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En la mente de la sociedad colombiana, existe la idea de que las comunidades negras afrocolombianas, llegaron a los territorios como un grupo homogéneo, teniendo así una idea errónea. La población afrocolombiana posee una diversidad cultural y regional, se incluye la población afro integradas en costas atlántica y pacífica, además de ello las comunidades raizales y palenqueras; quienes además consideran que la naturaleza es fuente de vida, el cuidado de la tierra, del agua, del aire es prioridad por cuanto todo ello genera el sostenimiento del planeta. Los afrocolombianos, vienen en una constante lucha por el reconocimiento de sus derechos como comunidad, el reconocimiento de su cultura, de sus territorios, de su economía, por la no discriminación racial entre otras situaciones. Así mismo, estas comparten una historia en común, una cultura y en especial unas prácticas tradicionales que sirvieron como base para definir su carácter étnico y así establecer que sus derechos territoriales deberían ser colectivos; de allí la lucha por el reconocimiento y titulación de las tierras, como fuente fundamental del sustento de las comunidades asentadas en estos territorios.

Hydrogels are attractive materials for tissue engineering, but efforts to date have shown limited ability to produce the microstructural features necessary to promote cellular self-organization into hierarchical three-dimensional (3D) organ models. Here we develop a hydrogel ink containing prefabricated gelatin fibres to print 3D organ-level scaffolds that recapitulate the intra- and intercellular organization of the heart. The addition of prefabricated gelatin fibres to hydrogels enables the tailoring of the ink rheology, allowing for a controlled sol-gel transition to achieve precise printing of free-standing 3D structures without additional supporting materials. Shear-induced alignment of fibres during ink extrusion provides microscale geometric cues that promote the self-organization of cultured human cardiomyocytes into anisotropic muscular tissues in vitro. The resulting 3D-printed ventricle in vitro model exhibited biomimetic anisotropic electrophysiological and contractile properties.

Human CD200R1 (hCD200R1), an immune inhibitory receptor expressed predominantly on T cells and myeloid cells, was identified as a promising immuno-oncology target by the 23andMe database. Blockade of CD200R1-dependent signaling enhances T cell-mediated antitumor activity in vitro and in vivo. 23ME–00610 is a potential first-in-class, humanized IgG1 investigational antibody that binds hCD200R1 with high affinity. We have previously shown that 23ME–00610 inhibits the hCD200R1 immune checkpoint function. Herein, we dissect the molecular mechanism of 23ME–00610 blockade of hCD200R1 by solving the crystal structure of 23ME–00610 Fab in complex with hCD200R1 and performing mutational studies, which show 23ME–00610 blocks the interaction between hCD200 and hCD200R1 through steric hindrance. However, 23ME–00610 does not bind CD200R1 of preclinical species such as cynomolgus monkey MfCD200R1. To enable preclinical toxicology studies of CD200R1 blockade in a pharmacologically relevant non-clinical species, we engineered a surrogate antibody with high affinity toward MfCD200R1. We used phage display libraries of 23ME–00610 variants with individual CDR residues randomized to all 20 amino acids, from which we identified mutations that switched on MfCD200R1 binding. Structural analysis suggests how the surrogate, named 23ME–00611, acquires the ortholog binding ability at the equivalent epitope of 23ME–00610. This engineering approach does not require a priori knowledge of structural and functional mapping of antibody–antigen interaction and thus is generally applicable for therapeutic antibody development when desired ortholog binding is lacking. These findings provide foundational insights as 23ME–00610 advances in clinical studies to gain understanding of the hCD200R1 immune checkpoint as a target in immuno-oncology.

Purpose: This study investigated the effectiveness of the stuttering modification intervention Kinder Dürfen Stottern (KIDS) in school-age children who stutter. Method: Seventy-three children who stutter were included in this multicenter, two-group parallel, randomized, wait-list controlled trial with a follow-up of 12 months. Children aged 7-11 years were recruited from 34 centers for speech therapy and randomized to either the immediate-treatment group or the 3 months delayed-treatment group. KIDS was provided by 26 clinicians who followed a treatment manual. Although the primary outcome measure was the impact of stuttering (Overall Assessment of the Speaker's Experience of Stuttering--School-Age [OASES-S]), the secondary outcomes included objective and subjective data on stuttering severity. Results: At 3 months postrandomization, the mean score changes of the OASES-S differed significantly between the experimental (n = 33) and control group (n = 29; p = 0.026). Furthermore, treatment outcomes up to 12 months were analyzed (n = 59), indicating large effects of time on the OASES-S score (p < 0.001, partial [eta-squared] = 0.324). This was paralleled by significant improvements in parental ratings and objective ratings (stuttering severity, frequency, and physical concomitants). Conclusions: The significant short-term treatment effects in the OASES-S are in line with the (initial) focus of KIDS on cognitive and affective aspects of stuttering. Over 12 months, these changes were maintained and accompanied by behavioral improvements. The results suggest that individual treatment with KIDS is an adequate treatment option for this age group.

Varicella is a childhood disease characterized by its self-limiting and benign nature. However, it can also affect the adult population due to risk factors, leading to infection with numerous complications involving the central nervous system, kidneys, respiratory system, and skin. Varicella pneumonia, one of the most feared complications in adults, occurs in approximately 1 out of 400 patients with the disease. This complication primarily affects male patients with a history of heavy smoking and immunosuppression, either due to an underlying disease such as HIV and cancer, drug use, pregnancy or pulmonary disease. It is recommended that this complication should be treated with intravenous acyclovir at a dose of 10 mg/kg/8 hours. The prognosis depends on the development of respiratory failure; up to 50 % of patients with this complication require invasive mechanical ventilation. Here, we report the clinical case of an immunocompetent patient with a typical presentation of varicella that rapidly progressed to a respiratory infection requiring antiviral treatment and invasive mechanical ventilation.

Abstract Remarkably little is known about the structure, formation, and dynamics of supply- and production networks that form one foundation of society. Neither the resilience of these networks is known, nor do we have ways to systematically monitor their ongoing change. Systemic risk contributions of individual companies were hitherto not quantifiable since data on supply networks on the firm-level do not exist with the exception of a very few countries. Here we use telecommunication meta data to reconstruct nationwide firm-level supply networks in almost real-time. We find the probability of observing a supply-link, given the existence of a strong communication-link between two companies, to be about 90%. The so reconstructed supply networks allow us to reliably quantify the systemic risk of individual companies and thus obtain an estimate for a country’s economic resilience. We identify about 65 companies, from a broad range of company sizes and from 22 different industry sectors, that could potentially cause massive damages. The method can be used for objectively monitoring change in production processes which might become essential during the green transition.

Abstract Aim To explore the experiences of Registered Nurses who administered medications to patients using the electronic medication administration record (eMAR) in Electronic Record for Intensive Care (eRIC) at one adult intensive care unit (ICU) in NSW, Australia. Design The study research design used a qualitative descriptive exploratory approach that took place in two stages. Methods Five participants attended one focus group followed by the observation of each participant as medications were administered to their assigned patient using the eMAR in eRIC. Results From the data, three themes and one subtheme were identified. Themes included forcing nurses to work outside legal boundaries; patient safety; with a subtheme titled experiencing computer fatigue; and taking time away from the patient. To practise safely, nurses were required to implement workaround practices when using the new eMAR in ICU. Nurses also were concerned that the eMAR in eRIC took time away from the patient at the bedside and ‘added more screen time’ to their day.

Objectives: Cardiothoracic (CT) surgeons with National Institutes of Health (NIH) R01 funding face a highly competitive renewal process. The factors that contribute to successful grant renewal for CT surgeons remain poorly defined. We hypothesized that renewed basic science grants are associated with high research output and scholarly impact during the preceding award cycle. Methods: Using a database of academic CT surgeons (n = 992) at accredited training institutions in 2018, we identified basic science R01 grants awarded to CT surgeon principal investigators since 1985. Data for each award were obtained from publicly available online sources. Scholarly impact was evaluated using the NIH-validated relative citation ratio (RCR), defined as an article's citation rate divided by that of R01-funded publications in the same field. Continuous data are presented as medians and analyzed using the Mann–Whitney test. Results: We identified 102 basic science R01 award cycles, including 33 that were renewed (32.4%). Renewed and nonrenewed awards had a similar start year and funding period. Principal investigators of renewed versus nonrenewed awards were similar in surgical subspecialty, research training, attending experience, academic rank, and previous NIH funding. Renewed awards produced more publications per year over the funding cycle (3.4 vs 1.5; P = .0010) and exhibited a greater median RCR during the funding cycle (0.84 vs 0.66; P = .0183). Conclusions: CT surgery basic science R01 grants are associated with high research output and scholarly impact. At the 50th percentile among renewed grants, CT surgeons published 3.4 funded manuscripts per year with a median RCR of 0.84 during the previous award cycle.

Clinical anti-drug-antibody (ADA) responses represent a substantial obstacle to the development of efficacious therapeutic antibodies. The enhanced ADA production against the idiotype (Id) often displayed by cancer immunotherapy antibodies (CitAbs) can lead to exposure loss and subsequently affect anti-tumor efficacy and cause undesired effects on safety. Thus, ADA responses contribute to prolonged clinical development and high attrition rates. Most conventional therapeutic antibodies are now of human origin or humanized proteins, and are hence immunologically tolerized in most patients. In contrast, the contribution of additional factors, other than the protein sequence, to the higher rates of clinical ADA to certain CitAbs, remains poorly understood. Here, we used human immunoglobulin gamma 1 (IgG1) transgenic mice (named “hIgG1 transgenic mice” or “TG”), which are immunologically tolerant to human IgG1, to study the immunogenicity of 13 conventional antibodies and 2 CitAbs. We found that tolerance to non-germline encoded Ids is maintained in part by the function of neonatal Fc-receptor (FcRn). Additionally, the incorporation of T cell-engaging moieties like an interleukin 2 (IL-2)-based immunocytokine or a CD3ε-specific antigen-binding fragment (Fab) was sufficient to revert tolerance and trigger ADA production directed to the Id of these compounds. We postulate that T cell receptor or IL-2 receptor activation may result in activation of unresponsive T cells specific for the crystallizable fragment (Fc) that typically inactivate Id-specific B cells and mediate “linked-antigen tolerance”. Reversal of this unresponsiveness by the action of CitAbs on T cells may be the cause of undesired ADA responses.Abbreviations ADA Anti-Drug Antibodies; BCR B Cell Receptor; BId Idiotype-specific B Cell; BiTE Bispecific T cell Engager; BMC Bone Marrow Chimeric Mice; BSA Bovine Serum Albumin; CDR Complementary Determining Region; CEA Carcinoembryonic Antigen; CIT Cancer Immunotherapy; CitAbs Cancer Immunotherapy Antibodies; DC Dendritic Cell; ELISA Enzyme-Linked Immunosorbent Assay; FcRn Neonatal Fc Receptor; FcyR Fc gamma Receptor; GM-CSF Granulocyte-Macrophage Colony Stimulating Factor; gMFI Geometric Mean Fluorescence Intensity; H Heavy Chain; IC Immune Complex; Id Idiotype; IgA Immunoglobulin alpha; IgG1 Immunoglobulin gamma 1; IL-2 Interleukin 2; IL-2R Interleukin 2 Receptor; IL2v Interleukin 2 Variant; IVIG1 Intravenous Immunoglobulin 1; KLH Keyhole Limpet Hemocyanin; L Light Chain; MAPPs MHC-associated Peptide Proteomics; MHC Major Histocompatibility Complex; PBMC Peripheral Blood Mononuclear Cells; PBS Phosphate Buffered Saline; SHM Somatic Hypermutation; scFv Single-chain Variable Fragment; TCR T cell Receptor; TFc Fc-specific T cell; TId Id-specific T cell; UV Ultraviolet; V Variable.

Abstract Behavioral gender differences have been found for a wide range of human activities including the way people communicate, move, provision themselves, or organize leisure activities. Using mobile phone data from 1.2 million devices in Austria (15% of the population) across the first phase of the COVID-19 crisis, we quantify gender-specific patterns of communication intensity, mobility, and circadian rhythms. We show the resilience of behavioral patterns with respect to the shock imposed by a strict nation-wide lock-down that Austria experienced in the beginning of the crisis with severe implications on public and private life. We find drastic differences in gender-specific responses during the different phases of the pandemic. After the lock-down gender differences in mobility and communication patterns increased massively, while circadian rhythms tended to synchronize. In particular, women had fewer but longer phone calls than men during the lock-down. Mobility declined massively for both genders, however, women tended to restrict their movement stronger than men. Women showed a stronger tendency to avoid shopping centers and more men frequented recreational areas. After the lock-down, males returned back to normal quicker than women; young age-cohorts return much quicker. Differences are driven by the young and adolescent population. An age stratification highlights the role of retirement on behavioral differences. We find that the length of a day of men and women is reduced by 1 h. We interpret and discuss these findings as signals for underlying social, biological and psychological gender differences when coping with crisis and taking risks.

Differences in building operator strategies can significantly affect building energy use and occupant comfort. However, it seems that the daily work of building operators and facility managers is still largely based on heuristics and individual experiences. In this work, we have investigated the current data collection methods during the operation and its daily use in buildings as well as the handling of occupant behavior, comfort, and user complaints based on interviews with ten building operators in Germany. These interviews were conducted as part of an international study of building operator OCC (Occupant-Centric Control) strategies, under the auspices of the IEA EBC Annex 79. The results of the interviews clearly reflect, that until now, communication between building operators and building occupants plays a more important role in optimizing or adjusting building operations to meet occupant needs than the data collected by BAS, which is mainly used to detect faults and check the system status of key HVAC components when faults occur. In some cases, the real-time data are applied for the adjustment of set points and schedules depending on measured conditions; however, customization of set points considering the user’s preferred temperature or ventilation rate or building operation based on occupancy detection has not yet been implemented in the considered buildings. The overall objective of this contribution to building operation research is to highlight best practices and identify white spaces that fulfill occupant requirements and achieve a high level of energy-efficiency. The presented findings identify current gaps between science and practice in the field of sustainable optimization of building operation, but also point out real-world starting points for future research and development.

Background and aims: The Hepatitis E virus hijacks the endosomal system for its release. These structures are highly dependent on cholesterol. Hence, this study investigates the impact of HEV on cholesterol-metabolism, the effect of intracellular cholesterol content on HEV-release and the potential of cholesterol-modulators to serve as antivirals. Methods: Intracellular cholesterol-content of cells was modulated and impacts on HEV were monitored using qPCR, Western blot, microscopy, virus-titration and density-gradient centrifugation. Blood-lipids and HEV-RNA were routinely quantified in chronically infected patients during follow-up visits. Results: In HEV-infected cells, decreased levels of cholesterol are found. In patients, HEV infection decreases serum-lipid concentrations. Importantly, statin treatment herein increases viral titers. Similarly, reduction of intracellular cholesterol via simvastatin treatment increases viral release in vitro. On the contrary, elevating intracellular cholesterol via LDL or 25-hydroxycholesterol strongly reduces viral release due to enhanced lysosomal degradation of HEV. Drug-induced elevation of intracellular cholesterol via fenofibrate or PSC833 impairs HEV release via the same mechanism. Conclusions: This study analyses the crosstalk between HEV and intracellular cholesterol. The results highlight the importance of an intact cholesterol homeostasis for HEV-release and thereby identify a potential target for antiviral strategies. Especially fenofibrate is considered a promising novel antiviral against HEV. Beyond this, the study may help clinicians evaluating co-treatments of HEV-infected patients with statins, as this may be counter indicated.

The drivers behind regional differences of SARS-CoV-2 spread on finer spatio-temporal scales are yet to be fully understood. Here we develop a data-driven modelling approach based on an age-structured compartmental model that compares 116 Austrian regions to a suitably chosen control set of regions to explain variations in local transmission rates through a combination of meteorological factors, non-pharmaceutical interventions and mobility. We find that more than 60% of the observed regional variations can be explained by these factors. Decreasing temperature and humidity, increasing cloudiness, precipitation and the absence of mitigation measures for public events are the strongest drivers for increased virus transmission, leading in combination to a doubling of the transmission rates compared to regions with more favourable weather. We conjecture that regions with little mitigation measures for large events that experience shifts toward unfavourable weather conditions are particularly predisposed as nucleation points for the next seasonal SARS-CoV-2 waves.

The exploitation of the photoelectric effect is a prominent method for the in situ measurement of the absolute work function of a surface. In the case of metallic surfaces, the Fowler theory is routinely applied for fitting or extrapolating the measured photoelectric yield data to determine the work function value. However, for the reliable application of the Fowler method, attention must be paid to the experimental sensitivity to the photoelectric behavior close to the threshold, which is mainly determined by the signal-to-noise ratio for photocurrent detection and the available photon energies used for irradiation. This is illustrated by means of applying a photoelectric work function measurement system during a Cs coating process of a metal surface, where insufficiently low photon energies or an unfavorable noise level can lead to a severe overestimation of the work function of the order of 1 eV. By a sufficient enhancement of the photoelectric sensitivity, it is now unveiled that ultra-low surface work functions of 1.25 ± 0.10 eV can be generated via caesiation of metallic surfaces (here molybdenum and stainless steel) under vacuum conditions of 10−6–10−5 mbar, which is most probably the result of the formation of an oxidized Cs adlayer.

El objetivo del estudio fue analizar la práctica evaluativa del profesorado en los niveles de básica secundaria en las sedes de la Institución Educativa Ciro Pupo Martínez del municipio La Paz, del departamento del Cesar, Colombia. Metodológicamente, se ubicó en el paradigma cualitativo, bajo el enfoque sociocrítico, en la investigación acción que se desarrolló en descripción de la situación problema, construcción de las bases teóricas, diseño metodológico, trabajo de campo, análisis e interpretación de los instrumentos, implementación de la propuesta, análisis final, recomendaciones y conclusiones. La unidad de trabajo fueron ocho docentes. Para la recolección de la información se utilizó un cuestionario semiestructurado, el diario de campo y la lista de cotejo. Se concluyó que, el profesorado es consciente de su papel, llamado a transformar los escenarios educativos mediante la adopción de herramientas innovadoras, apoyadas en los círculos de acción docente, con una metodología que mejore su práctica pedagógica y los integre como equipo.

The neutral beam injection systems for the international fusion experiment ITER used for heating, current drive, and diagnostic purposes are based on RF-driven negative hydrogen ion sources with a source area of roughly 0.9 m × 1.9 m. The sources operate at 0.3 Pa in hydrogen and in deuterium using a total available RF generator power of 800 kW per source at a frequency of 1 MHz. In order to fulfill the challenging requirements for ITER and beyond (like a DEMOnstration power plant, DEMO), worldwide developments are underway addressing the topics of plasma generation, ion extraction together with the issue of reducing and stabilizing the co-extracted electron current, and the beam properties. At the example of the activities at the ITER prototype source and the size scaling experiment ELISE, the present status and its challenges are summarized. The RF power transfer efficiency of these sources is only about 65% in maximum, giving significant room for improvements to relax the demands on the RF generator and ensure reliable operation. The plasma uniformity in front of the large extraction system is the result of plasma drifts. They have a huge impact on the nonuniformity of the co-extracted electrons and influence the ions and thus the beam properties as well. Understanding the optics of such large beams composed of hundreds of beamlets is a crucial task and is under continuous improvement. The main challenge, however, is still the fulfillment of the ITER requirements for deuterium, in particular, for long pulses. The management of caesium, which is evaporated into the source to generate sufficient negative ions by the surface conversion process, is one of the keys for stable and reliable operation.