bluuebunny/crossref_metadata_2025 huggingface dataset:
Efficacy and safety of BORTEZOMIB treatment for refractory acute antibody‐mediated rejection—a pilot study
Authors: Slatinska Janka , Slavcev Antonij , Honsova Eva , Hruba Petra , Kratochvilova Iva , Rohal Tomas , Viklicky Ondrej
Published: August 2018

A novel therapeutic approach to refractory acute antibody‐mediated rejection (AMR) in kidney transplant recipients was applied in 23 patients based on administration of Bortezomib, intravenous corticosteroids, plasmapheresis and Rituximab. Application of Bortezomib regimen led to diminishing of donor‐specific antibodies (DSA) to HLA‐B (P = 0.004) and HLA‐DR (P = 0.0005), but not to HLA‐A (P = 0.106) and HLA‐DQ antigens (P = 0.18). Patients with good clinical response to treatment had significantly better allograft survival than recipients with continuing deterioration of graft function (P = 0.019). Graft survival after therapy of refractory AMR was significantly worse than survival after first transplantation and was comparable with outcomes after retransplantation. In conclusion, therapy with Bortezomib was well tolerated and effective in decreasing the levels of HLA‐B and ‐DR antibodies, however, was not successful in depleting HLA‐A and ‐DQ DSA.
Propagation of changes in demand through international trade: A case study of China
Authors: Andritzky Jochen , Kassner Bernhard , Reuter Wolf Heinrich
Published: August 2018

China’s economy, the second largest in the world, is undergoing a fundamental transition. Its transition from a strong focus on investment and exports towards a larger share of consumption could have important ramifications for China’s trading partners. Using China as a case study, this paper deploys a sectoral input–output (IO) analysis to take into account higher‐round spillovers from a reduction of import demand or a shift in the composition of the Chinese economy. This approach demonstrates strong indirect effects that exceed by far the initial shock from direct trade links, reflecting China’s integration into a closely knit global value chain. The result suggests that the ongoing transition in China will have important effects on the global economy.
Catechol‐o‐methyltransferase genotypes are associated with progression and biological behaviour of canine mammary tumours
Authors: Canadas Ana , Santos Marta , Pinto Ricardo , Medeiros Rui , Dias‐Pereira Patrícia
Published: August 2018

The enzyme catechol‐o‐methyltransferase (COMT) is responsible for inactivation of catechol estrogens, which are well‐recognized carcinogenic metabolites. Two single‐nucleotide polymorphisms (SNPs) in canine COMT gene were previously associated with the age of onset of mammary tumours and with the clinical progression of the disease. However, no information is available regarding the impact of other known SNPs in COMT gene in canine mammary tumours. The aim of the present study is to evaluate the influence of COMT SNP in clinicopathological features and outcome of canine mammary tumours. A case series study was conducted involving 155 non‐neutered bitches with mammary tumours submitted to follow‐up for 24 months after surgery. Three genotypes were considered: Genotype 1 (rs853046495); Genotype 2 (rs23350589, rs23322686, rs23336579, and rs852564758); Genotype 3 (rs851328636 and rs853133060). Genotype 1 was associated to low degree of tubular differentiation. Genotype 2 was related to the development of intermediate/high‐histological‐grade carcinomas and to vascular invasion. Genotype 3 was associated to reduced nuclear pleomorphism and well‐differentiated carcinomas. Data from the present investigation allowed the identification of COMT genetic profiles associated with pathological features of mammary tumours that constitute relevant prognostic factors. The assessment of the COMT genotypes may represent a helpful tool in the clinical management of canine mammary tumours, assisting in the selection of individualized preventive and therapeutic strategies, according to the animals' genetic profile.
Loyalty Points on the Blockchain
Authors: Agrawal Dhwani , Jureczek Natalia , Gopalakrishnan Gajane , Guzman Margaret Natalie , McDonald Michael , Kim Henry
Published: August 2018

Although some organizations are contemplating the potential impact of blockchain technology in today’s economy, blockchain, itself, is quickly emerging to be a disruptive force. This is especially true in the circumstance of loyalty programs. Blockchain is a public, digital, and distributed database solution providing decentralized management of transactional data. This technology is transforming society in ways that were previously unimaginable. Whether it be the way individuals use their phones, cars, or the healthcare system, blockchain is applicable for a variety of economic sectors and transactions. Although many may argue that blockchain is in its early development stage, it still possesses the power to revolutionize industries and consumer habits at a global scale. Through implementation of blockchain for loyalty networks, companies eliminate the limitations and inefficiencies while elevating the customer experience with secure and immediate redemption options from a variety of vendors. Despite evolving rapidly, its implementations provide better security, privacy, performance, usability, data integrity, and scalability, to name a few. Hence, blockchain is likely to entice any individual for instantaneous incentives for every purchase.This paper aims to analyze the current, traditional loyalty programs and the challenges associated with them. It highlights how blockchain can resolve these challenges and provide a better experience. This report further explores the various types of loyalty programs that currently exist in the blockchain ecosystem and provides potential future implementations. Finally, the paper analyzes the implementation of coupons in comparison with loyalty points programs, highlighting the vast spread of blockchain implementation.
In situ liquid cell crystallization and imaging of thiamethoxam by helium ion microscopy
Authors: Belianinov Alex , Pawlicki Alison , Burch Matt , Kim Songkil , Ievlev Anton , Fowler Jeff , Ovchinnikova Olga
Published: August 2018

Pest insect control is an essential component for crop protection and public health. Neonicotinoids are a relatively new class of insecticides developed in the last four decades. Thiamethoxam, a member of the neonicotinoid class, has shown outstanding potency for crop protection against a variety of piercing-sucking pests. However, its use in industrial-volume packing and transportation is complicated by crystallization dynamics. In this work, a helium ion microscope (HIM) with a Protochips liquid cell was utilized to crystallize and image thiamethoxam in situ. The results of the study illustrate the growth and morphology of the thiamethoxam crystals at different He+ exposure doses, which is markedly different from what has been typically observed. Energy-dispersive x-ray spectroscopy results confirm the presence of the thiamethoxam on the liquid cell membrane. This imaging study illustrates the HIM ability to image and induce the crystallization in soft materials in liquid environments, and attempts to shed light onto the key processes involved in liquid imaging.
Thermionic cooling efficiency of functionalized carbon nanotube thin films
Authors: Jin Feng , Carter Dustin
Published: August 2018

A large thermionic cooling effect is observed from a functionalized carbon nanotube cathode surface, and the cooling efficiency, defined as thermionic cooling power as a percentage of total input heating power to the surface, is reported. The cathode consists of a thin tungsten ribbon covered with low work function barium strontium oxide coated carbon nanotubes. It has both a low work function surface and a large Schottky field effect induced by the carbon nanotubes. The combination of the two leads to a strong thermionic emission and hence a relatively large thermionic cooling effect and high cooling efficiency. Detailed measurements of the cathode temperature profiles are presented together with the analysis of the cooling efficiency. The highest cooling efficiency obtained in this study is 5.9% at 1099 °C of cathode temperature and 114.5 mA of thermionic emission current. The dependencies of the cooling efficiency on the cathode temperature and on the emission current are also presented. Prospects of further improvements are discussed as well.
The impact of reverberation on speech intelligibility in cochlear implant recipients
Authors: Kressner Abigail Anne , Westermann Adam , Buchholz Jörg M.
Published: August 2018

Listening to speech in an environment with reverberation can be challenging for both the normal and impaired auditory system. However, it has been shown for both normal- and impaired-hearing listeners that it is the late reflections that are responsible for degrading intelligibility, whereas early reflections actually aid intelligibility by increasing the effective signal-to-noise ratio. Contrastingly, studies conducted with cochlear implant (CI) recipients have suggested that CI recipients have almost no tolerance for reverberation and that they are negatively impacted by both early and late reflections. The main objective of the current study is to re-evaluate the influence of reverberation on speech intelligibility in CI recipients using more authentic virtual auditory environments. Unlike previous studies in this area, this study was conducted using a loudspeaker-based auralization system rather than non-individualized binaural room simulations. Speech intelligibility was measured in simulations of a range of actual physical rooms with plausible source−receiver distances, both with and without late reflections. The results show that the effect of reverberation is much smaller than previously suggested, especially with short source−receiver distances. Furthermore, the results suggest that, in contrast to previous literature, early reflections may not actually be detrimental to CI recipients.
Subjective and objective rating of the sound insulation of residential building façades against road traffic noise
Authors: Hongisto Valtteri , Oliva David , Rekola Laura
Published: August 2018

Sound insulation in a building façade plays a key role in the control of road-traffic noise. Façade performance can be described using various internationally standardized single-number quantities (SNQs) with different frequency weightings. The purpose of this study was to evaluate how 25 different SNQs explain the subjective ratings of spectrally different road-traffic sounds transmitted through a façade. Forty-three participants took part in a psychoacoustic laboratory experiment. The task was to evaluate five spectrally different road-traffic sound types transmitted through 12 simulated façade constructions. The participants rated both the loudness and the annoyance of 60 sounds. The playback levels were between 12 and 46 dB LAeq, covering the essential range of road-traffic noise usually measured inside residential dwellings. Linear correlations were determined between the SNQ values of the façades and the subjective ratings. Rw + C50–3150 explained the subjective ratings best when the five sound types were equally considered. It was also the most suitable SNQ for the standard road-traffic spectrum of ISO 717-1. The results of this study can be useful in the development of future standards.
Continuous relaxation spectra for constitutive models in medium-amplitude oscillatory shear
Authors: Martinetti Luca , Soulages Johannes M. , Ewoldt Randy H.
Published: August 2018

We derive and demonstrate how analytical solutions for strain-controlled medium-amplitude oscillatory shear (MAOS) can be coupled with a continuous distribution of relaxation times. This applies generally to the vast library of existing MAOS models, including those that are not time-strain separable. The theoretical results are important for improved certainty in model parameters, since their number can be reduced dramatically compared to a discrete distribution of relaxation times. We exemplify this continuous spectrum MAOS approach by modeling experimental data for a transient network formed from an aqueous semidilute unentangled solution of poly(vinyl alcohol) and sodium tetraborate (Borax). The full frequency-dependent MAOS signatures are fit well by only five parameters: three linear parameters for a log-normal spectral distribution and two nonlinear parameters for the strength of the nonlinearity and its cutoff time scale. Remarkably, longer modes (τ>τw) are not activated in the asymptotically nonlinear regime. Although this may be compatible with the possible mechanisms for the shear nonlinearities, the reason for the hard cutoff of time scales is currently unknown. Our results also suggest that the sign change location for the third-harmonic viscous nonlinearity may be sensitive to large-scale structural features (such as molar mass distribution or long-chain branching) that control the polydispersity of terminal relaxation times.
Small metabolites, possible big changes: a microbiota-centered view of non-alcoholic fatty liver disease
Authors: Chu Huikuan , Duan Yi , Yang Ling , Schnabl Bernd
Published: August 2018

The spectrum of non-alcoholic fatty liver disease (NAFLD) ranges from simple hepatic steatosis, commonly associated with obesity, to non-alcoholic steatohepatitis, which can progress to fibrosis, cirrhosis and hepatocellular carcinoma. NAFLD pathophysiology involves environmental, genetic and metabolic factors, as well as changes in the intestinal microbiota and their products. Dysfunction of the intestinal barrier can contribute to NAFLD development and progression. Although there are technical limitations in assessing intestinal permeability in humans and the number of patients in these studies is rather small, fewer than half of the patients have increased intestinal permeability and translocation of bacterial products. Microbe-derived metabolites and the signalling pathways they affect might play more important roles in development of NAFLD. We review the microbial metabolites that contribute to the development of NAFLD, such as trimethylamine, bile acids, short-chain fatty acids and ethanol. We discuss the mechanisms by which metabolites produced by microbes might affect disease progression and/or serve as therapeutic targets or biomarkers for NAFLD.
Chronic kidney disease in cats and dogs: managing proteinuria
Authors: Maniaki Evangelia , Finch Natalie
Published: August 2018

Chronic kidney disease (CKD) is defined as a chronic sustained reduction in renal function and/or structural change. CKD therefore, by this definition, includes patients with tubulointerstitial nephritis, considered the typical finding in CKD, and also patients with primary glomerular disease. The distinction between these is important as they may differ in aetiology and approach to management. In patients with CKD, proteinuria can develop as a result of tubular or glomerular injury. In addition, proteinuria may cause renal injury and contribute to the progression of CKD. This article will review the pathophysiology of proteinuria in CKD, its diagnostic workup and management.
Hugh Munro Pirie
Authors: Wright Norman , Murray Max , Boyd Jack , Jarrett Oswald
Published: August 2018

A world‐renowned investigative veterinary pathologist who made an outstanding contribution to education and research.
Time domain reflectometry (TDR) potential for soil condition monitoring of geotechnical assets
Authors: Curioni Giulio , Chapman David N. , Royal Alexander C.D. , Metje Nicole , Dashwood Ben , Gunn David A. , Inauen Cornelia M. , Chambers Jonathan E. , Meldrum Philip I. , Wilkinson Paul B. , Swift Russell T. , Reeves Helen J.
Published: August 2018

The performance of geotechnical assets is influenced by various external factors including time and changing loading and environmental conditions. These changes could reduce the asset’s ability to maintain its function, potentially resulting in failure, which could be extremely disruptive and expensive to remediate; thus, the ability to monitor the long-term condition of the ground is clearly desirable as this could function as an early-warning system, permitting intervention prior to failure. This study demonstrates, for the first time, the potential of using time domain reflectometry (TDR) for long-term monitoring of the relative health of an asset (via water content and dry density) in a field trial where a clayey sandy silt was exposed to leaking water from a pipe. TDR sensors were able to provide detailed information on the variation in the soil conditions and detect abrupt changes that would relay a prompt for asset inspections or interventions. It is proposed that TDR could be used alone or together with other shallow geophysical techniques for long-term condition monitoring of critical geotechnical assets. Early-warning systems could be based on thresholds defined from the values or the relative change of the measured parameters.
Evaluation of the effect of deflection waveform on fatigue performance of asphalt mixture in the four point bending beam test
Authors: Pintarelli Mariana Gaertner , Staub de Melo João Victor
Published: August 2018

An experimental study was conducted to determine the effect of deflection waveform on four-point flexural fatigue test results for hot mix asphalt. This paper reports how the waveform affects the fatigue resistance of an asphalt mixture and, consequently, the fatigue models of the material. The mix was tested at different strain levels under both haversine and sinusoidal deflection-controlled modes. The findings indicate that haversine displacement control testing results in a sinusoidal strain response of half the intended amplitude. This outcome was attributed to the viscoelastic nature of asphalt mixes. In the deflection controlled haversine test, permanent deformations lead to a new equilibrium neutral position of the beam and the force output follows a sinusoidal waveform. This produces erroneous fatigue results since the test assumptions do not match the actual test conditions. It is recommended to use a sinusoidal waveform to obtain consistent results.
Observation of ultra-fine structures in energy levels of prolate nuclei
Authors: Hassanabadi Hassan , Sobhani Hadi
Published: August 2018

This work discusses the observation of splitting in the energy levels of prolate nuclei. Similar effects in atomic physics are known as the Zeeman effect, but in nuclear physics the feasibility of such phenomena has not been observed. After introducing a deformation in the commutation relation in three dimensions, we used these commutation relations in X(3) model. After enough derivation, we then evaluate the energy spectrum relation for the considered system, which has resulted in energy splitting. With these observations in the energy splitting we referred to such an effect as the ultra-fine structures in energy levels. At the end some plots have been depicted to illustrate the results.
Panax notoginseng Inhibits Tumor Growth through Activating Macrophage to M1 Polarization
Authors: Kim Bosung , Kim Eun-Yeong , Lee Eun-Ji , Han Jung Ho , Kwak Chung-Hwan , Jung Yeon-Seop , Lee Syng-Ook , Chung Tae-Wook , Ha Ki-Tae
Published: August 2018

Among the herbal ingredients of HangAmDan-B, a medicinal formula that redirects macrophages to become tumoricidal effectors, we found that Panax notoginseng (Burk.) F. H. Chen is the active component responsible for its macrophage-mediated antitumor activity. The water extracted roots of P. notoginseng (PN) did not affect the viability of RAW264.7 murine macrophage-like cells and murine Lewis lung carcinoma (LLC) cells up to a concentration of 100[Formula: see text][Formula: see text]g/mL. However, the transfer of culture media from PN-treated RAW264.7 cells suppressed the growth of LLC cells. The expression of classically activated (M1) markers, such as interleukin (IL)-1[Formula: see text], monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-[Formula: see text], and inducible nitric oxide synthase (iNOS), was increased by PN treatment. The expression of alternatively activated (M2) markers including CD206, IL-10, and [Formula: see text]-[Formula: see text]-acetylhexosaminidases (YM-1) was reduced by PN treatment in the presence of IL-4. Flow cytometry also revealed that PN drives M1 activation of RAW264.7 cells. The transfer of culture media from PN-treated RAW264.7 cells induced the apoptosis of LLC cells as measured by flow cytometry using Annexin-V staining and western blot analysis for caspase cascade-related proteins. In addition, the results from in vivo tumor allograft model demonstrated that PN reduced both tumor volume and weight. The activation of macrophages toward an M1 phenotype was confirmed in the tumor allograft tumor model. These results collectively show that PN can serve as a potent anticancer agent through reeducation of macrophages toward an M1 phenotype.
Enriching SPARQL Queries by User Preferences for Results Adaptation
Authors: Banouar Oumayma , Raghay Said
Published: August 2018

Systems of data integration using ontologies aim to implement a collaborative environment between sources for sharing data and services to respond a user request for information. Their users’ requests are an exact expression of their needs. However, the multiplicity of data sources, their scalability and the increasing difficulty to control their descriptions and their contents are the reasons behind the implacability of this assumption today. The users now may not know the data sources they questioned, nor their description or content. Consequently, their queries reflect no more a need that must be satisfied but an intention that must be refined according to data sources available at the time of interrogation. In this work, we present a semantic-based approach to enrich user’ queries expressed in SPARQL Language by his preferences in order to adapt the returned results and make them more precise and more relevant. The proposed approach is applied on a movies management system based on the standard MovieLens dataset. The obtained results are compared to existing approaches according to precision and recall measures. Our approach improved the precision with 26% and the recall with 7% comparing to those of previous study using collaborative filtering.
Duality for dyadic triangles
Authors: Matczak K. , Mućka A. , Romanowska A. B.
Published: August 2018

This paper is a direct continuation of the paper “Duality for dyadic intervals” by the same authors, and can be considered as its second part.

Dyadic rationals are rationals whose denominator is a power of 2. Dyadic triangles and dyadic polygons are, respectively, defined as the intersections with the dyadic plane of a triangle or polygon in the real plane whose vertices lie in the dyadic plane. The one-dimensional analogues are dyadic intervals. Algebraically, dyadic polygons carry the structure of a commutative, entropic and idempotent groupoid under the binary operation of arithmetic mean.

The first paper dealt with the structure of finitely generated subgroupoids of the dyadic line, which were shown to be isomorphic to dyadic intervals. Then a duality between the class of dyadic intervals and the class of certain subgroupoids of the dyadic unit square was described.

The present paper extends the results of the first paper, provides some characterizations of dyadic triangles, and describes a duality for the class of dyadic triangles. As in the case of intervals, the duality is given by an infinite dualizing (schizophrenic) object, the dyadic unit interval. The dual spaces are certain subgroupoids of the dyadic unit cube, considered as (commutative, idempotent and entropic) groupoids with additional constant operations.
The monoids of the patience sorting algorithm
Authors: Cain Alan J. , Malheiro António , Silva Fábio M.
Published: August 2018

The left patience sorting ([Formula: see text][Formula: see text]PS) monoid, also known in the literature as the Bell monoid, and the right patient sorting ([Formula: see text]PS) monoid are introduced by defining certain congruences on words. Such congruences are constructed using insertion algorithms based on the concept of decreasing subsequences. Presentations for these monoids are given.

Each finite-rank [Formula: see text]PS monoid is shown to have polynomial growth and to satisfy a nontrivial identity (dependent on its rank), while the infinite rank [Formula: see text]PS monoid does not satisfy any nontrivial identity. Each [Formula: see text][Formula: see text]PS monoid of finite rank has exponential growth and does not satisfy any nontrivial identity. The complexity of the insertion algorithms is discussed.

[Formula: see text]PS monoids of finite rank are shown to be automatic and to have recursive complete presentations. When the rank is [Formula: see text] or [Formula: see text], they are also biautomatic. [Formula: see text][Formula: see text]PS monoids of finite rank are shown to have finite complete presentations and to be biautomatic.
The Reissner–Nordström black hole surrounded by quintessence and a cloud of strings: Thermodynamics and quasinormal modes
Authors: Toledo J. M. , Bezerra V. B.
Published: August 2018

We obtain the solution corresponding to a static charged black hole (Reissner–Nordström black hole) surrounded by quintessence and a cloud of strings, study its thermodynamics and calculate the quasinormal frequencies for a scalar field in this background spacetime. The mass, Hawking temperature and heat capacity are analyzed and the roles played by the sources corresponding to the quintessence and the cloud of strings are showed up. In what concerns the quasinormal modes, we fixed the value of the quintessence parameter [Formula: see text], taking [Formula: see text], calculate the quasinormal frequencies and emphasize the effects due to the cloud of strings.
CATASTROPHE INSURANCE DERIVATIVES PRICING USING A COX PROCESS WITH JUMP DIFFUSION CIR INTENSITY
Authors: JANG JIWOOK , PARK JONG JUN , JANG HYUN JIN
Published: August 2018

We propose an analytical pricing method for stop-loss reinsurance contracts and catastrophe insurance derivatives using a Cox process with jump diffusion Cox–Ingersoll–Ross (CIR) intensity. The expected payoff of these contracts is expressed by the Laplace transform of the integration of the jump diffusion CIR process and the first moment of the aggregate loss. To confirm that the proposed analytical formula provides stable and accurate insurance derivative prices, we simulate them using a full Monte Carlo method compared to those obtained from its theoretical expectation. It shows that it is much faster way to obtain them than the full Monte Carlo method. We also conduct sensitivity analysis by changing the relevant parameters in the loss intensity providing their figures.
Power spectral density-based nearinfrared sub-band detection for noninvasive blood glucose prediction in both in-vitro and in-vivo studies
Authors: Akkaya Ibrahim , Selim Erman , Altintas Mert , Engin Mehmet
Published: August 2018

Diabetes is a widespread and serious disease and noninvasive measurement has been in high demand. To address this problem, a power spectral density-based method was offered for determining glucose sensitive sub-bands in the nearinfrared (NIR) spectrum. The experiments were conducted using phantoms of different optical properties in-vitro conditions. The optical bands 1200–1300[Formula: see text]nm and 2100–2200[Formula: see text]nm were found feasible for measuring blood glucose. After that, a photoplethysmography (PPG)-based low cost and portable optical system was designed. It has six different NIR wavelength LEDs for illumination and an InGaAs photodiode for detection. Optical density values were calculated through the system and used as independent variables for multiple linear regression analysis. The results of blood glucose levels for 24 known healthy subjects showed that the optical system prediction was nearly 80% in the A zone and 20% in the B zone according to the Clarke Error Grid analysis. It was shown that a promising easy-use, continuous, and compact optical system had been designed.
Characterization of Ammonia–Water Absorption Chiller and Application
Authors: Anand Gopalakrishnan , Erickson Donald C. , Makar Ellen
Published: August 2018

Ammonia-absorption refrigeration units (AARUS) can supply subfreezing refrigeration for many industrial applications. Such units are usually driven by waste heat or renewable energy at relatively low temperatures. The performance of the chiller is highly dependent on the temperatures of the driving heat, the chilling load, and the cooling water. In this paper, the performance of an advanced industrial-scale ammonia-absorption unit is modeled over a representative operating range. The performance is then characterized by a set of simple equations incorporating the three external temperatures. This simple model helps to evaluate potential applications, predict performance, and perform initial optimization. Case studies are presented highlighting the application of the model.
Inflammasome, pyroptosis, and cytokines in myocardial ischemia-reperfusion injury
Authors: Toldo Stefano , Mauro Adolfo G. , Cutter Zachary , Abbate Antonio
Published: August 2018

Myocardial ischemia-reperfusion injury induces a sterile inflammatory response, leading to further injury that contributes to the final infarct size. Locally released danger-associated molecular patterns lead to priming and triggering of the NOD-like receptor protein 3 inflammasome and amplification of the inflammatory response and cell death by activation of caspase-1. We review strategies inhibiting priming, triggering, or caspase-1 activity or blockade of the inflammasome-related cytokines interleukin-1β and interleukin-18, focusing on the beneficial effects in experimental models of acute myocardial infarction in animals and the initial results of clinical translational research trials.
UBC-Nepal expedition: upper and lower limb conduit artery shear stress and flow-mediated dilation on ascent to 5,050 m in lowlanders and Sherpa
Authors: Tremblay Joshua C. , Hoiland Ryan L. , Carter Howard H. , Howe Connor A. , Stembridge Mike , Willie Christopher K. , Gasho Christopher , MacLeod David B. , Pyke Kyra E. , Ainslie Philip N.
Published: August 2018

The study of conduit artery endothelial adaptation to hypoxia has been restricted to the brachial artery, and comparisons with highlanders have been confounded by differences in altitude exposure, exercise, and unknown levels of blood viscosity. To address these gaps, we tested the hypothesis that lowlanders, but not Sherpa, would demonstrate decreased mean shear stress and increased retrograde shear stress and subsequently reduced flow-mediated dilation (FMD) in the upper and lower limb conduit arteries on ascent to 5,050 m. Healthy lowlanders (means ± SD, n = 22, 28 ± 6 yr) and Sherpa ( n = 12, 34 ± 11 yr) ascended over 10 days, with measurements taken on nontrekking days at 1,400 m (baseline), 3,440 m ( day 4), 4,371 m ( day 7), and 5,050 m ( day 10). Arterial blood gases, blood viscosity, shear stress, and FMD [duplex ultrasound of the brachial and superficial femoral arteries (BA and SFA, respectively)] were acquired at each time point. Ascent decreased mean and increased retrograde shear stress in the upper and lower limb of lowlanders and Sherpa. Although BA FMD decreased in lowlanders from 7.1 ± 3.9% to 3.8 ± 2.8% at 5,050 versus 1,400 m ( P < 0.001), SFA FMD was preserved. In Sherpa, neither BA nor SFA FMD were changed upon ascent to 5,050 m. In lowlanders, the ascent-related exercise may favorably influence endothelial function in the active limb (SFA); selective impairment in FMD in the BA in lowlanders is likely mediated via the low mean or high oscillatory baseline shear stress. In contrast, Sherpa presented protected endothelial function, suggesting a potential vascular aspect of high-altitude acclimatization/adaptation.

NEW & NOTEWORTHY Upper and lower limb arterial shear stress and flow-mediated dilation (FMD) were assessed on matched ascent from 1,400 to 5,050 m in lowlanders and Sherpa. A shear stress pattern associated with vascular dysfunction/risk manifested in both limbs of lowlanders and Sherpa. FMD was impaired only in the upper limb of lowlanders. The findings indicate a limb-specific impact of high-altitude trekking on FMD and a vascular basis to acclimatization wherein endothelial function is protected in Sherpa on ascent
Comutations in DNA Damage Response Pathways Serve as Potential Biomarkers for Immune Checkpoint Blockade
Authors: Wang Zhijie , Zhao Jing , Wang Guoqiang , Zhang Fan , Zhang Zemin , Zhang Fan , Zhang Yuzi , Dong Hua , Zhao Xiaochen , Duan Jianchun , Bai Hua , Tian Yanhua , Wan Rui , Han Miao , Cao Yan , Xiong Lei , Liu Li , Wang Shuhang , Cai Shangli , Mok Tony S.K. , Wang Jie
Published: August 2018

Biomarkers such as programmed death receptor 1 ligand (PD-L1) expression, tumor mutational burden (TMB), and high microsatellite instability are potentially applicable to predict the efficacy of immune checkpoint blockade (ICB). However, several challenges such as defining the cut-off value, test platform uniformity, and low frequencies limit their broad clinical application. Here we identify comutations in the DNA damage response (DDR) pathways of homologous recombination repair and mismatch repair (HRR-MMR) or HRR and base excision repair (HRR-BER; defined as co-mut+) that are associated with increased TMB and neoantigen load and increased levels of immune gene expression signatures. In four public clinical cohorts, co-mut+ patients presented a higher objective response rate and a longer progression-free survival or overall survival than co-mut− patients. Overall, identification of DDR comutations in HRR-MMR or HRR-BER as predictors of response to ICB provides a potentially convenient approach for future clinical practice.

Significance: Identification of comutations in specific DDR pathways as predictors of superior survival outcomes in response to immune checkpoint blockade provide a clinically convenient approach for estimation of tumor mutational burden and delivery of ICB therapy. Cancer Res; 78(22); 6486–96. ©2018 AACR.
A Five-MicroRNA Signature Predicts Survival and Disease Control of Patients with Head and Neck Cancer Negative for HPV Infection
Authors: Hess Julia , Unger Kristian , Maihoefer Cornelius , Schüttrumpf Lars , Wintergerst Ludmila , Heider Theresa , Weber Peter , Marschner Sebastian , Braselmann Herbert , Samaga Daniel , Kuger Sebastian , Pflugradt Ulrike , Baumeister Philipp , Walch Axel , Woischke Christine , Kirchner Thomas , Werner Martin , Werner Kristin , Baumann Michael , Budach Volker , Combs Stephanie E. , Debus Jürgen , Grosu Anca-Ligia , Krause Mechthild , Linge Annett , Rödel Claus , Stuschke Martin , Zips Daniel , Zitzelsberger Horst , Ganswindt Ute , Henke Michael , Belka Claus
Published: August 2018

Purpose:

Human papillomavirus (HPV)–negative head and neck squamous cell carcinoma (HNSCC) is associated with unfavorable prognosis, while independent prognostic markers remain to be defined.

Experimental Design:

We retrospectively performed miRNA expression profiling. Patients were operated for locally advanced HPV-negative HNSCC and had received radiochemotherapy in eight different hospitals (DKTK-ROG; n = 85). Selection fulfilled comparable demographic, treatment, and follow-up characteristics. Findings were validated in an independent single-center patient sample (LMU-KKG; n = 77). A prognostic miRNA signature was developed for freedom from recurrence and tested for other endpoints. Recursive-partitioning analysis was performed on the miRNA signature, tumor and nodal stage, and extracapsular nodal spread. Technical validation used qRT-PCR. An miRNA–mRNA target network was generated and analyzed.

Results:

For DKTK-ROG and LMU-KKG patients, the median follow-up was 5.1 and 5.3 years, and the 5-year freedom from recurrence rate was 63.5% and 75.3%, respectively. A five-miRNA signature (hsa-let-7g-3p, hsa-miR-6508-5p, hsa-miR-210-5p, hsa-miR-4306, and hsa-miR-7161-3p) predicted freedom from recurrence in DKTK-ROG [hazard ratio (HR) 4.42; 95% confidence interval (CI), 1.98−9.88, P < 0.001], which was confirmed in LMU-KKG (HR 4.24; 95% CI, 1.40−12.81, P = 0.005). The signature also predicted overall survival (HR 3.03; 95% CI, 1.50−6.12, P = 0.001), recurrence-free survival (HR 3.16; 95% CI, 1.65−6.04, P < 0.001), and disease-specific survival (HR 5.12; 95% CI, 1.88−13.92, P < 0.001), all confirmed in LMU-KKG data. Adjustment for relevant covariates maintained the miRNA signature predicting all endpoints. Recursive-partitioning analysis of both samples combined classified patients into low (n = 17), low-intermediate (n = 80), high-intermediate (n = 48), or high risk (n = 17) for recurrence (P < 0.001).

Conclusions:

The five-miRNA signature is a strong and independent prognostic factor for disease recurrence and survival of patients with HPV-negative HNSCC.

See related commentary by Clump et al., p. 1441
Rare but Recurrent ROS1 Fusions Resulting From Chromosome 6q22 Microdeletions are Targetable Oncogenes in Glioma
Authors: Davare Monika A. , Henderson Jacob J. , Agarwal Anupriya , Wagner Jacob P. , Iyer Sudarshan R. , Shah Nameeta , Woltjer Randy , Somwar Romel , Gilheeney Stephen W. , DeCarvalo Ana , Mikkelson Tom , Van Meir Erwin G. , Ladanyi Marc , Druker Brian J.
Published: August 2018

Purpose:

Gliomas, a genetically heterogeneous group of primary central nervous system tumors, continue to pose a significant clinical challenge. Discovery of chromosomal rearrangements involving kinase genes has enabled precision therapy, and improved outcomes in several malignancies.

Experimental Design:

Positing that similar benefit could be accomplished for patients with brain cancer, we evaluated The Cancer Genome Atlas (TCGA) glioblastoma dataset. Functional validation of the oncogenic potential and inhibitory sensitivity of discovered ROS1 fusions was performed using three independent cell-based model systems, and an in vivo murine xenograft study.

Results:

In silico analysis revealed previously unreported intrachromosomal 6q22 microdeletions that generate ROS1-fusions from TCGA glioblastoma dataset. ROS1 fusions in primary glioma and ependymoma were independently corroborated from MSK-IMPACT and Foundation Medicine clinical datasets. GOPC–ROS1 is a recurrent ROS1 fusion in primary central nervous system (CNS) tumors. CEP85L–ROS1 and GOPC–ROS1 are transforming oncogenes in cells of astrocytic lineage, and amenable to pharmacologic inhibition with several ROS1 inhibitors even when occurring concurrently with other cancer hotspot aberrations frequently associated with glioblastoma. Oral monotherapy with a brain-permeable ROS1 inhibitor, lorlatinib, significantly prolonged survival in an intracranially xenografted tumor model generated from a ROS1 fusion-positive glioblastoma cell line.

Conclusions:

Our findings highlight that CNS tumors should be specifically interrogated for these rare intrachromosomal 6q22 microdeletion events that generate actionable ROS1 fusions. ROS1 fusions in primary brain cancer may be amenable for clinical intervention with kinase inhibitors, and this holds the potential of novel treatment paradigms in these treatment-refractory cancer types, particularly in glioblastoma.
How Does Continuous Renal Replacement Therapy Affect Septic Acute Kidney Injury?
Authors: Zhang Jingxiao , Tian Jiakun , Sun Hongzhi , Digvijay Kumar , Neri Mauro , Bhargava Vinant , Yin Yongjie , Ronco Claudio
Published: August 2018

Sepsis is the leading cause of acute kidney injury (AKI) in the intensive care unit. As the most common treatment of septic AKI, it is believed that continuous renal replacement therapy (CRRT) can not only maintain the water balance and excrete the metabolic products but also regulate the inflammation and promote kidney recovery. CRRT can remove the inflammatory cytokines to regulate the metabolic adaption in kidney and restore the kidney recovery to protect the kidney in septic AKI. Second, CRRT can provide extra energy supply in septic AKI to improve the kidney energy balance in septic AKI. Third, the anticoagulant used in CRRT also regulates the inflammation in septic AKI. CRRT is not only a treatment to deal with the water balance and metabolic products, but also a method to regulate the inflammation in septic AKI. Video Journal Club ‘Cappuccino with Claudio Ronco’ at https://www.karger.com/Journal/ArticleNews/223997?​sponsor=52.
A Case Report of Intravitreal Bevacizumab for Iris Metastasis of Small Cell Lung Carcinoma with Neovascular Glaucoma
Authors: Hidaka Takako , Chuman Hideki , Nao-i Nobuhisa
Published: August 2018

A 79-year-old man who had been diagnosed with small cell lung carcinoma (SCLC) complained of right ocular pain and blurred vision. His right intraocular pressure (IOP) was 30 mm Hg, and anterior chamber cells and multiple grayish white iris masses associated with peripheral anterior synechia (PAS) and neovascularization of the right iris were observed. We presumed that the iris masses were iris metastasis of SCLC. Despite therapy with topical eye drops and oral acetazolamide, the IOP was poorly controlled, so we injected intravitreal bevacizumab into his right eye for neovascular glaucoma. Neovascular glaucoma disappeared rapidly, but the IOP did not improve because of total PAS. To our knowledge, there is only one report of the use of intravitreal bevacizumab for SCLC metastasis in that eye and they reported that intravitreal injection resulted in successful short-term regression of presumed iris metastasis and improved control of secondary neovascular glaucoma, and the case had over one-half PAS. The previous report and our results suggest that secondary neovascular glaucoma with iris metastasis may be controlled by early intravitreal bevacizumab injection.
Fatores associados à fissura em usuários de crack:
Authors: Silveira Karine Langmantel , Oliveira Michele Mandagará , Alves Poliana Farias
Published: August 2018

Objetivo: identificar publicações relacionadas à influência dos fatores associados à variação dos níveis de fissura em usuários de crack. Metodologia: revisão de literatura sistemática, em que se rastreou estudos publicados no Brasil e exterior. As bases de dados utilizadas foram Publisher Medline, Literatura Latino-Americana e do Caribe em Ciências da Saúde e Scientific Electronic Library. Resultados: foram selecionados nove artigos, após a utilização dos critérios de inclusão e exclusão. Os fatores associados observados estão relacionados ao padrão de uso do crack, relações familiares, atividade profissional, utilização de outras substâncias, estratégias de redução de danos e ansiedade. Conclusão: acredita-se que a fissura pode interferir no consumo abusivo de crack e, assim, ocasionar diversos problemas tanto de ordem social como de saúde.
Violência relacionada ao trabalho na psiquiatria:
Authors: Paula Glaudston Silva de , Oliveira Elias Barbosa de , Silva Alexandre Vicente da , Souza Silvia Regina Carvalho de , Fabri Janaina Mengal Gomes , Guerra Olivia De Andrade
Published: August 2018

Objetivou-se, neste estudo, analisar os tipos de violência relacionados ao trabalho em unidade de internação psiquiátrica, de acordo com a percepção dos trabalhadores de enfermagem, e discutir as repercussões para a saúde dos integrantes do grupo. Pesquisa qualitativa, descritiva, realizada em unidade de internação psiquiátrica de hospital universitário. Utilizouse a técnica de entrevista semiestruturada, com 16 trabalhadores de enfermagem. Aplicada a análise de conteúdo aos depoimentos, identificou-se que tanto a violência psicológica quanto a institucional, decorrentes das condições inadequadas de trabalho, prejudicam os trabalhadores e a prática de enfermagem. Conclui-se, então, a importância de a instituição investir em ações preventivas no intuito de promover a saúde do grupo, bem como a qualidade do serviço ofertada.
Avaliação de uma intervenção preventiva em motoristas usuários e não usuários de álcool - um estudo piloto
Authors: Andrade André Luiz Monezi , Scatena Adriana , Micheli Denise De
Published: August 2018

Neste estudo piloto avaliamos os comportamentos de beber e dirigir e os conceitos de autocrítica sobre este tema em indivíduos que pretendiam dirigir após a saída de bares e restaurantes. Também avaliamos a eficácia de uma intervenção preventiva em seus comportamentos futuros de beber e dirigir. Os participantes tiveram seus níveis de alcoolemia (BAC) avaliados e responderam um questionário, recebendo um folheto informativo durante a intervenção breve. A maioria dos participantes (69%) apresentaram BAC abaixo dos limites criminais estabelecidos por lei e 31% acima deste limite. Após um mês, o questionário foi novamente aplicado e não se observou redução significativa no comportamento de beber e dirigir após um mês, indicando a necessidade de intervenções mais efetivas.
Uso de substâncias psicoativas por profissionais de saúde
Authors: Fernandes Márcia Astrês , Silva Joyce Soares e , Vilarinho Jessica De Oliveira Veloso , Seabra Larissa De Oliveira , Feitosa Carla Danielle Araújo
Published: August 2018

Objetivou-se conhecer quais fatores levam os profissionais de saúde a utilizarem substâncias psicoativas, identificar as mais utilizadas e as consequências para vida do trabalhador. Trata-se de uma revisão integrativa, com buscas na biblioteca virtual em saúde, que resultou em 88 artigos, dos quais após avaliação restaram-se 12. Constatou-se que os fatores desencadeadores estavam relacionados à cobrança no trabalho, riscos ambientais e individuais e que apesar de reconhecerem os riscos do uso, consumiam drogas de ação central. Conclui-se que se faz importante a realização de pesquisas sobre o perfil profissional com o intuito de implementar ações preventivas em saúde para esta população.
Temperature Variability and Mortality: Evidence from 16 Asian Countries
Authors: Deschenes Olivier
Published: August 2018

This paper presents an empirical analysis devised to understand the complex relationship between extreme temperatures and mortality in 16 Asian countries where more than 50% of the world's population resides. Using a country-year panel on mortality rates and various measures of high temperatures for 1960–2015, the analysis produces two primary findings. First, high temperatures significantly increase annual mortality rates in Asia. Second, this increase is larger in countries with cooler climates where high temperatures are infrequent. These empirical estimates can help inform climate change impact projections on human health for Asia, which is considered to be highly vulnerable to climate change. The results indicate that unabated warming until the end of the century could increase annual mortality rates by more than 40%, highlighting the need for concrete and rapid actions to help individuals and communities adapt to climate change.
Indonesia's Moratorium on Palm Oil Expansion from Natural Forests: Economy-Wide Impacts and the Role of International Transfers
Authors: Yusuf Arief A. , Roos Elizabeth L. , Horridge Jonathan M.
Published: August 2018

Indonesia has introduced a moratorium on the conversion of natural forests to land used for palm oil production. Using a dynamic, bottom-up, interregional computable general equilibrium model of the Indonesian economy, we assess several scenarios of the moratorium and discuss its impacts on the domestic economy as well as on regional economies within Indonesia. We find the moratorium reduces Indonesian economic growth and other macroeconomic indicators, but international transfers can more than compensate the welfare losses. The impacts also vary across regions. Sumatra, which is highly dependent on palm oil and is home to forests that no longer have a high carbon stock, receives fewer transfers and suffers the greatest economic loss. Kalimantan, which is relatively less dependent on palm oil and has forests with a relatively high carbon stock, receives more transfers and gets greater benefit. This implies that additional policy measures anticipating the unbalanced impacts of the moratorium are required if the trade-off between conservation and reducing interregional economic disparity is to be reconciled.