bluuebunny/crossref_metadata_2025 huggingface dataset:
Comparison of level set models in image segmentation
Authors: Rahmat Roushanak , Harris‐Birtill David
Published: August 2018

Image segmentation is one of the most important tasks in modern imaging applications, which leads to shape reconstruction, volume estimation, object detection and classification. One of the most popular active segmentation models is level set models which are used extensively as an important category of modern image segmentation technique with many different available models to tackle different image applications. Level sets are designed to overcome the topology problems during the evolution of curves in their process of segmentation while the previous algorithms cannot deal with this problem effectively. As a result, there is often considerable investigation into the performance of several level set models for a given segmentation problem. It would therefore be helpful to know the characteristics of a range of level set models before applying to a given segmentation problem. In this study, the authors review a range of level set models and their application to image segmentation work and explain in detail their properties for practical use.
Robust image registration of printed circuit boards using improved SIFT‐PSO algorithm
Authors: Dai Linhui , Guan Qiao , Liu Hong
Published: August 2018

Printed circuit board (PCB) layout is becoming high density, high performance, light, and short. In the automatic PCB defect detection system, image registration of PCB plays an important role. However, most of the traditional registration methods are inefficient, and cannot cope with the problems of image distortion, affine, noise, and so on. To address this issue, the authors propose an improved scale invariant feature transform (SIFT) feature extraction algorithm combined with particle swarm optimisation (PSO) to register the images of PCB which placed on a conveyor belt. The advantage of the presented approach is that the registration results are more robust and efficient by optimising the existing PCB image matching framework. The experimental results on the proposed PCB datasets show that the speed of the proposed method (improved SIFT‐PSO) is faster than the traditional SIFT feature registration method, and the average computing time of processing single picture can be improved by 10 s, the registration accuracy can be improved by 3–4%. Compared with the experimental results of other algorithms, the root‐mean‐square error can be reduced to 0.5146 by using the proposed method. Thus, the proposed method (improved SIFT‐PSO) is more accurate and robust in real‐time inspection system of PCB.
Efficient community detection method based on attribution of nodes in complex network
Authors: Cai Biao , Sang Qiang , Zeng Lina , Wu Jiang
Published: August 2018

The research of network science is of great significance to the study of human society. The discovery of community structure in a network is an important research direction in the network science. Based on the research of traditional community discovery, this study found that sporadic nodes at the edge of a network only belong to the community to which the node is connected. Therefore, the community attributions of these sporadic edge nodes are stronger than that of the network central nodes. Based on this finding, the authors proposed a community discovery method based on the calculation of network node belongingness. In this proposed method, the community detection is first carried out based on the node attributions. Second, a simple method that determines the number of communities is defined. At last, the communities are optimally combined according to the average node attributions of the network so as to realise the community discovery of the network. This proposed algorithm has low time complexity and high detection accuracy in low coverage networks.
Boundary node detection for WSNs based on simple community percolation
Authors: Cai Biao , Sang Qiang , Yang Kaixue
Published: August 2018

The coverage holes in wireless sensor networks (WSNs) have severe negative effects on their life cycle and reliability. This study describes a study of WSN coverage holes based on the community percolation theory in complex networks. In the absence of information about node locations, detection algorithms and parameter optimisation with boundaries covering holes and the outer boundary of the network as the subject were studied. According to the percolation theory, changes in the state of any node in the network may cause changes in the entire network. Based on that, changes in the states of different nodes corresponding to changes in the state of a specific node were investigated to detect coverage holes in the network. Analogue simulations indicated detection of over 90% boundary nodes.
Synthetic training samples for enhanced locality‐constrained dictionary learning
Authors: Zhang Yanghao , Zeng Shaoning , Zeng Wei , Jiang Hui
Published: August 2018

Dictionary learning serves as a considerable role in image processing and pattern recognition. However, when applied to face classification, it may suffer from the issue of the limited quantity of training samples. Therefore, it becomes a challenge to obtain a robust and discriminative dictionary. Recently, locality‐constrained and label embedding dictionary learning (LCLE‐DL) takes the locality and label information of atoms into account to achieve an effective performance in image classification. In this study, the authors exploit a new approach which uses synthetic training samples to enhance this dictionary learning algorithm, so they name it STS‐DL. Firstly, they strengthen the diversities of training samples by producing virtual samples. Secondly, the LCLE‐DL algorithm is used to calculate two deviations on the basis of the original training samples and the authors’ newly synthetic samples, respectively. Finally, they integrate them together to perform the classification task, which produces a more promising performance for image recognition. Abundant experiments have been conducted on several benchmark databases, the experimental results illustrate that the proposed STS‐DL shows a higher accuracy than the LCLE‐DL method, as well as some state‐of‐the‐art dictionary learning and sparse representation algorithms in image classification.
AM of three‐dimensional spongy microstructures for a piezoelectric sprayer
Authors: Chen Chin‐Tai , Hsu Shin‐Fang
Published: August 2018

Additive manufacturing (AM) of spongy (cancellous) microstructures in the development and application of piezoelectric sprayers was investigated. The structures featuring microfluidic channels were made of solid polylactic acid (PLA) by fused deposition modelling (FDM) designed with a width of 35 mm, a depth of 25 mm, a height of 56 mm, and a cross‐layer thickness of 2 mm. In total nine network structures were altered with the line widths (Wd) from 300 to 500 μm and the line spacing (Sd) from 250 to 400 μm. Then, one piezoelectric plate and another micronozzle array were assembled with the structures as a microactuator. The piezoelectric actuator had a resonance frequency of 107.8 ± 1 kHz, in which it generated microsprays of 3 ml water with a typical volumetric rate of ∼1.1 ml/min. On the basis of FDM with PLA, the works’ dimensional error analysis showed that the minimum AM errors (<5%) between the design and actual dimensions occurred with the Wd of 350 μm and the Sd of 300–350 μm. In addition, they experimentally discovered anisotropic wettability and different roughness of the PLA layered surfaces, largely concerning the microfluidic performance of the network structures of the piezoelectric sprayer.
Realisation of one‐dimensional (Si/SiO2)N PC filter in visible light band
Authors: Yang Yibiao , You Yi , Zhao Xiaodan , Chen Zhihui , Zhang Mingda , Fei Hongming
Published: August 2018

The work proposes a one‐dimensional photonic crystal (PC) filter with (Si/SiO2)N structure, which is used to filter in the visible light band. The optical properties are simulated theoretically by using the transfer matrix method. Propagating properties under different incident angles and different period numbers for both Transverse Electric (TE) mode and Transverse Magnetic (TM) mode are studied. A photonic bandgap (PBG) is found between 450 and 700 nm. For both TE and TM modes, the blue shift can be found as the incident angle increases. The PC films are prepared by radio‐frequency (RF) magnetron sputtering experimentally. The experimental results are in accordance with the simulation results. The results indicate that the PBG is related to the incident angle and the period number, and increasing the period number is a feasible way to ensure the stability of the PBG. The studies are beneficial to the design of the PC filter in the future.
The EDIBLES survey
Authors: Elyajouri M. , Lallement R. , Cox N. L. J. , Cami J. , Cordiner M. A. , Smoker J. V. , Fahrang A. , Sarre P. J. , Linnartz H.
Published: August 2018

Context. An unambiguous identification of the carriers of the diffuse interstellar bands (DIBs) would provide important clues to the life cycle of interstellar matter. The so-called C2-DIBs are a class of very weak bands that fall in the blue part of the optical spectrum and are associated with high column densities of the C2 molecule. DIB profile structures constrain potential molecular carriers, but their measurement requires high signal-to-noise, high-resolution spectra and the use of sightlines without Doppler splitting, as typical for a single-cloud situation.

Aims. Spectra from the ESO Diffuse Interstellar Bands Large Exploration Survey (EDIBLES) conducted at the Very Large Telescope (ESO/Paranal) were explored to identify single-cloud and high C2 column sightlines, extract the corresponding C2-DIBs and study their strengths and profiles, and to investigate in detail any sub-structures.

Methods. The target selection was made based on profile-fitting of the 3303 and 5895 Å Na I doublets and the detection of C2 lines. The C2 (2–0) (8750–8849 Å) Phillips system was fitted using a physical model of the host cloud. C2 column densities, temperatures as well as gas densities were derived for each sightline.

Results. Eighteen known C2-DIBs and eight strong non-C2 DIBs were extracted towards eight targets, comprising seven single-cloud and one multi-cloud line-of-sights. Correlational studies revealed a tight association of the former group with the C2 columns, whereas the non-C2 DIBs are primarily correlated with reddening. We report three new weak diffuse band candidates at 4737.5, 5547.4, and 5769.8 Å. We show for the first time that at least 14 C2-DIBs exhibit spectral sub-structures which are consistent with unresolved rotational branches of molecular carriers. The variability of their peak separations among the bands for a given sightline implies that their carriers are different molecules with quite different sizes. We also illustrate how profiles of the same DIB vary among targets and as a function of physical parameters, and provide tables defining the sub-structures to be compared with future models and experimental results.
CO destruction in protoplanetary disk midplanes: Inside versus outside the CO snow surface
Authors: Bosman Arthur D. , Walsh Catherine , van Dishoeck Ewine F.
Published: August 2018

Context. The total gas mass is one of the most fundamental properties of disks around young stars, because it controls their evolution and their potential to form planets. To measure disk gas masses, CO has long been thought to be the best tracer as it is readily detected at (sub)mm wavelengths in many disks. However, inferred gas masses from CO in recent ALMA observations of large samples of disks in the 1–5 Myr age range seem inconsistent with their inferred dust masses. The derived gas-to-dust mass ratios from CO are between one and two orders of magnitude lower than the ISM value of ~100 even if photodissociation and freeze-out are included. In contrast, Herschel measurements of hydrogen deuteride line emission of a few disks imply gas masses in line with gas-to-dust mass ratios of 100. This suggests that at least one additional mechanism is removing CO from the gas phase.

Aims. Here we test the suggestion that the bulk of the CO is chemically processed and that the carbon is sequestered into less volatile species such as CO2, CH3OH, and CH4 in the dense, shielded midplane regions of the disk. This study therefore also addresses the carbon reservoir of the material which ultimately becomes incorporated into planetesimals.

Methods. Using our gas-grain chemical code, we performed a parameter exploration and follow the CO abundance evolution over a range of conditions representative of shielded disk midplanes.

Results. Consistent with previous studies, we find that no chemical processing of CO takes place on 1–3 Myr timescales for low cosmic-ray ionisation rates, <5 × 10−18 s−1. Assuming an ionisation rate of 10−17 s−1, more than 90% of the CO is converted into other species, but only in the cold parts of the disk below 30 K. This order of magnitude destruction of CO is robust against the choice of grain-surface reaction rate parameters, such as the tunnelling efficiency and diffusion barrier height, for temperatures between 20 and 30 K. Below 20 K there is a strong dependence on the assumed efficiency of H tunnelling.

Conclusions. The low temperatures needed for CO chemical processing indicate that the exact disk temperature structure is important, with warm disks around luminous Herbig stars expected to have little to no CO conversion. In contrast, for cold disks around sun-like T Tauri stars, a large fraction of the emitting CO layer is affected unless the disks are young (<1 Myr). This can lead to inferred gas masses that are up to two orders of magnitude lower. Moreover, unless CO is locked up early in large grains, the volatile carbon composition of the icy pebbles and planetesimals forming in the midplane and drifting to the inner disk will be dominated by CH3OH, CO2 and/or hydrocarbons.
Julius Kaljuvee, Ivan Reinwald, and Estonian pioneering ideas on meteorite impacts and cosmic neocatastrophism in the early 20th century
Authors: Racki Grzegorz , Viik Tõnu , Puura Väino
Published: August 2018

The article comprehensively presents little known Estonian contribution to the recognition of first meteorite impact structures in Europe, related to works of Julius Kaljuvee (Kalkun; 1869–1940) and Ivan Reinwald (Reinwaldt; 1878–1941). As an active educator specialized in geoscience, Kaljuvee was the first to hypothesize in 1922 that Kaali lake cirque in Saaremaa Island, Estonia, was created by meteorite impact. Thanks to mining engineer Reinwald, this assumption was accepted since 1928 due to the exhaustive field and borehole works of the latter (also as a result of exploration by several German scholars, including renowned Alfred Wegener). The impact origin of Kaali structure was proved finally in 1937 by finding of meteoritic iron splinters (as the first European site). Reinwald was not only outstanding investigator of meteorite cratering process, but also successful propagator of the Estonian discoveries in Anglophone mainstream science in 1930s. In addition, in his 1933 book, Kaljuvee first highlighted an impact explanation of enigmatic Ries structure in Bavaria, as well as probable magmatic activation in distant regions due to “the impulse of a giant meteorite”. He also outlined ideas of the inevitable periodic cosmic collisions in geological past (“rare event” theory nowadays), and resulting biotic crises. In a general conceptual context, the ideas of Kaljuvee were in noteworthy direct or indirect link with concepts of the great French naturalists – Laplace, Cuvier and Élie de Beaumont. However, some other Kaljuvee’s notions, albeit recurrent also later in geoscientific literature, are queer at the present time (e.g., the large-body impact as a driving force of continental drift and change the Earth axis, resulting in the Pleistocene glaciation). Thus, the Kaljuvee thought-provocative but premature dissertation is rather a record of distinguishing erudite activity, but not a real neocatastrophic landmark in geosciences history. Nevertheless, several concepts of Kaljuvee were revived as the key elements in the current geological paradigm.
Linked color imaging reduces the miss rate of neoplastic lesions in the right colon: a randomized tandem colonoscopy study
Authors: Paggi Silvia , Mogavero Giuseppe , Amato Arnaldo , Rondonotti Emanuele , Andrealli Alida , Imperiali Gianni , Lenoci Nicoletta , Mandelli Giovanna , Terreni Natalia , Conforti Francesco , Conte Dario , Spinzi Giancarlo , Radaelli Franco
Published: August 2018

Background Linked color imaging (LCI) is a newly developed image-enhancing endoscopy technology that provides bright endoscopic images and increases color contrast. We investigated whether LCI improves the detection of neoplastic lesions in the right colon when compared with high definition white-light imaging (WLI).

Methods Consecutive patients undergoing colonoscopy were randomized (1:1) after cecal intubation into right colon inspection at first pass by LCI or by WLI. At the hepatic flexure, the scope was reintroduced to the cecum under LCI and a second right colon inspection was performed under WLI in previously LCI-scoped patients (LCI–WLI group) and vice versa (WLI–LCI group). Lesions detected on first- and second-pass examinations were used to calculate detection and miss rates, respectively. The primary outcome was the right colon adenoma miss rate.

Results Of the 600 patients enrolled, 142 had at least one adenoma in the right colon, with similar right colon adenoma detection rates (r-ADR) in the two groups (22.7 % in LCI–WLI and 24.7 % in WLI–LCI). At per-polyp analysis, double inspection of the right colon in the LCI–WLI and WLI–LCI groups resulted in an 11.8 % and 30.6 % adenoma miss rate, respectively (P < 0.001). No significant difference in miss rate was found for advanced adenomas or sessile serrated lesions. At per-patient analysis, at least one adenoma was identified in the second pass only (incremental ADR) in 2 of 300 patients (0.7 %) in the LCI – WLI group and in 13 of 300 patients (4.3 %) in the WLI – LCI group (P = 0.01).

Conclusions LCI could reduce the miss rate of neoplastic lesions in the right colon.
Outcomes after endoscopic resection of large laterally spreading lesions of the papilla and conventional ampullary adenomas are equivalent
Authors: Klein Amir , Qi Zhengyan , Bahin Farzan , Awadie Halim , Nayyar Dhruv , Ma Michael , Voermans Rogier , Williams Stephen , Lee Eric , Bourke Michael
Published: August 2018

Background Endoscopic resection of ampullary adenomas is a safe and effective alternative to surgical resection. A subgroup of patients have large laterally spreading lesions of the papilla Vateri (LSL-P), which are frequently managed surgically. Data on endoscopic resection of LSL-P are limited and long-term outcomes are unknown. The aim of this study was to compare the outcomes of endoscopic resection of LSL-P with those of standard ampullary adenomas.

Methods A retrospective analysis of a prospectively collected and maintained database was conducted. LSL-P was defined as extension of the lesion ≥ 10 mm from the edge of the ampullary mound. Piecemeal endoscopic mucosal resection of the laterally spreading component was followed by resection of the ampulla. Patient, lesion, and procedural data, as well as results of endoscopic follow-up, were collected.

Results 125 lesions were resected. Complete endoscopic resection was achieved in 97.6 % at the index procedure (median lesion size 20 mm, interquartile range [IQR] 13 – 30 mm). Compared with ampullary adenomas, LSL-Ps were significantly larger (median 35 mm vs. 15 mm), contained a higher rate of advanced pathology (38.6 % vs. 18.5 %), and had higher rates of intraprocedural bleeding (50 % vs. 24.7 %) and delayed bleeding (25.0 % vs. 12.3 %). Both groups had similar rates of histologically proven recurrence at first surveillance (16.4 % vs. 17.9 %). Median follow-up for the entire cohort was 18.5 months. For patients with at least two surveillance endoscopies (n = 68; median follow-up 29 months, IQR 18 – 48 months), 95.6 % were clear of disease and considered cured.

Conclusions LSL-P can be resected endoscopically with comparable outcomes to standard ampullectomy, albeit with a higher risk of bleeding. Endoscopic treatment should be considered as an alternative to surgical resection, even for large LSL-P.
Dilation or biodegradable stent placement for recurrent benign esophageal strictures: a randomized controlled trial
Authors: Walter Daisy , van den Berg Maarten , Hirdes Meike , Vleggaar Frank , Repici Alessandro , Deprez Pierre , Viedma Bartolomé , Lovat Laurence , Weusten Bas , Bisschops Raf , Haidry Rehan , Ferrara Elisa , Sanborn Keith , O’Leary Erin , van Hooft Jeanin , Siersema Peter
Published: August 2018

Background Dilation is the standard of care for recurrent benign esophageal strictures (BES). Biodegradable stents may prolong the effect of dilation and reduce recurrences. Efficacy and safety of dilation and biodegradable stent placement early in the treatment algorithm of recurrent BES were compared.

Methods This multicenter, randomized study enrolled patients with BES treated with previous dilations to ≥ 16 mm. The primary end point was number of repeat endoscopic dilations for recurrent stricture within 3 and 6 months. Secondary outcomes through 12 months included safety, time to first dilation for recurrent stricture, dysphagia, and level of activity.

Results At 3 months, the biodegradable stent group (n = 32) underwent significantly fewer endoscopic dilations for recurrent stricture compared with the dilation group (n = 34; P < 0.001). By 6 months, the groups were similar. The number of patients experiencing adverse events was similar between the groups. Two patients in the biodegradable stent group died after developing tracheoesophageal fistulas at 95 and 96 days post-placement; no deaths were attributed to the stent. Median time to first dilation of recurrent stricture for the biodegradable stent group was significantly longer (106 vs. 41.5 days; P = 0.003). Dysphagia scores improved for both groups. Patients in the biodegradable stent group had a significantly higher level of activity through 12 months (P < 0.001).

Conclusion Biodegradable stent placement is associated with temporary reduction in number of repeat dilations and prolonged time to recurrent dysphagia compared with dilation. Additional studies are needed to better define the exact role of biodegradable stent placement to treat recurrent BES.
Reliability and accuracy of a novel classification system using peroral cholangioscopy for the diagnosis of bile duct lesions
Authors: Robles-Medranda Carlos , Valero Manuel , Soria-Alcivar Miguel , Puga-Tejada Miguel , Oleas Roberto , Ospina-Arboleda Jesenia , Alvarado-Escobar Haydee , Baquerizo-Burgos Jorge , Robles-Jara Carlos , Pitanga-Lukashok Hannah
Published: August 2018

Background The aim of this study was to propose a novel, comprehensive, macroscopic classification for bile duct lesions.

Methods A two-stage protocol was designed. In Stage I, a retrospective study (September 2013 to September 2015) of patients with bile duct lesions detected by peroral cholangioscopy (POCS) was performed. A total of 315 images with at least 6 months of follow-up were recorded, analyzed, and correlated to histology, and were classified as non-neoplastic (one of three types, 1 – 3) or neoplastic (one of four types, 1 – 4) based on morphological and vascular patterns. In Stage II, a prospective, nonrandomized, double-blind study was performed from December 2015 to December 2016 to validate the proposed classification. Sensitivity, specificity, positive and negative predictive values (PPV and NPV, respectively), and positive and negative likelihood ratios (LR + and LR – , respectively) were calculated (gold standard: 6-month follow-up). Inter- and intraobserver agreement (kappa value, κ) among experts and non-experts were calculated.

Results 171 patients were included (65 retrospective; 106 prospective). In Stage I, 28/65 cases were neoplastic and 37 /65 were non-neoplastic, according to the final diagnosis. In Stage II, 56/106 were neoplastic with a sensitivity, specificity, PPV, NPV, LR + , and LR – for neoplastic diagnosis of 96.3 %, 92.3 %, 92.9 %, 96 %, 12.52, and 0.04, respectively. The proposed classification presented high reproducibility among observers, for both neoplastic and subtypes categories. However, it was better for experts (κ > 80 %) than non-experts (κ 64.7 % – 81.9 %).

Conclusion The novel classification system could help physicians to distinguish non-neoplastic from neoplastic bile duct lesions.
Evaluation of genotoxicity related to oral methylene blue chromoendoscopy
Authors: Repici Alessandro , Ciscato Camilla , Wallace Michael , Sharma Prateek , Anderloni Andrea , Carrara Silvia , Di Leo Milena , Hassan Cesare
Published: August 2018

Background An oral formulation of methylene blue with colonic delivery (MB-MMX) has been developed to increase detection of colorectal polys during colonoscopy. Traditionally, there have been safety concerns regarding DNA damage when methylene blue is exposed to white light. The aim of this study was to evaluate DNA damage in colonic mucosa after MB-MMX chromoendoscopy.

Methods This was an open-label phase II safety study to assess for genotoxicity on colorectal biopsies of patients undergoing two sequential colonoscopies before and after an oral dose of 200 mg MB-MMX added to their bowel prep. Analysis of a biomarker of double-stranded DNA breaks, γH2AX, was performed on biopsy specimens.

Results Ten patients were included in the study. The mean expression of γH2AX ± 95 % confidence intervals of the 50 biopsies before and after MB-MMX administration were 0.58 ± 0.08 and 0.62 ± 0.09, respectively (P = 0.24). None of the analyzed samples showed excess positive γH2AX expression, confirming the absence of DNA damage on biopsies after methylene blue exposure. No deaths or serious adverse events occurred.

Conclusions An oral dose of 200 mg of MB-MMX did not result in any detectable DNA damage.
Using Probability for Pathological Complete Response (pCR) as a Decision Support Marker for Neoadjuvant Chemotherapy in HER2 Negative Breast Cancer Patients – a Survey Among Physicians
Authors: Gass Paul , Untch Michael , Müller Volkmar , Möbus Volker , Thomssen Christoph , Häberle Lothar , Erber Ramona , Hein Alexander , Jud Sebastian , Lux Michael , Hack Carolin , Hartmann Arndt , Kolberg Hans-Christian , Ettl Johannes , Lüftner Diana , Jackisch Christian , Beckmann Matthias , Janni Wolfgang , Schneeweiss Andreas , Fasching Peter , Nabieva Naiba
Published: August 2018

Background In women with early breast cancer, a pathological complete response (pCR) after neoadjuvant chemotherapy is reported to be associated with an improvement of the survival. The aim of this survey among physicians was to investigate whether the probability of achieving pCR in patients with a hormone receptor-positive, HER2-negative disease encourages physicians to recommend neoadjuvant chemotherapy.

Methods The study was conducted via an online survey that was sent to 493 physicians, who were either known as members of national guideline committees, heads of breast cancer centers, being high recruiters in clinical trials or leading a private practice. Participants were asked about a specific case that should resemble patients for whom it is unclear, whether they should be treated with chemotherapy.

Results 113 (24.5%) physicians participated at the survey, out of which 96.5% had a work experience of more than 10 years and 94.7% were board certified in their specialty. A total of 84.1% would consider pCR for a decision concerning neoadjuvant chemotherapy. With regard to the pCR probability, 2.7 and 10.6% of the participants demanded at least a pCR rate of 5 and 10%, respectively, while 25.7% were satisfied with 20% probability, and another 25.7% with a pCR rate of 30%.

Conclusions The vast majority of the long-term experienced physicians would embrace the implementation of a further method such as the prediction of pCR probability in clinical routine to support decision making regarding the necessity of neoadjuvant chemotherapy. The cut-off of around 30% pCR probability seems to be a realizable rate to distinguish patient groups.
Leitlinien „Chorea/Morbus Huntington“ für die deutschsprachigen Länder neu überarbeitet
Authors: Saft Carsten , Bonelli Raphael , Burgunder Jean-Marc , Dose Matthias , Epplen Jörg , Jung Hans , Priller Josef , Reilmann Ralf , Rudnik Sabine , Seppi Klaus , Landwehrmeyer G. Bernhard
Published: August 2018

Die neu überarbeiteten Leitlinien Chorea/Morbus Huntington geben auf S2k Niveau einen Überblick über den Stand der Forschung zum Erkrankungsverlauf sowie zu neuen Ansätzen der symptomatischen und verlaufsmodifizierenden Therapie bei der Huntington-Krankheit. Im Gegensatz zu vielen anderen Leitlinien bevorzugen die Autoren aus den deutschsprachigen Ländern als Erstlinienbehandlung der Chorea Tiaprid. Aufgrund von Nebenwirkungen, welche unter Tetrabenazin auftreten können – wie etwa Depression oder Akathisie, ist es gängige Praxis, Tetrabenazin erst in zweiter Linie einzusetzen. Die Leitlinien nehmen Stellung zu rechtlichen Fragen der Präimplantationsdiagnostik (PID) und der pränatalen Diagnostik (PD) in Deutschland, Österreich und der Schweiz sowie zu den Unterschieden zwischen dem prädiktiven und dem differenzialdiagnostischen Einsatz der molekulargenetischen Diagnostik. In den Leitlinien wird darüber hinaus sehr ausführlich zu den möglichen Differenzialdiagnosen bei einer Chorea ungeklärter Ätiologie Stellung genommen.
Between Scylla and Charybdis: Charting the Wicked Problem of Reusing Health Data for Clinical Research Informatics
Authors: Lea Nathan , Nicholls Jacqueline , Fitzpatrick Natalie
Published: August 2018

Objectives: Recognising dilemmas posed by the sharing and reuse of health data as a classic wicked problem and uncover some current key challenges to clinical research informatics.

Methods: A modified thematic review process including identification of agreed critical research questions, appropriate query terms and search strategy, identification of relevant papers in accordance with inclusion criteria, and authors' co-review of full text papers.

Results: Queries returned 4,779 papers published between January 2014 and November 2017. A shortlist of 197 abstracts was analysed and 18 papers were finally selected for review. Thematic assessment of findings revealed four key challenges: (1) uncertain reliability of consent as a cornerstone of trust due to the limits to understanding and awareness of data sharing; (2) ethical challenges around equity and autonomy; (3) ambitious overly theoretical governance frameworks lacking practical validity; and (4) a clear desire for further public and individual engagement to achieve clearer and more nuanced knowledge dissemination around data sharing practice and governance frameworks.

Conclusions: Understanding the wicked problem of reusing clinically acquired health data for research purposes is essential if clinical research is to benefit from informatics advances. A lack of understanding around the context of data acquisition and sharing undermines the foundations of patient-professional trust. Efforts to protect privacy, where tailoring to specific contexts is a key driver, should support the development of solutions which more adequately honour privacy needs, justify access, and protect equity and autonomy.
Clinical Research Informatics: Contributions from 2017
Authors: Daniel Christel , Kalra Dipak ,   Section Editors for the IMIA Yearbook Section on Clinical Research Informatics
Published: August 2018

Objectives: To summarize key contributions to current research in the field of Clinical Research Informatics (CRI) and to select best papers published in 2017.

Method: A bibliographic search using a combination of MeSH descriptors and free terms on CRI was performed using PubMed, followed by a double-blind review in order to select a list of candidate best papers to be then peer-reviewed by external reviewers. A consensus meeting between the two section editors and the editorial team was organized to finally conclude on the selection of best papers.

Results: Among the 741 returned papers published in 2017 in the various areas of CRI, the full review process selected five best papers. The first best paper reports on the implementation of consent management considering patient preferences for the use of de-identified data of electronic health records for research. The second best paper describes an approach using natural language processing to extract symptoms of severe mental illness from clinical text. The authors of the third best paper describe the challenges and lessons learned when leveraging the EHR4CR platform to support patient inclusion in academic studies in the context of an important collaboration between private industry and public health institutions. The fourth best paper describes a method and an interactive tool for case-crossover analyses of electronic medical records for patient safety. The last best paper proposes a new method for bias reduction in association studies using electronic health records data.

Conclusions: Research in the CRI field continues to accelerate and to mature, leading to tools and platforms deployed at national or international scales with encouraging results. Beyond securing these new platforms for exploiting large-scale health data, another major challenge is the limitation of biases related to the use of “real-world” data. Controlling these biases is a prerequisite for the development of learning health systems.
Behavioral Economics Interventions in Clinical Decision Support Systems
Authors: Cho Insook , Bates David
Published: August 2018

Background: Clinical decision support (CDS) systems can improve safety and facilitate evidence-based practice. However, clinical decisions are often affected by the cognitive biases and heuristics of clinicians, which is increasing the interest in behavioral and cognitive science approaches in the medical field.

Objectives: This review aimed to identify decision biases that lead clinicians to exhibit irrational behaviors or responses, and to show how behavioral economics can be applied to interventions in order to promote and reveal the contributions of CDS to improving health care quality.

Methods: We performed a systematic review of studies published in 2016 and 2017 and applied a snowball citationsearch method to identify topical publications related to studies forming part of the BEARI (Application of Behavioral Economics to Improve the Treatment of Acute Respiratory Infections) multisite, cluster-randomized controlled trial performed in the United States.

Results: We found that 10 behavioral economics concepts with nine cognitive biases were addressed and investigated for clinician decision-making, and that the following five concepts, which were actively explored, had an impact in CDS applications: social norms, framing effect, status-quo bias, heuristics, and overconfidence bias.

Conclusions: Our review revealed that the use of behavioral economics techniques is increasing in areas such as antibiotics prescribing and preventive care, and that additional tests of the concepts and heuristics described would be useful in other areas of CDS. An improved understanding of the benefits and limitations of behavioral economics techniques is also still needed. Future studies should focus on successful design strategies and how to combine them with CDS functions for motivating clinicians.
CHARACTERIZATION OF THe HUMAN FACTOR XII GENE
Authors: Cool D E , MacGillivray R T A
Published: August 2018

Surface activation of the plasma systems involved with coagulation, fibrinolysis, renin formation and kinin generation involves factor XII (Hageman factor). This protein is a 76,000 dalton glycoprotein which circulates in plasma as an inactive form of a serine protease. A human liver cDNA coding for factor XII was used to screen a human genomic phage library. Two overlapping clones were isolated, XHXII27 and XHXII76, and contain the entire gene for human factor XII. The gene is 13.5 Kbp in length and consists of 14 exons and 13 introns. The transcriptional start site of the mRNA was determined using S1 mapping and primer extension analysis. The results indicate that the 5′ untranslated end of the mRNA has a leader sequence of 47 bp and is not interrupted by an intron in the gene. DNA sequence analysis of the region upstream of the transcriptional start site does not contain TATA or CAAT sequences, which are often found in other genes transcribed by RNA polymerase II. The positions of the introns in the coding sequence separate the protein into domains which are homologous to similar regions found in fibronectin and tissue-type plasminogen activator. Furthermore, wherever protein homologies are found, the positions of the introns in the triplet codon occur in the same reading frame as in the tissue-type plasminogen activator, urokinase plasminogen activator and factor XII genes. The intron/exon organization of the factor XII gene is different to the organization of other coagulation genes such as prothrombin, factor IX and factor X. Therefore, factor XII appears to have evolved as a member of the plasminogen activator family of genes rather than as a member of the clotting factor gene family.
THE ORGANIZATION OF THE HUMAN FACTOR XI GENE: CORRELATION OF INTRON AND EXON LOCATIONS WITH STRUCTURAL DOMAINS
Authors: Chung D W , Asakai R , Davie E W
Published: August 2018

Factor XI (plasma thromboplastin antecedent) is a plasma glycoprotein that participates in the contact activation of blood coagulation. In the present study, the organization of the gene for human factor XI has been elucidated. The gene for human factor XI has been isolated from two independent human genomic λ phage libraries using a full length cDNA for human factor XI as a hybridization probe. Four overlapping recombinant λ phage containing the human factor XI gene have been isolated and characterized. Restriction mapping, Southern blotting and hybridization studies indicate that the entire gene for human factor XI is 25 kilobases in length. Overlapping regions of the gene have been subcloned and the DNA sequence of selective regions has been determined. These results show that the gene for factor XI is composed of 15 exons and 14 introns. Exon I codes for the 5′ noncoding sequences and exon II codes for the signal peptide of 18 amino acid residues. The four tandem repeats that constitute the heavy chain of factor XIa are each encoded by two consecutive exons (exons III and IV, V and VI, VII and VIII, IX and X). The location of the introns and the junction type among these four tandem repeats are strictly conserved. Exon XI, XII, XIII, XIV and XV code for the light chain of factor XIa that contains the serine protease part of the molecule. The location of the introns and the junction types in this region of the gene are identical to those in the corresponding regions of the genes for human tissue plasminogen activator and porcine urokinase. These results show that gene duplication and exon shuffling play a significant role in the evolution of the human factor XI gene. (Supported in part by NIH Grant HL 16919 and AHA Grant 82-221.)
ON THE KINETICS OF THE INHIBITION OF PLASMINOGEN ACTIVATORS BY THE PLASMINOGEN ACTIVATOR INHIBITOR PAI-1
Authors: Chmielewska J , Wiman B
Published: August 2018

The kinetics of the inhibition of the following plasminogen activators: one- and two-chain tissue plasminogen activator (t-PA) and low and high molecular weight urokinase (UK) by PAI-1 was studied. For this purpose direct systems were employed and the reactions were studied in the presence of different concentrations of plasminogen activator chromogenic substrates. The second-order rate constant of the association reaction was estimated from the initial decline in plasminogen activator activity. Determination of the rate constants in the absence of substrates was performed by plotting the rate constants versus the substrate concentrations and extrapolation to zero concentration. The rate constants with all plasminogen activators were very similar and estimated as 2 - 4 x 107 M-1 x s-1. The reactions were also studied in the presence of 6-aminohexanoic acid, lysine, arginine, guanidinium chloride (final concentrations for all substances about 1 mmol/L) and heparin (10 mg/L), without any significant effect on the rate constants. The effect of soluble fibrin (bathroxobin-digested fibrinogen in urea) at 10 - 300 nmol/L was also studied. With one-chain t-PA the rate constant was decreased about 10-fold with the highest fibrin concentration and about 2-fold at 30 nmol/L. In contrast, the reactions with urokinase or two-chain t-PA were not influenced by fibrin at these concentrations. These findings may have a physiological significance: the one-chain t-PA adsorbed to the fibrin surface and actively involved in fibrinolysis would be protected against inactivation by PAI. This phenomenon adds further to the physiological fibrin specificity of one-chain t-PA.
OXYGEN FREE RADICAL-DEPENDENT STEP IN THE CYTOTOXICITY OF DEC-TREATED PLATELETS
Authors: Caebron J Y , Joseph M , Vorng H , Pincemail J , Lagaede M , Capron A
Published: August 2018

Over the past 35 years, diethylcarbamazine (DEC) has been the most widely used agent for the treatment of filarial diseases. However, in spite of millions of individuals treated, the mode of action of this drug remained unexplained until recently when we reported that the microfilaricidal activity of DEC was mediated by blood platelets with the additional triggering of a filarial excretory antigen (FEA) (Nature, 1987).

To set up the mechanism of the larvicidal action of platelets activatedby both DEC and FEA, various inhibitors of the arachidonic acid metabolism were added in the cytotoxic assay. Aspirin failed to modify the platelet activity, whilst nordihydroguaiaretic acid, esculetin, and 5,8,11,14-heneicosatetraynoic acid dose-dependently inhibited the killing of parasites. This relationship suggested the production of a putative cytotoxic lipoxygenase product. Surprisingly, no increase in oxygenated metabolites was noted both by thin layer chromatography and by high pressure liquid chromatography.

Thus, we investigated the involvement of oxygen free radicals. The hydroxyl radical scavengers tested (benzoate, uric acid, mannitol, methylene blue... ) more or less inhibited the platelet killing activity. In addition, Fe2 + (down to 10-11M) enhanced the DEC-induced cytotoxicity which was abolished in the presence of the Fe2 + chelator o-phenantroline. Finally, using the electronspin resonance technique it was possible to drop OH radicals from platelets with DMPO, but only in the presence of both DEC and FEA.

These results, taken with those concerning the interaction of either IgE/anti-IgE (Nature, 1983, 303, 810-812) or CRP (Science, 1986, 231, 153-156) with platelets, should be regarded as a significant insight into the involvement of platelets in various pathological processes.
INCREASED SULFATION INCREASES THE BLEEDING SIDE-EFFECTS OF GLYCOSAMINOGLYCANS
Authors: Van Ryn-Mckenna J , Ofosu F A , Johnson E A , Hirsh J , Buchanan M R
Published: August 2018

We and others have shown that the bleeding side-effect of heparin is not related to the ex vivo anticoagulant effect of heparin, as measured by traditional clotting tests or chromo-genic assays. In recent experimental studies, using a rabbit ear bleeding model, we found that a highly sulfated low molecular weight heparin (LMWH) fraction enhanced blood loss 10-fold, whereas its unfractionated LMWH parent compound only enhanced blood loss 2-fold. We therefore, performed studies to investigate the relationship between the degree of sulfation of 7 sulfated polysaccharides (SPSs) and their bleeding side-effects usina the above model. Blood loss was measured as the increase in 51Cr-red cells lost from 5 standardized cuts in the rabbit ear. The dose of each SPS studied was 20 or 40 times the doses which were required to inhibit thrombosis by ∼75% in a jugular vein/hypercoagulation/stasis model. Ex vivo, we measured the effect of the SPSs on collagen-induced platelet aggregation. Sulfation of each SPS was measured as meq/g of SPS. The*re was a positive correlation between the degree of sulfation of the SPS and blood loss, p<0.05 (Figure a), ie. the greater the degree of sulfation, the greater the amount of blood lost. There was also a correlation between the degree of sulfation of the SPS and inhibition of platelet aggregation, p<0.001 (Figure b). Thus, the dose of each SPS that enhanced blood loss also inhibited platelet aggregation. We conclude that the degree of sulfation of SPS contributes to increased blood loss associated with heparin treatment, and that this effect is due, in part, to the inhibition of platelet aggregation.
PLATELET 12-HYDROXY-5,8,10-HEPTADECATRIENOIC ACID (HHT) STIMULATES PROSTACYCLIN PRODUCTION BY ENDOTHELIAL CELLS
Authors: Stuart M J , Sadowitz P D , Setty B N Y
Published: August 2018

Although HHT accounts for approximately one third of the ara-chidonic acid (AA) metabolites produced by stimulated platelets, no well defined function has been attributed to this platelet product. We report that HHT stimulates prostacyclin production by endothelial cells, and have identified the mechanism for this effect. In human umbilical venous endothelial cells HHT (0.5 and 1pM) stimulated prostacyclin (RIA for 6KPGF1α) by 32±10% (1 SE) and 42±13% (P<0.05 and (0.01). Similar changes were observed when the effect of HHT on exogenous [1 -14C] AA metabolism in fetal bovine aortic endothelial cells (FBAECs) was studied. 6KPGF1α was stimulated by 25±9% and 30±6% at HHT cones, of 0.5 and 1μM (P<0.05) . While prelabelling experiments with [1-14c] AA revealed that HHT (1μM) did not affect the ionophore stimulated release of AA from FBAEC membrane lipids (29521±11837 cpm/well control vs 32458+8811 in HHT treated cells, mean ±1SD) kinetic analyses revealed that HHT affected vascular cyclooxygenase. HHT (1μM) increased Vmax in test microsomes (706±21 pmol/mg/min) when compared to controls (529±20; P<0.02). No effect on Km was observed (6.2±0.3μM control vs. 7.2±0.4 in HHT treated microsomes). The effect of HHT on platelet AA metabolism was next studied. Preincubation of washed platelets with HHT (1μM) did not enhance thrombin (0.2 U/ml) induced pit. TXB2 (2.27±1.34 pmol/106 platelets control vs 2.28±1.62 in HHT treated platelets). In platelets prelabelled with [ 1-14c] AA, HHT (1μM) also had no effect on AA release post thrombin stimulation (5794_423 cpm per 108 platelets control vs. 6135±612 for paired HHT treated cells). Conversion to cyclooxygenase metabolites was also not enhanced (2605±265 vs 2806±332 for test platelets). HHT thus stimulates vascular prostacyclin without a concomitant effect on platelet AA metabolism. Our findings may explain the discrepancies relative to prostacyclin production in atherosclerosis and diabetes. In these disorders while ex vivo production of prostacyclin by vascular tissue is decreased, in vivo production is elevated. HHT may also be an important local modulator of platelet plug formation and could play a protective antithrombotic role by its hitherto unrecognized effect on vascular prostacyclin.