bluuebunny/crossref_metadata_2025 huggingface dataset:
X-ray absorption towards high-redshift sources: probing the intergalactic medium with blazars
Authors: Arcodia R. , Campana S. , Salvaterra R. , Ghisellini G.
Published: April 2018

The role played by the intergalactic medium (IGM) in the X-ray absorption towards high-redshift sources has recently drawn more attention in spectral analysis studies. Here, we study the X-ray absorption towards 15 flat-spectrum radio quasars at z > 2, relying on high counting statistic (≳10 000 photons) provided by XMM-Newton, with additional NuSTAR (and simultaneous Swift-XRT) observations when available. Blazars can be confidently considered to have negligible X-ray absorption along the line of sight within the host galaxy, likely swept by the kpc-scale relativistic jet. This makes our sources ideal for testing the absorption component along the IGM. Our new approach is to revisit the origin of the soft X-ray spectral hardening observed in high-z blazars in terms of X-ray absorption occurring along the IGM, with the help of a low-z sample used as comparison. We have verified that the presence of absorption in excess of the Galactic value is the preferred explanation to explain the observed hardening, while intrinsic energy breaks, predicted by blazars’ emission models, can easily occur out of the observing energy band in most sources. First, we performed an indirect analysis comparing the inferred amount of absorption in excess of the Galactic value with a simulated IGM absorption contribution, that increases with redshift and includes both a minimum component from diffuse IGM metals, and the additional contribution of discrete denser intervening regions. Then, we directly investigated the warm-hot IGM with a spectral model on the best candidates of our sample, obtaining an average IGM density of n0 = 1.01−0.72+0.53 × 10−7 cm−3 and temperature of log(T/K) = 6.45−2.12+0.51. A more dedicated study is currently beyond our reach, but our results can be used as a stepping stone for future more accurate analysis, involving Athena.
C IV broad absorption line disappearance in a large SDSS QSO sample
Authors: De Cicco D. , Brandt W. N. , Grier C. J. , Paolillo M. , Filiz Ak N. , Schneider D. P. , Trump J. R.
Published: April 2018

Context. Broad absorption lines (BALs) in the spectra of quasi-stellar objects (QSOs) originate from outflowing winds along our line of sight; winds are thought to originate from the inner regions of the QSO accretion disk, close to the central supermassive black hole (SMBH). These winds likely play a role in galaxy evolution and are responsible for aiding the accretion mechanism onto the SMBH. Several works have shown that BAL equivalent widths can change on typical timescales from months to years; such variability is generally attributed to changes in the covering factor (due to rotation and/or changes in the wind structure) and/or in the ionization level of the gas.

Aims. We investigate BAL variability, focusing on BAL disappearance.

Methods. We analyze multi-epoch spectra of more than 1500 QSOs – the largest sample ever used for such a study – observed by different programs from the Sloan Digital Sky Survey-I/II/III (SDSS-I/II/III), and search for disappearing C IV BALs. The spectra cover a rest-frame time baseline ranging from 0.28 to 4.9 yr; the source redshifts range from 1.68 to 4.27.

Results. We detect 73 disappearing BALs in the spectra of 67 unique sources. This corresponds to 3.9% of BALs disappearing within 4.9 yr (rest frame), and 5.1% of our BAL QSOs exhibit at least one disappearing BAL within 4.9 yr (rest frame). We estimate the average lifetime of a BAL along our line of sight (≈80–100 yr), which appears consistent with the accretion disk orbital time at distances where winds are thought to originate. We inspect various properties of the disappearing BAL sample and compare them to the corresponding properties of our main sample. We also investigate the existence of a correlation in the variability of multiple troughs in the same spectrum, and find it persistent at large velocity offsets between BAL pairs, suggesting that a mechanism extending on a global scale is necessary to explain the phenomenon. We select a more reliable sample of disappearing BALs on the basis of some criteria adopted in a previous publication, where a subset of our current sample was analyzed, and compare the findings from the two works, obtaining generally consistent results.
Impact of maternal dietary lipids on human health
Authors: Guesnet Philippe , Marmonier Corinne , Boyer Constance , Delplanque Bernadette
Published: April 2018

During the perinatal period, maternal dietary polyunsaturated fatty acids (PUFA) ensure optimal infant development. Observational studies on cognitive and visual development reported that a specific deficit intake in n-3 PUFA in pregnant women was associated with a reduction in visual acuity in 2-months-old infants. Moreover, a low docosahexaenoic acid (DHA) content associated with a high level of n-6 PUFA in breast milk was negatively associated with the degree of cognitive development in 6-years-old children. As regards to adipose tissue development, only observational human data agree with the hypothesis that excessive dietary intakes of n-6 PUFA compared with n-3 PUFA could promote the development of adipose tissue and obesity. With regard to immune system development, observational and clinical studies suggest that long-chain n-3 PUFA consumption during pregnancy may prevent the incidence of allergic diseases in children. Lastly, specific association between the maternal ingestion of food groups and the infant health has been studied mainly on allergic outcomes (fish, dairy products). Nutritional recommendations for PUFA intake in pregnant and lactating women were mainly based on brain development data, corresponding to breast milk levels of 10% of total fatty acids for linoleic acid, 1.5% for α-linolenic acid and 0.4% for DHA.
La correction de la classe II chez les adolescents à l’aide de l’orthodontie linguale totalement individualisée
Authors: Alouini Ons , Wiechmann Dirk
Published: April 2018

Introduction : L’orthodontie linguale totalement individualisée nous permet de proposer une solution efficace, prévisible et esthétique à nos patients. Les adolescents présentant une classe II dentaire représentent la majorité des patients dans les cabinets d’orthodontie. Plusieurs moyens sont alors disponibles pour corriger ce décalage sagittal tels que les élastiques inter-maxillaires, les propulseurs mandibulaires souples ou rigides, la distalisation maxillaire par mini-vis, les extractions ou une combinaison de ces différentes solutions. Leur choix dépend de plusieurs critères de décision dont les plus importants sont la sévérité de la malocclusion, la symétrie du décalage de la classe II, ainsi que l’âge et la motivation du patient. Matériels et méthodes : À travers cet article, les auteurs préciseront les stratégies thérapeutiques actuelles de correction de la classe II dentaire chez les adolescents grâce à un appareil lingual totalement individualisé (ALTI). Conclusion : Il n’est pas plus difficile de corriger une classe II importante en technique linguale qu’avec des techniques vestibulaires, l’orthodontie linguale totalement individualisée présentant, de plus, certains avantages permettant de faciliter le traitement.
Comment parfaire l’esthétique du sourire : toujours en rose !
Authors: Monnet-Corti Virginie , Antezack Angeline , Pignoly Marion
Published: April 2018

Introduction :L’esthétique du sourire s’appuie sur des données numériques, physiques, physiologiques et psychologiques de la beauté, sans oublier les désirs du patient. Elle est déterminée par la forme, la couleur et la position des lèvres, des dents et des tissus gingivaux. L’examen du parodonte dans le cadre facial, puis dans le cadre labial permet d’analyser la visibilité de la gencive lors du sourire naturel et forcé, la santé parodontale, le contour gingival, la ligne esthétique gingivale, la présence des papilles.Matériels et méthodes :L’ensemble de ces données va permettre d’établir un score d’esthétique gingivale, de déterminer les origines de la disharmonie et les traitements envisagés.Discussion :Au moment du plan de traitement global orthodontique, la chirurgie plastique parodontale peut modifier l’aspect et la morphologie gingivale afin de rétablir une harmonie du sourire. La chirurgie plastique parodontale soustractive traite les défauts d’espace biologiques et les excès de tissus perçus lors des éruptions passives incomplètes par gingivectomie ou déplacement apical des tissus gingivaux associés ou non à une ostéoplastie ou une ostéoectomie. Enfin, des injections d’acide hyaluronique dans les papilles permettent de les repulper et de minimiser l’aspect des trous noirs.
Existiert ein epidemischer Vitamin D-Mangel bei weiblichen Inhaftierten und in der deutschen Wohnbevölkerung? Ergebnisse einer Studie unter Inhaftierten und einer systematischen Literaturrecherche
Authors: Pürner Friedrich , Böhmer Merle M. , Wildner Manfred
Published: April 2018

Hintergrund Die Auswirkungen einer langjährigen Haftstrafe auf den Vitamin D (VitD)-Haushalt von Strafgefangenen in Deutschland wurden bislang nicht systematisch untersucht. Besondere Lebensumstände in der Justizvollzugsanstalt (JVA) – wenig Sonnenlicht bei geringer Aufenthaltszeit im Freien – könnten bei Inhaftierten zu VitD-Mangel führen. Ziel der Studie war es, den VitD-Status bei der deutschen Wohnbevölkerung und Inhaftierten zu betrachten, um das Ausmaß eines VitD-Mangels in beiden Gruppen zu quantifizieren.

Methoden Im Zeitraum Mai 2012–Juni 2013 wurde der VitD-Spiegel (Nachweis 25(OH) D) in Blutseren von Insassinnen einer deutschen JVA getestet. Verwendete Definitionen waren: leichter VitD-Mangel: 10-<20 µg/l; schwerer Mangel:<10 µg/l. Um die JVA-Ergebnisse mit entsprechenden Werten in der Wohnbevölkerung in Deutschland vergleichen zu können, wurde eine systematische Literaturrecherche in der elektronischen Datenbank PubMed durchgeführt.

Ergebnisse Es wurden Blutseren von 84 Inhaftierten (Altersmedian: 43 Jahre; Spanne: 19–75) untersucht. Bei 30 Frauen (36%) lag ein schwerer VitD-Mangel vor, bei 47 (56%) ein leichter. Zehn Studien zum VitD-Status konnten identifiziert werden, in denen übereinstimmend ein beträchtlicher VitD-Mangel in der Wohnbevölkerung berichtet wurde.

Schlussfolgerung In Deutschland scheinen sowohl weibliche Inhaftierte als auch die Wohnbevölkerung nicht ausreichend mit VitD versorgt. Im Gegensatz zu Inhaftierten kann die nicht-institutionalisierte Bevölkerung wesentlich freier entscheiden, ob, wann und wie lange sie sich der Sonne aussetzen möchte. Auch kann sie durch VitD-reiche Nahrung einem Mangel entgegensteuern. Dies ist Inhaftierten versagt. Um den langfristigen Auswirkungen eines VitD-Mangels bei Strafgefangenen vorzubeugen, erscheint das Angebot einer Substitution mit VitD-Präparaten für die Dauer der Inhaftierung sinnvoll.
Copper-Catalyzed Cascade Synthesis of [1,2,4]-Triazoloquinazolinones
Authors: Lou Zhenbang , Man Ningning , Yang Haijun , Zhu Changjin , Fu Hua
Published: April 2018

An efficient and practical method for the synthesis of 1,2,4-triazolo[5,1-b]quinazolin-9(3H)-ones has been developed via the copper-catalyzed domino reactions of readily available substituted N′-acetyl-2-bromobenzohydrazides with cyanamide. The protocol uses inexpensive CuI as the catalyst, and no other ligand or additive was required. The target products were prepared in good to excellent yields with tolerance of various functional groups.
Minimally Invasive Interventional Management of Gastric Outlet Obstructions
Authors: Zhou Wei-Zhong , Yang Zheng-Qiang
Published: April 2018

Gastric outlet obstruction (GOO) is a clinical consequence of any disease that produces intrinsic or extrinsic obstruction of the pyloric channel or duodenum. The most common symptoms of GOO include nausea, vomiting, abdominal pain, and weight loss. Traditionally, surgery is regarded as the standard treatment modality. However, with the development of mini-invasive technologies, fluoroscopic or endoscopic stenting and balloon dilatation have become the mainstream of the therapies. The initial recommended treatment for malignant GOO is self-expanding metal stent placement. The stent can be classified into covered and uncovered stent according to whether it is coated with a membrane. Covered stent seems to have longer stent patency, while uncovered stent has the advantage of a lower migration rate. Regarding the etiology of benign GOO, peptic ulcer disease and corrosive injury are the two main reasons. Balloon dilatation is a simple and convenient way to treat the benign GOO. Stent placement has recently been reported for the treatment of benign GOO; however, it needs further more studies to verify its effect. This article presents a concise review of current fluoroscopic or endoscopic stenting practice for malignant GOO and balloon dilatation or stenting for benign GOO.
Hip Capsular Management
Authors: Kunze Kyle , Leong Natalie , Nho Shane , Neal William
Published: April 2018

Due to both the currently available technology and anatomic constraints of the hip joint, capsulotomy is necessary to perform hip arthroscopy. Proper management of the hip capsule is a crucial component of hip arthroscopy that has evolved with increased awareness that capsular closure during hip arthroscopy reestablishes the normal anatomy of the iliofemoral ligament and thus restores the biomechanical characteristics of the hip joint. This article reviews the biomechanical rationale for hip access and closure, as well as recent clinical studies on patient-reported outcomes with regard to capsular closure. Additionally, capsulotomy techniques including capsulectomy as well as interportal and T-capsulotomy techniques are reviewed, and the authors' preferred technique for capsular management is described. While capsular closure is technically challenging and increases operative time, meticulous closure improves outcomes by reducing postoperative micro- and gross instability.
Älter werden – gesund und motiviert bleiben
Authors: Röhr Anneli
Published: April 2018

Damit auch ältere Mitarbeiter in der Pflege möglichst lange in ihrem Beruf verbleiben können, ist es wichtig, sie darin zu stärken, mit Belastungen umzugehen.
Eine Möglichkeit bietet das Konzept der Resilienz – der Stärkung der Widerstandsfähigkeit des Einzelnen.
Relativistic Eulerian rarefied gas with internal structure
Authors: Pennisi Sebastiano , Ruggeri Tommaso
Published: April 2018

Recently Pennisi and Ruggeri [Ann. Phys. 377, 414 (2017)] proposed a casual hyperbolic model for a dissipative relativistic gas with internal structure. In this paper, we consider the particular case of the model when dissipation is negligible (Eulerian gas). We study in particular the energy behavior in comparison with the Synge energy which is valid for monatomic gas and we evaluate the characteristic velocities proving the hyperbolicity of the differential system. The second part of the paper is devoted to the ultra-relativistic limit of the model and we prove that there exists a critical value of the degree of freedom such that for smaller values of this quantity the ultra-relativistic limit of the energy of a gas with structure is the same as the Synge energy, while for larger degrees of freedom the energy increases with the degree of freedom itself.
Compositional segregation and electrical properties characterization of [001]- and [011]-oriented co-growth Pb(In1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3 single crystal
Authors: Song Kexin , Li Zhenrong , Guo Haisheng , Xu Zhuo , Fan Shiji
Published: April 2018

A Pb(In1/2Nb1/2)O3-Pb(Mg1/3Nb2/3)O3-PbTiO3 relaxor ferroelectric single crystal boule of 3 in. diameter was grown using [001]- and [011]-oriented co-growth crystals as seeds by the modified Bridgman method. The as-grown crystal boule was divided into two growth regions [001] and [011]. The composition and the electrical properties of samples of the two regions were characterized in detail along the growth direction in the whole crystal boule. The PT content of [001]-grown samples increased from 27.7 to 36.8 mol. % along the growth direction, especially they are averagely higher about 0.7 mol. % than those of [011]-grown samples at the same growth position. The PMN content of [001]-grown samples decreased from 43.0 to 34.8 mol. %, which is lower than that of the corresponding [011]-grown samples. The compositional segregation behavior along [001] and [011] growth directions was discussed based on the crystal growth theories. Variations in the rhombohedral to tetragonal phase transition temperature (TRT), the piezoelectric properties, the coercive electric field and the remnant polarization of [001] samples were discussed according to changes in compositional segregation and crystal anisotropy. Under the exact same growth conditions, the [011]-grown crystal has a larger composition segregation effect than that of the [001]-grown crystal. This result provides a positive effect on analysing the nature and reducing the effect of compositional segregation.
Reversing an S-kink effect caused by interface degradation in organic solar cells through gold ion implantation in the PEDOT:PSS layer
Authors: Brenes-Badilla D. , Coutinho D. J. , Amorim D. R. B. , Faria R. M. , Salvadori M. C.
Published: April 2018

In this work, we performed a study on the recovery of the photovoltaic performance of an ITO/PEDOT:PSS/P3HT:PCBM/Ca/Al solar cell after the hole transport layer (PEDOT:PSS) had been degraded by contact with the environment. A device that was fully built in an inert environment exhibited a fill factor (FF) of 0.64, while the device whose hole transport layer was exposed to air presented a FF equal to 0.2. In addition, the J-V characteristic curve of the degraded device did not follow the photovoltaic pattern exhibiting the degenerate S shape. However, the elimination of the deleterious effect was achieved by bombarding gold ions on the contaminated surface of PEDOT:PSS by means of the Metal Plasma Immersion Ion Implantation technique. Due to the low energy of the ionic beam of gold, the implanted gold atoms were located at few nanometers off the surface, forming nanometric clusters, that is, gold nanoparticles. Most probably, the degradation of the J-V photovoltaic curve, represented by the S-kink effect, was caused by the appearance of a potential barrier at PEDOT:PSS/P3HT:PCBM interface, which was demolished by the gold nanoparticles that have work function close to HOMO of P3HT. This S-kink effect was also simulated by using an equivalent circuit model constituted by a two-diode circuit, one of which plays the role of the undesirable potential barrier formed at the PEDOT:PSS/P3HT:PCBM interface. Our analysis shows that deposition of gold nanoparticles next to the interface recovers the good hole injection condition from the PEDOT:PSS into the active layer, restoring the fill factor and the device efficiency.
Retrieval of the thickness and refractive index dispersion of parallel plate from a single interferogram recorded in both spectral and angular domains
Authors: Dong Jingtao , Lu Rongsheng
Published: April 2018

The principle of retrieving the thickness and refractive index dispersion of a parallel glass plate is reported based on single interferogram recording and phase analysis. With the parallel plate illuminated by a convergent light sheet, the transmitted light interfering in both spectral and angular domains is recorded. The phase recovered from the single interferogram by Fourier analysis is used to retrieve the thickness and refractive index dispersion without periodic ambiguity. Experimental results of an optical substrate standard show that the accuracy of refractive index dispersion is less than 2.5 × 10−5 and the relative uncertainty of thickness is 6 × 10−5 (3σ). This method is confirmed to be robust against the intensity noises, indicating the capability of stable and accurate measurement.
Bulk hydrodynamic stability and turbulent saturation in compressing hot spots
Authors: Davidovits Seth , Fisch Nathaniel J.
Published: April 2018

For hot spots compressed at constant velocity, we give a hydrodynamic stability criterion that describes the expected energy behavior of non-radial hydrodynamic motion for different classes of trajectories (in ρR — T space). For a given compression velocity, this criterion depends on ρR, T, and dT/d(ρR) (the trajectory slope) and applies point-wise so that the expected behavior can be determined instantaneously along the trajectory. Among the classes of trajectories are those where the hydromotion is guaranteed to decrease and those where the hydromotion is bounded by a saturated value. We calculate this saturated value and find the compression velocities for which hydromotion may be a substantial fraction of hot-spot energy at burn time. The Lindl (Phys. Plasmas 2, 3933 (1995)] “attractor” trajectory is shown to experience non-radial hydrodynamic energy that grows towards this saturated state. Comparing the saturation value with the available detailed 3D simulation results, we find that the fluctuating velocities in these simulations reach substantial fractions of the saturated value.
Electron scattering at interfaces in nano-scale vertical interconnects: A combined experimental and ab initio study
Authors: Lanzillo Nicholas A. , Restrepo Oscar D. , Bhosale Prasad S. , Cruz-Silva Eduardo , Yang Chih-Chao , Youp Kim Byoung , Spooner Terry , Standaert Theodorus , Child Craig , Bonilla Griselda , Murali Kota V. R. M.
Published: April 2018

We present a combined theoretical and experimental study on the electron transport characteristics across several representative interface structures found in back-end-of-line interconnect stacks for advanced semiconductor manufacturing: Cu/Ta(N)/Co/Cu and Cu/Ta(N)/Ru/Cu. In particular, we evaluate the impact of replacing a thin TaN barrier with Ta while considering both Co and Ru as wetting layers. Both theory and experiment indicate a pronounced reduction in vertical resistance when replacing TaN with Ta, regardless of whether a Co or Ru wetting layer is used. This indicates that a significant portion of the total vertical resistance is determined by electron scattering at the Cu/Ta(N) interface. The electronic structure of these nano-sized interconnects is analyzed in terms of the atom-resolved projected density of states and k-resolved transmission spectra at the Fermi level. This work further develops a fundamental understanding of electron transport and material characteristics in nano-sized interconnects.
Hospitality networks, British travel writers, and the dissemination of competing Transylvanian claims to civilization, 1830s–1930s
Authors: Davis Sacha E.
Published: April 2018

Hungarian, Saxon, and Romanian nationalist activists in Transylvania disseminated competing claims to “Westernness” by swaying visiting British travel writers' descriptions through hospitality networks that guided what writers saw and heard, assuring that travelers favored the nationalists' classifications of the region's ethnicities. Although the qualities British travelers valued varied depending on individual differences and intellectual currents such as enlightened reform, scientific racism, and the romantic revival, travelers consistently ascribed the qualities they best favored to the nationality on whose hospitality they relied. Wealth and time of travel determined which hospitality networks travelers favored. The Hungarian noble elites hosted most travelers until 1918, when the newly dominant Romanian nobility replaced them. Throughout, peasant voices especially remained marginalized.
Construction of Rhodococcus expression vectors and expression of the aminoalcohol dehydrogenase gene in Rhodococcus erythropolis
Authors: Yamamura Ei-Tora
Published: April 2018

NADP+-dependent aminoalcohol dehydrogenase (AADH) of Rhodococcus erythropolis MAK154 produces double chiral aminoalcohols, which are used as pharmaceuticals. However, the genetic manipulation of Rhodococcus strains to increase their production of such industrially important enzymes is not well studied. Therefore, I aimed to construct Rhodococcus expression vectors, derived from the Rhodococcus–Escherichia coli shuttle vector pRET1102, to express aadh. The plasmid pRET1102 could be transformed into many actinomycete strains, including R. erythropolis. The transformation efﬁciency for a species closely related to R. erythropolis was higher than that for other actinomycete strains. Promoters of various strengths, hsp, 1200rep, and TRR, were obtained from Gram-positive bacteria. The activity of TRR was stronger than that of hsp and 1200rep. The aadh-expressing plasmid pRET1172 with TRR could be transformed into many actinomycete strains to increase their AADH production. The Rhodococcus expression vector, pRET11100, constructed by removing aadh from the pRET1172 plasmid may be useful for bioconversion.
Linear and nonlinear optical analysis on semiorganic
L
-proline cadmium chloride single crystal
Authors: Anis Mohd , Baig M I , Hussaini S S , Shirsat M D , Shkir Mohd , Ghramh H A
Published: April 2018

In the current investigation,
L
-proline cadmium chloride monohydrate (LPCC) single crystal is grown by a slow solvent evaporation technique to identify its credibility for nonlinear optical device applications. The constituent elements of LPCC crystal are determined by the energy dispersive spectroscopic (EDS) technique. The single crystal x-ray diffraction technique is used to determine the structural dimensions of LPCC crystal. The UV-visible studies are carried out within a wavelength range of 200 nm–1100 nm to determine the optical transmittance of LPCC crystal. The linear optical parameters of LPCC crystal are evaluated using the transmittance data to discuss its importance for distinct optical devices. The Nd:YAG laser assisted Kurtz–Perry test is carried out to determine the enhancement in second harmonic generation efficiency of LPCC crystal with reference to KDP crystal. The Z-scan technique is employed to assess the third order nonlinear optical (TONLO) properties of LPCC crystal at 632.8 nm. The Z-scan data are utilized to evaluate the TONLO refraction, absorption and susceptibility of LPCC crystal. The color oriented luminescence behavior of LPCC crystal is investigated within a spectral range of 350 nm–700 nm. The dependence of dielectric constant and dielectric loss on temperature and frequency is evaluated through the dielectric measurement studies.
Commentary on “Differentiable dynamical systems” by Stephen Smale
Authors: Zworski Maciej
Published: April 2018

Immediately following the commentary below, this previously published article is reprinted in its entirety: Stephen Smale, “Differentiable dynamical systems”, Bull. Amer. Math. Soc. 73 (1967), no. 6, 747–817.
Commentary on “Longest increasing subsequences: from patience sorting to the Baik–Deift–Johansson theorem” by David Aldous and Persi Diaconis
Authors: Corwin Ivan
Published: April 2018

Immediately following the commentary below, this previously published article is reprinted in its entirety: David Aldous and Persi Diaconis, “Longest increasing subsequences: from patience sorting to the Baik–Deift–Johansson theorem”,Bull. Amer. Math. Soc. (N.S.)36(1999), no. 4, 413–432.
Microbiota–Host Crosstalk: A Bridge Between Cardiovascular Risk Factors, Diet, and Cardiovascular Disease
Authors: Amar Jacques
Published: April 2018

Cardiovascular disease is the leading cause of death and is also a major cause of disability worldwide. Indeed, even in well-treated patients for hypertension or dyslipidemia, there is still a high cardiovascular risk called residual risk. It is of utmost importance to identify the pathway leading from risk factors to cardiovascular disease to further improve stroke and myocardial infarction prevention. In this review, we presented some of experimental and epidemiological evidences suggesting that microbiota–host crosstalk is involved in this pathway and bridges the gap between cardiovascular risk factors, diet, and cardiovascular residual risk. We considered the 3 participants in this dialogue: the gut microbiota, the intestinal barrier, and bacterial translocation. We analyzed their relations with cardiovascular risk factors and cardiovascular diseases. Also, we presented some of therapeutic strategies aiming to control microbiota to further prevent cardiovascular disease and the take home messages that can be drawn for clinical practice.
EMUDRA: Ensemble of Multiple Drug Repositioning Approaches to improve prediction accuracy
Authors: Zhou Xianxiao , Wang Minghui , Katsyv Igor , Irie Hanna , Zhang Bin
Published: April 2018

Motivation

Availability of large-scale genomic, epigenetic and proteomic data in complex diseases makes it possible to objectively and comprehensively identify the therapeutic targets that can lead to new therapies. The Connectivity Map has been widely used to explore novel indications of existing drugs. However, the prediction accuracy of the existing methods, such as Kolmogorov–Smirnov statistic remains low. Here we present a novel high-performance drug repositioning approach that improves over the state-of-the-art methods.

Results

We first designed an expression weighted cosine (EWCos) method to minimize the influence of the uninformative expression changes and then developed an ensemble approach termed ensemble of multiple drug repositioning approaches (EMUDRA) to integrate EWCos and three existing state-of-the-art methods. EMUDRA significantly outperformed individual drug repositioning methods when applied to simulated and independent evaluation datasets. We predicted using EMUDRA and experimentally validated an antibiotic rifabutin as an inhibitor of cell growth in triple negative breast cancer. EMUDRA can identify drugs that more effectively target disease gene signatures and will thus be a useful tool for identifying novel therapies for complex diseases and predicting new indications for existing drugs.

Availability and implementation

The EMUDRA R package is available at doi: 10.7303/syn11510888.

Supplementary information

Supplementary data are available at Bioinformatics online.
Intermediate Susceptibility Dose-Dependent Breakpoints For High-Dose Rifampin, Isoniazid, and Pyrazinamide Treatment in Multidrug-Resistant Tuberculosis Programs
Authors: Zuur Marlanka A , Pasipanodya Jotam G , van Soolingen Dick , van der Werf Tjip S , Gumbo Tawanda , Alffenaar Jan-Willem C
Published: April 2018

Background

Bacterial susceptibility is categorized as susceptible, intermediate-susceptible dose-dependent (ISDD), and resistant. The strategy is to use higher doses of first-line agents in the ISDD category, thereby preserving the use of these drugs. This system has not been applied to antituberculosis drugs. Pharmacokinetic/pharmacodynamic (PK/PD) target exposures, in tandem with Monte Carlo experiments, recently identified susceptibility breakpoints of 0.0312 mg/L for isoniazid, 0.0625 mg/L for rifampin, and 50 mg/L for pyrazinamide. These have been confirmed in clinical studies.

Methods

Target attainment studies were carried out using Monte Carlo experiments to investigate whether rifampin, isoniazid, and pyrazinamide dose increases would achieve the PK/PD target in >90% of 10000 patients with tuberculosis caused by bacteria, revealing minimum inhibitory concentrations (MICs) between the proposed and the traditional breakpoints.

Results

We found that an isoniazid dose of 900 mg/day identified a new ISDD MIC range of 0.0312–0.25 mg/L and resistance at MIC ≥0.5 mg/L. Rifampin 1800 mg/day would result in an ISDD of 0.0625–0.25 mg/L and resistance at MIC ≥0.5 mg/L. At a dose of pyrazinamide 4 g/day, the ISDD MIC range was 37.5–50 mg/L and resistance at MIC ≥100 mg/L. Based on MIC distributions, 93% (isoniazid), 78% (rifampin), and 27% (pyrazinamide) of isolates would be within the ISDD range.

Conclusions

Drug susceptibility testing at 2 concentrations delineating the ISDD range, and subsequently using higher doses, could prevent switching to a more toxic second-line treatment. Confirmatory clinical studies would provide evidence to change treatment guidelines.
Clinical Impact of a Multiplex Gastrointestinal Polymerase Chain Reaction Panel in Patients With Acute Gastroenteritis
Authors: Cybulski Robert J , Bateman Allen C , Bourassa Lori , Bryan Andrew , Beail Barb , Matsumoto Jason , Cookson Brad T , Fang Ferric C
Published: April 2018

Background

Molecular syndromic diagnostic panels can enhance pathogen identification in the approximately 2–4 billion episodes of acute gastroenteritis that occur annually worldwide. However, the clinical utility of these panels has not been established.

Methods

We conducted a prospective, multi-center study to investigate the impact of the BioFire FilmArray Gastrointestinal polymerase chain reaction panel on clinical diagnosis and decision-making, and compared the clinical acuity of patients with positive results obtained exclusively with the FilmArray with those detected by conventional stool culture. A total of 1887 consecutive fecal specimens were tested in parallel by FilmArray and stool culture. Laboratory and medical records were reviewed to determine rates of detection, turnaround times, clinical features, and the nature and timing of clinical decisions.

Results

FilmArray detected pathogens in 35.3% of specimens, compared to 6.0% for culture. Median time from collection to result was 18 hours for FilmArray and 47 hours for culture. Median time from collection to initiation of antimicrobial therapy was 22 hours for FilmArray and 72 hours for culture. Patients diagnosed by FilmArray were more likely to receive targeted rather than empirical therapy, compared to those diagnosed by culture (P = .0148). Positive Shiga-like toxin-producing E. coli results were reported 47 hours faster with FilmArray and facilitated discontinuation of empirical antimicrobials. Patients diagnosed exclusively by FilmArray had clinical characteristics similar to those identified by culture.

Conclusions

FilmArray markedly improved clinical sensitivity in patients with acute diarrhea, identified cases with clinical acuity comparable to those identified by culture, and enabled clinicians to make more timely and targeted therapeutic decisions.
Affine Wreath Product Algebras
Authors: Savage Alistair
Published: April 2018

We study the structure and representation theory of affine wreath product algebras and their cyclotomic quotients. These algebras, which appear naturally in Heisenberg categorification, simultaneously unify and generalize many important algebras appearing in the literature. In particular, special cases include degenerate affine Hecke algebras, affine Sergeev algebras (degenerate affine Hecke–Clifford algebras), and wreath Hecke algebras. In some cases, specializing the results of the current paper recovers known results, but with unified and simplified proofs. In other cases, we obtain new results, including proofs of two open conjectures of Kleshchev and Muth.
Prognosis vs Treatment Interaction
Authors: Cuzick Jack
Published: April 2018

There is a somewhat confused belief that a biomarker must show an interaction effect with a treatment before it can be used to determine the need for such a treatment. This is rarely true for well-established clinical markers such as tumor size or regional lymph node involvement. In many cases, this is also not true for biomarkers, especially when considering nontargeted therapies. Here I argue that for nontargeted treatments prognosis is often more important than interaction with treatment, because it is the absolute and not the relative benefit that matters, and when there is no treatment interaction, the same relative benefit translates into a larger absolute benefit for poor prognosis patients.
Preventable Diabetic Complications After a Cancer Diagnosis in Patients With Diabetes: A Population-Based Cohort Study
Authors: Worndl Erin , Fung Kinwah , Fischer Hadas D , Austin Peter C , Krzyzanowska Monika K , Lipscombe Lorraine L
Published: April 2018

Background

A cancer diagnosis may disrupt diabetes management, increasing the risk of preventable complications. The objective was to determine whether a cancer diagnosis in patients with diabetes is associated with an increased risk of diabetic complications.

Methods

This retrospective cohort study using health care data from Ontario, Canada, included persons age 50 years or older diagnosed with diabetes from 2007 to 2011 and followed until 2014. We examined the effects of cancer as a time-varying covariate: breast cancer (in women), prostate cancer (in men), colorectal cancer, and other cancers (in men and women). Each cancer exposure was categorized as stage I–III, IV, or unknown, and by time since cancer diagnosis (0–1 year, >1–3 years, and >3 years). The primary outcome was hospital visits for diabetic emergencies. Secondary outcomes were hospital visits for skin and soft tissue infections and cardiovascular events.

Results

Of 817 060 patients with diabetes (mean age = 64.9 +/- 10.7 years), there were 9759 (1.2%) colorectal and 45 705 (5.6%) other cancers, 6714 (1.7%) breast cancers among 384 257 women and 10 331 (2.4%) prostate cancers among 432 803 men. For all cancers except stage I–III prostate cancer, rates of diabetic complications were significantly higher zero years to one year after diagnosis compared with no cancer (adjusted relative rates ranging from 1.26, 95% confidence interval [CI] = 1.08 to 1.49, to 4.07, 95% CI = 3.80 to 4.36); these differences were attenuated in the subsequent periods after cancer diagnosis.

Conclusions

Patients with diabetes are at increased risk for preventable complications after a cancer diagnosis. Better diabetes care is needed during this vulnerable period.
The Association Between Dietary Quality and Overall and Cancer-Specific Mortality Among Cancer Survivors, NHANES III
Authors: Deshmukh Ashish A , Shirvani Shervin M , Likhacheva Anna , Chhatwal Jagpreet , Chiao Elizabeth Y , Sonawane Kalyani
Published: April 2018

Given the recent emphasis on the totality of the diet by national guidelines, we examined the relationship between the quality of diet and overall and cancer-specific mortality among cancer survivors. From the Third National Health and Nutrition Examination Survey (NHANES III), 1191 participants diagnosed with cancer were identified. Healthy Eating Index (HEI) scores were utilized; higher HEI score indicated better adherence to dietary recommendations. During a median follow-up of 17.2 years, a total of 607 cancer-specific deaths occurred. A high-quality diet (highest-quartile HEI score) was associated with decreased risk of overall (hazard ratio [HR] = 0.59, 95% confidence interval [CI] = 0.45 to 0.77) and cancer-specific (HR = 0.35, 95% CI = 0.19 to 0.63) mortality when compared with a poor-quality diet (lowest-quartile HEI score). Among individual dietary components, the highest-quartile score for saturated fat intake was associated decreased cancer-specific mortality (HR = 0.55, 95% CI = 0.36 to 0.86). Our results highlight the importance of a “total diet” approach to improving survival among cancer patients.
The spin-down state change and mode change associated with glitch activity of PSR B2035+36
Authors: Kou F F , Yuan J P , Wang N , Yan W M , Dang S J
Published: April 2018

We presented timing results of PSR B2035+36 using ∼9-yr observations with the Nanshan 25-m radio telescope. PSR B2035+36 was reported to exhibit significant changes in pulse profile correlated with spin-down state variations. We found that the pulsar underwent a glitch with a jump in frequency of $\Delta {\nu }\sim 12.4(5)\, \rm nHz$ around MJD 52950. Unusually, the spin-down rate increased persistently over 800 d after the glitch, and the average spin-down rate post-glitch was about $9.6 \, {per\,cent}$ larger than that pre-glitch. After the glitch activity, the pulse profile became narrower and the pulsar began to switch between two emission modes, with pulse widths ($W_{\ 50 \rm mean}$) of 8.5(7)° and 3.7(3)°, respectively. In addition to that, the relatively narrow pulse profile gradually became dominant. All of the observations indicate that there should be a connection between magnetospheric behaviour and glitch activity. We discuss one possibility of magnetosphere fluctuation triggered by the glitch event.
Informational needs of brain metastases patients and their
caregivers
Authors: Papadakos Janet , Agarwal Arnav , Charow Rebecca , Quartey Naa Kwarley , D’souza Anna , Giuliani Meredith , Millar Barbara-Ann , Massey Christine , Shultz David , Chung Caroline
Published: April 2018

Background

In response to a dearth of formal health information targeted towards patients with brain metastases and their caregivers, a formal informational and supportive care needs assessment was conducted.

Methods

Brain metastases patients and caregivers who attended a clinic focused on the treatment of brain metastases at a tertiary medical center completed a self-report survey to assess informational needs across 6 domains: medical, physical, practical, social, emotional, and spiritual informational needs. Univariate and multivariate analyses of associations between variables was conducted using linear regression models.

Results

A total of 109 patients and 77 caregivers participated. Patients and caregivers both prioritized medical and physical informational domains, with a large focus on symptoms and side-effect profiles, significance of brain metastases locations and their implications, available treatment options and their risks and benefits, prognoses and follow-ups if treatment is completed, and end-of-life experiences and supports. One-on-one counseling was preferred by both caregivers and patients for these domains, as well as for practical informational needs; while patients preferred pamphlets to address social, emotional and spiritual informational needs, caregivers preferred one-on-one counseling for the former two domains as well.

Conclusions

Brain metastases patients and their caregivers prioritize medical and physical informational needs, with one-on-one counseling and pamphlets being the most preferred modalities for information provision. Further exploration regarding existing non-validated resources and the development of tailored resources to address the unique needs of these patient and caregiver populations are warranted.
Smoking, Systemic Inflammation, and Airflow Limitation: A Mendelian Randomization Analysis of 98 085 Individuals From the General Population
Authors: Çolak Yunus , Afzal Shoaib , Lange Peter , Nordestgaard Børge G
Published: April 2018

Introduction

Smoking is associated with systemic and local inflammation in the lungs. Furthermore, in chronic obstructive pulmonary disease, which is often caused by smoking, there is often systemic inflammation that is linked to lung function impairment. However, the causal pathways linking smoking, systemic inflammation, and airflow limitation are still unknown. We tested whether higher tobacco consumption is associated with higher systemic inflammation, observationally and genetically and whether genetically higher systemic inflammation is associated with airflow limitation.

Methods

We included 98 085 individuals aged 20–100 years from the Copenhagen General Population Study; 36589 were former smokers and 16172 were current smokers. CHRNA3 rs1051730 genotype was used as a proxy for higher tobacco consumption and the IL6R rs2228145 genotype was used for higher systemic inflammation. Airflow limitation was defined as forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <70%.

Results

Difference in plasma level of C-reactive protein was 4.8% (95% CI = 4.4% to 5.2%) per 10 pack-year increase and 1.6% (95% CI = 0.4% to 2.8%) per T allele. Corresponding differences were 1.2% (95% CI = 1.1% to 1.3%) and 0.5% (95% CI = 0.3% to 0.8%) for fibrinogen, 1.2% (95% CI = 1.2% to 1.3%) and 0.7% (95% CI = 0.5% to 1.0%) for α1-antitrypsin, 2.0% (95% CI = 1.8% to 2.1%) and 0.7% (95% CI = 0.4% to 1.1%) for leukocytes, 1.9% (95% CI = 1.8% to 2.1%) and 0.8% (95% CI = 0.4% to 1.2%) for neutrophils, and 0.8% (95% CI = 0.7% to 1.0%) and 0.4% (95% CI = 0.1% to 0.7%) for thrombocytes. The differences in these levels were lower for former smokers compared with current smokers. The IL6R rs2228145 genotype was associated with higher plasma acute-phase reactants but not with airflow limitation. Compared with the C/C genotype, the odds ratio for airflow limitation was 0.95 (95% CI = 0.89 to 1.02) for A/C genotype and 0.94 (95% CI = 0.87 to 1.01) for A/A genotype.

Conclusions

Higher tobacco consumption is associated with higher systemic inflammation both genetically and observationally, whereas systemic inflammation was not associated with airflow limitation genetically.

Implications

The association between higher tobacco consumption and higher systemic inflammation may be causal, and the association is stronger among current smokers compared to former smokers, indicating that smoking cessation may reduce the effects of smoking on systemic inflammation. Systemic inflammation does not seem to be a causal driver in development of airflow limitation. These findings can help to understand the pathogenic effects of smoking and the interplay between smoking, systemic inflammation, and airflow limitation and hence development and progression of chronic obstructive pulmonary disease.
Incidental Findings on Coronary Computed Tomography Angiography in Human Immunodeficiency Virus (HIV)-Positive and HIV-Negative Persons
Authors: Reinschmidt Sara , Turk Teja , Tarr Philip E , Kouyos Roger , Hauser Christoph , Schmid Patrick , Weber Rainer , Kaufmann Philipp , Buechel Ronny R , Kovari Helen ,   Swiss HIV Cohort Study, Anagnostopoulos A , Battegay M , Bernasconi E , Böni J , Braun D L , Bucher H C , Calmy A , Cavassini M , Ciuffi A , Dollenmaier G , Egger M , Elzi L , Fehr J , Fellay J , Furrer H , Fux C A , Günthard H F , Haerry D , Hasse B , Hirsch H H , Hoffmann M , Hösli I , Huber M , Kahlert C , Kaiser L , Keiser O , Klimkait T , Kouyos R D , Kovari H , Ledergerber B , Martinetti G , Martinez de Tejada B , Marzolini C , Metzner K J , Müller N , Nicca D , Paioni P , Pantaleo G , Perreau M , Rauch A , Rudin C , Scherrer A U , Schmid P , Speck R , Stöckle M , Tarr P , Trkola A , Vernazza P , Wandeler G , Weber R , Yerly S
Published: April 2018

Background

Incidental findings on coronary computed tomography angiography (CCTA) have a great impact on the benefits and costs of testing for cardiovascular disease. The number of incidental findings might be increased in human immunodeficiency virus (HIV)-positive individuals compared with the general population. Data are limited regarding the association between incidental findings and HIV infection.

Methods

We assessed the prevalence and factors associated with incidental findings among HIV-positive and HIV-negative participants ≥45 years undergoing CCTA. Logistic regression was performed to evaluate the factors associated with incidental findings in the HIV-positive and HIV-negative groups. For the analysis of the HIV effect, a propensity score-matched dataset of HIV-positive/HIV-negative participants was used.

Results

We included 553 participants, 341 with and 212 without HIV infection. Incidental findings were observed in 291 of 553 (53%) patients. In 42 of 553 (7.6%) participants, an incidental finding resulted in additional workup. A malignancy was diagnosed in 2 persons. In the HIV-positive group, age (1.31 per 5 years, 1.10–1.56) and smoking (2.29, 1.43–3.70) were associated with incidental findings; in the HIV-negative group, age (1.26, 1.01–1.59) and a CAC score >0 (2.08, 1.09–4.02) were associated with incidental findings. Human immunodeficiency virus seropositivity did not affect the risk of incidental findings.

Conclusions

Incidental findings were highly prevalent among HIV-positive and HIV-negative persons. Human immunodeficiency virus infection was not associated with an increased risk of incidental findings.