bluuebunny/crossref_metadata_2025 huggingface dataset:
FRACTALS AND CHAOS CHARACTERISTICS OF ACOUSTIC EMISSION ENERGY ABOUT GAS-BEARING COAL DURING LOADED FAILURE
Authors: KONG XIANGGUO , WANG ENYUAN , LI SHUGANG , LIN HAIFEI , XIAO PENG , ZHANG KAIZHI
Published: April 2019

To study the damage evolution mechanism of gas-bearing coal and formation causes of acoustic emission signals during this process, the loaded experiments of gas-bearing coal were performed, and acoustic emission (AE) data radiated in this process were collected. Based on the multifractal theory, the causes of AE were explored in various loaded phases. The results showed that at the low stress stage, the fractures close and the friction/slip could cause low-energy acoustic emission events, and the multifractal spectrum had a smaller width. By contrast, at the high stress stage, the cracks expand, penetrate, and rupture, which would lead to AE events with the release of high energy, reflecting an increase in the width of the multifractal spectrum. At the initial loading stage, the time-varying multifractal spectrum was characterized by a chaotic behavior, but as the loading progressed, it gradually became orderly. In the elastic stage, coal experienced elastic deformation without damage, the ratio of strong and weak AE signals was almost the same, and both [Formula: see text] and [Formula: see text] were close to 0. In the plastic fracture stage, coal body consumed huge amounts of energy and suffered fracture. This also caused the coal body to radiate a large amount of AE signals. An analysis of these signals indicated that strong signals dominated and showed an increasing trend, and [Formula: see text] was less than 0 and continued to decrease. The time-varying multifractal characteristics reveal the formation mechanism of AE signals from gas-bearing coal, which contributes to improve our understanding of the mechanism of gas-bearing coal damage.
PARAMETRIC ITERATIVE FUNCTION SYSTEM FOR THE CONTINUUM GROWTH: CANTOR SET CASE
Authors: GUTIÉRREZ-HERNÁNDEZ SEBASTIÁN , BORY-REYES JUAN
Published: April 2019

In this paper, we present examples of one-parametric iterated function systems converging to the standard middle-third Cantor set. The main goal is the study of the continuous growth of the attractor of the corresponding parametrization.
CHARACTERISTIC POLYNOMIAL OF ADJACENCY OR LAPLACIAN MATRIX FOR WEIGHTED TREELIKE NETWORKS
Authors: DAI MEIFENG , HOU YONGBO , DAI CHANGXI , JU TINGTING , SUN YU , SU WEIYI
Published: April 2019

In recent years, weighted networks have been extensively studied in various fields. This paper studies characteristic polynomial of adjacency or Laplacian matrix for weighted treelike networks. First, a class of weighted treelike networks with a weight factor is introduced. Then, the relationships of adjacency or the Laplacian matrix at two successive generations are obtained. Finally, according to the operation of the block matrix, we obtain the analytic expression of the characteristic polynomial of the adjacency or the Laplacian matrix. The obtained results lay the foundation for the future study of adjacency spectrum or Laplacian spectrum.
Exploring Social CRM for Development of SMEs in Mauritius
Authors: Roopchund Randhir
Published: April 2019

This paper explores different Customer Relationship Management (CRM) solutions that may be adopted by SMEs in Mauritius. The Mauritian government has the ambition of increasing the contribution of SMEs to the overall GDP of Mauritius from 40 to 65% by year 2025. CRM is about building and enhancing relationships so as to increase long term profitability of the company. The aim of the research is to consider different Social CRM strategies that may be adopted by SMEs to achieve the national exports strategy. This research shows that SMEs consider websites and social media marketing more important as compared to other digital tools. In addition, SMEs are careful about some negative aspects of social media marketing such as negative comments and lack of social metrics. However, most SMEs believe that Social CRM is of great importance for being successful. The research ontology that has been adopted is that the use of CRM may be of great use for SMEs to improve their overall marketing capability.
Relative cohomology of complexes based on cotorsion pairs
Authors: Zhongkui Liu , Zongyang Xie
Published: April 2019

Let [Formula: see text] be an associative ring with identity. The purpose of this paper is to establish relative cohomology theories based on cotorsion pairs in the setting of unbounded complexes of modules over [Formula: see text]. Let [Formula: see text] be a complete hereditary cotorsion pair in [Formula: see text]-Mod. Then [Formula: see text] and [Formula: see text] are complete hereditary cotorsion pairs in the category of [Formula: see text]-complexes. For any complexes [Formula: see text] and [Formula: see text] and any [Formula: see text], we define the [Formula: see text]th relative cohomology groups [Formula: see text] and [Formula: see text] by special [Formula: see text]-precovers of [Formula: see text] and by special [Formula: see text]-preenvelopes of [Formula: see text], respectively. They are common generalizations of absolute cohomology groups and Gorenstein cohomology groups of complexes. Some induced exact sequences concerning relative cohomology groups are considered. It is also shown that the relative cohomology functor of complexes we considered is balanced.
Decomposing Frobenius Heisenberg categories
Authors: Gandhi Raj
Published: April 2019

We give two alternate presentations of the Frobenius Heisenberg category, [Formula: see text], defined by Savage, when the Frobenius algebra [Formula: see text] decomposes as a direct sum of Frobenius subalgebras. In these alternate presentations, the morphism spaces of [Formula: see text] are given in terms of planar diagrams consisting of strands “colored” by integers [Formula: see text], where a strand of color [Formula: see text] carries tokens labelled by elements of [Formula: see text] In addition, we prove that when [Formula: see text] decomposes this way, the tensor product of Frobenius Heisenberg categories, [Formula: see text] is equivalent to a certain subcategory of the Karoubi envelope of [Formula: see text] that we call the partial Karoubi envelope of [Formula: see text].
Minimal surfaces in the three-dimensional sphere with high symmetry
Authors: Bai Sheng , Wang Chao , Wang Shicheng
Published: April 2019

Using the Lawson existence theorem of minimal surfaces and the symmetries of the Hopf fibration, we will construct symmetric embedded closed minimal surfaces in the three-dimensional sphere. These surfaces contain the Clifford torus, the Lawson’s minimal surfaces, and seven new minimal surfaces with genera [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text] and [Formula: see text]. We will also discuss the relation between such surfaces and the maximal extendable group actions on subsurfaces of the three-dimensional sphere.
CROP DIVERSIFICATION AS CLIMATE CHANGE ADAPTATION: HOW DO BANGLADESHI FARMERS PERFORM?
Authors: MONIRUZZAMAN SHAIKH
Published: April 2019

This research is based on the theoretical framework of risk in rural agricultural economy where farmers consider climate change as idiosyncratic risk of production. Under the inter-temporal household consumption smoothing model, this paper considers crop diversification as an ex ante measure to tackle permanent income shock from climate change. This paper examines empirically whether crop diversity is affected by climate change and how this diversity will respond to different climate scenarios. Negative binomial regression models are estimated from a nationally representative sample of 11,389 farmers across Bangladesh and 30-year average of seasonal climatic variables to find the effects of climatic variables on crop diversity. This paper finds that crop diversity is climate-sensitive and this diversity in different locations varies with climatic conditions. This research unveils structural instability between different single cross-sectional models to simulate the effects of climatic variables on crop diversity. It also finds that increases in mean annual temperature by [Formula: see text]C by 2030 and [Formula: see text]C by 2100 have resulted in 26.40% and 149.83% increases in crop diversity compared to its baseline of 2010, respectively. The effects of rainfall scenarios on crop diversity are much lower compared to the effects of temperature.
Fossil biomass preserved as graphitic carbon in a late Paleoproterozoic banded iron formation metamorphosed at more than 550°C
Authors: Papineau Dominic , De Gregorio Bradley T. , Sagar James , Thorogate Richard , Wang Jianhua , Nittler Larry , Kilcoyne David A. , Marbach Hubertus , Drost Martin , Thornton Geoff
Published: April 2019

Metamorphism is thought to destroy microfossils, partly through devolatilization and graphitization of biogenic organic matter. However, the extent to which there is a loss of molecular, elemental and isotope signatures from biomass during high-temperature metamorphism is not clearly established. We report on graphitic structures inside and coating apatite grains from the
c.
1850 Ma Michigamme silicate banded iron formation from Michigan, metamorphosed above 550°C. Traces of N, S, O, H, Ca and Fe are preserved in this graphitic carbon and X-ray spectra show traces of aliphatic groups. Graphitic carbon has an expanded lattice around 3.6 Å, forms microscopic concentrically-layered and radiating polygonal flakes and has homogeneous δ
13
C values around −22‰, identical to bulk analyses. Graphitic carbon inside apatite is associated with nanometre-size ammoniated phyllosilicate. Precursors of these metamorphic minerals and graphitic carbon originated from ferruginous clay-rich sediments with biomass. We conclude that graphite coatings and inclusions in apatite grains indicate fluid remobilization during amphibolite-facies metamorphism of precursor biomass. This new evidence fills in observational gaps of metamorphosed biomass into graphite and supports the existence of biosignatures in the highly metamorphosed iron formation from the Eoarchean Akilia Association, which dates from the beginning of the sedimentary rock record.

Supplementary material:
Figures illustrating the petrography and analytical results are available at:
https://doi.org/10.6084/m9.figshare.c.4430609
A Lightweight Cryptographic Protocol with Certificateless Signature for the Internet of Things
Authors: Zhou Lu , Su Chunhua , Yeh Kuo-Hui
Published: April 2019

The universality of smart-devices has brought rapid development and the significant advancement of ubiquitous applications for the Internet of Things (IoT). Designing new types of IoT-compatible cryptographic protocols has become a more popular way to secure IoT-based applications. Significant attention has been dedicated to the challenge of implementing a lightweight and secure cryptographic protocol for IoT devices. In this study, we propose a lightweight cryptographic protocol integrating certificateless signature and bilinear pairing crypto-primitives. In the proposed protocol, we elegantly refine the processes to account for computation-limited IoT devices during security operations. Rigorous security analyses are conducted to guarantee the robustness of the proposed cryptographic protocol. In addition, we demonstrate a thorough performance evaluation, where an IoT-based test-bed, i.e., the Raspberry PI, is simulated as the underlying platform of the implementation of our proposed cryptographic protocol. The results show the practicability of the proposed protocol.
Sustained hypoxemia in late gestation potentiates hepatic gluconeogenic gene expression but does not activate glucose production in the ovine fetus
Authors: Jones Amanda K. , Rozance Paul J. , Brown Laura D. , Goldstrohm David A. , Hay William W. , Limesand Sean W. , Wesolowski Stephanie R.
Published: April 2019

Fetal hypoxemia is associated with pregnancy conditions that cause an early activation of fetal glucose production. However, the independent role of hypoxemia to activate this pathway is not well understood. We hypothesized that fetal hypoxemia would activate fetal glucose production by decreasing umbilical glucose uptake and increasing counter-regulatory hormone concentrations. We induced hypoxemia for 9 days with maternal tracheal N2 gas insufflation to reduce maternal and fetal arterial Po2 by ~20% (HOX) compared with fetuses from ewes receiving intratracheal compressed air (CON). At 0.9 of gestation, fetal metabolic studies were performed ( n = 7 CON, 11 HOX). Umbilical blood flow rates, net fetal oxygen and glucose uptake rates, and fetal arterial plasma glucose concentrations were not different between the two groups. Fetal glucose utilization rates were lower in HOX versus CON fetuses but not different from umbilical glucose uptake rates, demonstrating the absence of endogenous glucose production. In liver tissue, mRNA expression of gluconeogenic genes G6PC (P < 0.01) and PCK1 ( P = 0.06) were six- and threefold greater in HOX fetuses versus CON fetuses. Increased fetal norepinephrine and cortisol concentrations and hepatic G6PC and PCK1 expression were inversely related to fetal arterial Po2. These findings support a role for fetal hypoxemia to act with counter-regulatory hormones to potentiate fetal hepatic gluconeogenic gene expression. However, in the absence of decreased net fetal glucose uptake rates and plasma glucose concentrations, hypoxemia-induced gluconeogenic gene activation is not sufficient to activate fetal glucose production.
Blood Glucose Levels May Aid the Decision for CT Scan in Minor Head Trauma
Authors: Alexiou George A. , Sotiropoulos Athanasios , Lianos Georgios D. , Zigouris Andreas , Metaxas Dimitrios , Nasios Anastasios , Michos Evaggelos , Mitsis Michail , Pachatouridis Dimitrios , Voulgaris Spyridon
Published: April 2019

Traumatic brain injury has been associated with increased blood glucose levels. In the present study, we set out to investigate if blood glucose level in mild head trauma could predict the need for CT. One hundred fifty-nine patients with minor TBI (GCS 13-15) and a mean age of44.8±23.8years were included in the study. The most common mechanism of trauma was falls. Patients with positive CT findings had significantly higher glucose levels than patients with negative CT findings. Using ROC curve analysis, serum glucose levels higher than 120 mg dl-1were the optimal cutoff value for the detection of patients with positive CT findings with a sensitivity of 74.4% and a specificity of 90.7%. Serum glucose level evaluation at presentation in the emergency department may aid CT decision-making in mild TBI.
Jackknife Model Averaging Prediction Methods for Complex Phenotypes with Gene Expression Levels by Integrating External Pathway Information
Authors: Yu Xinghao , Xiao Lishun , Zeng Ping , Huang Shuiping
Published: April 2019

Motivation. In the past few years many prediction approaches have been proposed and widely employed in high dimensional genetic data for disease risk evaluation. However, those approaches typically ignore in model fitting the important group structures that naturally exists in genetic data. Methods. In the present study, we applied a novel model-averaging approach, called jackknife model averaging prediction (JMAP), for high dimensional genetic risk prediction while incorporating pathway information into the model specification. JMAP selects the optimal weights across candidate models by minimizing a cross validation criterion in a jackknife way. Compared with previous approaches, one of the primary features of JMAP is to allow model weights to vary from 0 to 1 but without the limitation that the summation of weights is equal to one. We evaluated the performance of JMAP using extensive simulation studies and compared it with existing methods. We finally applied JMAP to four real cancer datasets that are publicly available from TCGA. Results. The simulations showed that compared with other existing approaches (e.g., gsslasso), JMAP performed best or is among the best methods across a range of scenarios. For example, among 14 out of 16 simulation settings with PVE = 0.3, JMAP has an average of 0.075 higher prediction accuracy compared with gsslasso. We further found that in the simulation, the model weights for the true candidate models have much smaller chances to be zero compared with those for the null candidate models and are substantially greater in magnitude. In the real data application, JMAP also behaves comparably or better compared with the other methods for continuous phenotypes. For example, for the COAD, CRC, and PAAD datasets, the average gains of predictive accuracy of JMAP are 0.019, 0.064, and 0.052 compared with gsslasso. Conclusion. The proposed method JMAP is a novel model-averaging approach for high dimensional genetic risk prediction while incorporating external useful group structures into the model specification.
General Decrease of Taste Sensitivity Is Related to Increase of BMI: A Simple Method to Monitor Eating Behavior
Authors: Vignini Arianna , Borroni Francesca , Sabbatinelli Jacopo , Pugnaloni Sofia , Alia Sonila , Taus Marina , Ferrante Luigi , Mazzanti Laura , Fabri Mara
Published: April 2019

Background and Objectives. The present study was conducted to evaluate the relationship between taste identification ability and body mass index (BMI) by studying the response to the administration of different taste stimuli to both sides of the tongue in three different groups of subjects. Subjects and Methods. Thirty healthy normal-weight volunteers, 19 healthy overweight subjects, and 22 obese subjects were enrolled. For each subject, the lateralization Oldfield score, body weight, height, and blood pressure were determined. The taste test is based on filter paper strips soaked with 4 taste stimuli presented at different concentrations to evoke 4 basic taste qualities (salty, sour, sweet, and bitter); pure rapeseed oil and water were also administered to evoke fat and neutral taste qualities. The stimuli were applied to each side of the protruded tongue. Subjects were asked to identify the taste from a list of eight descriptions according to a multiple choice paradigm. Results. The results showed a general lowering of taste sensitivity with the increase of BMI, except for the taste of fat with rapeseed oil as the stimulus. Other variables affecting taste sensitivity are age (negative association), gender (women generally show higher sensitivity), and taste stimuli concentration (positive association). Conclusions. Our findings could provide important insights into how new therapies could be designed for weight loss and long-term weight maintenance and how diets could be planned combining the correct caloric and nutritional supply with individual taste preferences.
Exercise for Prevention and Relief of Cardiovascular Disease: Prognoses, Mechanisms, and Approaches
Authors: Tian Danyang , Meng Jinqi
Published: April 2019

This review is aimed at summarizing the new findings about the multiple benefits of exercise on cardiovascular disease (CVD). We pay attention to the prevalence and risk factors of CVD and mechanisms and recommendations of physical activity. Physical activity can improve insulin sensitivity, alleviate plasma dyslipidemia, normalize elevated blood pressure, decrease blood viscosity, promote endothelial nitric oxide production, and improve leptin sensitivity to protect the heart and vessels. Besides, the protective role of exercise on the body involves not only animal models in the laboratory but also clinical studies which is demonstrated by WHO recommendations. The general exercise intensity for humans recommended by the American Heart Association to prevent CVD is moderate exercise of 30 minutes, 5 times a week. However, even the easiest activity is better than nothing. What is more, owing to the different physical fitness of individuals, a standard exercise training cannot provide the exact treatment for everyone. So personalization of exercise will be an irresistible trend and bring more beneficial effects with less inefficient physical activities. This paper reviews the benefits of exercise contributing to the body especially in CVD through the recent mechanism studies.
Expression Analysis of Fibronectin Type III Domain-Containing (FNDC) Genes in Inflammatory Bowel Disease and Colorectal Cancer
Authors: Wuensch Tilo , Wizenty Jonas , Quint Janina , Spitz Wolfgang , Bosma Madeleen , Becker Olaf , Adler Andreas , Veltzke-Schlieker Wilfried , Stockmann Martin , Weiss Sascha , Biebl Matthias , Pratschke Johann , Aigner Felix
Published: April 2019

Background. Fibronectin type III domain-containing (FNDC) proteins fulfill manifold functions in tissue development and regulation of cellular metabolism. FNDC4 was described as anti-inflammatory factor, upregulated in inflammatory bowel disease (IBD). FNDC signaling includes direct cell-cell interaction as well as release of bioactive peptides, like shown for FNDC4 or FNDC5. The G-protein-coupled receptor 116 (GPR116) was found as a putative FNDC4 receptor. We here aim to comprehensively analyze the mRNA expression of FNDC1, FNDC3A, FNDC3B, FNDC4, FNDC5, and GPR116 in nonaffected and affected mucosal samples of patients with IBD or colorectal cancer (CRC). Methods. Mucosa samples were obtained from 30 patients undergoing diagnostic colonoscopy or from surgical resection of IBD or CRC. Gene expression was determined by quantitative real-time PCR. In addition, FNDC expression data from publicly available Gene Expression Omnibus (GEO) data sets (GDS4296, GDS4515, and GDS5232) were analyzed. Results. Basal mucosal expression revealed higher expression of FNDC3A and FNDC5 in the ileum compared to colonic segments. FNDC1 and FNDC4 were significantly upregulated in IBD. None of the investigated FNDCs was differentially expressed in CRC, just FNDC3A trended to be upregulated. The GEO data set analysis revealed significantly downregulated FNDC4 and upregulated GPR116 in microsatellite unstable (MSI) CRCs. The expression of FNDCs and GPR116 was independent of age and sex. Conclusions. FNDC1 and FNDC4 may play a relevant role in the pathobiology of IBD, but none of the investigated FNDCs is regulated in CRC. GPR116 may be upregulated in advanced or MSI CRC. Further studies should validate the altered FNDC expression results on protein levels and examine the corresponding functional consequences.
Recoverable Resource Prediction of Shallow Geothermal Energy in Small Towns Using the Finite Volume Method: Taking the Central Urban Area of Danyang City, Jiangsu Province, as an Example
Authors: Zhang Qing , Ge Weiya , Jia Junyuan , Tian Fujin , Chang Xiaojun , Xing Huaixue , Lei Ting
Published: April 2019

The ground‐coupled ground‐source heat pump (GSHP) system is a common method for shallow geothermal energy exploitation and utilization. GSHP has a great heat exchange rate and wide application range. In order to effectively exploit shallow geothermal energy in the central urban area of Danyang City, Jiangsu Province, based on finite volume method, it is adopted to simulate the amount of recoverable shallow geothermal energy in the study area through ground‐coupled heat exchange. The simulation is conducted on the development trend of thermal transport and thermal balance in the study area from early June 2015 to the end of May 2025 to obtain the temperature distribution at different times. Under the presupposed working conditions, with the operation of a ground‐coupled GSHP, thermal accumulation occurs in parts of the study area. To mitigate the problem of thermal accumulation, two schemes are proposed: (1) adding auxiliary cooling towers and (2) increasing the amount heated domestic water in spring and autumn. Both schemes mitigate thermal accumulation. For Scheme  1, the total heat supply for shallow geothermal energy in the central urban area of Danyang City in winter is 2.91 × 106 kW, and the total heat release in summer is 3.53 × 106 kW. For Scheme  2, the total heat release in summer is 3.52 × 106 kW and the total heat supply in winter is 2.90 × 106 kW. A ground‐coupled GSHP system has significant applicability in the central urban area of Danyang City, where shallow geothermal energy has good exploitation prospects.
Effect of a Semirigid Ankle Brace on the In Vivo Kinematics of Patients with Functional Ankle Instability during the Stance Phase of Walking
Authors: Zhang Gonghao , Cao Shengxuan , Wang Chen , Ma Xin , Wang Xu , Huang Jiazhang , Zhang Chao
Published: April 2019

An ankle brace is commonly used by patients after they suffer from initial ankle sprains, reducing the incidents of recurrent sprain or limiting laxity in joints with functional ankle instability (FAI). However, whether the application of a semirigid ankle brace can improve the abnormal ankle gait kinematics of patients with FAI remains unknown. This study aimed to determine the effect of a semirigid ankle brace on the gait kinematics of ankle joints through 3D-2D fluoroscopy image registration. A total of 8 subjects with FAI (3 males and 5 females, 10 feet) as FAI group and 10 subjects without FAI (6 males and 4 females, 10 feet) as control group were enrolled in this study. Three-dimensional bone models created from computed tomography images were matched to fluoroscopic images to compute the 6 degrees of freedom (DOF) talocrural, subtalar, and ankle joints complex kinematics for control and FAI group with or without brace during the stance phase of walking. FAI patients had significantly less ROMs in inversion/eversion rotation of the talocrural and subtalar joint after wearing semirigid ankle brace. Laxity was observed in most of the displacements of the talocrural and subtalar joints in FAI group. The brace partly altered the ankle joints movement in opposite directions, especially joint rotation, and restricted the talocrural and subtalar joints in the dorsiflexion position during the touch down phase of walking.
Flexural Behavior of the Innovative CA-UHPC Slabs with High and Low Reinforcement Ratios
Authors: Feng Yu , Qi Jianan , Wang Jingquan , Liu Jiaping , Liu Jianzhong
Published: April 2019

This paper presents an experimental study on the flexural behavior of an innovative CA-UHPC (ultrahigh-performance concrete containing coarse aggregate) slab with high and low reinforcement ratios. A total of eighteen CA-UHPC slabs were tested to failure under the parameters of longitudinal reinforcement ratio, curing method, and maximum aggregate size. Test results indicated that sufficient longitudinal reinforcement should be embedded to prevent the brittle failure and disastrous damage. High ductile failure mode was observed for specimens with high reinforcement ratio compared with specimens with low reinforcement ratio. Instead of extensively crushing as normal strength concrete, delamination failure appeared in the compression zone of the CA-UHPC slabs owing to the fibers’ bridging effect, the yielding of longitudinal reinforcement, and the large expansion of flexural cracks which led to the final failure. The reinforced CA-UHPC slabs demonstrated excellent deformability, and ultimate ratio of deflection to span increased from 1/281 to 1/12 when the reinforcement ratio raised from 0% to 3.45%. Stiffness of the reinforced specimens at the flexural cracking state was about 88% and only approximately 6% at the ultimate state, but nearly 50% of the initial stiffness remained when the longitudinal reinforcements yielded, which indicated superior load resistance ability and excellent postcracking deformability. A new ductility index was proposed to evaluate the postcracking ductility of the CA-UHPC specimens. Finally, test results were compared with the flexural strength predictions of CECS 38-2004, ACI 544.4R, and BS EN 1992.
A Cox-Based Risk Prediction Model for Early Detection of Cardiovascular Disease: Identification of Key Risk Factors for the Development of a 10-Year CVD Risk Prediction
Authors: Jia Xiaona , Baig Mirza Mansoor , Mirza Farhaan , GholamHosseini Hamid
Published: April 2019

Background and Objective. Current cardiovascular disease (CVD) risk models are typically based on traditional laboratory-based predictors. The objective of this research was to identify key risk factors that affect the CVD risk prediction and to develop a 10-year CVD risk prediction model using the identified risk factors. Methods. A Cox proportional hazard regression method was applied to generate the proposed risk model. We used the dataset from Framingham Original Cohort of 5079 men and women aged 30-62 years, who had no overt symptoms of CVD at the baseline; among the selected cohort 3189 had a CVD event. Results. A 10-year CVD risk model based on multiple risk factors (such as age, sex, body mass index (BMI), hypertension, systolic blood pressure (SBP), cigarettes per day, pulse rate, and diabetes) was developed in which heart rate was identified as one of the novel risk factors. The proposed model achieved a good discrimination and calibration ability with C-index (receiver operating characteristic (ROC)) being 0.71 in the validation dataset. We validated the model via statistical and empirical validation. Conclusion. The proposed CVD risk prediction model is based on standard risk factors, which could help reduce the cost and time required for conducting the clinical/laboratory tests. Healthcare providers, clinicians, and patients can use this tool to see the 10-year risk of CVD for an individual. Heart rate was incorporated as a novel predictor, which extends the predictive ability of the past existing risk equations.
Analysis of the CDKN2A Gene in FAMMM Syndrome Families Reveals Early Age of Onset for Additional Syndromic Cancers
Authors: Middlebrooks Candace D. , Stacey Mark L. , Li Qing , Snyder Carrie , Shaw Trudy G. , Richardson-Nelson Tami , Rendell Marc , Ferguson Claire , Silberstein Peter , Casey Murray J. , Bailey-Wilson Joan E. , Lynch Henry T.
Published: April 2019

Familial atypical multiple mole melanoma (FAMMM) syndrome is a hereditary cancer syndrome that results from mutations in several genes, including the CDKN2A gene. In addition to melanoma, certain other malignancies such as pancreatic cancer are known to occur more frequently in family members who carry the mutation. However, as these families have been followed over time, additional cancers have been observed in both carriers and noncarriers. We sought to determine whether these additional cancers occur at higher frequencies in carriers than noncarriers. We performed survival analyses using 10 FAMMM syndrome families (N = 1,085 individuals) as well as a mixed effects Cox regression, with age at last visit to the clinic or age at cancer diagnosis as our time variable. This analysis was done separately for the known FAMMM-related cancers and “other” cancer groups. The survival curves showed a significant age effect with carriers having a younger age at cancer onset than noncarriers for FAMMM-related cancers (as expected) as well as for newly associated cancers. The Cox regression reflected what was seen in the survival curves, with all models being highly significant (P = 7.15E−20 and P = 5.00E−13 for the FAMMM-related and other cancers, respectively). These analyses support the hypothesis that CDKN2A mutation carriers in FAMMM syndrome families have increased risk for early onset of several cancer types beyond the known cancers. Therefore, these individuals should be screened for additional cancers, and mutation screening should be extended to more than first-degree relatives of an index carrier patient.

Significance:

This study shows that carriers of mutations in the CDKN2A gene in FAMMM syndrome are at increased risk for early onset of several cancer types beyond the known cancers.
Predictors of Long-Term Survival among High-Grade Serous Ovarian Cancer Patients
Authors: Clarke Christina L. , Kushi Lawrence H. , Chubak Jessica , Pawloski Pamala A. , Bulkley Joanna E. , Epstein Mara M. , Burnett-Hartman Andrea N. , Powell Bethan , Pearce Celeste L. , Spencer Feigelson Heather
Published: April 2019

Background:

Relatively little is known about factors associated with long-term survival (LTS) following a diagnosis of ovarian cancer.

Methods:

We conducted a retrospective study of high-grade serous ovarian cancer (HGSOC) to explore predictors of LTS (defined as ≥7 years of survival) using electronic medical record data from a network of integrated health care systems. Multivariable logistic regression with forward selection was used to compare characteristics of women who survived ≥7 years after diagnosis (n = 148) to those who died within 7 years of diagnosis (n = 494).

Results:

Our final model included study site, age, stage at diagnosis, CA-125, comorbidity score, receipt of chemotherapy, BMI, and four separate comorbid conditions: weight loss, depression, hypothyroidism, and liver disease. Of these, only younger age, lower stage, and depression were statistically significantly associated with LTS.

Conclusions:

We did not identify any new characteristics associated with HGSOC survival.

Impact:

Prognosis of ovarian cancer generally remains poor. Large, pooled studies of ovarian cancer are needed to identify characteristics that may improve survival.
Survival Following Chemotherapy in Ovarian Clear Cell Carcinoma Is Not Associated with Pathological Misclassification of Tumor Histotype
Authors: Takenaka Masataka , Köbel Martin , Garsed Dale W. , Fereday Sian , Pandey Ahwan , Etemadmoghadam Dariush , Hendley Joy , Kawabata Ayako , Noguchi Daito , Yanaihara Nozomu , Takahashi Hiroyuki , Kiyokawa Takako , Ikegami Masahiro , Takano Hirokuni , Isonishi Seiji , Ochiai Kazuhiko , Traficante Nadia , Gadipally Sreeja , Semple Timothy , Vassiliadis Dane , Amarasinghe Kausyalya , Li Jason , Mir Arnau Gisela , Okamoto Aikou , Friedlander Michael , Bowtell David D. L.
Published: April 2019

Purpose:

Although ovarian clear cell carcinomas (OCCC) are commonly resistant to platinum-based chemotherapy, good clinical outcomes are observed in a subset of patients. The explanation for this is unknown but may be due to misclassification of high-grade serous ovarian cancer (HGSOC) as OCCC or mixed histology.

Experimental Design:

To discover potential biomarkers of survival benefit following platinum-based chemotherapy, we ascertained a cohort of 68 Japanese and Australian patients in whom progression-free survival (PFS) and overall survival (OS) could be assessed. We performed IHC reclassification of tumors, and targeted sequencing and immunohistochemistry of known driver genes. Exome sequencing was performed in 10 patients who had either unusually long survival (N = 5) or had a very short time to progression (N = 5).

Results:

The majority of mixed OCCC (N = 6, 85.7%) and a small proportion of pure OCCC (N = 3, 4.9%) were reclassified as likely HGSOC. However, the PFS and OS of patients with misclassified samples were similar to that of patients with pathologically validated OCCC. Absent HNF1B expression was significantly correlated with longer PFS and OS (P = 0.0194 and 0.0395, respectively). Mutations in ARID1A, PIK3CA, PPP2R1A, and TP53 were frequent, but did not explain length of PFS and OS. An exploratory exome analysis of patients with favorable and unfavorable outcomes did not identify novel outcome-associated driver mutations.

Conclusions:

Survival benefit following chemotherapy in OCCC was not associated with pathological misclassification of tumor histotype. HNF1B loss may help identify the subset of patients with OCCC with a more favorable outcome.
Stadien des Prostatakarzinoms und Unmet Medical Need
Authors: Klier Jörg
Published: April 2019

Männer mit Prostatakarzinom haben eine gute Prognose, wenn die Erkrankung in einem frühen Stadium erkannt und behandelt wird. In späteren Stadien steigt das Progressions- und Mortalitätsrisiko hingegen deutlich. Das gilt auch für das nicht-metastasierte kastrationsresistente Prostatakarzinom (M0CRPC, nm-CRPC), bei dem das Progressionsrisiko insbesondere bei kurzer PSA-Verdopplungszeit deutlich erhöht ist. Für entsprechende Patienten gab es lange - außer der klassischen Androgendeprivation - keine Therapieoptionen.
Can Biomarkers of Coagulation, Platelet Activation, and Inflammation Predict Venous Thromboembolism in Patients with Haematological Malignancies?
Authors: Elmoamly Shereef , Mattar Mervat , Yacoub Maha F. , Afif Alaa
Published: April 2019

Background: The incidence of venous thromboembolism (VTE) in haematological malignancies varies according to the type and grade of the disease and clinical variables, and there is a need to develop a tool to predict the occurrence of VTE in cancer patients at diagnosis to tailor prophylactic anticoagulation use during treatment. Objective: To study the incidence of VTE in haematological malignancies and clarify whether vascular and inflammatory biomarkers could be used as predictors of VTE in those patients. Methods: This was a prospective observational cohort study. Hypercoagulability and inflammatory biomarkers were assayed in a group of 171 patients with haematological malignancies at diagnosis. These markers included (1) coagulation and fibrinolysis activation markers (D-dimer, fibrinogen, antithrombin, plasminogen activator inhibitor 1), (2) endothelial and platelet activation markers (von Willebrand factor and soluble P-selectin), and (3) inflammatory markers (tumour necrosis factor αand interleukin 6). The end point was mortality or symptomatic VTE. Results/Conclusion: The incidence of symptomatic VTE was 7%. None of the tested biomarkers showed statistical significance as predictors for the occurrence of VTE in haematological malignancies. However, there were statistically significant associations between the occurrence of VTE and central venous access device insertion, the prothrombin time, and the erythrocyte sedimentation rate. An ESR above 106.5 mm/h is associated with increased VTE occurrence.
Lack of Evidence for Time or Dose Relationship between Antenatal Magnesium Sulfate and Intestinal Injury in Extremely Preterm Neonates
Authors: Mikhael Michel , Bronson Cheryl , Zhang Lishi , Curran Mark , Rodriguez Helen , Bhakta Kushal Y.
Published: April 2019

Background: Recent studies reported conflicting results on the relationship between antenatal magnesium sulfate (MgSO4) exposure and neonatal intestinal injury. Most studies have not assessed MgSO4 exposure quantitatively and none reported the exposure timing. Objectives: The aim of this work was to assess whether there is a temporal or dose-dependent relationship between antenatal MgSO4 exposure and intestinal injury in extremely preterm neonates. Methods: A retrospective study was made of inborn neonates with gestational age ≤28 weeks and/or birth weights ≤1,000 g. Primary outcomes included necrotizing enterocolitis (NEC), spontaneous intestinal perforation (SIP), and/or death prior to discharge or in the first 2 weeks of life. Outcome comparisons were made based on the timing of MgSO4 exposure, within 7 days (Mg7D) or within 3 days (Mg3D) of birth. Total cumulative doses for the Mg3D group were also computed. Results: A total of 302 neonates were included, 210 in the Mg7D group, out of whom 179 (85.2%) constituted the Mg3D group. There were no differences noted when comparing MgSO4 exposure timing and the likelihood of NEC, SIP, and/or death. This remained the same for subgroup analysis of neonates < 26 weeks’ gestation. Each 10-g increase in MgSO4 cumulative dose correlated with a decrease in SIP/NEC/death by 18.9% prior to discharge and by 21.9% in the first 2 weeks of life. Small for gestational age (SGA) was a potential effect modifier by a likelihood ratio test with p = 0.07. Conclusions: Antenatal MgSO4 exposure in extremely preterm neonates was not associated with an increased risk of intestinal injury or death, and might have reduced these complications in a dose-dependent manner in our study. This protective effect was more noticeable in SGA neonates.
Higher in vivo Cortical Intracellular Volume Fraction Associated with Lithium Therapy in Bipolar Disorder: A Multicenter NODDI Study
Authors: Sarrazin Samuel , Poupon Cyril , Teillac Achille , Mangin Jean-François , Polosan Mircea , Favre Pauline , Laidi Charles , D'Albis Marc-Antoine , Leboyer Marion , Lledo Pierre-Marie , Henry Chantal , Houenou Josselin
Published: April 2019

Background: MRI studies in patients with bipolar disorder have suggested that lithium is associated with grey matter increases that may underlie its therapeutic effects. However, the relationship between grey matter volume and cellular microstructural changes is not straightforward, as modifications of different cellular compartments of grey matter may be involved. Objectives: Our aim was to test the hypothesis that dendritic density is higher in patients undergoing lithium therapy than in patients without lithium, using advanced modelling of water diffusion investigated with MRI. Method: We included 41 patients and 40 controls matched for age and gender from two sites. All subjects underwent 3T MRI with 3 shells of diffusion. We used neurite orientation dispersion and density imaging to compare the grey matter neurite density between patients undergoing lithium therapy or not and control subjects. Results: We found a significant group effect in the left prefrontal region (p = 0.001, Bonferroni corrected): patients without lithium had a lower frontal neurite density than controls (p = 0.009), while those on lithium had a higher mean neurite density than those without (p < 0.001). Patients on lithium were not different from controls (p = 0.08). Conclusions: This is the first study to report in vivo evidence of preserved neurite density of the prefrontal cortex in humans associated with lithium intake. Changes of intracellular volume fraction are thought to reflect changes of grey matter microstructural organization. This reinforces the hypothesis of lithium having a positive effect on the neuronal compartment in humans.
Familial Hydrocephalus and Dysgenesis of the Corpus Callosum Associated with Xp22.33 Duplication and Stenosis of the Aqueduct of Sylvius with X-Linked Recessive Inheritance Pattern
Authors: Alhousseini Ali , Zeineddine Salam , Husseini Abraham , Baddah Heba , Saker Homam , Mody Swati , Ibrahim Salah A. , Thakur Mili , Hernandez-Andrade Edgar , Bahado-Singh Ray
Published: April 2019

Introduction: X-linked recessive mutations predominantly affect male fetuses with milder or no abnormalities in female siblings. Most reports show only one affected member in the family. We are reporting a family affected with hydrocephalus, stenosis of the aqueduct of Sylvius, dysgenesis of the corpus callosum, and Xp22.33 microduplication. Case Presentation: Eighteen-year-old patient was evaluated for her 2 pregnancies; the first was a male fetus with severe hydrocephalus and the second a female fetus with mild hydrocephalus. Postnatal MRI evaluation of the male neonate revealed stenosis of the aqueduct of Sylvius, dysgenesis of the corpus callosum, and severe hydrocephalus requiring ventriculoperitoneal shunt. Postnatal MRI evaluation of the female neonate revealed mild hydrocephalus, stenosis of the aqueduct of Sylvius, and mild dysgenesis of the corpus callosum. The female baby did not require surgical intervention. Genetic testing of the mother and the 2 children revealed a 439 Kb duplication of Xp22.33. Discussion: This family demonstrates typical X-linked recessive heritability. X-inactivation is a compensatory mechanism that explains the mild symptoms of the female child and the severe symptoms of the male child. This familial case shows the importance of prenatal testing and genetic counseling and testing, including karyotype and chromosomal microarray.
Medium and large sized mammals of the Boqueirão da Onça, North of Bahia State, Brazil
Authors: Campos Cláudia Bueno de , Esteves Carolina Franco , Dias Douglas De Matos , Rodrigues Flávio Henrique Guimarães
Published: April 2019

The mosaic of protected areas of Boqueirão da Onça (8.636 km²), created in the north of Bahia state, is located in the Caatinga, an exclusively Brazilian biome, but exposed to a range of anthropic impacts that threaten its species and natural resources. Few data are available for various zoological groups in Caatinga, including mammals. In order to characterize the community of mammals of this region, considering species richness, we installed 80 camera-trap stations. With a sampling effort of 10,370 camera-days we recorded 28 species (22 wild and six domestic). Opportunistically, we recorded four mammals, resulting in a total richness of 32 species, five of which are included in the global list of endangered species, and seven in the national list. The results are significant, since the richness of wild mammals of the Boqueirão da Onça (S = 26) presented a high value when compared to other Caatinga localities. During the study we found evidence of human activities threatening the conservation of the region, such as poaching and deforestation. Therefore, there is an urgent need in the publication of the Management Plan of the recently created Boqueirão da Onça National Park, to minimize negative impacts on biodiversity and ensure the maintenance of ecological processes.
Influence of Baseline Anemia on Dual Antiplatelet Therapy Cessation and Risk of Adverse Events After Percutaneous Coronary Intervention
Authors: Faggioni Michela , Baber Usman , Sartori Samantha , Chandrasekhar Jaya , Cohen David J. , Henry Timothy D. , Claessen Bimmer E. , Dangas George D. , Gibson C. Michael , Krucoff Mitchell W. , Vogel Birgit , Moliterno David J. , Sorrentino Sabato , Colombo Antonio , Chieffo Alaide , Kini Annapoorna , Farhan Serdar , Ariti Cono , Witzenbichler Bernard , Weisz Giora , Steg Philippe Gabriel , Pocock Stuart , Mehran Roxana
Published: April 2019

Background:

Anemia is a well-recognized risk factor for both bleeding and ischemic events after percutaneous coronary intervention (PCI). We sought to determine the impact of baseline anemia on dual antiplatelet therapy (DAPT) cessation patterns ≤2 years after PCI and the subsequent risk of clinical adverse events.

Methods and Results:

PARIS (Patterns of Non-Adherence to Dual Anti-Platelet Regimen in Stented Patients) was a prospective multicenter observational registry of PCI-treated patients (n=5018). Anemia was defined as baseline Hb (hemoglobin) <12 g/dL for men and <11 g/dL for women. DAPT cessation modes included physician-recommended discontinuation, temporary interruption (≤14 days), and disruption due to bleeding or noncompliance. The primary end point was 2-year major adverse cardiovascular events (MACE), a composite of cardiac death, myocardial infarction, or target vessel revascularization. We identified 824 (18%) anemic and 4194 (82%) nonanemic patients. Anemic patients were older and had a higher rate of diabetes mellitus, hypertension, and prior PCI. DAPT interruption and disruption were significantly more common in anemic patients throughout 2 years after PCI, whereas physician-recommended discontinuation occurred more often in anemic patients during the first year after PCI and in nonanemic patients during the second year. The 2-year adjusted risks of MACE and Bleeding Academic Research Consortium 3 or 5 bleeding events were significantly higher in anemic patients. Compared with uninterrupted DAPT, disruption, but not interruption and physician-recommended discontinuation, was associated with a higher risk of myocardial infarction in nonanemic patients and a higher risk of both myocardial infarction and MACE in anemic patients. There was no significant interaction between anemia and risk of clinical outcomes associated with each DAPT cessation mode.

Conclusions:

Baseline anemia was associated with a significantly higher adjusted risk of MACE and major bleeding. Physicians more frequently recommend DAPT discontinuation to anemic patients during the first year, and to nonanemic patients during the second year after PCI. DAPT disruption was associated with a higher risk of MACE outcomes.