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The EU-GEI Project was funded by grant agreement Health-F2-2010-241909 from the European Community’s Seventh Framework program. The Brazilian study was funded by grant 2012-0417-0 from the São Paulo Research Foundation, D'Andrea, Giuseppe; Lal, Jatin; Tosato, Sarah;Gayer-Anderson, Charlotte;Jongsma, Hannah E.;Stilo, Simona A.; van der Ven, Els;Quattrone, Diego;Velthorst, Eva;Berardi, Domenico;Rossi Menezes, Paulo; Arango, Celso; Parellada, Mara; Lasalvia, Antonio; La Cascia, Caterina; Ferraro, Laura; La Barbera, Daniele; Sideli, Lucia; Bobes, Julio; Bernardo, Miguel; Sanjuan, Julio; Santos, Jose Luis; Arrojo, Manuel; Marta Del-Ben, Cristina; Tripoli, Giada; Llorca, Pierre-Michel; de Haan, Lieuwe; Selten, Jean-Paul; Tortelli, Andrea; Szoke, Andrei; Muratori, Roberto; Rutten, Bart P.; van Os, Jim; Jones, Peter B.; Kirkbride, James B.; Murray, Robin M.; di Forti, Marta; Tarricone, Ilaria; Morgan, Craig

Experimental studies suggest that the fracture toughness of rocks increases with the confining pressure. Among many methods to quantify this dependency, a so-called burst experiment (Abou-Sayed, 1978) may be the most widely applied in practice. Its thick wall cylinder geometry leads to a stress state resembling the subsurface condition of a pressurized wellbore with bi-wing fractures. The fracture toughness of a sample, under a given confinement pressure, can be recovered from the critical pressure upon which the bi-wing cracks propagate. Traditionally, this critical pressure is thought to correspond to a sudden drop in injection pressure. However, as the standard configuration was deliberately designed to obtain stable fracture growth at the onset, propagation can take place well before this drop in pressure, and one may overestimate the fracture toughness from measured pressures. Here, we study crack stability in the burst experiment and propose modifications to the experimental design which promotes unstable fracture growth and makes the critical pressure less ambiguous to interpret. We found that experiments with the original, stable design can lead to inconsistent measurement of fracture toughness under confining pressure, while results from unstable configurations are more consistent. Our claim on the stability was also supported by the recorded acoustic emissions from both stable and unstable experiments.

This research is a Classroom Action Research which aims to enhance physics learning outcomes through a problem-based learning model. 39 students from class X at TKJ 2 SMK Negeri 1 Lhokseumawe in the odd semester of the academic year served as the subjects of this study. The research was carried out over two cycles and included the following four activities: arranging, executing activities, observing and reflecting. There were two meetings in Cycle I, and there were three meetings in Cycle II. This study used an observation sheet to collect information about teaching and learning situations as well as data on students' physics learning outcomes from the tests taken for each cycle. The results of the quantitative analysis using the learning outcomes test in the evaluation of physics subjects in cycle I revealed that 14 students achieved scores above the Minimum Completeness Criteria (KKM), or 35.90 percent. There were 32 students in cycle II who scored higher than the KKM, or 82.05 percent. Based on the results of this study, it can be concluded that using the Problem-Based Learning Model can improve the physics learning outcomes of grade X students of TKJ 2 SMK Negeri 1 Lhokseumawe on the work and energy lesson

This research seeks to ascertain how Class X TE students at SMK Negeri 1 Lhokseumawe can improve their learning outcomes in physics for Temperature and Heat topic using simple visual aids during the even semester of the 2019–2020 academic year. This type of research includes descriptive research with an action research approach. The subjects in this study were students of class X TE of SMK Negeri 1 Lhokseumawe in the academic year 2019/2020, with a total of 28 students. Determination of the subject was obtained based on the results of the investigation of the class to be studied and based on the results of referrals from the Principal. The results of the descriptive analysis revealed that with the following data: Cycle I, the average learning achievement for Physics was 69 with a percentage of completeness of 89%, and in cycle II, the average learning achievement for Mathematics increased to 77 with a percentage of 100%. The percentage of activeness students in the class are as follows: Cycle I, average percentage of student learning activeness from 56.2% to 84.2%. Therefore, it is possible to draw the conclusion that Class X TE students at SMK Negeri 1 Lhokseumawe's Physics learning outcomes of Temperature and Heat lesson can benefit from simple teaching aids. In order to properly accomplish learning goals, the authors advise teachers to use simple visual aids in Physics lessons, particularly when covering the topic of temperature and heat

This study is intended for forest owners considering options to increase the efficiency of the production of forest seedlings in automated nurseries. In the short rotation technology of the Scots pine (Pinus sylvestris L.), the production of seedlings was integrated in the process of grading seeds by spectrometric features, followed by the fall outplanting of containerized seedlings to a restorable post-pyrogenic site. There are studies of the spectrometric effect grading viable seeds, but a negligible amount of testing has been conducted on the seedling’s field performance from these seeds. It was very important for us to evaluate the morphogenesis of juvenile Scots pine trees in relation to the change in morphological features—increase in root collar diameter (RCD-increment) and increase in stem height (SH-increment)—in the second and third growing season from the field outplanting. To determine the nature of the interaction between independent (RCD increase), dependent (SH-increment), and categorical (seed spectrometric categories and timespans) variables, a regression analysis was performed using the R statistical software. All coefficients of the linear models are statistically significant at the 1% significance level, and all are positively associated with an increase in seedling height. On average, a RCD increment by 0.1 cm causes a SH-increment by 0.72 ± 0.16 cm (p = 9.779 × 10−6). In addition, in 2020, compared to 2019, the SH-increment was 5.46 ± 0.37 cm (p < 0.001). The seeds’ differentiation into spectrometric categories is strongly correlated with the stem height increment (p < 0.001). Thus, in order to improve the plant propagation protocol, it seems advisable to first condition the seeds in accordance with the spectrometric feature, and to then apply a coating (by pelleting or encapsulating) in order to improve the storage and seeding conditions. For a medium-term assessment of the short rotation technology with an integrated seed spectrometric grading in the future, the morphogenesis of Scots pine trees at 5, 7 and 10 growing seasons from the seedlings field outplanting is controlled.

The use of the erythrocyte sedimentation rate (ESR) method has been recognized in monitoring the inflammation process, with a proven role of proinflammatory factors in the ESR increase. The aim. To reveal the role of group antibodies in thespecific increase of ESR. Methods. For the study erythrocytes with EDTA anticoagulant were used. ESR was measured after thecontact oferythrocytes with saline (negative control), standard anti-A and anti-B antibodies of the IgM class, polyclonal anti-A, anti- B, anti-A, B sera (experiment), as well as serum ofgroupAB in aratio 1 : 3: 0.2 ml of erythrocytes and 0.6 ml of saline or serum. The results were evaluated after one and 12hours ofincubation, at room temperature and at 4 °C. Results. Contact ofanti-A IgM antibodies at a dilution of 1:30 with A erythrocytes led to an increase of ESR (from (3.25±0.50)mm/h to (83.7± 1.60) mm/h) (p < 0.001) with apresence of a red precipitate. The contact oferythrocytes with polyclonal citrate plasma (or serum) inaratio of1 : 2 led to a similar increase in ESR in cases ofthespecific binding. Anti-A, B serum increased ESR ofA erythrocytes up to (53.00 ± 2.64) mm/h (p < 0.001) with thepresence of a red precipitate, while anti-B serum did not show such effect: (ESR — (5.25±0.50)mm/h) (p> 0.05). It should be noted that the serum absorbed by the corresponding erythrocytes showed reduced ESR values. After the absorption of anti-A antibodies by Aerythrocytes the serum lost the ability to specifically increase the ESR of A erythrocytes. Conclusions. Group antibodies are able to specifically promote ESR. Thefound ability can be reduced by the method of specific absorption oftheserum. Thephysicians may consider the role ofgroup specific autoimmune antibodies in developing high values of ESR. Thetherapy aimed to regulate the autoimmune humoral activation and specific absorption might be useful in normalization theESR parameter., Використання методу визначення швидкості осідання ерит­роцитів (ШОЕ) визнано для моніторингу запального процесу, при цьому досліджено роль прозапальних білків у підвищенні ШОЕ. Мета. Оцінити роль групових антитіл у специфічному підвищенні ШОЕ. Методи. Для дослідження використовували еритроцити з антикоагулянтом ЕДТА. ШОЕ вимірювали після контакту еритроцитів з фізіологічним розчином (негативний контроль), стандартними антитілами анти-А і анти-В класу IgM, поліклональними сироватками анти-А, анти-В, анти-А, В (дослід), а також сироваткою крові групи АВ у співвідношенні 1 : 3: 0,2 мл еритроцитів і 0,6 мл фізіологічного розчину або сироватки. Результати оцінювали через одну та 12год інкубації за кімнатної температури та 4°C. Результати. Контакт антитіл IgM анти-А у розведенні 1 : 30 з еритроцитами А призводив до підвищення ШОЕ (від (3,25±0,50) до (83,7 ±1,60))мм/год (p < 0,001) з наявністю червоного осаду. Контакт еритроцитів з поліклональною цитратною плазмою (або сироваткою) у співвідношенні 1:2 призводив до аналогічного підвищення ШОЕ зі специфічним зв’язуванням. Анти-А, В сироватка підвищувала ШОЕ уАерит­роцитів (до (53,00 ±2,64)мм/год) (p < 0,001) з наявністю червоного осаду, а анти-В сироватка не мала такого ефекту: ШОЕ— (5,25±0,50) мм/год (p > 0,05). Сироватка крові, поглинена відповідними еритроцитами, показала знижені значення ШОЕ. Після абсорбції анти-А-антитіл А-еритроцитами сироватка крові втратила здатність специфічно підвищувати ШОЕ у А еритроцитів. Висновки. Групові антитіла здатні специфiчно підвищувати ШОЕ. Винайдена властивість може бути зменшена методом специфічної абсорбції сироваток. Лікарі можуть розглядати роль групових аутоімунних антитіл у підвищенні ШОЕ у пацієнтів. Для нормалізації цього показника може бути корисною терапія, спрямована на регуляцію аутоімунної гуморальної активації та специфічну абсорбцію.

Purpose Even if migraine is not fatal, it is a common and challenging disease with adverse effects on individuals' lives. The lack of objective diagnostic tools causes delays in diagnosis and treatment initiation. The primary aim of this study is to reveal the diagnostic value of Calcitonin Gene-Related Peptide (CGRP) and Pentraxin-3 (PTX-3) in acute migraine. To this aim, we compared the serum CGRP and PTX-3 levels of migraine patients with acute attacks to those in healthy individuals. Material and method A total of 135 individuals (85 patients with migraine attacks with or without aura and 50 healthy controls) participated in the study. Serum CGRP and PTX-3 levels were measured with ELISA analysis. A p value less than 0.05 was considered significant. Results Serum CGRP [146.70 (21.52-413.67) vs. 65.90 (3.80-256.60) pg/mL] and PTX-3 levels [12.71 (0.62-33.97) vs. 1.01 (0.06-9.48) ng/mL] were higher in patients with migraine attack than the control group (p < 0.01 and p < 0.01, respectively). ROC analysis showed that the cutoff value for serum CGRP was 121.39 pg/mL (AUC: 0.751, Sen:%61, Spe:%64) whereas the cutoff value for PTX-3 was 4,06 ng/mL (AUC:0.876, Sen:%73, Spe:%76). Serum CGRP levels were positively correlated with pain intensity. Serum CGRP and PTX-3 levels did not differ across gender groups and presence of aura in subgroup analysis. Conclusion Patients with acute migraine attacks have higher serum CGRP and PTX-3 levels than controls. Both biomarkers show high potential for the diagnosis of a migraine attack.

Purpose To determine corneal cross-linking (CXL) efficacy and chromophore penetration after excimer laser-assisted patterned de-epithelialization. Methods Two-hundred-twenty porcine eyes were de-epithelialized ex vivo, either fully (mechanical; n = 88) or patterned (excimer laser; n = 132). Consecutively, corneas were impregnated with hypo- or hyperosmolar riboflavin (RF; n = 20, RF-D; n = 40, respectively) or water-soluble taurine (WST11; n = 40, and WST-D; n = 40, respectively), or kept unimpregnated (n = 80). Sixty corneas were subsequently irradiated, inducing CXL, with paired contralateral eyes serving as controls. Outcome measurements included strip extensiometry to assess CXL efficacy, and spectrophotometry and fluorescence microscopy to determine stromal chromophore penetration. Results All tested chromophores induced significant CXL (p < 0.001), ranging from 7.6% to 14.6%, with similar stiffening for all formulations (p = 0.60) and both de-epithelialization methods (p = 0.56). Light transmittance was significantly lower (p < 0.001) after full compared with patterned de-epithelialization. Stromal chromophore penetration was comparable between fully and patterned de-epithelialized samples, with full penetration in RD and RF-D samples and penetration depths measuring 591.7 +/- 42.8 mu m and 592.9 +/- 63.5 mu m for WST11 (p = 0.963) and 504.2 +/- 43.2 mu m and 488.8 +/- 93.1 mu m for WST-D (p = 0.669), respectively. Conclusions Excimer laser-assisted patterned de-epithelialization allows for effective CXL. Stromal chromophore concentration is, however, reduced, which may have safety implications given the need for sufficient UVA attenuation in RF/UVA CXL. The different safety profile of near-infrared (NIR) may allow safe WST11/NIR CXL even with reduced stromal chromophore concentration values. In vivo studies are needed to evaluate the benefits and further assess safety of excimer laser-assisted patterned de-epithelialization for corneal CXL.

How can we get Japanese university students to give longer answers in spoken English? Longer answers come from being comfortable with using the target language. In this study, first I review some of the previous literature about increasing speaking output. Then, I will report on my own research. Two sections of the same class were taught by the same teacher for both 1st and 2nd year university students. The target independent variable was use of the Flipgrid website for oral submissions as well as reviewing other submissions. The working hypothesis is that being able to practice and being able to hear other submissions will lead to students giving longer oral responses during speaking tests. The two test groups used the Flipgrid website throughout the semester, and the two control groups did not.'Using Flipgrid'means to upload a submission as well as review at least two others for each of 6 assignments. Beginning and end-of-semester oral exams were given to 4 groups of students. The number of words per response for every student were calculated, and the results are presented in this study. I will reflect upon how the results of my study compare with what the previous literature on the topic says, and hope to use the results in future classes.

ObjectiveTo identify the determinants of uncontrolled allergic rhinitis (UCAR) in a hospital setting in Kinshasa, Democratic Republic of Congo.MethodsHospital-based cross-sectional study of 153 patients with allergic rhinitis (AR). The diagnosis of AR was based on clinical grounds according to the Allergic Rhinitis and its Impact on Asthma (ARIA) criteria. Categorization into controlled AR (CAR) and UCAR was based on the visual analog scale (VAS with cut off point of 5). Binary logistic regression was used to identify factors associated with UCAR.ResultsPatients with UCAR (60.1%) proportionally outnumbered those with CAR (39.9%). There were significantly more patients younger than 30 years of age among patients with UCAR. Factors significantly associated with UCAR were age below 30 years (OR = 3.31; 95% CI: 1.49–7.36; p = 0.003), low serum vitamin D level (OR = 3.86; 95% CI: 1.72–8.68; p = 0.001), persistent form (OR = 3.11; 95% CI: 1.39–6.98; p = 0.006) and moderate to severe form of AR (OR = 4.31; 95% CI: 1.77–10.49; p = 0.001).ConclusionsFactors associated with UCAR in this study population were younger age less than 30 years, low vitamin D level, and persistent as well as moderate to severe AR. Further studies are needed to elucidate the underlying mechanisms favoring the occurrence of these factors.

As prospective guidance and counseling teachers, students of the Faculty of Teacher Training and Education are required to have the ability to speak in public, especially in front of the class together with students when conducting counseling services. This study aims to look at content services to be able to increase student confidence, especially in the third semester. In this study, the research design used was a qualitative method (Sugiyono, 2008) explaining that qualitative itself is a research based on post-positivism philosophy, the research is intended to examine objects that are natural, in this study experiment is the opposite and the researcher himself is the key instrument. Data collection techniques in qualitative, data analysis itself is inductive/qualitative. The results of qualitative research itself emphasize more on meaning than generalization, the data collection method used uses primary data sources and secondary data sources. Through this study, it was found that the efforts made to increase self-confidence through content mastery services were able to significantly increase student confidence, {"references":["Adiningtyas, S. W. (2016). Meningkatkan Keterampilan Belajar Siswa Melalui Layanan Penguasaan Konten. Jurnal Dimensi, 5(3).","Bidjuni, H. (2016). Hubungan kepercayaan diri dengan penyesuaian diri Pada mahasiswa baru di program studi ilmu keperawatan fakultas kedokteran Universitas Sam Ratulangi Manado. Jurnal Keperawatan, 4(2)","Febriana, G., Dwityanto, A., & Psi, S. (2016). Hubungan Antara Harga Diri Dengan Kepercayaan Diri Mahasiswa Psikologi Universitas Muhammadiyah Surakarta (Doctoral dissertation, Universitas Muhammadiyah Surakarta).","Fitri, E., Zola, N., & Ifdil, I. (2018). Profil kepercayaan diri remaja serta faktor-faktor yang mempengaruhi. JPPI (Jurnal Penelitian Pendidikan Indonesia), 4(1), 1-5.","Gutara, M. Y., Rangka, I. B., & Prasetyaningtyas, W. E. (2017). Layanan Penguasaan Konten untuk Meningkatkan Keterampilan Berbicara di Depan Umum Bagi Siswa. Jurnal Fokus Konseling, 3(2), 138-147","Hasanah, U., Ahmad, R., & Karneli, Y. (2017). Efektivitas layanan penguasaan konten untuk meningkatkan konsentrasi belajar siswa.","Hasanah, N., & Saugi, W. (2021). Fenomena Ketidakpercayaan Diri Mahasiswa Iain Samarinda Ketika Berbicara Di Depan Umum. Borneo Journal of Islamic Education I (1), 1-12","Ifdil, I., Denich, A. U., & Ilyas, A. (2017). Hubungan body image dengan kepercayaan diri remaja putri. Jurnal Kajian Bimbingan dan Konseling, 2(3), 107-113."]}

Oscillatory activity in the cerebellum and linked networks is an important aspect of neuronal processing and functional implementation of behavior. So far, it was challenging to quantify and study cerebellar oscillatory signatures in human neuroscience due to the constraints of non-invasive cerebellar electrophysiological recording and interventional techniques. The emerging cerebellar transcranial alternating current stimulation technique (CB-tACS) is a promising tool, which may partially overcome this challenge and provides an exciting non-invasive opportunity to better understand cerebellar physiology. Several studies have successfully demonstrated that CB-tACS can modulate the cerebellar outflow and cerebellum-linked behavior. In the present narrative review, we summarize current studies employing the CB-tACS approach and discuss open research questions. Hereby, we aim to provide an overview on this emerging electrophysiological technique and strive to promote future research in the field. CB-tACS will contribute in the further deciphering of cerebellar oscillatory signatures and its role for motor, cognitive, or affective functions. In long term, CB-tACS could develop into a therapeutic tool for retuning disturbed oscillatory activity in cerebellar networks underlying brain disorders.

During the recent years, more often sports specialist are focusing on improving the content of sports curriculum at the schools of higher education. The PURPOSE of the training program is to improve and develop the physical characteristic of strength in students / men /. The METHODS used to achieve the goal in the research are: theoretical analysis, sports-pedagogical testing, pedagogical experiment, pedagogical observation, graphic analysis, comparative analysis. The experiment was conducted in the academic year 2019, with the first and second year students of the Faculty of Veterinary Medicine, Faculty of Agriculture, Faculty of Economics at the Thracian University. The number of the observed students was 70, who were randomly divided into experimental and control groups. When analyzing the RESULTS obtained from the performed tests, it was found an increase in some indicators. The used training program proved its effectiveness with the results from the study. CONCLUSION: This program can be successfully applied in the classes of physical education and sports at the Higher Schools.

Marine carbon cycle processes are important for taking up atmospheric CO2 thereby reducing climate change. Net primary and export production are important pathways of carbon from the surface to the deep ocean where it is stored for millennia. Climate change can interact with marine ecosystems via changes in the ocean stratification and ocean circulation. In this study we use results from the Community Earth System Model version 2 (CESM2) to assess the effect of a changing climate on biological production and phytoplankton composition in the high latitude North Atlantic Ocean. We find a shift in phytoplankton type dominance from diatoms to small phytoplankton which reduces net primary and export productivity. Using a conceptual carbon-cycle model forced with CESM2 results, we give a rough estimate of a positive phytoplankton composition-atmospheric CO2 feedback of approximately 60 GtCO2/°C warming in the North Atlantic which lowers the 1.5° and 2.0°C warming safe carbon budgets.

Background In unilateral lambdoid craniosynostosis (ULC), the posteriorly situated lambdoid suture of the cranial vault fuses prematurely. Positional posterior plagiocephaly (PPP) causes flattening of the posterior side of the head, either through external forces or through underlying differences in brain development. Both conditions cause occipital flattening of the head, but the aetiology is different. Materials and Methods Eight ULC children were compared with 16 sex- and age-matched PPP children. 3D computer tomography scans of all 24 children were analysed with Dolphin imaging software. The location and symmetry of the temporomandibular joint (Co), and the symmetry of the maxillary anterior nasal spine (ANS) and the mandibular symphysis (Pgn) were analysed. Furthermore, the mandibular bone (Co-Pgn) length, corpus length, ramus height, positional changes in the external acoustic meatus (PoL) and the distance from the orbital margin to the articular fossa were measured. Results In all eight ULC children, the Co was anteriorly displaced on the affected side compared with the unaffected side. In all ULC and PPP children, the ANS, which is considered the bony maxillary midpoint, was shifted towards the affected side. In all ULC children, the mandibular bone (Co-Pgn) was shorter on the affected side. The PoL was antero-inferiorly positioned in all ULC children on the affected side compared with the unaffected side. Conclusions Our results show that both types of posterior plagiocephaly are associated with an asymmetric position of the Co and asymmetry of the mandible and maxilla. Facial asymmetry was more frequently seen in ULC than PPP children.

Biopharmazeutika werden zur Therapie einer Vielzahl von schwerwiegenden Krankheiten wie Krebs und Autoimmunerkrankungen verwendet. Sie zeichnen sich insbesondere in der Onkologie durch eine im Vergleich zu chemischen Medikamenten deutlich höhere Spezifität und ein reduzierteres Nebenwirkungsspektrum aus. Die Hauptgruppe der Biopharmazeutika sind heutzutage monoklonale Antikörper, die hauptsächlich in CHO-Zellen hergestellt werden. Denn CHO-Zellen besitzen gegenüber anderen Expressionssystemen. einige entscheidende Vorteile für die biopharmazeutische Produktion. Ein stetig wachsender Markt und die steigende Nachfrage zwingen die biopharmazeutische Industrie Zelllinien schneller zu entwickeln und höhere Titer zu erreichen. In dieser Arbeit wurden verschiedene Herangehensweisen verwendet, um die Entwicklung einer CHO-Produktionszelllinie zu optimieren. Es konnte am Beispiel von Antikörpern gezeigt werden, dass die genetische Konfiguration der CHO-Hostzelle einen Einfluss sowohl auf den Titer, als auch auf den Zeitbedarf für die Zelllinienentwicklung hat. Dazu wurden verschiedene molekulare Werkzeuge verwendet, mit denen die Ausbeuten eines full size IgG und eines Antikörperfragments gesteigert werden konnten. Dabei wurden verschiedene Engpässe umgangen, die während der Proteinbiosynthese innerhalb der Zelle auftreten und so die Produktion gesteigert: a) Durch die Optimierung der Transkription mit Hilfe von Signalpeptiden konnte die Quantität des full size Antikörpers um mehr als das Doppelte gesteigert werden. b) Durch den Einsatz eines UCOEs, einem Chromatin modifizierenden Element, das die Zugänglichkeit des Gens für die Transkription verbessert, konnte die Quantität des Antikörperfragments um das 0,7-fache gegenüber einer Referenz ohne UCOE erhöht werden. c) Durch die Überexpression eines Gens, das die Sekretion verbessert, konnte die Quantität des Antikörperfragments um das Vierfache gesteigert werden. Neben der Produktionssteigerung wurde auch die Methodik der Zelllinienentwicklung optimiert. So konnte gezeigt werden, dass ein Screening auf der Ebene von „Minipools“ deutlich mehr Hochproduzenten hervorbrachte, die eine höhere Quantität des full size Antikörpers vorwiesen, als ein einziger „Largepool“. Der Aufwand für das multiparallele Screening auf Hochproduzenten wurde durch die Etablierung eines MicroFlask Systems, mit dem bis zu 24 Pools parallel in kleinem Volumen in einer Platte kultiviert werden können, signifikant verringert. Ein Vergleich zwischen einem klassischen Fed-Batch mit einem vereinfachten Simple-Fed-Batch, bei dem eine Glukoselösung als einzige Nährstoffzugabe hinzugefügt wurde, zeigte, dass mit weniger Aufwand schneller vergleichbare Ergebnisse erzielt werden können., Biopharmaceuticals are used for the treatment of a variety of serious diseases such as cancer and autoimmune diseases. In oncology in particular, they are characterized by significantly higher specificity and reduced side effects compared to chemical drugs. The main group of biopharmaceuticals today are monoclonal antibodies, which are mainly produced in CHO cells. These cells possess some key advantages over other expression systems. For biopharmaceutical production a steadily growing market and increasing demand are forcing the biopharmaceutical industry to develop cell lines faster and achieve higher titres. In this work, different approaches were used to optimize the development of a CHO production cell line. It was shown for antibodies that the genetic configuration of the CHO host cell has an impact on both the titre and the time need for cell line development. For this purpose, different molecular tools were used to increase the yields of a full size IgG and an antibody fragment. Several bottlenecks that occur during protein biosynthesis within the cell were bypassed to increase production: a) By optimizing transcription using signal peptides, the quantity of a full size antibody was increased more than twofold. b) Using a UCOE, a chromatin modifying element that improves the accessibility of the gene for transcription, increased the quantity of the antibody fragment by 0.7-fold compared to a reference without a UCOE. c) Overexpression of a gene that enhances secretion increased the quantity of antibody fragment fourfold. In addition to the increase in production, the methodology of cell line development was also optimized. It was shown that screening at the level of "minipools" yielded significantly more high producers, which had a higher quantity of the full size antibody, than a single "largepool". The effort required for multiparallel screening for high producers was significantly reduced by establishing a MicroFlask system that allows up to 24 pools to be cultured in parallel in small volume in one plate. A comparison between a classical fed-batch with a simplified simple fed-batch, where only a glucose solution serves as nutrition add-on, showed that comparable results can be achieved faster with less effort.

La actividad empresarial en Colombia y su enfoque hacia el desarrollo de emprendimientos se genera en una perspectiva muy básica que generan conflictos y problemas que ponen en riesgo las ideas de negocio llevándolas al fracaso o al estancamiento. Es por esto que se deben tener en cuenta las características que exigen los mercados actuales para los emprendedores y la forma en la que se deben poner en practica, con el fin de generar empresas solidas, de alta proyección y de competitividad robusta para el buen desempeño en los mercados. Business activity in Colombia and its approach to the development of ventures is generated from a very basic perspective that generates conflicts and problems that put business ideas at risk, leading them to failure or stagnation. This is why the characteristics that current markets demand for entrepreneurs must be taken into account and the way in which they must be put into practice, in order to generate solid companies, with high projection and robust competitiveness for good performance. in the markets. Pregrado

In recent years, the emerging fear of an energy crisis in central Europe has caused an increased demand for distributed energy resources (DER), especially small photovoltaic rooftop installations up to 10 kWp. From a technical point of view, distributed PV in low-voltage networks is associated with the risk of power quality violation, overvoltage, voltage unbalance, harmonics, and violation of the thermal limit of phase conductors, neutral conductors, and transformers. Distribution system operators (DSO) are currently in a position to determine the amount of installed PV power for which reliable and safe network operation is ensured, also known as the photovoltaic hosting capacity (PVHC). The presented study describes a stochastic methodology for PVHC estimation and uses it to analyze a typical LV rural network in the Slovak Republic. Detailed and precise calculations are performed on the 4-wire LV model with accurate results. In this study, we, thus, profoundly analyze the problems with voltage violation, unbalanced voltage energy losses, and the thermal loading effect of increasing PV penetration. The results show that overvoltage events are the main factor limiting the PVHC in LV systems. This conclusion is in accordance with the experience of the DSO in the Slovak and Czech Republic. Subsequently, the study focuses on the possibilities of increasing PVHC using those tools typically available for DSO, such as changes in PV inverter power factors and no-load tap changer transformers. The results are compared with those derived from similar analyses, but we ultimately find that the proposed solution is problematic due to the high variability of approaches and boundary conditions. In conclusion, the paper discusses the issue of the acceptable risk of overvoltage violation in the context of PVHC and lowering losses in LV networks.

Background: Increase in lipid levels associated with the treatment of inflammatory bowel disease (IBD) has previously been reported. However, it is unknown if this effect is similar for all IBD drug classes.Aim: To precisely assess the effect of different IBD drug classes on lipid profilesMethods: We performed a systematic literature search of randomised controlled trials and observational cohort studies that assessed lipid levels before and after induction (10 weeks) of IBD treatment. Data of 11 studies (1663 patients) were pooled using random effects models. The influence of patient and disease characteristics on treatment effects on total cholesterol levels was analysed in 6 studies (1211 patients) for which individual data were available, using linear mixed models.Results: A statistically significant increase in total cholesterol was observed after induction treatment with corticosteroids (+1.19 mmol/L, 95% confidence interval [CI95] +0.52 to +2.59), and tofacitinib (+0.66 mmol/L, CI95 +0.42 to +0.79), but not after anti-TNF alpha treatment (-0.11 mmol/L, CI95 -0.26 to +0.36 mmol/L). Similar differences were observed after maintenance treatment. Treatment effects were significantly related to age, but not with other factors. Lipid changes were inversely correlated with but not modified by CRP changes.Conclusions: Increase in total cholesterol levels was strongest for corticosteroids followed by tofacitinib but was not observed for anti-TNF alpha agents. Whether total cholesterol change associated with IBD treatment has an effect on cardiovascular risk requires further study.

Background: Increase in lipid levels associated with the treatment of inflammatory bowel disease (IBD) has previously been reported. However, it is unknown if this effect is similar for all IBD drug classes.Aim: To precisely assess the effect of different IBD drug classes on lipid profilesMethods: We performed a systematic literature search of randomised controlled trials and observational cohort studies that assessed lipid levels before and after induction (10 weeks) of IBD treatment. Data of 11 studies (1663 patients) were pooled using random effects models. The influence of patient and disease characteristics on treatment effects on total cholesterol levels was analysed in 6 studies (1211 patients) for which individual data were available, using linear mixed models.Results: A statistically significant increase in total cholesterol was observed after induction treatment with corticosteroids (+1.19 mmol/L, 95% confidence interval [CI95] +0.52 to +2.59), and tofacitinib (+0.66 mmol/L, CI95 +0.42 to +0.79), but not after anti-TNF alpha treatment (-0.11 mmol/L, CI95 -0.26 to +0.36 mmol/L). Similar differences were observed after maintenance treatment. Treatment effects were significantly related to age, but not with other factors. Lipid changes were inversely correlated with but not modified by CRP changes.Conclusions: Increase in total cholesterol levels was strongest for corticosteroids followed by tofacitinib but was not observed for anti-TNF alpha agents. Whether total cholesterol change associated with IBD treatment has an effect on cardiovascular risk requires further study.

Background: The present study determined whether or not the regular intake of red wine causes any significant changes in testicular and body weight parameters, given the simmering controversy over the effect of alcoholic beverages on health system. Methods: Ten male albino Wistar rats –experimental model with average body weight of 140 g were divided into two groups, A and B, (n=5 each). Group A received distilled water being the control while group B was administered a single daily dose of 5 ml/kg body weight of red wine (Carlo Rossi) for 21 days. An electronic weighing scale (G&G® Neuss, Germany) was used to take record of the initial and final body weights. The animals were anesthetized with isoflurane on the 22nd day to enable collection of the testes which were also weighed and thereafter fixed in 10% neutral formalin for routine histological studies. The analysis of variance (ANOVA) was used with the ‘R’ software to analyze the statistical data, while P Results: The micro-anatomical investigation revealed enhanced perfusion of the tissue and normal morphology of the seminiferous tubules with constituent spermatogenic cells at different stages of maturation. The biometric assessment of the organ (testis) weight showed no significant difference; whereas there was a statistically significant increase in the final body weight of the treated-experimental model when compared with the control. Conclusion: The findings indicate that the intake of red wine at the investigated amount may maintain the integrity of the primary reproductive structure and lead to body weight gain in males.

This report applies the framework to diagnose the opportunities and constraints faced by the rural economy and households and to assess policy options to address these constraints. The approach builds on four steps. The first step consists in examining the socio-demographic profile and living conditions of rural households. The second step assesses opportunities to increase the income of rural households. The third step investigates the key constraints preventing rural households from taking advantage of these opportunities and explores the sequencing and overlap of the constraints. The final step examines the feasible policy actions that would help rural households overcome the key constraints to increasing their income. Details are provided in Figure 9. The analysis selects the key constraints that prevent households from taking advantage of identified opportunities. Prioritization of constraints requires assessing the likely benefits of pursuing the opportunities compared against the costs of relaxing the constraints. There are four criteria suggested by Hill (2018) that are used to identify the priority constraints that need to be address: (1) the constraint limits several important sources of income; (2) strength of evidence that addressing the constraint will help income growth, (3) the constraint has a stronger impact on poorer households or regions, and (4) existing evidence on the need to address the constraint first before other constraints can be addressed. Potential feasible policy solutions are suggested to the prioritized constraints. The potential for the policy solutions to address the constraints, their feasibility, and the size and breadth of their impact is graded based on the review of evidence and discussion with experts and stakeholders operating in the field.

This study investigates solar variability between 650 CE and 1900 based on new and published 14C records with a time resolution of two years or higher. The new high-resolution 14C data presented here are derived from Danish oak and span the period 1058–1250 CE. We determine the durations of past solar minima and periods with moderate solar activity from the solar modulation potential calculated using a carbon-box model with the high-resolution 14C records as input. The observed intervals of solar minima and intermittent periods with moderate activity levels suggest that a Maunder-type minimum occurred in 656–707 CE. We tentatively propose to name this minimum the Horrebow Minimum after Christian Horrebow, an early Danish astronomer who studied the occurrence of sunspots and was the first to propose that they follow a cyclic behaviour. Changes in amplitude and cycle length of the 11-year solar cycle are investigated by bandpass filtering 23 individual 14C records. The filtered 14C data indicate that the length of the 11-year solar cycle may be prolonged before the onset of the Oort, Maunder, and Spörer minima. The amplitude of the 11-year solar cycle associated with solar minima and periods with moderate solar activity between 650 CE and 1900 is estimated to 1.1‰. A two-sample Kolmogorov-Smirnov goodness-of-fit test indicates that there is no significant difference between the amplitude distribution of 11-year solar cycles during solar minima and periods of moderate solar activity. A review of the high-resolution 14C records encompassing the near-Earth supernova events that occurred in 1006 CE, 1054, 1181, 1572, and 1604 suggests that these events were not accompanied by distinct changes in the 14C production rate. Nonetheless, an unusual increase of c. 10‰ in Δ14C between 1048 CE and 1055 is observed and discussed.

A recent synthesis study found 54% of the high-latitude peatlands have been drying and 32% have been wetting over the past centuries, illustrating their complex ecohydrological dynamics and highly uncertain responses to a warming climate. High-latitude peatlands are changing rapidly in response to climate change, including permafrost thaw. Here, we reconstruct hydrological conditions since the seventeenth century using testate amoeba data from 103 high-latitude peat archives. We show that 54% of the peatlands have been drying and 32% have been wetting over this period, illustrating the complex ecohydrological dynamics of high latitude peatlands and their highly uncertain responses to a warming climate.

Por medio del presente escrito se relacionan un plan de mejora frente aspectos problemáticos encontrados en el transcurso de las prácticas profesionales empleadas en la empresa; Distribuidora Los Autos de Colombia S.A.S ( Los Coches ), donde se mostrara los procesos encontrados en el área de importaciones de vehículos automotores. Identificando aspectos por medio de una análisis DOFA ( Debilidades, Oportunidades, Fortalezas y Amenazas), determinando ciertos objetivos, para el avance y desarrollo en el área de importaciones de la compañía, por medio de métodos innovadores o estrategias enfocadas en el crecimiento y gestión de procesos en obtención de mejor rendimiento y resultado, así mismo tener enfoque en las deficiencias encontradas, en el flujo de trabajo y los procesos teniendo en cuenta la acumulacion de trabajo, por época de pandemia Covid -19 , y lograr retomar los procesos de la manera más satisfactoria en el principio de la Post-pandemic estableciendo una mejora continua y una mejor gestión de procesos By means of this writing, an improvement plan is related to problematic aspects found in the course of the professional practices used in the company; Distributor Los Autos de Colombia S.A.S (Los Coches), where the processes found in the area of ​​imports of motor vehicles will be shown. Identifying aspects through a SWOT analysis (Strengths, Weaknesses, Opportunities and Threats), determining certain objectives, for the advancement and development in the company's import area, through innovative methods or strategies focused on the growth and management of processes to obtain better performance and results, as well as having a focus on the deficiencies found, on the workflow and the processes, taking into account the accumulation of work, due to the Covid-19 pandemic, and managing to resume the processes in the way more satisfactory at the beginning of the Post-pandemic by establishing continuous improvement and better process management Profesional en Negocios Internacionales Pregrado

The protection mediated by the bioactive sphingolipid sphingosine-1-phosphate (S1P) declines during Alzheimer's disease (AD) progression, especially in patients carrying the apolipoprotein E ε4 (APOE4) isoform. The drug FTY720 mimics S1P bioactivity, but its efficacy in treating AD is unclear. Two doses of FTY720 (0.1 mg / kg and 0.5 mg / kg daily) were given by oral gavage for 15 weeks to transgenic mouse models of familial AD carrying human apolipoprotein E (APOE) APOE3 (E3FAD) or APOE4 (E4FAD). After 12 weeks of treatment, animals were subjected to behavioral tests for memory, locomotion, and anxiety. Blood was withdrawn at different time points and brains were collected for sphingolipids analysis by mass spectrometry, gene expression by RT-PCR and Aβ quantification by ELISA. We discovered that low levels of S1P in the plasma is associated with a higher probability of failing the memory test and that FTY720 prevents memory impairments in E4FAD. The beneficial effect of FTY720 was induced by a shift of the sphingolipid metabolism in the brain towards a lower production of toxic metabolites, like ceramide d18:1/16:0 and d18:1/22:0, and reduction of amyloid-β burden and inflammation. In conclusion, we provide further evidence of the druggability of the sphingolipid system in AD. ispartof: BIOMEDICINE & PHARMACOTHERAPY vol:152 ispartof: location:France status: published

Free school meals (FSM) are a well-recognized intervention for tackling food insecurity among school children. National school closures during the COVID-19 pandemic meant that there was a need to rapidly adapt the delivery of FSM. A range of food-assistance policies were implemented, but it is not clear if they were evidence-based. This study aimed to determine the transparency of evidence use and identify other competing influences in the UK’s FSM policy decisions. Thematic content analysis was used to review 50 publicly available policy documents and debate transcripts on FSM policy published between March 2020 and 2021. This period covered the first national school closures (March 2020–July 2020), school holidays, and the second national school closures (January 2021–March 2021). The Evidence Transparency Framework (ETF) was used to assess the transparency of evidence use in policy documents. We found that overall transparency of evidence use was poor but was better for the Holiday Activities and Food (HAF) program. The Government showed preference for replacing FSM with food parcels, rather than more agentic modes of food assistance, such as cash-vouchers. This preference appeared to be closely aligned with ideological views on the welfare state. With an absence of evidence, value-based reasoning took precedent and was polarized by social media. This article highlights the need for a formal review into FSM, one which includes a comparison of low and high agentic food assistance policies. Such a review would address the evidence gap, improve food assistance policy, and aid policymakers in future periods of uncertainty.

This article synthesizes recent findings on antecedents of healthy eating. We discuss consumer-related and environment-related forces that influence consumers' healthy food choices and emphasize the duality of these forces so that they can facilitate but also prevent healthy eating. Specifically, our review documents how consumer lay beliefs, goals, and habits shape eating patterns. We further document the impact of environment-related forces on healthy consumption-focusing on intervention strategies and environmental changes (i.e., the trend towards online retail channels). Finally, we discuss three salient tensions (i.e., an innate craving for unhealthy food, a focus on single decisions, and a selective focus on self-control dilemmas) that emerge when taking a holistic view on existing research.

Aims Here, we investigated the association between depressive symptoms and leisure-time physical activity (LTPA) in type 1 diabetes. Methods Data from adult individuals with type 1 diabetes without evidence of diabetic kidney disease or macrovascular complications, participating in the Finnish Diabetic Nephropathy Study, were included. Based on a questionnaire, weekly LTPA as metabolic equivalent of task hour was calculated. Activity levels (inactive, moderately active, active), weekly frequencies ( 2), intensities (low, moderate, high), and single session durations ( 60 min) were assessed. Depressive symptomatology was evaluated using the Beck Depression Inventory (BDI). We calculated a continuous BDI score and divided participants into those with (BDI score ≥ 16) and without (BDI score Results Of the 1339 participants (41.7% men, median age 41 years), 150 (11.2%) reported symptoms of depression. After adjustments, both higher BDI scores and depressive symptomatology were associated with more inactive lifestyle, and lower frequency and intensity of the LTPA. The BDI score was additionally associated with shorter single session duration. For antidepressant purchases, lower odds were observed in those with higher intensity and longer single session duration of LTPA. Conclusions Depressive mood is harmfully related to LTPA in type 1 diabetes. In order to improve the long-term health of individuals with type 1 diabetes, efforts to increase both mental well-being and physical activity should be taken.

Leases and rent play a key role in agricultural production. Rental payments represent a significant part of production costs. Practice shows that in order not to lose the already occupied areas, producers increase the amount of payments to owners. The aim of the study is to track the dynamics of average prices for lease agreements for the South-Eastern region of Bulgaria. Basic and chain indices of price dynamics were used. There was a continuous growth of increase in rent paymentsТракийски университет - Стара Загора.

This study investigated the spatiotemporal changes, including long-term trends and abrupt changes in the heatwave (HW)-related climatic characteristics of Turkey, such as the heatwave number (HWN), duration (HWD), frequency (HWF), magnitude (HWM), and amplitude (HWA). Heatwave-related indices in Turkey based on 88 meteorological stations were calculated considering the 90th percentile of the daily minimum air temperature (Tn90p) and the 90th percentile of the daily maximum air temperature (Tx90p). Trend analysis of the heatwave characteristics indicated that Turkey has experienced more frequent, longer, and hotter heatwaves since 1950. The most significant increasing trends observed in the series of HWNs, HWFs, and HWDs and the Tn90p series were characterized generally with greater trend values. Geographically, the largest changes in the heatwave characteristics of Turkey were detected to occur after the middle of the 1990s in the Black Sea and the Mediterranean coasts, which are in agreement with previous studies performed for various regions of the Mediterranean basin. Long-term trends in almost all country-based heatwave indices of Turkey, except trends in the Tn90p series of HWM values, particularly the Tn90p and Tx90p time series of HWN, HWF, and HWD, and the Tn90p time series of HWA values are statistically significant at the 0.000 level. Statistical comparisons of the means and variances of the Tn90p and Tx90p time series of HWN, HWF, and HWD between the periods of 1950-1984 and 1985-2018 are statistically significant at the 0.005 level. These results indicate abrupt changes towards increased heatwave conditions after the year 1984.

Background: Longitudinal changes in cerebrospinal fluid (CSF) biomarkers are seldom studied. Furthermore, data on biomarker gradient between lumbar (L-) and ventricular (V-) compartments seems to be discordant. Objective: To examine alteration of CSF biomarkers reflecting Alzheimer's disease (AD)-related amyloid-beta (A beta) aggregation, tau pathology, neurodegeneration, and early synaptic degeneration by CSF shunt surgery in idiopathic normal pressure hydrocephalus (iNPH) in relation to AD-related changes in brain biopsy. In addition, biomarker levels in L- and V-CSF were compared. Methods: L-CSF was collected prior to shunt placement and, together with V-CSF, 3-73 months after surgery. Thereafter, additional CSF sampling took place at 3, 6, and 18 months after the baseline sample from 26 iNPH patients with confirmed A beta plaques in frontal cortical brain biopsy and 13 iNPH patients without A beta pathology. CSF Amyloid-beta(42) (A beta(42)), total tau (T-tau), phosphorylated tau (P-tau(181)), neurofilament light (NFL), and neurogranin (NRGN) were analyzed with customized ELISAs. Results: All biomarkers but A beta(42) increased notably by 140-810% in L-CSF after CSF diversion and then stabilized. A beta(42) instead showed divergent longitudinal decrease between A beta-positive and -negative patients in L-CSF, and thereafter increase in A beta-negative iNPH patients in both L- and V-CSF. All five biomarkers correlated highly between V-CSF and L-CSF (A beta(42) R = 0.87, T-tau R = 0.83, P-tau R = 0.92, NFL R = 0.94, NRGN R = 0.9; all p < 0.0001) but were systematically lower in V-CSF (A beta(42) 14 %, T-tau 22%, P-tau 20%, NFL 32%, NRGN 19%). With APOE genotype-grouping, only A beta(42) showed higher concentration in non-carriers of allele epsilon 4. Conclusion: Longitudinal follow up shows that after an initial post-surgery increase, T-tau, P-tau, and NRGN are stable in iNPH patients regardless of brain biopsy A beta pathology, while NFL normalized toward its pre-shunt levels. A beta(42) as biomarker seems to be the least affected by the surgical procedure or shunt and may be the best predictor of AD risk in iNPH patients. All biomarker concentrations were lower in V-than L-CSF yet showing strong correlations.

The subject of the research is the theoretical, methodological principles, and practical proposals for increasing the agricultural enterprises’ competitiveness based on improving its components accounting, evaluation, and modeling. The purpose of the article is to substantiate the increase of agricultural enterprises’ competitiveness and managing it through improving accounting, evaluation, and modeling of its quantitative indices and indicators. The methodological basis of the article is the fundamentals of economic theory, business economics, and accounting; works of leading scientists on competitiveness issues; legal regulations on various aspects of agricultural enterprises and markets development. The historical and monographic methods and methods of system-structural analysis and synthesis, rating evaluation and ranking, accounting, model of competitive space are used. The results of the article. The essence of agricultural enterprises’ competitiveness is generalized, the problems of its formation are revealed and directions of improving its management are offered based on building the model of competitive space taking into account indicators of financial and economic sustainability of agribusiness, market share, and products competitiveness, and involvement of the marketing plan as well. Field of application of results. The results obtained should be used in the management of agribusiness enterprises; in the educational process of the faculties of economics and management of higher education institutions. Conclusions. Modeling of increasing the agricultural enterprises’ competitiveness and its forward-looking management is based on improving the accounting and evaluation of indicators of its factors and components. Its result can be a three-factor model of competitive space based on the following indicators: the level of competitiveness of products, the level of financial and economic sustainability, the market share size. The key to increasing the competitiveness of agricultural entities depending on the model chosen and strategies of functioning in the market space is called innovation, compliance with specialization, marketing plans.

The subject of the research is theoretical-methodical and practical aspects of formation and ensuring the agricultural enterprises’ competitiveness taking into account the levels, dynamics, and other features of their financial and economic sustainability and economic security. The purpose of the article is to substantiate the theoretical and methodological principles and practical ways of increasing agricultural enterprises’ competitiveness based on their financial and economic sustainability and security. The methodological bases of the article are general methodological approaches, namely: dialectical, historical, monographic, system-structural analysis, and synthesis to the study of economic phenomena and processes. Legislative and normative-legal regulations for development and formation of agricultural enterprises’ competitiveness, their financial and economic sustainability and security; scientific works of leading domestic and foreign scientists on the theory and practice of competitiveness as one of the main categories of market mechanism and management in agriculture; analytical and statistical materials of the State Statistics Service are used in the work. In the work the methods of economic researches are used: abstract and logical – for substantiation of theoretical and methodical bases of agricultural enterprises’ competitiveness formation in the conditions of their financial and economic sustainability and security; in the formation of theoretical generalizations, factors and principles of competitiveness management, critical analysis of other authors’ research; statistical and economic – in determining the competitiveness of agricultural enterprises; marketing –when researching the food market and assessing market conditions for the future; comparative – when comparing indicators of enterprises’ competitiveness of the given region and agro sphere industry with the other ones; graphic – to determine structural changes in the food market; system-structural – to analyze the resource potential of agricultural enterprises’ competitiveness; analytical forecasting – to determine the system of measures of organizational and economic mechanism for its provision; economic and mathematical modelling – to substantiate the increasing of agricultural enterprises’ competitiveness, taking into account the levels of their financial and economic sustainability and security. The results of the article. It is determined that the leading importance in ensuring the agricultural enterprises’ competitiveness belongs to the competitive advantages, as well as their financial and economic sustainability and economic security. The factors and components of providing the latter are determined. A set of measures to increase financial and economic sustainability, ensure economic security as a basis for stable competitiveness, and assurance of its growth in the future is proposed. Field of application of results. The results can be used in the management of agricultural enterprises, in the educational process of higher education institutions, in training the specialists in economics and management. Conclusions. It is determined that the most significant feature of the theory and practice of rural green tourism enterprises in European countries is the expansion of their functions from purely business to more socially necessary and significant – as tools for preservation and reproduction of rural areas, including depressed ones. This provides for their greater support at the level of local communities and government, which is appropriate for all uses. It also makes sense to use the well-tested mechanisms and forms of tourism in the countryside.

Old-growth forests have an important role in maintaining animal and plant diversity, are important carbon (C) reservoirs and are privileged sites to study long-term plant physiological responses, long-term forest dynamics and climate change impact on forest ecosystems. Several studies have highlighted how old-living trees undergo age-related declines with hydraulic limitations and reduction in photosynthesis, though some recent works have suggested that such a decline is not always observed. Our study aims at understanding the role of atmospheric CO2 increase on tree C uptake and stomatal conductance (gs) in old-living trees by analysing the long-term patterns of tree growth and intrinsic water use efficiency (iWUE) in three old-growth forests in the Balkans (Bosnia-Herzegovina and Montenegro), using dendrochronology and isotopic analysis. We hypothesised a long-term increase in iWUE in the studied old-growth forests, mostly related to enhanced photosynthesis rather than reduced stomatal conductance. Tree cores were sampled from dominant silver fir (Abies alba Mill.) trees in each forest. Tree-ring widths were measured and basal area increments (BAI) were assessed for each sampled tree and, from the six longest chronologies, five decades were chosen for cellulose extraction, its isotopic analysis (δ13C, δ18O), iWUE and leaf water 18O evaporative enrichment above the source water (Δ18OL) determination. We observed a continuous and significant increase in iWUE from 1800 to 2010 in the sampled dominant trees at all the three old-growth forests. Our BAI data and our estimates of Δ18OL across the study period support the idea that enhanced photosynthesis rather than reduced stomatal conductance is the major driver of the measured iWUE increase. Thus, our results support some recent findings challenging the hypothesis that iWUE in forests is primarily the result of a CO2-induced reduction in stomatal conductance as well as the so called hydraulic limitation hypothesis.

La prevención de riesgos laborales es un derecho básico de los trabajadores, por su evidente conexión con el derecho a la vida y a la salud. Su relevancia y complejidad jurídica merecen conocer cómo se regula el deber de seguridad en el ordenamiento jurídico chileno, cuáles son sus características más relevantes y cuál es el alcance de esta obligación empresarial The prevention of occupational hazards is a basic right of workers, connected with the right to life. It is important to know how it is regulated in the Chilean law, and analyze its most important characteristics. Universidad Pablo de Olavide

RESUMEN | Se realizaron análisis de correlación múltiple exploratorio y correlaciones entre las variables del análisis en fresco (Grado de condición de hepatopáncreas, Gregarinas y Epibiontes) y el Incremento Semanal Promedio -ISP- de 76 estanques de cultivo de camarones en Sonora, México. Aunque estas variables del análisis en fresco presentaron tendencias de correlaciones negativas con el ISP, únicamente la infestación de gregarinas presentó una correlación significativa con el ISP, sugiriendo que la parasitosis provoca efectos negativos sobre el crecimiento de los cultivos, incluso en organismos que no están severamente infestados. ABSTRACT | Analyzes of multiple explorations and correlations between the variables of the wet mount analysis (degree of condition of hepatopancreas, Gregarines and Epibionts) and the Average Weekly Increase -AWI- of 76 shrimp ponds in Sonora, Mexico, were performed. Although the wet mount analysis variables showed negative correlation trends with the AWI, only the gregarine infestation showed significant evidence with the AWI, suggesting that parasitosis causes negative effects on shrimp growth, even in organisms that are not severely affected.

Analyzes of multiple explorations and correlations between the variables of the wet mount analysis (degree of condition of hepatopancreas, Gregarines and Epibionts) and the Average Weekly Increase -AWI- of 76 shrimp ponds in Sonora, Mexico, were performed. Although the wet mount analysis variables showed negative correlation trends with the AWI, only the gregarine infestation showed significant evidence with the AWI, suggesting that parasitosis causes negative effects on shrimp growth, even in organisms that are not severely affected., Se realizan análisis estadísticos sobre los resultados de 76 estanques de cultivo de camarones en Sonora, México. En ellos, se evalúa la correlación entre tres variables predictivas propuestas: Grado de condición de hepatopáncreas, Gregarinas y Epibiontes. Estableciendo al Incremento Semanal Promedio (ISP), como variable de respuesta. Se aplica un Análisis de componentes principales, en el cual se observa que estas variables presentaron correlaciones negativas con el ISP. Al realizar análisis de regresión lineal y ANOVA, no se detectan correlaciones a p

La presente idea de negocio surge como respuesta a la alta demanda y al crecimiento del sector gastronómico evidenciado en el sector de La Candelaria en Bogotá, puesto que, la oferta en el sector de restaurantes cómodos, agradables y que ofrezcan servicio de calidad disminuyó como consecuencia de la pandemia. This business idea arises in response to the high demand and growth of the gastronomic sector evidenced in the La Candelaria sector in Bogotá, since the offer in the sector of comfortable, pleasant restaurants that offer quality service decreased as a consequence. of the pandemic. Administrador de empresas Pregrado

El taller tropical es un proyecto arquitectónico planteado para la comunidad del barrio Moravia en la ciudad de Medellín – Antioquia, el cual cuenta con una gran diversidad de culturas dado que su crecimiento se dio en forma de invasión ya que este era el antiguo basurero de la ciudad y los desplazados por la violencia encontraron entre los desechos una luz de esperanza para un nuevo comienzo, pero este crecimiento se dio muy acelerado y sin ningún tipo de planificación, provocando que en estos momentos el sector carezca de espacios adecuados para la interacción social, equipamientos educativos, espacios públicos, zonas verdes entre otras. Es por esto que la comunidad adecuo un lugar provisional en el cual ubicaron un taller tropical en el que desarrollan toda clase de actividades para dar a conocer sus diferentes culturas, pero este se encuentra ubicado en una de las terrazas de una vivienda, la cual no pueden seguir arrendando, además que el lugar es demasiado pequeño para la cantidad de habitantes del sector. Por ello se empieza la búsqueda de un nuevo lote donde ubicarse de forma definitiva y brindarle a los habitantes de Moravia y turistas zonas en las cuales se sientan ajusto y puedan dar a conocer un poquito de sus raíces. Se toma uno de los pocos lotes sin habitar y se plantea un proyecto en el cual se le regale a la comunidad la mayor parte para espacio publico y zonas verdes. Pero igual brindándoles espacios amplios y diversos donde puedan desarrollar toda clase de actividades y muestras culturales. The Taller Tropical is an architectural project proposed for the community of the Moravia neighborhood in Medellin - Antioquia city, which has a great diversity of cultures, since its growth was by invasion since this was the old dump of the city, and those displaced by violence found in the waste a light of hope for a new beginning, but this growth was very accelerated and without any planning, causing that in this time the sector does not have adequate spaces for social interaction, educational facilities, public spaces, green areas and others. That is why the community adapted a provisional place in which they located a Taller Tropical in which they develop all kinds of activities to divulge their different cultures, but this is located on one of the terraces of a house, which cannot continue to pay rent, plus the place is too small for the number of population of the sector. For this reason, we are looking for a new place where we can settle down definitively and offer the population of Moravia and tourists areas in which they feel comfortable and can show a little bit of their cultural roots. One of the few uninhabited places is taken and a project is planned in which the community is given most of the public space and green areas. But in the same way we offer them wide and diverse spaces where they can develop all kinds of activities and show their cultures. Pregrado

Background The current study aims to identify the relationships between coagulation factors and plasma thrombin generation in a large population-based study by comparing individuals with a history of arterial or venous thrombosis to cardiovascular healthy individuals. Methods This study comprised 502 individuals with a history of arterial disease, 195 with history of venous thrombosis and 1402 cardiovascular healthy individuals (reference group) from the population-based Gutenberg Health Study (GHS). Calibrated Automated Thrombography was assessed and coagulation factors were measured by means of BCS XP Systems. To assess the biochemical determinants of TG variables, a multiple linear regression analysis, adjusted for age, sex and antithrombotic therapy, was conducted. Results The lag time, the time to form the first thrombin, was mainly positively associated with the natural coagulant and anti-coagulant factors in the reference group, i.e. higher factors result in a longer lag time. The same determinants were negative for individuals with a history of arterial or venous thrombosis, with a 10 times higher effect size. Endogenous thrombin potential, or area under the curve, was predominantly positively determined by factor II, VIII, X and IX in all groups. However, the effect sizes of the reported associations were 4 times higher for the arterial and venous disease groups in comparison to the reference group. Conclusion This large-scale analysis demonstrated a stronger effect of the coagulant and natural anti-coagulant factors on the thrombin potential in individuals with a history of arterial or venous thrombosis as compared to healthy individuals, which implicates sustained alterations in the plasma coagulome in subjects with a history of thrombotic vascular disease, despite intake of antithrombotic therapy.

Background In the current century, sleep apnoea has become a significant public health problem due to the obesity epidemic. To increase awareness, improve diagnostics, and improve treatment, Finland implemented a national sleep apnoea programme from 2002 to 2010. Here, we present changes in the societal burden caused by sleep apnoea from 1996 to 2018. Methods National register data were collected from the Care Register for Health Care, Statistics Finland, the Social Insurance Institution of Finland, and the Finnish Centre for Pensions. Disease prevalence, use of healthcare and social services, and societal costs were estimated. Findings The number of sleep apnoea patients increased in secondary care from 8 600 in 1996 to 61 000 in 2018. There was a continuous increase in outpatient visits in secondary care from 9 700 in 1996 to 122 000 in 2018 (1 160%) and in primary care from 10 000 in 2015 to 29 000 in 2018 (190%). Accordingly, the cumulative annual number of days off work for sleep apnoea increased from 1 100 to 46 000. However, disability pensions for sleep apnoea decreased from 820 to 550 (33%) during the observation period. Societal costs per patient decreased over 50% during the observation period ((sic) 2 800 to (sic)1 200). Interpretation The number of sleep apnoea patients in Finland increased remarkably during the observation period. To control this burden, diagnostic methods and treatment were revised and follow up was reorganised. Consequently, there was a significant decrease in societal costs per patient. The decrease in disability pensions suggests earlier diagnosis and improved treatment. The national sleep apnoea programme was one of the initiators for these improved outcomes. Funding The Finnish Institute for Health and Welfare and the Hospital District of Helsinki and Uusimaa (HUH), Helsinki, Finland. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)

What role do immigrants play in firms’ ability to absorb and apply foreign knowledge? Based on a matched employer–employee dataset from Danish manufacturing firms over the period 2001–2011, this study examines the impact of foreign knowledge accessible by firms’ immigrant employees on firm-level total factor productivity (TFP). We construct various firm-specific absorbable foreign knowledge measures that link firms’ immigrant employees to the technological knowledge base of their country of origin. The empirical results suggest that firms employing immigrant employees have higher firm-level TFP outcomes and a higher probability of new firm-level patent applications. The average productivity gain associated with the hiring of one immigrant employee is about 1.5% in the year following the firm’s hiring decision. Additional results show that the estimated productivity increase varies with the level of education and the occupational positions of the immigrant employees. The results are robust to the inclusion of a large range of firm-specific controls and various sensitivity checks.

This study aims to determine the effectiveness of simple KIT-based media in improving student learning achievement in dynamic electricity material. The sample used was the students of class grade 12 of IPA-3 Madrasah Aliyah Negeri 2 Mojokerto, totaling 35 students. The type of research used is research development (Research and Development). The research data were obtained from questionnaire responses during learning and the results of the pre-test and post-test. The questionnaire's responses were as many as 85.14% of students who thought that the development of KIT-based learning media was very effective in using dynamic electricity learning. Moreover, as many as 14.85% think that KIT-based learning media is creative and interactive learning and is an additional supplement in the teaching and learning process. From the test results given to students, there was a significant increase in students' achievements. This indicator can be seen from the t count value is smaller than the t table (t count

The biodiversity crisis has increased interest in understanding the role of biodiversity for ecosystem functioning. Functional traits are often used to infer ecosystem functions to increase our understanding of these relationships over larger spatial scales. The links between specific traits and ecosystem functioning are, however, not always well established. We investigated how the choice of analyzing either individual species, selected modalities, or trait combinations affected the spatial patterns observed on a sandflat and how this was related to the natural variability in ecosystem functioning. A large dataset of 400 benthic macrofauna samples was used to explore distribution patterns. We hypothesized that (1) if multiple species (redundancy) represent a trait combination or a modality their spatial patterns would be smoothed out, and (2) the lost spatial variability within a trait combination or modality, due to the smoothing effect, would potentially affect their utility for predicting ecosystem functioning (tested on a dataset of 24 samples). We predicted that species would show heterogeneous small spatial patterns, while modalities and trait combinations would show larger and more homogeneous patterns because they would represent a collection of many distributions. If modalities and trait combinations are better predictors of ecosystem functioning than species, then the smoother spatial patterns of modalities and trait combinations would result in a more homogeneous landscape of ecosystem function and the number of species exhibiting specific traits would provide functional redundancy. Our results showed some smoothing of spatial patterns progressing from species through modalities to trait combinations, but generally spatial patterns reflected a few dominant key species. Moreover, some individual modalities and species explained more or equal proportions of the variance in the ecosystem functioning than the combined traits. The findings thus suggest that only some spatial variability is lost when species are combined into modalities and trait combinations and that a homogeneous landscape of ecosystem function is not likely., Functional traits are often used to infer ecosystem functioning across larger scales, but how do they reflect species distributions and how well do they actually explain the natural spatial variability in ecosystem functioning? This was examined with a rarely seen extensive dataset of benthic macrofauna samples and solute flux measurements across the sediment–water interface.

Prepublication peer review is a cornerstone of science. Overburdened reviewers invest millions of hours in this voluntary activity. In this scoping review, we aimed at identifying motivations for performing prepublication peer review of scholarly manuscripts. Original research studies investigating actual peer reviewers' motivations were included. We excluded modeling studies, studies related to other types of peer review, guidelines, peer review processes in particular journals. Medline, WoS, and Scopus were searched in February 2016, with no language or time limitations, and the search was updated in July 2019. The search yielded 5,250 records, and 382 were chosen for full text analysis, out of which 10 were appropriate for synthesis. Reference snowballing identified one eligible study. Eleven studies were appropriate for synthesis: four qualitative, four mixed qualitative/quantitative, and three qualitative studies, published from 1998 to 2018, involving 6,667 respondents. Major internal incentive was "communal obligations and reciprocity." Major external incentives were "career advancement," "being recognized as an expert," and "building relationships with journals and editors." Major disincentive was the "lack of time." Editors could incentivize peer review process by choosing highest quality articles, improving communication with peer reviewers, in order to make the process of peer review as short and efficient as possible. The gaps in research concern disincentives to review.

Fermentation is considered a promising way to increase the bioactive substance content as well as the curing efficacy of foods and herbal medicines. However, in the vast majority of cases, it remains unknown what bioactive ingredient and physiological activity are altered in traditional herbs after fermentation. Here, in order to find the effect of fermentation on the bioactive compound content and health efficacy of Cornus officinalis fruit, an important Chinese traditional medicine, its total phenolic content, total flavonoid content, antioxidant activity and anti-tyrosinase activity were estimated during Bifidobacterium bifidum fermentation process. The results showed that, during COF (Cornus officinalis fruit)’s fermentation, the total phenolic contents were significantly increased, however, the total flavonoid contents weren’t obviously changed, and that the antioxidant activity as well as the anti-tyrosinase activity was enhanced. In addition, the total phenolic content was positively related not only to the antioxidant activity but also to the anti-tyrosinase activity. This research can help us better understand the alterations of ingredients and physiological activities of fermented traditional medicines that influence curing efficacy.

Ethane is the most abundant non-methane hydrocarbon in the Earth’s atmosphere and an important precursor of tropospheric ozone through various chemical pathways. Ethane is also an indirect greenhouse gas (global warming potential), influencing the atmospheric lifetime of methane through the consumption of the hydroxyl radical (OH). Understanding the development of trends and identifying trend reversals in atmospheric ethane is therefore crucial. Our dataset consists of four series of daily ethane columns. As with many other decadal time series, our data are characterized by autocorrelation, heteroskedasticity, and seasonal effects. Additionally, missing observations due to instrument failure or unfavorable measurement conditions are common in such series. The goal of this paper is therefore to analyze trends in atmospheric ethane with statistical tools that correctly address these data features. We present selected methods designed for the analysis of time trends and trend reversals. We consider bootstrap inference on broken linear trends and smoothly varying nonlinear trends. In particular, for the broken trend model, we propose a bootstrap method for inference on the break location and the corresponding changes in slope. For the smooth trend model, we construct simultaneous confidence bands around the nonparametrically estimated trend. Our autoregressive wild bootstrap approach, combined with a seasonal filter, is able to handle all issues mentioned above (we provide R code for all proposed methods on https://www.stephansmeekes.nl/code.)., Horizon 2020 https://doi.org/10.13039/501100007601, Fonds De La Recherche Scientifique - FNRS https://doi.org/10.13039/501100002661

The subject of research is the theoretical and practical aspects of the definition and implementation of innovations, forms and directions of innovation in order to increase the competitiveness of rural green tourism enterprises. The aim of the work is to identify innovative sources of increasing the competitiveness of rural green tourism enterprises and substantiate the factors, components and tools for innovation in a knowledge economy, digital technologies, non-cash payments, high-speed Internet. The methodological basis of the article were the theoretical and methodological provisions of modern business economics, historical and monographic methods of scientific knowledge, as well as system-structural analysis and synthesis of the study of phenomena and processes, problem-based approach in justifying types, forms and directions of innovation. Results of work. The sources and offered components, directions and tools of introduction of innovations in work of the enterprises of rural green tourism, including in the form of organizational and administrative, marketing, product groups of them are revealed; in the form of IT startups, touring and digital systems and backup networks; timesharing, clustering, strategic alliances and clubs; smart Internet projects, software organization and management of the actual agro-villages and tourist enterprises in the countryside to increase their competitiveness. Field of application of results. Conclusions and results can be used in the work of rural green tourism enterprises, rural communities, public organizations, local governments; in the educational and scientific process of economic faculties of universities, colleges of tourist specialization, other institutions of higher education. Conclusions. Innovative activity in the system of strategic goals, priorities and guidelines for increasing the competitiveness of rural green tourism enterprises in the era of knowledge economy and digitalization will take a leading place. The realization of their important socio-economic functions, as well as other subjects of social life is becoming increasingly associated with an innovative type of development. In turn, it is based on a continuous and purposeful process of finding, preparing and implementing innovations. The possibility and motivation to obtain higher incomes and the need to increase the efficiency of financial and investment resources forces the participants of the tourism business in the countryside to purposefully create new tastes, interests and needs, introduce fundamentally new products, products, services and technologies. All this is also connected with the acceleration of innovation processes.

AIMS/HYPOTHESIS: This paper presents the relationship between islet autoantibodies, precursors of type 1 diabetes, and the development of persistent asthma, allergic rhinitis and atopic eczema. METHODS: A total of 2159 newborns who had a first-degree relative with type 1 diabetes and selected HLA genotypes were followed until the youngest participant reached 10 years of age. Islet cell antibodies (ICA) were detected using indirect immunofluorescence. Autoantibodies to insulin (IAA), GAD (GADA), the tyrosine phosphatase-related insulinoma-associated 2 molecule (IA-2A) and zinc transporter 8 (ZnT8A) were quantified with the use of specific radiobinding assays. As an ancillary study, the incidence of asthma, allergic rhinitis and eczema was assessed in 1106 of these children using the International Study of Asthma and Allergies in Childhood (ISAAC) core questionnaire when the children were 9–11 years old. HRs with 95% CIs were calculated to depict the incidence of these diseases following seroconversion to autoantibody positivity. RESULTS: The cumulative incidence of atopic eczema, allergic rhinitis and persistent asthma were 22%, 9% and 7.5%, respectively, by 9–11 years of age. The occurrence of diabetes-related autoantibodies showed a protective association with subsequently reported incidence of asthma and eczema. The incidence of rhinitis was not significantly related to the occurrence of IAA or GADA (statistical power was limited), but demonstrated the same inverse relationship as did the other diseases with ICA or when multiple autoantibodies first appeared together. CONCLUSIONS/INTERPRETATION: The findings add evidence to the relationships between these atopic diseases and diabetes-related autoimmunity and also suggest that, for eczema, the interaction depends upon which autoantibody appeared first. TRIAL REGISTRATION: ClinicalTrials.gov NCT00179777