached in doubtful cases, thus avoiding the necessity of a second sample.
Vascular and right ventricular remodelling in chronic thromboembolic pulmonary hypertension
Authors: Delcroix Marion , Vonk Noordegraaf Anton , Fadel Elie , Lang Irene , Simonneau Gérald , Naeije Robert
Published: August 2012

In chronic thromboembolic pulmonary hypertension (CTEPH) increased pulmonary vascular resistance is caused by fibrotic organisation of unresolved thromboemboli. CTEPH mainly differs from pulmonary arterial hypertension (PAH) by the proximal location of pulmonary artery obliteration, although distal arteriopathy can be observed as a consequence of non-occluded area over-perfusion. Accordingly, there is proportionally more wave reflection in CTEPH, impacting on pressure and flow wave morphology. However, the time constant,i.e.resistance×compliance, is not different in CTEPH and PAH, indicating only trivial effects of proximal wave reflection on hydraulic right ventricular load. More discriminative is the analysis of the pressure decay after pulmonary arterial occlusion, which is more rapid in the absence of significant distal arteriopathy.

Structure and function of the right ventricle show a similar pattern to right ventricular hypertrophy, namely dilatation and wall thickening, as well as loss of function in CTEPH and PAH. This is probably related to similar loading conditions. Hyperventilation with hypocapnia is characteristic of both PAH and CTEPH. Ventilatory equivalents for carbon dioxide, as a function of arterial carbon dioxide tension, conform to the alveolar ventilation equation in both conditions, indicating a predominant role of increased chemosensitivity. However, a slight increase in the arterial to end-tidal carbon dioxide tension gradient in CTEPH shows a contribution of increased dead space ventilation.
Second-line anti-tuberculosis drug concentrations for susceptibility testing in the MODS assay
Authors: Fitzwater Sean Patrick , Sechler G. Andrew , Jave Oswaldo , Coronel Jorge , Mendoza Alberto , Gilman Robert H. , Friedland Jon S. , Moore David A.J.
Published: August 2012

Multidrug-resistant tuberculosis (TB) threatens TB control worldwide. The microscopic observation drug susceptibility (MODS) assay is a low-cost, high-performance TB diagnostic tool for rapid liquid culture and direct isoniazid and rifampicin drug susceptibility testing (DST). The objective of this study was to explore the potential for extending the MODS assay to rapid second-line DST and to identify critical concentrations of candidate drugs for prospective testing.

Sputum samples from 94 TB culture-positive patients receiving second-line TB agents were cultured following standardised MODS protocols, with a range of titrations of antimicrobial drugs added. Critical concentrations were determined using a modified Kaplan–Meier survival curve analysis.

Candidate critical concentrations were determined for capreomycin (10 μg·mL−1), ciprofloxacin (1.25 μg·mL−1), cycloserine (40 μg·mL−1), ethambutol (10 μg·mL−1), ethionamide (5 μg·mL−1), kanamycin (5 μg·mL−1), para-aminosalicylic acid (10 μg·mL−1) and streptomycin (10 μg·mL−1). No cut-off point was identified for the other second-line drugs or for pyrazinamide.

At particular concentrations of some second-line TB drugs this novel Kaplan–Meier analysis clearly differentiated populations that were susceptible or resistant. These candidate critical concentrations should now be tested in a range of epidemiological settings to define the performance of direct, second-line TB DST with MODS, offering potential low-cost second-line TB DST capacity.
Prediction of in-hospital death from community-acquired pneumonia by varying CRB-age groups
Authors: Ewig Santiago , Bauer Torsten , Richter Klaus , Szenscenyi Joachim , Heller Günther , Strauss Richard , Welte Tobias
Published: August 2012

C(U)RB-65 (confusion, (urea >7 mol·L−1,) respiratory frequency ≥30 breaths·min−1, systolic blood pressure <90 mmHg or diastolic blood pressure ≤60 mmHg and age ≥65 years) is now the generally accepted severity score for patients with community-acquired pneumonia (CAP) in Europe.

In an observational study based on the large database from the German nationwide performance measurement programme in healthcare quality, including data from all hospitalised patients with CAP during 2008–2010, different CRB-age groups (≥50 and ≥60 years) across the total CAP population and three entities of CAP (younger population aged <65 years, patients aged ≥65 years not residing in nursing homes and those with nursing home-acquired pneumonia (NHAP)) were validated for their potential to predict in-hospital death.

660 594 patients were investigated. Mortality was n=93 958 (14.0%). In the total population, CRB-80 had the optimal area under the curve (0.690, 95% CI 0.688–0.691). However, in the younger cohort, CRB-50 performed best (0.730, 95% CI 0.724–0.736), with good identification of low-risk patients (CRB-50 risk class 1: 1.28% deaths, negative predictive value 98.7%). In the elderly, CRB-80 as the optimal age group performed worse (0.663, 95% CI 0.660–0.655 in patients not residing in nursing homes; 0.608, 95% CI 0.605–0.611 in those with NHAP). In the latter group, all CRB-age groups failed to identify low-risk patients (CRB-80 risk class 1: 22.75% deaths, negative predictive value 81.8%).

Patients with hospitalised CAP aged <65 years may be assessed by the CRB-50 score. In those aged ≥65 years (not NHAP) assessed by the CRB-65 score, low-risk patients are already are at an increased risk of death. In NHAP patients, even the use of CRB-80 does not identify low-risk patients and should be accompanied by the evaluation of functional status and comorbidity.
The significance of early recurrent wheeze for asthma outcomes in late childhood
Authors: Hovland Vegard , Riiser Amund , Mowinckel Petter , Carlsen Kai-Håkon , Lødrup Carlsen Karin C.
Published: August 2012

Recurrent early life wheeze is not always asthma, and up to 50% of children are reported to remit. With reports of adult asthma symptom relapse, we assessed the prognosis of recurrent bronchial obstruction (rBO) through adolescence in the Environment and Childhood Asthma (ECA) prospective birth cohort study.

The present study is based on data from investigations at ages 2, 10 and 16 years of 550 young people (52% males) attending at 16 years of age. Based on the presence of rBO from 0–2 years, defined as recurrent (at least two episodes) doctor-diagnosed wheeze, and asthma from 2–10 years and 10–16 years, defined as at least two episodes of doctor-diagnosed asthma, symptoms and medication use, prognosis of rBO was assessed. Bronchial hyperresponsiveness (BHR) was diagnosed by a metacholine provocation dose ≤8 μmol that caused 20% reduction in the forced expiratory volume in 1 s.

At 10–16 years, 34% of the 143 rBO children had asthma. All children with rBO had reduced lung function compared with the never asthmatics. Of the rBO children in remission, 48.4% had asthma symptoms, medication use and/or BHR compared with 26.7% with never asthma (p<0.001).

Only 34.3% of rBO children were without asthma symptoms, medication use or BHR by 16 years, possibly indicating future asthma risk.
Smoking and asthma: dangerous liaisons
Authors: Polosa Riccardo , Thomson Neil C.
Published: August 2012

Cigarette smoking and asthma interact to induce important adverse effects on clinical, prognostic and therapeutic outcomes. This review examines recent evidence on the harmful effects of smoking in asthma, possible underlying inflammatory mechanisms for this altered response, management options for these patients and potential future therapeutic directions. Active smokers, particularly females, are at risk of developing asthma. Prevalence rates for smoking in asthma are relatively close to those found in the general population. Smokers with asthma experience worse asthma control than nonsmokers with asthma. Mechanisms for the adverse effects of smoking in asthma include altered airway inflammation and corticosteroid insensitivity. Quitting smoking can improve symptoms and lung function, but the low rates of smoking cessation highlights the need for improved strategies for managing these patients. Clinical trials assessing new therapies for asthma need to enrol smokers to identify treatments that are effective in the asthma smoking phenotype.
Cardiovascular biomarkers predict susceptibility to lung injury in World Trade Center dust-exposed firefighters
Authors: Weiden Michael D. , Naveed Bushra , Kwon Sophia , Cho Soo Jung , Comfort Ashley L. , Prezant David J. , Rom William N. , Nolan Anna
Published: August 2012

Pulmonary vascular loss is an early feature of chronic obstructive pulmonary disease. Biomarkers of inflammation and of metabolic syndrome predict loss of lung function in World Trade Center (WTC) lung injury (LI). We investigated if other cardiovascular disease (CVD) biomarkers also predicted WTC-LI.

This nested case–cohort study used 801 never-smoker, WTC-exposed firefighters with normal pre-9/11 lung function presenting for subspecialty pulmonary evaluation (SPE) before March 2008. A representative subcohort of 124 out of 801 subjects with serum drawn within 6 months of 9/11 defined CVD biomarker distribution. Post-9/11 forced expiratory volume in 1 s (FEV1) at defined cases were as follows: susceptible WTC-LI cases with FEV1≤77% predicted (66 out of 801) and resistant WTC-LI cases with FEV1≥107% predicted (68 out of 801). All models were adjusted for WTC exposure intensity, body mass index at SPE, age on 9/11 and pre-9/11 FEV1.

Susceptible WTC-LI cases had higher levels of apolipoprotein-AII, C-reactive protein and macrophage inflammatory protein-4 with significant relative risks (RRs) of 3.85, 3.93 and 0.26, respectively, with an area under the curve (AUC) of 0.858. Resistant WTC-LI cases had significantly higher soluble vascular cell adhesion molecule and lower myeloperoxidase, with RRs of 2.24 and 2.89, respectively (AUC 0.830).

Biomarkers of CVD in serum 6 months post-9/11 predicted either susceptibility or resistance to WTC-LI. These biomarkers may define pathways either producing or protecting subjects from pulmonary vascular disease and associated loss of lung function after an irritant exposure.
Haemodynamic responses to exercise in patients with COPD
Authors: Hilde Janne Mykland , Skjørten Ingunn , Hansteen Viggo , Melsom Morten Nissen , Hisdal Jonny , Humerfelt Sjur , Steine Kjetil
Published: August 2012

The present study aimed to explore the prevalence of pre-capillary pulmonary hypertension (PH) and characterise haemodynamic vascular responses to physical exercise in chronic obstructive pulmonary disease (COPD) outpatients, where left ventricular dysfunction and comorbidities were excluded.

98 patients with COPD underwent right heart catheterisation at rest and during supine exercise. Mean pulmonary artery pressure (Ppa), pulmonary capillary wedge pressure (Ppcw) and cardiac output (CO) were measured at rest and during exercise. Exercise-induced increase in meanPpawas interpreted relative to increase in blood flow, meanPpa/CO, workload (W) and meanPpa/W. Pulmonary vascular resistance (PVR) and pulmonary artery compliance (PAC) were calculated. PH at rest was defined as meanPpaat rest ≥25 mmHg andPpcwat rest <15 mmHg.

Prevalence of PH was 5%, 27% and 53% in Global Initiative for Chronic Obstructive Lung Disease stages II, III and IV, respectively. The absolute exercise-induced rise in meanPpadid not differ between subjects with and without PH. Patients without PH showed similar abnormal haemodynamic responses to exercise as the PH group, with increased PVR, reduced PAC and steeper slopes for meanPpa/CO and meanPpa/W.

Exercise revealed abnormal physiological haemodynamic responses in the majority of the COPD patients. The future definition of PH on exercise in COPD should rely on the slope of meanPparelated to cardiac output and workload rather than the absolute values of meanPpa.
Short cigarette smoke exposure facilitates sensitisation and asthma development in mice
Authors: Lanckacker Ellen A. , Tournoy Kurt G. , Hammad Hamida , Holtappels Gabriele , Lambrecht Bart N. , Joos Guy F. , Maes Tania
Published: August 2012

Epidemiological studies indicate that cigarette smoke exposure is a risk factor for increased sensitisation and asthma development. The aim of this study was to examine the impact of cigarette smoke on sensitisation and allergic airway inflammation in response to a low dose of house dust mite (HDM), and to obtain potential mechanistic insights.

Mice were exposed to low doses of HDM extract combined with air or cigarette smoke exposure, either during allergen sensitisation or during the development of allergic airway disease.

Mice concomitantly exposed to low-dose HDM, combined with cigarette smoke for 3 weeks, demonstrated an asthmatic phenotype with significantly increased airway eosinophilia, goblet cell metaplasia, airway hyperresponsiveness and a rise in HDM-specific serum immunoglobulin G1, compared to sole HDM or cigarette smoke exposure. In addition, short cigarette smoke inhalation, during the initial contact with HDM allergens, was sufficient to facilitate sensitisation and development of a complete asthmatic phenotype after rechallenge with HDM. Mechanistically, short cigarette smoke exposure amplified dendritic cell-mediated transport of fluorescein isothiocyanate-labelled HDM allergens to the intrathoracic lymph nodes and generated a local T-helper cell type 2 response.

Short cigarette smoke exposure is sufficient to facilitate allergic sensitisation and the development of low-dose HDM-induced allergic asthma, possibly by affecting dendritic cell function.
Granulomatosis-associated common variable immunodeficiency disorder: a case–control studyversussarcoidosis
Authors: Bouvry Diane , Mouthon Luc , Brillet Pierre-Yves , Kambouchner Marianne , Ducroix Jean-Pierre , Cottin Vincent , Haroche Julien , Viallard Jean-Francois , Lazor Romain , Lebargy François , Tazi Abdellatif , Wallaert Benoît , Smail Amar , Pellegrin Jean-Luc , Nunes Hilario , Amoura Zahir , Cordier Jean-François , Valeyre Dominique , Naccache Jean-Marc ,   the Groupe Sarcoïdose Francophone
Published: August 2012

The aim of the present study was to investigate to what extent interstitial lung disease (ILD) in common variable immunodeficiency disorder (CVID)-associated granulomatous disease (GD) is similar to pulmonary sarcoidosis

20 patients with CVID/GD were included in a retrospective study conducted by the Groupe Sarcoïdose Francophone. Medical records were centralised. Patients were compared with 60 controls with sarcoidosis.

Clinical examination showed more frequent crackles in patients than controls (45%versus1.7%, respectively; p<0.001). On thoracic computed tomography scans, nodules (often multiple and with smooth margins), air bronchograms and halo signs were more frequent in patients than controls (80%versus42%, respectively; p=0.004) as well as bronchiectasis (65%versus23%, respectively; p<0.001). The micronodule distribution was perilymphatic in 100% of controls and in 42% of patients (p<0.001). Bronchoalveolar lavage analysis showed lower T-cell CD4/CD8 ratios in patients than in controls (mean±sd1.6±1.1versus5.3±4, respectively; p<0.01). On pathological analysis, nodules and consolidations corresponded to granulomatous lesions with or without lymphocytic disorders in most cases. Mortality was higher in patients than controls (30%versus0%, respectively) and resulted from common variable immunodeficiency complications.

ILD in CVID/GD presents a specific clinical picture and evolution that are markedly different from those of sarcoidosis.
Sleep apnoea is a common occurrence in females
Authors: Franklin Karl A. , Sahlin Carin , Stenlund Hans , Lindberg Eva
Published: August 2012

Obstructive sleep apnoea (OSA) is primarily regarded as a male disorder, presenting with snoring, daytime sleepiness and cardiovascular disease. We aimed to determine the frequency of sleep apnoea among females in the general population.

We investigated 400 females from a population-based random sample of 10,000 females aged 20–70 yrs. They answered a questionnaire and performed overnight polysomnography.

OSA (apnoea/hypopnoea index (AHI) ≥5) was found in 50% (95% CI 45–55%) of females aged 20–70 yrs. Sleep apnoea was related to age, obesity and hypertension, but not to daytime sleepiness. Severe sleep apnoea (AHI ≥30) was present in 14% (95% CI 8.1–21%) of females aged 55–70 yrs and in 31% (95% CI 12–50%) of obese females with a body mass index of ≥30 kg·m−2aged 55–70 yrs. Sleep apnoea with daytime sleepiness and sleep apnoea with hypertension were observed as two different phenotypes of OSA.

OSA occurs in 50% of females aged 20–70 yrs. 20% of females have moderate and 6% severe sleep apnoea. Sleep apnoea in females is related to age, obesity and hypertension, but not to daytime sleepiness. When searching for sleep apnoea in females, females with hypertension or obesity should be investigated.
Reconstructing DNA copy number by joint segmentation of multiple sequences
Authors: Zhang Zhongyang , Lange Kenneth , Sabatti Chiara
Published: August 2012

Background

Variations in DNA copy number carry information on the modalities of genome evolution and mis-regulation of DNA replication in cancer cells. Their study can help localize tumor suppressor genes, distinguish different populations of cancerous cells, and identify genomic variations responsible for disease phenotypes. A number of different high throughput technologies can be used to identify copy number variable sites, and the literature documents multiple effective algorithms. We focus here on the specific problem of detecting regions where variation in copy number is relatively common in the sample at hand. This problem encompasses the cases of copy number polymorphisms, related samples, technical replicates, and cancerous sub-populations from the same individual.

Results

We present a segmentation method named generalized fused lasso (GFL) to reconstruct copy number variant regions. GFL is based on penalized estimation and is capable of processing multiple signals jointly. Our approach is computationally very attractive and leads to sensitivity and specificity levels comparable to those of state-of-the-art specialized methodologies. We illustrate its applicability with simulated and real data sets.

Conclusions

The flexibility of our framework makes it applicable to data obtained with a wide range of technology. Its versatility and speed make GFL particularly useful in the initial screening stages of large data sets.
Insights into the evolution of sorbitol metabolism: phylogenetic analysis of SDR196C family
Authors: Sola-Carvajal Agustín , García-García María I , García-Carmona Francisco , Sánchez-Ferrer Álvaro
Published: August 2012

Background

Short chain dehydrogenases/reductases (SDR) are NAD(P)(H)-dependent oxidoreductases with a highly conserved 3D structure and of an early origin, which has allowed them to diverge into several families and enzymatic activities. The SDR196C family (http://www.sdr-enzymes.org) groups bacterial sorbitol dehydrogenases (SDH), which are of great industrial interest. In this study, we examine the phylogenetic relationship between the members of this family, and based on the findings and some sequence conserved blocks, a new and a more accurate classification is proposed.

Results

The distribution of the 66 bacterial SDH species analyzed was limited to Gram-negative bacteria. Six different bacterial families were found, encompassing α-, β- and γ-proteobacteria. This broad distribution in terms of bacteria and niches agrees with that of SDR, which are found in all forms of life. A cluster analysis of sorbitol dehydrogenase revealed different types of gene organization, although with a common pattern in which the SDH gene is surrounded by sugar ABC transporter proteins, another SDR, a kinase, and several gene regulators.

According to the obtained trees, six different lineages and three sublineages can be discerned. The phylogenetic analysis also suggested two different origins for SDH in β-proteobacteria and four origins for γ-proteobacteria.

Finally, this subdivision was further confirmed by the differences observed in the sequence of the conserved blocks described for SDR and some specific blocks of SDH, and by a functional divergence analysis, which made it possible to establish new consensus sequences and specific fingerprints for the lineages and sub lineages.

Conclusion

SDH distribution agrees with that observed for SDR, indicating the importance of the polyol metabolism, as an alternative source of carbon and energy. The phylogenetic analysis pointed to six clearly defined lineages and three sub lineages, and great variability in the origin of this gene, despite its well conserved 3D structure. This suggests that SDH are very old and emerged early during the evolution. This study also opens up a new and more accurate classification of SDR196C family, introducing two numbers at the end of the family name, which indicate the lineage and the sublineage of each member, i.e, SDR196C6.3.
Characterization of biofilm-like structures formed by Pseudomonas aeruginosa in a synthetic mucus medium
Authors: Haley Cecily L , Colmer-Hamood Jane A , Hamood Abdul N
Published: August 2012

Background

The accumulation of thick stagnant mucus provides a suitable environment for the growth of Pseudomonas aeruginosa and Staphylococcus aureus within the lung alveoli of cystic fibrosis (CF) patients. These infections cause significant lung damage, leading to respiratory failure and death. In an artificial mucin containing medium ASM+, P. aeruginosa forms structures that resemble typical biofilms but are not attached to any surface. We refer to these structures as biofilm like structures (BLS). Using ASM+ in a static microtiter plate culture system, we examined the roles of mucin, extracellular DNA, environmental oxygen (EO2), and quorum sensing (QS) in the development of biofilm-like structures (BLS) by P. aeruginosa; and the effect of EO2 and P. aeruginosa on S. aureus BLS.

Results

Under 20% EO2, P. aeruginosa strain PAO1 produced BLS that resemble typical biofilms but are confined to the ASM+ and not attached to the surface. Levels of mucin and extracellular DNA within the ASM+ were optimized to produce robust well developed BLS. At 10% EO2, PAO1 produced thicker, more developed BLS, while under 0% EO2, BLS production was diminished. In contrast, the S. aureus strain AH133 produced well-developed BLS only under 20% EO2. In PAO1, loss of the QS system genes rhlI and rhlR affected the formation of BLS in ASM+ in terms of both structure and architecture. Whether co-inoculated into ASM+ with AH133, or added to established AH133 BLS, PAO1 eliminated AH133 within 48–56 h.

Conclusions

The thick, viscous ASM+, which contains mucin and extracellular DNA levels similar to those found in the CF lung, supports the formation of biofilm-like structures similar to the aggregates described within CF airways. Alterations in environmental conditions or in the QS genes of P. aeruginosa, as occurs naturally during the progression of CF lung infection, affect the architecture and quantitative structural features of these BLS. Thus, ASM+ provides an in vitro medium in which the effect of changing levels of substances produced by the host and the bacteria can be analyzed to determine the effect on such structures and on the susceptibility of the bacteria within the BLS to various treatments.