bluuebunny/crossref_metadata_2025 huggingface dataset:
Study of internal flame front structure of accelerating hydrogen/oxygen flames with detailed chemical kinetics and diffusion models
Authors: Bykov V. , Koksharov A.
Published: January 2019

The problem of Detonation to Deflagration (DDT) is revisited. A stoichiometric hydrogen/oxygen combustion system is considered. The study focuses on the investigation of the system solution in the thermo-chemical state space of the system. The Σ model is implemented to study the flame acceleration and DDT in 1D formulation. The model was suggested to take into account wrinkling of the flame surface. In this way, the problem becomes treatable numerically even with the detailed mechanism of chemical kinetics and with detailed models for molecular diffusion. In order to treat and integrate the model a recently developed numerical scheme to deal with very stiff systems both in time and in space is introduced and applied. Typical system solution profiles of the ignition, quasi-deflagration, flame acceleration, DDT and detonation stages are considered to study the structure of the flame front in the system thermo-chemical state space. The results of computations show that at the stages of the ignition, deflagration and acceleration the flame structure in the state/composition space moderately depends on Σ, however, significant influence shows up during later stages of the flame acceleration and DDT. Moreover, the path of the solution in the detonation regime significantly deviates from that of deflagration. This means that accurate and quantitative study of the DDT is not possible without reliable mechanisms of chemical kinetics able to describe the system state space during the transient.
Reconsidering the fundamental movement skills construct: Implications for assessment
Authors: Ng Jonathan Leo , Button Chris
Published: January 2019

A wide range of movement experiences over the early years of life is crucial for the development of expertise in skill later in adulthood. A set of movements termed Fundamental Movement Skills has been suggested as a precursor for performance of more complex movement. The attainment of FMS during childhood is certainly a noble and worthwhile aim. However, we argue that mastery of FMS as demonstrated through movement assessment batteries does not sufficiently capture movement competence in the general population. Contemporary views of motor development, such as Ecological Dynamics, suggest instead, that regardless of prior acquisition of a “fundamental” set of skills, an individual’s motor competence is the result of self-organisation under constraint to achieve outcome goals. We propose a working definition of movement competence that stresses the importance of the role of affordance detection and utilisation throughout the lifespan. Thus, what should be considered “foundational” is a wide range of movement experiences that allows an individual adequate opportunities for exploration and refinement in order to build expertise. Encouragingly, new movement assessment tools are emerging that apply these important theoretical concepts and help to reveal how individuals can demonstrate their movement adaptability instead of performing isolated movements based upon an “ideal” standard.
Leitliniengerechte Verordnung von krankheitsmodifizierenden Arzneimitteln bei Patienten mit rheumatoider Arthritis – eine Analyse auf Basis von GKV-Routinedaten
Authors: Neubauer Sarah , Zeidler Henning , Linder Roland , Zeidler Jan
Published: January 2019

Hintergrund Mit Einführung der Biologika hat sich die Therapie der rheumatoiden Arthritis (RA) hinsichtlich der Wirksamkeit und Kosten grundlegend gewandelt. Ziel dieser Studie ist es, die der S1-Leitlinie der DGRh entsprechende Versorgung von RA-Patienten mit krankheitsmodifizierenden Medikamenten (disease-modifying anti-rheumatic drugs; DMARDs) anhand von Routinedaten der gesetzlichen Krankenversicherung zu analysieren.

Methodik Die Abrechnungsdaten der Techniker Krankenkasse wurden retrospektiv für die Jahre 2011 – 2014 analysiert. Im Rahmen von Subgruppenanalysen wurden Verschreibungs- und Versorgungsunterschiede einzelner in der Leitlinie empfohlener Wirkstoffe wie konventionelle DMARDs und Biologika analysiert.

Ergebnisse Die Studienpopulation umfasste 55 538 RA-Patienten (29,7 % inzidente, 70,3 % prävalente; 22,3 % M05: Seropositive chronische Polyarthritis, 77,7 % M06: Sonstige chronische Polyarthritis). Lediglich 21 616 Versicherte (38,9 %) bekamen mindestens einmal innerhalb eines Jahres nach der Erstdiagnose ein in der Leitlinie empfohlenes konventionelles DMARD oder Biologikum verordnet. Bei den inzidenten Patienten lag die Versorgungsquote mit krankheitsmodifizierenden Medikamenten unterhalb der prävalenten Patienten (31,5 vs. 42,1 %). 60,9 % der M05-Patienten und nur 29,7 % der M06-Patienten erhielten einen Einzelwirkstoff nach Index-Diagnose. Wenn ein Basistherapeutikum verordnet wurde, dann wurde dies durchschnittlich innerhalb eines Quartals nach Erstdiagnose verschrieben. Die führende Rolle in der Verschreibung von Basistherapeutika für die Indexmedikation übernimmt der Rheumatologe. Dennoch zeigte sich, dass nur 68,3 % der Patienten mindestens einmal innerhalb eines Jahres nach der Erstdiagnose einen rheumatologisch tätigen Facharzt konsultierten.

Schlussfolgerung Mittels einer großen Stichprobe konnten Unterschiede in der leitliniengerechten Verordnung von krankheitsmodifizierenden Arzneimitteln für verschiedene Subgruppen sowie eine Unterversorgung bei nicht vom internistischen Rheumatologen behandelten Patienten aufgezeigt werden.
Follicular Fluid Levels of Adrenomedullin 2, Vascular Endothelial Growth Factor and its Soluble Receptors Are Associated with Ovarian Response During ART Cycles
Authors: Ranjbaran Ali , Nejabati Hamid , Ghasemnejad Tohid , Latifi Zeinab , Hamdi Kobra , Hajipour Hamed , Raffel Nathalie , Bahrami-asl Zahra , Hakimi Parvin , Mihanfar Aynaz , Nouri Mohammad , Fattahi Amir
Published: January 2019

Introduction Adrenomedullin 2 (ADM2) and vascular endothelial growth factor (VEGF) affect ovarian function, especially angiogenesis and follicular development. The actions of VEGF can be antagonized by its soluble receptors, soluble Fms-like tyrosine kinase-1 (sFlt-1) and soluble VEGF receptor 2 (sVEGFR-2), as they decrease its free form. In the present study, we evaluated the relationship between follicular fluid (FF) levels of AMD2, VEGF and its soluble receptors, and ICSI outcomes.

Materials and Methods ICSI cycle outcomes were evaluated and FF levels of VEGF, sFlt-1, sVEGFR-2 and ADM2 were determined using ELISA kits.

Results FF levels of ADM2, VEGF, and sVEGFR-2 were significantly higher in non-responders compared to other ovarian response groups (p < 0.05). There were significant correlations between ADM2, VEGF and sVEGFR-2 levels as well as VEGF/sFlt-1 and VEGF/sVEGFR-2 ratios (r = 0.586, 0.482, 0.260, and − 0.366, respectively). Based on the ROC curve, the cutoff value for ADM2 as a non-responder predictor was 348.55 (pg/ml) with a sensitivity of 67.7% and a specificity of 94.6%.

Conclusions For the first time we measured FF ADM2 levels to determine the relationship to VEGF and its soluble receptors. We suggest that ADM2 could be a potential predictive marker for non-responders. Although the exact function of ADM2 in ovarian angiogenesis is not yet understood, our study may shed light on the possible role of ADM2 in folliculogenesis and ovulation.
SpyGlass DS-guided lithotripsy for pancreatic duct stones in symptomatic treatment-refractory chronic calcifying pancreatitis
Authors: Gerges Christian , Pullmann David , Bahin Farzan , Schneider Markus , Siersema Peter , Neuhaus Horst , van Geenen Erwin-Jan , Beyna Torsten
Published: January 2019

Background and study aims Endoscopic retrograde cholangiopancreatography (ERCP) and/or extracorporeal shock wave lithotripsy are first-line therapies for draining an obstructed pancreatic duct (PD) in painful chronic calcifying pancreatitis (CCP). Pancreaticoscopy has shown promising success rates in small series.

Materials and methods This study was a retrospective analysis of a clinical database. Included were all digital single-operator digital video (SOV) pancreaticoscopy-guided interventions (n = 23) on CCP patients (n = 20) between 2015 and 2017. Success and complication rates were collected from the database. Clinical success was determined by assessing pain level score (NRS) and quality of life (QoL) using standardized questionnaires.

Results Overall technical success rate (successful SOV-pancreaticoscopy and PD drainage) was 95 %. Adverse events occurred in 7 of 23 procedures (30 %) and included extravasation from the PD (n = 1), self-limiting post-sphincterotomy bleeding (n = 1) and post-ERCP pancreatitis (PEP) (n = 6). At 3- to 6-month follow-up, 95 % of patients reported improvement in symptoms and reduction in intake of analgesics. Mean NRS decreased from 5.4 (±1.6) to 2.8 (± 1.8) (P < 0.01). Clinical success was achieved in 95 % of patients.

Conclusions Digital SOV-guided lithotripsy was found to be safe and effective in this highly selected population of CCP patients. PD decompression had a beneficial effect on pain reduction and QoL.
Concept of Viral Inhibitors via NTCP
Authors: Fukano Kento , Tsukuda Senko , Watashi Koichi , Wakita Takaji
Published: January 2019

Identification of sodium taurocholate cotransporting polypeptide (NTCP) as an entry receptor for hepatitis B and D viruses (HBV and HDV) has not only promoted our understanding of the mechanism underlying the viral entry process, but also provided cell culture models supporting viral infection. These models have greatly facilitated cell-based chemical screening for the discovery of entry inhibitors, and mode of action studies using such inhibitors have shown the advantages of NTCP as a drug target. Furthermore, in vitro chemical screening by application of high-throughput affinity-based technologies that target NTCP has identified a variety of unique small molecules that interfere with viral entry. This review summarizes this hot topic in the development of HBV/HDV entry inhibitors, with special focus on the use of NTCP as a drug target.
Nonsurgical Management of Single-Sided Deafness: Contralateral Routing of Signal
Authors: Snapp Hillary
Published: January 2019

In recent years, an increasing research effort has been directed toward remediation of single-sided deafness. Contralateral routing of signal (CROS) is the longest standing rehabilitation solution for individuals with single-sided deafness. The primary goal of CROS technology is to transfer the signal received at the deaf ear to the better hearing ear, thereby reducing the impact of the acoustic head-shadow. This allows for individuals with single-sided deafness to regain access to sounds located at the deaf ear. The hearing deficits associated with single-sided deafness are often debilitating. While surgical management of single-sided deafness is on the rise, CROS hearing aids offer a nonsurgical option to compensate for some of the deficits that occur when a listener is limited to a single ear. Limitations of early CROS devices resulted in poor adoption and acceptance in those with single-sided deafness. Following significant advances in both design and technology, the acceptance of CROS devices has increased in recent years. This paper reviews relevant literature in CROS application for the management of single-sided deafness. Technological advances, benefits, limitations, and clinical considerations are also reviewed in this article.
Distribution spaces and a new construction of stochastic processes associated with the Grassmann algebra
Authors: Alpay Daniel , Paiva Ismael L. , Struppa Daniele C.
Published: January 2019

We associate with the Grassmann algebra a topological algebra of distributions, which allows the study of processes analogous to the corresponding free stochastic processes with stationary increments, as well as their derivatives.
Electrical and optical properties of scandium nitride nanolayers on MgO (100) substrate
Authors: More-Chevalier Joris , Cichoň Stanislav , Bulíř Jiří , Poupon Morgane , Hubík Pavel , Fekete Ladislav , Lančok Ján
Published: January 2019

Scandium nitride (ScN) is a rocksalt-structure semiconductor that has attracted attention for its potential applications in thermoelectric energy conversion devices, as a semiconducting component in epitaxial metal/semiconductor superlattices. ScN nanolayers of 30 nm thickness were deposited on MgO (001) substrate by reactive sputtering. Epitaxial growth of ScN(002) was observed with a mosaicity between grains around the {002} growth axis. Both direct band gaps theoretically predicted were measured at 2.59 eV and 4.25 eV for the energy gaps between the valence band and the conductance band at the X point and the Γ point respectively. Electrical and optical properties were observed to be strongly influenced by the crystalline order and the carrier concentration.
Ferromagnetism in the multiferroic alloy systems BiFeO3-BaTiO3 and BiFeO3-SrTiO3: Intrinsic or extrinsic?
Authors: Kumar Amit , Kumar Avinash , Saha Sujoy , Basumatary Himalay , Ranjan Rajeev
Published: January 2019

Among the different bulk alloys of the room temperature multiferroic compound BiFeO3, alloying with ATiO3 (A = Ba, Sr, Pb) is interesting as they have been reported to induce ferromagnetism under certain conditions. While this makes them interesting as potential multiferroic magnetoelectric materials, there is a lack of clarity on the origin of ferromagnetism in these systems. We have performed a detailed magneto-structural analysis on two alloys, namely, BiFeO3-BaTiO3 and BiFeO3-SrTiO3, and found the systems' propensity for the formation of ferrimagnetic hexaferrite (BaFe12O19 and SrFe12O19) phases. Though insignificantly small to the extent of being undetectable by x-ray powder diffraction, we prove that the ferromagnetic character of the specimen is entirely due to spontaneous precipitation of the hexaferrite grains. While our results suggest that care should be exercised before attributing ferromagnetism in such alloy systems as intrinsic to the perovskite phase, the propensity for the spontaneous precipitation of the hexaferrite phase in these multiferroic alloy systems is encouraging as it provides an opportunity for designing self-grown ferroelectric-ferromagnetic composites with good magnetoelectric coupling.
Fractional stochastic modeling: New approach to capture more heterogeneity
Authors: Atangana A. , Bonyah E.
Published: January 2019

To further capture holding complexities of nature that arise in many fields of science, technology, and engineering, we suggested in this paper a novel approach of modeling. The novel approach is a coupling of fractional differential and integral operators with the stochastic approach. The approach is texted using systems of chaotic problems. The numerical simulation impulsively shows that the new approach is able to capture hiding behaviors that could not be captured by fractional differential and integral operators and the stochastic approach only. We believe that this approach is the future way to model complex problems.
High-speed STT MRAM incorporating antiferromagnetic layer
Authors: Shadman Abir , Zhu Jian-Gang (Jimmy)
Published: January 2019

A previous theoretical study has shown that spin-polarized current can excite ultra-high frequency spin precessions in collinear antiferromagnetic (AF) films due to the strong antiferromagnetic coupling with the frequency spanning over a wide spectrum from giga-hertz to tera-hertz. In this paper, we present a design to incorporate the AF-based spin torque oscillator into a conventional spin transfer torque magnetic random-access memory. The AF-based oscillator consists of a perpendicular spin polarization layer and an AF layer, separated by a normal metallic interlayer. The AF layer is then exchange-coupled to the free layer on the side that is opposite to the tunnel barrier of the magnetic tunnel junction. Magnetization of the perpendicular spin polarization layer always orients in the opposite direction to that of the reference layer on the other side of the tunnel barrier. When the AF layer thickness and materials are adequately designed, the lateral spin precession in the AF layer excited by the write current provides significant assistance to the magnetization switching of the free layer, resulting in substantial reduction of the switching current threshold and the switching time.
The traces of positive charge interactions at surface dielectric barrier discharge
Authors: Kim Sang-You , Chung Kyu-Sun
Published: January 2019

This study presents an experimental confirmation of the surface positive charges drifting to the exposed electrode in the cathode layer of atmospheric surface dielectric barrier discharges (SDBD) using the etching method. Local surface erosion around the microprotrusions on the polyimide near the exposed electrode provides an experimental confirmation of the interaction of the positive surface charges with the exposed electrode in SDBD.
Language contact and prosodic change in Slavic and Baltic
Authors: Pronk Tijmen
Published: January 2019

This paper discusses several Slavic and Baltic dialects which have undergone stress shifts as a result of language contact. Two types of change are discussed: (1) stress retractions from the final syllable onto the initial syllable of a prosodic word, and (2) the rise of fixed stress replacing earlier free stress. It is argued that in all cases discussed in the paper, contact with a language with fixed initial stress caused a stress shift. Examples from Croatian and Lithuanian demonstrate that pitch contours played an important role in these shifts. The results of the shifts are not always identical, but the underlying mechanism is the same in each of these cases: the lexical pitch contour of the donor language was imposed on the target language, thereby introducing constraints on the position of stress in the target language. It is argued that a similar mechanism operated in West Slavic, where languages with free stress introduced fixed stress on the initial or penultimate syllable due to contact with German and possibly Hungarian.
Intermediate states of literariness
Authors: Hanauer David I.
Published: January 2019

This study utilizes texts which sit between the literary and non-literary to explore the outcomes and mechanisms
of literariness. Literariness can be activated by (a) linguistic foregrounding and (b) paratextual specification. In a 2 × 2
design, manipulated versions of two soldier narratives were produced (poetry/fiction; poetry/fact; prose/fiction; prose/poetry).
215 participants were randomly assigned to read one of the textual versions and respond to rating scales dealing with perception
of textual features, empathy, sympathy, and cognitive perspective-taking. The results show that poetic form elicits significantly
higher ratings for empathy and sympathy and that paratextual information specifying that a text is factual elicits significantly
higher ratings for empathy and cognitive perspective-taking. Two structural equation models were defined: (a) a literariness model
and (b) a factual accuracy model. The results suggest an additive dual model of processing in which both poetic form and factual
definition contribute to outcomes characteristic of literariness. These results offer some support for the hypotheses of the
Neuro-Cognitive Poetics Model proposed by (Jacobs, 2011).
Kant and the transparency of the mind
Authors: Newton Alexandra M.
Published: January 2019

It has become standard to treat Kant'scharacterization of pure apperception as involving the claim that questions about what I think are transparent to questions about the world. By contrast, empirical apperception is thought to be non-transparent, since it involves a kind of inner observation of my mental states. I propose a reading that reverses this: pure apperception is non-transparent, because conscious only of itself, whereas empirical apperception is transparent to the world. The reading I offer, unlike the standard one, can accommodate Kant'sclaim that the I of pure apperception is the same as the I of empirical apperception.
Myosin IIB assembly state determines its mechanosensitive dynamics
Authors: Schiffhauer Eric S. , Ren Yixin , Iglesias Vicente A. , Kothari Priyanka , Iglesias Pablo A. , Robinson Douglas N.
Published: January 2019

Dynamical cell shape changes require a highly sensitive cellular system that can respond to chemical and mechanical inputs. Myosin IIs are key players in the cell’s ability to react to mechanical inputs, demonstrating an ability to accumulate in response to applied stress. Here, we show that inputs that influence the ability of myosin II to assemble into filaments impact the ability of myosin to respond to stress in a predictable manner. Using mathematical modeling for Dictyostelium myosin II, we predict that myosin II mechanoresponsiveness will be biphasic with an optimum established by the percentage of myosin II assembled into bipolar filaments. In HeLa and NIH 3T3 cells, heavy chain phosphorylation of NMIIB by PKCζ, as well as expression of NMIIA, can control the ability of NMIIB to mechanorespond by influencing its assembly state. These data demonstrate that multiple inputs to the myosin II assembly state integrate at the level of myosin II to govern the cellular response to mechanical inputs.
Functional data analysis for computational biology
Authors: Cremona Marzia A , Xu Hongyan , Makova Kateryna D , Reimherr Matthew , Chiaromonte Francesca , Madrigal Pedro
Published: January 2019

Supplementary information:  Supplementary data are available at Bioinformatics online.
Competition, Capitation, and Coding: Do Public Primary Care Providers Respond to Increased Competition?
Authors: Dackehag Margareta , Ellegård Lina Maria
Published: January 2019

The case for competition in health-care markets rests on economic models in which providers seek to maximize profits. However, little is known regarding how public health-care providers, who might not have a profit motive, react to increased competition from private providers. This study considers the heterogeneous effects of a primary health-care reform in a Swedish region that considerably loosened entry restrictions and increased patients’ freedom of choice, thus enabling increased competition. Our difference-in-differences analysis contrasts local markets that were affected by both entry and choice with local monopoly markets, which were unaffected by the reforms. Using detailed administrative data on all visits to public health centers in 2008–2011, we find that providers in markets with increasing competition registered more diagnoses in an administrative database, thus increasing their reimbursement per patient. Although the economic significance of the effect is small, the result suggests that public providers are indeed sensitive to competition.
Raillietiniaisis in a Toddler From Hawaii: A Case of Mistaken Tapeworm Identity
Authors: Davis Richard E , Mathison Blaine A , Couturier Marc Roger
Published: January 2019

We present the first reported case from the United States of human infection with the intestinal cestode Raillietina, a parasite primarily of rodents and poultry. As the differential diagnosis between the morphologically similar Dipylidium caninum was challenging, we discuss the biology, epidemiology, and clinical management of this rare parasite.
Lansoprazole alleviates pressure overload-induced cardiac hypertrophy and heart failure in mice by blocking the activation of β-catenin
Authors: Lin Hairuo , Li Yang , Zhu Hailin , Wang Qiancheng , Chen Zhenhuan , Chen Lin , Zhu Yingqi , Zheng Cankun , Wang Yuegang , Liao Wangjun , Bin Jianping , Kitakaze Masafumi , Liao Yulin
Published: January 2019

Aims

Proton pump inhibitors (PPIs) are widely used in patients receiving percutaneous coronary intervention to prevent gastric bleeding, but whether PPIs are beneficial for the heart is controversial. Here, we investigated the effects of lansoprazole on cardiac hypertrophy and heart failure, as well as the underlying mechanisms.

Methods and results

Adult male C57 mice were subjected to transverse aortic constriction (TAC) or sham surgery and then were treated with lansoprazole or vehicle for 5 weeks. In addition, cultured neonatal rat ventricular cardiomyocytes and fibroblasts were exposed to angiotensin II in the presence or absence of lansoprazole. At 5 weeks after TAC, the heart weight/body weight ratio was lower in lansoprazole-treated mice than in untreated mice, as was the lung weight/body weight ratio, while left ventricular (LV) fractional shortening and the maximum and minimum rates of change of the LV pressure were higher in lansoprazole-treated mice, along with less cardiac fibrosis. In cultured cardiomyocytes, lansoprazole inhibited angiotensin II-induced protein synthesis and hypertrophy, as well as inhibiting proliferation of fibroblasts. Lansoprazole decreased myocardial levels of phosphorylated Akt, phosphorylated glycogen synthase kinase 3β, and active β-catenin in TAC mice and in angiotensin II-stimulated cardiomyocytes. After overexpression of active β-catenin or knockdown of H+/K+-ATPase α-subunit, lansoprazole still significantly attenuated myocyte hypertrophy.

Conclusion

Lansoprazole inhibits cardiac remodelling by suppressing activation of the Akt/GSK3β/β-catenin pathway independent of H+/K+-ATPase inhibition, and these findings may provide a novel insight into the pharmacological effects of PPIs with regard to alleviation of cardiac remodelling.
Oral Histories, Public Engagement and the Making of Positive in Prison
Authors: Weston Janet
Published: January 2019

How might creative practices surrounding oral history contribute to public engagement and to historical research itself? These questions are considered here through a reflective account of the making of the audio drama Positive in Prison: HIV Stories from a Dublin Jail. Positive in Prison is based on oral histories of HIV/AIDS in the Republic of Ireland, gathered in 2016–17 as part of the Wellcome Trust-funded project ‘Prisons, Medical Care and Entitlement to Health in England and Ireland, 1850–2000’. This piece reviews the processes and practical considerations behind the making of the audio drama and its associated launch events, alongside a summary of the history of HIV/AIDS and of prisons that was being produced and shared. It also offers reflections on the advantages and disadvantages of this particular project in relation to public engagement, the uses of oral histories, and creative history-telling.
Antisymmetric Paramodular Forms of Weights 2 and 3
Authors: Gritsenko Valery , Poor Cris , Yuen David S
Published: January 2019

We define an algebraic set in $23$-dimensional projective space whose ${{\mathbb{Q}}}$-rational points correspond to meromorphic, antisymmetric, paramodular Borcherds products. We know two lines inside this algebraic set. Some rational points on these lines give holomorphic Borcherds products and thus construct examples of Siegel modular forms on degree 2 paramodular groups. Weight $3$ examples provide antisymmetric canonical differential forms on Siegel modular three-folds. Weight $2$ is the minimal weight and these examples, via the paramodular conjecture, give evidence for the modularity of some rank 1 abelian surfaces defined over $\mathbb{Q}$.
Identification of a chemical modulator of EZH2-mediated silencing by cell-based high-throughput screening assay
Authors: Murashima Akihiro , Shinjo Keiko , Katsushima Keisuke , Onuki Tetsuo , Kondoh Yasumitsu , Osada Hiroyuki , Kagaya Noritaka , Shin-ya Kazuo , Kimura Hiroshi , Yoshida Minoru , Murakami Shingo , Kondo Yutaka
Published: January 2019

Dysregulation of enhancer of zeste homologue 2 (EZH2), a methyltransferase component of polycomb repressive complex 2, is found in many types of cancers especially those that are highly progressive and aggressive. Specific catalytic inhibitors of EZH2 have high anti-tumour activity, particularly in lymphomas with EZH2 activating mutations. However, the clinical benefits of EZH2 catalytic inhibitors in tumours overexpressing EZH2 are still limited. Here, we identified NPD13668, a novel modulator of EZH2-mediated gene silencing, from 329,049 small chemical compounds using a cell-based high-throughput screening assay. NPD13668 reactivated the expression of silenced H3K27me3 target genes together with depletion of the H3K27me3 modification. In addition, NPD13668 repressed the cell growth of prostate cancer cell lines (PC3 and LNCaP) and ovarian cancer cell lines (SKOV3 and NIH-OVCAR3). NPD13668 partially inhibited the methyltransferase activity of EZH2 in vitro. Genome-wide expression analysis revealed that after NPD13668 treatment, about half of the upregulated genes overlapped with genes upregulated after treatment with GSK126, well-known EZH2 catalytic inhibitor, indicating that NPD13668 is a potential modulator of EZH2 methyltransferase activity. Our data demonstrated that targeting the pharmacological inhibition of EZH2 activity by NPD13668 might be a novel cancer treatment.
Can Bureaucrats Really Be Paid Like Ceos? Substitution Between Incentives and Resources Among School Administrators in China
Authors: Luo Renfu , Miller Grant , Rozelle Scott , Sylvia Sean , Vera-Hernández Marcos
Published: January 2019

Unlike performance incentives for private sector managers, little is known about performance incentives for managers in public sector bureaucracies. Through a randomized trial in rural China, we study performance incentives rewarding school administrators for reducing student anemia—as well as complementarity between incentives and orthogonally assigned discretionary resources. Large (but not small) incentives and unrestricted grants both reduced anemia, but incentives were more cost-effective. Although unrestricted grants and small incentives do not interact, grants fully crowd-out the effect of larger incentives. Our findings suggest that performance incentives can be effective in bureaucratic environments, but they are not complementary to discretionary resources.
Good Booms, Bad Booms
Authors: Gorton Gary , Ordoñez Guillermo
Published: January 2019

Credit booms are not rare, some end in a crisis (bad booms) whereas others do not (good booms). We document that credit booms start with an increase in productivity growth, which subsequently falls faster during bad booms. We develop a model in which a crisis happens when a credit boom transits toward an information regime with careful examination of collateral. As this examination is more valuable when collateral backs projects with low productivity, crises are more likely during booms that display larger productivity declines. We test the main predictions of the model and identify the default probability as the main component of measured productivity that lies behind crises.
Concept and Overview of Neuropathic Pain
Authors: Cheng Jianguo
Published: January 2019

Neuropathic pain is defined as pain arising from a lesion or disease of the somatosensory nervous system. It is highly prevalent, afflicting 7–18% of the general population. Its incidences are much higher, ranging from 20% to 77%, in patients with spine disorder, hip and knee osteoarthritis, or cancer. Neuropathic pain can be severely disabling, with significant personal, societal, and economic cost. Patients with neuropathic pain disorders have significantly reduced health-related quality of life and their treatment costs three times that for matched control subjects. There are enormous challenges in understanding and managing neuropathic pain given the diversity of causes, pathology, mechanisms, and clinical presentations of neuropathic pain conditions. Along with these challenges are opportunities for advancing the mechanistic understanding of neuropathic pain and developing promising therapeutic modalities that include new pharmacological agents, emerging stem cell therapy, and novel neuromodulation paradigms.
Mechanisms of Neuropathic Pain
Authors: Cheng Jianguo
Published: January 2019

Neuropathic pain arises as a direct consequence of a lesion or a disease affecting the somatosensory system. The mechanisms of neuropathic pain are often complex and difficult to study given the diversity of causes, pathology, and clinical presentation of various neuropathic pain conditions. Common mechanisms include peripheral and central sensitizations. Peripheral sensitization refers to increased responsiveness and reduced threshold of nociceptive neurons in the periphery to the stimulation of their receptive fields. Central sensitization refers to the augmented response of central signaling neurons. The mechanisms of peripheral and central sensitization are understood at the cellular and molecular levels. The processes of neuroplasticity involve activation of inflammatory cells, such as macrophages (and microglia in the central nervous system) and other immune cells, and release of inflammatory mediators, such as cytokines, chemokines, and a host of other mediators. Interactions of these mediators with specific receptors in the nociceptors or the spinal cord neurons may lead to phosphorylation or changes in expression of ion channels, receptors, transporters, and other effectors through specific signaling pathways. These events ultimately lead to changes in excitability, conductivity, and transmissibility of neurons in the pain processing pathways. Other factors may include disinhibition of interneurons, changes in descending inhibitory and excitatory pathways, and reorganization of the cortical areas and their interconnections.
Nonpharmacological Treatment of Neuropathic Pain
Authors: Mirpuri Ravi , Perret Danielle
Published: January 2019

This chapter discusses various nonpharmacological treatments for neuropathic pain. Physiotherapy, tai chi, and yoga are all methods that incorporate movement exercise to treat biomechanical imbalances and reduce kinesiophobia, or “fear of movement.” Additionally, this chapter discusses treatments targeted at the peripheral nervous system, such as structured graded desensitization, heat/cold physical modalities, transcutaneous electrical nerve stimulation, and acupuncture, all of which have varying levels of efficacy. The chapter reviews the different psychotherapy approaches to treating neuropathic pain: cognitive-behavioral therapy (CBT), operant-behavioral therapy, mindfulness-based stress reduction (MBSR), and acceptance and commitment therapy (ACT). It is important to note that many of the therapies discussed are intended to be incorporated with other pharmacological or interventional approaches to provide a multimodal level of care and increase chances of outcome success. Other treatments discussed include orthotics, mirror therapy, and transcranial magnetic stimulation for a variety of neuropathic conditions.
Pharmacological Treatment of Neuropathic Pain
Authors: Brewer Randall P. , Shah Rinoo V. , Casserly Elizabeth
Published: January 2019

Neuropathic pain is a result of a somatosensory lesion or disease process, either centrally or peripherally. Prevalence is estimated to be in the millions and high as 8% in the general population. Neuropathic pain is often associated with depression, sleep disturbances, compromised physical and emotional functionality, and reduced productivity. Pharmacotherapy is a key component of a multidisciplinary approach to the management of neuropathic pain and is a treatment limited by analgesic efficacy and dose-related side effects. First-line medications for neuropathic pain include tricyclic antidepressants (TCAs), serotonin-noradrenaline reuptake inhibitors (SNRIs), calcium channel alpha2delta-1 ligands (gabapentin and pregabalin), topical lidocaine (lidocaine patch 5%), and topical capsaicin (capsaicin 8% patch). Tramadol is generally considered second-line medication. Sources for this chapter have come from randomized control trials, systematic reviews, meta-analysis, and the IASP NeuPSIG guidelines for the treatment of neuropathic pain.
Interventional Treatment of Neuropathic Pain
Authors: Wu Jiang , Cheng Jianguo
Published: January 2019

Neuropathic pain has been reported to be highly prevalent, severely disabling, and often refractory to pharmacological and noninterventional conservative treatment. There is an emerging body of exciting evidence to support interventional therapies in selected refractory neuropathic pain states, although more randomized controlled trials or comparative effective trials are needed. This chapter updates the scientific evidence in support of the efficacy of neural blockade techniques and neural ablative procedures in neuropathic pain states, including peripheral compression or trauma-related neuropathic pain, herpes zoster and postherpetic neuralgia (PHN), lumbosacral and cervical radiculopathy, sympathetically maintained pain, complex regional pain syndrome (CRPS), trigeminal neuralgia and trigeminal neuropathy, and painful diabetic polyneuropathies.
Postsurgical Neuralgia
Authors: Kenny John P. , Elmofty Dalia
Published: January 2019

The development of post-surgical neuralgia (PSN) is multi-factorial and many questions still remain unanswered. PSN results from traumatic nerve injury during a surgical procedure. Little is known about the correlation between the mechanism of injury and the clinical presentation. PSN is often unrecogonized and misdiagnosed. It can be severely debilitating. The consequences of postsurgical neuralgia not only affect a patient’s quality of life, but also have a profound impact on healthcare costs. Identifying predisposing risk factors, utilizing a preventative approach, proper and timely detection, enhancing awareness amongst physicians and early pain management referral are imperative steps in the treatment of PSN. Surgeons and anesthesiologist have a crucial role in the prevention of PSN. Identifying high risk patients and high risk surgery types along with collaborative efforts to implement a multimodal perioperative analgesic plan is recommended.
Post-Traumatic Neuralgia
Authors: Anitescu Magdalena , Frenkel Joshua , Silva Bradley A.
Published: January 2019

Peripheral nerve damage is classified into three categories based on severity: neurapraxia, axonotmesis, and neurotmesis. Peripheral nerve damage is the second most common category of in anesthesia related complications. The “double-crush” phenomenon is a term used to describe preexisting neurological injury that limits the neurological reserve of affected nerves. The risk of clinical deficits from a subsequent nerve injury is increased with the double crush phenomenon. Noniatrogenic traumatic nerve injury is most common in young adult males. Management of post-traumatic neuralgia often involves consultation with pain medicine, neurology, and neurosurgery. This multidisciplinary approach has two central goals, restoring nerve function and minimizing chronic neuropathic pain. Pharmacotherapy and procedural therapies are the treatments for neuropathic pain. Pharmacological agents include secondary amine tricyclic antidepressants (e.g., nortriptyline, desipramine), calcium channel α‎-2-δ‎ ligand anticonvulsants (e.g., pregabalin, gabapentin), opioids, ketamine, and topical lidocaine. Procedural interventions may be indicated when pain remains refractory to multiple pharmacological therapies. Procedures include nerve blocks, ablation, and neurostimulation, designed to interfere with, interrupt, or modulate pain pathways.
Entrapment Syndromes
Authors: Eskander Jonathan P. , Malik Zeeshan , Shah Rinoo V.
Published: January 2019

Entrapment syndromes, also known as nerve compression or compression neuropathy, are caused by compression or pressure on the nerve. These nerves may become compressed within various joints and regions of tight anatomy that result in symptoms of pain, numbness, and tingling. Within these “tunnel” regions the nerve continues to cause neuropathic pain and chronically may present with weakness of the distal muscles. Typically, entrapment syndromes are caused by trauma, surgery, inflammation, anatomic abnormalities, or autoimmune diseases. One way of diagnosing entrapment syndromes is through nerve conduction studies such as an electromyelogram (EMG), in conjunction with radiologic imaging such as Magnetic Resonance Imaging (MRI’s). This chapter focuses on the common entrapment neuropathies with example cases and treatment choices.
Stump Pain
Authors: Devarajan Jagan , Minzter Beth H.
Published: January 2019

This chapter discusses stump pain or residual limb pain, which arises from the distal end of the stump after amputation. The initial phase, which lasts for 6 weeks, manifests as nociceptive pain that may be followed by neuropathic pain. In 5%–10% of patients with stump pain, the pain evolves to become predominantly neuropathic. In addition, stump pain can be arthrogenic, osteogenic, or infectious. History and physical examination are important in order to determine the origin of pain. Residual persistent ischemia of the stump should be ruled out. The stump should be examined and investigated to rule out the presence of a neuroma. Occasionally, radicular pain, which arises from the lumbosacral levels, presents as stump pain. The most effective management of stump pain is multidisciplinary and multimodal. Acute stump pain is treated with either epidural analgesia or, more commonly, peripheral nerve blocks. Chronic neuropathic pain is treated with antiepileptics such as gabapentin or pregabalin and NMDA receptor antagonists. Transcutaneous electrical nerve stimulation, spinal cord stimulation, and peripheral nerve stimulation play a limited role in management of stump pain. Neuromas are treated with radiofrequency ablation, cryoablation, or coblation. Surgery is the least successful modality to treat neuroma.
Metabolic, Endocrine, and Other Toxic Neuropathies
Authors: Carney Martin J. , Jones Mark R. , Jhita Preya K. , Campbell Harold J. , Romain Michelle , Motejunas Mark , Kaye Alan D.
Published: January 2019

Neuropathic pain permeates a variety of disease processes and remains a consistent challenge for patient treatment at all levels. Diabetes continues to plague a distinct proportion of healthcare in the United States. Without proper preventative measures, these patients are at high risk for acquiring diabetic peripheral neuropathy (DPN). Similarly, rampant alcohol abuse can likely lead to chronic neuropathic sequelae. These issues increase in proportion with an aging population. There are a variety of malnutrition-based disorders, which can manifest into specific neurological issues. Specifically, vitamins B1, B12, and E and copper deficiencies can all lead to neuropathic disorders that become difficult to treat after prolonged periods of nutritional deprivation. Finally, various chemotherapeutic regimens have many known neuropathic complications. These conglomerations of disease manifestation make metabolic neuropathies a complex topic to fully categorize and understand, but certain pearls are vital in a foundational understanding of this topic.
Trigeminal Neuralgia
Authors: Grandhe Radhika , Johnson Harris Eli , Koshkin Eugene
Published: January 2019

Trigeminal neuralgia is a rare neuropathic pain condition but can be very disabling. The hallmark is brief episodes of intense, radiating pain within the territory of trigeminal nerve distribution. It is typically unilateral, often accompanied by facial spasms and can be triggered by facial movements in a majority of patients. Microvascular compression of trigeminal ganglion is the etiology for most patients with classical trigeminal neuralgia. Some patients can have continuous facial pain in addition to paroxysms of pain. Trigeminal neuralgia is a clinical diagnosis, but MRI is done to rule out secondary causes or to detect microvascular compression. Pharmacological therapy with first-line agents—carbamazepine or oxcarbazepine—is the preferred treatment. Patients with failed pharmacological therapy are considered for surgical decompression, ablation procedures, or Gamma Knife surgery.
Pathways in Prosthetic Joint Infection
Authors: Khan Umraz , Perks Graeme , Morgan-Jones Rhidian , James Peter , Esler Colin , Smyth Vince , Gant Vanya
Published: January 2019

This book provides a concise overview of methods of assessing and managing prosthetic joint infection (PJI). It covers the classification of PJI sites, risk factors, and preoperative assessment, before considering safe patient pathways. Drawn from the authors’ clinical experience and a review of the current literature, the book also explains surgical and drug management of acute infection, the management of chronic infection, and specific microbiology issues relating to PJI. Proposed models for revision arthroplasty networks are discussed and future aims are considered. The proposed pathways are backed by illustrated case histories.
Principles of public health
Authors: Stewart-Brown Sarah
Published: January 2019

Public health is an art and science that has been successfully applied to physical health. It is a practice for which the principles are now well known. Public mental health is a new application to which many of the principles are directly transferable. However, the nature of mental health challenges some of these principles and means that they need to be applied with a degree of caution. New principles need to be developed to allow for consideration of complexity and the need for system change, as well as of positive states of health and enabling personal development.
Circumstellar CO in metal-poor stellar winds: the highly irradiated globular cluster star 47 Tucanae V3
Authors: McDonald I , Boyer M L , Groenewegen M A T , Lagadec E , Richards A M S , Sloan G C , Zijlstra A A
Published: January 2019

We report the first detection of circumstellar CO in a globular cluster. Observations with ALMA have detected the CO J = 3–2 and SiO v = 1 J = 8 − 7 transitions at 345 and 344 GHz, respectively, around V3 in 47 Tucanae (NGC 104; [Fe/H]  = –0.72 dex), a star on the asymptotic giant branch. The CO line is detected at 7σ at a rest velocity vLSR  = –40.6 km s−1 and expansion velocity of 3.2 ± ∼0.4 km s−1. The brighter, asymmetric SiO line may indicate a circumstellar maser. The stellar wind is slow compared to similar Galactic stars, but the dust opacity remains similar to Galactic comparisons. We suggest that the mass-loss rate is set by the levitation of material into the circumstellar environment by pulsations, but that the terminal wind-expansion velocity is determined by radiation pressure on the dust: a pulsation-enhanced dust-driven wind. We suggest the metal-poor nature of the star decreases the grain size, slowing the wind and increasing its density and opacity. Metallic alloys at high altitudes above the photosphere could also provide an opacity increase. The CO line is weaker than expected from Galactic AGB stars, but its strength confirms a model that includes CO dissociation by the strong interstellar radiation field present inside globular clusters.