bluuebunny/crossref_metadata_2025 huggingface dataset:
Steroid dependency and trends in prescribing for inflammatory bowel disease – a 20‐year national population‐based study
Authors: Chhaya V. , Saxena S. , Cecil E. , Subramanian V. , Curcin V. , Majeed A. , Pollok R. C.
Published: July 2016

Background

It is unclear whether adherence to prescribing standards has been achieved in inflammatory bowel disease (IBD).

Aim

To determine how prescribing of 5‐aminosalicylates (5‐ASAs), steroids and thiopurines has changed in response to emerging evidence.

Methods

We examined trends in oral and topical therapies in 23 509 incident IBD cases (6997 with Crohn's disease and 16 512 with ulcerative colitis) using a nationally representative sample between 1990 and 2010. We created five eras according to the year of diagnosis: era 1 (1990–1993), era 2 (1994–1997), era 3 (1998–2001), era 4 (2002–2005) and era 5 (2006–2010). We calculated the proportion of patients treated with prolonged 5‐ASAs (>12 months) and steroid dependency, defined as prolonged steroids (>3 months) or recurrent (restarting within 3 months) steroid exposure. We calculated the cumulative probability of receiving each medication using survival analysis.

Results

Half of the Crohn's disease patients were prescribed prolonged oral 5‐ASAs during the study, although this decreased between era 3 and 5 from 61.8% to 56.4% (P = 0.002). Thiopurine use increased from 14.0% to 47.1% (P < 0.001) between era 1 and 5. This coincided with a decrease in steroid dependency from 36.5% to 26.8% (P < 0.001) between era 1 and 2 and era 4 and 5 respectively.

In ulcerative colitis, 49% of patients were maintained on prolonged oral 5‐ASAs. Despite increasing thiopurine use, repeated steroid exposure increased from 15.3% to 17.8% (P = 0.02) between era 1 and 2 and era 4 and 5 respectively.

Conclusions

Prescribing in clinical practice insufficiently mirrors the evidence base. Physicians should direct management towards reducing steroid dependency and optimising 5‐ASA use in patients with IBD.
Collectively coping with contact: The role of intragroup support in dealing with the challenges of intergroup mixing in residential contexts
Authors: Stevenson Clifford , Sagherian‐Dickey Thia
Published: July 2016

The social identity approach to stress has shown how intragroup support processes shape individuals' responses to stress across health care, workplace, and community settings. However, the issue of how these ‘social cure’ processes can help cope with the stress of intergroup contact has yet to be explored. This is particularly important given the pivotal role of intergroup threat and anxiety in the experience of contact as well as the effect of contact on extending the boundaries of group inclusion. This study applies this perspective to a real‐life instance of residential contact in a divided society. Semi‐structured interviews with 14 Catholic and 13 Protestant new residents of increasingly mixed areas of Belfast city, Northern Ireland, were thematically analysed. Results highlight that transitioning to mixed communities was fraught with intergroup anxiety, especially for those coming from ‘single identity’ areas. Help from existing residents, especially when offered by members of other religious denominations, signalled a ‘mixed community ethos’ to new residents, which facilitated adopting and sharing this identity. This shared identity then enabled them to deal with unexpected intergroup threats and provided resilience to future sectarian division. New residents who did not adopt this shared identity remained isolated, fearful, and prone to negative contact.
Socioeconomic factors and penile cancer risk and mortality; a population‐based study
Authors: Torbrand Christian , Wigertz Annette , Drevin Linda , Folkvaljon Yasin , Lambe Mats , Håkansson Ulf , Kirrander Peter
Published: July 2016

Objective

To investigate possible associations between socioeconomic status (SES) and penile cancer risk, stage at diagnosis, and mortality.

Patients/subjects and methods

A population‐based register study including men in Sweden diagnosed with penile cancer between 2000 and 2012 (1676 men) and randomly chosen controls (9872 men). Data were retrieved from the National Penile Cancer Register (NPECR) and several other population‐based healthcare and sociodemographic registers. Educational level, disposable income, marital status, and number of individuals in the household, were assessed as indicators of SES. The risk of penile cancer and penile cancer death in relation to SES were estimated using logistic regression and proportional hazards models, respectively. Cumulative cause‐specific mortality (CSM) estimates by SES were calculated using the Kaplan–Meier method.

Results

A low educational level and low disposable income were associated with an increased risk of invasive penile cancer. Furthermore, low educational level was associated with more advanced primary tumour stage. Divorced and never married men had a generally increased risk of penile cancer and were diagnosed with more advanced primary tumour stages. However, neither educational level nor marital status was associated with lymph node or distant metastases. Also, men in single‐person households had an increased risk of both non‐invasive and invasive disease. In men with invasive penile cancer, there were no significant associations of indicators of SES and CSM.

Conclusions

Low educational level, low disposable income, being divorced or never married, and living in a single‐person household, all increase the risk of advanced stage penile cancer, but not lymph node or distant metastases. The assessed indicators of SES did not influence penile CSM. In conclusion, our findings indicates that SES influences the risk and stage of penile cancer, but not survival.
Exploring and Comparing Clusterings of Multivariate Data Sets Using Persistent Homology
Authors: Rieck B. , Leitte H.
Published: July 2016

Clustering algorithms support exploratory data analysis by grouping inputs that share similar features. Especially the clustering of unlabelled data is said to be a fiendishly difficult problem, because users not only have to choose a suitable clustering algorithm but also a suitable number of clusters. The known issues of existing clustering validity measures comprise instabilities in the presence of noise and restrictive assumptions about cluster shapes. In addition, they cannot evaluate individual clusters locally. We present a new measure for assessing and comparing different clusterings both on a global and on a local level. Our measure is based on the topological method of persistent homology, which is stable and unbiased towards cluster shapes. Based on our measure, we also describe a new visualization that displays similarities between different clusterings (using a global graph view) and supports their comparison on the individual cluster level (using a local glyph view). We demonstrate how our visualization helps detect different—but equally valid—clusterings of data sets from multiple application domains.
Space‐Time Bifurcation Lines for Extraction of 2D Lagrangian Coherent Structures
Authors: Machado Gustavo , Boblest Sebastian , Ertl Thomas , Sadlo Filip
Published: July 2016

We present a novel and efficient technique to extract Lagrangian coherent structures in two‐dimensional time‐dependent vector fields. We show that this can be achieved by employing bifurcation line extraction in the space‐time representation of the vector field, and generating space‐time bifurcation manifolds therefrom. To show the utility and applicability of our approach, we provide an evaluation of existing extraction techniques for Lagrangian coherent structures, and compare them to our approach.
Visualizing the Impact of Geographical Variations on Multivariate Clustering
Authors: Zhang Y. , Luo W. , Mack E. A. , Maciejewski R.
Published: July 2016

Traditional multivariate clustering approaches are common in many geovisualization applications. These algorithms are used to define geodemographic profiles, ecosystems and various other land use patterns that are based on multivariate measures. Cluster labels are then projected onto a choropleth map to enable analysts to explore spatial dependencies and heterogeneity within the multivariate attributes. However, local variations in the data and choices of clustering parameters can greatly impact the resultant visualization. In this work, we develop a visual analytics framework for exploring and comparing the impact of geographical variations for multivariate clustering. Our framework employs a variety of graphical configurations and summary statistics to explore the spatial extents of clustering. It also allows users to discover patterns that can be concealed by traditional global clustering via several interactive visualization techniques including a novel drag & drop clustering difference view. We demonstrate the applicability of our framework over a demographics dataset containing quick facts about counties in the continental United States and demonstrate the need for analytical tools that can enable users to explore and compare clustering results over varying geographical features and scales.
Visibility Equalizer Cutaway Visualization of Mesoscopic Biological Models
Authors: Le Muzic M. , Mindek P. , Sorger J. , Autin L. , Goodsell D. S. , Viola I.
Published: July 2016

In scientific illustrations and visualization, cutaway views are often employed as an effective technique for occlusion management in densely packed scenes. We propose a novel method for authoring cutaway illustrations of mesoscopic biological models. In contrast to the existing cutaway algorithms, we take advantage of the specific nature of the biological models. These models consist of thousands of instances with a comparably smaller number of different types. Our method constitutes a two stage process. In the first step, clipping objects are placed in the scene, creating a cutaway visualization of the model. During this process, a hierarchical list of stacked bars inform the user about the instance visibility distribution of each individual molecular type in the scene. In the second step, the visibility of each molecular type is fine‐tuned through these bars, which at this point act as interactive visibility equalizers. An evaluation of our technique with domain experts confirmed that our equalizer‐based approach for visibility specification is valuable and effective for both, scientific and educational purposes.
Cytosplore: Interactive Immune Cell Phenotyping for Large Single‐Cell Datasets
Authors: Höllt T. , Pezzotti N. , van Unen V. , Koning F. , Eisemann E. , Lelieveldt B. , Vilanova A.
Published: July 2016

To understand how the immune system works, one needs to have a clear picture of its cellular compositon and the cells' corresponding properties and functionality. Mass cytometry is a novel technique to determine the properties of single‐cells with unprecedented detail. This amount of detail allows for much finer differentiation but also comes at the cost of more complex analysis. In this work, we present Cytosplore, implementing an interactive workflow to analyze mass cytometry data in an integrated system, providing multiple linked views, showing different levels of detail and enabling the rapid definition of known and unknown cell types. Cytosplore handles millions of cells, each represented as a high‐dimensional data point, facilitates hypothesis generation and confirmation, and provides a significant speed up of the current workflow. We show the effectiveness of Cytosplore in a case study evaluation.
Parallel Marching Blocks: A Practical Isosurfacing Algorithm for Large Data on Many‐Core Architectures
Authors: Liu Baoquan , Clapworthy Gordon J. , Dong Feng , Wu Enhua
Published: July 2016

Interactive isosurface visualisation has been made possible by mapping algorithms to GPU architectures. However, current state‐of‐the‐art isosurfacing algorithms usually consume large amounts of GPU memory owing to the additional acceleration structures they require. As a result, the continued limitations on available GPU memory mean that they are unable to deal with the larger datasets that are now increasingly becoming prevalent.

This paper proposes a new parallel isosurface‐extraction algorithm that exploits the blocked organisation of the parallel threads found in modern many‐core platforms to achieve fast isosurface extraction and reduce the associated memory requirements. This is achieved by optimising thread co‐operation within thread‐blocks and reducing redundant computation; ultimately, an indexed triangular mesh can be produced.

Experiments have shown that the proposed algorithm is much faster (up to 10×) than state‐of‐the‐art GPU algorithms and has a much smaller memory footprint, enabling it to handle much larger datasets (up to 64×) on the same GPU.
Faceted Views of Varying Emphasis (FaVVEs): a framework for visualising multi‐perspective small multiples
Authors: Beecham R. , Rooney C. , Meier S. , Dykes J. , Slingsby A. , Turkay C. , Wood J. , Wong B.L. W.
Published: July 2016

Many datasets have multiple perspectives – for example space, time and description – and often analysts are required to study these multiple perspectives concurrently. This concurrent analysis becomes difficult when data are grouped and split into small multiples for comparison. A design challenge is thus to provide representations that enable multiple perspectives, split into small multiples, to be viewed simultaneously in ways that neither clutter nor overload. We present a design framework that allows us to do this. We claim that multi‐perspective comparison across small multiples may be possible by superimposing perspectives on one another rather than juxtaposing those perspectives side‐by‐side. This approach defies conventional wisdom and likely results in visual and informational clutter. For this reason we propose designs at three levels of abstraction for each perspective. By flexibly varying the abstraction level, certain perspectives can be brought into, or out of, focus. We evaluate our framework through laboratory‐style user tests. We find that superimposing, rather than juxtaposing, perspective views has little effect on performance of a low‐level comparison task. We reflect on the user study and its design to further identify analysis situations for which our framework may be desirable. Although the user study findings were insufficiently discriminating, we believe our framework opens up a new design space for multi‐perspective visual analysis.
Visual Debugging Techniques for Reactive Data Visualization
Authors: Hoffswell Jane , Satyanarayan Arvind , Heer Jeffrey
Published: July 2016

Interaction is critical to effective visualization, but can be difficult to author and debug due to dependencies among input events, program state, and visual output. Recent advances leverage reactive semantics to support declarative design and avoid the “spaghetti code” of imperative event handlers. While reactive programming improves many aspects of development, textual specifications still fail to convey the complex runtime dynamics. In response, we contribute a set of visual debugging techniques to reveal the runtime behavior of reactive visualizations. A timeline view records input events and dynamic variable updates, allowing designers to replay and inspect the propagation of values step‐by‐step. On‐demand annotations overlay the output visualization to expose relevant state and scale mappings in‐situ. Dynamic tables visualize how backing datasets change over time. To evaluate the effectiveness of these techniques, we study how first‐time Vega users debug interactions in faulty, unfamiliar specifications; with no prior knowledge, participants were able to accurately trace errors through the specification.
BubbleNet: A Cyber Security Dashboard for Visualizing Patterns
Authors: McKenna S. , Staheli D. , Fulcher C. , Meyer M.
Published: July 2016

The field of cyber security is faced with ever‐expanding amounts of data and a constant barrage of cyber attacks. Within this space, we have designed BubbleNet as a cyber security dashboard to help network analysts identify and summarize patterns within the data. This design study faced a range of interesting constraints from limited time with various expert users and working with users beyond the network analyst, such as network managers. To overcome these constraints, the design study employed a user‐centered design process and a variety of methods to incorporate user feedback throughout the design of BubbleNet. This approach resulted in a successfully evaluated dashboard with users and further deployments of these ideas in both research and operational environments. By explaining these methods and the process, it can benefit future visualization designers to help overcome similar challenges in cyber security or alternative domains.
Semi‐automatic Vortex Flow Classification in 4D PC‐MRI Data of the Aorta
Authors: Meuschke M. , Köhler B. , Preim U. , Preim B. , Lawonn K.
Published: July 2016

We present an Aortic Vortex Classification (AVOCLA) that allows to classify vortices in the human aorta semi‐automatically. Current medical studies assume a strong relation between cardiovascular diseases and blood flow patterns such as vortices. Such vortices are extracted and manually classified according to specific, unstandardized properties. We employ an agglomerative hierarchical clustering to group vortex‐representing path lines as basis for the subsequent classification. Classes are based on the vortex' size, orientation and shape, its temporal occurrence relative to the cardiac cycle as well as its spatial position relative to the vessel course. The classification results are presented by a 2D and 3D visualization technique. To confirm the usefulness of both approaches, we report on the results of a user study. Moreover, AVOCLA was applied to 15 datasets of healthy volunteers and patients with different cardiovascular diseases. The results of the semi‐automatic classification were qualitatively compared to a manually generated ground truth of two domain experts considering the vortex number and five specific properties.
Critical Points of Gaussian‐Distributed Scalar Fields on Simplicial Grids
Authors: Liebmann T. , Scheuermann G.
Published: July 2016

Simulations and measurements often result in scalar fields with uncertainty due to errors or output sensitivity estimates. Methods for analyzing topological features of such fields usually are not capable of handling all aspects of the data. They either are not deterministic due to using Monte Carlo approaches, approximate the data with confidence intervals, or miss out on incorporating important properties, such as correlation. In this paper, we focus on the analysis of critical points of Gaussian‐distributed scalar fields. We introduce methods to deterministically extract critical points, approximate their probability with high precision, and even capture relations between them resulting in an abstract graph representation. Unlike many other methods, we incorporate all information contained in the data including global correlation. Our work therefore is a first step towards a reliable and complete description of topological features of Gaussian‐distributed scalar fields.
Location‐dependent generalization of road networks based on equivalent destinations
Authors: van Dijk Thomas C. , Haunert Jan‐Henrik , Oehrlein Johannes
Published: July 2016

Suppose a user located at a certain vertex in a road network wants to plan a route using a wayfinding map. The user's exact destination may be irrelevant for planning most of the route, because many destinations will be equivalent in the sense that they allow the user to choose almost the same paths. We propose a method to find such groups of destinations automatically and to contract the resulting clusters in a detailed map to achieve a simplified visualization. We model the problem as a clustering problem in rooted, edge‐weighted trees. Two vertices are allowed to be in the same cluster if and only if they share at least a given fraction of their path to the root. We analyze some properties of these clusterings and give a linear‐time algorithm to compute the minimum‐cardinality clustering. This algorithm may have various other applications in network visualization and graph drawing, but in this paper we apply it specifically to focus‐and‐context map generalization. When contracting shortest‐path trees in a geographic network, the computed clustering additionally provides a constant‐factor bound on the detour that results from routing using the generalized network instead of the full network. This is a desirable property for wayfinding maps.
AVOCADO: Visualization of Workflow–Derived Data Provenance for Reproducible Biomedical Research
Authors: Stitz H. , Luger S. , Streit M. , Gehlenborg N.
Published: July 2016

A major challenge in data‐driven biomedical research lies in the collection and representation of data provenance information to ensure that findings are reproducibile. In order to communicate and reproduce multi‐step analysis workflows executed on datasets that contain data for dozens or hundreds of samples, it is crucial to be able to visualize the provenance graph at different levels of aggregation. Most existing approaches are based on node‐link diagrams, which do not scale to the complexity of typical data provenance graphs. In our proposed approach, we reduce the complexity of the graph using hierarchical and motif‐based aggregation. Based on user action and graph attributes, a modular degree‐of‐interest (DoI) function is applied to expand parts of the graph that are relevant to the user. This interest‐driven adaptive approach to provenance visualization allows users to review and communicate complex multi‐step analyses, which can be based on hundreds of files that are processed by numerous workflows. We have integrated our approach into an analysis platform that captures extensive data provenance information, and demonstrate its effectiveness by means of a biomedical usage scenario.
Visual Analysis of Biomolecular Cavities: State of the Art
Authors: Krone M. , Kozlíková B. , Lindow N. , Baaden M. , Baum D. , Parulek J. , Hege H.‐C. , Viola I.
Published: July 2016

In this report we review and structure the branch of molecular visualization that is concerned with the visual analysis of cavities in macromolecular protein structures. First the necessary background, the domain terminology, and the goals of analytical reasoning are introduced. Based on a comprehensive collection of relevant research works, we present a novel classification for cavity detection approaches and structure them into four distinct classes: grid‐based, Voronoi‐based, surface‐based, and probe‐based methods. The subclasses are then formed by their combinations. We match these approaches with corresponding visualization technologies starting with direct 3D visualization, followed with non‐spatial visualization techniques that for example abstract the interactions between structures into a relational graph, straighten the cavity of interest to see its profile in one view, or aggregate the time sequence into a single contour plot. We also discuss the current state of methods for the visual analysis of cavities in dynamic data such as molecular dynamics simulations. Finally, we give an overview of the most common tools that are actively developed and used in the structural biology and biochemistry research. Our report is concluded by an outlook on future challenges in the field.
State‐of‐the‐Art Report in Web‐based Visualization
Authors: Mwalongo F. , Krone M. , Reina G. , Ertl T.
Published: July 2016

In this report, we review the current state of the art of web‐based visualization applications. Recently, an increasing number of web‐based visualization applications have emerged. This is due to the fact that new technologies offered by modern browsers greatly increased the capabilities for visualizations on the web. We first review these technical aspects that are enabling this development. This includes not only improvements for local rendering like WebGL and HTML5, but also infrastructures like grid or cloud computing platforms. Another important factor is the transfer of data between the server and the client. Therefore, we also discuss advances in this field, for example methods to reduce bandwidth requirements like compression and other optimizations such as progressive rendering and streaming. After establishing these technical foundations, we review existing web‐based visualization applications and prototypes from various application domains. Furthermore, we propose a classification of these web‐based applications based on the technologies and algorithms they employ. Finally, we also discuss promising application areas that would benefit from web‐based visualization and assess their feasibility based on the existing approaches.
State of the Art in Transfer Functions for Direct Volume Rendering
Authors: Ljung Patric , Krüger Jens , Groller Eduard , Hadwiger Markus , Hansen Charles D. , Ynnerman Anders
Published: July 2016

A central topic in scientific visualization is the transfer function (TF) for volume rendering. The TF serves a fundamental role in translating scalar and multivariate data into color and opacity to express and reveal the relevant features present in the data studied. Beyond this core functionality, TFs also serve as a tool for encoding and utilizing domain knowledge and as an expression for visual design of material appearances. TFs also enable interactive volumetric exploration of complex data. The purpose of this state‐of‐the‐art report (STAR) is to provide an overview of research into the various aspects of TFs, which lead to interpretation of the underlying data through the use of meaningful visual representations. The STAR classifies TF research into the following aspects: dimensionality, derived attributes, aggregated attributes, rendering aspects, automation, and user interfaces. The STAR concludes with some interesting research challenges that form the basis of an agenda for the development of next generation TF tools and methodologies.
Formalizing Emphasis in Information Visualization
Authors: Hall K. Wm. , Perin C. , Kusalik P. G. , Gutwin C. , Carpendale S.
Published: July 2016

We provide afresh look at the use and prevalence of emphasis effects in Infovis. Through a survey of existing emphasis frameworks, we extract a set‐based approach that uses visual prominence to link visually and algorithmically diverse emphasis effects. Visual prominence provides a basis for describing, comparing and generating emphasis effects when combined with a set of general features of emphasis effects. Therefore, we use visual prominence and these general features to construct a new mathematical Framework for Information Visualization Emphasis, FIVE. The concepts we introduce to describe FIVE unite the emphasis literature and point to several new research directions for emphasis in information visualization.
Sacral nerve stimulation lead implantation in partial sacral agenesis using intra‐operative computerized tomography
Authors: Castillo J. , Cristóbal L. , Alonso J. , Martín R. , Suárez D. , Martínez M. A. , Cagigas C. , Gómez‐Ruiz M. , Gómez‐Fleitas M. , Vázquez‐Barquero A.
Published: July 2016

Aim

Sacral nerve stimulation (SNS) lead implantation is a straightforward procedure for individuals with intact spinal vertebrae. When sacral anomalies are present, however, the anatomical and radiological reference points used for the accurate placement of the electrode may be absent or difficult to identify.

Method

We describe an innovative surgical procedure of percutaneous nerve evaluation for SNS in a patient with faecal incontinence secondary to a congenital imperforate anus and partial sacral agenesis using a surgical imaging platform (O‐arm system) under neurophysiological control.

Results

Using intra‐operative CT and neuronavigation, the insertion point at the skin was identified. The lead was introduced into the right‐sided S3 foramen and placed at the correct depth. An appropriate motor response was obtained after stimulation and neurophysiological control confirmed that the right S3 root was being stimulated.

Conclusion

Our experience showed that O‐arm guided navigation can be used to overcome the difficulty of SNS lead placement in patients with partial sacral agenesis who have faecal incontinence.
Consistent Extinction Risk Assessment under the U.S. Endangered Species Act
Authors: Boyd Charlotte , DeMaster Douglas P. , Waples Robin S. , Ward Eric J. , Taylor Barbara L.
Published: July 2016

Identifying species at risk of extinction is essential for effective conservation priority‐setting in the face of accelerating biodiversity loss. However, the levels of risk that lead to endangered or threatened listing decisions under the United States Endangered Species Act (ESA) are not well defined. We used a Bayesian population modeling approach to estimate levels of risk consistently for 14 marine species previously assessed under the ESA. For each species, we assessed the risks of declining below various abundance thresholds over various time horizons. We found that high risks of declining below 250 mature individuals within five generations matched well with ESA endangered status, while number of populations was useful for distinguishing between threatened and “not warranted” species. The risk assessment framework developed here could enable more consistent, predictable, and transparent ESA status assessments in the future.
Significant and Timely Ivory Trade Restrictions in Both China and the United States are Critical to Save Elephants
Authors: Yu Yang , Wetzler Andrew , Yang Xuan , Tang Ruchun , Zhang Li
Published: July 2016

The United States and China have committed to enact “nearly complete bans” on the import and export of elephant ivory, including putting in place significant and timely restrictions on the import of ivory as hunting trophies, and taking swift steps to halt their domestic ivory trade. Unlike the United States, China has to move forward on its commitment to further restrict its domestic commercial trade. This is primarily due to China's existing certificated ivory manufacturers and retailers who own huge legal ivory stockpiles. We propose that the Chinese government use its eco‐compensation funds to purchase back all legal ivory from the market. This “decommodification” could help save the elephant population worldwide. Alternatively, China could enact a domestic ban with a short phase‐in period (a similar approach has been adopted by several U.S. States) to allow legal ivory merchants to sell their stockpiles. A hybrid of these two approaches could also be considered.
Spiritual well‐being and coping in scleroderma, lupus erythematosus, and melanoma
Authors: Pilch Michaela , Scharf Sabina Nadine , Lukanz Martin , Wutte Nora Johanna , Fink‐Puches Regina , Glawischnig‐­Goschnik Monika , Unterrainer Human‐Friedrich , Aberer Elisabeth
Published: July 2016

Background and objectives

Religious/spiritual (R‐S) well‐being is associated with greater vitality and lower depression scores. In this study, we investigated strategies for coping with disease and the role of religiosity/spirituality with respect to improving subjective well‐being.

Patients and methods

One hundred and forty‐nine patients (107 women), 44 of whom with systemic sclerosis (SSc), 48 with lupus erythematosus (LE), and 57 with stage I or II malignant melanoma (MM) were surveyed using a self‐designed questionnaire, which addressed subjective well‐being and disease‐related circumstances, as well as the Multidimensional Inventory for Religious/Spiritual Well‐Being (MI‐RSWB).

Results

At the time of diagnosis, disease burden is greater in LE patients than in patients with SSc and MM. Only after several years are SSc and LE patients able to accept their disease. Compared with healthy individuals, the overall score of R‐S well‐being is significantly lower in LE patients. In LE, photosensitivity and joint pain are inversely correlated with the ability to forgive. SSc patients with facial lesions and pulmonary involvement show greater religiosity. MM patients display significantly higher values for transcendental hope.

Conclusion

Talks about the disease and psychological support are the most important needs of patients with SSc, LE, and MM. At present, programs aimed at improving R‐S coping skills do not seem to play a significant role, but could be an important resource that should be addressed in the future.
Checkpoint‐Inhibitoren in der Immuntherapie: Ein Meilenstein in der Behandlung des malignen Melanoms
Authors: Wilden Sophia M. , Lang Berenice M. , Mohr Peter , Grabbe Stephan
Published: July 2016

Seit Jahrzehnten ist bekannt, dass Tumoren vom Immunsystem erkannt und zerstört werden können. Diese, vor allem in Tierversuchen gewonnene Erkenntnis konnte jedoch in der Vergangenheit nicht zum Nutzen unserer Patienten umgesetzt werden, da immunonkologische Therapieansätze in den letzten Jahrzehnten in der Anwendung beim Menschen stets versagt haben. Daher hat, mit Ausnahme der adjuvanten Interferontherapie, keines dieser Verfahren den Einzug in die klinische Versorgung gefunden. Langzeitüberleben unter guter Lebensqualität war dabei sehr wenigen Patienten vorbehalten. Mit den neuen immunologischen Therapieansätzen wird jedoch sowohl das Langzeitüberleben als auch die Lebensqualität onkologischer Patienten neu definiert. Auf die neuen „Immun‐Checkpoint‐Inhibitoren“ spricht erstmals ein relevanter Teil der behandelten Patienten an und diese zeigen in der Regel langandauernde Remissionen bis hin zur Heilung. Schon jetzt ist klar, dass die Immuntherapie in Zukunft eine der wesentlichen Therapiesäulen bei der Behandlung des metastasierten Melanoms und auch vieler anderer fortgeschrittener Tumoren bilden wird. In dieser Übersicht werden die wichtigsten neuen Therapiemodalitäten besprochen und sowohl deren Wirkprinzip als auch klinische Daten zum Therapieansprechen und zu erwartenden Nebenwirkungen der Therapie referiert.
Nebenwirkungsmanagement bei Immun‐Checkpoint‐Blockade durch CTLA‐4‐ und PD1‐Antikörper beim metastasierten Melanom
Authors: Kähler Katharina C. , Hassel Jessica C. , Heinzerling Lucie , Loquai Carmen , Mössner Rotraut , Ugurel Selma , Zimmer Lisa , Gutzmer Ralf ,   für das Komitee „Kutane Nebenwirkungen“ der Arbeitsgemeinschaft Dermatologische Onkologie (ADO)
Published: July 2016

CTLA‐4 und PD‐1 sind mögliche Angriffspunkte für eine Tumor‐bedingte Herunterregulation lymphozytärer Immunantworten. Immuncheckpoint‐modulierende monoklonale Antikörper wirken gegenteilig und induzieren eine Immunantwort gegen diverse Tumoren. CTLA‐4‐ und PD1‐Antikörper modulieren die Interaktion von Tumor, Antigen‐präsentierenden Zellen und T‐Lymphozyten. Die Therapie mit dem CTLA‐4‐Antikörper Ipilimumab und den PD1‐Antikörpern Nivolumab und Pembrolizumab konnte in klinischen Studien einen Vorteil für das Gesamtüberleben der Patienten zeigen, so dass nach einer Zulassung für Ipilimumab im Jahr 2011 dann im Sommer 2015 die Zulassung der beiden PD1‐Antikörper erfolgte.

Eine derartig induzierte und verstärkte Immunantwort bringt unweigerlich in analoger Wirkung Autoimmunphänomene mit sich. Die Kenntnis dieses Nebenwirkungsspektrums ist für Prophylaxe und Management durch den behandelnden Arzt unerlässlich. Als schwere Nebenwirkung ist mit einer Kolitis zu rechnen, welche sich schon früh in ausgeprägten und anhaltenden Diarrhöen bemerkbar macht. Daneben sind auch andere immunvermittelte Erkrankungen wie die Dermatitis, die Hypophysitis, die Thyreoiditis, die Hepatitis, Iridozyklitis und weitere, eher seltenere Autoimmunphänomene beschrieben worden. Durch eine frühzeitige Diagnosestellung und Therapieeinleitung können Risiken und Folgeschäden für Patienten reduziert werden.

Diese Übersichtsarbeit beschreibt die Wirkung einer Immun‐Checkpoint‐Blockade beim metastasierten Melanom und stellt detailliert das Nebenwirkungsspektrum und ‐management dieser Therapeutika dar.
Challenging Gendered Inequalities in Global Health: Dilemmas for NGOs
Authors: Gideon Jasmine , Porter Fenella
Published: July 2016

This article considers the implications of the changing funding landscape in global health for NGOs in the health sector, particularly where they have aspired to promote gender equality and justice through their health work. The article reflects on the tensions that arise as a result of the growing influence of business norms within health funding alongside what critics have termed the ‘scientization’ of global health, and it considers the gendered implications of these developments. It is argued that it is due to the under‐valuation and marginalization of community‐based work that provides spaces for women's voices in the design and delivery of health interventions that large‐scale ‘technical’ interventions receive priority. The article examines what this means in terms of NGOs’ ability to work towards producing transformative change around gender — and indeed racial — equality.
Just Global Health?
Authors: Reid‐Henry Simon
Published: July 2016

Some 40 years ago, the public health philosopher Dan Beauchamp suggested that ‘public health should be a way of doing justice’. The argument put forward in this essay is that global health should be a way of doing global justice, by ameliorating the health inequalities that exclude many millions of people globally from enjoying a healthy life and from the benefits of a fuller inclusion in modern society. The essay develops this argument in three stages. First, it sets out some points of intersection between the politics of (global) health and competing ideas of justice. It offers a very basic typology of global health policy and practice that divides it into ‘market‐justice’ and ‘social‐justice’ models, and shows why it is the market‐justice model that at present dominates. Second, the essay explores how mainstream ‘market‐justice’ approaches to global health deal with the problem of health inequality rather weakly, and it is suggested that there are both historical and geographical reasons for this. Third, three ‘social‐justice’ approaches to global health are explored that better take those historical and geographical conditions into account. In conclusion the essay offers some thoughts on the political uses of theories of justice.
Quantifying passive muscle stiffness in children with and without cerebral palsy using ultrasound shear wave elastography
Authors: Brandenburg Joline E , Eby Sarah F , Song Pengfei , Kingsley‐Berg Shirley , Bamlet William , Sieck Gary C , An Kai‐Nan
Published: July 2016

Aim

The aim of this study was to compare passive muscle stiffness in children with cerebral palsy (CP) and children with typical development using a novel ultrasound technique: ultrasound shear wave elastography (SWE).

Method

We conducted a prospective study of 13 children with CP (six females and seven males, median age 5y 1mo [interquartile range 4y 4mo–7y 8mo]) and 13 children with typical development (six females and seven males, median age 5y 3mo [interquartile range 4y 4mo–9y 4mo]). Demographic information and physical exam measurements were obtained in addition to shear modulus measurements (passive muscle stiffness) of the lateral gastrocnemius muscle at 20° plantar flexion, 10° plantar flexion, and 0° plantar flexion using SWE.

Results

Children with CP had significantly greater shear modulus measurements at all three foot positions (p<0.050). When the shear modulus values were normalized to the baseline value for each child, there was no significant difference between the two groups.

Interpretation

Passive muscle stiffness, measured without the influence of spasticity, is greater in children with CP than in children with typical development when a muscle is at slack and at stretch. When shear modulus was normalized, the results indicate that muscle in children in both groups responds similarly to passive stretch. Further work includes evaluating effect of botulinum toxin on passive muscle properties.
Efficacy and safety of liraglutide compared to sulphonylurea during Ramadan in patients with type 2 diabetes (LIRA‐Ramadan): a randomized trial
Authors: Azar S. T. , Echtay A. , Wan Bebakar W. M. , Al Araj S. , Berrah A. , Omar M. , Mutha A. , Tornøe K. , Kaltoft M. S. , Shehadeh N.
Published: July 2016

Aims

Compare effects of liraglutide 1.8 mg and sulphonylurea, both combined with metformin, on glycaemic control in patients with type 2 diabetes (T2D) fasting during Ramadan.

Materials and methods

In this up to 33‐week, open‐label, active‐controlled, parallel‐group trial, adults [glycated haemoglobin (HbA1c) 7%‐10% (53‐86 mmol/mol); body mass index ≥20 kg/m2; intent to fast] were randomized (1:1) ≥10 weeks before Ramadan to either switch to once‐daily liraglutide (final dose 1.8 mg) or continue pre‐trial sulphonylurea at maximum tolerated dose, both with metformin. Primary endpoint: change in fructosamine, a validated marker of short‐term glycaemic control, during Ramadan.

Results

Similar reductions in fructosamine levels were observed for both groups during Ramadan [liraglutide (−12.8 µmol/L); sulphonylurea (−16.4 µmol/L); estimated treatment difference (ETD) 3.51 µmol/L (95% CI: −5.26; 12.28); p = 0.43], despite lower fructosamine levels in the liraglutide group at start of Ramadan. Fewer documented symptomatic hypoglycaemic episodes were reported in liraglutide‐treated (2%, three subjects) versus sulphonylurea‐treated patients (11%, 18 subjects). No severe hypoglycaemic episodes were reported by either group. Body weight decreased more during Ramadan with liraglutide (ETD: −0.54 kg; 95% CI: −0.94;−0.14; p = 0.0091). The proportion of patients reporting adverse events was similar between groups. Liraglutide led to greater HbA1c reduction [ETD: −0.59% (−6.40 mmol/mol), 95% CI: −0.79; −0.38%; −8.63; −4.17 mmol/mol; p < 0.0001].

Conclusions

Despite lower fructosamine levels and body weight at the beginning of Ramadan, use of liraglutide showed similar glycaemic improvements, fewer hypoglycaemic episodes and greater body weight reduction compared with sulphonylurea. LIRA‐Ramadan provides evidence for liraglutide being safe and efficacious for management of T2D during Ramadan fasting.
Cardiovascular safety of empagliflozin in patients with type 2 diabetes: a meta‐analysis of data from randomized placebo‐controlled trials
Authors: Salsali A. , Kim G. , Woerle H. J. , Broedl U. C. , Hantel S.
Published: July 2016

Aim

To assess the effect of empagliflozin on cardiovascular (CV) risk in patients with type 2 diabetes (T2DM) through a meta‐analysis of data from eight placebo‐controlled trials.

Methods

Data were analysed from eight randomized placebo‐controlled trials undertaken to investigate the efficacy and safety of empagliflozin 10 and 25 mg once daily in patients with T2DM, comprising patients at low/medium and high CV risk. Suspected CV events were prospectively adjudicated. The empagliflozin 10 and 25 mg groups were pooled for the primary analysis. The primary endpoint was a composite of CV death, non‐fatal myocardial infarction (MI), non‐fatal stroke and hospitalization for unstable angina [4‐point major adverse CV events (MACE)]. The secondary endpoint was a composite of CV death, non‐fatal MI and non‐fatal stroke (3‐point MACE). Risk estimates were calculated using Cox regression analysis.

Results

A total of 3835 patients received placebo and 7457 received empagliflozin. Total exposure was 7448.3 years for placebo and 15482.1 years for empagliflozin. Four‐point MACE occurred in 365 (9.5%) patients receiving placebo and 635 (8.5%) patients receiving empagliflozin [hazard ratio for empagliflozin vs. placebo 0.86 (95% CI 0.76, 0.98)]. Three‐point MACE occurred in 307 (8.0%) patients receiving placebo and 522 (7.0%) patients receiving empagliflozin [hazard ratio for empagliflozin vs. placebo 0.84 (95% CI 0.73, 0.96)].

Conclusions

In a meta‐analysis of data from eight randomized trials involving 11 292 patients with T2DM at low/medium or high CV risk, empagliflozin was associated with a reduced risk of 4‐point MACE and 3‐point MACE compared with placebo.
Spike‐timing dependent inhibitory plasticity to learn a selective gating of backpropagating action potentials
Authors: Wilmes Katharina Anna , Schleimer Jan‐Hendrik , Schreiber Susanne
Published: July 2016

Inhibition is known to influence the forward‐directed flow of information within neurons. However, also regulation of backward‐directed signals, such as backpropagating action potentials (bAPs), can enrich the functional repertoire of local circuits. Inhibitory control of bAP spread, for example, can provide a switch for the plasticity of excitatory synapses. Although such a mechanism is possible, it requires a precise timing of inhibition to annihilate bAPs without impairment of forward‐directed excitatory information flow. Here, we propose a specific learning rule for inhibitory synapses to automatically generate the correct timing to gate bAPs in pyramidal cells when embedded in a local circuit of feedforward inhibition. Based on computational modeling of multi‐compartmental neurons with physiological properties, we demonstrate that a learning rule with anti‐Hebbian shape can establish the required temporal precision. In contrast to classical spike‐timing dependent plasticity of excitatory synapses, the proposed inhibitory learning mechanism does not necessarily require the definition of an upper bound of synaptic weights because of its tendency to self‐terminate once annihilation of bAPs has been reached. Our study provides a functional context in which one of the many time‐dependent learning rules that have been observed experimentally – specifically, a learning rule with anti‐Hebbian shape – is assigned a relevant role for inhibitory synapses. Moreover, the described mechanism is compatible with an upregulation of excitatory plasticity by disinhibition.
Sensing of soil bulk density for more accurate carbon accounting
Authors: Lobsey C. R. , Viscarra Rossel R. A.
Published: July 2016

Measurements of soil bulk density can aid our understanding of soil functions and the effects of land use and climate change on soil organic carbon (C) stocks. Current methods for measuring bulk density are laborious and expensive, subject to errors and complicated by the need to measure below the soil surface. These shortcomings are emphasized when there is need to characterize the spatial (lateral and vertical) and temporal variation of soil bulk density and related properties. We developed a technique that combines gamma‐ray attenuation and visible–near infrared (vis–NIR) spectroscopy to measure ex situ the bulk density of 1‐m soil cores that are sampled freshly, wet and under field conditions. We found that the accuracy of the sensor measurements was similar to that of the conventional single‐ring method, but sensing is rapid, inexpensive, non‐destructive and practical. Sensing can be used to measure many soil cores efficiently at fine depth resolutions (e.g. every 2 cm along the core), thereby allowing effective characterization of spatial variation in both lateral and vertical directions. The measurements can be made in the field, on wet soil cores, which reduces the costs and errors associated with transport, handling, oven‐drying and laboratory measurements. We show that sensing of bulk density can be used to measure organic C stocks on either a fixed‐depth (FD) or cumulative soil mass (CSM) basis. Our sensing approach to measure bulk density meets all the requirements for inclusion in a well‐designed soil organic C accounting system; it provides accurate and verifiable data on the spatial variation of soil bulk density so that changes in C stocks might be attributed more accurately to changes in either bulk density or in C content.

Highlights

Proximal soil sensors enable practical, accurate, verifiable and inexpensive measurements of bulk density for C accounting.

We describe a new sensing approach for measuring soil bulk density.

Measurements are rapid, accurate, verifiable and can be made on wet soil under field conditions and to depth.

Sensing enables measurements of C stocks using both fixed‐depth or cumulative soil mass.