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This chapter treats Apollodorus the Mythographer (regularly referred to as Ps.-Apollodorus), the probably 1st-century ce writer who produced the Bibliotheca (Library), the most complete—although not perfectly so—and finest work of systematizing mythographer to survive from antiquity. A summary account is provided of our knowledge of the otherwise unknown author, evidence for his date, the nature of his work, his literary and intellectual ambitions, and the nature of the narrative, which gives a broad overview of Greek myth arranged chronologically from primordial times to the generation after the Trojan War. Attention is given as well to the question of Apollodorus’s sources, which has dominated modern scholarship. An account of the state of the text and how it was passed down is sketched.

The main aim of this chapter is to survey and problematize our current state of knowledge of mythographical scholarship during the Hellenistic period. This era is widely considered crucial in the formation of mythography, but aside from the surviving work of Palaephatus, all the other evidence is scattered, fragmentary, and difficult to interpret. The chapter presents three case studies considering the work of Asclepiades of Tragilus, Lysimachus of Alexandria, and Apollodorus of Athens to test the identification of these three authors as mythographers and finds the evidence inconclusive, highlighting the need for new and further research into myth reception in the Hellenistic era.

This introduction provides an overview of the contents of the handbook and attempts to situate the information and arguments of the individual chapters in the context of Greek and Roman mythographical studies today, which have changed dramatically in the last three decades. Additionally, a brief survey of the shifting modes of mythography in antiquity is presented. While a simple exposition is impossible and a complete overarching theory and definition cannot be provided, we note how many of the contributions point toward mythography as a mental orientation or intellectual impulse rather than a clear-cut genre—which better explains the great variety of mythographical products and the numerous occasions where mythography was integrated into other writing practices in the ancient world.

Tracing the role of myth and mythography throughout the main periods of a student’s career, this chapter articulates the way that educational practices reflect and reinforce a mythographical mindset, one that organizes and employs mythical data in a variety of ways. From the very beginning students were asked to learn mythical names and combine like with like, then (under a grammaticus) copy and create their own mythical narratives (systematic mythography); as their rhetorical training progressed (under a rhetor), these same students were asked to manipulate myths in new ways, to raise objections (similar to rationalization), to defend the account (similar to allegorizing), and to create more advanced compositions in encomium, comparison and ethopoiia.

Many people with hemophilia A (PwHA) undergo surgery in their lifetime, often because of complications of their disease. Emicizumab is the first bispecific monoclonal antibody prophylactic therapy for PwHA, and its efficacy and safety have been previously demonstrated; however, there is a need to build an evidence base on the management of PwHA on emicizumab undergoing surgery. Data from the HAVEN 1-4 phase 3 clinical trials were pooled to provide a summary of all minor and major surgeries in PwHA with or without factor VIII (FVIII) inhibitors who were receiving emicizumab prophylaxis. Overall, 233 surgeries were carried out during the HAVEN 1-4 trials: 215 minor surgeries (including minor dental and joint procedures, central venous access device placement or removal, and endoscopies) in 115 PwHA (64 with FVIII inhibitors) and 18 major surgeries (including arthroplasty and synovectomy) in 18 PwHA (10 with FVIII inhibitors). Perioperative hemostatic support was at the discretion of the treating physician. Overall, the median (interquartile range [IQR]) age was 33.5 (13.0-49.0) years and the median (IQR) emicizumab exposure time before surgery was 278.0 (177.0-431.0) days. Among the 215 minor surgeries, 141 (65.6%) were managed without additional prophylactic factor concentrate, and of those, 121 (85.8%) were not associated with a postoperative bleed. The majority (15 of 18 [83.3%]) of major surgeries were managed with additional prophylactic factor concentrate. Twelve (80.0%) of these 15 surgeries were associated with no intraoperative or postoperative bleeds. The data demonstrate that minor and major surgeries can be performed safely in PwHA receiving emicizumab prophylaxis. These trials are registered at www.clinicaltrials.gov as #NCT02622321, #NCT02795767, #NCT02847637, and #NCT03020160.

Sports coaching is traditionally a male-dominated profession all over the world, though there is no explicit evidence that either gender outperforms the other in this profession. The current paper aimed to uncover the differences between female and male coaches regarding their pedagogical and professional beliefs. A total of 357 basketball coaches (30.8% women and 69.2% men) working in Hungary responded to an online questionnaire. A background analysis of the sample revealed that most of the coaches manage youth teams and that women coach younger age groups than men. Female coaches proved to be more educated than their male counterparts, both in general and on a professional level. The results showed that, regardless of gender, the coaches were well aware of their pedagogical functions. Significant differences were found in terms of relationships, personal development, motivation, and discipline; the women reported higher values in all cases. Female coaches were also more concerned about factors that help gain respect and appreciation. Based on the results, education, qualifications, and pedagogical and professional views of coaches do not justify the underrepresentation of women in sports coaching. Club managers, sports federation boards, and other decision makers should promote programs that are aimed at engaging more women in sports coaching.

This chapter centres on Heliodorus 2.4.1–4, where the reader encounters a lament delivered by the hero Theagenes over his apparent loss of Chariclea at a point in the narrative almost immediately after another lament by the same character for the same reason. Following the lead of medieval readers such as Philagathos of Cerami, Michael Psellos, and one of the writers of the Digenes Akrites tradition, whose works reveal a keen interest in and specific mode of reception of the passage in question in connection with lamentation and grief, an interpretation is offered that connects the twin laments of Theagenes with other doubled features of Heliodorus’ narrative in the first book of the novel, creating an interwoven set of correspondences that function both structurally and narratively to ‘train’ readers to read the Aethiopica.

The 32-item Motor Function Measure (MFM32) is an assessment of motor function used to evaluate fine and gross motor ability in patients with neuromuscular disorders, including spinal muscular atrophy (SMA). Reliability and validity of the MFM32 have been documented in individuals with SMA. Through semi-structured qualitative interviews (N = 40) and an online survey in eight countries (N = 217) with individuals with Types 2 and 3 SMA aged 2–59 years old and caregivers, the meaning of changes on a patient-friendly version of the MFM32 was explored. In an independent analysis of clinical trial data, anchor- and distribution-based analyses were conducted in a sample of individuals with Type 2 and non-ambulant Type 3 SMA to estimate patient-centered quantitative MFM32 meaningful change thresholds. The results from this study demonstrate that, based on patient and caregiver insights, maintaining functional ability as assessed by a patient-friendly version of the MFM32 is an important outcome. Quantitative analyses using multiple anchors (median age range of 5–8 years old across anchor groups) indicated that an ~3-point improvement in MFM32 total score represents meaningful change at the individual patient level. Overall, the qualitative and quantitative findings from this study support the importance of examining a range of meaningful change thresholds on the MFM32 including ≥0 points change reflecting stabilization or improvement and ≥3 points change reflecting a higher threshold of improvement. Future research is needed to explore quantitative differences in meaningful change on the MFM32 based on age and functional subgroups.

Spatial chromatin organization is crucial for transcriptional regulation and might be particularly important in neurons since they dramatically change their transcriptome in response to external stimuli. We show that stimulation of neurons causes condensation of large chromatin domains. This phenomenon can be observed in vitro in cultured rat hippocampal neurons as well as in vivo in the amygdala and hippocampal neurons. Activity-induced chromatin condensation is an active, rapid, energy-dependent, and reversible process. It involves calcium-dependent pathways but is independent of active transcription. It is accompanied by the redistribution of posttranslational histone modifications and rearrangements in the spatial organization of chromosome territories. Moreover, it leads to the reorganization of nuclear speckles and active domains located in their proximity. Finally, we find that the histone deacetylase HDAC1 is the key regulator of this process. Our results suggest that HDAC1-dependent chromatin reorganization constitutes an important level of transcriptional regulation in neurons., This work was supported by the National Science Centre grant nos. UMO-2015/18/E/NZ3/00730 (A.M., A.G., H.S.N., E.J. and Y.Y.), 2014/15/N/NZ2/00379 and 2017/24/T/NZ2/00307 (P.T.), 2019/35/O/ST6/02484 (D.P. and G.B.), and 2014/14/M/NZ4/00561 (K.H.O. and R.K.F.). B.W. and B.G. were supported by the Foundation for Polish Science TEAM-TECH Core Facility project “NGS platform for comprehensive diagnostics and personalized therapy in neuro-oncology,” Foundation for Polish Science co-financed by the European Union under the European Regional Development Fund (TEAM to D.P.). A.M.G. was supported by the H2020-MSCA-COFUND-2014 grant Bio4Med (GA no. 665735).

Cancer patients often experience loss in body weight and also a decrease in muscle mass, which results in the reduction of physical activity and mobilization of the patient. To decelerate the loss of muscle mass, as part of the cancer treatment patients frequently undergo physical therapy and considering the physical capabilities of the patients, with moderate loads. Moreover, frequent studies also observed for cancer patients, together with the decrease in muscle mass a shift into fast-twitch muscle fibers from slow-twitch fibers. The aim of our study therefore was to determine how motor fibers behave under moderate isometric load executed until total exhaustion. 11 university students (G1), and 14 elite athletes (G2) participated in the study. 65% of the maximal voluntary contraction (MVC) was determined for the biceps brachii muscle, and with this load holding a weight, participants had to sustain a 90 deg. isometric elbow flexion in a standing posture until complete fatigue occurred. EMG activity for the biceps brachii muscle was measured and frequency analysis was performed. 3 windows were determined in the fatiguing protocol: the first (W1), middle (W2), and last (W3) 5 s, and also frequency analysis for MVC was performed (MAX) between 0 and 260 Hz with 20 Hz wide frequency bands. The results indicate, that as the protocol progressed in time and the effect of fatigue increased (from W1 to W3) the activity of low frequency muscle fibers significantly increased (0-40 Hz) while activity of high frequency muscle fibers (60-260 Hz) significantly decreased for G1 and G2 groups identically. We can conclude, that training applied with constant moderate tension as fatigue increases will result in the increased activation of the lower frequency slow–twitch muscle fibers, but the increase of fatigue in the lower frequency fibers will not result in the increase in the activation level of the higher frequency fast-twitch fibers. Consequently, because as slow-twitch fibers are being used at moderate loads and even when fatigue occurs in these fibers the fast-twitch fibers will not work, higher muscle loads are needed if the aim is to activate fast-twitch fibers. Considering the shift into fast-twitch muscle fibers from slow-twitch fibers for cancer patients, in some cases if the patient’s age and physical status allows during the physical treatment, higher loads and consequently higher levels of activation might be beneficial for the retardment of loss concerning the fast-twitch fiber mass.

Jednym z fundamentalnych pytań w dziedzinie biologii jest to, w jaki sposób dwumetrowa nić DNA upakowana jest w jądrze o średnicy około 10 µm. Odpowiedzi na to pytanie udzielić może mikroskopia XXI w. Choć pierwsze mikroskopy powstały już w XVI w., to dopiero od kilkunastu lat (dzięki obejściu bariery dyfrakcyjnej ograniczającej rozdzielczość) możemy mówić o mikroskopii superrozdzielczej. Z każdym rokiem zaawansowane techniki mikroskopowe, wraz z rozwojem metod biochemicznych oraz obliczeniowych, przybliżają nas do odpowiedzi na to pytanie. Niniejsza praca ma na celu przedstawienie Czytelnikowi wstępu do badań nad organizacją chromatyny oraz przegląd technik mikroskopowych stosowanych w tych badaniach, z uwzględnieniem ich zalet oraz ograniczeń. Przy każdej z metod przedstawiono przykłady prac i odkryć uzyskanych dzięki nim. Ponieważ mikroskopia rozwija się bardzo dynamicznie w przeciągu ostatnich kilkunastu lat, opisane zostały w większości przypadków prace najnowsze. Przykłady te pozwalają Czytelnikowi zorientować się w postępie w badaniach nad organizacją chromatyny, a także (w połączeniu z opisem samych technik) w wybraniu odpowiednich metod obrazowania na etapie planowania własnych badań.

BackgroundBioimaging techniques offer a robust tool for studying molecular pathways and morphological phenotypes of cell populations subjected to various conditions. As modern high resolution 3D microscopy provides access to an ever-increasing amount of high quality images, there arises a need for their analysis in an automated, unbiased and simple way.Segmentation of structures within cell nucleus, which is the focus of this paper, presents a new layer of complexity in the form of dense packing and significant signal overlap.At the same time the available segmentation tools provide a steep learning curve for new users with limited technical background. This is especially apparent in bulk processing of image sets, which requires the use of some form of programming notation.ResultsIn this paper, we present PartSeg, a tool for segmentation and reconstruction of 3D microscopy images, optimised for the study of cell nucleus. PartSeg integrates refined versions of several state-of-the-art algorithms, including a new multi-scale approach for segmentation and quantitative analysis of 3D microscopy images.The features and user-friendly interface of PartSeg were carefully planned with biologists in mind, based on analysis of multiple use cases and difficulties encountered with other tools, to offer ergonomic interface with a minimal entry barrier. Bulk processing in an ad-hoc manner is possible without the need for programmer support. As the size of datasets of interest grows, such bulk processing solutions become essential for proper statistical analysis of results.Advanced users can use PartSeg components as a library within Python data processing and visualisation pipelines, for example within Jupyter notebooks. The tool is extensible so that new functionality and algorithms can be added by the use of plugins.For biologists the utility of PartSeg is presented in several scenarios, showing the quantitative analysis of nuclear structures.ConclusionsIn this paper, we have presented PartSeg which is a tool for precise and verifiable segmentation and reconstruction of 3D microscopy images. PartSeg is optimised for cell nucleus analysis and offers multiscale segmentation algorithms best-suited for this task. PartSeg can also be used for bulk processing of multiple images and its components can be reused in other systems or computational experiments.Contactg.bokota@cent.uw.edu.pl, a.magalska@nencki.edu.pl, d.plewczynski@cent.uw.edu.pl

Spatial chromatin organization is crucial for transcriptional regulation and might therefore be particularly dynamic in neurons since these terminally differentiated cells dramatically change their transcriptome in response to external stimuli. Here, we show that stimulation of neurons causes condensation of large chromatin domains. We find that this phenomenon is not only induced in rat hippocampal neurons cultured in vitro, but is also present in vivo in amygdala neurons of rats subjected to fear conditioning, and hippocampal neurons of animals subjected to kainate evoked seizures or High-Frequency Stimulation (HFS). The activity-induced chromatin condensation is an active, very rapid, and reversible process, that is independent of transcription and precedes the expression of Immediate Early Genes (IEG). It is accompanied by the redistribution of posttranslational modifications of histones, and rearrangements in the spatial organization of chromosome territories. Moreover, it leads to the reorganization of nuclear speckles and active domains located in their proximity. Finally, we find that neurons depleted of the histone deacetylase HDAC1 fail to condense chromatin upon stimulation, a phenomenon that can be fully reversed by the introduction of human HDAC1. Taken together, our results suggest that the HDAC1-dependent chromatin reorganization might constitute an important level of fine-tuning of transcriptional regulation in stimulated neurons.

Purpose The multidimensional role of hamstring muscle group strength in athletic performance and injury prevention is well documented, and nordic hamstring exercise (NHE) is a popular method for the development of hamstring strength. Our aim was to examine the EMG characteristics of the eccentric NHE as well as the effects of long-term eccentric NHE training on muscle strength and vertical jump performance in 10- to 11-year-old female handball players. Methods Players from the same handball team were randomly assigned to an eccentric NHE training (13 players) or a control group (10 players). Both groups continued their regular handball training routine, but the NHE group performed additional eccentric NHE exercises once or twice a week, with progressively increasing volume, over 20 weeks. To test training effects, countermovement jump (CMJ) height, eccentric hamstring impulse, peak torque, and angle of peak torque were evaluated before, during and after the training period. In the pre-exercise test, EMG activity of the medial and lateral hamstring muscle was also assessed during NHE. Results Hamstring activities ranged between 98 and 129%. Lateral hamstring activity was greater than medial only in the right leg during NHE. Eccentric hamstring impulse improved in both legs at 10 weeks in both groups. Then, at 20 weeks, it remained unchanged in the NHE but decreased in controls. A similar adaptation was seen in eccentric hamstring torque, without change in the optimum knee angle. CMJ height improved only in the NHE. Conclusion It is concluded that NHE activates the hamstring musculature effectively, and a favourable mechanical adaptation to long-term NHE exercise in girls can be triggered as early as 11 years of age.

OBJECTIVE Constitutional delay of growth and puberty (CDGP) is a tempo variant with a good prognosis. Healthy late-maturing adolescents grow slower than postulated by age-related references, and therefore, CDGP is frequently confused with growth hormone deficiency (GHD). For differential diagnosis, height velocity references for CDGP are needed. DESIGN AND PATIENTS Here, we provide height velocity data for late-maturing boys based on mixed longitudinal and cross-sectional observations in a group of 38 German adolescents with proven CDGP and compare them with cross-sectional observations in a group of 164 adolescents with organic GHD from the National Cooperative Growth Study registry. RESULTS In the critical age interval from 13.4 to 14.9 years, the growth of prepubertal adolescents with CDGP was faster (mean/median height velocity, 5.2/5.4 cm/years; quartiles, 4.4-6.2 cm/years) than that of prepubertal adolescents with organic GHD (3.5/3.2 cm/years; quartiles, 2.0-4.4 cm/years) in the cross-sectional analysis (p

The human genome is extensively folded into 3-dimensional organization, yet the detailed 3D chromatin folding structures have not been fully visualized due to the lack of robust and ultra- resolution imaging capability. Here, we report the development of a novel electron microscopy method that combines serial block-face scanning electron microscopy with in situ hybridization (3D-EMISH) to visualize 3D chromatin folding at targeted genomic regions with ultra-resolution (5×5×30 nm in xyz dimensions, respectively). We applied 3D-EMISH to human lymphoblastoid cells at a 1.7 Mb segment of the genome and visualized a large number of distinctive 3D chromatin folding structures in high ultra-resolution. We further quantitatively characterized the reconstituted chromatin folding structures by identifying sub-domains, and uncovered a high level of heterogeneity in chromatin folding ultrastructures, suggestive of extensive dynamic fluidity in 3D chromatin states.

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Background Recent efficacy studies of asthma biologics have included highly enriched patient populations. Using a similar approach, we examined factors that predict response to omalizumab to facilitate selection of patients most likely to derive the greatest clinical benefit from therapy. Methods Data from two phase III clinical trials of omalizumab in patients with allergic asthma were examined. Differences in rates of asthma exacerbations between omalizumab and placebo groups during the 16-week inhaled corticosteroid (ICS) dose-stable phase were evaluated with respect to baseline blood eosinophil counts (eosinophils

Asthma is one of the most common chronic diseases of childhood. Allergen sensitization and high frequencies of comorbid allergic diseases are characteristic of severe asthma in children. Omalizumab, an anti-IgE mAb, is the first targeted biologic therapeutic approved for the treatment of moderate-to-severe persistent allergic asthma (AA) that remains uncontrolled despite high-dose inhaled corticosteroids plus other controller medications. Since its initial licensing for use in adults and adolescents 12 years of age and older, the clinical efficacy, safety, and tolerability of omalizumab have been demonstrated in several published clinical trials in children aged 6 to less than 12 years with moderate-to-severe AA. These studies supported the approval of the pediatric indication (use in children aged ≥6 years) by the European Medicines Agency in 2009 and the US Food and Drug Administration in 2016. After this most recent change in licensing, we review the outcomes from clinical trials in children with persistent AA receiving omalizumab therapy and observational studies from the past 7 years of clinical experience in Europe. Data sources were identified by using PubMed in 2016. Guidelines and management recommendations and materials from the recent US Food and Drug Administration's Pediatric Advisory Committee meeting are also reviewed.

The aim of this study was to review the literature dealing with the force-time characteristics of different forms of physical activity performed with upper limbs by the elderly and the disabled (Nordic Walking and using a wheelchair, respectively) and of manual techniques used by physiotherapists. Values of work and power were analysed as well. Based on the analysis of the literature concerning the substantive areas included in this article, we believe that objective measurements will expand the present knowledge about values of force developed by upper limbs during different forms of human activity. It seems to be of particular significance in the application of manual therapy techniques, because currently values of force exerted upon the patient while applying these techniques are selected by a physiotherapist intuitively and are neither objective nor systematically controlled. The identification of the values of force developed with upper limbs by the elderly, the disabled and physiotherapists during the aforementioned forms of activity will make an original contribution to the broadly defined physical culture, especially rehabilitation and health promotion.

Introduction: Emicizumab is a subcutaneously administered, bispecific, humanized monoclonal antibody that bridges factor (F)IXa and FX to restore the function of missing activated FVIII in persons with hemophilia A (PwHA). This study (NCT03361137) was designed to evaluate the safety and efficacy of emicizumab prophylaxis in PwHA with or without FVIII inhibitors undergoing minor surgical procedures without additional prophylaxis with bypassing agents (BPAs; for patients with FVIII inhibitors) or FVIII (for patients without FVIII inhibitors). Methods: This Phase IV, multicenter, single-arm, open-label study enrolled PwHA of any age, with or without FVIII inhibitors, who were scheduled to undergo minor surgical procedures. Patients were required to have received a minimum of four loading doses of emicizumab (3mg/kg once weekly for 4 weeks) prior to surgical procedure; subsequent maintenance doses of emicizumab were 1.5mg/kg once weekly, 3mg/kg every 2 weeks, or 6mg/kg every 4 weeks. Patients were required to be adherent to emicizumab prophylaxis. Treatment with emicizumab was scheduled to continue for at least 1 month after surgery. No other prophylactic treatment with coagulation factor was permitted. Outcome measures included incidence of excessive bleeding intra-operatively and until discharge from surgery, use of BPAs or FVIII to control bleeding (intra- and post-operatively), incidence of adverse events (AEs), and the percentage of patients with complications requiring hospitalization or return to surgery. Excessive bleeding was defined as a rating of fair to poor on the hemostatic rating scale and translates to an intra- and/or post-operative blood loss of ≥25% over expectation for a patient without hemophilia prior to discharge from surgery. Patients were followed for 28 days following discharge from surgery. Results: Between June 28, 2018 and March 13, 2020, 14 PwHA undergoing minor surgeries were enrolled (with FVIII inhibitors n=11; without FVIII inhibitors n=3); one PwHA with FVIII inhibitors enrolled but did not have surgery and discontinued prematurely, therefore the surgery analysis population comprised 13 patients (with FVIII inhibitors n=10; without FVIII inhibitors n=3). The majority (78.6%) of those enrolled were Conclusions: In this study of mostly pediatric PwHA with and without FVIII inhibitors receiving emicizumab prophylaxis, minor surgeries were safely performed. The majority of surgeries were performed without additional prophylactic coagulation factor, however the small sample size should be considered here. There were no serious AEs, TEs, TMAs, or deaths. These findings are consistent with results from previous studies of patients undergoing minor surgery while receiving emicizumab prophylaxis. Disclosures Escobar: National Hemophilia Foundation: Consultancy, Membership on an entity's Board of Directors or advisory committees; Genentech, Inc.: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Consultancy, Membership on an entity's Board of Directors or advisory committees; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees. Dunn:Genentech, Inc.: Consultancy; Nationwide Children's Hospital: Current Employment; World Federation of Hemophilia USA: Membership on an entity's Board of Directors or advisory committees; Medscape: Honoraria; Spire: Honoraria; ATHN: Research Funding; Takeda: Research Funding; BioMarin: Research Funding; uniQure: Consultancy. Quon:Octapharma: Honoraria; Bayer: Honoraria; Biomarin: Honoraria, Speakers Bureau; Bioverativ/Sanofi: Honoraria, Speakers Bureau; Genentech, Inc./F. Hoffmann-La Roche Ltd: Honoraria, Speakers Bureau; Novo Nordisk: Honoraria, Speakers Bureau; Shire/Takeda: Speakers Bureau; Orthopaedic Institute for Children: Current Employment. Trzaskoma:Genentech, Inc.: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Lee:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Ko:Genentech, Inc.: Current Employment; F. Hoffmann-La Roche Ltd: Current equity holder in publicly-traded company. Carpenter:Novo Nordisk: Honoraria; Genentech, Inc.: Honoraria; American Thrombosis and Hemostasis Network: Membership on an entity's Board of Directors or advisory committees; CSL Behring: Research Funding; Shire: Research Funding; Hemostasis & Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees; American Academy of Pediatrics: Other: PREP Heme/Onc editorial board; Kedrion: Honoraria.

The human genome is extensively folded into 3-dimensional organization. However, the detailed 3D chromatin folding structures have not been fully visualized due to the lack of robust and ultra-resolution imaging capability. Here, we report the development of an electron microscopy method that combines serial block-face scanning electron microscopy with in situ hybridization (3D-EMISH) to visualize 3D chromatin folding at targeted genomic regions with ultra-resolution (5 × 5 × 30 nm in xyz dimensions) that is superior to the current super-resolution by fluorescence light microscopy. We apply 3D-EMISH to human lymphoblastoid cells at a 1.7 Mb segment of the genome and visualize a large number of distinctive 3D chromatin folding structures in ultra-resolution. We further quantitatively characterize the reconstituted chromatin folding structures by identifying sub-domains, and uncover a high level heterogeneity of chromatin folding ultrastructures in individual nuclei, suggestive of extensive dynamic fluidity in 3D chromatin states., The genome is folded in 3-dimensions, though the lack of robust ultra-resolution imaging makes this difficult to visualise. Here, the authors present 3D-EMISH that combines serial block-face scanning electron microscopy with in situ hybridization.

Background Omalizumab improves clinical outcomes in patients with asthma. Several studies have shown lung function improvements with omalizumab; however, this has not been examined exclusively in adolescents. Objective To assess the effect of omalizumab on lung function and eosinophil counts in adolescents with uncontrolled moderate-to-severe allergic asthma. Methods In this post hoc analysis, data from adolescents aged 12 to 17 years from 8 randomized trials of omalizumab were pooled (studies 008, 009, and 011, and SOLAR, INNOVATE, ALTO, ETOPA, and EXTRA). Changes from baseline to end of study in forced expiratory volume in 1 second (FEV1), percent predicted FEV1 (ppFEV1), forced vital capacity (FVC), and blood eosinophil counts were assessed by fitting an analysis of covariance model and calculating least squares mean (LSM) difference for omalizumab vs placebo. Results A total of 340 adolescents were identified (omalizumab, n = 203 [59.7%]; placebo, n = 137 [40.3%]). Omalizumab increased all baseline lung function variables more than placebo by end of study: LSM treatment differences (95% confidence interval) were 3.0% (0.2%-5.7%; P = .035), 120.9 mL (30.6-211.2 mL; P = .009), and 101.5 mL (8.3-194.6 mL; P = .033) for ppFEV1, absolute FEV1, and FVC, respectively. The LSM difference demonstrated a greater reduction in eosinophil counts for omalizumab vs placebo: −85.9 cells/μL (−137.1 to −34.6 cells/μL; P = .001). Conclusion Omalizumab was associated with lung function improvements and circulating eosinophil counts reductions in adolescents with moderate-to-severe uncontrolled asthma. Findings emphasize the effect of omalizumab in young patients and the need to optimize treatment early in the disease course. https://clinicaltrials.gov/: NCT00314574, NCT00046748, NCT00401596

Die vorliegende Arbeit beschäftigt sich mit dem Vergleich der Zeit, die die ÜbersetzerInnen brauchen, um einen neuronal maschinell erstellten Fachtext nachzubearbeiten und einen Fachtext ohne Einsatz der maschinellen Übersetzung zu übertragen. Beide Fachtexte werden im Sprachenpaar Deutsch-Polnisch analysiert. Zusätzlich wird die Einstellung der ÜbersetzerInnen zu der neuronalen maschinellen Übersetzung und ihrem Post-Editing untersucht. Aufgrund der vorhandenen Theorien wurden Hypothesen aufgestellt und Forschungsfragen gestellt. Es wird zunächst ein Überblick über die maschinelle Übersetzung mit besonderem Schwerpunkt auf der neuronalen maschinellen Übersetzung sowie die Einstellung der ÜbersetzerInnen zur maschinellen Übersetzung anhand der aktuellen Forschungsergebnisse gegeben. Des Weiteren werden der Begriff Post-Editing und die Einstellung der ÜbersetzerInnen zum Post-Editing analysiert. Das besondere Augenmerk wird dabei auf die Unterschiede zwischen Post-Editing und Humanübersetzung sowie die aktuellen Untersuchungen in Bezug auf den unterschiedlichen Zeitaufwand des Post-Editings und der Humanübersetzung gelenkt. Anschließend wird der Stand der polnischen Sprache in der digitalen Sprachindustrie diskutiert. Im empirischen Teil werden anhand von 15 „fortgeschrittenen“ Studenten, genannt ÜbersetzerInnen, die Ergebnisse der Untersuchung darstellt. Anhand ihrer posteditierten und manuell übersetzten Fachtexte zusammen mit Screen-Recording-Videos wird sowohl die Zeit des Post-Editings und der Übersetzung ohne Einsatz der maschinellen Übersetzung als auch die Einstellung zur neuronalen maschinellen Übersetzung und ihrem Post-Editing gemessen. Die Ergebnisse zeigen, dass das Post-Editing des neuronal maschinell erstellten Fachtextes im Polnischen weniger Zeit in Anspruch nimmt als die selbständige Übersetzung aus dem Deutschen ins Polnische. Außerdem hat sich ergeben, dass die maschinelle Übersetzung die Arbeit der ÜbersetzerInnen erleichtert. Die kürzere Zeit für das Post-Editing hängt jedoch von einer breiteren Palette von Faktoren ab, als nur eine schnelle Erstellung der Übersetzung. Die Ergebnisse sind für die vorliegende Arbeit relevant und können einen Beitrag zur weiteren Verbesserung bzw. Entwicklung der neuronalen maschinellen Übersetzung leisten., The present paper focuses on the comparison of the time translators need to post-edit a neuronally generated technical text and to translate a technical text without using machine translation. Both technical texts are analyzed in the language pair German-Polish. In addition, the translators' attitude to neuronal machine translation and its post-editing is examined. The hypotheses and research questions were based on the current theories. First, an overview of the machine translation with a focus on neuronal machine translation and the attitude of the translators towards machine translation based on current research results is provided. Furthermore, the term post-editing and the attitude of translators to post-editing will be analyzed. The importance will be paid to the differences between post-editing and human translation, as well as to current research on the time required for post-editing and human translation. Afterwards, the state of the Polish language in the digital language industry will be discussed. The empirical part presents the results of the study. Using post-edited and manually translated technical texts by 15 “advanced” students, called translators, together with screen recording videos, both the time of post-editing and translation without the use of machine translation and the attitude towards neural machine translation and its post-editing will be measured. The results show that the post-editing of the neuronally machine-translated technical text in Polish takes less time than the manual translation from German into Polish. It has also been shown that machine translation makes the work of translators easier. However, the shorter time of post-editing depends on a wider range of factors than just a quick translation. The results are relevant to this paper and may contribute to the further improvement or development of neuronal machine translation.

Background: Declines in percent predicted FVC (% predicted FVC), declines in 6-min walk distance (6MWD), and respiratory hospitalizations are events associated with disease progression and mortality in idiopathic pulmonary fibrosis. The incidence of multiple events in the same patient over 12 months of pirfenidone treatment is unknown. Methods: Patients who received pirfenidone 2,403 mg/d (n = 623) or placebo (n = 624) in the ASCEND (study 016; NCT01366209) and CAPACITY (studies 004 and 006; NCT00287716 and NCT00287729) phase III trials were included in this post hoc analysis. Disease progression events were defined as relative decline in % predicted FVC ≥ 10%, absolute decline in 6MWD ≥ 50 m, respiratory hospitalization, or death from any cause. The incidence of disease progression events over 12 months was assessed. Results: The most frequent disease progression events were declines in % predicted FVC (pirfenidone vs placebo; 202 vs 304 events) and declines in 6MWD (pirfenidone vs placebo; 265 vs 348 events). Fewer patients who received pirfenidone had more than one progression event compared with placebo (17.0% vs 30.1%; P

[This corrects the article DOI: 10.1371/journal.pone.0236266.].

Summary Study aim: to investigate the impact of heels of different height on static balance of teenagers and young women not accustomed to high heels. Material and methods: The study involved 71 young women aged 21.09 ± 2.91 years. We used a stabilometric platform to take measurements barefoot and with heels: of 4 cm and of 10 cm. Two types of measurements were taken: with eyes open and with eyes closed. Results: Statistical analysis revealed a significant increase in values of the measured stabilographic parameters with 4 cm and 10 cm heels, in comparison to measurements taken with bare feet. Measurements with eyes closed revealed significantly greater distortions to static balance than measurements with eyes open. A comparison of measurements – both with eyes open and with eyes closed – barefoot, with 4 cm heels and with 10 cm heels revealed statistically significant differences. Conclusions: High heels in the population of young women significantly worsen static balance. Heel height and the exclusion of visual control are important factors diminishing static balance.