bluuebunny/crossref_metadata_2025 huggingface dataset:
Density parameter estimation for finding clusters of homologous proteins—tracing actinobacterial pathogenicity lifestyles
Authors: Röttger Richard , Kalaghatgi Prabhav , Sun Peng , Soares Siomar de Castro , Azevedo Vasco , Wittkop Tobias , Baumbach Jan
Published: November 2012

Motivation: Homology detection is a long-standing challenge in computational biology. To tackle this problem, typically all-versus-all BLAST results are coupled with data partitioning approaches resulting in clusters of putative homologous proteins. One of the main problems, however, has been widely neglected: all clustering tools need a density parameter that adjusts the number and size of the clusters. This parameter is crucial but hard to estimate without gold standard data at hand. Developing a gold standard, however, is a difficult and time consuming task. Having a reliable method for detecting clusters of homologous proteins between a huge set of species would open opportunities for better understanding the genetic repertoire of bacteria with different lifestyles.

Results: Our main contribution is a method for identifying a suitable and robust density parameter for protein homology detection without a given gold standard. Therefore, we study the core genome of 89 actinobacteria. This allows us to incorporate background knowledge, i.e. the assumption that a set of evolutionarily closely related species should share a comparably high number of evolutionarily conserved proteins (emerging from phylum-specific housekeeping genes). We apply our strategy to find genes/proteins that are specific for certain actinobacterial lifestyles, i.e. different types of pathogenicity. The whole study was performed with transitivity clustering, as it only requires a single intuitive density parameter and has been shown to be well applicable for the task of protein sequence clustering. Note, however, that the presented strategy generally does not depend on our clustering method but can easily be adapted to other clustering approaches.

Availability: All results are publicly available at http://transclust.mmci.uni-saarland.de/actino_core/ or as Supplementary Material of this article.

Contact:  roettger@mpi-inf.mpg.de

Supplementary information:  Supplementary data are available at Bioinformatics online.
iBAG: integrative Bayesian analysis of high-dimensional multiplatform genomics data
Authors: Wang Wenting , Baladandayuthapani Veerabhadran , Morris Jeffrey S. , Broom Bradley M. , Manyam Ganiraju , Do Kim-Anh
Published: November 2012

Motivation: Analyzing data from multi-platform genomics experiments combined with patients’ clinical outcomes helps us understand the complex biological processes that characterize a disease, as well as how these processes relate to the development of the disease. Current data integration approaches are limited in that they do not consider the fundamental biological relationships that exist among the data obtained from different platforms.

Statistical Model: We propose an integrative Bayesian analysis of genomics data (iBAG) framework for identifying important genes/biomarkers that are associated with clinical outcome. This framework uses hierarchical modeling to combine the data obtained from multiple platforms into one model.

Results: We assess the performance of our methods using several synthetic and real examples. Simulations show our integrative methods to have higher power to detect disease-related genes than non-integrative methods. Using the Cancer Genome Atlas glioblastoma dataset, we apply the iBAG model to integrate gene expression and methylation data to study their associations with patient survival. Our proposed method discovers multiple methylation-regulated genes that are related to patient survival, most of which have important biological functions in other diseases but have not been previously studied in glioblastoma.

Availability:  http://odin.mdacc.tmc.edu/∼vbaladan/.

Contact:  veera@mdanderson.org

Supplementary information:  Supplementary data are available at Bioinformatics online.
Relationship of circulating matrix biomarkers to myocardial matrix metabolism in advanced heart failure
Authors: Kaye David M. , Khammy Ouda , Mariani Justin , Maeder Micha T.
Published: November 2012

Aims

Interstitial fibrosis is a key component of myocardial remodelling in heart failure (HF). Many studies have measured peripheral blood levels of procollagens and matrix metalloproteinases (MMPs), as a surrogate for myocardial matrix metabolism, particularly to evaluate the effect of interventions and their prognostic relevance. However, the relationship between peripheral biomarker levels and actual cardiac turnover in HF is not known. We aimed to determine whether peripheral levels of relevant biomarkers reflect cardiac release in patients with advanced HF.

Methods and results

We determined whether the failing human heart releases collagen precursors [procollagen I N‐terminal peptide (PINP) and procollagen III N‐terminal peptide (PIIINP)], or key matrix metalloproteinases (MMP9) and MMP inhibitors [tissue inhibitor of metalloproteinase 1 (TIMP1)] by performing transcardiac blood sampling in healthy controls (n = 9) and in patients with advanced HF (n = 18, left ventricular ejection fraction 22 ± 2%). HF patients had higher arterial levels of PIIINP compared with controls (7.0 ± 0.7 vs. 4.0 ± 0.2 µg/L, P < 0.001). PIIINP was closely correlated with the pulmonary capillary wedge pressure (r = 0.54, P = 0.01) and the estimated glomerular filtration rate (r = –0.50, P = 0.01). Transcardiac blood sampling demonstrated that there was no net release of either PINP or PIIINP in controls or HF patients. The transcardiac MMP9 gradient was significantly lower in HF patients (P < 0.05), and was negatively correlated with left ventricular mass (r = –0.51, P = 0.01).

Conclusions

Our study shows that the concentration of circulating levels of PINP, PIIINP, MMP9, and TIMP1 do not accurately reflect cardiac turnover. This study highlights the importance of performing transcardiac blood sampling to validate the utility of emerging cardiac biomarkers.
Heart failure determines the myocardial inflammatory response to injury
Authors: Kortekaas Kirsten A. , Lindeman Jan H. , Versteegh Michel I. , van Beelen Els , Kleemann Robert , Klautz Robert J.
Published: November 2012

Aims

Systemic complications after cardiac surgery are common in heart failure patients. However, the pathophysiological mechanisms, such as a different local inflammatory response of failing hearts, remain in question. This study examines whether failing hearts respond differently to cardioplegic arrest and reperfusion compared with non‐failing hearts (controls).

Methods and results

The inflammatory response was evaluated in samples collected simultaneously from the radial artery and coronary sinus, and myocardial tissue in 62 patients undergoing cardiac surgery. No myocardial release of inflammatory mediators was observed upon reperfusion in controls (n = 19). In contrast, in patients with heart failure, reperfusion was characterized by a myocardial release of several cytokines. Myocardial interleukin‐6 was 115% increased in non‐ischaemic heart failure (n = 18, P = 0.002) as compared with a 117% increase in patients with ischaemic heart failure (n = 25, P = 0.01). Furthermore, a myocardial release of monocyte chemoattractant protein‐1 was observed in both patient groups: a 109% (P = 0.001) and 114% (P = 0.01) increase in patients with non‐ischaemic heart failure and ischaemic heart failure, respectively. Post‐operative myocardial damage, expression of inflammatory mediators, and p65‐nuclear factor‐κB activity were similar in all patient groups. Inflammatory cell content was increased in early ischaemic myocardial tissue in both heart failure groups compared with controls.

Conclusion

Heart failure patients show a clear myocardial inflammatory response upon reperfusion, probably explained by degranulation of infiltrated inflammatory cells. Results in controls indicate that they better withstand cardioplegic arrest and reperfusion without an explicit myocardial inflammatory response.
Computational modelling of T-cell formation kinetics: output regulated by initial proliferation-linked deferral of developmental competence
Authors: Manesso Erica , Chickarmane Vijay , Kueh Hao Yuan , Rothenberg Ellen V. , Peterson Carsten
Published: November 2012

Bone-marrow-derived progenitors must continually enter the thymus of an adult mouse to sustain T-cell homeostasis, yet only a few input cells per day are sufficient to support a yield of 5 × 10
7
immature T-cells per day and an eventual output of 1–2 × 10
6
mature cells per day. While substantial progress has been made to delineate the developmental pathway of T-cell lineage commitment, still little is known about the relationship between differentiation competence and the remarkable expansion of the earliest (DN1 stage) T-cell progenitors. To address this question, we developed computational models where the probability to progress to the next stage (DN2) is related to division number. To satisfy differentiation kinetics and overall cell yield data, our models require that adult DN1 cells divide multiple times before becoming competent to progress into DN2 stage. Our findings were subsequently tested by
in vitro
experiments, where putative early and later-stage DN1 progenitors from the thymus were purified and their progression into DN2 was measured. These experiments showed that the two DN1 sub-populations divided with similar rates, but progressed to the DN2 stage with different rates, thus providing experimental evidence that DN1 cells increase their commitment probability in a cell-intrinsic manner as they undergo cell division. Proliferation-linked shifts in eligibility of DN1 cells to undergo specification thus control kinetics of T-cell generation.
A new polymorphic form of bis(acetato-κO)bis[2-(pyridin-2-yl)ethanol-κ2N,O]nickel(II)
Authors: Trdin Miha , Lah Nina
Published: November 2012

A new polymorph of a mononuclear nickel(II) acetate complex with 2-(pyridin-2-yl)ethanol ligands, [Ni(CH3COO)2(C7H9NO)2], has been prepared and structurally characterized. Its molecular structure resembles the structures of two previously reported polymorphs in that the NiIIatom is located on an inversion centre and is coordinated by pairs of acetate and 2-(pyridin-2-yl)ethanol ligands. The acetate anions are coordinated in a monodentate manner, while the 2-(pyridin-2-yl)ethanol ligands are coordinated in a bidentate chelating mode involving the endocyclic N atom and the hydroxy O atom of the ligand side chain. A strong bifurcated intramolecular hydrogen-bond interaction was observed involving the hydroxy O atom as donor and both acetate O atoms as acceptors. No classical intermolecular hydrogen-bond contacts were observed. However, the crystal packing is effected through π–π and C—H...π interactions, giving rise to a different packing arrangement. A brief comparison of the three polymorphic forms is presented.
Ascertaining the nanocluster formation within an ion-irradiated Pt/Ni/C multi-trilayer with X-ray absorption spectroscopy
Authors: Ramanan Nitya , Roy Sumalay , Lahiri Debdutta , Sharma Surinder M. , Dev B. N.
Published: November 2012

In this work nanoclusters formed in a Pt/Ni/C multi-trilayer by the ion-irradiated method of synthesis are characterized. In particular, an attempt to understand the role of interfaces in the synthesis is made. With this objective, ion-irradiation-induced structural changes in a Pt/Ni/C multi-trilayer using X-ray absorption spectroscopy (at the NiK-edge) in conjunction with the X-ray standing-wave technique are investigated. The XANES analysis identifies chemical binding at pristine Ni/C and Ni/Pt interfaces, in contrast with physical adsorption at the Pt/C interface. The chemical nature of the interfaces determines their relative stability with respect to irradiation and controls the extent of metallic diffusion. The most interesting structural change, upon irradiation, is the disruption of the Pt/C interface and subsequent migration of Pt atoms towards pre-diffused Ni atoms within the C layer, leading to the formation of Ni-centered Ni–Pt bimetallic nanoclusters (with Ni:Pt = 60:40). These clusters are highly disordered beyond their nearest neighbor and find wide-scale applications as, for example, magnetic devicesetc. The implications of these findings on the design goals are discussed.
A simultaneous multiple angle-wavelength dispersive X-ray reflectometer using a bent-twisted polychromator crystal
Authors: Matsushita Tadashi , Arakawa Etsuo , Voegeli Wolfgang , Yano Yohko F.
Published: November 2012

An X-ray reflectometer has been developed, which can simultaneously measure the whole specular X-ray reflectivity curve with no need for rotation of the sample, detector or monochromator crystal during the measurement. A bent-twisted crystal polychromator is used to realise a convergent X-ray beam which has continuously varying energyE(wavelength λ) and glancing angle α to the sample surface as a function of horizontal direction. This convergent beam is reflected in the vertical direction by the sample placed horizontally at the focus and then diverges horizontally and vertically. The normalized intensity distribution of the reflected beam measured downstream of the specimen with a two-dimensional pixel array detector (PILATUS 100K) represents the reflectivity curve. Specular X-ray reflectivity curves were measured from a commercially available silicon (100) wafer, a thin gold film coated on a silicon single-crystal substrate and the surface of liquid ethylene glycol with data collection times of 0.01 to 1000 s using synchrotron radiation from a bending-magnet source of a 6.5 GeV electron storage ring. A typical value of the simultaneously covered range of the momentum transfer was 0.01–0.45 Å−1for the silicon wafer sample. The potential of this reflectometer for time-resolved X-ray studies of irreversible structural changes is discussed.
Effect of conspecific and heterospecific urine odors on the foraging behavior of the golden spiny mouse
Authors: BAUDOIN Claude , HAIM Abraham , DURAND Jean‐Luc
Published: November 2012

The common spiny mouse (Acomys cahirinus) inhibits the foraging activity of the golden spiny mouse (A. russatus). These two sympatric species of spiny mice, which are considered habitat competitors, occur in extreme arid environments. To test this theory of competition, the influence of urinary odors of both conspecific and heterospecific mice on the foraging behavior of A. russatus was studied under controlled laboratory conditions. Twenty adult males, born in captivity and unfamiliar to the odors of the donor mice, were tested in 3 experimental conditions choosing between 2 seed patches that were scented with urine of either heterospecifics (A. cahirinus), conspecifics (A. russatus) or controls (odors of the tested individual). Of the 20 males, 12 were also tested with urine of unfamiliar gerbils, bushy‐tailed jird, considered as competitors in the field. Both conspecific and heterospecific urine samples from Acomys significantly reduced foraging behavior of A. russatus when compared to the control odor. The inhibitory effect of the Acomys urine does not result from the novelty of chemical stimuli of the urine because no effect was shown with unfamiliar gerbil urine. The findings are in accordance with the general theory that A. cahirinus dominates the foraging activity of A. russatus. We hypothesize that chemical cues in the urine of Acomys spp. might induce a negative effect on the foraging behavior of A. russatus.
Selling with Money‐Back Guarantees: The Impact on Prices, Quantities, and Retail Profitability
Authors: Akçay Yalçın , Boyacı Tamer , Zhang Dan
Published: November 2012

In this paper, we consider a retailer adopting a “money‐back‐guaranteed” (MBG) sales policy, which allows customers to return products that do not meet their expectations to the retailer for a full or partial refund. The retailer either salvages returned products or resells them as open‐box items at a discount. We develop a model in which the retailer decides on the quantity to procure, the price for new products, the refund amount, as well as the price of returned products when they are sold as open‐box. Our model captures important features of MBG sales including demand uncertainty, consumer valuation uncertainty, consumer returns, the sale of returned products as open‐box items, and consumer choice between new and returned products and possibility of exchanges when restocking is considered. We show that selling with MBGs increases retail sales and profit. Furthermore, the second‐sale opportunity created by restocking returned products enables the retailer to generate additional revenues. Our analysis identifies the ideal conditions under which this practice is most beneficial to the retailer. Offering an MBG without restocking increases the new product price. We show that if the retailer decides to resell the returned items as open‐box, the price of the new product further increases, while open‐box items are sold at a discount. On the other hand, customers enjoy more generous refunds along with lower restocking fees. The opportunity to resell returned products also generally decreases the initial stocking levels of the retailer. Our extensive numerical study substantiates the analytical results and sharpens our insights into the drivers of performance of MBG policies and their impact on retail decisions.
Effect of acute hypoxia on blood flow in vertebral and internal carotid arteries
Authors: Ogoh Shigehiko , Sato Kohei , Nakahara Hidehiro , Okazaki Kazunobu , Subudhi Andrew W. , Miyamoto Tadayoshi
Published: November 2012

New Findings

What is the central question of this study?

Does hypoxia enhance blood flow to all parts of the brain uniformly?

What is the main finding and its importance?

During hypoxia, internal carotid artery flow is maintained despite a reduction in (end‐tidal) carbon dioxide tension, while vertebral artery blood flow increases. Only with maintained end‐tidal carbon dioxide tension is there an increase in both vertebral and internal carotid blood flow during hypoxia.

Hypoxia changes the regional distribution of cerebral blood flow and stimulates the ventilatory chemoreflex, thereby reducing CO2 tension. We examined the effects of both hypoxia and isocapnic hypoxia on acute changes in internal carotid (ICA) and vertebral artery (VA) blood flow. Ten healthy male subjects underwent the following two randomly assigned respiratory interventions after a resting baseline period with room air: (i) hypoxia; and (ii) isocapnic hypoxia with a controlled gas mixture (12% O2; inspiratory mmHg). In the isocapnic hypoxia intervention, subjects were instructed to maintain the rate and depth of breathing to maintain the level of end‐tidal partial pressure of CO2 () during the resting baseline period. The ICA and VA blood flow (velocity × cross‐sectional area) were measured using Doppler ultrasonography. The was decreased (−6.3 ± 0.9%, P < 0.001) during hypoxia by hyperventilation (minute ventilation +12.9 ± 2.2%, P < 0.001), while was unchanged during isocapnic hypoxia. The ICA blood flow was unchanged (P= 0.429), while VA blood flow increased (+10.3 ± 3.1%, P= 0.010) during hypoxia. In contrast, isocapnic hypoxia increased both ICA (+14.5 ± 1.4%, P < 0.001) and VA blood flows (+10.9 ± 2.4%, P < 0.001). Thus, hypoxic vasodilatation outweighed hypocapnic vasoconstriction in the VA, but not in the ICA. These findings suggest that acute hypoxia elicits an increase in posterior cerebral blood flow, possibly to maintain essential homeostatic functions of the brainstem.
Immobilization increases interleukin‐6, but not tumour necrosis factor‐α, release from the leg during exercise in humans
Authors: Reihmane Dace , Hansen Andreas Vigelsø , Gram Martin , Kuhlman Anja Birk , Nørregaard Jesper , Pedersen Helene Pape , Lund Michael Taulo , Helge Jørn Wulff , Dela Flemming
Published: November 2012

New Findings

What is the central question of this study?

Does physical inactivity influence the exercise‐induced release of tumour necrosis factor‐α and interleukin‐6 in healthy humans? In young, healthy subjects, we immobilized one leg for 2 weeks, followed by 45 min two‐legged exercise where one leg served as the control and the other was the previously inactive leg.

What is the main finding and its importance?

We found that prior physical inactivity enhances interleukin‐6 release during exercise, and it is released in the blood from the legs during exercise much faster than previously known. However, tumour necrosis factor‐α is not released in the blood with exercise, even from a previously inactive leg.

Data on interleukin‐6 (IL‐6) and tumour necrosis factor‐α (TNF‐α) release during acute exercise are not conclusive, and information is lacking about the impact of physical inactivity. Some studies have shown an increase, but others report no changes in IL‐6 and TNF‐α release during exercise. We have now studied the temporal relationship of leg IL‐6 and TNF‐α release before and during isolated two‐legged exercise after 14 days of one‐leg immobilization (IM) while the other leg served as the control (CON) leg. Fifteen healthy male subjects (mean ± SEM age, 23 ± 1 years; body mass index, 23.6 ± 0.7 kg m−2; and maximal oxygen uptake, 46.8 ± 1.4 ml kg−1 min−1) performed 45 min of two‐legged dynamic knee‐extensor exercise at 19.6 ± 0.8 W. Arterial and femoral venous blood samples from the CON and the IM leg were collected every 15 min during exercise, and leg blood flow was measured with Doppler ultrasound. The arterial plasma IL‐6 concentration increased (P < 0.05) with exercise (rest, 1.3 ± 0.1 pg ml−1; 15 min, 1.9 ± 0.2 pg ml−1; 30 min, 2.4 ± 0.2 pg ml−1; and 45 min, 3.1 ± 0.3 pg ml−1). Interleukin‐6 release occurred after 15 min of exercise, and the release from the IM leg was significantly greater compared with the CON leg after 45 min (1114 ± 152 versus 606 ± 14 pg min−1, respectively, P < 0.05). Tumour necrosis factor‐α release did not differ between the CON and the IM leg, and arterial concentrations remained unchanged during exercise (P > 0.05). In conclusion, prior immobilization enhances release of IL‐6 from the leg during exercise at a moderate workload, and the release is already present in the early phase of exercise. Neither immobilization nor exercise had an effect on TNF‐α release in the working legs.
Deficiency in pulmonary surfactant proteins in mice with fatty acid binding protein 4‐Cre‐mediated knockout of the tuberous sclerosis complex 1 gene
Authors: Xiang Xinxin , Yuan Fang , Zhao Jing , Li Ziru , Wang Xian , Guan Youfei , Tang Chaoshu , Sun Guang , Li Yin , Zhang Weizhen
Published: November 2012

New findings

What is the central question of this study?

Does tuberous sclerosis complex 1–mammalian target of rapamycin (mTOR) signalling regulate the synthesis of surfactant proteins A and B and, if so, can this contribute to the postnatal death of Fabp4‐Tsc1cKO mice?

What is the main finding and its importance?

Our study reveals a novel mechanism for the regulation of alveolar surfactant proteins. Tuberous sclerosis complex 1–mTOR signalling contributes to the regulation of synthesis of surfactant proteins A and B. Deficiency of tuberous sclerosis complex 1 in alveolar epithelial cells may contribute to the postnatal death of Fabp4‐Tsc1cKO mice.

Tuberous sclerosis complex 1 (TSC1) forms a heterodimmer with tuberous sclerosis complex 2, to inhibit signalling by the mammalian target of rapamycin (mTOR) complex 1 (mTORC1). The mTORC1 stimulates cell growth by promoting anabolic cellular processes, such as gene transcription and protein translation, in response to growth factors and nutrient signals. Originally designed to test the role of TSC1 in adipocyte function, mice in which the gene for TSC1 was specifically deleted by the fatty acid binding protein 4 (FABP4)‐Cre (Fabp4‐Tsc1cKO mice) died prematurely within 48 h after birth. The Fabp4‐Tsc1cKO mouse revealed a much smaller phenotype relative to the wild‐type littermates. Maternal administration of rapamycin, a classical mTOR inhibitor, significantly increased the survival time of Fabp4‐Tsc1cKO mice for up to 23 days. Both macroscopic and microscopic haemorrhages were observed in the lungs of Fabp4‐Tsc1cKO mice, while other tissues showed no significant changes. Levels of surfactant proteins A and B demonstrated a significant decrease in the Fabp4‐Tsc1cKO mice, which was rescued by maternal injection of rapamycin. Co‐localization of FABP4 or TSC1 with surfactant protein B was also detected in neonatal pulmonary tissues. Our study suggests that TSC1–mTORC1 may be critical for the synthesis of surfactant proteins A and B.
Relationships between black tea consumption and key health indicators in the world: an ecological study
Authors: Beresniak Ariel , Duru Gerard , Berger Genevieve , Bremond-Gignac Dominique
Published: November 2012

Objectives

The aim of this study was to investigate potential statistical relationships between black tea consumption and key health indicators in the world. The research question is: Does tea consumption is correlated with one or more epidemiological indicators?

Design

Ecological study using a systematic data-mining approach in which the unit of the analysis is a population of one country.

Setting

Six variables, black tea consumption data and prevalence data of respiratory diseases, infectious diseases, cancer, cardiovascular diseases and diabetes, have been studied at a global level.

Participants

Data from 50 participating countries in the World Health Survey were investigated.

Primary and secondary outcomes measures

Level of statistical relationships between variables.

Results

Principal component analysis established a very high contribution of the black tea consumption parameter on the third axis (81%). The correlation circle confirmed that the ‘black tea’ vector was negatively correlated with the diabetes vector and was not correlated with any of the other four health indicators. A linear correlation model then confirmed a significant statistical correlation between high black tea consumption and low diabetes prevalence.

Conclusions

This innovative study establishes a linear statistical correlation between high black tea consumption and low diabetes prevalence in the world. These results are consistent with biological and physiological studies conducted on the effect of black tea on diabetes and confirm the results of a previous ecological study in Europe. Further epidemiological research and randomised studies are necessary to investigate the causality.
A randomised trial comparing the clinical effectiveness of different emergency department healthcare professionals in soft tissue injury management
Authors: McClellan Carey Middleton , Cramp Fiona , Powell Jane , Benger Jonathan Richard
Published: November 2012

Objectives

To evaluate the clinical effectiveness of soft tissue injury management by emergency nurse practitioners (ENPs) and extended scope physiotherapists (ESPs) compared to the routine care provided by doctors in a UK emergency department (ED).

Design

Randomised, pragmatic trial of equivalence.

Setting

One adult ED in England.

Participants

372 patients were randomised; 126 to the ESP group, 123 to the ENP group and 123 to the doctor group. Participants were adults (older than 16 years) presenting to the ED with a peripheral soft tissue injury eligible for management by any of the three professional groups. Patients were excluded if they had any of the following: injury greater than 72 hours old; systemic disease; dislocated joints; recent surgery; unable to give informed consent (eg, dementia), open wounds; major deformities; opiate analgesia required; concurrent chest/rib injury; neurovascular deficits and associated fracture.

Interventions

Patients were randomised to treatment by ESPs, ENPs or routine care provided by doctors (of all grades).

Main outcome measures

Upper-limb and lower-limb functional scores, quality of life, physical well-being, preference-based health measures and the number of days off work.

Results

The clinical outcomes of soft tissue injury treated by ESPs and ENPs in the ED were equivalent to routine care provided by doctors.

Conclusions

As all groups were clinically equivalent it is other factors such as cost, workforce sustainability, service provision and skill mix that become important. This result validates the role of the ENP, which is becoming established as an integral part of minor injuries care, and demonstrates that the ESP should be considered as part of the clinical skill mix without detriment to outcomes.

ISRCTN-ISRCTN trials register number

70891354.
Regional and temporal variation in the treatment of rheumatoid arthritis across the UK: a descriptive register-based cohort study
Authors: Edwards Christopher John , Campbell Jennifer , van Staa Tjeerd , Arden Nigel K
Published: November 2012

Objectives

To describe current disease-modifying antirheumatic drugs (DMARDs) prescription in rheumatoid arthritis (RA) with reference to best practice and to identify temporal and regional trends in the UK.

Design

Descriptive, register-based cohort study.

Participants

Permanently registered patients aged ≥18 years with a recorded diagnosis of RA between 1 January 1995 and 31 March 2010 and matched controls. Participants with RA were identified through screening of all patients in the General Practice Research Database (GPRD) with a clinical or referral record for RA and at least 1 day of follow-up.

Setting

639 general practices in the UK supplying data to the GPRD.

Main outcome measures

Medication prescribing between 3 and 12 months of RA diagnosis by region and time period (1995–1999, 2000–2005 and 2006–April 2010).

Results

Of the 35 911 patients in the full RA cohort, 15 259 patients (42%) had incident RA. Analysis of prescribing in incident RA patients demonstrated that between 1995 (baseline) and 2010 there was a substantial increase in DMARD, and specifically methotrexate, prescribing across all regions with a less marked increase in combination DMARD prescribing. Taking 12-month prescribing as a snapshot: DMARD prescribing was 19–49% at baseline increasing to 45–74% by 2006–April 2010; methotrexate prescribing was 4–16% at baseline increasing to 32–60%; combination DMARD prescribing was 0–8% at baseline increasing to 3–17%. However, there was marked regional variation in the proportion of RA patients receiving DMARD regardless of time period.

Conclusions

There has been a substantial increase in prescribing of DMARDs for RA since 1995; however, regional variation persists across the UK with relative undertreatment, according to established best practice. Improved implementation of evidence-based best clinical practice to facilitate removal of treatment variation is warranted. This may occur as a result of the implementation of published national guidance.
Estimation of cocaine consumption in the community: a critical comparison of the results from three complimentary techniques
Authors: Reid Malcolm J , Langford Katherine H , Grung Merete , Gjerde Hallvard , Amundsen Ellen J , Morland Jorg , Thomas Kevin V
Published: November 2012

Objectives

A range of approaches are now available to estimate the level of drug use in the community so it is desirable to critically compare results from the differing techniques. This paper presents a comparison of the results from three methods for estimating the level of cocaine use in the general population.

Design

The comparison applies to; a set of regional-scale sample survey questionnaires, a representative sample survey on drug use among drivers and an analysis of the quantity of cocaine-related metabolites in sewage.

Setting

14 438 participants provided data for the set of regional-scale sample survey questionnaires; 2341 drivers provided oral-fluid samples and untreated sewage from 570 000 people was analysed for biomarkers of cocaine use. All data were collected in Oslo, Norway.

Results

0.70 (0.36–1.03) % of drivers tested positive for cocaine use which suggest a prevalence that is higher than the 0.22 (0.13–0.30) % (per day) figure derived from regional-scale survey questionnaires, but the degree to which cocaine consumption in the driver population follows the general population is an unanswered question. Despite the comparatively low-prevalence figure the survey questionnaires did provide estimates of the volume of consumption that are comparable with the amount of cocaine-related metabolites in sewage. Per-user consumption estimates are however highlighted as a significant source of uncertainty as little or no data on the quantities consumed by individuals are available, and much of the existing data are contradictory.

Conclusions

The comparison carried out in the present study can provide an excellent means of checking the quality and accuracy of the three measurement techniques because they each approach the problem from a different viewpoint. Together the three complimentary techniques provide a well-balanced assessment of the drug-use situation in a given community and identify areas where more research is needed.
The welfare burden of adolescent anxiety and depression: a prospective study of 7500 young Norwegians and their families: the HUNT study
Authors: Pape Kristine , Bjørngaard Johan Håkon , Holmen Turid Lingaas , Krokstad Steinar
Published: November 2012

Objectives

To examine the association between anxiety and depression symptoms in adolescents and their families and later medical benefit receipt in young adulthood.

Design

Prospective cohort study. Norwegian population study linked to national registers.

Participants

Data from the Nord-Trøndelag Health Study 1995–1997 (HUNT) gave information on anxiety and depression symptoms as self-reported by 7497 school-attending adolescents (Hopkins Symptoms Checklist—SCL-5 score) and their parents (Hospital Anxiety and Depression Scale score). There were 2711 adolescents with one or more siblings in the cohort.

Outcome measures

Adolescents were followed for 10 years in national social security registers, identifying long-term receipt of medical benefits (main outcome) and unemployment benefits for comparison from ages 20–29.

Methods

We used logistic regression to estimate OR of benefit receipt for groups according to adolescent and parental anxiety and depression symptom load (high vs low symptom loads) and for a one point increase in the continuous SCL-5 score (range 1–4). We adjusted for family-level confounders by comparing siblings differentially exposed to anxiety and depression symptoms.

Results

Comparing siblings, a one point increase in the mean SCL-5 score was associated with a 65% increase in the odds ofmedicalbenefit receipt from age 20–29 (adjusted OR, 1.65, 95% CI 1.10 to 2.48). Parental anxiety and depression symptom load was an indicator of their adolescent's future risk of medical benefit receipt, and adolescents with both parents reporting high symptom loads seemed to be at a particularly high risk. The anxiety and depression symptom load was only weakly associated withunemploymentbenefits.

Conclusions

Adolescents in families hampered by anxiety and depression symptoms are at a substantially higher risk of medical welfare dependence in young adulthood. The prevention and treatment of anxiety and depression in adolescence should be family-oriented and aimed at ensuring work-life integration.
Opinion editorials: the science and art of combining evidence with opinion
Authors: Marchildon Gregory P , Verma Jennifer Y , Roos Noralou
Published: November 2012

In the policy environment, the news media play a powerful and influential role, determining not only what issues are on the broad policy agenda, but also how the public and politicians perceive these issues. Ensuring that reporters and editors have access to information, that is, credible and evidence-based is critical for stimulating healthy public discourse and constructive political debates. EvidenceNetwork.ca is a non-partisan web-based project that makes the latest evidence on controversial health-policy issues available to the Canadian news media. This article introduces EvidenceNetwork.ca, the benefits it offers to journalists and researchers, and the important niche it occupies in working with the news media to build a more productive dialogue around healthcare.
Stimulant treatment and injury among children with attention deficit hyperactivity disorder: an application of the self-controlled case series study design
Authors: Raman Sudha R , Marshall Stephen W , Haynes Kevin , Gaynes Bradley N , Naftel Albert Jackson , Stürmer Til
Published: November 2012

Objective

The aim of the present work was to assess the short-term effects of stimulant medication use on risk of injury among children diagnosed as having attention deficit hyperactivity disorder (ADHD).

Methods

The study group for this self-controlled case series study was children aged 1–18 years old diagnosed as having ADHD who experienced an incident medically-attended injury event and received at least one prescription for stimulant medication between 1993 and 2008 (n=328), identified from The Health Improvement Network primary care database from the UK. Conditional Poisson regression was used to estimate incident rate ratios (IRR) and 95% CIs for injury comparing periods of time exposed to stimulant medication to unexposed periods.

Results

Among children with ADHD prescribed stimulant medication, the rate of medically-attended injury was decreased during periods of stimulant medication use as compared to unexposed periods (IRR 0.68, 95% CI 0.50 to 0.91). There was evidence of a protective association among males and among children aged 10–14 years. This effect did not change over time on treatment.

Conclusions

Stimulant medication use may decrease the risk of injury among children treated for ADHD, although unmeasured time varying confounding may be an alternative explanation. Injury risk may be considered during the decision-making process with regard to medication continuation among children with ADHD.
Acute occupational injury among adolescent farmworkers from South Texas
Authors: Shipp Eva M , Cooper Sharon P , del Junco Deborah J , Cooper Charles J , Whitworth Ryan E
Published: November 2012

Purpose

This combined cross-sectional/cohort study addressed research gaps by estimating the rate of non-fatal occupational injury and identifying potential determinants among a population of adolescent farmworkers who are largely Hispanic and migrant.

Methods

The cohort included 410 farmworkers (aged 13–19 years) attending high school in South Texas along the border with Mexico. Data collection involved a self-administered, Web-based survey that solicited information on demographics, farm work variables including person-time at risk, occupational injury, health status and health risk behaviours. Cox regression was used to identify potential risk factors for non-fatal injury events experienced during a 9-month recall period.

Results

Depending on the definition of injury, the rate of non-fatal injury ranged from 27.0–73.6/100 full time equivalents. Variables with an increased and statistically significant HR in an adjusted Cox model included: age groups <15 years-old (5.82) and 16 years-old (4.47), usually sleeping <8 h during the week (2.10), feeling tense, stressed or anxious sometimes/often (2.25), not watching TV (2.65), working around ditches (2.01) and detasseling (2.70).

Conclusions

The high observed rates of non-fatal injury combined with the potential negative consequences and cost of these injuries signifies a compelling need for injury prevention efforts targeting adolescent, Hispanic, farmworkers.
Offering older hospitalised patients the choice to die in their preferred place
Authors: Ahearn David Jonathan , Nidh Niamh , Kallat Arun , Adenwala Yousouf , Varman Surendra
Published: November 2012

Background

A significant proportion of older people state a preference to die at home. However, the vast majority of people in hospital recognised as dying subsequently die there.

Objectives

To identify the proportion of older people dying in hospital where the possibility of ending life elsewhere was explored. To identify factors that could support hospital staff to enable patients' wishes to be met.

Methods

Retrospective case-note review of 100 older patients (>75 years) who died during 2009 in an English Hospital.

Results

Age range 75–97 years. Time from admission to death ranged from 0–118 days (median 8.5). 16% died within the first 48 h, rising to 30% for those from care homes. In only 8 patients was a potential alternative place of death discussed. Although subjective, in 10 patients it was considered admission could have been avoided through Advance Care Planning (ACP) to allow patients with poor prognosis to die in their normal place of residence or a hospice. 55% of Do-Not-Attempt-Resuscitation orders were made within 48 h of admission. 38% were commenced on the Liverpool Care Pathway (LCP), 1–504 h before death (median 16).

Conclusions

In few cases are the preferred places of death discussed in older people who die in our hospital. Although hospital admission was largely appropriate, in a minority judicious ACP could have avoided death in hospital. We recommend (1) increased use of ACP, with appropriate practicalities planned in advance (2) wide-scale introduction of the ‘Rapid Discharge Home of the Dying Patient pathway’ (3) routinely discussing preferred place of death in appropriate key situations (eg, discussion of resuscitation status or commencing the LCP).
Heart rate, heart rate variability and behaviour of horses during air transport
Authors: Munsters C. C. B. M. , de Gooijer J‐W. , van den Broek J. , van Oldruitenborgh‐Oosterbaan M. M. Sloet
Published: November 2012

Heart rate (HR), HR variability (HRV) and behaviour score (BS) of nine horses were evaluated during an eight‐hour air transport between The Netherlands and New York. HR and HRV parameters were calculated every five minutes during the air transport. Compared with transit (40±3), mean HRs were higher during loading into the jet stall (67±21, P<0.001), loading into the aircraft (47±6, P=0.011), taxiing (50±8, P=0.001), and during periods of in‐flight turbulence (46±7, P=0.017). During the flight, individual horses showed differences in mean HR (P=0.005) and peak HR (P<0.001). By contrast with HR data, HRV data did not differ between stages or horses. BS was highest during turbulence (3.2±0.4). However, behaviour did not always correspond with HR measurements: the least responsive horse had the highest HR. Loading into the jet stall caused the highest increase in HR and was considered the most stressful event. During transit, HR was generally comparable with resting rates. Previous studies have shown that loading and transporting by road caused more elevation in HR than during loading and transporting by air. HRV data were not found to be useful, and caution is needed when interpreting HRV data. Not every horse exhibited stress through visible (evasive) behaviour, and HR measurements may provide an additional tool to assess stress in horses.
The good, the bad, and the ugly: space use and intraguild interactions among three opportunistic predators—cat (Felis catus), dog (Canis lupus familiaris), and red fox (Vulpes vulpes)—under human pressure
Authors: Krauze-Gryz D. , Gryz J.B. , Goszczyński J. , Chylarecki P. , ̇Zmihorski M.
Published: November 2012

Examples of interspecific interactions have been described for mammalian predators, but less is known regarding disturbances of native predator guilds by domestic predators. We investigated intraguild interactions among three opportunistic predators (dog ( Canis lupus familiaris L., 1758), cat ( Felis catus L., 1758), and red fox ( Vulpes vulpes (L., 1758)) co-occurring in the extensive farmlands of central Poland. Their space use was monitored using tracking stations distributed in field and forest plots along a distance gradient from buildings and analyzed using the occupancy-modeling framework. For all three species occupancy decreased with increased distance from buildings, although for the fox the pattern was relatively weak. The occurrence of cats at the stations was higher in the forest than in the field; for fox and dog, there was a strong variation between study plots. For all three predators, the probability of detection was higher during the night than during the day and varied between the seasons; however, the exact patterns were species-specific. The presence of one predator was also linked to the presence of the other two species—generally, a given species was detected more frequently in the absence of the other two species. We recorded spatiotemporal niche segregation among the three species. We conclude that interspecific antagonistic interactions and differences in foraging ecology are the main drivers shaping co-occurrence of the three species in the agriculture landscape.
MEtop—a generator for single top production via FCNC interactions
Authors: Coimbra Rita , Onofre António , Santos Rui , Won Miguel
Published: November 2012

We present a generator for single top-quark production via flavour-changing neutral currents. The MEtop event generator allows for Next-to-Leading-Order direct top production pp→t and Leading-Order production of several other single top processes. A few packages with definite sets of dimension six operators are available. We discuss how to improve the bounds on the effective operators and how well new physics can be probed with each set of independent dimension six operators.
GPU-accelerated path rendering
Authors: Kilgard Mark J. , Bolz Jeff
Published: November 2012

For thirty years, resolution-independent 2D standards (e.g. PostScript, SVG) have depended on CPU-based algorithms for the filling and stroking of paths. Advances in graphics hardware have largely ignored accelerating resolution-independent 2D graphics rendered from paths.

We introduce a two-step "Stencil, then Cover" (StC) programming interface. Our GPU-based approach builds upon existing techniques for curve rendering using the stencil buffer, but we
explicitly
decouple in our programming interface the
stencil step
to determine a path's filled or stroked coverage from the subsequent
cover step
to rasterize conservative geometry intended to test and reset the coverage determinations of the first step while shading color samples within the path. Our goals are completeness, correctness, quality, and performance---yet we go further to unify path rendering with OpenGL's established 3D and shading pipeline. We have built and productized our approach to accelerate path rendering as an OpenGL extension.
Lightweight binocular facial performance capture under uncontrolled lighting
Authors: Valgaerts Levi , Wu Chenglei , Bruhn Andrés , Seidel Hans-Peter , Theobalt Christian
Published: November 2012

Recent progress in passive facial performance capture has shown impressively detailed results on highly articulated motion. However, most methods rely on complex multi-camera set-ups, controlled lighting or fiducial markers. This prevents them from being used in general environments, outdoor scenes, during live action on a film set, or by freelance animators and everyday users who want to capture their digital selves. In this paper, we therefore propose a lightweight passive facial performance capture approach that is able to reconstruct high-quality dynamic facial geometry from only a single pair of stereo cameras. Our method succeeds under uncontrolled and time-varying lighting, and also in outdoor scenes. Our approach builds upon and extends recent image-based scene flow computation, lighting estimation and shading-based refinement algorithms. It integrates them into a pipeline that is specifically tailored towards facial performance reconstruction from challenging binocular footage under uncontrolled lighting. In an experimental evaluation, the strong capabilities of our method become explicit: We achieve detailed and spatio-temporally coherent results for expressive facial motion in both indoor and outdoor scenes -- even from low quality input images recorded with a hand-held consumer stereo camera. We believe that our approach is the first to capture facial performances of such high quality from a single stereo rig and we demonstrate that it brings facial performance capture out of the studio, into the wild, and within the reach of everybody.