bluuebunny/crossref_metadata_2025 huggingface dataset:
Mental Health and Dysphonia: Which Comes First, and Does That Change Care Utilization?
Authors: Jordan Victoria A. , Cohen Seth , Lunos Scott , Horvath Keith J. , Sieger Gretchen , Misono Stephanie
Published: February 2020

Objectives

Voice patients with voice disorders have a high prevalence of distress and mental health (MH) comorbidities, but it is unknown to what extent distress precedes or follows voice disorder diagnoses. Objectives were to compare 1) proportions of voice patients with MH diagnoses who received MH diagnoses first versus voice‐related diagnoses first, 2) voice‐related diagnoses and care utilization, and 3) time to specialty evaluation in each group.

Methods

Patients with voice and MH diagnoses were identified using International Classification of Diseases, Ninth and Tenth Revisions codes in a large health system data repository from January 2005 through July 2017. Sociodemographics, comorbidities, MH‐ and voice‐related diagnoses, and voice‐related care utilization were analyzed using descriptive statistics and multivariable regression modeling.

Results

Among the 11,419 patients with both voice and MH diagnoses, 63% (n = 7,251) received MH diagnoses prior to voice diagnoses, compared with 37% with a voice diagnosis first (P < 0.0001). The latter group received more specific voice‐related diagnoses (e.g., laryngeal cancer [odds ratio (OR) 4.27], benign laryngeal neoplasm [OR 1.60]), and were more likely to ever see an otolaryngologist than those receiving MH diagnoses first (P < 0.0001).

Conclusion

Most patients with voice and MH diagnoses received a MH diagnosis first. Patients who receive MH diagnoses first appeared to have different voice‐related healthcare compared to those who received voice diagnoses first.

Level of Evidence

NA

Laryngoscope, 130:1243–1248, 2020
Lysosome and Inflammatory Defects in GBA1‐Mutant Astrocytes Are Normalized by LRRK2 Inhibition
Authors: Sanyal Anwesha , DeAndrade Mark P. , Novis Hailey S. , Lin Steven , Chang Jianjun , Lengacher Nathalie , Tomlinson Julianna J. , Tansey Malú G. , LaVoie Matthew J.
Published: February 2020

Background

Autosomal recessive mutations in the glucocerebrosidase gene, Beta‐glucocerebrosidase 1 (GBA1), cause the lysosomal storage disorder Gaucher's disease. Heterozygous carriers of most GBA1 mutations have dramatically increased Parkinson's disease (PD) risk, but the mechanisms and cells affected remain unknown. Glucocerebrosidase expression is relatively enriched in astrocytes, yet the impact of its mutation in these cells has not yet been addressed.

Objectives

Emerging data supporting non‐cell‐autonomous mechanisms driving PD pathogenesis inspired the first characterization of GBA1‐mutant astrocytes. In addition, we asked whether LRRK2, likewise linked to PD and enriched in astrocytes, intersected with GBA1 phenotypes.

Methods

Using heterozygous and homozygous GBA1 D409V knockin mouse astrocytes, we conducted rigorous biochemical and image‐based analyses of lysosomal function and morphology. We also examined basal and evoked cytokine response at the transcriptional and secretory levels.

Results

The D409V knockin astrocytes manifested broad deficits in lysosomal morphology and function, as expected. This, however, is the first study to show dramatic defects in basal and TLR4‐dependent cytokine production. Albeit to different extents, both the lysosomal dysfunction and inflammatory responses were normalized by inhibition of LRRK2 kinase activity, suggesting functional intracellular crosstalk between glucocerebrosidase and LRRK2 activities in astrocytes.

Conclusions

These data demonstrate novel pathologic effects of a GBA1 mutation on inflammatory responses in astrocytes, indicating the likelihood of broader immunologic changes in GBA‐PD patients. Our findings support the involvement of non‐cell‐autonomous mechanisms contributing to the pathogenesis of GBA1‐linked PD and identify new opportunities to correct these changes with pharmacological intervention. © 2020 International Parkinson and Movement Disorder Society
Stability of Rothe difference scheme for the reverse parabolic problem with integral boundary condition
Authors: Ashyralyyev Charyyar
Published: February 2020

In this paper, we study the approximation of reverse parabolic problem with integral boundary condition. The Rothe difference scheme for an approximate solution of reverse problem is discussed. We establish stability and coercive stability estimates for the solution of the Rothe difference scheme. In sequel, we investigate the first order of accuracy difference scheme for approximation of boundary value problem for multidimensional reverse parabolic equation and obtain stability estimates for its solution. Finally, we give numerical results together with an explanation on the realization in one‐ and two‐dimensional test examples.
Inclusion‐body myositis and primary Sjögren syndrome: mechanisms for shared etiologies
Authors: Limaye Vidya S. , Cash Kathy , Smith Caroline , Koszyca Barbara , Patel Sandy , Greenberg Steven A. , Hissaria Pravin
Published: February 2020

Herein we report a case of sporadic inclusion‐body myositis (sIBM) occurring at an unusually young age in a patient with primary Sjögren syndrome, and use the case to explore possible shared mechanisms for disease susceptibility. Possible factors may include the association of both conditions with the 8.1 ancestral haplotype; the presence of anti‐cN1A antibodies, which, although considered specific for sIBM, are also seen in pSS; and the shared association with T‐cell large granular lymphocyte leukemia (T‐LGLL). Further evaluation of this patient did in fact reveal underlying T‐LGLL and mechanisms by which T cells in sIBM may escape immune regulation and contribute to disease phenotype are explored. Despite myofiber infiltration with CD8‐positive T cells in sIBM, and, although sIBM is traditionally considered treatment‐refractory, we report a significant response to the anti‐CD20 monoclonal antibody, rituximab, and discuss possible mechanisms by which this response may be mediated.
Ultrasonic Extrusion of NR Gum and Its Effect on the Structure and Properties of Unfilled and Silica‐Filled NR
Authors: Liang Tian , Isayev Avraam I.
Published: February 2020

Natural rubber (NR) has been extruded without and with ultrasonic treatment at various ultrasonic amplitudes. The effect of ultrasonic treatment on structure of NR, its compounds with silica and silica/silane and their vulcanizates have been studied. Processing‐structure‐properties relationship of untreated and treated materials has been established. With the increase of ultrasonic amplitude power consumption is increased and die pressure is reduced. Size exclusion chromatography measurements show that the NR molecular weight is reduced with the ultrasonic treatment. The storage modulus and loss modulus, complex viscosity and loss tangent results also confirmed the degradation of NR chains by imposition of ultrasound, especially after treatment at high amplitude. After mixing with silica and silica/silane, it was found that degradation of NR caused a reduction in the rubber–filler interaction, an increase in the filler–filler interaction and flocculation upon heating. Physical properties of vulcanizates including M100, ultimate elongation, and stress at break are also deteriorated. POLYM. ENG. SCI., 60:925–934, 2020. © 2020 Society of Plastics Engineers
Aclonifen targets solanesyl diphosphate synthase, representing a novel mode of action for herbicides
Authors: Kahlau Sabine , Schröder Florian , Freigang Jörg , Laber Bernd , Lange Gudrun , Passon Daniel , Kleeßen Sabrina , Lohse Marc , Schulz Arno , von Koskull‐Döring Pascal , Klie Sebastian , Gille Sascha
Published: February 2020

BACKGROUND

Aclonifen is a unique diphenyl ether herbicide. Despite its structural similarities to known inhibitors of the protoporphyrinogen oxidase (e.g. acifluorfen, bifenox or oxadiazon), which result in leaf necrosis, aclonifen causes a different phenotype that is described as bleaching. This also is reflected by the Herbicide Resistance Action Committee (HRAC) classification that categorizes aclonifen as an inhibitor of pigment biosynthesis with an unknown target.

RESULTS

A comprehensive Arabidopsis thaliana RNAseq dataset comprising 49 different inhibitor treatments and covering 40 known target pathways was used to predict the aclonifen mode of action (MoA) by a random forest classifier. The classifier predicts for aclonifen a MoA within the carotenoid biosynthesis pathway similar to the reference compound norflurazon that inhibits the phytoene desaturase. Upon aclonifen treatment, the phytoene desaturation reaction is disturbed, resulting in a characteristic phytoene accumulation in vivo. However, direct enzyme inhibition by the herbicide was excluded for known herbicidal targets such as phytoene desaturase, 4‐hydroxyphenylpyruvate dioxygenase and homogentisate solanesyltransferase. Eventually, the solanesyl diphosphate synthase (SPS), providing one of the two homogentisate solanesyltransferase substrate molecules, could be identified as the molecular target of aclonifen. Inhibition was confirmed using biochemical activity assays for the A. thaliana SPSs 1 and 2. Furthermore, a Chlamydomonas reinhardtii homolog was used for co‐crystallization of the enzyme–inhibitor complex, showing that one inhibitor molecule binds at the interface between two protein monomers.

CONCLUSION

Solanesyl diphosphate synthase was identified as the target of aclonifen, representing a novel mode of action for herbicides. © 2020 Society of Chemical Industry
Parametric Generation of Propagating Spin Waves in Ultrathin Yttrium Iron Garnet Waveguides
Authors: Mohseni Morteza , Kewenig Martin , Verba Roman , Wang Qi , Schneider Michael , Heinz Björn , Kohl Felix , Dubs Carsten , Lägel Bert , Serga Alexander A. , Hillebrands Burkard , Chumak Andrii V. , Pirro Philipp
Published: February 2020

Herein, experimental demonstration of the parallel parametric generation of spin waves in a microscaled yttrium iron garnet waveguide with nanoscale thickness is presented. Using Brillouin light scattering microscopy, the parametric excitation of the first and second waveguide modes by a stripline microwave pumping source is observed. Micromagnetic simulations reveal the wave vector of the parametrically generated spin waves. Based on analytical calculations, which are in excellent agreement with experiments and simulations, it is proved that the spin‐wave radiation losses are the determinative term of the parametric instability threshold in this miniaturized system. The used method enables the direct excitation and amplification of nanometer spin waves dominated by exchange interactions. The presented results pave the way for integrated magnonics based on insulating nanomagnets.
Analysis of the video motion tracking system “Kinovea” to assess surgical movements during robot‐assisted radical prostatectomy
Authors: Beulens Alexander J. W. , Namba Hanae F. , Brinkman Willem M. , Meijer Richard P. , Koldewijn Evert L. , Hendrikx Ad J. M. , van Basten Jean‐Paul , van Merriënboer Jeroen J. G. , Van der Poel Henk G. , Bangma Chris , Wagner Cordula
Published: February 2020

Backgrounds

Robot‐assisted surgery facilitated the possibility to evaluate the surgeon's skills by recording and evaluating the robot surgical images. The aim of this study was to investigate the possibility of using a computer programme (Kinovea) for objective assessment of surgical movements in previously recorded in existing robot‐assisted radical prostatectomy (RARP) videos.

Methods

Twelve entire RARP procedures were analysed by a trained researcher using the computer programme “Kinovea” to perform semi‐automated assessment of surgical movements.

Results

Data analysis showed Kinovea was on average able to automatically assess only 22% of the total surgical duration per video of the robot‐assisted surgery. On average, it lasted 4 hours of continued monitoring by the researcher to assess one RARP using Kinovea.

Conclusion

Although we proved it is technically possible to use the Kinovea system in retrospective analysis of surgical movement in robot‐assisted surgery, the acquired data do not give a comprehensive enough analysis of the video to be used in skills assessment.
Biallelic correction of sickle cell disease-derived induced pluripotent stem cells (iPSCs) confirmed at the protein level through serum-free iPS-sac/erythroid differentiation
Authors: Haro-Mora Juan J. , Uchida Naoya , Demirci Selami , Wang Qi , Zou Jizhong , Tisdale John F.
Published: February 2020

New technologies of induced pluripotent stem cells (iPSCs) and genome editing have emerged, allowing for the development of autologous transfusion therapies. We previously demonstrated definitive β-globin production from human embryonic stem cell (hESC)-derived erythroid cell generation via hemangioblast-like ES-sacs. In this study, we demonstrated normal β-globin protein production from biallelic corrected sickle cell disease (SCD) iPSCs. We optimized our ES/iPS-sac method for feeder cell-free hESC maintenance followed by serum-free ES-sac generation, which is preferred for electroporation-based genome editing. Surprisingly, the optimized protocol improved yields of ES-sacs (25.9-fold), hematopoietic-like spherical cells (14.8-fold), and erythroid cells (5.8-fold), compared with our standard ES-sac generation. We performed viral vector-free gene correction in SCD iPSCs, resulting in one clone with monoallelic and one clone with biallelic correction, and using this serum-free iPS-sac culture, corrected iPSC-generated erythroid cells with normal β-globin, confirmed at DNA and protein levels. Our serum-free ES/iPS-sac protocol with gene correction will be useful to develop regenerative transfusion therapies for SCD.

Significance statement The sickle mutation in induced pluripotent stem cells (iPSCs) derived from a patient with sickle cell disease has successfully been corrected using an improved serum-free method for the generation of ES/iPS-sacs, a hemangioblast-like structure containing hematopoietic stem and progenitor cells that can be differentiated into erythroid cells containing mostly definitive globins, including γ- and β-globins.
Intracellular signaling dynamics and their role in coordinating tissue repair
Authors: Ghilardi Samuel J. , O'Reilly Breanna M. , Sgro Allyson E.
Published: February 2020

Tissue repair is a complex process that requires effective communication and coordination between cells across multiple tissues and organ systems. Two of the initial intracellular signals that encode injury signals and initiate tissue repair responses are calcium and extracellular signal‐regulated kinase (ERK). However, calcium and ERK signaling control a variety of cellular behaviors important for injury repair including cellular motility, contractility, and proliferation, as well as the activity of several different transcription factors, making it challenging to relate specific injury signals to their respective repair programs. This knowledge gap ultimately hinders the development of new wound healing therapies that could take advantage of native cellular signaling programs to more effectively repair tissue damage. The objective of this review is to highlight the roles of calcium and ERK signaling dynamics as mechanisms that link specific injury signals to specific cellular repair programs during epithelial and stromal injury repair. We detail how the signaling networks controlling calcium and ERK can now also be dissected using classical signal processing techniques with the advent of new biosensors and optogenetic signal controllers. Finally, we advocate the importance of recognizing calcium and ERK dynamics as key links between injury detection and injury repair programs that both organize and execute a coordinated tissue repair response between cells across different tissues and organs.

This article is categorized under:

Models of Systems Properties and Processes > Mechanistic Models

Biological Mechanisms > Cell Signaling

Laboratory Methods and Technologies > Imaging

Models of Systems Properties and Processes > Organ, Tissue, and Physiological Models
Rooting out letters: octagonal symbol alphabets and algebraic number theory
Authors: Bourjaily Jacob L. , McLeod Andrew J. , Vergu Cristian , Volk Matthias , von Hippel Matt , Wilhelm Matthias
Published: February 2020

Abstract

It is widely expected that NMHV amplitudes in planar, maximally supersymmetric Yang-Mills theory require symbol letters that are not rationally expressible in terms of momentum-twistor (or cluster) variables starting at two loops for eight particles. Re- cent advances in loop integration technology have made this an ‘experimentally testable’ hypothesis: compute the amplitude at some kinematic point, and see if algebraic symbol letters arise. We demonstrate the feasibility of such a test by directly integrating the most difficult of the two-loop topologies required. This integral, together with its rotated image, suffices to determine the simplest NMHV component amplitude: the unique component finite at this order. Although each of these integrals involve algebraic symbol alphabets, the combination contributing to this amplitude is — surprisingly — rational. We describe the steps involved in this analysis, which requires several novel tricks of loop integration and also a considerable degree of algebraic number theory. We find dramatic and unusual simplifications, in which the two symbols initially expressed as almost ten million terms in over two thousand letters combine in a form that can be written in five thousand terms and twenty-five letters.
The classical double copy of a point charge
Authors: Kim Kwangeon , Lee Kanghoon , Monteiro Ricardo , Nicholson Isabel , Veiga David Peinador
Published: February 2020

Abstract

The classical double copy relates solutions to the equations of motion in gauge theory and in gravity. In this paper, we present two double-copy formalisms for relating the Coulomb solution in gauge theory to the two-parameter Janis-Newman-Winicour solution in gravity. The latter is a static, spherically symmetric, asymptotically fiat solution that generically includes a dilaton field, but also admits the Schwarzschild solution as a special case. We first present the classical double copy as a perturbative construction, similar to its formulation for scattering amplitudes, and then present it as an exact map, with a novel generalisation of the Kerr-Schild double copy motivated by double field theory. The latter formalism exhibits the relation between the Kerr-Schild classical double copy and the string theory origin of the double copy for scattering amplitudes.
Three-loop contributions to the ρ parameter and iterated integrals of modular forms
Authors: Abreu Samuel , Becchetti Matteo , Duhr Claude , Marzucca Robin
Published: February 2020

Abstract

We compute fully analytic results for the three-loop diagrams involving two different massive quark flavours contributing to theρparameter in the Standard Model. We find that the results involve exactly the same class of functions that appears in the well-known sunrise and banana graphs, namely elliptic polylogarithms and iterated integrals of modular forms. Using recent developments in the understanding of these functions, we analytically continue all the iterated integrals of modular forms to all regions of the parameter space, and in each region we obtain manifestly real and fast-converging series expansions for these functions.
Homogenization for Generalized Langevin Equations with Applications to Anomalous Diffusion
Authors: Lim Soon Hoe , Wehr Jan , Lewenstein Maciej
Published: February 2020

We study homogenization for a class of generalized Langevin equations (GLEs) with state-dependent coefficients and exhibiting multiple time scales. In addition to the small mass limit, we focus on homogenization limits, which involve taking to zero the inertial time scale and, possibly, some of the memory time scales and noise correlation time scales. The latter are meaningful limits for a class of GLEs modeling anomalous diffusion. We find that, in general, the limiting stochastic differential equations for the slow degrees of freedom contain non-trivial drift correction terms and are driven by non-Markov noise processes. These results follow from a general homogenization theorem stated and proven here. We illustrate them using stochastic models of particle diffusion.
Outcome of conservative treatment for triangular fibrocartilage complex lesions with stable distal radioulnar joint
Authors: Sander Anna Lena , Sommer Katharina , Kaiser Antonia Katharina , Marzi Ingo , Frank Johannes
Published: February 2020

Purpose

Triangular fibrocartilage complex (TFCC) lesions have high clinical relevance. Although multiple studies have been done in the past, there is a lack of data after conservative treatment and controversy remains regarding management. The purpose of this study was to compare the outcome of symptomatic TFCC lesions after conservative treatment and arthroscopic debridement.

Methods

Between 2012 and 2017, 33 patients were included. 16 patients were treated conservatively and 17 patients with arthroscopic debridement. The average age was 41 years (range 18–63). The mean follow-up was 22.2 months (range 6–74). Evaluation included pain, range of motion (ROM), grip strength, Disabilities of the Arm, Shoulder, and Hand (DASH) score, Modified Mayo Wrist Score (MMWS), and Purdue Pegboard test.

Results

Pain averaged 0.1 (range 0–1) in the conservative group compared to 1.3 (range 0–6) in the arthroscopic group. The mean ROM was 99% for wrist extension, and 100% for flexion and pro-/supination in the conservative group, and 96% for extension and flexion, and 100% for pro-/supination in the arthoscopic group compared to the contralateral side. Grip strength was 88% (range 63–100) in the conservative group versus 89% (range 33–100) in the arthroscopic group. The conservative group reached a DASH score of 16.8 and MMWS of 94.3 compared to 22.1 and 87.2 in the arthroscopic group. The differences were not statistically significant.

Conclusions

Our study demonstrated similar results of conservative compared to arthroscopic treatment. Because conservative treatment was a sufficient and reliable option, we propose it as first-line treatment for TFCC lesions with stable distal radioulnar joint.
Comment on “Minimization of maximum failure criterion of laminated composite shell structure by optimizing distributed-material orientation” by Shimoda M., Muramatsu Y., Tsukihara R.
Authors: Kobelev V.
Published: February 2020

The new “modified Tsai-Hill failure criterion” introduced in Shimoda et al. (SAMO, 2020) does not possess a convex fracture envelope for all possible set of its coefficients. An extended version of the “modified Tsai-Hill failure criterion” is introduced. The extended version encompasses several known failure criterions for the anisotropic materials. The convexity of the fracture envelope for composite materials and metallic alloys is briefly discussed. Albeit the convexity of the failure envelope is not necessary from the physical viewpoint, the convexity is favorable for the application of optimization methods.
Effective balance equations for poroelastic composites
Authors: Miller Laura , Penta Raimondo
Published: February 2020

We derive the quasi-static governing equations for the macroscale behaviour of a linear elastic porous composite comprising a matrix interacting with inclusions and/or fibres, and an incompressible Newtonian fluid flowing in the pores. We assume that the size of the pores (the microscale) is comparable with the distance between adjacent subphases and is much smaller than the size of the whole domain (the macroscale). We then decouple spatial scales embracing the asymptotic (periodic) homogenization technique to derive the new macroscale model by upscaling the fluid–structure interaction problem between the elastic constituents and the fluid phase. The resulting system of partial differential equations is of poroelastic type and encodes the properties of the microstructure in the coefficients of the model, which are to be computed by solving appropriate cell problems which reflect the complexity of the given microstructure. The model reduces to the limit case of simple composites when there are no pores, and standard Biot’s poroelasticity whenever only the matrix–fluid interaction is considered. We further prove rigorous properties of the coefficients, namely (a) major and minor symmetries of the effective elasticity tensor, (b) positive definiteness of the resulting Biot’s modulus, and (c) analytical identities which allow us to define an effective Biot’s coefficient. This model is applicable when the interactions between multiple solid phases occur at the porescale, as in the case of various systems such as biological aggregates, constructs, bone, tendons, as well as rocks and soil.
Motor congruency and multisensory integration jointly facilitate visual information processing before movement execution
Authors: Elshout J. A. , Van der Stoep N. , Nijboer T. C. W. , Van der Stigchel S.
Published: February 2020

Attention allows us to select important sensory information and enhances sensory information processing. Attention and our motor system are tightly coupled: attention is shifted to the target location before a goal-directed eye- or hand movement is executed. Congruent eye–hand movements to the same target can boost the effect of this pre-movement shift of attention. Moreover, visual information processing can be enhanced by, for example, auditory input presented in spatial and temporal proximity of visual input via multisensory integration (MSI). In this study, we investigated whether the combination of MSI and motor congruency can synergistically enhance visual information processing beyond what can be observed using motor congruency alone. Participants performed congruent eye- and hand movements during a 2-AFC visual discrimination task. The discrimination target was presented in the planning phase of the movements at the movement target location or a movement irrelevant location. Three conditions were compared: (1) a visual target without sound, (2) a visual target with sound spatially and temporally aligned (MSI) and (3) a visual target with sound temporally misaligned (no MSI). Performance was enhanced at the movement-relevant location when congruent motor actions and MSI coincide compared to the other conditions. Congruence in the motor system and MSI together therefore lead to enhanced sensory information processing beyond the effects of motor congruency alone, before a movement is executed. Such a synergy implies that the boost of attention previously observed for the independent factors is not at ceiling level, but can be increased even further when the right conditions are met.
How visual information influences dual-task driving and tracking
Authors: Broeker Laura , Haeger Mathias , Bock Otmar , Kretschmann Bettina , Ewolds Harald , Künzell Stefan , Raab Markus
Published: February 2020

The study examined the impact of visual predictability on dual-task performance in driving and tracking tasks. Participants (N = 27) performed a simulated driving task and a pursuit tracking task. In either task, visual predictability was manipulated by systematically varying the amount of advance visual information: in the driving task, participants drove at night with low beam, at night with high beam, or in daylight; in the tracking task, participants saw a white line that specified the future target trajectory for 200, 400 or 800 ms. Concurrently with driving or tracking, participants performed an auditory task. They had to discriminate between two sounds and press a pedal upon hearing the higher sound. Results show that in general, visual predictability benefited driving and tracking; however, dual-task driving performance was best with highest visual predictability (daylight), dual-task tracking performance was best with medium visual predictability (400 ms). Braking/reaction times were higher in dual tasks compared to single tasks, but were unaffected by visual predictability, showing that its beneficial effects did not transfer to the auditory task. In both tasks, manual accuracy decreased around the moment the foot pressed the pedal, indicating interference between tasks. We, therefore, conclude that despite a general beneficial impact of predictability, the integration of visual information seems to be rather task specific, and that interference between driving and audiomotor tasks, and tracking and audiomotor tasks, seems comparable.
Predicting the chemical composition of juvenile and mature woods in Scots pine (Pinus sylvestris L.) using FTIR spectroscopy
Authors: Funda Tomas , Fundova Irena , Gorzsás András , Fries Anders , Wu Harry X.
Published: February 2020

The chemical composition of wood is one of the key features that determine wood quality. The focus of this study was on identifying differences between juvenile and mature woods in Scots pine (Pinus sylvestrisL.) and developing models for predicting the chemical composition of these two wood types. Chemical traits, determined by traditional wet chemistry techniques, included the proportion of lignin, polysaccharides and extractives. Partial least squares regression of Fourier transform infrared (FTIR) spectra was used for model building. The model performance was primarily evaluated by root mean squared error of predictions (RMSEP). High predictive power was attained for the content of lignin (RMSEP of 0.476 and 0.495 for juvenile and mature woods, respectively) and extractives (0.302 and 0.471), good predictive power for cellulose (0.715 and 0.696) and hemicelluloses in juvenile wood (0.719) and low predictive power for hemicelluloses in mature wood (0.823). A distinct band was observed at 1693 cm−1, and its intensity was strongly associated with the content of extractives (r = 0.968 and 0.861 in juvenile and mature woods, respectively). FTIR has proved suitable for the rapid, non-destructive, cost-efficient assessment of the chemical composition of juvenile and mature woods in Scots pine. The band at 1693 cm−1is to be further investigated to unravel its link with individual extractive components.
Evaluation of the bioequivalence and food effect on the bioavailability of CC-486 (oral azacitidine) tablets in adult patients with cancer
Authors: Babiker Hani M. , Milhem Mohammed , Aisner Joseph , Edenfield William , Shepard Dale , Savona Michael , Iyer Swaminathan , Abdelrahim Maen , Beach C. L. , Skikne Barry , Laille Eric , Tsai Kao-Tai , Ho Thai
Published: February 2020

Purpose

CC-486 is an oral formulation of azacitidine that allows for extended dosing schedules to prolong azacitidine exposure to malignant cells and maximize clinical activity. CC-486 300 mg daily, administered for 14 or 21 days of 28-day treatment cycles, is currently under investigation in two ongoing phase III trials. The 300-mg daily dose in these studies is administered as two 150-mg tablets (Formulation A).

Methods

We evaluated the bioequivalence of one 300-mg CC-486 tablet (Formulation B) with Formulation A and food effect on Formulation B, in adult patients with cancer in a 2-stage crossover design study.

Results

The ratios of the geometric means of the maximum azacitidine plasma concentration (Cmax) and of the area under the plasma concentration–time curve from time 0 extrapolated to infinity (AUC∞) were 101.5% and 105.7%, demonstrating the bioequivalence of Formulations A and B. Formulation B was rapidly absorbed under fasted and fed conditions. The geometric mean of Cmax was significantly decreased by ~ 21% in the fed state. Median Tmax was reached at 2 h and 1 h post-dose in fed and fasted states, respectively (P < 0.001). Nevertheless, systemic drug exposure (AUC) in fed and fasted states was within the 80–125% boundaries of bioequivalence and differences in Cmax and Tmax are not expected to have a clinical impact.

Conclusion

The single 300-mg CC-486 tablet was bioequivalent to two 150-mg tablets, which have shown to be efficacious and generally well-tolerated in clinical trials, and can be taken with or without food.
Effects of disease-modifying therapy on peripheral leukocytes in patients with multiple sclerosis
Authors: Schweitzer F. , Laurent S. , Fink G. R. , Barnett Michael H. , Hartung H. P. , Warnke C.
Published: February 2020

Modern disease-modifying therapies (DMTs) in multiple sclerosis (MS) have variable modes of action and selectively suppress or modulate the immune system. In this review, we summarize the predicted and intended as well as unwanted adverse effects on leukocytes in peripheral blood as a result of treatment with DMTs for MS. We link changes in laboratory tests to the possible therapeutic risks that include secondary autoimmunity, infections, and impaired response to vaccinations. Profound knowledge of the intended effects on leukocyte counts, in particular lymphocytes, explained by the mode of action, and adverse effects which may require additional laboratory and clinical vigilance or even drug discontinuation, is needed when prescribing DMTs to treat patients with MS.
Cognition and mental wellbeing after electrical accidents: a survey and a clinical study among Swedish male electricians
Authors: Thomée Sara , Österberg Kai , Rådman Lisa , Jakobsson Kristina
Published: February 2020

Purpose

The purpose was to examine long-term consequences of exposure to electrical current passing through the body. We investigated (1) whether electricians after having experienced an electrical accident report more cognitive problems and lower mental wellbeing and (2) have objectively verifiable reduced cognitive function; and (3) which circumstances at the time of the accident affect long-term subjective cognitive function and mental wellbeing?

Methods

A survey of male electricians who had experienced electrical accidents (n = 510) and a clinical study in a subsample (n = 23) who reported residual health problems was carried out. Both groups were examined regarding subjective cognitive function (Euroquest-9) and mental wellbeing (Symptom Checklist-90 subscales). The clinical study included neuropsychological tests of memory, attention, spatial function, and premorbid intellectual capacity. A matched control group was retrieved from reference data.

Results

The survey participants reported more cognitive problems and lower mental wellbeing than referents. Of the examined circumstances, having experienced mortal fear at the time of the accident and health complaints, especially mental symptoms, for > 1 week after the accident were the most significant risk factors for later subjective cognitive problems and lower mental wellbeing. The only statistically significant difference in neuropsychological tests was better performance in part of the memory tests by the clinical study group compared to the control group.

Conclusions

The participants reported more cognitive problems and lower mental wellbeing than referents, but no long-term objective cognitive dysfunction was detected. Emotional response at the time of the accident and health complaints in the aftermath of the accident may constitute important indications for medical and psychological follow-ups.
Distribution and development of the external sense organ pattern on the appendages of postembryonic and adult stages of the spider Parasteatoda tepidariorum
Authors: Schacht Magdalena Ines , Francesconi Martina , Stollewerk Angelika
Published: February 2020

Spiders are equipped with a large number of innervated cuticular specializations, which respond to various sensory stimuli. The physiological function of mechanosensory organs has been analysed in great detail in some model spider species (e.g.Cupiennius salei); however, much less is known about the distribution and function of chemosensory organs. Furthermore, our knowledge on how the sense organ pattern develops on the spider appendages is limited. Here we analyse the development of the pattern and distribution of six different external mechano- and chemosensory organs in all postembryonic stages and in adult male and female spiders of the speciesParasteatoda tepidariorum. We show that except for small mechanosensory setae, external sense organs appear in fixed positions on the pedipalps and first walking legs, arranged in longitudinal rows along the proximal-distal axis or in invariable positions relative to morphological landmarks (joints, distal tarsal tip). A comparison to other Entelegynae spiders shows that these features are conserved. We hope that this study lays the foundation for future molecular analysis to address the question how this conserved pattern is generated.
Comparative multi-assay evaluation of Determine™ HIV-1/2 Ag/Ab Combo rapid diagnostic tests in acute and chronic HIV infection
Authors: Wratil Paul R. , Rabenau Holger F. , Eberle Josef , Stern Marcel , Münchhoff Maximilian , Friedrichs Imke , Stürmer Martin , Berger Annemarie , Kuttner-May Susanne , Münstermann Dieter , Lucht Andreas , Meixenberger Karolin , Bannert Norbert , Keppler Oliver T.
Published: February 2020

In resource-limited or point-of-care settings, rapid diagnostic tests (RDTs), that aim to simultaneously detect HIV antibodies and p24 capsid (p24CA) antigen with high sensitivity, can pose important alternatives to screen for early infections. We evaluated the performance of the antibody and antigen components of the old and novel version of the Determine™ HIV-1/2 Ag/Ab Combo RDTs in parallel to quantifications in a fourth-generation antigen/antibody immunoassay (4G-EIA), p24CA antigen immunoassay (p24CA-EIA), immunoblots, and nucleic acid quantification. We included plasma samples of acute, treatment-naïve HIV-1 infections (Fiebig stages I–VI, subtypes A1, B, C, F, CRF02_AG, CRF02_AE, URF) or chronic HIV-1 and HIV-2 infections. The tests’ antigen component was evaluated also for a panel of subtype B HIV-1 transmitted/founder (T/F) viruses, HIV-2 strains and HIV-2 primary isolates. Furthermore, we assessed the analytical sensitivity of the RDTs to detect p24CA using a highly purified HIV-1NL4-3 p24CA standard. We found that 77% of plasma samples from acutely infected, immunoblot-negative HIV-1 patients in Fiebig stages II–III were identified by the new RDT, while only 25% scored positive in the old RDT. Both RDTs reacted to all samples from chronically HIV-1-infected and acutely HIV-1-infected patients with positive immunoblots. All specimens from chronically infected HIV-2 patients scored positive in the new RDT. Of note, the sensitivity of the RDTs to detect recombinant p24CA from a subtype B virus ranged between 50 and 200 pg/mL, mirrored also by the detection of HIV-1 T/F viruses only at antigen concentrations tenfold higher than suggested by the manufacturer. The RTD failed to recognize any of the HIV-2 viruses tested. Our results indicate that the new version of the Determine™ HIV-1/2 Ag/Ab Combo displays an increased sensitivity to detect HIV-1 p24CA-positive, immunoblot-negative plasma samples compared to the precursor version. The sensitivity of 4G-EIA and p24CA-EIA to detect the major structural HIV antigen, and thus to diagnose acute infections prior to seroconversion, is still superior.
Guidelines for uveal melanoma: a critical appraisal of systematically identified guidelines using the AGREE II and AGREE-REX instrument
Authors: Steeb Theresa , Hayani Kinan M. , Förster Paul , Liegl Raffael , Toussaint Frédéric , Schlaak Max , Berking Carola , Heppt Markus V.
Published: February 2020

Purpose

Clinical practice guidelines provide recommendations for the management of diseases. In orphan conditions such as uveal melanoma (UM), guideline developers are challenged to provide practical and useful guidance even in the absence of high-quality evidence. Here, we assessed the methodological quality and identified deficiencies of international guidelines on UM as a base for future guideline development.

Methods

A systematic search was carried out in guideline databases, Medline and Embase until 27th May 2019 for guidelines on UM published between 2004 and 2019. Five independent reviewers assessed the methodological quality of the identified guidelines using the instruments “Appraisal of Guidelines for Research and Evaluation II” (AGREE II) and AGREE-REX (Recommendation EXcellence). Descriptive analysis was performed and subgroup differences were explored with the Kruskal–Wallis (H) test. The relationship between the individual domains and items of the instruments were examined using Spearman’s correlation.

Results

Five guidelines published from 2014 to 2018 by consortia of the United States of America, Canada and the United Kingdom (UK) were included. The highest scores were obtained by the UK guideline fulfilling 48–86% of criteria in AGREE II and 30–60% for AGREE-REX. All guidelines showed deficiencies in the domains “editorial independence”, “applicability”, and “recommendation”. Subgroup differences were identified only for the domain “editorial independence”.

Conclusion

The UK guideline achieved the highest scores with both instruments and may serve as a basis for future guideline development in UM. The domains “editorial independence”, “recommendation”, and “applicability” were identified as methodological weaknesses and require particular attention and improvement in future guidelines.
Design methodology for 360° immersive video applications: the case study of a cultural heritage virtual tour
Authors: Argyriou Lemonia , Economou Daphne , Bouki Vassiliki
Published: February 2020

Three hundred sixty–degree (360°) immersive video applications for Head Mounted Display (HMD) devices offer great potential in providing engaging forms of experiential media solutions especially in Cultural Heritage education. Design challenges emerge though by this new kind of immersive media due to the 2D form of resources used for their construction, the lack of depth, the limited interaction and the need to address the sense of presence. In addition, the use of Virtual Reality (VR) headsets often causes nausea, or motion sickness effects imposing further implications in moderate motion design tasks. This paper introduces a methodological categorisation of tasks and techniques for the design of 360° immersive video applications. Following the design approach presented, a testbed application has been created as an immersive interactive virtual tour at the historical centre of the city of Rethymno in Crete, Greece, which has undergone user trials. Based on the analysis of the results of this study, a set of design guidelines for the implementation of 360° immersive video virtual tours is proposed.
Fast multi-language LSTM-based online handwriting recognition
Authors: Carbune Victor , Gonnet Pedro , Deselaers Thomas , Rowley Henry A. , Daryin Alexander , Calvo Marcos , Wang Li-Lun , Keysers Daniel , Feuz Sandro , Gervais Philippe
Published: February 2020

We describe an online handwriting system that is able to support 102 languages using a deep neural network architecture. This new system has completely replaced our previous segment-and-decode-based system and reduced the error rate by 20–40% relative for most languages. Further, we report new state-of-the-art results on IAM-OnDB for both the open and closed dataset setting. The system combines methods from sequence recognition with a new input encoding using Bézier curves. This leads to up to$$10\times $$10×faster recognition times compared to our previous system. Through a series of experiments, we determine the optimal configuration of our models and report the results of our setup on a number of additional public datasets.
Expressions of collective grievance as a feedback in multi-actor adaptation to water risks in Mexico City
Authors: Eakin Hallie , Shelton Rebecca , Baeza Andrés , Bojórquez-Tapia Luis A. , Flores Shalae , Parajuli Jagadish , Grave Ileana , Estrada Barón Alejandra , Hernández Bertha
Published: February 2020

Effective adaptation assumes a feedback between the experience or anticipation of harm, and the actions of those individuals whose decisions and actions are necessary to reduce that harm. In urban areas, citizens often expect support from the public sector to facilitate their adaptation efforts and to protect them from exposure. This expectation—grounded in notions of the social contract between citizens and the state—presumes efficient feedback between public sector actors and residents concerning vulnerable states and adaptation needs. Through a case study of Mexico City, we analyze the role of social mobilization, specifically, neighborhood protests associated with water scarcity, as an informal means for a vulnerable population to communicate its needs to those actors with the mandate and capacity to alter risk exposure. On the basis of the findings from the case study, we propose a simple framework to begin a more systematic process of analyzing the expression of grievances as a feedback among actors involved in urban adaptation. We argue that by making visible these expressions as an informal mechanism of feedback between risk exposure, impact, decision-making, and the biophysical environment, we can reveal a potentially important lever on system change: one that highlights existing asymmetries in power, equity, and rights in urban adaptation.
Teacher burnout profiles and proactive strategies
Authors: Pyhältö Kirsi , Pietarinen Janne , Haverinen Kaisa , Tikkanen Lotta , Soini Tiina
Published: February 2020

Teacher burnout has been identified as a significant occupational hazard. However, our understanding about individual variations in burnout risk among in-service teachers is still less than sufficient. This study explored socio-contextual burnout risk profiles and their association with the reported use of proactive strategies among in-service teachers by using a person-oriented approach. The survey data were collected from 2310 Finnish in-service primary and lower secondary school teachers using a probability sampling method. In the latent profile analysis, five socio-contextual burnout profiles were identified. The profiles differed from each other in terms of burnout symptoms and proactive strategy use. Results suggested that there is individual variation in teachers’ risk of burnout. In addition, the results imply that well-developed proactive strategies, both in terms of self- and co-regulative strategies, are related to lower risk of experiencing socio-contextual burnout. The utilization of strong co-regulative strategies was related to lower risk of experiencing exhaustion and inadequacy during teacher-pupil interactions. However, strong self-regulation combined with low levels of co-regulation was related to an increased risk of experiencing cynicism. This implies that learning proactive strategies may be useful in preventing teacher burnout.