bluuebunny/crossref_metadata_2025 huggingface dataset:
Information asymmetry around S&P 500 index changes
Authors: Ravi Rahul , Hong Youna
Published: April 2015

Purpose

– This study aims to explore information asymmetry (IA) (as measured by the adverse selection component of the bid-ask spread) around S&P 500 revisions.

Design/methodology/approach

– The authors use adverse selection cost of trading measures to examine the effects of S&P 500 index composition changes on the trading environment from 2001 to 2010.

Findings

– The authors find that the adverse selection cost of trading significantly decreases post-addition and increases post-deletion. However, the intraday price dynamics of additions to the index seem to be distinct from those of deletions from the index. The event period cumulative abnormal returns (CARs) for additions are significantly associated with the change in the adverse selection cost of trading. However, this association is non-significant for deletions. The CARs for deletion events are found to be significantly associated with the change in realized spreads. Realized spreads are a measure of revenue earned by liquidity providers in the market.

Originality/value

– This study helps better understand the dynamics of two types of IA – one from a firm to investor and the other between investors – and presents evidence of the role of adverse selection in index changes. By doing so, it helps better understand the mechanism driving price formation post-addition to and deletion from an index.
Understanding coach dismissals in European professional football
Authors: Nissen Rasmus
Published: April 2015

Purpose

– The purpose of this paper is to outline a theoretical framework that can be used to understand coach dismissals in professional football.

Design/methodology/approach

– In order to embed the suggested framework empirically and thereby strengthen the argumentation, a total of 90 management accounts from 18 Danish professional football clubs have been analyzed using a qualitative content analysis approach. The accounts cover a period of five consecutive seasons.

Findings

– The analysis shows that dismissing the coach is a frequent occurrence in Danish clubs. This finding is included in the discussion, in which it is suggested that a coach dismissal may be the outcome of mimetic, coercive or normative isomorphism.

Research limitations/implications

– The applied methodology makes it difficult to assess whether coach dismissals actually stem from institutional forces. A more extensive research design and methodological setup is required in order to elaborate the proposed framework.

Practical implications

– By focussing on the dynamics of club-stakeholder relationships, the proposed framework can be seen as an attempt to clarify key features of the decision-making process surrounding coach dismissals in European professional football. Furthermore, the framework suggests that in order for a club to stay attractive to its stakeholders, and thereby increase its chances of securing future financial support, club directors should pay attention to their external environment.

Originality/value

– In contrast to existing research, this study does not aim at assessing whether a coach dismissal pays off in terms of wins on the pitch. Instead, a qualitative approach has been selected in order to offer a framework that aims at providing an in-depth understanding of coach dismissals in professional football.
Predictable communities of soil bacteria in relation to nutrient concentration and successional stage in a laboratory culture experiment
Authors: Song Woojin , Kim Mincheol , Tripathi Binu M. , Kim Hyoki , Adams Jonathan M.
Published: April 2015

It is difficult to understand the processes that structure immensely complex bacterial communities in the soil environment, necessitating a simplifying experimental approach. Here, we set up a microcosm culturing experiment with soil bacteria, at a range of nutrient concentrations, and compared these over time to understand the relationship between soil bacterial community structure and time/nutrient concentration. DNA from each replicate was analysed using HiSeq2000 Illumina sequencing of the 16S rRNA gene. We found that each nutrient treatment, and each time point during the experiment, produces characteristic bacterial communities that occur predictably between replicates. It is clear that within the context of this experiment, many soil bacteria have distinct niches from one another, in terms of both nutrient concentration, and successional time point since a resource first became available. This fine niche differentiation may in part help to explain the coexistence of a diversity of bacteria in soils. In this experiment, we show that the unimodal relationship between nutrient concentration/time and species diversity often reported in communities of larger organisms is also evident in microbial communities.
Short‐selling pressure and last‐resort debt finance: evidence from 144A high‐yield risk‐adjusted debt
Authors: Tan Kelvin Jui Keng , Lee Jia Min , Faff Robert W.
Published: April 2015

This study examines why non‐financial publicly traded firms knowingly issue wealth destroying Rule 144A debt, which is associated with a negative announcement return and a higher yield. We provide a plausible ‘demand‐side’ explanation (i.e. last‐resort debt financing) for the motivation for issuing such debt. We also provide evidence as to what drives this negative reaction. Our findings suggest that the negative market impact is mainly driven by short‐selling pressure from convertible bond arbitrageurs.
The association between speed of transition from initiation to subsequent use of cannabis and later problematic cannabis use, abuse and dependence
Authors: Hines Lindsey A. , Morley Katherine I. , Strang John , Agrawal Arpana , Nelson Elliot C. , Statham Dixie , Martin Nicholas G. , Lynskey Michael T.
Published: April 2015

Aims

To test whether speed of transition from initiation use to subsequent use of cannabis is associated with likelihood of later cannabis dependence and other outcomes, and whether transition speed is attributable to genetic or environmental factors.

Design

Cross‐sectional interview study.

Setting

Australia.

Participants

A total of 2239 twins and siblings who reported using cannabis at least twice [mean age at time of survey = 32.0, 95% confidence interval (CI) = 31.9 – 32.1, range = 22–45].

Measurements

Time between initiation and subsequent cannabis use (within 1 week; within 3 months; between 3 and 12 months; more than 1 year later), later use of cannabis and symptoms of DSM‐IV cannabis abuse/dependence. Multinomial regression analyses (comparison group: more than 1 year later) adjusted the association between speed of transition and the outcomes of cannabis daily use, abuse/dependence and treatment‐seeking after controlling for socio‐demographic, childhood, mental health, peer and licit drug factors. Twin modelling estimated the proportion of variance in transition speed attributable to genetic (A), common environment (C) and unique environmental (E) factors.

Findings

Subsequent use of cannabis within 1 week of initiation was associated with daily use [odds ratio (OR) = 2.64, 95% CI = 1.75–3.99], abuse and/or dependence (OR = 3.25, 95% CI = 2.31–4.56) and treatment‐seeking for cannabis problems (OR = 1.89, 95% CI = 1.03–3.46). Subsequent use within 3 months was associated with abuse and/or dependence (OR = 1.61, 95% CI = 1.18–2.19). The majority of the variation of the speed of transition was accounted for by unique environment factors (0.75).

Conclusions

Rapid transition from initiation to subsequent use of cannabis is associated with increased likelihood of subsequent daily cannabis use and abuse/dependence.
Nocturnal blood pressure in primary open‐angle glaucoma
Authors: Pillunat Karin R. , Spoerl Eberhard , Jasper Carolin , Furashova Olga , Hermann Cosima , Borrmann Anne , Passauer Jens , Middeke Martin , Pillunat Lutz E.
Published: April 2015

Purpose

To evaluate the nocturnal blood pressure (BP) dipping‐pattern in patients with manifest primary open‐angle glaucoma (POAG) and to find possible associations with the severity of visual field damage.

Methods

A number of 314 patients suffering from POAG were consecutively enrolled in this cross‐sectional hospital‐based study. Each patient had diurnal intraocular pressure (IOP) measurements, 24‐hr BP monitoring and computerized perimetry with the Humphrey 30‐2 sita Standard program. Inclusion criteria were a mean IOP of less than 15 mmHg with fluctuations of less than 5 mmHg and a visual acuity of at least 20/40. One eye was randomly selected. Based on the night–day BP ratio, a mean arterial nocturnal BP drop of less than 10% was considered as non‐dipping, between 10% and 20% as physiological dipping and of more than 20% as over‐dipping.

Results

Glaucoma patients with daytime systemic normotension on the average had more visual field loss in the over‐dipper group (MD = − 16.6 dB, IQR = −18.9 to −2.7 dB) than glaucoma patients with daytime systemic hypertension, who had less visual field defects in the over‐dipper group (MD = −3.9 dB, IQR = −6.2 to −1.9 dB) (p = 0.004). This result was also found taking age, glaucoma duration, visual acuity, gender, systemic and topical medication as covariates into account.

Conclusions

To judge the nocturnal BP situation of an individual patient, it is important to do this in relation to the daytime BP level. Twenty‐four‐hour BP evaluation might be important for all patients with POAG, as nocturnal BP could be a modifiable risk factor for glaucoma severity and progression.
Iran's Nuclear Program: Regional Implications and Possible Outcomes
Authors: Ismail Muhammad
Published: April 2015

As a result of its geostrategic, geopolitical, and geocultural position, Iran has a special influence on regional politics. Iran's nuclear program can tilt the balance of power in West Asia in its own favor, but the competing states from the region are expected to oppose such a program. Iran's choice of nonconventional weapons would be extremely likely to influence neighboring countries to start their own nuclear weapons programs to maintain the balance of power in the West Asian region. This article contends that the Iranian nuclear issue should be dealt with immediately. It concludes that the issue of Iran's nuclear ambitions must be properly resolved because it can lead to a new round of regional and global nuclear proliferation.
Drug disposition and modelling before and after gastric bypass: immediate and controlled‐release metoprolol formulations
Authors: Gesquiere Ina , Darwich Adam S. , Van der Schueren Bart , de Hoon Jan , Lannoo Matthias , Matthys Christophe , Rostami Amin , Foulon Veerle , Augustijns Patrick
Published: April 2015

Aims

The aim of the present study was to evaluate the disposition of metoprolol after oral administration of an immediate and controlled‐release formulation before and after Roux‐en‐Y gastric bypass (RYGB) surgery in the same individuals and to validate a physiologically based pharmacokinetic (PBPK) model for predicting oral bioavailability following RYGB.

Methods

A single‐dose pharmacokinetic study of metoprolol tartrate 200 mg immediate release and controlled release was performed in 14 volunteers before and 6–8 months after RYGB. The observed data were compared with predicted results from the PBPK modelling and simulation of metoprolol tartrate immediate and controlled‐release formulation before and after RYGB.

Results

After administration of metoprolol immediate and controlled release, no statistically significant difference in the observed area under the curve (AUC0–24 h) was shown, although a tendency towards an increased oral exposure could be observed as the AUC0–24 h was 32.4% [95% confidence interval (CI) 1.36, 63.5] and 55.9% (95% CI 5.73, 106) higher following RYGB for the immediate and controlled‐release formulation, respectively. This could be explained by surgery‐related weight loss and a reduced presystemic biotransformation in the proximal gastrointestinal tract. The PBPK values predicted by modelling and simulation were similar to the observed data, confirming its validity.

Conclusions

The disposition of metoprolol from an immediate‐release and a controlled‐release formulation was not significantly altered after RYGB; there was a tendency to an increase, which was also predicted by PBPK modelling and simulation.
Measuring ICT use and contributing conditions in primary schools
Authors: Vanderlinde Ruben , Aesaert Koen , van Braak Johan
Published: April 2015

Information and communication technology (ICT) use became of major importance for primary schools across the world as ICT has the potential to foster teaching and learning processes. ICT use is therefore a central measurement concept (dependent variable) in many ICT integration studies. This data paper presents two datasets (2008 and 2011) that contain measurements on ICT use in primary schools on the one hand and contributing conditions on the other hand. In both datasets, ICT use refers to different types of use: basic ICT use, ICT as a learning tool and ICT as an information tool. The influencing conditions refer to variables situated on the individual teacher level (eg, ICT competences, ICT professional development, etc) and the school organization level (eg, ICT school vision, ICT leadership, etc) that support or hinder the use of ICT for teaching and learning.
Sedimentary indications and absolute chronology of Holocene relative sea‐level changes retrieved from coastal lagoon deposits on Samsø, Denmark
Authors: Sander Lasse , Fruergaard Mikkel , Koch Julian , Johannessen Peter N. , Pejrup Morten
Published: April 2015

Coastal lagoons are a typical feature of the landscape in central Denmark. The lagoons formed when basins within the inherited glacial topography were flooded by the mid‐Holocene sea‐level rise. The transgression initiated coastal geomorphological processes and prompted marine sedimentation in the inundated areas. Despite their common occurrence and wide distribution in the area, coastal lagoons and their deposits have rarely been studied as sedimentary archives. The absolute chronology established for the basal marine deposits in sediment cores retrieved from coastal lagoons on the island of Samsø, southern Kattegat Sea, central Denmark, is evidence of a nearly synchronous onset of marine sedimentation at different elevations. This is interpreted as a new indication of a period of very rapid relative sea‐level (RSL) rise between 7.6 and 7.2 ka BP. Following a period of RSL highstand, a marked facies change in the deposits from an inactive lagoon yields consistent ages of around 4.1 ka BP and may be an indication of a marked RSL fall. This study illustrates the potential of coastal lagoons as sedimentary archives for the reconstruction of RSL in SW Scandinavia and in similar coastal environments elsewhere.
Receptors involved in the modulation of guinea pig urinary bladder motility by prostaglandin D2
Authors: Guan Na N , Svennersten Karl , de Verdier Petra J , Wiklund N Peter , Gustafsson Lars E
Published: April 2015

Background and Purpose

We have described a urothelium‐dependent release of PGD2‐like activity which had inhibitory effects on the motility of guinea pig urinary bladder. Here, we have pharmacologically characterized the receptors involved and localized the sites of PGD2 formation and of its receptors.

Experimental Approach

In the presence of selective DP and TP receptor antagonists alone or combined, PGD2 was applied to urothelium‐denuded diclofenac‐treated urinary bladder strips mounted in organ baths. Antibodies against PGD2 synthase and DP1 receptors were used with Western blots and for histochemistry.

Key Results

PGD2 inhibited nerve stimulation ‐induced contractions in strips of guinea pig urinary bladder with estimated pIC50 of 7.55 ± 0.15 (n = 13), an effect blocked by the DP1 receptor antagonist BW‐A868C. After blockade of DP1 receptors, PGD2 enhanced the contractions, an effect abolished by the TP receptor antagonist SQ‐29548. Histochemistry revealed strong immunoreactivity for PGD synthase in the urothelium/suburothelium with strongest reaction in the suburothelium. Immunoreactive DP1 receptors were found in the smooth muscle of the bladder wall with a dominant localization to smooth muscle membranes.

Conclusions and Implications

In guinea pig urinary bladder, the main effect of PGD2 is an inhibitory action via DP1 receptors localized to the smooth muscle, but an excitatory effect via TP receptors can also be evoked. The urothelium with its suburothelium might signal to the smooth muscle which is rich in PGD2 receptors of the DP1 type. The results are important for our understanding of regulation of bladder motility.
Immunoinflammatory diseases of the central nervous system – the tale of two cytokines
Authors: Hofer M J , Campbell I L
Published: April 2015

Cytokines are potent mediators of cellular communication that have crucial roles in the regulation of innate and adaptive immunoinflammatory responses. Clear evidence has emerged in recent years that the dysregulated production of cytokines may in itself be causative in the pathogenesis of certain immunoinflammatory disorders. Here we review current evidence for the involvement of two different cytokines, IFN‐α and IL‐6, as principal mediators of specific immunoinflammatory disorders of the CNS. IFN‐α belongs to the type I IFN family and is causally linked to the development of inflammatory encephalopathy exemplified by the genetic disorder, Aicardi–Goutières syndrome. IL‐6 belongs to the gp130 family of cytokines and is causally linked to a number of immunoinflammatory disorders of the CNS including neuromyelitis optica, idiopathic transverse myelitis and genetically linked autoinflammatory neurological disease. In addition to clinical evidence, experimental studies, particularly in genetically engineered mouse models with astrocyte‐targeted, CNS‐restricted production of IFN‐α or IL‐6 replicate many of the cardinal neuropathological features of these human cytokine‐linked immunoinflammatory neurological disorders giving crucial evidence for a direct causative role of these cytokines and providing further rationale for the therapeutic targeting of these cytokines in neurological diseases where indicated.

Linked Articles

This article is part of a themed section on Inflammation: maladies, models, mechanisms and molecules. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2016.173.issue-4
A novel snake venom‐derived GPIb antagonist, anfibatide, protects mice from acute experimental ischaemic stroke and reperfusion injury
Authors: Li Ting‐Ting , Fan Man‐Li , Hou Shi‐Xiang , Li Xiao‐Yi , Barry Devin M , Jin Hui , Luo Sheng‐Yong , Kong Feng , Lau Lit‐Fui , Dai Xiang‐Rong , Zhang Guo‐Hui , Zhou Lan‐Lan
Published: April 2015

Background and Purpose

Ischaemic stroke is a serious disease with limited therapy options. Glycoprotein (GP)Ib binding to von Willebrand factor (vWF) exposed at vascular injury initiates platelet adhesion and contributes to platelet aggregation. GPIb has been suggested as an effective target for antithrombotic therapy in stroke. Anfibatide is a GPIb antagonist derived from snake venom and we investigated its protective effect on experimental brain ischaemia in mice.

Experimental Approach

Focal cerebral ischaemia was induced by 90 min of transient middle cerebral artery occlusion (MCAO). These mice were then treated with anfibatide (4, 2, 1 μg·kg−1), injected i.v., after 90 min of MCAO, followed by 1 h of reperfusion. Tirofiban, a GPIIb/IIIα antagonist, was used as a positive control.

Key Results

Twenty‐four hours after MCAO, anfibatide‐treated mice showed significantly improved ischaemic lesions in a dose‐dependent manner. The mice had smaller infarct volumes, less severe neurological deficits and histopathology of cerebrum tissues compared with the untreated MCAO mice. Moreover, anfibatide decreased the amount of GPIbα, vWF and accumulation of fibrin(ogen) in the vasculature of the ischaemic hemisphere. Tirofiban had similar effects on infarct size and fibrin(ogen) deposition compared with the MCAO group. Importantly, the anfibatide‐treated mice showed a lower incidence of intracerebral haemorrhage and shorter tail bleeding time compared with the tirofiban‐treated mice.

Conclusions and Implications

Our data indicate anfibatide is a safe GPIb antagonist that exerts a protective effect on cerebral ischaemia and reperfusion injury. Anfibatide is a promising candidate that could be beneficial for the treatment of ischaemic stroke.
Political Pugilists: Recuperative Gender Strategies in Canadian Electoral Politics
Authors: Maiolino Elise
Published: April 2015

This paper offers the concept recuperative gender strategies to describe how political leaders work to restore their public gender identities. The author examines a charity‐boxing match between two Canadian politicians, Justin Trudeau and Patrick Brazeau. Trudeau is the current leader of the Liberal Party of Canada and son of former Prime Minister, Pierre Trudeau. Brazeau was a Conservative Senator. Through a discourse analysis of 222 national newspaper articles published on the match, this paper chronicles Justin Trudeau's transition from “precariously masculine” to “sufficiently masculine” and discusses the significance of this transformation for Trudeau's suitability for Liberal Party leadership.

Cet article propose le concept de stratégies de récupération des sexes pour décrire et expliquer comment des dirigeants politiques travaillent à rétablir leurs identités sexuelles publiques. J’analyse la couverture médiatique du combat de boxe caritatif datant de mars 2012 et opposant deux politiciens canadiens : Justin Trudeau, le chef du Parti libéral du Canada, et Patrick Brazeau, un sénateur conservateur. En m'appuyant sur une analyse de discours de 222 articles de journaux nationaux publiés au sujet de ce combat, je détaille la transition de Justin Trudeau d'une forme de masculinité « précaire » à une « masculinité suffisante », et je discute de l'importance de cette transformation pour l'aptitude perçue de Trudeau comme chef du Parti libéral.
Evaluation of noise‐induced hearing loss by auditory steady‐state and auditory brainstem‐evoked responses
Authors: Karawani H. , Attias J. , Shemesh R. , Nageris B.
Published: April 2015

Objectives

Noise‐induced hearing loss (NIHL) may result from occupational noise exposures and is considered as an ‘Occupational Disease’; therefore, it is compensable. To verify the existence and severity of the work‐related hearing loss, there is a need of an objective, reliable auditory measure in cases of arbitration of financial disputes to resolve any medicolegal aspects. The objective of the study was to compare between the ABR and ASSR for predicting the behavioural threshold in subjects with normal hearing or NIHL.

Design

The study included 82 subjects regularly exposed to high levels of occupational noise, with normal hearing and NIHL. ABR to clicks and to tone bursts were recorded followed by multiple‐frequency ASSR. Physiological and behavioural thresholds were compared for specific frequencies (1000, 2000 Hz) and average of high‐frequency range (2000 and 4000 Hz). In addition, Pearson correlations and the specificity and sensitivity of each measure were also calculated using receiver operating characteristic (ROC) curves.

Results

In the NIHL group, there was a significantly smaller difference between the behavioural threshold and click‐ABR than the ASSR in high‐frequency range. Pearson correlations were significantly higher for click‐ABR. Analysis of specific frequencies yielded a smaller difference between behavioural and ASSR than tone‐burst‐ABR thresholds, with a slightly better correlation for ASSR than tone‐burst‐ABR. Higher sensitivity but lower specificity was suggested for ASSR than ABR.

Conclusions

ASSR is associated with high‐frequency specificity, shorter test sessions and good correlations with behavioural thresholds, making it a potentially better measure than ABR for predicting audiograms in subjects with NIHL. These findings have diagnostic implications, especially in cases of workers' compensation when subjects may be uncooperative.
Use of antiseptic hand rubs in the health and community services industry: an Australian population‐based survey
Authors: MacFarlane Ewan , LaMontagne Anthony D. , Driscoll Tim , Nixon Rosemary L. , Keegel Tessa
Published: April 2015

Background

The use of antiseptic hand rubs (AHRs), rather than washing with soap and water, is considered to be the gold standard for reducing the frequency of nosocomial infections, as well as being less damaging to the hands than washing with soap and water, but little is known at a population level about usage patterns for AHRs.

Objectives

To describe AHR use patterns among workers in the health and community services industry in Australia.

Methods

Using data from a population‐based survey of Australian workers, we focused on health and community services workers' exposure to chemicals at work, including the use of AHRs. Data regarding the frequency of hand‐washing were also collected.

Results

Nine hundred and fifty‐six health and community service workers participated in the Australian National Hazard Exposure Worker Surveillance survey. Of these, 11% reported using AHRs, and 31% reported hand‐washing >20 times per shift. According to an adjusted logistic regression model, professional workers [adjusted odds ratio (aOR) 2.29, 95% confidence interval (CI): 1.40–3.72] and frequent hand washers (aOR 3.08, 95%CI: 1.92−4.93) were more likely to use AHRs.

Conclusions

AHR use by health and community service workers was generally lower than expected. AHR use was most likely to be reported by professionals and frequent hand washers, suggesting that AHRs are used as an adjunct to conventional hand‐washing.
A double‐blinded randomized multicentre study to investigate the effect of changes in stimulation parameters on sacral nerve stimulation for constipation
Authors: Thomas G. P. , Duelund‐Jakobsen J. , Dudding T. C. , Bradshaw E. , Nicholls R. J. , Alam A. , Emmanuel A. , Thin N. , Knowles C. H. , Laurberg S. , Vaizey C. J.
Published: April 2015

Aim

Sacral nerve stimulation (SNS) may be offered to patients with constipation who have failed to improve with conservative treatment. The response to SNS is variable, with a significant loss of efficacy in some patients. An increased frequency of stimulation may improve the efficacy of SNS for faecal incontinence. This study aimed to see if alteration of the pulse width or frequency improved the outcome for those with constipation.

Method

Eleven patients with constipation currently being treated by SNS were recruited from three centres. They were randomized to five different protocols of stimulation each applied for 5 weeks. Group 1 used standard settings (pulse width 210 μs, frequency 14 Hz); in the other four groups (Groups 2–5) the pulse width and/or frequency were halved or doubled. Patients and investigators were blinded to the group allocation.

Results

The Cleveland Clinic constipation score varied significantly between the five groups. Group 1 achieved the lowest score mean (± SD) 13.4 (± 4.4) (P = 0.03). The number of digitations per defaecation was the lowest in Group 4, 90 μs and 14 Hz (P < 0.01). No other variable changed significantly. Standard settings were the most preferred by the recruited patients.

Conclusion

Alteration of pulse width or frequency of stimulation had no significant effect on the outcome of SNS for constipation.
The role of EBUS‐TBNA and standard bronchoscopic modalities in the diagnosis of sarcoidosis
Authors: Dziedzic Dariusz Adam , Peryt Adam , Orlowski Tadeusz
Published: April 2015

Background and Aims

Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) is an accurate and minimally invasive technique that has been shown to have excellent diagnostic yield in the diagnosis of mediastinal and hilar lymphadenopathy. However, endoscopic bronchial biopsy (EBB) and transbronchial lung biopsy (TBLB) are still the standard method for making a pathologic diagnosis of sarcoidosis. The aim of this study was to compare the diagnostic yield of EBUS‐TBNA and TBLB through a flexible bronchoscope in patients with stage I and II sarcoidosis.

Methods

A total of 653 patients with suspected stage I and II sarcoidosis were included in this retrospective study. After radiological assessment, patients were qualified to bronchoscopy. Patients underwent sequential EBUS‐TBNA followed by TBLB and/or EBB. In all patients, 1056 biopsies from mediastinal lymph nodes group were taken.

Results

In all of the biopsied lymph nodes, positive results were obtained in 549 patients (84%). In 180 patients with stage II TBLB, a biopsy was taken from affected part of the lung. Positive results were found in 79 patients (43.9%). EBB was performed in 340 patients, with a positive result in 101 (29.7%). Mediastinoscopy was performed in 60 patients (9.2%) with a negative result in EBUS‐TBNA, TBLB and/or EBB. Non‐caseating granulomas were found in 48 patients. The sensitivity of TBLB technique alone was significantly lower at 43.9% (79/180) (P < 0.001). The sensitivity of EBB was significantly lower than EBUS‐TBNA and TBLB and reached 29.7% (101/340) (P < 0.0001, P < 0.003). The overall diagnostic accuracy for EBUS‐TBNA was 84%, and the combination of EBUS‐TBNA with standard bronchoscopic techniques had a diagnostic accuracy of 89%.

Conclusion

The diagnostic yield of the EBUS‐TBNA for stage I and II sarcoidosis is clearly higher than for TBLB and EBB. The combination of EBUS‐TBNA with standard bronchoscopic techniques is safe and feasible, and optimizes the diagnostic yield in patients with pulmonary sarcoidosis and enlarged intrathoracic lymph nodes. EBUS‐TBNA in combination with standard bronchoscopy may be considered to be the first‐line investigation in patients with suspected sarcoidosis and enlarged intrathoracic lymphadenopathy.
Downregulation of immune responses in asthmatic humans by ES products of Marshallagia marshalli
Authors: Jabbari Azad Farahzad , Kiaee Fatemeh , Rezaei Abdorahim , Farid Hosseini Reza , Soleimani Nooshinmehr , Borji Hassan
Published: April 2015

Background and Aims

Helminths and their products are considered to possess therapeutic capability to control or even prevent immune‐mediated diseases. Studies suggest that helminths induce a systemic immunomodulatory network, including regulatory T cells and anti‐inflammatory interleukin‐10 (IL‐10), which might play a key role in the protection against the allergic phenotype. Thus, helminthic therapy is becoming of a major interest, and several researchers are enthusiastically tended to explore its role in allergic diseases.

Methods

Peripheral blood mononuclear cells (PBMCs) from 25 asthmatic and 25 healthy human were collected. After isolation of PBMCs, they were stimulated with excretory/secretory (ES) antigen of M. marshalli, in incubator with 5% CO2, 37°C. Total RNA was isolated from all cells from antigen stimulated and non‐stimulated control PBMC in asthmatic and healthy human after 6 h. The concentration of Th1 type cytokines [interferon‐γ (IFN‐γ)] and Th2 type cytokines (IL‐4) and T‐reg cytokines [transforming growth factor‐β (TGF‐β), IL‐10] was determined using real‐time polymerase chain reaction.

Results

Results showed that the IFN‐γ expression was significantly decreased in culture condition with ES Ag of M. marshalli in healthy and asthmatic patients (P < 0.05). Similar data were obtained for IL‐4 expression in both healthy individuals (<0.006) and asthmatic patients (<0.001). The increment of regulatory cytokines IL‐10 and TGF‐β expression was considerably increased in our investigation.

Conclusion

To our knowledge, this is the first report to document the suppressive effect that the M. marshalli ES product has on PBMSC cell culture of asthmatic patients. The present study provides new insights into understanding the immune modulation governed by parasite‐derived products and the development of new asthma treatment strategies.
Endobronchial ultrasound‐guided transbronchial needle aspiration for diagnosing mediastinal lymphadenectasis: a cohort study from a single center
Authors: Zhu Jun , Zhang Hai‐ping , Ni Jian , Gu Ye , Wu Chun‐yan , Song Jiong , Ji Xiao‐bin , Lu Hai‐wen , Wei Ping , Zhou Cai‐cun , Xu Jin‐fu
Published: April 2015

Objective

Endobronchial ultrasound‐guided transbronchial needle aspiration (EBUS‐TBNA) is commonly used for clinical diagnosis of mediastinal lymphadenectasis. This study aimed to evaluate the diagnostic significance of EBUS‐TBNA for mediastinal lymphadenectasis in a large single center.

Methods

A total of 846 patients who were not definitively diagnosed with mediastinal lymphadenectasis underwent EBUS‐TBNA were retrospectively analyzed in this study.

Results

In total, 842 patients underwent EBUS‐TBNA successfully. There were 589 patients with malignancy, including squamous carcinoma (118 cases; 20.6%), adenocarcinoma (187 cases; 32.7%) and small cell carcinoma (88 cases; 15.4%). A total of 253 patients were diagnosed with benign disease, including tuberculosis (111 cases; 43.9%) and sarcoidosis (93 cases; 36.7%). The diagnostic sensitivity of lung cancer, tuberculosis and sarcoidosis were 94.4%, 81.1% and 51.6%, respectively. The overall sensitivity of EBUS‐TBNA was 92.0%. N2 stage in lung cancer patients who were diagnosed by EBUS‐TBNA was significantly higher than other stages. The positive rate of targeted puncture is high for the lymph nodes whose short‐axis diameters were larger than 1 cm.

Conclusion

The operation risk of EBUS‐TBNA is relatively small. In diseases complicated by mediastinal lymphadenectasis, malignant diseases are most, and benign diseases mainly are granulomatous. EBUS‐TBNA is a valuable diagnostic technique in patients with mediastinal lymphadenectasis whose diagnosis have not been determined.
The evaluation of clinical usefulness of transbrochoscopic lung biopsy in undefined interstitial lung diseases: a retrospective study
Authors: Han Qian , Luo Qun , Chen Xiaobo , Xie Jiaxing , Wu Lulu , Chen Rongchang
Published: April 2015

Background and Aims

Previous studies mostly focused on the diagnostic accuracy of transbronchoscopic lung biopsy (TBLB) in the diagnosis of interstitial lung diseases (ILDs). We aimed to explore the clinical usefulness of TBLB results in the diagnostic procedure of undefined ILDs.

Methods

The retrospective analysis included patients undergoing TBLB for the diagnosis of undefined ILDs from January 2007 to December 2010. The clinically useful TBLB was defined as that lead to a specific histopathological diagnosis or that was consistent with the working diagnosis based on existing clinical and radiological data.

Results

A total of 664 patients were included in the study. TBLB failed to obtain lung parenchyma in 155 cases (23.3%). TBLB was considered clinically helpful in 202 procedures (30.4%), including 114 cases that provided definitive histopathological diagnoses and 88 cases that were consistent with working diagnoses. Among 202 cases of clinically useful TBLBs, the majority were diagnosed as pulmonary alveolar proteinosis (PAP) (67 cases, 33.2%), connective tissue disease‐related ILDs (CTD‐ILDs) (65, 32.2%) and idiopathic pulmonary fibrosis (IPF) (33, 16.3%). Although TBLB could provide definitive histopathological diagnoses in all cases diagnosed as PAP, only few cases of IPF (7, 21.2% of IPF diagnoses) and CTD‐ILDs (9, 13.8% of CTD‐ILD diagnoses) could be identified by TBLBs.

Conclusion

The clinical usefulness of TBLB, in conjunction with thorough clinical and radiological data, in the diagnosis of ILDs may be varied depending on different subtypes. The use of histopathological analysis and the type of biopsy employed should therefore be considered on a case‐by‐case basis.
Social development of children born very preterm: a systematic review
Authors: Ritchie Kirsten , Bora Samudragupta , Woodward Lianne J
Published: April 2015

Aim

To review systematically studies examining the development of social competence in children born very preterm (VPT) (gestation <33wks) and identify neonatal and family predictors.

Method

Peer‐reviewed original articles were extracted from PubMed and PsycINFO following Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) guidelines. Selection criteria included children born VPT and comparison children born at term, sample born after 1990, and children assessed between 0 and 17 years on at least one measure of social competence spanning social adjustment, performance, and/or social skills.

Results

Twenty‐three studies were included. Seven focused on social competence and another 16 examined social competence within a range of outcomes. Study quality was low. Limitations included reliance on single informant data, cross‐sectional measurement, use of brief screening tools, absence of child or peer report, and no conceptual model. In terms of social adjustment, 16 out of 21 studies found children born VPT had more peer problems and social withdrawal. Findings of social performance were mixed, with some studies suggesting differences in prosocial behavior (4/14) and others not. Social skills were assessed in four studies and showed children born VPT had poorer skills than children born at term. Predictors of social competence included gestational age, neonatal brain abnormalities, and family socio‐economic status.

Interpretation

Children born VPT have poorer social competence. These difficulties emerge early and persist throughout childhood.
Ambulatory children with cerebral palsy do not exhibit unhealthy weight gain following selective dorsal rhizotomy
Authors: Gutknecht Sarah M , Schwartz Michael H , Munger Meghan E
Published: April 2015

Aim

The aim of this study was to retrospectively analyze changes in age‐ and sex‐adjusted body mass index (BMI) in ambulatory children with cerebral palsy (CP) who underwent selective dorsal rhizotomy (SDR).

Method

Raw BMI, age‐ and sex‐adjusted BMI z‐scores, weight classification status, energy expenditure, and ambulation function were calculated before and after SDR at multiple post‐SDR time points: 6 to <24 months, 24 to <48 months, 48 to <72, and 72 to <96 months. Linear mixed models were used to analyze changes in raw BMI, BMI z‐scores, energy expenditure, and ambulation function.

Results

Pre‐ and post‐surgical data were available for 363 children diagnosed with CP who underwent SDR (219 males, 144 females; mean age 6y [SD 2y 1mo]; mean BMI z‐score 0.09 [SD 1.21]). Data from additional post‐surgical time points were collected on subsamples. Although raw BMI significantly increased (p<0.01), these increases were consistent with anticipated growth. BMI z‐scores did not significantly change over the 10‐year study period.

Interpretation

Concerns of unhealthy weight gain following SDR are not supported by this study. Further work examining possible risk factors for BMI increase following SDR, as well as examining disparities in existing criteria for patient selection, is merited.
How low can we go? Recognizing infants at high risk of cerebral palsy earlier
Authors: McIntyre Sarah
Published: April 2015

This commentary is on the original article by Granild‐Jensen et al. on pages 931–935 of this issue.
Relative roles of ecological and energetic constraints, diversification rates and region history on global species richness gradients
Authors: Belmaker Jonathan , Jetz Walter
Published: April 2015

Regions worldwide differ markedly in species richness. Here, for birds and mammals worldwide, we directly compare four sets of hypotheses regarding geographical richness gradients: (1) evolutionary, emphasising heterogeneity in diversification rates, (2) historical, related to differences in region ages and sizes, (3) energetic, associated with variation in productive or ambient energy and (4) ecological, reflecting differences in ecological niche diversity. Among highly independent regions, or ‘evolutionary arenas’, we find that richness is weakly influenced by richness‐standardised ecological niche diversity, questioning the significance of ecological constraints for producing large‐scale diversity gradients. In contrast, we find strong evidence for the importance of region area and its changes over time, together with a role for temperature. These predictors affect richness predominately directly without concomitant positive effects on diversification rates. This suggests that regional richness is governed by historical and evolutionary processes, which promote region‐specific accumulation of diversity through time or following asymmetrical dispersal.
Characteristics in childhood and adolescence associated with future multiple sclerosis risk in men: cohort study
Authors: Gunnarsson M. , Udumyan R. , Bahmanyar S. , Nilsagård Y. , Montgomery S.
Published: April 2015

Background and purpose

Associations with multiple sclerosis (MS) of living conditions in childhood and characteristics in adolescence including physical fitness, cognitive function and psychological stress resilience were investigated.

Methods

A cohort of male Swedish residents born 1952–1956 who were included in the Swedish Military Conscription Register was used to create a nested case−control study comprising 628 MS cases and 6187 controls matched on birth year, county of residence and vital status at time of diagnosis. Conscription examination records were linked with other national register data. Conditional logistic regression was used to evaluate associations with MS subsequent to the conscription examination.

Results and conclusions

Men with MS were less likely to be from more crowded households in childhood (>two persons per room) with an adjusted odds ratio of 0.67 (95% confidence interval 0.51–0.86, P = 0.023). They had lower physical working capacity in adolescence with adjusted odds ratio of 0.94 (95% confidence interval 0.89–0.99, P = 0.026). Cognitive function and stress resilience scores displayed no significant differences between cases and controls. Parental occupation in childhood and body mass index in adolescence were not associated with future MS risk. The inverse association of MS risk with higher levels of household crowding may reflect environmental factors such as the pattern of exposure to microorganisms. Lower physical fitness in men at MS risk may indicate a protective effect of exercise or could be due to prodromal disease activity, although there was no association with cognitive function. Poor psychological stress resilience (and thus risk of chronic stress arousal) was not associated with MS.
Intelligence after traumatic brain injury: meta‐analysis of outcomes and prognosis
Authors: Königs M. , Engenhorst P. J. , Oosterlaan J.
Published: April 2015

Worldwide, 54–60 million individuals sustain traumatic brain injury (TBI) each year. This meta‐analysis aimed to quantify intelligence impairments after TBI and to determine the value of age and injury severity in the prognosis of TBI. An electronic database search identified 81 relevant peer‐reviewed articles encompassing 3890 patients. Full‐scale IQ (FSIQ), performance IQ (PIQ) and verbal IQ (VIQ) impairments were quantified (Cohen's d) for patients with mild, moderate and severe TBI in the subacute phase of recovery and the chronic phase. Meta‐regressions explored prognostic values of age and injury severity measures for intelligence impairments. The results showed that, in the subacute phase, FSIQ impairments were absent for patients with mild TBI, medium‐sized for patients with moderate TBI (d = −0.61, P < 0.001) and large for patients with severe TBI (d = −1.09, P < 0.001). In the chronic phase, FSIQ impairments were small for patients with mild or moderate TBI (d = −0.37 and −0.19, P ≤ 0.008) and large for patients with severe TBI (d = −0.80, P < 0.001). Adults with mild TBI had larger PIQ and VIQ impairments in the chronic phase than children (both Q ≥ 5.21, P ≤ 0.02), whilst children with severe TBI had larger FSIQ and VIQ impairments than adults (both Q ≥ 4.40, P ≤ 0.04). Glasgow Coma Scale score, duration of loss of consciousness and post‐traumatic amnesia duration moderately to strongly predicted FSIQ, PIQ and VIQ impairments (0.41 ≤ r ≤ 0.82, P ≤ 0.02), but no differences in predictive value were observed. In conclusion, TBI causes persisting intelligence impairments, where children may have better recovery from mild TBI and poorer recovery from severe TBI than adults. Injury severity measures predict intelligence impairments and do not outperform one another.
The Framingham cardiovascular risk score in multiple sclerosis
Authors: Moccia M. , Lanzillo R. , Palladino R. , Maniscalco G. T. , De Rosa A. , Russo C. , Massarelli M. , Carotenuto A. , Postiglione E. , Caporale O. , Triassi M. , Brescia Morra V.
Published: April 2015

Background and purpose

Cardiovascular risk factors can increase the risk of multiple sclerosis (MS) and modify its course. However, such factors possibly interact, determining a global cardiovascular risk. Our aim was to compare the global cardiovascular risk of subjects with and without MS with the simplified 10‐year Framingham General Cardiovascular Disease Risk Score (FR) and to evaluate its importance on MS‐related outcomes.

Methods

Age, gender, smoking status, body mass index, systolic blood pressure, type II diabetes and use of antihypertensive medications were recorded in subjects with and without MS to estimate the FR, an individualized percentage risk score estimating the 10‐year likelihood of cardiovascular events.

Results

In total, 265 MS subjects were identified with 530 matched controls. A t test showed similar FR in cases and controls (P = 0.212). Secondary progressive MS presented significantly higher FR compared to relapsing−remitting MS (P < 0.001). Linear regression analysis showed a direct relationship between FR and Expanded Disability Status Scale (P < 0.001) and MS Severity Scale (P < 0.001).

Conclusion

The FR, evaluating the global cardiovascular health by the interaction amongst different risk factors, relates to MS disability, severity and course.
Therapies for inherited skin fragility disorders
Authors: Has Cristina , Kiritsi Dimitra
Published: April 2015

Inherited skin fragility comprises disorders characterized by mechanical induced blistering and erosions within the skin and mucosal membranes as a consequence of mutations in genes encoding proteins involved in intra‐epidermal or dermal–epidermal adhesion. As the molecular pathology is largely known, it is a prototype group of disorders for which numerous experimental treatments have been developed. However, it became clear that single therapeutic strategies will not be able to address all molecular and clinical aspects. Significant progress has been achieved in gene, cell and protein therapies. Although the way towards clinical application seems obvious, major challenges must be addressed before these therapies become largely accessible. Until curative treatments will become available, alternative strategies which aim at increasing protein stability, amending apoptosis, inflammation and scarring may alleviate skin fragility and prevent or delay the onset of complications.