bluuebunny/crossref_metadata_2025 huggingface dataset:
Increased coronary heart disease and stroke hospitalisations from ambient temperatures in Ontario
Authors: Bai Li , Li Qiongsi , Wang Jun , Lavigne Eric , Gasparrini Antonio , Copes Ray , Yagouti Abderrahmane , Burnett Richard T , Goldberg Mark S , Cakmak Sabit , Chen Hong
Published: November 2017

Objective

To assess the associations between ambient temperatures and hospitalisations for coronary heart disease (CHD) and stroke.

Methods

Our study comprised all residents living in Ontario, Canada, 1996–2013. For each of 14 health regions, we fitted a distributed lag non-linear model to estimate the cold and heat effects on hospitalisations from CHD, acute myocardial infarction (AMI), stroke and ischaemic stroke, respectively. These effects were pooled using a multivariate meta-analysis. We computed attributable hospitalisations for cold and heat, defined as temperatures above and below the optimum temperature (corresponding to the temperature of minimum morbidity) and for moderate and extreme temperatures, defined using cut-offs at the 2.5th and 97.5th temperature percentiles.

Results

Between 1996 and 2013, we identified 1.4 million hospitalisations from CHD and 355 837 from stroke across Ontario. On cold days with temperature corresponding to the 1st percentile of temperature distribution, we found a 9% increase in daily hospitalisations for CHD (95% CI 1% to 16%), 29% increase for AMI (95% CI 15% to 45%) and 11% increase for stroke (95% CI 1% to 22%) relative to days with an optimal temperature. High temperatures (the 99th percentile) also increased CHD hospitalisations by 6% (95% CI 1% to 11%) relative to the optimal temperature. These estimates translate into 2.49% of CHD hospitalisations attributable to cold and 1.20% from heat. Additionally, 1.71% of stroke hospitalisations were attributable to cold. Importantly, moderate temperatures, rather than extreme temperatures, yielded the most of the cardiovascular burdens from temperatures.

Conclusions

Ambient temperatures, especially in moderate ranges, may be an important risk factor for cardiovascular-related hospitalisations.
Biomarkers of cardiovascular stress and fibrosis in preclinical hypertrophic cardiomyopathy
Authors: Ho Jennifer E , Shi Ling , Day Sharlene M , Colan Steven D , Russell Mark W , Towbin Jeffrey A , Sherrid Mark V , Canter Charles E , Jefferies John Lynn , Murphy Anne , Taylor Matthew , Mestroni Luisa , Cirino Allison L , Sleeper Lynn A , Jarolim Peter , Lopez Begoña , Gonzalez Arantxa , Diez Javier , Orav E John , Ho Carolyn Y
Published: November 2017

Objective

Sarcomeric gene mutation carriers without overt left ventricular hypertrophy (G+/LVH−) can harbour subclinical changes in cardiovascular structure and function that precede the development of hypertrophic cardiomyopathy (HCM). We sought to investigate if circulating biomarkers of cardiovascular stress and collagen metabolism among G+/LVH− individuals, measured at rest and following exercise provocation, yield further insights into the underlying biology of HCM.

Methods

We studied 76 individuals with overt HCM, 50 G+/LVH− individuals and 41 genotype-negative related controls enrolled in a cross-sectional, multicentre observational study (HCMNet). Biomarkers of cardiac stress (N-terminal pro-B-type natriuretic peptide, NT-proBNP; high-sensitivity troponin I, hsTnI; soluble ST2) and fibrosis (carboxy-terminal propeptide of procollagen type I; C-terminal telopeptide of type I collagen; galectin-3; periostin) were measured.

Results

Individuals with overt HCM had elevated NT-proBNP and hsTnI compared with G+/LVH− subjects and controls at rest, along with an exaggerated increase in NT-proBNP and hsTnI in response to exercise. We found no detectable differences in resting or exercise-provoked biomarker profiles of cardiovascular stress and fibrosis among G+/LVH− individuals compared with healthy controls despite subtle echocardiographic differences in cardiac structure and function.

Conclusion

Dynamic exercise testing exaggerated resting differences in natriuretic peptides and troponin elevations among individuals with overt HCM. In contrast, we found no differences in biomarker profiles of cardiovascular stress and fibrosis among G+/LVH− individuals compared with controls even after maximal exercise provocation. Our findings highlight the need for continued investigation into early phenotypes of sarcomeric gene mutations and the evolution of HCM.
Lupus myelopathy
Authors: Raciborska Dominika D , Noyce Alastair John , Pyne Dev , Turner Benjamin P
Published: November 2017

Although neurological manifestations of systemic lupus erythematosus (SLE) are well recognised, myelopathy complicating SLE is rare. A 35-year-old woman presented with non-specific symptoms and a respiratory tract infection but had serological evidence of SLE. She subsequently deteriorated rapidly, developing a catastrophic spinal cord syndrome. Her initial MRI was normal; but after 1 month, her encephalopathy having progressed, repeat imaging showed characteristic myelitic changes. She responded only slowly to a combination of cyclophosphamide and corticosteroids. This case exemplifies the mixed presentations of SLE, including the under-recognised ‘subpial leukomyelopathy’ of central nervous system lupus. It highlights the challenges in managing lupus-related myelopathy and the benefits of a multidisciplinary approach to care.
High-fat, simple-carbohydrate diet intake induces hypothalamic–pituitary–thyroid axis dysregulation in C57BL/6J male mice
Authors: Swarnalatha Nagaraj Banavara , Roy Neena , Gouda Mahesh Manjunath , Moger Rajeish , Abraham Asha
Published: November 2017

Given the association between subclinical hypothyroidism and metabolic syndrome, we wanted to explore if high-fat, simple-carbohydrate (HFSC) diet affects hypothalamus–pituitary–thyroid axis. One-month-old male C57BL/6J mice were fed with control (C) and HFSC (T) feed (n = 18 each), respectively, for 5 months. There was a significant increase in triiodothyronine in the T group (13.5%) compared with the age-matched C group by the fifth month. Thyroid-stimulating hormone was significantly higher (1 month: 1.9-fold; 3 months: 2.66-fold; 5 months: 3.5-fold) from the first to fifth months in the T group compared with age-matched C group. Thyrotropin-releasing hormone (TRH) gene expression showed significant decrease (1 month: 83.2%; 5 months: 40.7%) in the T group compared with the age-matched C group. TRHR1 showed significant decrease in the T group compared with the age-matched C group throughout the study (1 month: 82.8%; 3 months: 45.7%; 5 months: 75.2%). However, TRHR2 showed dynamic change during the study. Initially there was significant (1 month: 0.104-fold) downregulation, followed by significant upregulation (3 months: 3.6-fold) and downregulation (0.73-fold) by the fifth month in the T group compared with the age-matched C group. There was marked depletion of functional follicular cells and colloid substance in the thyroid glands of the T group by the fifth month compared with the C group. Leptin receptors ObRa (1 month: 48.25%; 5 months: 88%) and ObRb (1 month: 46.9%; 5 months: 63.3%) were significantly downregulated in the T group compared with the age-matched C group in the first and fifth months of feeding the respective diets. The expression of p-STAT3, a transcription factor known to have a role in energy balance, intermediate metabolism, and leptin signalling was seen to decrease significantly (6.25-fold) in the hypothalamus of the T group compared with the age-matched C group. In conclusion, HFSC feed disrupts the hypothalamus–pituitary–thyroid axis in male C57BL/6J mice.
Numerical study for nonlinear radiative peristaltic flow in a rotating frame
Authors: Zahir H. , Hayat T. , Alsaedi A. , Ahmad B.
Published: November 2017

Peristaltic flow of third-grade fluid in a tapered asymmetric channel is discussed. The whole system is considered in a rotating frame. Unlike the traditional situation, the nonlinear version of thermal radiation is invoked. The resulting problems are solved numerically. Comparative study between rotating and inertial frames is presented. The results of velocity, temperature, and heat transfer rate are analyzed for different parameters of interest.
A model of mesons in finite extra-dimension
Authors: Lahkar Jugal , Choudhury D.K. , Roy S. , Bordoloi N.S.
Published: November 2017

Recently, the problem of stability of the H atom has been reported in extra-finite dimension, and found out that it is stable in extra-finite dimension of size R ≤ a0/4, where a0 is the Bohr radius. Assuming that heavy flavoured mesons also have such stability controlled by the scale of the coupling constant, we obtain corresponding QCD Bohr radius, and it is found to be well within the present theoretical and experimental limit of higher dimension. We then study its consequences in their masses using effective string-inspired potential model in higher dimension. Our analysis suggests that an extra-dimension of size 0.007 × 10−15 m ≤ L ≤ 0.13 × 10−15 m can account for the masses of heavy flavoured mesons under study within their experimental uncertainty without confinement effects. This range is well below the present theoretical and experimental limits on the size of extra-dimension.
On the algebraic quantization of a massive scalar field in anti-de Sitter spacetime
Authors: Dappiaggi Claudio , Ferreira Hugo R. C.
Published: November 2017

We discuss the algebraic quantization of a real, massive scalar field in the Poincaré patch of the [Formula: see text]-dimensional anti-de Sitter spacetime, with arbitrary boundary conditions. By using the functional formalism, we show that it is always possible to associate to such system an algebra of observables enjoying the standard properties of causality, time-slice axiom and F-locality. In addition, we characterize the wavefront set of the ground state associated to the system under investigation. As a consequence, we are able to generalize the definition of Hadamard states and construct a global algebra of Wick polynomials.
On the asymptotic expansions of the Kashaev invariant of hyperbolic knots with seven crossings
Authors: Ohtsuki Tomotada
Published: November 2017

We give presentations of the asymptotic expansions of the Kashaev invariant of hyperbolic knots with seven crossings. As the volume conjecture states, the leading terms of the expansions present the hyperbolic volume and the Chern–Simons invariant of the complements of the knots. As coefficients of the expansions, we obtain a series of new invariants of the knots. This paper is a continuation of the previous papers [T. Ohtsuki, On the asymptotic expansion of the Kashaev invariant of the [Formula: see text] knot, Quantum Topol. 7 (2016) 669–735; T. Ohtsuki and Y. Yokota, On the asymptotic expansion of the Kashaev invariant of the knots with 6 crossings, to appear in Math. Proc. Cambridge Philos. Soc.], where the asymptotic expansions of the Kashaev invariant are calculated for hyperbolic knots with five and six crossings. A technical difficulty of this paper is to use 4-variable saddle point method, whose concrete calculations are far more complicated than the previous papers.
NOT ALL GOODS ARE CREATED EQUAL: TARIFF CONCESSIONS IN THE KOREA–CHINA FREE TRADE AGREEMENT
Authors: IM HYEJOON
Published: November 2017

In this paper, we use a multinomial logit model and identify the important factors in determining the staging categories of Korean tariff concessions in the Korea–China free trade agreement (FTA). We find that most-favored-nation (MFN) tariff rates and whether a product is agricultural or not are the most influential determinants of tariff concessions in the FTA. The results also show that the effects of the determinants are heterogeneous over industries: the influence of the Chinese import share is more pronounced for agricultural products than for manufactured goods, while that of MFN tariffs is less prominent for agricultural products. The latter result implies that quite a few Korean agricultural products are heavily protected in the FTA, despite their relatively low MFN rates.
Inflation versus collapse in brane matter
Authors: Zheltukhin A. A.
Published: November 2017

Mapping of fundamental branes to their worldsheet (ws) multiplets originating from spontaneous breaking of the Poincaré symmetry is studied. The interaction Lagrangian for fields of the Nambu–Goldstone multiplet is shown to encode [Formula: see text] gravity on the ws. The power law [Formula: see text] for the [Formula: see text] gauge coupling [Formula: see text] as the function of the [Formula: see text]-brane tension [Formula: see text] is assumed. It points to the presence of asymptotic freedom and confinement phases in brane matter. Their connection with collapse and inflation of the branes is discussed.
Do event horizons exist?
Authors: Baccetti Valentina , Mann Robert B. , Terno Daniel R.
Published: November 2017

Event horizons are the defining feature of classical black holes. They are the key ingredient of the information loss paradox which, as paradoxes in quantum foundations, is built on a combination of predictions of quantum theory and counterfactual classical features: neither horizon formation nor its crossing by a test body can be detected by a distant observer. Furthermore, horizons are unnecessary for the production of Hawking-like radiation. We demonstrate that when this radiation is taken into account, it can prevent horizon crossing/formation in a large class of models. We conjecture that horizon avoidance is a general feature of collapse. The nonexistence of event horizons dispels the paradox, but opens up important questions about thermodynamic properties of the resulting objects and correlations between different degrees of freedom.
Measuring the effects of loop quantum cosmology in the CMB data
Authors: Basilakos Spyros , Kamali Vahid , Mehrabi Ahmad
Published: November 2017

In this paper we investigate the observational signatures of Loop Quantum Cosmology (LQC) in the CMB data. First, we concentrate on the dynamics of LQC and we provide the basic cosmological functions. We then obtain the power spectrum of scalar and tensor perturbations in order to study the performance of LQC against the latest CMB data. We find that LQC provides a robust prediction for the main slow-roll parameters, like the scalar spectral index and the tensor-to-scalar fluctuation ratio, which are in excellent agreement within [Formula: see text] with the values recently measured by the Planck collaboration. This result indicates that LQC can be seen as an alternative scenario with respect to that of standard inflation.
Gravity, stability and cosmological models
Authors: Yahalom Asher
Published: November 2017

Stability analysis plays a major rule in our understanding of nature. For example it was shown that among empty flat spacetimes only those with a Lorentzian metric are stable [A. Yahalom, Found Phys. 38 (2008) 489–497; Int. J. Mod. Phys. D 18(4) (2009) 2155–2158]. However, the universe is not empty and the energy momentum tensor is metric dependent an thus effects stability. In this essay we concentrate on simple perturbations of the standard cosmological model with and without cosmological constant which is based on a uniform mass distribution. The results suggest that while Euclidean, open or closed section models are valid solutions, the choice of stable solutions is limited. In particular, the popular Lambda-CDM model is unstable.
Discrete duality for De Morgan Algebras with operators
Authors: Gregori Verónica
Published: November 2017

A discrete duality is a relationship between classes of algebras and classes of relational systems (frames). In this paper, discrete dualities are presented for De Morgan algebras with various kind of unary operators. To do this, we will extend the discrete duality given in [W. Dzik, E. Orłowska and C. van Alten, Relational representation theorems for general lattices with negations, in Relations and Kleene Algebra in Computer Science, Lecture Notes in Computer Science, Vol. 4136 (Springer, Berlin, 2006), pp. 162–176], for De Morgan algebras.
Superconcentrated aqueous electrolyte to enhance energy density for advanced supercapacitors
Authors: Tian Zengying , Deng Wenjun , Wang Xusheng , Liu Chunyi , Li Chang , Chen Jitao , Xue Mianqi , Li Rui , Pan Feng
Published: November 2017

We here report a superconcentrated potassium acetate (KAC) solution (75[Formula: see text]wt.%, K : H2O [Formula: see text] 1 : 1.8, called as “water-in-salt”) as an aqueous electrolyte to improve the working voltage and increasing capacitance in enhancing the energy density of the active carbon-based aqueous supercapacitor. The stability potential window of the superconcentrated electrolyte realizes an AC//AC symmetric supercapacitor with operating voltage of 2.0 V and excellent cyclic performance. Meanwhile, the energy density of such supercapacitor achieves about twice as high as that of the supercapacitor using normal concentration of electrolyte.
Sol–gel synthesis of erbium-doped ZnO with nest structure for photocatalysis
Authors: Li Chun , Yan Zuoyun , Zhou Yuan , Zhao Shuang , Zhang Xiaotao , Sheng Xianliang
Published: November 2017

Rare earth erbium-doped ZnO samples were synthesized via a facile sol–gel method. The influences of Er-doping on structural properties, morphological features and optical properties were characterized by XRD, BET, SEM and UV–Vis DRS techniques. The results showed that the as-synthesized products were well crystallined in the absence of impurity phases and Er-doping resulted in the reduction of bandgap energy deducted from the UV–Vis DRS results. Amongst the samples, layer-like 0.5% Er-doped ZnO with nest structure achieved the highest photodegradation (90.7%) of methylene blue (MB) after UV light irradiation for 2[Formula: see text]h. The kinetic studies of MB degradation over different Er-doped ZnO were also conducted and proved to obey the pseudo-first-order kinetics.
Spectra of the generalized edge corona of graphs
Authors: Luo Yanyan , Yan Weigen
Published: November 2017

Let [Formula: see text] be a simple graph with [Formula: see text] edges and [Formula: see text], [Formula: see text] be [Formula: see text] simple graphs. The generalized edge corona, denoted by [Formula: see text], is the graph obtained by taking one copy of graphs [Formula: see text], [Formula: see text], [Formula: see text] and then joining two end-vertices of the [Formula: see text]th edge [Formula: see text] of [Formula: see text] to every vertex of [Formula: see text] for [Formula: see text]. In this paper, we determine and study the characteristic polynomial, Laplacian polynomial and signless Laplacian polynomial of [Formula: see text]. As an application, we also count the number of spanning trees of the generalized edge corona.
Requiring adjacent chords in cycles
Authors: McKee Terry A.
Published: November 2017

Define a new class of graphs by cycles of length 5 or more always having adjacent chords. This is equivalent to cycles of length 5 or more always having noncrossing chords, which is a property that has a known forbidden induced subgraph characterization. Another characterization comes from viewing the graphs in this class in contrast to distance-hereditary graphs (which are characterized by cycles of length 5 or more always having crossing chords). Moreover, the graphs in the new class are those in which every edge of every cycle [Formula: see text] of length 5 or more forms a triangle with a third vertex of [Formula: see text] (generalizing that a graph is chordal if and only if every edge of every cycle [Formula: see text] of length 4 or more forms a triangle with a third vertex of [Formula: see text]). This leads to a strategically-required subgraph characterization of the new class.
An Emotion Cause Corpus for Chinese Microblogs with Multiple-User Structures
Authors: Cheng Xiyao , Chen Ying , Cheng Bixiao , Li Shoushan , Zhou Guodong
Published: November 2017

A notably challenging problem in emotion analysis is recognizing the cause of an emotion. Although there have been a few studies on emotion cause detection, most of them work on news reports or a few of them focus on microblogs using a single-user structure (i.e., all texts in a microblog are written by the same user). In this article, we focus on emotion cause detection for Chinese microblogs using a multiple-user structure (i.e., texts in a microblog are successively written by several users). First, based on the fact that the causes of an emotion of a focused user may be provided by other users in a microblog with the multiple-user structure, we design an emotion cause annotation scheme which can deal with such a complicated case, and then provide an emotion cause corpus using the annotation scheme. Second, based on the analysis of the emotion cause corpus, we formalize two emotion cause detection tasks for microblogs (current-subtweet-based emotion cause detection and original-subtweet-based emotion cause detection). Furthermore, in order to examine the difficulty of the two emotion cause detection tasks and the contributions of texts written by different users in a microblog with the multiple-user structure, we choose two popular classification methods (SVM and LSTM) to do emotion cause detection. Our experiments show that the current-subtweet-based emotion cause detection is much more difficult than the original-subtweet-based emotion cause detection, and texts written by different users are very helpful for both emotion cause detection tasks. This study presents a pilot study of emotion cause detection which deals with Chinese microblogs using a complicated structure.
Cleaning of Online Bangla Free-form Handwritten Text
Authors: Bhattacharya Nilanjana , Pal Umapada , Roy Partha Pratim
Published: November 2017

In the normal free-form handwritten text, repetition (repeated writing of the same stroke several times in the same place), over-writing, and crossing out are very common. In this article, we call the presence of these three types of writing as “noise.” Cleaning to extract useful text from such types of noisy text is an important task for robust recognition. To the best of our knowledge, no work has been reported on cleaning of such noise from online text in any scripts and hence, in this article, we propose an automatic text-cleaning approach for online handwriting recognition. Here, at first, crossing out noise with straight strike-through lines is detected using the straightness criteria of online strokes. Next, regions containing repetition, over-writing, and other types of crossing out are located using the positional information of the overlapping strokes. Stroke density, self-intersections of strokes etc. are computed from the strokes of located regions to predict the type of noise and this type of information is used as follows for their cleaning. For cleaning of crossing outs, all strokes of the crossing-out region are removed. For cleaning repetition and over-writing, strokes written earlier are removed, keeping the latest strokes. Finally, delayed strokes are properly arranged and word is passed to online recognizer. Though recognition of free-form handwriting is quite difficult, in this attempt, we obtained up to 70.71% improvement in word-recognition accuracy after noise cleaning.
Restricting the Use of Solitary Confinement
Authors: Haney Craig
Published: November 2017

A robust scientific literature has established the negative psychological effects of solitary confinement. The empirical findings are supported by a theoretical framework that underscores the importance of social contact to psychological as well as physical well-being. In essence, human beings have a basic need to establish and maintain connections to others and the deprivation of opportunities to do so has a range of deleterious consequences. These scientific conclusions, as well as concerns about the high cost and lack of any demonstrated penological purpose that solitary confinement reliably serves, have led to an emerging consensus among correctional as well as professional, mental health, legal, and human rights organizations to drastically limit the practice.
Preparation of Dicalcium Phosphate Anhydrous (Monetite) Biological Coating on Titanium by Spray-Drying Method
Authors: Shi Xingling , Zhao Chao , Xu Lingli , Wang Qingliang
Published: November 2017

Titanium and its alloys have been widely used in the manufacture of endosseous implants due to excellent biocompatibility, low elastic modulus, and good chemical stability. However, the titanium based metals are essentially bioinert materials. In order to improve their bioactivity, biological coatings are usually applied. Recent studies found that, compared with hydroxyapatite coating, dicalcium phosphate anhydrous (DCPA, Monetite) coating maybe more bioactive due to higher solubility and release of Ca and P ions. In this work, DCPA coating was prepared through a novel and simple method. Briefly, high concentration DCPA solution was sprayed onto superhydrophilic titanium and the specimens were dried fast in an air-circulating oven. After repeating the process over 100 times, a compact coating was fabricated. The microstructure, chemical composition, wettability, and in vitro bioactivity of the coating were analyzed and evaluated. Results showed that the coating fully covered the substrate and consisted of a large number of uniformly sized DCPA granules that packed together closely. The coating showed good wettability and could keep the property for a long time. After immersion in simulated body fluid for 2 weeks, a large amount of bone-like apatite with low crystallinity was induced implying a good bioactivity.
Proteobacteria: A Common Factor in Human Diseases
Authors: Rizzatti G. , Lopetuso L. R. , Gibiino G. , Binda C. , Gasbarrini A.
Published: November 2017

Microbiota represents the entire microbial community present in the gut host. It serves several functions establishing a mutualistic relation with the host. Latest years have seen a burst in the number of studies focusing on this topic, in particular on intestinal diseases. In this scenario, Proteobacteria are one of the most abundant phyla, comprising several known human pathogens. This review highlights the latest findings on the role of Proteobacteria not only in intestinal but also in extraintestinal diseases. Indeed, an increasing amount of data identifies Proteobacteria as a possible microbial signature of disease. Several studies demonstrate an increased abundance of members belonging to this phylum in such conditions. Major evidences currently involve metabolic disorders and inflammatory bowel disease. However, more recent studies suggest a role also in lung diseases, such as asthma and chronic obstructive pulmonary disease, but evidences are still scant. Notably, all these conditions are sustained by various degree of inflammation, which thus represents a core aspect of Proteobacteria-related diseases.
Experiment on Seepage Property and Sand Inrush Criterion for Granular Rock Mass
Authors: Zhang Kai , Zhang Boyang , Liu Jiangfeng , Ma Dan , Bai Haibo
Published: November 2017

Water and sand inrush is one of the most serious threats in some shallow coal mines in China. In order to understand the process of sand inrush, experiments were performed to obtain the criterion for sand inrush. First, seepage tests were carried out to study the hydraulic properties of granular sandstone. The results indicate that seepage velocity has a linear relation with the porosity and particle-size distribution parameter. Then, sand inrush tests were conducted to investigate the critical conditions for sand inrush occurrence. It is determined that the sand inrush zone can be clearly distinguished based on the values of porosity and particle-size distribution parameter. Additionally, sand inrush tended to happen in the conditions of high porosity, high seepage velocity, and large particle-size distribution parameter. Further, general principles for preventing the water and sand inrush were proposed, such as reducing the porosity, improving the pore structure, and decreasing the seepage velocity. The proposed principles have been successfully used in situ to control the water and sand inrush.
The Phenomena of Naturopathic Practitioner: Predictors of a High Patient Throughput
Authors: Goetz Katja , Kattge Stefanie , Steinhäuser Jost
Published: November 2017

Objective. The aim of the current study was to evaluate which factors predicted a high patient throughput to add more evidence to the phenomena of naturopathic practitioners. Methods. The cross‐sectional study was based on a questionnaire with a sample of 1,096 naturopathic practitioners in the German Federal State of Schleswig‐Holstein. Besides, sociodemographic data and practice characteristics topics like job satisfaction and feeling for the job were evaluated. This was supplemented with an evaluation of patient traits which were perceived as challenging. Descriptive statistics and binary regression analysis were computed to identify potential predictors to a high patient throughput. Results. A response rate of 29.4% (322/1096 participants) was observed for the study. In general, our sample of the naturopathic practitioners was very satisfied with their job (mean = 6.38). Naturopathic practitioners described that 40% of their patients are challenging. The highest rate was for “aggressive patients.” A high patient throughput was predicted with a higher satisfaction rate with the “opportunity to use abilities” and more direct contact with the patient. Conclusions. Therapeutic freedom and time with patients are important factors which are accountable for a high patient throughput. Moreover, our study provides evidence for the understanding of the phenomena of naturopathic practitioners.
Differential Expression of Homing Receptor Ligands on Tumor-Associated Vasculature that Control CD8 Effector T-cell Entry
Authors: Woods Amber N. , Wilson Ashley L. , Srivinisan Nithya , Zeng Jianhao , Dutta Arun B. , Peske J. David , Tewalt Eric F. , Gregg Randal K. , Ferguson Andrew R. , Engelhard Victor H.
Published: November 2017

Although CD8+ T cells are critical for controlling tumors, how they are recruited and home to primary and metastatic lesions is incompletely understood. We characterized the homing receptor (HR) ligands on tumor vasculature to determine what drives their expression and their role in T-cell entry. The anatomic location of B16-OVA tumors affected the expression of E-selectin, MadCAM-1, and VCAM-1, whereas the HR ligands CXCL9 and ICAM-1 were expressed on the vasculature regardless of location. VCAM-1 and CXCL9 expression was induced by IFNγ-secreting adaptive immune cells. VCAM-1 and CXCL9/10 enabled CD8+ T-cell effectors expressing α4β1 integrin and CXCR3 to enter both subcutaneous and peritoneal tumors, whereas E-selectin enabled E-selectin ligand+ effectors to enter subcutaneous tumors. However, MadCAM-1 did not mediate α4β7+ effector entry into peritoneal tumors due to an unexpected lack of luminal expression. These data establish the relative importance of certain HRs expressed on activated effectors and certain HR ligands expressed on tumor vasculature in the effective immune control of tumors. Cancer Immunol Res; 5(12); 1062–73. ©2017 AACR.
Cisplatin Alters Antitumor Immunity and Synergizes with PD-1/PD-L1 Inhibition in Head and Neck Squamous Cell Carcinoma
Authors: Tran Linda , Allen Clint T. , Xiao Roy , Moore Ellen , Davis Ruth , Park So-Jin , Spielbauer Katie , Van Waes Carter , Schmitt Nicole C.
Published: November 2017

Head and neck squamous cell carcinoma (HNSCC) has been treated for decades with cisplatin chemotherapy, and anti–PD-1 immunotherapy has recently been approved for the treatment of this disease. However, preclinical studies of how antitumor immunity in HNSCC is affected by cisplatin alone or in combination with immunotherapies are lacking. Here, we show that sublethal doses of cisplatin may enhance antigen presentation and T-cell killing in vitro, though cisplatin also upregulates tumor cell expression of PD-L1 and may impair T-cell function at higher doses. In a syngeneic mouse model of HNSCC, concurrent use of cisplatin and anti–PD-L1/PD-1 delayed tumor growth and enhanced survival without significantly reducing the number or function of tumor-infiltrating immune cells or increasing cisplatin-induced toxicities. These results suggest that moderate doses of cisplatin may enhance antitumor immunity by mechanisms other than direct tumor cell killing, which may be further enhanced by anti–PD-L1/PD-1 therapy. Cancer Immunol Res; 5(12); 1141–51. ©2017 AACR.
Intratumoral CD8+ T-cell Apoptosis Is a Major Component of T-cell Dysfunction and Impedes Antitumor Immunity
Authors: Horton Brendan L. , Williams Jason B. , Cabanov Alexandra , Spranger Stefani , Gajewski Thomas F.
Published: November 2017

Subsets of human tumors are infiltrated with tumor antigen–specific CD8+ T cells [tumor-infiltrating lymphocytes (TILs)] despite tumor progression. These TILs are thought to be inactivated by the immunosuppressive tumor microenvironment, through the engagement of inhibitory receptors such as CTLA-4 and PD-1. However, antigen-specific CD8+ TILs are not functionally inert but are undergoing activation in situ. Here, we show that antigen-specific CD8+ TILs are actively proliferating, yet also undergo high rates of apoptosis, leading to a vicious cycle of activation and death that limits immune efficacy. Preventing CD8+ TIL apoptosis by Bcl-xL overexpression enabled accumulation and improved tumor control. Effective combination immunotherapy with an agonist 4-1BB mAb plus either CTLA-4 or PD-L1 neutralization led to a marked accumulation of specific CD8+ TILs through decreased apoptosis rather than increased T-cell entry or proliferation. Our data suggest that antigen-driven apoptosis of CD8+ TILs is a barrier to effective spontaneous antitumor immunity and should be considered as a critical factor in the development of cancer immunotherapies. Cancer Immunol Res; 6(1); 14–24. ©2017 AACR.
Combination of CD40 Agonism and CSF-1R Blockade Reconditions Tumor-Associated Macrophages and Drives Potent Antitumor Immunity
Authors: Wiehagen Karla R. , Girgis Natasha M. , Yamada Douglas H. , Smith Andressa A. , Chan Szeman Ruby , Grewal Iqbal S. , Quigley Michael , Verona Raluca I.
Published: November 2017

Efficacious antitumor immune responses must overcome multiple suppressive mechanisms in the tumor microenvironment to control cancer progression. In this study, we demonstrate that dual targeting of suppressive myeloid populations by inhibiting CSF-1/CSF-1R signaling and activation of antigen-presenting cells with agonist anti-CD40 treatment confers superior antitumor efficacy and increased survival compared with monotherapy treatment in preclinical tumor models. Concurrent CSF-1R blockade and CD40 agonism lead to profound changes in the composition of immune infiltrates, causing an overall decrease in immunosuppressive cells and a shift toward a more inflammatory milieu. Anti-CD40/anti–CSF-1R–treated tumors contain decreased tumor-associated macrophages and Foxp3+ regulatory T cells. This combination approach increases maturation and differentiation of proinflammatory macrophages and dendritic cells and also drives potent priming of effector T cells in draining lymph nodes. As a result, tumor-infiltrating effector T cells exhibit improved responses to tumor antigen rechallenge. These studies show that combining therapeutic approaches may simultaneously remove inhibitory immune populations and sustain endogenous antitumor immune responses to successfully impair cancer progression. Cancer Immunol Res; 5(12); 1109–21. ©2017 AACR.
Changing Characteristics of Obese Children and Adolescents Entering Pediatric Lifestyle Intervention Programs in Germany over the Last 11 Years: An Adiposity Patients Registry Multicenter Analysis of 65,453 Children and Adolescents
Authors: Bohn Barbara , Wiegand Susanna , Kiess Wieland , Reinehr Thomas , Stachow Rainer , Oepen Johannes , Langhof Helmut , Hermann Thomas , Widhalm Kurt , Wabitsch Martin , Gellhaus Ines , Holl Reinhard ,   for the APV Initiative and the German Competence Network Obesity
Published: November 2017

Objective: To examine whether characteristics of children and adolescents who start lifestyle intervention (LI) for obesity in Germany changed over the last decade. Methods: 65,453 subjects (<21 years) from the APV database (Adiposity Patients Registry) with a BMI ≥ 90th percentile were included (years 2005-2015). Logistic regression models (confounders: age, sex, migration background) were created for overweight, obesity, extreme obesity, and obesity-related comorbidities. Comorbidities were further adjusted for weight category. Results were stratified by inpatient or outpatient care. Results: Extreme obesity was found to be more frequent at the onset of LI (2005: 11.6; 2015: 12.7%) with a similar trend in subgroups (p < 0.001). Obesity increased (2005: 50.3%; 2015: 55.1%), and overweight decreased (2005: 34.1%; 2015: 29.0%) in the whole study population. Trends were similar for inpatient or outpatient care (all p < 0.001). Hypertension increased from 45.7% to 49.2% in the whole study population, and similar data were obtained in the subgroup of inpatients (both p < 0.0001). Dyslipidemia increased in all patients (2005: 21.9%; 2015: 28.0%) and in inpatients (2005: 20.2%; 2015: 25.7%; both p < 0.0001). Abnormal carbohydrate metabolism rose in all patients (from 5.2 to 6.4%; p = 0.0002) without significant trends in subgroups. Conclusion: During the last decade, children and adolescents presented with higher BMI SDS at the onset of LI and the proportion with obesity-related comorbidities increased. Particularly the presence of comorbidities differed between outpatients and inpatients.
Facial Papules in Frontal Fibrosing Alopecia: Beyond Vellus Hair Follicle Involvement
Authors: Pirmez Rodrigo , Barreto Taynara , Duque-Estrada Bruna , Quintella Danielle C. , Cuzzi Tullia
Published: November 2017

Background: Frontal fibrosing alopecia (FFA) is considered a variant of lichen planopilaris affecting mainly the frontotemporal hairline. Since the first report in 1994, several other clinical features have been associated with the disease, such as facial papules (FP). Even though FP have been linked to facial vellus hair follicle involvement, how this finding alone could lead to the formation of clinically evident FP in FFA patients had not yet been addressed. Objective: To describe histopathological findings of FP in the context of FFA and to highlight features that may be linked to their clinical formation. Methods: Cutaneous FP biopsies of FFA patients performed between January 2016 and May 2017 were retrieved from our pathology database and reexamined by 2 pathologists. Results: Histological sections of thirteen 3.0-mm punch biopsy specimens (2 horizontally and 11 vertically oriented) were collected from 7 patients. Eleven specimens demonstrated prominent sebaceous glands and 10 dilated sebaceous ducts. Pinkus acid orcein staining revealed reduction and fragmentation of the elastic fibers in 12 samples and, in 7 of these, this finding was observed in both the papillary and reticular dermis, particularly around sebaceous lobules. Vellus hair follicle involvement was only seen in 2 samples. Conclusions: Prominent sebaceous lobules with dilated ducts associated with an abnormal elastic framework seem to be the main explanation for the formation of FP in the context of FFA.
Exploring Factors Associated with Depression and Anxiety among Hospitalized Patients with Type 2 Diabetes Mellitus
Authors: AlBekairy Abdulkareem , AbuRuz Salah , Alsabani Bandar , Alshehri Abdulmajeed , Aldebasi Tariq , Alkatheri Abdulmalik , Almodaimegh Hind
Published: November 2017

Objectives: The aims of the current study were to determine the prevalence and severity of anxiety and depression, and to explore associated factors among hospitalized patients with type 2 diabetes mellitus. Subjects and Methods: All patients with type 2 diabetes (160 patients) who were admitted to the Internal Medicine Wards of the King Abdulaziz Medical City, Riyadh, Saudi Arabia, from January to August 2015 were asked to participate, and 158 patients agreed to do so. A self-administered questionnaire consisting of 2 parts was used. The first part was on sociodemographic information, and the second part was a validated screening tool for assessing depression and anxiety. The severity of anxiety and depression was classified as normal, mild, moderate, and severe. Logistic regression was carried out to identify variables that were independently associated with anxiety and depression. Results: Using the screening tool, 85 (53.8%) and 80 (50.6%) study patients were identified as patients who suffered from depression and anxiety, respectively. The severity of distress was moderate/severe in 36 (42.4%) patients with depression and 41 (51.3%) patients with anxiety. The factors independently associated with the risk for anxiety in hospitalized patients with diabetes were physical inactivity and staying 8 days or longer in the hospital. On the other hand, factors that were independently associated with the risk for depression were older age, low income, and nephropathy. Conclusion: The majority of hospitalized patients with diabetes developed moderate/severe anxiety or depression, or both, during hospitalization. Hence, screening for anxiety and depression in high-risk hospitalized diabetic patients is recommended during hospitalization.
Midlife Systemic Inflammation, Late-Life White Matter Integrity, and Cerebral Small Vessel Disease
Authors: Walker Keenan A. , Power Melinda C. , Hoogeveen Ron C. , Folsom Aaron R. , Ballantyne Christie M. , Knopman David S. , Windham B. Gwen , Selvin Elizabeth , Jack Clifford R. , Gottesman Rebecca F.
Published: November 2017

Background and Purpose—

It is currently unclear whether midlife systemic inflammation promotes the development of white matter (WM) abnormalities and small vessel disease in the elderly. We examined the association of midlife systemic inflammation with late-life WM hyperintensity volume, deep and periventricular WM microstructural integrity (fractional anisotropy and mean diffusivity [MD]), cerebral infarcts, and microbleeds in a biracial prospective cohort study.

Methods—

Linear and logistic regression examined the relation between midlife high-sensitivity C-reactive protein (CRP)—a nonspecific marker of inflammation—and brain magnetic resonance imaging markers assessed 21 years later in the Atherosclerosis Risk in Communities Study.

Results—

We included 1485 participants (baseline age, 56[5]; 28% black). After adjusting for demographic factors and cardiovascular disease, each SD increase in midlife CRP was associated with lower fractional anisotropy (−0.09 SD; 95% confidence interval, −0.15 to −0.02) and greater MD (0.08 SD; 95% confidence interval, 0.03–0.15) in deep WM and lower fractional anisotropy (−0.07 SD; 95% confidence interval, −0.13 to 0.00) in periventricular WM. We found stronger associations between CRP and periventricular WM microstructural integrity among black participants (
P
interaction=0.011). Although an association between higher CRP levels and greater WM hyperintensity volume was found only among
APOE
ε4-positive participants in our primary analysis (0.14 SD; 95% confidence interval, 0.01–0.26;
P
interaction=0.028), this relationship extended to the entire sample after accounting for differential attrition. Midlife CRP was not associated with the presence of cerebral infarcts or microbleeds in late life.

Conclusions—

Our findings support the hypothesis that midlife systemic inflammation may promote the development of chronic microangiopathic structural WM abnormalities in the elderly.
Hêlēl ben-Šaḥar and the Chthonic Sun: A New Suggestion for the Mythological Background of Isa 14:12-15
Authors: Quick Laura
Published: November 2017

This paper will explore the oft investigated problem of the mythological referents which inform Isa 14:12-15. Crucial to this will be a reinterpretation of the mysterious hêlēl ben-šaḥar of v. 12, almost universally understood by commentators and translators alike to refer to the ‘Day Star, son of the Dawn’, and thus taken to refer to the ‘morning star’, the planet Venus. Much of the scholarship has approached the ancient Near Eastern material with this meaning in mind, yet no myth hitherto proposed has provided a complete analogy to Isa 14:12-15. Thus I will begin by exploring the problems with these previous analogies, before reconsidering the meaning of hêlēl ben-šaḥar. Understanding the phrase to metonymically remind of the sun itself, the Ugaritic conception of the chthonic sun will be proposed to provide a much more satisfying parallel with our Isaiah passage.
The Negation of Abnegation
Authors: Landa Ishay
Published: November 2017

This essay revisits Karl Marx’s understanding of consumption, in an effort to rescue it from the overshadowing legacy of critical theory which has construed Marx as inveighing against false needs. It is argued that Marx regarded the expansion of needs entailed by capitalism in a generally favourable way, but saw capitalism as a system yoking use-value to the imperatives of profit accumulation, hence limiting and subjugating the consumption of the masses. While Marx’s position was radically different from conventional anti-consumerism it is equally incompatible with complacent affirmations of ‘the consumer society’ in that Marx at all times aimed at a revolutionary change which will transform consumption both quantitatively and qualitatively. Marx’s views are first discussed as expressed in the perennially-cited text, the 1844Economic and Philosophical Manuscripts. The second part moves on to examine the further evolution of Marx’s ideas as found in later texts, particularly theGrundrisse.
Morphosyntactic variation in Modern Greek dialects
Authors: Lekakou Marika
Published: November 2017

This introduction lays out the issues in the study of morphosyntactic variation in Modern Greek dialects and summarizes the contents of the papers included herein.
“‘Her Chinese Attended to Almost Everything’: Relationships of Power in the Hackett Medical College for Women, Guangzhou, China, 1901–1915”
Authors: Shemo Connie
Published: November 2017

This essay uses a 1915 crisis at the American Presbyterian Hackett Medical College for Women in Guangzhou, China as a lens to explore the level of control Chinese women, who were known as “assistants,” exercised at the school. Official literature of the Hackett portrays the American woman missionary physician Dr. Mary Fulton as controlling the college, but in fact its Chinese women graduates largely ran the institution for some years before 1915. Challenging images of American women missionary physicians either as heroines or imperialists, this article describes instead how Chinese women shaped the institution. Placing the Hackett into the broader context of American Presbyterian medical education for Chinese women since 1879, it argues that rather than only interpreting and adapting missionary ideologies, many of the Chinese women medical students in Guangzhou brought their own conceptions of women practicing medicine. In the case of medical education for women in Guangzhou before 1915, American missionaries were partially responding to Chinese traditions and demands. Ultimately, this essay presents a more complex view of cultural transfer in the women’s foreign mission movement of this period.