bluuebunny/crossref_metadata_2025_split huggingface dataset:
Identifying Targets for Antimicrobial Stewardship in Children's Hospitals
Authors: Gerber Jeffrey S. , Kronman Matthew P. , Ross Rachael K. , Hersh Adam L. , Newland Jason G. , Metjian Talene A. , Zaoutis Theoklis E. 
Published: October 2013

Objective.Antimicrobial stewardship programs (ASPs) are recommended to optimize antimicrobial use for hospitalized patients. Although mechanisms for the implementation of ASPs have been described, data-driven approaches to prioritize specific conditions and antimicrobials for intervention have not been established. We aimed to develop a strategy for identifying high-impact targets for antimicrobial stewardship efforts.Design.Retrospective cross-sectional study.Setting and Patients.Children admitted to 32 freestanding children's hospitals in the United States in 2010.Methods.We identified the conditions with the largest proportional contribution to the total days of antibiotic therapy prescribed to all hospitalized children. For the 4 highest-using conditions, we examined variability between hospitals in antibiotic selection patterns for use of either first- or second-line therapies depending on the condition. Antibiotic use was determined using standardized probability of exposure to selected agents and standardized days of therapy per 1,000 patient-days, adjusting for patient demographics and severity of illness.Results.In 2010, 524,364 children received 2,082,929 days of antibiotic therapy. Surgical patients received 43% of all antibiotics. The 4 highest-using conditions—pneumonia, appendicitis, cystic fibrosis, and skin and soft-tissue infection—represent 1% of all conditions yet accounted for more than 10% of all antibiotic use. Wide variability in antibiotic use occurred for 3 of these 4 conditions.Conclusions.Antibiotic use in children's hospitals varied broadly across institutions when examining diagnoses individually and adjusting for severity of illness. Identifying conditions with both frequent and variable antimicrobial use informs the prioritization of high-impact targets for future antimicrobial stewardship interventions.
Telling metabolic stories to explore metabolomics data: a case study on the yeast response to cadmium exposure
Authors: Milreu Paulo Vieira , Klein Cecilia Coimbra , Cottret Ludovic , Acuña Vicente , Birmelé Etienne , Borassi Michele , Junot Christophe , Marchetti-Spaccamela Alberto , Marino Andrea , Stougie Leen , Jourdan Fabien , Crescenzi Pierluigi , Lacroix Vincent , Sagot Marie-France 
Published: October 2013

Abstract
Motivation: The increasing availability of metabolomics data enables to better understand the metabolic processes involved in the immediate response of an organism to environmental changes and stress. The data usually come in the form of a list of metabolites whose concentrations significantly changed under some conditions, and are thus not easy to interpret without being able to precisely visualize how such metabolites are interconnected.
Results: We present a method that enables to organize the data from any metabolomics experiment into metabolic stories. Each story corresponds to a possible scenario explaining the flow of matter between the metabolites of interest. These scenarios may then be ranked in different ways depending on which interpretation one wishes to emphasize for the causal link between two affected metabolites: enzyme activation, enzyme inhibition or domino effect on the concentration changes of substrates and products. Equally probable stories under any selected ranking scheme can be further grouped into a single anthology that summarizes, in a unique subnetwork, all equivalently plausible alternative stories. An anthology is simply a union of such stories. We detail an application of the method to the response of yeast to cadmium exposure. We use this system as a proof of concept for our method, and we show that we are able to find a story that reproduces very well the current knowledge about the yeast response to cadmium. We further show that this response is mostly based on enzyme activation. We also provide a framework for exploring the alternative pathways or side effects this local response is expected to have in the rest of the network. We discuss several interpretations for the changes we see, and we suggest hypotheses that could in principle be experimentally tested. Noticeably, our method requires simple input data and could be used in a wide variety of applications.
Availability and implementation: The code for the method presented in this article is available at http://gobbolino.gforge.inria.fr.
Contact: pvmilreu@gmail.com; vincent.lacroix@univ-lyon1.fr; marie-france.sagot@inria.fr
Supplementary information: Supplementary data are available at Bioinformatics online.
Fast pairwise IBD association testing in genome-wide association studies
Authors: Han Buhm , Kang Eun Yong , Raychaudhuri Soumya , de Bakker Paul I. W. , Eskin Eleazar 
Published: October 2013

Abstract
Motivation: Recently, investigators have proposed state-of-the-art Identity-by-descent (IBD) mapping methods to detect IBD segments between purportedly unrelated individuals. The IBD information can then be used for association testing in genetic association studies. One approach for this IBD association testing strategy is to test for excessive IBD between pairs of cases (‘pairwise method’). However, this approach is inefficient because it requires a large number of permutations. Moreover, a limited number of permutations define a lower bound for P-values, which makes fine-mapping of associated regions difficult because, in practice, a much larger genomic region is implicated than the region that is actually associated.
Results: In this article, we introduce a new pairwise method ‘Fast-Pairwise’. Fast-Pairwise uses importance sampling to improve efficiency and enable approximation of extremely small P-values. Fast-Pairwise method takes only days to complete a genome-wide scan. In the application to the WTCCC type 1 diabetes data, Fast-Pairwise successfully fine-maps a known human leukocyte antigen gene that is known to cause the disease.
Availability: Fast-Pairwise is publicly available at: http://genetics.cs.ucla.edu/graphibd.
Contact: eeskin@cs.ucla.edu
Supplementary information: Supplementary data are available at Bioinformatics online.
Influence of Bioprocessed Wheat Bran on the Physical and Chemical Properties of Dough and on Wheat Bread Texture
Authors: Hartikainen Katri , Poutanen Kaisa , Katina Kati 
Published: October 2013

ABSTRACTThe aim of this work was to assess the influence of wheat bran addition on the rheological properties of dough and on subsequent wheat bread volume and texture. Two types of bioprocessed bran (fermentation with yeast or with yeast plus enzymes) were studied in breadmaking at a substitution level of 20% (sufficient to deliver 6 g of dietary fiber per 100 g of product, the minimum for the European Food Safety Authority high‐fiber nutrition claim). Fermentation activated endogenous enzymes of bran, which together with exogenous enzymes modified the state of fiber in bran, resulting in solubilization of arabinoxylans and slight degradation of the insoluble fiber. Fermentation and enzyme treatment of bran compensated for the increased hardness (+100%) and the volume‐decreasing (–21%) effect observed with untreated bran. Analysis with partial least squares regression suggested the efficacy of bioprocessing to be based on solubilization of arabinoxylans, smaller particle size of bran, lower pasting viscosity of starch, improved resistance to extension, and accelerated CO2 production.
Optimized Development of Sebaceous Fingermarks on Nonporous Substrates with Conformal Columnar Thin Films
Authors: Muhlberger Sarah A. , Pulsifer Drew P. , Lakhtakia Akhlesh , Martín‐Palma Raúl J. , Shaler Robert C. 
Published: October 2013

AbstractA form of physical vapor deposition, called the conformal‐evaporated‐film‐by‐rotation (CEFR) method, was optimized for the conformal deposition of columnar thin films (CTFs) on sebaceous fingermarks. Relying on the surface topology of the fingermark, the CTF development technique is different from traditional development techniques. After the optimization of the development conditions, the CTF development technique was found to be superior to traditional development methods on several nonporous substrates: the smooth side of Scotch® Multitask, Gorilla®, and Scotch® Duct tapes; clear and black soft plastics; stained and sealed walnut and cherry woods; partial bloody fingermarks on stainless steel; and discharged cartridge casings. It was equally as good as other development techniques on other substrates, but worse on a few. The optimization study is expected to assist in designing a mobile CEFR apparatus capable of on‐scene development of fingermarks.
Deciphering the relationship between vulnerability to ethanol‐induced behavioral sensitization and ethanol consumption in outbred mice
Authors: Legastelois Rémi , Botia Béatrice , Coune Fabien , Jeanblanc Jérôme , Naassila Mickaël 
Published: October 2013

AbstractEthanol (EtOH)‐induced behavioral sensitization (EIBS) is proposed to play a role in early and recurring steps of alcohol dependence, but its impact on alcohol abuse is not clear. EIBS development is dependent upon animal species, strain and also individual factors. We proposed here to decipher the co‐expression of EIBS and EtOH intake in individual animals among outbred Swiss mice, which exhibit heterogeneity that parallels what may occur in humans. To do so, mice were exposed to a two‐bottle choice with free access to water or 10% EtOH for 6 days just before and immediately after chronic intraperitoneal 2.5 g/kg ethanol injections once a day for 10 consecutive days. Based on their sensitization scores, mice were split into resistant and sensitized animals. First, we showed that individual susceptibility to EIBS is inversely correlated with voluntary EtOH consumption. Exposure to repeated EtOH during EIBS development increased subsequent EtOH intake among the entire population. Very interestingly, subsequent analyses suggested that the less the mice are sensitized the more they increase their EtOH intake; however, resistant mice were sensitive to EtOH adulteration with quinine, whereas sensitized ones maintained their EtOH intake levels, therefore exhibiting a compulsive‐like drinking pattern. In addition, we showed that resistant mice do not exhibit a weaker sensitivity to the aversive properties of EtOH that may contribute to their higher level of EtOH intake compared to sensitized mice. This study confirms and extends previous data showing a deep relationship between propensity for EtOH consumption and susceptibility to EIBS in Swiss mice.
Long‐lasting, experience‐dependent alcohol preference in Drosophila
Authors: Peru y Colón de Portugal Raniero L. , Ojelade Shamsideen A. , Penninti Pranav S. , Dove Rachel J. , Nye Matthew J. , Acevedo Summer F. , Lopez Antonio , Rodan Aylin R. , Rothenfluh Adrian 
Published: October 2013

AbstractTo understand the molecular and neural mechanisms underlying alcohol addiction, many models ranging from vertebrates to invertebrates have been developed. In Drosophila melanogaster, behavioral paradigms from assaying acute responses to alcohol and to behaviors more closely modeling addiction have emerged in recent years. However, both the CAFÉ assay, similar to a two‐bottle choice consumption assay, as well as conditioned odor preference, where ethanol is used as the reinforcer, are labor intensive and have low throughput. To address this limitation, we have established a novel ethanol consumption preference assay, called FRAPPÉ, which allows for fast, high throughput measurement of consumption in individual flies, using a fluorescence plate reader. We show that naïve flies do not prefer to consume ethanol, but various pre‐exposures, such as ethanol vapor or voluntary ethanol consumption, induce ethanol preference. This ethanol‐primed preference is long lasting and is not driven by calories contained in ethanol during the consumption choice. Our novel experience‐dependent model of ethanol preference in Drosophila—a highly genetically tractable organism—therefore recapitulates salient features of human alcohol abuse and will facilitate the molecular understanding of the development of alcohol preference.
Single institutional series of neuroendocrine tumors managed in the Australian Capital Territory
Authors: Malik Laeeq , Chua Yu Jo , Butt Nadeem S , Yip Desmond 
Published: October 2013

AbstractAimsRetrospective review of neuroendocrine tumors (NETs) treated within the Australian Capital Territory to describe the local epidemiology and assess prognostic clinicopathological factors.MethodsPatients with histologically proven non‐pulmonary low to intermediate grade NETs were identified from our hospital clinical database. Data were analyzed according to epidemiological, clinical and histopathological characteristics.ResultsOf the 107 included patients, the most common primary tumor site was jejunum/ileum (32%), followed by rectum (22%) and pancreas (11.2%). In total, 32% had distant metastases at presentation, most commonly in the liver. Most patients were symptomatic at diagnosis, while 22.4% of cases were found incidentally. Second malignancies, in particular of gastrointestinal origin, were diagnosed in 33.6%. Surgical debulking was the most common treatment (59.8%) while 18% had multimodality therapy. With a median follow‐up of 25 months from diagnosis, about 78% of patients are still alive. Median time to first relapse was 15 months and the 5‐year survival rate was 80% for NETs of jejunum/ileum. Univariate survival analysis revealed tumor location, high Ki67 index, raised plasma chromogranin A, and urine 5‐hydroxyindoleacetic acid upon diagnosis to be associated with shorter 5‐year survival.ConclusionThe epidemiologic characteristics and long‐term outcome in our series are comparable to other reported studies. This analysis presents some important prognostic factors which could be used for risk stratification in patients with NETs.
Intra‐arterial chemotherapy for retinoblastoma. Challenges of a prospective study
Authors: Parareda Andreu , Català Jaume , Carcaboso Angel M. , Sola Teresa , Cruz Ofelia , Díaz Jesús , Salvador Héctor , de Torres Carmen , Álvarez‐Sampons Alexandra , Suñol Mariona , Vinent Joan , Guimaraens Leopoldo , Prat Joan , Mora Jaume 
Published: October 2013

AbstractPurposeTo report the efficacy and complications of intra‐ophthalmic artery melphalan (IAM) for treatment of patients with advanced intra‐ocular retinoblastoma.MethodsPatients with newly diagnosed, unilateral, group D retinoblastoma were included in a phase II protocol. Children with relapsed‐refractory disease after systemic chemoreduction were later treated under the same guidelines. Melphalan (3–5 mg/procedure) was injected through a 1.2 F microcatheter placed into the ophthalmic artery every 21 days.ResultsEleven patients (12 eyes, eight as primary treatment) received 33 IAM procedures. The phase II protocol closed prematurely because of low accrual. The IAM technique was overall safe and could be performed successfully in 31 of 33 (94%) attempts. After the second administration of IAM, very good partial response was achieved in all treated eyes. With a median follow‐up time of 29.5 months (range 6–57), ocular salvage was achieved in 7 of 12 (58%) eyes. No systemic adverse events were observed. Two patients developed diffuse arteriolar sclerosis, hyperpigmentation of the retinal pigment epithelium and partial retinal atrophy after the second IAM. Both eyes were preserved with no tumour activity, good motility and perception of light, 56 and 30 months after the last IAM treatment. Multinucleated macrophages with intracytoplasmic foreign material were found in the choroid and the retina in 2 of 5 enucleated eyes.ConclusionOur study reports the activity and reproducibility of IAM in advanced retinoblastoma but also underlines the challenges of performing prospective studies on this treatment modality. Toxicity was limited to only ocular vascular events.
10 Shifting Territorialities under the Inka Empire: The Case of the Rapayán Valley in the Central Andean Highlands
Authors: Mantha Alexis 
Published: October 2013

ABSTRACTI examine the changing patterns of territoriality generated by the Inkas upon their conquest of a middle‐range society of the Rapayán Valley in the Upper Marañón drainage of the northern central Andes of Peru. The territorial‐hegemonic model as well as Robert Sack's conception of territoriality—considered a strategy of social control through space—are used to discuss architectural and settlement pattern changes characterizing the transition between the Late Intermediate Period (C.E. 1000–1450) and the Late Horizon (Inka; C.E. 1450–1532). I argue that before the Inka conquest, territoriality was achieved through ceremonies honoring the Rapayán Valley's founding ancestors held at the location of highly visible above‐ground mortuary monuments distributed across the Rapayán landscape. Upon their conquest of the Rapayán Valley, the Inkas attempted to redefine local territorial practices and categories through various means and used simultaneously direct and indirect strategies of governance. [territoriality, Inka, Andes, Rapayán, Upper Marañón]
Detrimental effects of acute hyperglycaemia on the rat heart
Authors: Mapanga R. F. , Joseph D. , Symington B. , Garson K.‐L. , Kimar C. , Kelly‐Laubscher R. , Essop M.Faadiel 
Published: October 2013

AbstractAimHyperglycaemia is an important risk factor for acute myocardial infarction. It can lead to increased induction of non‐oxidative glucose pathways (NOGPs) – polyol and hexosamine biosynthetic pathways, advanced glycation end products and protein kinase C – that may contribute to cardiovascular diseases onset. However, the precise underlying mechanisms remain poorly understood. Here we hypothesized that acute hyperglycaemia increases myocardial oxidative stress and NOGP activation resulting in cardiac dysfunction during ischaemia–reperfusion and that inhibition of, and/or shunting flux away from NOGPs [by benfotiamine (BFT) treatment], leads to cardioprotection.MethodsWe employed several experimental systems: (i) Isolated rat hearts were perfused ex vivo with Krebs‐Henseleit buffer containing 33 mm glucose vs. controls (11 mm glucose) ± global ischaemia and reperfusion ± BFT (first 20 min of reperfusion); (ii) Infarct size determination as per the ischaemic protocol, but with regional ischaemia and reperfusion ± BFT treatment; in separate experiments, NOGP inhibitors were also employed for (i) and (ii); and (iii) In vivo coronary ligations performed on streptozotocin‐treated rats ± BFT treatment (early reperfusion).ResultsAcute hyperglycaemia generated myocardial oxidative stress, NOGP activation and apoptosis, but caused no impairment of cardiac function during pre‐ischaemia, thereby priming hearts for later damage. Following ischaemia–reperfusion (under hyperglycaemic conditions), such effects were exacerbated together with cardiac contractile dysfunction. Moreover, inhibition of respective NOGPs and shunting away by BFT treatment (in part) improved cardiac function during ischaemia–reperfusion.ConclusionCoordinate NOGP activation in response to acute hyperglycaemia results in contractile dysfunction during ischaemia–reperfusion, allowing for the development of novel cardioprotective agents.
Electronic health records for biological sample collection: feasibility study of statin‐induced myopathy using the Clinical Practice Research Datalink
Authors: O'Meara Helen , Carr Daniel F. , Evely Jane , Hobbs Mark , McCann Gerard , van Staa Tjeerd , Pirmohamed Munir 
Published: October 2013

AimsElectronic healthcare records (EHRs) are increasingly used to store clinical information. A secondary benefit of EHRs is their use, in an anonymized form, for observational research. The Clinical Practice Research Datalink (CPRD) contains EHRs from primary care in the UK and, despite 1083 peer‐reviewed research publications, has never been used to obtain pharmacogenetic samples. Using a statin‐induced myopathy paradigm, we evaluated using the CPRD to obtain patient samples for a pharmacogenetic study targeting 250 cases and 500 controls from UK general practitioner (GP) practices.MethodsThe CPRD identified potential patients fitting specific case‐definition criteria (active rhabdomyolysis or creatine phosphokinase > four times the upper limit of normal), and corresponding GP practices were asked to invite patient participation. Consenting patients were requested to provide either saliva or blood samples and to complete an ethnicity questionnaire. Control subjects were recruited from the same GP practice (saliva) or a small number of practices (blood). Samples were forwarded for DNA extraction.ResultsThirty‐six months of recruitment yielded DNA samples from 149 statin‐induced myopathy cases and 587 tolerant controls. Data show that contacting patients through their GP is a reliable method for obtaining samples without compromising anonymity. Saliva collection directly from patients was considerably less effective than blood sampling. After 10 months of recruitment, saliva sampling was suspended in favour of blood sampling.ConclusionsWe demonstrate the potential of EHRs for identifying accurately phenotyped cases and controls for pharmacogenetic studies. Recruitment was successful only because of the willingness of GP practices to participate and the existence of strong doctor–patient relationships. The present study provides a model that can be implemented in future genetic analyses using EHRs.
A Comparison of Marginal and Conditional Models for Capture–Recapture Data with Application to Human Rights Violations Data
Authors: Mitchell Shira , Ozonoff Al , Zaslavsky Alan M. , Hedt-Gauthier Bethany , Lum Kristian , Coull Brent A. 
Published: October 2013

SummaryHuman rights data presents challenges for capture–recapture methodology. Lists of violent acts provided by many different groups create large, sparse tables of data for which saturated models are difficult to fit and for which simple models may be misspecified. We analyze data on killings and disappearances in Casanare, Colombia during years 1998 to 2007. Our estimates differ whether we choose to model marginal reporting probabilities and odds ratios, versus modeling the full reporting pattern in a conditional (log-linear) model. With 2629 observed killings, a marginal model we consider estimates over 9000 killings, while conditional models we consider estimate 6000–7000 killings. The latter agree with previous estimates, also from a conditional model. We see a twofold difference between the high sample coverage estimate of over 10,000 killings and low sample coverage lower bound estimate of 5200 killings. We use a simulation study to compare marginal and conditional models with at most two-way interactions and sample coverage estimators. The simulation results together with model selection criteria lead us to believe the previous estimates of total killings in Casanare may have been biased downward, suggesting that the violence was worse than previously thought. Model specification is an important consideration when interpreting population estimates from capture recapture analysis and the Casanare data is a protypical example of how that manifests.