bluuebunny/crossref_metadata_2025_split huggingface dataset:
New users of antipsychotic medication: A population-based cohort study of occupational outcome measures in relation to antipsychotic on-label and off-label prescribing practices
Authors: Baandrup L. , Kruse M. 
Published: October 2015

AbstractBackgroundTreatment with antipsychotic medication is thoroughly investigated in schizophrenia and bipolar disorder but is also widely applied for a diversity of off-label conditions, despite an uncertain risk-benefit ratio. This study examined the relationship between antipsychotic prescribing patterns and labor market affiliation, considering both authority approved and off-label prescriptions and the relation to polypharmacy.MethodsRegister-based cohort study using a dataset of 71,254 new antipsychotic users with a psychiatric diagnosis. Labor market affiliation and duration of welfare payments were analyzed using linear regression models and duration analysis. The analyses were adjusted for the following confounding variables: age, gender, diagnosis, marital status, length of education, and utilization of mental health care services.ResultsThe majority of new antipsychotic users received welfare payments for prolonged periods of time during the observation period, even more so for individuals treated with antipsychotic polypharmacy or other antipsychotic combination regimens. The risk of permanently leaving the labor market was also associated with antipsychotic combination regimen.ConclusionsAntipsychotic treatment, especially in combination with other antipsychotics or other psychotropic drugs, could serve as a marker of subjects with increased need for support to maintain the labor market affiliation. However, causality cannot be inferred from an observational study because of residual confounding that could not be adjusted for in this study.
A phase 1 study to evaluate the safety and pharmacokinetics of PQ912, a glutaminyl cyclase inhibitor, in healthy subjects
Authors: Lues Inge , Weber Frank , Meyer Antje , Bühring Uli , Hoffmann Torsten , Kühn‐Wache Kerstin , Manhart Susanne , Heiser Ulrich , Pokorny Rolf , Chiesa Joseph , Glund Konrad 
Published: October 2015

AbstractIntroductionPyroglutamate‐amyloid‐β (pE‐Aβ) peptides are major components of Aβ‐oligomers and Aβ‐plaques, which are regarded as key culprits of Alzheimer's disease (AD) pathology. PQ912 is a competitive inhibitor of the enzyme glutaminyl cyclase (QC), essential for the formation of pE‐Aβ peptides.MethodsA randomized, double‐blind, placebo‐controlled, single‐ and multiple‐ascending oral dose study investigated the safety, pharmacokinetics, and pharmacodynamics of PQ912 in healthy nonelderly and elderly subjects.ResultsPQ912 was considered safe and well tolerated with dose‐proportional pharmacokinetics up to doses of 200 mg. At higher doses up to 1800 mg, exposure was supraproportional and exposure in elderly subjects was approximately 1.5‐ to 2.1‐fold higher. Exposure in cerebrospinal fluid (CSF) was approximately 20% of the unbound drug in plasma, and both serum and CSF QC activity was inhibited in a dose‐related manner.DiscussionThis first‐in‐man study of a compound‐targeting QC inhibition justifies further development of PQ912 for the treatment of AD.
Second-order sensitivity of parallel shear flows and optimal spanwise-periodic flow modifications
Authors: Boujo E. , Fani A. , Gallaire F. 
Published: October 2015

The question of optimal spanwise-periodic modification for the stabilisation of spanwise-invariant flows is addressed. A second-order sensitivity analysis is conducted for the linear temporal stability of parallel flows $U_{0}$ subject to small-amplitude spanwise-periodic modification ${\it\epsilon}U_{1},{\it\epsilon}\ll 1$. It is known that spanwise-periodic flow modifications have a quadratic effect on stability properties, i.e. the first-order eigenvalue variation is zero, hence the need for a second-order analysis. A second-order sensitivity operator is computed from a one-dimensional calculation, which allows one to predict how eigenvalues are affected by any flow modification $U_{1}$, without actually solving for modified eigenvalues and eigenmodes. Comparisons with full two-dimensional stability calculations in a plane channel flow and in a mixing layer show excellent agreement. Next, optimisation is performed on the second-order sensitivity operator: for each eigenmode streamwise wavenumber ${\it\alpha}_{0}$ and base flow modification spanwise wavenumber ${\it\beta}$, the most stabilising/destabilising profiles $U_{1}$ are computed, together with lower/upper bounds for the variation in leading eigenvalue. These bounds increase like ${\it\beta}^{-2}$ as ${\it\beta}$ goes to zero, thus yielding a large stabilising potential. However, three-dimensional modes with wavenumbers ${\it\beta}_{0}=\pm {\it\beta}$, $\pm {\it\beta}/2$ are destabilised, and therefore larger control wavenumbers should be preferred. The most stabilising $U_{1}$ optimised for the most unstable streamwise wavenumber ${\it\alpha}_{0,max}$ has a stabilising effect on modes with other ${\it\alpha}_{0}$ values too. Finally, the potential of transient growth to amplify perturbations and stabilise the flow is assessed with a combined optimisation. Assuming a separation of time scales between the fast unstable mode and the slow transient evolution of the optimal perturbations, combined optimal perturbations that achieve the best balance between transient linear amplification and stabilisation of the nominal shear flow are determined. In the mixing layer with ${\it\beta}\leqslant 1.5$, these combined optimal perturbations appear similar to transient growth-only optimal perturbations, and achieve a more efficient overall stabilisation than optimal spanwise-periodic and spanwise-invariant modifications computed for stabilisation only. These results are consistent with the efficiency of streak-based control strategies.
Exact coherent states and connections to turbulent dynamics in minimal channel flow
Authors: Park Jae Sung , Graham Michael D. 
Published: October 2015

Several new families of nonlinear three-dimensional travelling wave solutions to the Navier–Stokes equation, also known as exact coherent states, are computed for Newtonian plane Poiseuille flow. The symmetries and streak/vortex structures are reported and their possible connections to critical layer dynamics are examined. While some of the solutions clearly display fluctuations that are localized around the critical layer (the surface on which the streamwise velocity matches the wave speed of the solution), for others this connection is not as clear. Dynamical trajectories along unstable directions of the solutions are computed. Over certain ranges of Reynolds number, two solution families are shown to lie on the basin boundary between laminar and turbulent flow. Direct comparison of nonlinear travelling wave solutions to turbulent flow in the same channel is presented. The state-space dynamics of the turbulent flow is organized around one of the newly identified travelling wave families, and in particular the lower-branch solutions of this family are closely approached during transient excursions away from the dominant behaviour. These observations provide a firm dynamical-systems foundation for prior observations that minimal channel turbulence displays time intervals of ‘active’ turbulence punctuated by brief periods of ‘hibernation’ (see, e.g., Xi & Graham, Phys. Rev. Lett., vol. 104, 2010, 218301). The hibernating intervals are approaches to lower-branch nonlinear travelling waves. Representing these solutions on a Prandtl–von Kármán plot illustrates how their bulk flow properties are related to those of Newtonian turbulence as well as the universal asymptotic state called maximum drag reduction (MDR) found in viscoelastic turbulent flow. In particular, the lower- and upper-branch solutions of the family around which the minimal channel dynamics is organized appear to approach the MDR asymptote and the classical Newtonian result respectively, in terms of both bulk velocity and mean velocity profile.
Peerhood in deep religious disagreements
Authors: REINING STEFAN 
Published: October 2015

AbstractMy aim in this article is to widen the scope of the current debate on peer disagreement by applying it to a kind of case it has hitherto remained silent about – namely, to cases of disagreement in which one of the disagreeing parties bases her opinion on a private religious experience to which the other party has no access. In order to do this, I will introduce a modified version of the notion of peerhood – a version that, in contrast to the one employed in the current debate, can be fruitfully applied to the troublesome kind of case in question. I will then employ this new notion in order to specify the degree of conciliation rationally required from the disagreeing parties in the kind of case in question.
Republicanism on the borders: Jewish activism and the refugee crisis in Strasbourg and Nice
Authors: SCOTT-WEAVER MEREDITH L. 
Published: October 2015

ABSTRACT:This case-study of Jewish activism in Strasbourg and Nice, interwar urban locales situated along the frontiers with National Socialist Germany and fascist Italy, respectively, examines critical facets of Jewish advocacy during the refugee crisis of the 1930s. It focuses on how urban spaces engendered dense thickets of community activism unlike that which took place in Paris. Whereas friction and ineffectiveness characterized aid efforts in Paris, these cities offer alternative views on the nature of the refugee crisis in France and the ways that Jews overcame obstacles to help asylum-seekers. It advances much-needed discourse on the complexity of French Jewish experiences during the interwar years and highlights the city as both location and a conduit for diverse activist strategies. Although circumstances varied in Strasbourg and Nice, Jews in these two borderland cities followed similar patterns of engaging urban civil society to build flexible networks that addressed the plight of refugees from multiple angles.
Metaphysics as Kant’s Coquette: Rousseau’s Influence on Dreams of a Spirit-Seer
Authors: Alberg Jeremiah 
Published: October 2015

AbstractKant’s notes known as Remarks in the ‘Observations on the Feeling of the Beautiful and the Sublime’ reveal a deep concern with the way in which the human drives to equality and unity lead inevitably to a drive for honour and its attendant delusions. He developed his thinking about these problems in the context of his reading of Rousseau. In his published Dreams of a Spirit-Seer, Kant tries to overcome the influence of the drive for honour by appealing to a metaphysics that is critical of itself. The problem is how to distinguish what is grounded in reason when that reason is so easily influenced by others.
Kant’s PoliticalZweckmässigkeit
Authors: Huseyinzadegan Dilek 
Published: October 2015

AbstractWhile Kant’s political writings employ a teleological language, the exact benefit of such language to his politics is far from clear. Against recent interpretations of Kant’s political thought, which downplay or dismiss the role of teleology, I restoreZweckmässigkeitto its place in Kant’s politics as a theoretically and practically useful material principle, and show that a teleological perspective complements the perspective stipulated by the formal principle ofRecht. By means of a systematic reconstruction of what I call ‘politicalZweckmässigkeit’, we gain a fuller portrayal of and a valuable insight into Kant’s political thought.
Transcendental Concepts, Transcendental Truths and Objective Validity
Authors: Lau Chong-Fuk 
Published: October 2015

AbstractKant insists that the use of concepts must be subject to empirical conditions if they are to have objective validity. This article analyses Kant’s principle of objective validity, focusing particularly on its application to transcendental concepts such as those of sensibility, understanding and transcendental apperception. It distinguishes between two orders of objective validity, based on Kant’s distinction between empirical and transcendental truths. Since transcendental concepts are pure concepts without spatio-temporal content, their objective validity is of the same second-order kind as that of unschematized categories. This characteristic of transcendental concepts implies that the cognitive powers picked out by them are not particular psychological mechanisms, but rather abstract functional structures. Transcendental concepts owe their objective validity to the realizability of the functional structures by empirical cognizers like humans. This relation in turn helps to explain the nature of transcendental truths.
Psyche at the end of life: Psychiatric symptoms are prevalent in patients admitted to a palliative care unit
Authors: Masel Eva K. , Berghoff Anna S. , Mladen Aleksandra , Schur Sophie , Maehr Bruno , Kirchhoff Magdalena , Simanek Ralph , Bauer Martin , Watzke Herbert H. , Amering Michaela 
Published: October 2015

AbstractObjective:Our aim was to evaluate the frequency and treatment of psychiatric symptoms in patients at palliative care units (PCUs).Method:Patients admitted to one of five participating PCUs in Austria were included. The short version of the Patient Health Questionnaire (PHQ–D) was used to evaluate their mental health status. Pain intensity was rated on a numeric rating scale (NRS) from 0 to 10 by patients and physicians. Patients with a previously diagnosed psychiatric disorder were compared to those without or with newly diagnosed psychiatric symptoms, based on PHQ–D results. Pain and psychopharmacological medication were assessed. Opioid doses were converted into oral morphine equivalents (OMEs).Results:Some 68 patients were included. Previously undetected psychiatric symptoms were identified in 38% (26 of 68), preexisting psychiatric comorbidities were evident in 25% (17), and no psychiatric symptoms were observed in 37% (25). Patients with a preexisting psychiatric comorbidity received antidepressants and benzodiazepines significantly more often than patients without or with previously undetected psychiatric symptoms (p < 0.001). Patient and physician median NRS ratings of pain intensity correlated significantly (p = 0.001). Median NRS rating showed no significant difference between patients with preexisting, previously undetected, or without psychiatric symptoms. OMEs did not differ significantly between preexisting, without, or previously undetected psychiatric symptoms. Patients with undetected and preexisting psychiatric comorbidities had a greater impairment in their activities of daily living than patients without psychiatric symptoms (p = 0.003).Significance of Results:Undetected psychiatric comorbidities are common in patients receiving palliative care. Screening for psychiatric symptoms should be integrated into standard palliative care to optimize treatment and reduce the psychosocial burden of the disease.
Endoplasmic reticulum stress-regulated CXCR3 pathway mediates inflammation and neuronal injury in acute glaucoma
Authors: Ha Y , Liu H , Xu Z , Yokota H , Narayanan S P , Lemtalsi T , Smith S B , Caldwell R W , Caldwell R B , Zhang W 
Published: October 2015

AbstractAcute glaucoma is a leading cause of irreversible blindness in East Asia. The mechanisms underlying retinal neuronal injury induced by a sudden rise in intraocular pressure (IOP) remain obscure. Here we demonstrate that the activation of CXCL10/CXCR3 axis, which mediates the recruitment and activation of inflammatory cells, has a critical role in a mouse model of acute glaucoma. The mRNA and protein expression levels of CXCL10 and CXCR3 were significantly increased after IOP-induced retinal ischemia. Blockade of the CXCR3 pathway by deleting CXCR3 gene significantly attenuated ischemic injury-induced upregulation of inflammatory molecules (interleukin-1βand E-selectin), inhibited the recruitment of microglia/monocyte to the superficial retina, reduced peroxynitrite formation, and prevented the loss of neurons within the ganglion cell layer. In contrast, intravitreal delivery of CXCL10 increased leukocyte recruitment and retinal cell apoptosis. Inhibition of endoplasmic reticulum (ER) stress with chemical chaperones partially blocked ischemic injury-induced CXCL10 upregulation, whereas induction of ER stress with tunicamycin enhanced CXCL10 expression in retina and primary retinal ganglion cells. Interestingly, deleting CXCR3 attenuated ER stress-induced retinal cell death. In conclusion, these results indicate that ER stress-medicated activation of CXCL10/CXCR3 pathway has an important role in retinal inflammation and neuronal injury after high IOP-induced ischemia.
Edge-mediated skyrmion chain and its collective dynamics in a confined geometry
Authors: Du Haifeng , Che Renchao , Kong Lingyao , Zhao Xuebing , Jin Chiming , Wang Chao , Yang Jiyong , Ning Wei , Li Runwei , Jin Changqing , Chen Xianhui , Zang Jiadong , Zhang Yuheng , Tian Mingliang 
Published: October 2015

AbstractThe emergence of a topologically nontrivial vortex-like magnetic structure, the magnetic skyrmion, has launched new concepts for memory devices. Extensive studies have theoretically demonstrated the ability to encode information bits by using a chain of skyrmions in one-dimensional nanostripes. Here, we report experimental observation of the skyrmion chain in FeGe nanostripes by using high-resolution Lorentz transmission electron microscopy. Under an applied magnetic field, we observe that the helical ground states with distorted edge spins evolve into individual skyrmions, which assemble in the form of a chain at low field and move collectively into the interior of the nanostripes at elevated fields. Such a skyrmion chain survives even when the width of the nanostripe is much larger than the size of single skyrmion. This discovery demonstrates a way of skyrmion formation through the edge effect, and might, in the long term, shed light on potential applications.
A novel siderophore system is essential for the growth of Pseudomonas aeruginosa in airway mucus
Authors: Gi Mia , Lee Kang-Mu , Kim Sang Cheol , Yoon Joo-Heon , Yoon Sang Sun , Choi Jae Young 
Published: October 2015

AbstractPseudomonas aeruginosa establishes airway infections in Cystic Fibrosis patients. Here, we investigate the molecular interactions between P. aeruginosa and airway mucus secretions (AMS) derived from the primary cultures of normal human tracheal epithelial (NHTE) cells. PAO1, a prototype strain of P. aeruginosa, was capable of proliferating during incubation with AMS, while all other tested bacterial species perished. A PAO1 mutant lacking PA4834 gene became susceptible to AMS treatment. The ΔPA4834 mutant was grown in AMS supplemented with 100 μM ferric iron, suggesting that the PA4834 gene product is involved in iron metabolism. Consistently, intracellular iron content was decreased in the mutant, but not in PAO1 after the AMS treatment. Importantly, a PAO1 mutant unable to produce both pyoverdine and pyochelin remained viable, suggesting that these two major siderophore molecules are dispensable for maintaining viability during incubation with AMS. The ΔPA4834 mutant was regrown in AMS amended with 100 μM nicotianamine, a phytosiderophore whose production is predicted to be mediated by the PA4836 gene. Infectivity of the ΔPA4834 mutant was also significantly compromised in vivo. Together, our results identify a genetic element encoding a novel iron acquisition system that plays a previously undiscovered role in P. aeruginosa airway infection.
Linking rapid erosion of the Mekong River delta to human activities
Authors: Anthony Edward J. , Brunier Guillaume , Besset Manon , Goichot Marc , Dussouillez Philippe , Nguyen Van Lap 
Published: October 2015

AbstractAs international concern for the survival of deltas grows, the Mekong River delta, the world’s third largest delta, densely populated, considered as Southeast Asia’s most important food basket and rich in biodiversity at the world scale, is also increasingly affected by human activities and exposed to subsidence and coastal erosion. Several dams have been constructed upstream of the delta and many more are now planned. We quantify from high-resolution SPOT 5 satellite images large-scale shoreline erosion and land loss between 2003 and 2012 that now affect over 50% of the once strongly advancing >600 km-long delta shoreline. Erosion, with no identified change in the river’s discharge and in wave and wind conditions over this recent period, is consistent with: (1) a reported significant decrease in coastal surface suspended sediment from the Mekong that may be linked to dam retention of its sediment, (2) large-scale commercial sand mining in the river and delta channels and (3) subsidence due to groundwater extraction. Shoreline erosion is already responsible for displacement of coastal populations. It is an additional hazard to the integrity of this Asian mega delta now considered particularly vulnerable to accelerated subsidence and sea-level rise and will be exacerbated by future hydropower dams.
Detection of novel CYP11A1-derived secosteroids in the human epidermis and serum and pig adrenal gland
Authors: Slominski Andrzej T. , Kim Tae-Kang , Li Wei , Postlethwaite Arnold , Tieu Elaine W. , Tang Edith K. Y. , Tuckey Robert C. 
Published: October 2015

AbstractTo investigate whether novel pathways of vitamin D3 (D3) and 7-dehydrocholesterol (7DHC) metabolism initiated by CYP11A1 and previously characterizedin vitro, occurin vivo, we analyzed samples of human serum and epidermis and pig adrenals for the presence of intermediates and products of these pathways. We extracted human epidermis from 13 individuals and sera from 13 individuals and analyzed them by LC/qTOF-MS alongside the corresponding standards. Pig adrenal glands were also analyzed for these steroids and secosteroids. Epidermal, serum and adrenal samples showed the presence of D3 hydroxy-derivatives corresponding to 20(OH)D3, 22(OH)D3, 25(OH)D3, 1,25(OH)2D3, 20,22(OH)2D3, 20,23(OH)2D3, 20,24(OH)2D3, 20,25(OH)2D3, 20,26(OH)2D3, 1,20,23(OH)3D3 and 17,20,23(OH)3D3, plus 1,20(OH)2D3 which was detectable only in the epidermis. Serum concentrations of 20(OH)D3 and 22(OH)D3 were only 30- and 15-fold lower than 25(OH)D3, respectively and at levels above those required for biological activity as measuredin vitro. We also detected 1,20,24(OH)3D3, 1,20,25(OH)3D3 and 1,20,26(OH)3D3 in the adrenals. Products of CYP11A1 action on 7DHC, namely 22(OH)7DHC, 20,22(OH)27DHC and 7-dehydropregnenolone were also detected in serum, epidermis and the adrenal. Thus, we have detected novel CYP11A1-derived secosteroids in the skin, serum and adrenal gland and based on their concentrations and biological activity suggest that they act as hormonesin vivo.
Storm deposition layer on the Fujian coast generated by Typhoon Saola (2012)
Authors: Li Yunhai , Li Haidong , Qiao Lei , Xu Yonghang , Yin Xijie , He Jianhua 
Published: October 2015

AbstractTyphoons have a significant effect on the marine depositional environment and depositional process. In this paper, we used the high-resolution Chirp sonar sub-bottom profiler and radioisotope detection techniques to examine the storm-deposited layer formed in the seawater near the path of Typhoon Saola along the coast of Fujian, China. The thickness of the typhoon-deposited layer acquired using these two methods was 10–25 cm. The thickness, sediment grain size and δ13C values of the deposited sedimentary layer indicated that it was mainly matter from the re-suspension and redistribution of seafloor sediments. The particle sizes of the sediments in the storm-deposited layer became coarser, indicating that the fine-grade compositions spread over a wider range out of the coastal zone.