bluuebunny/crossref_metadata_2025_split huggingface dataset:
Overdoses with Aripiprazole: Signs, Symptoms and Outcome in 239 Exposures Reported to the Danish Poison Information Centre
Authors: Christensen Amalie P. , Boegevig Soeren , Christensen Mikkel B. , Petersen Kasper M. , Dalhoff Kim P. , Petersen Tonny S. 
Published: September 2017

AbstractThe aim of this study was to characterize the clinical signs and symptoms of exposures to aripiprazole overdoses. We retrospectively identified all aripiprazole exposures reported to the Danish Poison Information Centre (DPIC) from June 2007 to May 2015. Information concerning demographics, ingested dose and symptoms was extracted from the DPIC database and medical records. Information on death and admission to hospital was obtained from Danish national registers. We analysed 239 cases, 86 concerning single‐drug exposures to aripiprazole, and 153 cases where aripiprazole had been taken with at least one other substance (mixed‐drug). The median ingested aripiprazole dose was 105 mg (IQR: 50‐1680 mg) in the single‐drug exposure group and 120 mg (IQR: 60‐225 mg) in the mixed‐drug exposure group. The most commonly reported symptom was light sedation, reported in 63% of the single‐drug group and 50% of the mixed‐drug exposure group. There were no malignant arrhythmias or ECG abnormalities after single‐drug exposures. No deaths were recorded in relation to the intake. We found a long‐term mortality rate of 13 deaths per 1000 person‐years (95% CI: 7; 23 per 1000 person‐years), which is significantly higher than in an age‐ and gender‐matched background population. In conclusion, we found that aripiprazole overdoses had few and mild symptoms predominantly related to the sedative properties. We detected a benign cardiovascular safety profile and no new safety concerns. Our findings may support an increased threshold of 300 mg for hospital admission after a single‐drug exposure with aripiprazole and symptoms not worse than light sedation.
Remyelination of regenerating axons
Authors: Neumann B. , Baror R. , van Wijngaarden P. , Franklin R.J. 
Published: September 2017

SummaryRemyelination depends on adult multipotent progenitor cells, called oligodendrocyte progenitor cells (OPCs) that give rise to remyelinating oligodendrocytes. With age, remyelination slows and axons remain demyelinated, rendering them vulnerable to ir‐ reversible degeneration. which eventually contributes to the accumulation of disability in patients with chronic demyelinating diseases, such as multiple sclerosis. The rate limiting step for remyelination in aged individuals is the maturation of OPCs into oligo‐ dendrocytes. Here we report that aged OPCs undergo inherent changes that prevent their differentiation. Using alternate day fasting to ameliorate the effects of ageing, we were able to restore remyelination in aged rats. Mechanistically, this involved the mo‐ lecular rejuvenation of aged OPCs and amelioration of ageing hallmarks. By exposing aged OPCs to metformin we were able to phenocopy the effects of fasting in vitro and in vivo. Our results suggest that implementation of remyelination therapies will require both understanding and overcoming the effects of ageing, as well as finding ways to modulate extrinsic factors to generate a permissive environment for regeneration.
Pressure sore risk calculators: some methodological issues
Authors: EDWARDS MARGARET 
Published: September 2017

SUMMARY
Pressure sore risk calculators have assumed a cardinal role in pressure sore prevention and management.
Doubts have been expressed as to the extent to which the use of risk calculators should direct care as they have not been found to display high levels of reliability and validity.
This paper raises important methodological issues regarding the reliability and validity of risk calculators in order to inform the debate as to the direction of future research in this area.
Urinary incontinence in bitches under primary veterinary care in England: prevalence and risk factors
Authors: O'Neill D. G. , Riddell A. , Church D. B. , Owen L. , Brodbelt D. C. , Hall J. L. 
Published: September 2017

ObjectivesTo estimate prevalence and demographic risk factors for urinary incontinence in bitches under primary veterinary care in England.MethodsThe study population included all bitches within the VetCompass database from September 1, 2009 to July 7, 2013. Electronic patient records were searched for urinary incontinence cases and additional demographic and clinical information was extracted.ResultsOf 100,397 bitches attending 119 clinics in England, an estimated 3108 were diagnosed with urinary incontinence. The prevalence of urinary incontinence was 3·14% (95% confidence intervals: 2·97 to 3·33). Medical therapy was prescribed to 45·6% cases. Predisposed breeds included the Irish setter (odds ratio: 8·09; 95% confidence intervals: 3·15 to 20·80; P< 0·001) and Dobermann (odds ratio: 7·98; 95% confidence intervals: 4·38 to 14·54; P< 0·001). Increased odds of a diagnosis of urinary incontinence were associated with: (1) weight at or above the mean adult bodyweight for the breed (odds ratio: 1·31; 95% confidence intervals: 1·12 to 1·54; P< 0·001), (2) age 9 to 12 years (odds ratio: 3·86; 95% confidence intervals: 2·86 to 5·20, P< 0·001), (3) neuter status (odds ratio: 2·23; 95% confidence intervals: 1·52 to 3·25, P< 0·001) and (4) being insured (odds ratio: 1·59; 95% confidence intervals: 1·34 to 1·88, P< 0·001).Clinical ImpactClinical Impact: Urinary incontinence affects just over 3% of bitches overall but affects more than 15% of bitches in high‐risk breeds including the Irish setter, Dobermann, bearded collie, rough collie and Dalmatian. These results provide an evidence base for clinicians to enhance clinical recommendations on neutering and weight control, especially in high‐risk breeds.
Language as a public good and national identity: Scotland's competing heritage languages
Authors: Chhim Chris , Bélanger Éric 
Published: September 2017

AbstractThe preservation of one or several historically and culturally important languages may be a salient political issue in some polities. Although they may not be used as an active means of communication, these languages can also serve a symbolic identitary function. These ‘heritage’ languages can be seen as ‘public goods’ and that even non‐speakers of these languages can have opinions regarding their importance to national identity. In the Scotland example, while Gaelic has been the focus of proactive government legislation and education initiatives, Scots is still struggling for status as a recognised language. Both languages are in some way constituent parts of Scottish identity that at times may seem in competition with one another. Using original survey data, we delve deeper into questions of language, identity and politics in Scotland. First, we describe how public opinion is divided over the importance of Gaelic and Scots to Scottish identity. Second, we use attitudes towards these languages as a dependent variable looking at Scottish identity and attachment. Finally, we use these attitudes towards Gaelic and Scots as an independent variable in models for party identification in Scotland.
Chloroplast position and photosynthetic characteristics in two monostromatic species,Monostroma angicavaandProtomonostroma undulatum(Ulvophyceae), having a shared ecological niche
Authors: Saco Jayvee Ablaña , Murakami Akio , Sekida Satoko , Mine Ichiro 
Published: September 2017

SUMMARYMonostroma angicavaandProtomonostroma undulatumare monostromatic green benthic algae (Ulvophyceae), which grow together in the same intertidal habitat of Muroran, Hokkaido, Japan, during the spring season. Commonly, both species have a single chloroplast with one pyrenoid per cell. The parietal chloroplast is located on the periphery of the thallus in both species, although the location of the chloroplast differs in the two. InM. angicava, the chloroplast was observed to be arranged on one‐side of the thallus surface, whereas, inP. undulatum, it was dispersed and randomly located on either side of the thallus or on the lateral face. The density of chlorophylls (Chls) assessed from the absorption spectra of the thallus and its solvent extract was higher inM. angicava, which appeared dark‐green in color, than in the light‐green coloredP. undulatum. The maximum photosynthetic rate per thallus area (μmol O2m−2s−1) was higher inM. angicava, whereas, per total chlorophyll content (μmol O2g Chla+ Chlb−1s−1) was higher inP. undulatum. Both species showed similar efficiency of photosynthesis at light‐limiting conditions. The efficiency of light absorption by photosystemII(PSII) inP. undulatumwas higher thanM. angicava, whereas the photoprotective response was higher inM. angicava. This indicates that more energy is utilized inM. angicavato protect itsPSIIdue to the chloroplast position, which has more direct exposure to light and, therefore, lowers the efficiency of light absorption byPSII. The higher density of chlorophylls inM. angicavacould explain higher photosynthesis per thallus area, whereas, higher efficiency of light absorption byPSIIinP. undulatumcould explain higher photosynthesis per total chlorophyll content. The differences in light absorption efficiency and quantum efficiency ofPSIImight be an important ecological strategy in these two species for their coexistence in the intertidal area.
On categories for quantized symplectic resolutions
Authors: Losev Ivan 
Published: September 2017

In this paper we study categories ${\mathcal{O}}$ over quantizations of symplectic resolutions admitting Hamiltonian tori actions with finitely many fixed points. In this generality, these categories were introduced by Braden et al. We establish a family of standardly stratified structures (in the sense of the author and Webster) on these categories ${\mathcal{O}}$. We use these structures to study shuffling functors of Braden et al. (called cross-walling functors in this paper). Most importantly, we prove that all cross-walling functors are derived equivalences that define an action of the Deligne groupoid of a suitable real hyperplane arrangement.
Population Pharmacokinetics of Posaconazole Tablets and Monte Carlo Simulations To Determine whether All Patients Should Receive the Same Dose
Authors: Petitcollin A. , Boglione-Kerrien C. , Tron C. , Nimubona S. , Lalanne S. , Lemaitre F. , Bellissant E. , Verdier M.-C. 
Published: August 2017

ABSTRACT

Posaconazole is extensively used for prophylaxis for invasive fungal infections. The gastro-resistant tablet formulation has allowed the bioavailability issues encountered with the oral suspension to be overcome. However, overexposure is now frequent. This study aimed to (i) describe the pharmacokinetics of posaconazole tablets in a real-life cohort of patients with hematological malignancies and (ii) perform Monte Carlo simulations to assess the possibility that the daily dose can be reduced while keeping a sufficient exposure. Forty-nine consecutive inpatients were prospectively included in the study. Posaconazole trough concentrations (TC) were measured once a week, and biological and demographic data were collected. The concentrations were analyzed by compartmental modeling, and Monte Carlo simulations were performed using estimated parameters to assess the rate of attainment of the target TC after dose reduction. The pharmacokinetics of posaconazole were well described using a one-compartment model with first-order absorption and elimination. The values of the parameters (interindividual variabilities) were as follows: the absorption constant (

k
a

) was 0.588 h
−1
(fixed), the volume of distribution (
V
/
F
) was 420 liters (28.2%), and clearance (CL/
F
) was 7.3 liters/h (24.2%) with 31.9% interoccasion variability. Forty-nine percent of the simulated patients had TC at steady state of ≥1.5 μg/ml and maintained a TC above 1 μg/ml after a reduction of the dose to 200 mg daily. A third of these patients eligible for a dose reduction had TC of ≥1.5 μg/ml as soon as 48 h of treatment. Though posaconazole tablets were less impacted by bioavailability issues than the oral suspension, the pharmacokinetics of posaconazole tablets remain highly variable. Simulations showed that approximately half of the patients would benefit from a reduction of the dose from 300 mg to 200 mg while keeping the TC above the minimal recommended target of 0.7 μg/ml, resulting in a 33% savings in the cost of this very expensive drug.
Imatinib dramatically alleviates pulmonary tumour thrombotic microangiopathy induced by gastric cancer
Authors: Kubota Kana , Shinozaki Taro , Imai Yasushi , Kario Kazuomi 
Published: September 2017

Pulmonary tumour thrombotic microangiopathy (PTTM) is a rare complication of cancer, which can be lethal due to progressive pulmonary hypertension (PH). Several case reports have demonstrated that imatinib, a platelet-derived growth factor receptor–tyrosine kinase inhibitor, can improve severe PH in patients with PTTM.We describe the case of a 56-year-old woman. Her mean pulmonary arterial pressure (mPAP) was 47 mm Hg, and her dyspnoea worsened rapidly over several days. Although pulmonary embolism was not observed on CT, enlargement of the para-aortic lymph nodes was detected. Gastro-oesophageal endoscopy revealed signet-ring cell carcinoma. We diagnosed her as having PTTM based on her clinical course, and started treatment with imatinib. Five days after its administration, her mPAP decreased dramatically. She was discharged and lived without symptoms of PH until her death due to systemic metastasis of carcinoma. In some cases of PTTM, imatinib may be an effective therapeutic option for PH.
Alterations in Bronchial Airway miRNA Expression for Lung Cancer Detection
Authors: Pavel Ana B. , Campbell Joshua D. , Liu Gang , Elashoff David , Dubinett Steven , Smith Kate , Whitney Duncan , Lenburg Marc E. , Spira Avrum 
Published: September 2017

AbstractWe have previously shown that gene expression alterations in normal-appearing bronchial epithelial cells can serve as a lung cancer detection biomarker in smokers. Given that miRNAs regulate airway gene expression responses to smoking, we evaluated whether miRNA expression is also altered in the bronchial epithelium of smokers with lung cancer. Using epithelial brushings from the mainstem bronchus of patients undergoing bronchoscopy for suspected lung cancer (as part of the AEGIS-1/2 clinical trials), we profiled miRNA expression via small-RNA sequencing from 347 current and former smokers for which gene expression data were also available. Patients were followed for one year postbronchoscopy until a final diagnosis of lung cancer (n = 194) or benign disease (n = 153) was made. Following removal of 6 low-quality samples, we used 138 patients (AEGIS-1) as a discovery set to identify four miRNAs (miR-146a-5p, miR-324-5p, miR-223-3p, and miR-223-5p) that were downregulated in the bronchial airway of lung cancer patients (ANOVA P &lt; 0.002, FDR &lt; 0.2). The expression of these miRNAs is significantly more negatively correlated with the expression of their mRNA targets than with the expression of other nontarget genes (K-S P &lt; 0.05). Furthermore, these mRNA targets are enriched among genes whose expression is elevated in cancer patients (GSEA FDR &lt; 0.001). Finally, we found that the addition of miR-146a-5p to an existing mRNA biomarker for lung cancer significantly improves its performance (AUC) in the 203 samples (AEGIS-1/2) serving an independent test set (DeLong P &lt; 0.05). Our findings suggest that there are miRNAs whose expression is altered in the cytologically normal bronchial epithelium of smokers with lung cancer, and that they may regulate cancer-associated gene expression differences. Cancer Prev Res; 10(11); 651–9. ©2017 AACR.
Antigen-Presenting Intratumoral B Cells Affect CD4+ TIL Phenotypes in Non–Small Cell Lung Cancer Patients
Authors: Bruno Tullia C. , Ebner Peggy J. , Moore Brandon L. , Squalls Olivia G. , Waugh Katherine A. , Eruslanov Evgeniy B. , Singhal Sunil , Mitchell John D. , Franklin Wilbur A. , Merrick Daniel T. , McCarter Martin D. , Palmer Brent E. , Kern Jeffrey A. , Slansky Jill E. 
Published: August 2017

Abstract
Effective immunotherapy options for patients with non–small cell lung cancer (NSCLC) are becoming increasingly available. The immunotherapy focus has been on tumor-infiltrating T cells (TILs); however, tumor-infiltrating B cells (TIL-Bs) have also been reported to correlate with NSCLC patient survival. The function of TIL-Bs in human cancer has been understudied, with little focus on their role as antigen-presenting cells and their influence on CD4+ TILs. Compared with other immune subsets detected in freshly isolated primary tumors from NSCLC patients, we observed increased numbers of intratumoral B cells relative to B cells from tumor-adjacent tissues. Furthermore, we demonstrated that TIL-Bs can efficiently present antigen to CD4+ TILs and alter the CD4+ TIL phenotype using an in vitro antigen-presentation assay. Specifically, we identified three CD4+ TIL responses to TIL-Bs, which we categorized as activated, antigen-associated, and nonresponsive. Within the activated and antigen-associated CD4+ TIL population, activated TIL-Bs (CD19+CD20+CD69+CD27+CD21+) were associated with an effector T-cell response (IFNγ+ CD4+ TILs). Alternatively, exhausted TIL-Bs (CD19+CD20+CD69+CD27−CD21−) were associated with a regulatory T-cell phenotype (FoxP3+ CD4+ TILs). Our results demonstrate a new role for TIL-Bs in NSCLC tumors in their interplay with CD4+ TILs in the tumor microenvironment, establishing them as a potential therapeutic target in NSCLC immunotherapy. Cancer Immunol Res; 5(10); 898–907. ©2017 AACR.
An Overview of European Efforts in Generating Climate Data Records
Authors: Su Z. , Timmermans W. , Zeng Y. , Schulz J. , John V. O. , Roebeling R. A. , Poli P. , Tan D. , Kaspar F. , Kaiser-Weiss A. K. , Swinnen E. , Toté C. , Gregow H. , Manninen T. , Riihelä A. , Calvet J.-C. , Ma Y. , Wen J. 
Published: September 2017

Abstract
The Coordinating Earth Observation Data Validation for Reanalysis for Climate Services project (CORE-CLIMAX) aimed to substantiate how Copernicus observations and products can contribute to climate change analyses. CORE-CLIMAX assessed the European capability to provide climate data records (CDRs) of essential climate variables (ECVs), prepared a structured process to derive CDRs, developed a harmonized approach for validating essential climate variable CDRs, identified the integration of CDRs into the reanalysis chain, and formulated a process to compare the results of different reanalysis techniques. With respect to the Copernicus Climate Change Service (C3S), the systematic application and further development of the CORE-CLIMAX system maturity matrix (SMM) and the spinoff application performance metric (APM) were strongly endorsed to be involved in future implementations of C3S. We concluded that many of the current CDRs are not yet sufficiently mature to be used in reanalysis or applied in climate studies. Thus, the production of consistent high-resolution data records remains a challenge that needs more research urgently. Extending ECVs to close climate cycle budgets (e.g., essential water variables) is a next step linking CDRs to sectoral applications.
Beyond the Rigid Lid: Baroclinic Modes in a Structured Atmosphere
Authors: Edman Jacob P. , Romps David M. 
Published: August 2017

Abstract
The baroclinic-mode decomposition is a fixture of the tropical-dynamics literature because of its simplicity and apparent usefulness in understanding a wide range of atmospheric phenomena. However, its derivation relies on the assumption that the tropopause is a rigid lid that artificially restricts the vertical propagation of wave energy. This causes tropospheric buoyancy anomalies of a single vertical mode to remain coherent for all time in the absence of dissipation. Here, the authors derive the Green’s functions for these baroclinic modes in a two-dimensional troposphere (or, equivalently, a three-dimensional troposphere with one translational symmetry) that is overlain by a stratosphere. These Green’s functions quantify the propagation and spreading of gravity waves generated by a horizontally localized heating, and they can be used to reconstruct the evolution of any tropospheric heating. For a first-baroclinic two-dimensional right-moving or left-moving gravity wave with a characteristic width of 100 km, its initial horizontal shape becomes unrecognizable after 4 h, at which point its initial amplitude has also been reduced by a factor of 1/π. After this time, the gravity wave assumes a universal shape that widens linearly in time. For gravity waves on a periodic domain the length of Earth’s circumference, it takes only 10 days for the gravity waves to spread their buoyancy throughout the entire domain.
Auditory Outcomes with Hearing Rehabilitation in Children with Unilateral Hearing Loss: A Systematic Review
Authors: Appachi Swathi , Specht Jessica. L. , Raol Nikhila , Lieu Judith E. C. , Cohen Michael S. , Dedhia Kavita , Anne Samantha 
Published: August 2017

ObjectiveOptions for management of unilateral hearing loss (UHL) in children include conventional hearing aids, bone‐conduction hearing devices, contralateral routing of signal (CROS) aids, and frequency‐modulating (FM) systems. The objective of this study was to systematically review the current literature to characterize auditory outcomes of hearing rehabilitation options in UHL.Data SourcesPubMed, EMBASE, Medline, CINAHL, and Cochrane Library were searched from inception to January 2016. Manual searches of bibliographies were also performed.Review MethodsStudies analyzing auditory outcomes of hearing amplification in children with UHL were included. Outcome measures included functional and objective auditory results. Two independent reviewers evaluated each abstract and article.ResultsOf the 249 articles identified, 12 met inclusion criteria. Seven articles solely focused on outcomes with bone‐conduction hearing devices. Outcomes favored improved pure‐tone averages, speech recognition thresholds, and sound localization in implanted patients. Five studies focused on FM systems, conventional hearing aids, or CROS hearing aids. Limited data are available but suggest a trend toward improvement in speech perception with hearing aids. FM systems were shown to have the most benefit for speech recognition in noise. Studies evaluating CROS hearing aids demonstrated variable outcomes.ConclusionsData evaluating functional and objective auditory measures following hearing amplification in children with UHL are limited. Most studies do suggest improvement in speech perception, speech recognition in noise, and sound localization with a hearing rehabilitation device.
Infrastructure and Development in Rural India
Authors: Ghosh Madhusudan 
Published: August 2017

This article evaluates rural infrastructure facilities in 16 major states of India, and examines their impacts on some income and non-income dimensions of rural development. Despite several public initiatives for infrastructure development in rural India, facilities continue to be poor and progress has been mostly unsatisfactory with differential performance across states. Estimates of regression coefficients of the composite indices and individual indicators of rural infrastructure reveal that improved physical and social infrastructure and livelihood opportunities enhance agricultural productivity and output, improve literacy and life expectancy, and reduce poverty and infant mortality. The results, showing the relative importance of various infrastructures, suggest that the government should prioritise additional investments in electricity, roads, irrigation, housing and telecommunications to enhance overall well-being. JEL Classification: H54, O15, O18, Q19