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    The transducer-like protein Tlp12 of Campylobacter jejuni is involved in glutamate and pyruvate chemotaxis 

    Lübke, Anastasia-Lisa; Minatelli, Sabrina; Riedel, Thomas; Lugert, Raimond; Schober, Isabel; Spröer, Cathrin; Overmann, Jörg; Groß, Uwe; Zautner, Andreas E; Bohne, Wolfgang
    2018; 18(1): Art. 111
    Abstract Background Campylobacter jejuni is one of the most common bacterial causes of food-borne enteritis worldwide. Chemotaxis in C. jejuni is known to be critical for the successful colonization of the host and key for the adaptation of the microbial species to different host environments. In C. jejuni, chemotaxis is regulated by a complex interplay of 13 or even more different chemoreceptors, also known as transducer-like proteins (Tlps). Recently, a novel chemoreceptor gene, tlp12, was described and found to be present in 29.5% of the investigated C. jejuni strains. Results In this study, we present a functional analysis of Tlp12 with the aid of a tlp12 knockout mutant of the C. jejuni strain A17. Substrate specificity was investigated by capillary chemotaxis assays and revealed that Tlp12 plays an important role in chemotaxis towards glutamate and pyruvate. Moreover, the Δtlp12 mutant shows increased swarming motility in soft agar assays, an enhanced invasion rate into Caco-2 cells and an increased autoagglutination rate. The growth rate was slightly reduced in the Δtlp12 mutant. The identified phenotypes were in partial restored by complementation with the wild type gene. Tlp12-harboring C. jejuni strains display a strong association with chicken, whose excreta are known to contain high glutamate levels. Conclusions TLP12 is a chemoreceptor for glutamate and pyruvate recognition. Deletion of tlp12 has an influence on distinct physiological features, such as growth rate, swarming motility, autoagglutination and invasiveness.
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    Biomechanical and histological analyses of the fracture healing process after direct or prolonged reduction 

    Peterburs, Benedikt; Mittelstaedt, Anke; Haas, Philipp; Petri, Maximilian; Westphal, Ralf; Dullin, Christian; Sehmisch, Stephan; Neunaber, Claudia
    2018; 23(1): Art. 39
    Abstract Background Reduction of femoral shaft fractures remains a challenging problem in orthopaedic surgery. Robot-assisted reduction might ease reduction and fracture treatment. However, the influence of different reduction pathways on patients’ physiology is not fully known yet. Therefore, the aim of this study was to examine the biomechanics and histology of fracture healing after direct and prolonged robot-assisted reduction in an in vivo rat model. Methods 144 male CD® rats were randomly assigned to 12 groups. Each animal received an external fixator and an osteotomy on the left femoral shaft. On the fourth postoperative day, the 1× reduction groups received a single reduction maneuver, whereas the 10× reduction groups received the same reduction pathway with ten repetitions. The control groups did not undergo any reduction maneuvers. Animals were killed after 1, 2, 3 and 4 weeks, respectively, and the composition of the fracture gap was analyzed by µCT and non-decalcified histology. Biomechanical properties were investigated by a three-point bending test, and the bone turnover markers PINP, bCTx, OPG, sRANKL, TRACP-5b, BALP, and OT/BGP were measured. Results One week after the reduction maneuver, µCT analysis showed a higher cortical bone volume in the 1× reduction group compared to the 10× reduction group. Biomechanically, the control group showed higher maximum force values measured by three-point bending test compared to both reduction groups. Furthermore, less collagen I formation was examined in the 10× reduction group compared to the control group after 1 week of fracture healing. PINP concentration was decreased in 10× reduction group after 1 week compared to control group. The same trend was seen after 3 weeks. Conclusion A single reduction maneuver has a beneficial effect in the early phase of the fracture healing process compared to repeated reduction maneuvers. In the later phase of fracture healing, no differences were found between the groups.
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    Age does not influence the disease course in a mouse model of Streptococcus pneumoniae serotype 3 meningitis 

    Manig, Anja; Ribes, Sandra; Diesselberg, Catharina; Bunkowski, Stephanie; Nau, Roland; Schütze, Sandra
    2018; 15(1): Art. 20
    Abstract In order to elucidate the causes for the increased mortality of aged patients with bacterial central nervous system (CNS) infections, we compared the course of Streptococcus pneumoniae (S. pneumoniae) meningitis in aged and young mice. Aged (21.2 ± 3.1 months, n = 40) and young (3.2 ± 0.9 months, n = 42) C57BL/6N and B6/SJL mice were infected by intracerebral injection of 50–70 CFU S. pneumoniae serotype 3 and monitored for 15 days. Aged and young mice did not differ concerning mortality (35% versus 38%), weight loss, development of clinical symptoms, bacterial concentrations in cerebellum and spleen as well as the number of leukocytes infiltrating the CNS. In contrast to results from our geriatric mouse model of Escherichia coli (E. coli) meningitis, where aged mice showed a higher mortality and an impaired elimination of bacteria, we did not find any differences between aged and young mice after intracerebral infection with S. pneumoniae serotype 3. This indicates that the increased susceptibility of aged mice to bacterial CNS infections is pathogen-specific: It appears less prominent in infections caused by hardly phagocytable pathogens with thick capsules like S. pneumoniae serotype 3, where the age-related decline of the phagocytic capacity of microglia and macrophages has a minor influence on the disease course.
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    Myocontrol is closed-loop control: incidental feedback is sufficient for scaling the prosthesis force in routine grasping 

    Markovic, Marko; Schweisfurth, Meike A.; Engels, Leonard F.; Farina, Dario; Dosen, Strahinja
    2018; 15(1): Art. 81
    Abstract Background Sensory feedback is critical for grasping in able-bodied subjects. Consequently, closing the loop in upper-limb prosthetics by providing artificial sensory feedback to the amputee is expected to improve the prosthesis utility. Nevertheless, even though amputees rate the prospect of sensory feedback high, its benefits in daily life are still very much debated. We argue that in order to measure the potential functional benefit of artificial sensory feedback, the baseline open-loop performance needs to be established. Methods The myoelectric control of naïve able-bodied subjects was evaluated during modulation of electromyographic signals (EMG task), and grasping with a prosthesis (Prosthesis task). The subjects needed to activate the wrist flexor muscles and close the prosthesis to reach a randomly selected target level (routine grasping). To assess the baseline performance, the tasks were performed with a different extent of implicit feedback (proprioception, prosthesis motion and sound). Finally, the prosthesis task was repeated with explicit visual force feedback. The subjects’ ability to scale the prosthesis command/force was assessed by testing for a statistically significant increase in the median of the generated commands/forces between neighboring levels. The quality of control was evaluated by computing the median absolute error (MAE) with respect to the target. Results The subjects could successfully scale their motor commands and generated prosthesis forces across target levels in all tasks, even with the least amount of implicit feedback (only muscle proprioception, EMG task). In addition, the deviation of the generated commands/forces from the target levels decreased with additional feedback. However, the increase in implicit feedback, from proprioception to prosthesis motion and sound, seemed to have a more substantial effect than the final introduction of explicit feedback. Explicit feedback improved the performance mainly at the higher target-force levels. Conclusions The study establishes the baseline performance of myoelectric control and prosthesis grasping force. The results demonstrate that even without additional feedback, naïve subjects can effectively modulate force with good accuracy with respect to that achieved when increasing the amount of feedback information.
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    Interlaboratory proficiency processing scheme in CSF aliquoting: implementation and assessment based on biomarkers of Alzheimer’s disease 

    Lewczuk, Piotr; Gaignaux, Amélie; Kofanova, Olga; Ermann, Natalia; Betsou, Fay; Brandner, Sebastian; Mroczko, Barbara; Blennow, Kaj; Strapagiel, Dominik; Paciotti, Silvia; et al.
    Vogelgsang, JonathanRoehrl, Michael HMendoza, SandraKornhuber, JohannesTeunissen, Charlotte
    2018; 10(1): Art. 87
    Abstract Background In this study, we tested to which extent possible between-center differences in standardized operating procedures (SOPs) for biobanking of cerebrospinal fluid (CSF) samples influence the homogeneity of the resulting aliquots and, consequently, the concentrations of the centrally analyzed selected Alzheimer’s disease biomarkers. Methods Proficiency processing samples (PPSs), prepared by pooling of four individual CSF samples, were sent to 10 participating centers, which were asked to perform aliquoting of the PPSs into two secondary aliquots (SAs) under their local SOPs. The resulting SAs were shipped to the central laboratory, where the concentrations of amyloid beta (Aβ) 1–42, pTau181, and albumin were measured in one run with validated routine analytical methods. Total variability of the concentrations, and its within-center and between-center components, were analyzed with hierarchical regression models. Results We observed neglectable variability in the concentrations of pTau181 and albumin across the centers and the aliquots. In contrast, the variability of the Aβ1–42 concentrations was much larger (overall coefficient of variation 31%), with 28% of the between-laboratory component and 10% of the within-laboratory (i.e., between-aliquot) component. We identified duration of the preparation of the aliquots and the centrifugation force as two potential confounders influencing within-center variability and biomarker concentrations, respectively. Conclusions Proficiency processing schemes provide objective evidence for the most critical preanalytical variables. Standardization of these variables may significantly enhance the quality of the collected biospecimens. Studies utilizing retrospective samples collected under different local SOPs need to consider such differences in the statistical evaluations of the data.
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    Membrane binding, internalization, and sorting of alpha-synuclein in the cell 

    Masaracchia, Caterina; Hnida, Marilena; Gerhardt, Ellen; Lopes da Fonseca, Tomás; Villar-Pique, Anna; Branco, Tiago; Stahlberg, Markus A; Dean, Camin; Fernández, Claudio O; Milosevic, Ira; et al.
    Outeiro, Tiago F
    2018; 6(1): Art. 79
    Abstract Alpha-synuclein (aSyn) plays a crucial role in Parkinson’s disease (PD) and other synucleinopathies, since it misfolds and accumulates in typical proteinaceous inclusions. While the function of aSyn is thought to be related to vesicle binding and trafficking, the precise molecular mechanisms linking aSyn with synucleinopathies are still obscure. aSyn can spread in a prion-like manner between interconnected neurons, contributing to the propagation of the pathology and to the progressive nature of synucleinopathies. Here, we investigated the interaction of aSyn with membranes and trafficking machinery pathways using cellular models of PD that are amenable to detailed molecular analyses. We found that different species of aSyn can enter cells and form high molecular weight species, and that membrane binding properties are important for the internalization of aSyn. Once internalized, aSyn accumulates in intracellular inclusions. Interestingly, we found that internalization is blocked in the presence of dynamin inhibitors (blocked membrane scission), suggesting the involvement of the endocytic pathway in the internalization of aSyn. By screening a pool of small Rab-GTPase proteins (Rabs) which regulate membrane trafficking, we found that internalized aSyn partially colocalized with Rab5A and Rab7. Initially, aSyn accumulated in Rab4A-labelled vesicles and, at later stages, it reached the autophagy-lysosomal pathway (ALP) where it gets degraded. In total, our study emphasizes the importance of membrane binding, not only as part of the normal function but also as an important step in the internalization and subsequent accumulation of aSyn. Importantly, we identified a fundamental role for Rab proteins in the modulation of aSyn processing, clearance and spreading, suggesting that targeting Rab proteins may hold important therapeutic value in PD and other synucleinopathies.
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    Attention decouples action potentials from the phase of local field potentials in macaque visual cortical area MT 

    Esghaei, Moein; Daliri, Mohammad R; Treue, Stefan
    2018; 16(1): Art. 86
    Abstract Background The timing of action potentials (“spikes”) of cortical neurons has been shown to be aligned to the phase of low-frequency (< 10 Hz) local field potentials (LFPs) in several cortical areas. However, across the areas, this alignment varies and the role of this spike-phase coupling (SPC) in cognitive functions is not well understood. Results Here, we propose a role in the coordination of neural activity by selective attention. After refining previous analytical methods for measuring SPC, we show that first, SPC is present along the dorsal processing pathway in macaque visual cortex (area MT); second, spikes occur in falling phases of the low-frequency LFP independent of the location of spatial attention; third, switching spatial attention into the receptive field (RF) of MT neurons decreases this coupling; and finally, the LFP phase causally influences the spikes. Conclusions Here, we show that spikes are coupled to the phase of low-frequency LFP along the dorsal visual pathway. Our data suggest that attention harnesses this spike-LFP coupling to de-synchronize neurons and thereby enhance the neural representation of the attended stimuli.
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    Postoperative long-term results for the comparison of the symmetry of the upper lip during lip closure according to Millard and Pfeifer 

    Kauffmann, Philipp; Cordesmeyer, Robert; Fouellefack, Giséle A; Schminke, Boris; Wiese, Karl-Günther
    2018; 40(1): Art. 18
    Abstract Background Clefts in newborns are associated with severe morphological and functional impairment. Especially the lip is of importance as if the treatment result is unsatisfactory, it can lead to psychological changes in the patient. Different operative procedures have been developed over the last decades. The aim of the presented study was the comparison of the surgical techniques according to Millard and Pfeifer regarding the temporal development of the postoperative symmetry of the lip height and mouth width. Methods Digitized photographs of patients from the department of oral and maxillofacial surgery at the University of Göttingen were evaluated from 1979 to 1996. With a video analysis program, the lip height and mouth width were analyzed regarding the symmetry. We demonstrated the symmetry values over a period of 8 years in order to show the influence of growth on postoperative results. Results The development of the vertical symmetry of the Philtrum and the lip vermillion on the cleft side in comparison to the healthy side behaves differently depending on Pfeifer and Millard. The lip height of the cleft lip was shorter in both techniques than on the healthy side, but Pfeifer’s difference was significantly more pronounced. The lip vermillion height on the cleft side was slightly shorter in the Millard group and markedly larger in the Pfeifer group. Both techniques can achieve good symmetry results for the vertical dimension of the lip. According to Pfeifer, the development of the horizontal dimension on the cleft side is bigger within the first 4 years than on the healthy side; according to the Millard technique, the horizontal development is smaller. These differences are greater within the first 6 years and approach between the 6th and 8th year. Conclusions The Millard technique demonstrates better results concerning the philtrum and vermillion symmetry during growth within the first 6 years. Over the whole study period, growth corrects the philtrum and vermillion symmetry within the Pfeifer group.
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    Small farmers’ preferences for weather index insurance: insights from Kenya 

    Sibiko, Kenneth W; Veettil, Prakashan C; Qaim, Matin
    2018; 7(1): Art. 53
    Abstract Background Smallholder farmers in developing countries are particularly vulnerable to climate shocks but often lack access to agricultural insurance. Weather index insurance (WII) could reduce some of the problems associated with traditional, indemnity-based insurance programs, but uptake has been lower than expected. One reason is that WII contracts are not yet sufficiently tailored to the needs and preferences of smallholder farmers. This study combines survey and choice-experimental data from Kenya to analyze the experience with an existing WII program and how specific changes in the contractual design might encourage uptake. Results Many smallholders struggle with fully understanding the functioning of the program, which undermines their confidence. Regular provision of relevant rainfall measurements and thresholds would significantly increase farmers’ willingness to pay for WII. Mechanisms to reduce basis risk are also positively valued by farmers, although not to the same extent as higher levels of transparency. Finally, offering contracts to small groups rather than individual farmers could increase insurance uptake. Conclusions Better training on WII and regular communication are needed. Group contracts may help to reduce transaction costs. Farmer groups can also be important platforms for learning about complex innovations, including novel risk transfer products. These concrete results are specific to Kenya; however, they provide some broader policy-relevant insights into typical issues of WII in a small-farm context.
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    Gall bladder wall thickening as non-invasive screening parameter for esophageal varices – a comparative endoscopic – sonographic study 

    Tsaknakis, Birgit; Masri, Rawan; Amanzada, Ahmad; Petzold, Golo; Ellenrieder, Volker; Neesse, Albrecht; Kunsch, Steffen
    2018; 18(1): Art. 123
    BACKGROUND: The mortality due to hemorrhage of esophageal varices (EV) is still high. The predominant cause for EV is liver cirrhosis, which has a high prevalence in Western Europe. Therefore, non-invasive screening markers for the presence of EV are of interest. Here, we aim to investigate whether non-inflammatory gall bladder wall thickening (GBWT) may serve as predictor for the presence of EV in comparison and combination with other non-invasive clinical and laboratory parameters. METHODS: One hundred ninety four patients were retrospectively enrolled in the study. Abdominal ultrasound, upper endoscopy and blood tests were evaluated. GBWT, spleen size and the presence of ascites were evaluated by ultrasound. Platelet count and Child-Pugh-score were also recorded. The study population was categorized in two groups: 122 patients without esophageal varices (non EV) compared to 72 patients with EV were analyzed by uni-and multivariate analysis. RESULTS: In the EV group 46% showed a non-inflammatory GBWT of ≥4 mm, compared to 12% in the non-EV group (p < 0.01). GBWT was significantly higher in EV patients compared to the non-EV group (mean: 4.4 mm vs. 2.8 mm, p < 0.0001), and multivariate analysis confirmed GBWT as independent predictor for EV (p < 0.04). The platelets/GBWT ratio (cut-off > 46.2) had a sensitivity and specificity of 78 and 86%, PPV 76% and NPV of 87%, and ROC analysis calculated the AUC of 0.864 (CI 0.809-0.919). CONCLUSIONS: GBWT occurs significantly more often in patients with EV. However, because of the low sensitivity, combination with other non-invasive parameters such as platelet count is recommended.
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    Introducing evolutionary biologists to the analysis of big data: guidelines to organize extended bioinformatics training courses 

    Faria, Rui; Triant, Deborah; Perdomo-Sabogal, Alvaro; Overduin, Bert; Bleidorn, Christoph; Santana, Clara I. B.; Langenberger, David; Dall’Olio, Giovanni M.; Indrischek, Henrike; Aerts, Jan; et al.
    Engelhardt, JanEngelken, JohannesLiebal, KatjaFasold, MarioRobb, SofiaGrath, SonjaKolora, Sree R. R.Carvalho, TiagoSalzburger, WalterJovanovic, VladimirNowick, Katja
    2018; 11(1): Art. 8
    Research in evolutionary biology has been progressively influenced by big data such as massive genome and transcriptome sequencing data, scalar measurements of several phenotypes on tens to thousands of individuals, as well as from collecting worldwide environmental data at an increasingly detailed scale. The handling and analysis of such data require computational skills that usually exceed the abilities of most traditionally trained evolutionary biologists. Here we discuss the advantages, challenges and considerations for organizing and running bioinformatics training courses of 2–3 weeks in length to introduce evolutionary biologists to the computational analysis of big data. Extended courses have the advantage of offering trainees the opportunity to learn a more comprehensive set of complementary topics and skills and allowing for more time to practice newly acquired competences. Many organizational aspects are common to any course, as the need to define precise learning objectives and the selection of appropriate and highly motivated instructors and trainees, among others. However, other features assume particular importance in extended bioinformatics training courses. To successfully implement a learning-by-doing philosophy, sufficient and enthusiastic teaching assistants (TAs) are necessary to offer prompt help to trainees. Further, a good balance between theoretical background and practice time needs to be provided and assured that the schedule includes enough flexibility for extra review sessions or further discussions if desired. A final project enables trainees to apply their newly learned skills to real data or case studies of their interest. To promote a friendly atmosphere throughout the course and to build a close-knit community after the course, allow time for some scientific discussions and social activities. In addition, to not exhaust trainees and TAs, some leisure time needs to be organized. Finally, all organization should be done while keeping the budget within fair limits. In order to create a sustainable course that constantly improves and adapts to the trainees’ needs, gathering short- and long-term feedback after the end of the course is important. Based on our experience we have collected a set of recommendations to effectively organize and run extended bioinformatics training courses for evolutionary biologists, which we here want to share with the community. They offer a complementary way for the practical teaching of modern evolutionary biology and reaching out to the biological community.
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    The presubiculum is preserved from neurodegenerative changes in Alzheimer’s disease 

    Murray, Christina E; Gami-Patel, Priya; Gkanatsiou, Eleni; Brinkmalm, Gunnar; Portelius, Erik; Wirths, Oliver; Heywood, Wendy; Blennow, Kaj; Ghiso, Jorge; Holton, Janice L; et al.
    Mills, KevinZetterberg, HenrikRevesz, TamasLashley, Tammaryn
    2018; 6(1): Art. 62
    Abstract In the majority of affected brain regions the pathological hallmarks of Alzheimer’s disease (AD) are β-amyloid (Aβ) deposits in the form of diffuse and neuritic plaques, tau pathology in the form of neurofibrillary tangles, neuropil threads and plaque-associated abnormal neurites in combination with an inflammatory response. However, the anatomical area of the presubiculum, is characterised by the presence of a single large evenly distributed ‘lake-like’ Aβ deposit with minimal tau deposition or accumulation of inflammatory markers. Post-mortem brain samples from sporadic AD (SAD) and familial AD (FAD) and two hereditary cerebral amyloid diseases, familial British dementia (FBD) and familial Danish dementia (FDD) were used to compare the morphology of the extracellular proteins deposited in the presubiculum compared to the entorhinal cortex. The level of tau pathology and the extent of microglial activation were quantitated in the two brain regions in SAD and FAD. Frozen tissue was used to investigate the Aβ species and proteomic differences between the two regions. Consistent with our previous investigations of FBD and FDD cases we were able to establish that the ‘lake-like’ pre-amyloid deposits of the presubiculum were not a unique feature of AD but they also found two non-Aβ amyloidosis. Comparing the presubiculum to the entorhinal cortex the number of neurofibrillary tangles and tau load were significantly reduced; there was a reduction in microglial activation; there were differences in the Aβ profiles and the investigation of the whole proteome showed significant changes in different protein pathways. In summary, understanding why the presubiculum has a different morphological appearance, biochemical and proteomic makeup compared to surrounding brain regions severely affected by neurodegeneration could lead us to understanding protective mechanisms in neurodegenerative diseases.
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    Can the health related quality of life measure QOLIBRI- overall scale (OS) be of use after stroke? A validation study 

    Heiberg, Guri; Pedersen, Synne G; Friborg, Oddgeir; Nielsen, Jørgen F; Holm, Henriette S; Steinbüchel von, Nicole; Arntzen, Cathrine; Anke, Audny
    2018; 18(1): Art. 98
    Abstract Background Brief measures of health-related quality of life (HRQOL) that assess both patient-reported functioning and well-being after stroke are scarce. The objective of this study was to examine reliability and validity of one of these measures, the patient-reported Quality of Life after Brain Injury–Overall Scale (QOLIBRI-OS), in patients after stroke. Methods Stroke survivors were examined prospectively using survey methods. Core survey data (n = 125) and retest data (n = 36) were obtained at 3 and 12 months, respectively. Item properties (distribution, floor and ceiling effects), psychometric properties (reliability and model fit), and validity (correlations with established measures of anxiety, depression and HRQOL) of the QOLIBRI-OS were examined. Results Missing responses on the questionnaire were low (0.5%). All items were positively skewed. No floor effects were present, whereas five out of six items showed ceiling effects. The summary QOLIBRI-OS score exhibited no floor or ceiling effects, and had excellent internal consistency (Cronbach’s α =0.93). All item-total correlations were high (0.73–0.88). The test-retest reliability of single items varied from 0.74 to 0.91 and was 0.93 for the overall score. The confirmatory factor analysis yielded an excellent fit for a five-item version and provided tentative support for the original six-item version. The convergent validity correlations were in the hypothesized directions, thus supporting the construct validity. Conclusions The brief QOLIBRI-OS is a valid and reliable brief health-related outcome measure that is appropriate for screening HRQOL in patients after stroke.
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    “Some fuzzy math”: relational information on debt value adjustments by managers and the financial press 

    Kaumanns, Sebastian
    Abstract This study provides comprehensive descriptive evidence on the occurrence, size, and reporting by managers and the financial press of debt value adjustments due to a change in own credit risk (DVAs). The study is motivated by a public debate about DVAs in which critics describe them as “counterintuitive” and claim that managers disclose DVA information strategically to make firms “look good”. Analyzing a sample of 405 firm-quarters of 19 US financial firms that report DVAs between 2007 and 2014, I found that positive and negative DVAs appear similarly often and with similar magnitude. I further found that managers provide more information on large negative DVAs compared to positive DVAs. Managers also provide more DVA information when they have strategic incentives to do so. Examining newspaper articles on 202 firm-quarters, I found that the financial press is more likely to cover large positive DVAs and DVAs about which managers provided more information. Analyzing the articles’ content, I found that the press is more likely to provide new DVA information if managers’ press releases contain little information. The findings are in line with popular claims of asymmetric DVA reporting by managers. They are further consistent with the financial press acting as a counterweight to such asymmetric reporting.
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    Population genetic structure and evolutionary history of Bale monkeys (Chlorocebus djamdjamensis) in the southern Ethiopian Highlands 

    Mekonnen, Addisu; Rueness, Eli K; Stenseth, Nils C; Fashing, Peter J; Bekele, Afework; Hernandez-Aguilar, R. Adriana; Missbach, Rose; Haus, Tanja; Zinner, Dietmar; Roos, Christian
    2018; 18(1): Art. 106
    Abstract Background Species with a restricted geographic distribution, and highly specialized habitat and dietary requirements, are particularly vulnerable to extinction. The Bale monkey (Chlorocebus djamdjamensis) is a little-known arboreal, bamboo-specialist primate endemic to the southern Ethiopian Highlands. While most Bale monkeys inhabit montane forests dominated by bamboo, some occupy forest fragments where bamboo is much less abundant. We used mitochondrial DNA (mtDNA) sequences to analyse the genetic structure and evolutionary history of Bale monkeys covering the majority of their remaining distribution range. We analysed 119 faecal samples from their two main habitats, continuous forest (CF) and fragmented forests (FF), and sequenced 735 bp of the hypervariable region I (HVI) of the control region. We added 12 orthologous sequences from congeneric vervets (C. pygerythrus) and grivets (C. aethiops) as well as animals identified as hybrids, previously collected in southern Ethiopia. Results We found strong genetic differentiation (with no shared mtDNA haplotypes) between Bale monkey populations from CF and FF. Phylogenetic analyses revealed two distinct and highly diverged clades: a Bale monkey clade containing only Bale monkeys from CF and a green monkey clade where Bale monkeys from FF cluster with grivets and vervets. Analyses of demographic history revealed that Bale monkey populations (CF and FF) have had stable population sizes over an extended period, but have all recently experienced population declines. Conclusions The pronounced genetic structure and deep mtDNA divergence between Bale monkey populations inhabiting CF and FF are likely to be the results of hybridization and introgression of the FF population with parapatric Chlorocebus species, in contrast to the CF population, which was most likely not impacted by hybridization. Hybridization in the FF population was probably enhanced by an alteration of the bamboo forest habitat towards a more open woodland habitat, which enabled the parapatric Chlorocebus species to invade the Bale monkey's range and introgress the FF population. We therefore propose that the CF and FF Bale monkey populations should be managed as separate units when developing conservation strategies for this threatened species.
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    Use of ECMO in ARDS: does the EOLIA trial really help? 

    Gattinoni, Luciano; Vasques, Francesco; Quintel, Michael
    2018; 22(1): Art. 171
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    How can we teach medical students to choose wisely? A randomised controlled cross-over study of video- versus text-based case scenarios 

    Ludwig, Sascha; Schuelper, Nikolai; Brown, Jamie; Anders, Sven; Raupach, Tobias
    2018; 16(1): Art. 107
    Background The Choosing Wisely campaign highlights the importance of clinical reasoning abilities for competent and reflective physicians. The principles of this campaign should be addressed in undergraduate medical education. Recent research suggests that answering questions on important steps in patient management promotes knowledge retention. It is less clear whether increasing the authenticity of educational material by the inclusion of videos further enhances learning outcome. Methods In a prospective randomised controlled cross-over study, we assessed whether repeated video-based testing is more effective than repeated text-based testing in training students to choose appropriate diagnostic tests, arrive at correct diagnoses and identify advisable therapies. Following an entry exam, fourth-year undergraduate medical students attended 10 weekly computer-based seminars during which they studied patient case histories. Each case contained five key feature questions (items) on the diagnosis and treatment of the presented patient. Students were randomly allocated to read text cases (control condition) or watch videos (intervention), and assignment to either text or video was switched between groups every week. Using a within-subjects design, student performance on video-based and text-based items was assessed 13 weeks (exit exam) and 9 months (retention test) after the first day of term. The primary outcome was the within-subject difference in performance on video-based and text-based items in the exit exam. Results Of 125 eligible students, 93 provided data for all three exams (response rate 74.4%). Percent scores were significantly higher for video-based than for text-based items in the exit exam (76.2 ± 19.4% vs. 72.4 ± 19.1%, p = 0.026) but not the retention test (69.2 ± 20.2% vs. 66.4 ± 20.3%, p = 0.108). An additional Bayesian analysis of this retention test suggested that video-based training is marginally more effective than text-based training in the long term (Bayes factor 2.36). Regardless of presentation format, student responses revealed a high prevalence of erroneous beliefs that, if applied to the clinical context, could place patients at risk. Conclusion Repeated video-based key feature testing produces superior short-term learning outcome compared to text-based testing. Given the high prevalence of misconceptions, efforts to improve clinical reasoning training in medical education are warranted. The Choosing Wisely campaign lends itself to being part of this process.
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    Enhancing oil production and harvest by combining the marine alga Nannochloropsis oceanica and the oleaginous fungus Mortierella elongata 

    Du, Zhi-Yan; Alvaro, Jonathan; Hyden, Brennan; Zienkiewicz, Krzysztof; Benning, Nils; Zienkiewicz, Agnieszka; Bonito, Gregory; Benning, Christoph
    2018; 11(1): Art. 174
    Background Although microalgal biofuels have potential advantages over conventional fossil fuels, high production costs limit their application in the market. We developed bio-flocculation and incubation methods for the marine alga, Nannochloropsis oceanica CCMP1779, and the oleaginous fungus, Mortierella elongata AG77, resulting in increased oil productivity. Results By growing separately and then combining the cells, the M. elongata mycelium could efficiently capture N. oceanica due to an intricate cellular interaction between the two species leading to bio-flocculation. Use of a high-salt culture medium induced accumulation of triacylglycerol (TAG) and enhanced the contents of polyunsaturated fatty acids (PUFAs) including arachidonic acid and docosahexaenoic acid in M. elongata. To increase TAG productivity in the alga, we developed an effective, reduced nitrogen-supply regime based on ammonium in environmental photobioreactors. Under optimized conditions, N. oceanica produced high levels of TAG that could be indirectly monitored by following chlorophyll content. Combining N. oceanica and M. elongata to initiate bio-flocculation yielded high levels of TAG and total fatty acids, with ~ 15 and 22% of total dry weight (DW), respectively, as well as high levels of PUFAs. Genetic engineering of N. oceanica for higher TAG content in nutrient-replete medium was accomplished by overexpressing DGTT5, a gene encoding the type II acyl-CoA:diacylglycerol acyltransferase 5. Combined with bio-flocculation, this approach led to increased production of TAG under nutrient-replete conditions (~ 10% of DW) compared to the wild type (~ 6% of DW). Conclusions The combined use of M. elongata and N. oceanica with available genomes and genetic engineering tools for both species opens up new avenues to improve biofuel productivity and allows for the engineering of polyunsaturated fatty acids.
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    In-depth proteomic analyses of Haliotis laevigata (greenlip abalone) nacre and prismatic organic shell matrix 

    Mann, Karlheinz; Cerveau, Nicolas; Gummich, Meike; Fritz, Monika; Mann, Matthias; Jackson, Daniel J
    2018; 16(1): Art. 11
    Abstract Background The shells of various Haliotis species have served as models of invertebrate biomineralization and physical shell properties for more than 20 years. A focus of this research has been the nacreous inner layer of the shell with its conspicuous arrangement of aragonite platelets, resembling in cross-section a brick-and-mortar wall. In comparison, the outer, less stable, calcitic prismatic layer has received much less attention. One of the first molluscan shell proteins to be characterized at the molecular level was Lustrin A, a component of the nacreous organic matrix of Haliotis rufescens. This was soon followed by the C-type lectin perlucin and the growth factor-binding perlustrin, both isolated from H. laevigata nacre, and the crystal growth-modulating AP7 and AP24, isolated from H. rufescens nacre. Mass spectrometry-based proteomics was subsequently applied to to Haliotis biomineralization research with the analysis of the H. asinina shell matrix and yielded 14 different shell-associated proteins. That study was the most comprehensive for a Haliotis species to date. Methods The shell proteomes of nacre and prismatic layer of the marine gastropod Haliotis laevigata were analyzed combining mass spectrometry-based proteomics and next generation sequencing. Results We identified 297 proteins from the nacreous shell layer and 350 proteins from the prismatic shell layer from the green lip abalone H. laevigata. Considering the overlap between the two sets we identified a total of 448 proteins. Fifty-one nacre proteins and 43 prismatic layer proteins were defined as major proteins based on their abundance at more than 0.2% of the total. The remaining proteins occurred at low abundance and may not play any significant role in shell fabrication. The overlap of major proteins between the two shell layers was 17, amounting to a total of 77 major proteins. Conclusions The H. laevigata shell proteome shares moderate sequence similarity at the protein level with other gastropod, bivalve and more distantly related invertebrate biomineralising proteomes. Features conserved in H. laevigata and other molluscan shell proteomes include short repetitive sequences of low complexity predicted to lack intrinsic three-dimensional structure, and domains such as tyrosinase, chitin-binding, and carbonic anhydrase. This catalogue of H. laevigata shell proteins represents the most comprehensive for a haliotid and should support future efforts to elucidate the molecular mechanisms of shell assembly.
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    The effect of a new lifetime-cardiovascular-risk display on patients’ motivation to participate in shared decision-making 

    Jegan, Nikita R A; Kürwitz, Sarah A; Kramer, Lena K; Heinzel-Gutenbrunner, Monika; Adarkwah, Charles C; Popert, Uwe; Donner-Banzhoff, Norbert
    2018; 19(1): Art. 84
    Abstract Background This study investigated the effects of three different risk displays used in a cardiovascular risk calculator on patients’ motivation for shared decision-making (SDM). We compared a newly developed time-to-event (TTE) display with two established absolute risk displays (i.e. emoticons and bar charts). The accessibility, that is, how understandable, helpful, and trustworthy patients found each display, was also investigated. Methods We analysed a sample of 353 patients recruited in general practices. After giving consent, patients were introduced to one of three fictional vignettes with low, medium or high cardiovascular risk. All three risk displays were shown in a randomized order. Patients were asked to rate each display with regard to motivation for SDM and accessibility. Two-factorial repeated measures analyses of variance were conducted to compare the displays and investigate possible interactions with age. Results Regarding motivation for SDM, the TTE elicited the highest motivation, followed by the emoticons and bar chart (p < .001). The displays had no differential influence on the age groups (p = .445). While the TTE was generally rated more accessible than the emoticons and bar chart (p < .001), the emoticons were only superior to the bar chart in the younger subsample. However, this was only to a small effect (interaction between display and age, p < .01, η 2  = 0.018). Conclusions Using fictional case vignettes, the novel TTE display was superior regarding motivation for SDM and accessibility when compared to established displays using emoticons and a bar chart. If future research can replicate these results in real-life consultations, the TTE display will be a valuable addition to current risk calculators and decision aids by improving patients’ participation.
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