bluuebunny/crossref_metadata_2025 huggingface dataset:
Dominance rank-associated immune gene expression is widespread, sex-specific, and a precursor to high social status in wild male baboons
Authors: Lea Amanda J. , Akinyi Mercy Y. , Nyakundi Ruth , Mareri Peter , Nyundo Fred , Kariuki Thomas , Alberts Susan C. , Archie Elizabeth A. , Tung Jenny
Published: July 2018

In humans and other hierarchical species, social status is tightly linked to variation in health and fitness-related traits. Experimental manipulations of social status in female rhesus macaques suggest that this relationship is partially explained by status effects on immune gene regulation. However, social hierarchies are established and maintained in different ways across species: while some are based on kin-directed nepotism, others emerge from direct physical competition. We investigated how this variation influences the relationship between social status and immune gene regulation in wild baboons, where hierarchies in males are based on fighting ability but female hierarchies are nepotistic. We measured rank-related variation in gene expression levels in adult baboons of both sexes at baseline and in response to ex vivo stimulation with the bacterial endotoxin lipopolysaccharide (LPS). We identified >2000 rank- associated genes in males, an order of magnitude more than in females. In males, high status predicted increased expression of genes involved in innate immunity and preferential activation of the NFkB-mediated pro-inflammatory pathway, a pattern previously associated with low status in female rhesus macaques. Using Mendelian randomization, we reconcile these observations by demonstrating that high status-associated gene expression patterns are precursors, not consequences, of high social status in males, in support of the idea that physiological condition determines who attains high rank. Together, our work provides the first test of the relationship between social status and immune gene regulation in wild primates. It also emphasizes the importance of social context in shaping the relationship between social status and immune function.

SIGNIFICANCE

Social status predicts fitness outcomes in social animals, motivating efforts to understand its physiological causes and consequences. We investigated the relationship between social status and immune gene expression in wild baboons, where female status is determined by kinship but male status is determined by fighting ability. We uncover pervasive status-gene expression associations in males, but not females. High status males exhibit high levels of pro-inflammatory gene expression, in contrast to previous findings in hierarchies that are not competitively determined. Using Mendelian randomization, we show that this status-associated variation precedes dominance rank attainment: males who compete successfully for high status are already immunologically distinct. The nature of social hierarchies thus fundamentally shapes the relationship between social status and immune function.
Ecological analyses of mycobacteria in showerhead biofilms and their relevance to human health
Authors: Gebert Matthew J. , Delgado-Baquerizo Manuel , Oliverio Angela M. , Webster Tara M. , Nichols Lauren M. , Honda Jennifer R. , Chan Edward D. , Adjemian Jennifer , Dunn Robert R. , Fierer Noah
Published: July 2018

Bacteria within the genusMycobacteriumcan be abundant in showerheads, and the inhalation of aerosolized mycobacteria while showering has been implicated as a mode of transmission in nontuberculous mycobacterial (NTM) lung infections. Despite their importance, the diversity, distributions, and environmental predictors of showerhead-associated mycobacteria remain largely unresolved. To address these knowledge gaps, we worked with citizen scientists to collect showerhead biofilm samples and associated water chemistry data from 656 households located across the U.S. and Europe. Our cultivation-independent analyses revealed that the genusMycobacteriumwas consistently the most abundant genus of bacteria detected in residential showerheads, yet mycobacterial diversity and abundances were highly variable. Mycobacteria were far more abundant, on average, in showerheads receiving municipal versus well water, and in U.S. households as compared to European households, patterns that are likely driven by differences in the use of chlorine disinfectants. Moreover, we found that water source, water chemistry, and household location also influenced the prevalence of specific mycobacterial lineages detected in showerheads. We identified geographic regions within the U.S. where showerheads have particularly high abundances of potentially pathogenic lineages of mycobacteria and these ‘hot spots’ generally overlapped with those regions where NTM lung disease is most prevalent. Together these results emphasize the public health relevance of mycobacteria in showerhead biofilms. They further demonstrate that mycobacterial distributions in showerhead biofilms are often predictable from household location and water chemistry, knowledge that advances our understanding of NTM transmission dynamics and the development of strategies to reduce exposures to these emerging pathogens.
TACN (1, 4, 7-Triazacyclononane) restores the activity of β-lactam antibiotics against Metallo-β-Lactamase producingEnterobacteriaceae: The exploration of potential Metallo-β-Lactamase inhibitors
Authors: Somboro Anou M. , Amoako Daniel G. , Sekyere John Osei , Kumalo Hezekiel M. , Khan René , Bester Linda A. , Essack Sabiha Y.
Published: July 2018

Metallo-β-lactamase producingEnterobacteriaceaeare of grave clinical concern particularly as there are no Metallo-β-lactamase (MBL) inhibitors approved for clinical use. The discovery and development of MBL inhibitors to restore the efficacy of available β-lactams are thus imperative. We investigated a zinc-chelating moiety, 1, 4, 7-triazacyclononane (TACN) for its inhibitory activity against clinical carbapenem-resistantEnterobacteriaceae. Minimum inhibitory concentrations (MICs), minimum bactericidal concentrations (MBCs), serum effect, fractional inhibitory concentrations index and time-kill kinetics were performed using broth microdilution techniques according to the Clinical Laboratory Standard Institute (CSLI) guidelines. Enzyme kinetic parameters and cytotoxicity effects of TACN were determined using spectrophotometric assays. The interactions of the enzyme-TACN complex were investigated by computational studies. Meropenem regained its activity against carbapenemase-producingEnterobacteriaceae, with the MIC decreasing to 0.03 mg/L in the presence of TACN. TACN-Meropenem combinations showed bactericidal effects with MIC/MBC ratio of ≤4, and synergistic activity was observed. Human serum effects on the MICs were insignificant, and TACN was found to be non-cytotoxic at concentrations above the MIC values. Computational studies predicted that TACN inhibits MBLs by targeting their catalytic active site pockets. This was supported by its inhibition constant Ki= 0.044 µM and inactivation constant kinact= 0.0406 (min-1) demonstrating that TACN inhibits MBLs efficiently and holds promise as a potential inhibitor.

Importance

Carbapenem-resistantEnterobacteriaceae(CRE)-mediated infections remain a significant public health concern and have been reported as critical in the World Health Organization’s Priority Pathogens List for the Research and Development of New Antibiotics. CRE produce enzymes such as Metallo-β-lactamases (MBLs), which inactivate β-lactam antibiotics. Combination therapies involving a β-lactam antibiotic and a β-lactamase inhibitor remain a major treatment option for infections caused by β-lactamase-producing organisms. Currently, no MBL inhibitor-β-lactam combination therapy is clinically available for MBL-positive bacterial infections. Hence, developing efficient molecules capable of inhibiting these enzymes could be a promising way to overcome this phenomenon. TACN played a significant role in the inhibitory activity of the tested molecules against CREs by potentiating the carbapenem. This study demonstrated that TACN inhibits MBLs efficiently and holds promises as a potential MBLs inhibitor to help curb the global health threat posed by MBL-producing CREs.
C. elegans Mediator 15 permits low temperature-induced longevity via regulation of lipid and protein homeostasis
Authors: Lee Dongyeop , An Seon Woo A. , Jung Yoonji , Yamaoka Yasuyo , Ryu Youngjae , Goh Grace Ying Shyen , Beigi Arshia , Ma Dengke , Ha Chang Man , Taubert Stefan , Lee Youngsook , Lee Seung-Jae V.
Published: July 2018

Low temperatures slow aging and extend lifespan in many organisms, including Caenorhabditis elegans. However, the metabolic and homeostatic aspects of low temperature-induced longevity remain poorly understood. Here, we show that changes in lipid composition regulated by MDT-15/Mediator 15, transcriptional co-regulator, is essential for low temperature-induced longevity and proteostasis in C. elegans. We find that inhibition of mdt-15 prevents animals from living long at low temperatures. We show that MDT-15 up-regulates fat-7, a fatty acid desaturase, at low temperatures, which increases the ratio of unsaturated to saturated fatty acids. We further demonstrate that maintaining this increased fatty acid ratio is essential for protein homeostasis and longevity at low temperatures. Thus, the homeostasis of lipid composition by MDT-15 appears to be a limiting factor for C. elegans proteostasis and longevity at low temperatures. Our findings highlight the crucial roles of fat regulation in maintaining normal organismal physiology under different environmental conditions.
Simvastatin mediates inhibition of exosome synthesis, localization and secretion via multicomponent interventions
Authors: Kulshreshtha Ankur , Singh Swati , Khanna Kritika , Agrawal Anurag , Ghosh Balaram
Published: July 2018

Discovery of exosomes as modulator of cellular communication has added a new dimension to our understanding of biological processes. Exosomes influence the biological systems by mediating trans-communication across tissues and cells, which has important implication for health and disease. Identification of strategies for exosome modulation may pave the way towards better understanding of exosome biology and development of novel therapeutics. In absence of well-characterized modulators of exosome biogenesis, an alternative option is to target pathways generating important exosomal components. Cholesterol represents one such essential component required for exosomal biogenesis. We initiated this study to test the hypothesis that owing to its cholesterol lowering effect, simvastatin, a HMG CoA inhibitor, might be able to alter exosome formation and secretion. Using previously established protocols for detecting secreted exosomes in biological fluids, simvastatin was tested for its effect on exosome secretion under various in-vitro and in-vivo settings. Murine model of AAI was used for further validation of our findings. Utilizing aforementioned systems, we demonstrate exosome-lowering potential of simvastatin in various in-vivo and in-vitro models, of AAI and atherosclerosis. We believe that the knowledge acquired in this study holds potential for extension to other exosome dominated pathologies and model systems.
Estimation of in vivo constitutive parameters of the aortic wall: a machine learning approach
Authors: Liu Minliang , Liang Liang , Sun Wei
Published: July 2018

The patient-specific biomechanical analysis of the aorta demands the in vivo mechanical properties of individual patients. Current inverse approaches have shown the feasibility of estimating the nonlinear, anisotropic material parameters from in vivo image data using certain optimization schemes. However, since such inverse methods are dependent on iterative nonlinear optimization, these methods are highly computation-intensive, which may take weeks to complete for only a single patient, inhibiting rapid feedback for clinical use. Recently, machine learning (ML) techniques have led to revolutionary breakthroughs in many applications. A potential paradigm-changing solution to the bottleneck associated with patient-specific computational modeling is to incorporate ML algorithms to expedite the procedure of in vivo material parameter identification. In this paper, we developed a ML-based approach to identify the material parameters from three-dimensional aorta geometries obtained at two different blood pressure levels, namely systolic and diastolic geometries. The nonlinear relationship between the two loaded shapes and the constitutive parameters are established by a ML-model, which was trained and tested using finite element (FE) simulation datasets. Cross-validation was used to adjust the ML-model structure on a training/validation dataset. The accuracy of the ML-model was examined using a testing dataset.
Crystal structure and Hirshfeld surface analysis of ethyl (E)-4-[(4-hydroxy-3-methoxy-5-nitrobenzylidene)amino]benzoate
Authors: Victoria Antony Samy , Sivajeyanthi Palaniyappan , Elangovan Natarajan , Balasubramani Kasthuri , Kolochi Thathan , Thanikasalam Kanagasabapathy
Published: July 2018

The title Schiff base compound, C17H16N2O6, has an E configuration with respect to the C=N bond, with a dihedral angle between the two benzene rings of 31.90 (12)°. There is an intramolecular O—H...Onitro hydrogen bond present forming an S(6) ring motif. In the crystal, molecules are linked by pairs of O—H...O hydrogen bonds, forming inversion dimers enclosing an R
2
2(4) ring motif. The dimers are linked about an inversion centre by pairs of C—H...O hydrogen bonds, which enclose R
2
2(22) loops, forming chains propagating along the [10\overline{3}] direction. Hirshfeld surface analysis and fingerprint plots show enrichment ratios for the H...H, O...H and C...H contacts, indicating a high propensity of such interactions in the crystal. Both the nitro group and the CH3–CH2–O– group are positionally disordered.
Prediction and optimization model of activated carbon double layer capacitors based on improved heuristic approach genetic algorithm neural network
Authors: Yang Zhen , Lin Yun , Gu Xingsheng , Liang Xiaoyi
Published: July 2018

Purpose

The purpose of this paper is to study the electrochemical properties of electrode material on activated carbon double layer capacitors. It also tries to develop a prediction model to evaluate pore size value.

Design/methodology/approach

Back-propagation neural network (BPNN) prediction model is used to evaluate pore size value. Also, an improved heuristic approach genetic algorithm (HAGA) is used to search for the optimal relationship between process parameters and electrochemical properties.

Findings

A three-layer ANN is found to be optimum with the architecture of three and six neurons in the first and second hidden layer and one neuron in output layer. The simulation results show that the optimized design model based on HAGA can get the suitable process parameters.

Originality/value

HAGA BPNN is proved to be a practical and efficient way for acquiring information and providing optimal parameters about the activated carbon double layer capacitor electrode material.
An evolutionary based framework for many-objective optimization problems
Authors: Bazargan Lari Kimia , Hamzeh Ali
Published: July 2018

Purpose

Recently, many-objective optimization evolutionary algorithms have been the main issue for researchers in the multi-objective optimization community. To deal with many-objective problems (typically for four or more objectives) some modern frameworks are proposed which have the potential of achieving the finest non-dominated solutions in many-objective spaces. The effectiveness of these algorithms deteriorates greatly as the problem’s dimension increases. Diversity reduction in the objective space is the main reason of this phenomenon.

Design/methodology/approach

To properly deal with this undesirable situation, this work introduces an indicator-based evolutionary framework that can preserve the population diversity by producing a set of discriminated solutions in high-dimensional objective space. This work attempts to diversify the objective space by proposing a fitness function capable of discriminating the chromosomes in high-dimensional space. The numerical results prove the potential of the proposed method, which had superior performance in most of test problems in comparison with state-of-the-art algorithms.

Findings

The achieved numerical results empirically prove the superiority of the proposed method to state-of-the-art counterparts in the most test problems of a known artificial benchmark.

Originality/value

This paper provides a new interpretation and important insights into the many-objective optimization realm by emphasizing on preserving the population diversity.
Innovation capabilities and performance: are they truly linked in SMEs?
Authors: Maldonado-Guzmán Gonzalo , Garza-Reyes Jose Arturo , Pinzón-Castro Sandra Yesenia , Kumar Vikas
Published: July 2018

Purpose

In an environment where business uncertainty is the norm, developing innovation capability in an organisation is increasingly important. The purpose of this paper is to investigate the effects that innovation capabilities have on the business performance of small- and medium-sized enterprises (SMEs) within the context of a regional developing and emerging economy of Mexico, in this case, Aguascalientes.

Design/methodology/approach

The approach of this study is quantitative. Four research hypotheses were formulated and tested using structural equation modelling (SEM). Data were collected through a questionnaire survey responded by 308 SMEs located in the Aguascalientes state of Mexico.

Findings

The results obtained show that innovation in products, processes, marketing and management has a positive and significant effect on the business return of Mexican SMEs.

Originality/value

The paper complements the limited body of knowledge currently existent in the SMEs innovation literature, particularly when compared to that of large organisations. Similar works in other settings have provided mixed results in regards to the effects that innovation capabilities have on the business performance of SMEs. Thus, this paper offers a refined understanding and validation of the relationship between innovation capabilities and business performance, especially within the context of SMEs, and insights into some of the innovation aspects that managers may consider when formulating the strategies of their organisations. Finally, it enables such relationship to be understood within a particular situation, contributing in this manner to expand the body of knowledge in the innovation field.
Prevalence and predictors of tobacco use among Bhutanese adolescents
Authors: Rinchen Sonam , Taneepanichskul Surasak , Dawa Namgay
Published: July 2018

Purpose

The purpose of this paper is to examine the prevalence of tobacco use and associated factors influencing the use of tobacco among adolescents in a school setting.

Design/methodology/approach

A cross-sectional descriptive study was conducted amongst Bhutanese adolescents studying at high schools in the district of Wangdue Phodrang in May 2016. A total of 378 eighth-grade students from four schools participated in the study. A self-administered questionnaire was used to collect data. Bivariate and multivariate logistic regressions were carried out to describe the predictors of tobacco use.

Findings

Of the 378 student participants, 52.90 percent were girls and 47.10 percent boys. The age ranged from 11 to 19 years, and the majority lived in school hostels (82 percent). The prevalence of smoking was 10.80 percent while smokeless tobacco users constituted 11.10 percent in the month preceding the study. Gender, tobacco use by siblings and friends, ever having tried alcohol, consumption of alcohol in the last 30 days, previous experimentation with cigarettes/bidi and smokeless tobacco/baba (p-value <0.05) were significantly related to the use of tobacco among students. In multivariate analysis, tobacco use by friends (AdjOR=1.09; 95%CI=0.01–2.48), ever having tried alcohol (AdjOR=2.24; 95%CI=1.75–3.72), current alcohol use (AdjOR=2.63; 95%CI=1.52–4.31), experimentation with cigarettes/bidi (AdjOR =39.46; 95%CI=11.91–90.63) or with smokeless tobacco/baba (AdjOR=32.61; 95%CI=11.78–90.30) were observed as the strong predictors of current tobacco use among adolescents.

Originality/value

These study results re-emphasized the rising public health concern of tobacco use among younger boys and girls. The findings may help the Bhutanese policy makers and managers to better understand the present situation of adolescent tobacco use and its associated determinants, and formulate appropriate tobacco control strategies for adolescents.
The impact of corporate social responsibility on brand equity
Authors: Yang Jing , Basile Kelly
Published: July 2018

Purpose

Despite the significant investment in research on corporate social responsibility (CSR), there still exists a lack of clarity in terms of how different types of CSR activities lead to the outcomes a firm desires with their investment in CSR. The purpose of this paper is to provide greater insight on the relationship between types of CSR activities and brand equity (BE). The authors develop and test a conceptual framework, which examines the unique relationship between each CSR dimension and BE, as well as the interaction of product-related CSR activities and employee-related CSR activities with CSR activities across the other dimensions.

Design/methodology/approach

The authors collected data from multiple secondary sources, including Kinder, Lydenberg and Domini (KLD) Research and Analytics Inc., Interbrand, Compustat and CMR. The authors used random-effect estimations to estimate panel regressions of BE as a function of the different dimensions of a firm’s CSR, interaction terms between CSR dimensions and product quality and interaction terms between employee relations and other CSR dimensions, as well as a set of control variables and Year dummy variables.

Findings

Based upon a large-scale panel data set including 78 firms for the period of 2000–2014, the results show that diversity- and governance-related CSR have a positive effect on BE, employee-related CSR has a negative effect on BE and both product and employee dimensions play important roles in the relationships between other CSR dimensions and BE. These results have important implications for both theory and practice.

Originality/value

This study makes several contributions to extant literature on CSR and brand strength. First, this study examines the impact of CSR on BE vs alternative measures of brand-related outcomes. This study uses the KLD database to determine scores for firm CSR activity. It is the first to use the extensive KLD database to examine the relationship between types of CSR activities and BE. Last, this study seeks to better understand some of the organizational factors which influence the success of CSR outcomes. Specifically, the research will examine the interaction of product-related and employee-related CSR activities with CSR activities across the other dimensions.
Reasonableness: legitimate reasons for illegitimate presentations at the ED
Authors: Wamsiedel Marius
Published: July 2018

Most studies on gatekeeping at the emergency department (ED) have emphasised the assessment of clients in terms of perceived legitimacy and deservingness, showing that lay considerations lead to exclusionary practices, and the ED contributes to the social reproduction of inequality. Some recent works have challenged this representation, providing compelling evidence of staff's concern for the access to care of the most vulnerable users. I extend this perspective by presenting the criterion of reasonableness of the visit to the ED that nurses in Romania commonly use during the triage admission interview. Reasonableness constitutes an acceptable departure from the mission of the ED that offsets the negative evaluation in terms of legitimacy. Patients deemed to have legitimate reasons for making illegitimate claims for admission escape staff's disciplining efforts. However, the staff‐devised understanding of reasonableness is restrictive and does not attend to most cultural and structural barriers in access to quality health care. I argue that reasonableness indexes structural sensitivity, a fragmentary, tacit, and imperfectly consistent orientation to structural deficiencies in the organisation and provision of primary care.
A BPA Approach to the Shroud of Turin
Authors: Borrini Matteo , Garlaschelli Luigi
Published: July 2018

An investigation into the arm and body position required to obtain the blood pattern visible in the image of the Shroud of Turin was performed using a living volunteer. The two short rivulets on the back of the left hand of the Shroud are only consistent with a standing subject with arms at a ca 45° angle. This angle is different from that necessary for the forearm stains, which require nearly vertical arms for a standing subject. The BPA of blood visible on the frontal side of the chest (the lance wound) shows that the Shroud represents the bleeding in a realistic manner for a standing position while the stains at the back—of a supposed postmortem bleeding from the same wound for a supine corpse—are totally unrealistic. Simulation of bleeding from the nail wounds contacting wood surfaces yielded unclear results.
Serum levels of immunoglobulins in an adult population and their relationship with nonalcoholic fatty liver disease
Authors: Sun Shao Mei , Wang Yan Yan , Zhang Qing , Liu Li , Meng Ge , Yao Zhan Xin , Wu Hong Mei , Xia Yang , Bao Xue , Gu Ye Qing , Wang Hong Lei , Shi Hong Bin , Xu Hai Yan , Wang Xing , Zhou Ming , Jiao Huan Li , Jia Qi Yu , Wang Bang Mao , Niu Kai Jun
Published: July 2018

OBJECTIVES

Few studies have reported the association between nonalcoholic fatty liver disease (NAFLD) and immunoglobulins. In this study, we aimed to investigate the relationship between serum immunoglobulin levels and NAFLD in a Chinese adult population.

METHODS

We performed a cross‐sectional study including 11 261 Chinese adults. NAFLD was diagnosed based on the Chinese Guidelines for the diagnosis and treatment of fatty liver diseases and an alcohol intake of <70 g/week in women and <140 g/week in men, and serum immunoglobulin (Ig) levels were determined using immune nephelometry. Multiple logistic regression analysis was done to assess relationships between concentrations of serum immunoglobulins and NAFLD.

RESULTS

Of the 11 261 adults recruited from January 2010 to December 2015, the prevalence of NAFLD was 40.8% (n = 4598). The geometric mean levels of IgG, IgM, IgE and IgA were 1177.49 mg/dL (95% confidence interval [CI] 1173.07–1181.93), 93.56 mg/dL (95% CI 92.70–94.42), 30.70 IU/mL (95% CI 29.92–31.49) and 216.64 mg/dL (95% CI 214.95–218.34), respectively. Compared with the lowest quintile, the multivariable adjusted odds ratio (95% CI) of NAFLD for the highest quintile of IgG, IgM, IgE, and IgA were 0.78 (0.66–0.92), 0.71 (0.60–0.84), 0.98 (0.84–1.15) and 1.41 (1.21–1.66), respectively.

CONCLUSION

Increased IgA and decreased IgG and IgM levels are independently associated with NAFLD prevalence. Further research is needed to explore the causal association between serum immunoglobulins and NAFLD.
Medical cannabis legalization and opioid prescriptions: evidence on US Medicaid enrollees during 1993–2014
Authors: Liang Di , Bao Yuhua , Wallace Mark , Grant Igor , Shi Yuyan
Published: July 2018

Background and Aims

While the United States has been experiencing an opioid epidemic, 29 states and Washington DC have legalized cannabis for medical use. This study examined whether state‐wide medical cannabis legalization was associated with reduction in opioids received by Medicaid enrollees.

Design

Secondary data analysis of state‐level opioid prescription records from 1993–2014 Medicaid State Drug Utilization Data. Linear time–series regressions assessed the associations between medical cannabis legalization and opioid prescriptions, controlling for state‐level time‐varying policy covariates (such as prescription drug monitoring programs) and socio‐economic covariates (such as income).

Setting

United States.

Participants

Drug prescription records for patients enrolled in fee‐for‐service Medicaid programs that primarily provide health‐care coverage to low‐income and disabled people.

Measurements

The primary outcomes were population‐adjusted number, dosage and Medicaid spending on opioid prescriptions. Outcomes for Schedule II opioids (e.g. hydrocodone, oxycodone) and Schedule III opioids (e.g. codeine) were analyzed separately. The primary policy variable of interest was the implementation of state‐wide medical cannabis legalization.

Findings

For Schedule III opioid prescriptions, medical cannabis legalization was associated with a 29.6% (P = 0.03) reduction in number of prescriptions, 29.9% (P = 0.02) reduction in dosage and 28.8% (P = 0.04) reduction in related Medicaid spending. No evidence was found to support the associations between medical cannabis legalization and Schedule II opioid prescriptions. Permitting medical cannabis dispensaries was not associated with Schedule II or Schedule III opioid prescriptions after controlling for medical cannabis legalization. It was estimated that, if all the states had legalized medical cannabis by 2014, Medicaid annual spending on opioid prescriptions would be reduced by 17.8 million dollars.

Conclusion

State‐wide medical cannabis legalization appears to have been associated with reductions in both prescriptions and dosages of Schedule III (but not Schedule II) opioids received by Medicaid enrollees in the United States.
Characteristics of older people in an inpatient haematology unit: A descriptive study
Authors: Thillainadesan Janani , Ng Lisa , Cunningham Ilona , Wong Doo Nicole , Naganathan Vasi
Published: July 2018

Objective

To characterise older inpatients in a haematology unit.

Methods

Hospital case‐mix data of haematology separations of all ages (n = 7419) and more extensive data restricted to older patients (age ≥75 years, n = 1025) were evaluated.

Results

From 2000 to 2014, there was a 200% increase in those aged ≥85 years who were more likely to have a geriatric syndrome as the principal diagnosis (P < 0.05), have delirium (P < 0.05), receive less intensive treatment (P < 0.001) and be discharged to a nursing home (P < 0.001). Compared to younger inpatients, those aged ≥75 years were more likely to be emergency admissions (48% vs 37%, P < 0.001) and die during the admission (8% vs 4%, P < 0.001).

Conclusion

Haematologists care for older inpatients who are complex with multidisciplinary health service needs. There may be value in conducting comprehensive geriatric assessments in this setting.
Interactive Analysis of Word Vector Embeddings
Authors: Heimerl F. , Gleicher M.
Published: July 2018

Word vector embeddings are an emerging tool for natural language processing. They have proven beneficial for a wide variety of language processing tasks. Their utility stems from the ability to encode word relationships within the vector space. Applications range from components in natural language processing systems to tools for linguistic analysis in the study of language and literature. In many of these applications, interpreting embeddings and understanding the encoded grammatical and semantic relations between words is useful, but challenging. Visualization can aid in such interpretation of embeddings. In this paper, we examine the role for visualization in working with word vector embeddings. We provide a literature survey to catalogue the range of tasks where the embeddings are employed across a broad range of applications. Based on this survey, we identify key tasks and their characteristics. Then, we present visual interactive designs that address many of these tasks. The designs integrate into an exploration and analysis environment for embeddings. Finally, we provide example use cases for them and discuss domain user feedback.
Analyzing Residue Surface Proximity to Interpret Molecular Dynamics
Authors: Lichtenberg N. , Menges R. , Ageev V. , George A. A. Paul , Heimer P. , Imhof D. , Lawonn K.
Published: July 2018

The surface of a molecule holds important information about the interaction behavior with other molecules. In dynamic folding or docking processes, residues of amino acids with different properties change their position within the molecule over time. The atoms of the residues that are accessible to the solvent can directly contribute to binding interactions, while residues buried within the molecular structure contribute to the stability of the molecule. Understanding patterns and causality of structural changes is important for experts in the pharmaceutical domain, e.g., in the process of drug design. We apply an iterative computation of the Solvent Accessible Surface in order to extract virtual layers of a molecule. The extraction allows to track the movement of residues in the body of the molecule, with respect to the distance of the residue to the surface or the core during dynamics simulations. We visualize the obtained layer information for the complete time span of the molecular dynamics simulation as a 2D‐map and for individual time‐steps as a 3D‐representation of the molecule. The data acquisition has been implemented alongside with further analysis functionality in a prototypical application, which is available to the public domain. We underline the feasibility of our approach with a study from the pharmaceutical domain, where our approach has been used for novel insights into the folding behavior of μ‐conotoxins.
Spatio‐Temporal Contours from Deep Volume Raycasting
Authors: Frey S.
Published: July 2018

We visualize contours for spatio‐temporal processes to indicate where and when non‐continuous changes occur or spatial bounds are encountered. All time steps are comprised densely in one visualization, with contours allowing to efficiently analyze processes in the data even in case of spatial or temporal overlap. Contours are determined on the basis of deep raycasting that collects samples across time and depth along each ray. For each sample along a ray, its closest neighbors from adjacent rays are identified, considering time, depth, and value in the process. Large distances are represented as contours in image space, using color to indicate temporal occurrence. This contour representation can easily be combined with volume rendering‐based techniques, providing both full spatial detail for individual time steps and an outline of the whole time series in one view. Our view‐dependent technique supports efficient progressive computation, and requires no prior assumptions regarding the shape or nature of processes in the data. We discuss and demonstrate the performance and utility of our approach via a variety of data sets, comparison and combination with an alternative technique, and feedback by a domain scientist.
Acetone clearance of mesocolic or mesorectal fat increases lymph node yield and may improve detection of high‐risk Stage II colorectal cancer patients
Authors: Leung C. A. W. , Fazzi G. E. , Melenhorst J. , Rennspiess D. , Grabsch H. I.
Published: July 2018

Aim

Lymph node (LN) status is key to determining the need for adjuvant therapy in colorectal cancer (CRC) and for disease which has progressed to Stage II (T3–T4, N0, M0). A yield of fewer than 12 LNs is considered a risk factor similar to high‐grade histology and vascular, lymphatic and perineural invasion. The aim of this retrospective study was to investigate the effect of acetone fat clearance of the mesocolon or mesorectum on LN yield and the identification of patients with high‐risk Stage II CRC.

Method

After conventional LN retrieval, fatty tissue derived from the mesocolon or mesorectum of 80 CRC specimens was incubated in acetone for 24 h. A second dissection was then performed by a trained technician. The total number of LNs as well as tumour involvement (LNpositive and LNnegative) were assessed at each stage. In addition, LN morphology was assessed and clinicopathological data were extracted from existing pathology reports.

Results

Eighty CRC specimens were available for study. 1548 (94%) LN were negative and 96 (6%) were positive. The median (range) LN yield per specimen was 12 (3–41) LN increasing to 18 (4–48) LN after fat clearance (P < 0.001). After fat clearance, 534 additional LNs were identified in 75 (94%) of the specimens, and all but 10 were negative. The pN stage did not change in six patients who were found to be LN positive after fat clearance. However, the number of high‐risk Stage II CRC patients decreased from 11 to 7. Although important for these patients, this downstaging did not reach statistical significance (P = 0.125).

Conclusion

Acetone clearance of mesocolic or mesorectal fat increases median LN yield and may in a larger study decrease the number of patients classified as having high‐risk Stage II CRC.
Vitiligo und Autoantikörper: Systematischer Review und Metaanalyse
Authors: Liu Che‐Wei , Huang Yu‐Chen
Published: July 2018

Über die Prävalenz von Autoantikörpern bei Patienten mit Vitiligo wurde zwar in zahlreichen berichtet belegt, die Ergebnisse waren jedoch bei einigen Autoantikörpern nicht konsistent. Ziel der vorliegenden Studie war es, eine systematische Übersicht über die Prävalenz von Autoantikörpern bei Vitiligo‐Patienten zu geben und eine Metaanalyse zu erstellen. Zu diesem Zweck wurde die gesamte Literatur bis zum 31. Dezember 2016 gesichtet. Berücksichtigt wurden Fall‐Kontroll‐Studien mit Vitiligo‐Patienten und einer Kontrollgruppe. Bei Vitiligo‐Patienten betrug die Prävalenz von Anti‐Thyreoperoxidase (ATPO)‐Antikörpern, Anti‐Thyreoglobulin (ATG)‐Antikörpern, antinukleären Antikörpern (ANA), Antikörpern gegen gastrische Parietalzellen (AGPCA), Antikörpern gegen glatte Muskulatur (anti‐smooth muscle antibodies, ASMA), antimitochondrialen Antikörpern (AMA) und Antikörpern gegen die Nebennieren 15,1 %, 9,7 %, 12,5 %, 11,7 %, 12,6 %, 0,2 % beziehungsweise 2,5 %. Die Prävalenz von ATPO‐Antikörpern (Odds‐Ratio [OR]: 3,975; 95 % Konfidenzintervall [CI]: 3,085–5,122), ATG‐Antikörpern (OR: 3,759, 95 % CI: 2,554–5,531), ANA (OR: 1,797, 95 % CI: 1,182–2,731), AGPCA (OR: 2,503, 95 % CI: 1,497–2,896) und Antikörpern gegen die Nebenniere (OR: 9,808, 95 % CI: 1,809–53,159) (Abbildung 2a–e) war bei Vitiligo‐Patienten signifikant höher als bei der Kontrollgruppe. Patienten mit Vitiligo sollten routinemäßig auf Antikörper gegen Schilddrüsenantigene überprüft werden, um diejenigen Patienten zu ermitteln, bei denen ein hohes Risiko besteht, eine autoimmune Schilddrüsenerkrankung zu entwickeln.
Positionspapier: Diagnostik und Therapie der Xerosis cutis
Authors: Augustin Matthias , Wilsmann‐Theis Dagmar , Körber Andreas , Kerscher Martina , Itschert Götz , Dippel Michaela , Staubach Petra
Published: July 2018

Hintergrund und Rationale

Die Xerosis cutis (Synonym: Xerodermie, trockene Haut, hydrolipidarme Haut) ist mit > 10 Millionen Betroffenen nicht nur eine der häufigsten dermatologischen Diagnosen in Deutschland, sondern auch Leitsymptom vieler dermatologischer, internistischer und neurologischer Erkrankungen. Trotz der medizinischen Relevanz der topischen Basistherapie für die Xerosis cutis gibt es in Deutschland für ihr Management bisher keinen wissenschaftlich belegten Diagnostik‐ und Therapiealgorithmus.

Ziel

Dieses Positionspapier vermittelt Ärzten fachübergreifend einen an individuellen Symptomen orientierten, praxisnahen Leitfaden für die Prävention, Diagnostik und Therapie der Xerosis cutis.

Methodik

Im Rahmen eines strukturierten Entscheidungsprozesses wurden von erfahrenen dermatologischen Experten zunächst praxisrelevante Fragestellungen definiert und systematisch aufgearbeitet. Auf der Basis von Evidenz und Expertenkonsens wurden daraus diagnostische und therapeutische Algorithmen mit Empfehlungen für die Praxis entwickelt und konsentiert.

Ergebnis

Die Xerosis cutis kann grundsätzlich klinisch diagnostiziert werden. Auslöser und/oder Grunderkrankungen müssen abgeklärt und vermieden bzw. spezifisch behandelt werden. Bei der Wahl der geeigneten Basistherapie ist es wichtig, dass nicht nur die Hauthydratation verbessert, sondern auch die Barrierefunktion der Haut wiederhergestellt wird. Sie sollte daher aus einer Kombination von rückfeuchtenden und rückfettenden Inhaltsstoffen bestehen. Je trockener die Haut, desto lipidhaltiger sollte die Hautpflege sein (bevorzugt Wasser‐in‐Öl‐Formulierungen). Die individuelle Auswahl der Inhaltsstoffe orientiert sich nach kausaler Prüfung an den Symptomen Schuppung (v.a. Urea), Fissuren/Rhagaden (v.a. Urea oder Dexpanthenol), Rötung (v.a. Licochalcone A) und Pruritus (v.a. Polidocanol), sowie an der Lokalisation und dem Alter der Patienten. Inhaltsstoffe bzw. Inhaltsstoffkombinationen mit guter Studienevidenz sind zu bevorzugen. Die mit Abstand beste Evidenz bei der Xerosis cutis weist Urea auf, dessen Wirksamkeit in Kombination mit anderen natürlichen Feuchthalte‐Komponenten und Ceramiden noch gesteigert werden kann. Zur Arbeitserleichterung am Patienten und zum besseren Erlernen wurde das Xerosimeter entwickelt, das die praktische Umsetzung der Diagnostik und Verlaufskontrolle, eine Klassifikation der Inhaltsstoffe und einen strukturierten Therapiealgorithmus enthält.

Schlussfolgerung

Das hier vorgeschlagene strukturierte symptom‐ und evidenzorientierte Vorgehen mit Diagnostik‐ und Behandlungspfad soll für die Prävention und frühzeitige Behandlung der Xerosis cutis sensibilisieren. Damit können die Lebensqualität verbessert und Folgeerkrankungen verhindert werden.
Effective and economical endoscopic resection using a novel multifunctional snare for small‐sized gastric neoplasms
Authors: Kobara Hideki , Mori Hirohito , Masaki Tsutomu
Published: July 2018

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Telomere shortening and frailty in Mexican older adults
Authors: Ortiz‐Ramírez Mauricio , Sánchez‐García Sergio , García‐Dela Torre Paola , Reyes‐Maldonado Elba , Sánchez‐Arenas Rosalinda , Rosas‐Vargas Haydeé
Published: July 2018

Aim

Telomere shortening has been associated with several age‐related diseases, in addition to being considered a hallmark of aging. Frailty is a clinical syndrome characterized by an accentuated physiological and functional decline that might be a predictor of an adverse condition in older age. The present study evaluated the relationship between frailty and telomere shortening in older adults from Mexico City, Mexico.

Methods

This was a cross‐sectional study. Data were collected from 323 frail older adults, including physical and environmental factors, such as body mass index, comorbidities, physical activity and tobacco consumption. Telomere length was measured by real‐time polymerase chain reaction. The frailty syndrome was diagnosed using the Fried criteria.

Results

An association between frailty and telomere shortening was found in both sexes. Telomere length decreased from 6.05 kb (5.54–6.48 kb) to 4.20 kb (3.80–4.54 kb; P < 0.001). It was also observed that tobacco consumption could be a significant modifying factor in the association between these two variables. Previous reports are contradictory, suggesting that there is no relationship between telomere length and frailty; however, it is possible that there are genetic and/or environmental variables to be elucidated, that might influence this association, particularly in the studied population.

Conclusions

Telomere length is inversely related to frailty in Mexican frail older adults, and tobacco consumption is the main environmental modifying factor. Geriatr Gerontol Int 2018; 18: 1286–1292.
Clinical relevance of 3D gait analysis in patients with haemophilia
Authors: Fouasson‐Chailloux A. , Maugars Y. , Vinatier C. , Trossaert M. , Menu P. , Rannou F. , Guicheux J. , Dauty M.
Published: July 2018

Haemophilia is characterized by a congenital deficiency of clotting factor VIII or IX. One of the consequences of haemophilia is joint bleedings. Repetitive haemathroses induce cartilage damage and chronic synovitis leading to joint deterioration, and to definitive haemophilic arthropathy which is source of walking disability. Three‐dimension gait analysis (3DGA) appears particularly relevant in the case of haemophilia because it allows an evaluation of several joints in weight‐bearing situations. The purpose of this study was to review the interest and the contribution of 3DGA in the management of patients with haemophilia. The greatest interest of gait analysis would be to detect early walking changes with a non‐invasive and well‐tolerated examination, especially in paediatric population. In adulthood, this technic may be also useful to help detect walking worsening in patients known to have already arthropathy. However, it takes time to realize and needs expensive equipment, which limits its possibility of routine use. Although generalizations of these results remain difficult, especially to compare patients with haemophilia to normal population. Indeed, in the studies, patient groups are small and usually heterogeneous in terms of age and target joints. It certainly results of the rarity of the disease. So, it could be interesting to perform a study with a larger cohort in order to allow subgroup analysis, helping to define clearly the place of 3DGA in the strategy of haemophilia evaluation.
HER2 immunohistochemistry in endometrial and ovarian clear cell carcinoma: discordance between antibodies and with in‐situ hybridisation
Authors: Koopman Timco , van der Vegt Bert , Dijkstra Marcel , Bart Joost , Duiker Evelien , Wisman G. Bea A. , de Bock Geertruida H. , Hollema Harry
Published: July 2018

Aims

Treatment with anti‐HER2 therapy could be beneficial for patients with HER2‐positive endometrial and ovarian clear cell carcinoma (CCC). We studied HER2 overexpression by immunohistochemistry (IHC) using three different antibodies, including concordance with amplification by in‐situ hybridisation (ISH).

Methods and results

IHC and ISH were performed on tissue microarrays of 101 tumours: 58 endometrial pure CCC, 19 endometrial mixed carcinomas with a CCC component and 24 ovarian pure CCC. IHC was performed using SP3, 4B5 and HercepTest antibodies, and was scored by two independent observers. ISH was performed using dual‐colour silver ISH. Using IHC, agreement was poor between SP3/4B5 (61.4%), poor between SP3/HercepTest (68.3%) and reasonable between 4B5/HercepTest (75.2%). Interobserver agreement was substantial to almost perfect for all antibodies (SP3: linear weighted κ = 0.89, 4B5: κ = 0.90, HercepTest: κ = 0.76). HER2‐positivity by ISH was 17.8% (endometrial pure CCC: 24.1%, endometrial mixed: 0%, ovarian pure CCC: 16.7%). IHC/ISH concordance was poor, with a high false‐negative rate of all three IHC antibodies: sensitivity (38.9–50.0%) and positive predictive value (PPV) (37.5–58.3%) were poor; specificity (81.9–94.0%) and negative predictive value (NPV) (87.1–88.3%) were reasonable. When excluding 2+ cases, sensitivity declined (26.7–43.8%) but PPV (80.0–87.5%) and specificity (98.6–98.7%) improved.

Conclusions

In ovarian and endometrial CCC, there is considerable difference in HER2 overexpression by different IHC antibodies and marked discordance with ISH. As such, no single antibody can be considered conclusive for determining HER2 status in CCC. Based on these results, the lack of predictive value of different HER2 testing methods, as used in other studies, could be explained.