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Purpose: Missense mutated von Hippel Lindau (VHL) protein (pVHL) maintains intrinsic function but undergoes proteasomal degradation and tumor initiation and/or progression in VHL disease. Vorinostat can rescue missense mutated pVHL and arrest tumor growth in preclinical models. We asked whether short-term oral vorinostat could rescue pVHL in central nervous system hemangioblastomas in patients with germline missense VHL. Patients and Methods: We administered oral vorinostat to 7 subjects (ages 46.0 ± 14.5 years) and then removed symptomatic hemangioblastomas surgically (ClinicalTrials.gov identifier NCT02108002). Results: Vorinostat was tolerated without serious adverse events by all patients. pVHL expression was elevated in neoplastic stromal cells compared with untreated hemangioblastomas from same patients. We found transcriptional suppression of downstream hypoxia-inducible factor (HIF) effectors. Mechanistically, vorinostat prevented Hsp90 recruitment to mutated pVHL in vitro. The effects of vorinostat on the Hsp90–pVHL interaction, pVHL rescue, and transcriptional repression of downstream HIF effectors was independent of the location of the missense mutation on the VHL locus. We confirmed a neoplastic stromal cell–specific effect in suppression of protumorigenic pathways with single-nucleus transcriptomic profiling. Conclusions: We found that oral vorinostat treatment in patients with germline missense VHL mutations has a potent biologic effect that warrants further clinical study. These results provide biologic evidence to support the use of proteostasis modulation for the treatment of syndromic solid tumors involving protein misfolding. Proteostasis modulation with vorinostat rescues missense mutated VHL protein. Further clinical trials are needed to demonstrate tumor growth arrest.

Advanced bladder tumor rarely metastasize to the skin. This is a result of intraperitoneal spread at least microscopically, determining a poor prognosis. We report 73 year old man who presented with skin lesion from pT2 urothelial carcinoma of the bladder. Skin biopsy revealed features of infiltrating urothelial carcinoma. In immunohistochemistry, proliferation expresses CK7 diffusely and CK20 more heterogeneously. It also expresses GATA3 expression of P63. Abdominal-pelvic CT reveled a focal thickening of the bladder dome on the right side of the body, extending over 6 cm and with a maximum thickness of 18 mm, with bilateral pyelocalic dilatation. Patient was referred to oncology for platinum-based chemotherapy. He had responded well to chemotherapy with stable lesions. In any patient followed for a bladder cancer, an atypical skin lesion should raise the alarm and make the patient seek a dermatological opinion for suspicion of a skin metastasis despite its rarity.

While innovation has evolved into a common concept for quite a few decades now, especially given the need for new forms of development that require technology transfer and creativity mechanisms, less so is the case of social innovation. The latter remains a rather controversial concept, caught between two extremes: some authors consider it to be useless for academic research given its vagueness, while others point to its sacrosanctity given the need for new ways of societal and political development. Knowledge-creation, idea generation and openness are mechanisms that any type of innovation relies upon. However, social innovation takes these concepts one step further and seeks to become a driving force for institutional change, therefore strongly linked with how liberal democracy works. The current paper aims to look at how social innovation is linked to the participative component of liberal democracy by looking at case studies from the European Union.

This work features preliminary results from a recent experimental campaign at IFIN-HH, Romania, aimed at measuring lifetimes of excited states in the neutron-rich 180Hf, by means of the RDDS technique. The 181Ta(11B,12C)180Hf proton pick-up reaction was used to populate excited states in the 180Hf nucleus. The ROSPHERE array loaded with 25 HPGe detectors was employed for the detection of the γ transitions depopulating the levels of interest. The array was coupled to the SORCERER particle detector and a plunger device enabling the study of p-γ and p-γ-γ coinciding events. Six different plunger foil distances were chosen, allowing for the construction of the decay curves of the observed γ transitions of interest, from which the corresponding level lifetimes can subsequently be deduced.

In this paper, we use attribute grammars as a formal approach for model checkers development. Our aim is to design an Alternating-Time Temporal Logic (ATL) model checker from a context-free grammar which generates the language of the ATL formulae. An attribute grammar may be informally defined as a context-free grammar which is extended with a set of attributes and a collection of semantic rules. We provide a formal definition for an attribute grammar used as input for Another Tool for Language Recognition (ANTLR) to generate an ATL model checker. The original implementation of the model-checking algorithm is based on Relational Databases and Web Services. Several database systems and Web Services technologies were used for evaluating the system performance in verification of large ATL models.

The energy-dispersive neutron spectra transmitted through single crystals are characterized by sharp Bragg dips at specific wavelengths, where Bragg's law is being fulfilled for certain crystallographic planes. This phenomenon allows for developing methods for crystal-orientation determination techniques similar to electron backscatter diffraction and X-ray diffraction microscopy. This work presents a new procedure to recover the orientation matrix for single crystals using transmission spectra recorded during rotation of a crystal about an axis perpendicular to a polychromatic neutron beam. The proposed method consists of an initial transformation of the as-collected wavelength–rotation maps to a wavevector K space, resulting in linear pseudo-Kossel lines that are suitable for analysis and indexing using image-processing procedures. Simulated neutron transmission spectra through a copper crystal with known orientations were used to set and prove the numerical approach. This technique may be expanded for cases where the neutron beam intersects multiple single-crystal grains with different orientations.

A new method to recover the orientation matrix of a single crystal with a known unit cell by analyzing synthesized pseudo-Kossel lines from time-of-flight neutron transmission data has been outlined in a companion article [Dessieux et al. (2023). J. Appl. Cryst. 56, https://dx.doi.org/10.1107/S1600576723001346; referred to here as Article I]. In this work, validation of this new technique is presented by employing experimental neutron transmission and diffraction measurements performed on two copper single-crystal specimens. Time-of-flight spectra were recorded during rotation (ω) of the single crystals about a vertical axis perpendicular to the incident neutron beam. The λ–ω maps recorded in transmission are utilized to determine the crystal orientation with respect to the neutron beam, following the procedure presented in Article I. To validate the indexing procedure, the crystal orientations are compared with those obtained via conventional methods using the diffraction data. The resulting pseudo-Kossel lines across the 2D detectors are also observed for the first time.

Presented here is a proof of concept demonstration of the templated grain growth (TGG) process for the development of [001]c fibre-textured Pb(ZrxTi1-x)O3 (PZT) ceramics. BaTiO3 platelets (5 and 10 vol.%) were selected to seed growth of highly oriented PZT grains resulting in texture fractions as high as 94%. The TGG process in PZT was observed to be critically dependent upon the addition of excess PbO liquid phase and may be driven by BaTiO3 dissolution into the matrix. Solid solution incorporation of BaTiO3 during sintering resulted in a structural shift away from the PZT morphotropic phase boundary (MPB) and a decrease in Curie temperature (TC) by ~ 40 °C which still exceeded > 300 °C. Modification of the Zr:Ti ratio in untextured ceramic analogues was explored as a strategy to tailor dielectric, ferroelectric, and electromechanical properties. An initial PZT matrix composition of Pb(Zr0.56Ti0.44)O3 resulted in a final bulk Pb0.947Ba0.053(Zr0.531Ti0.469)O3 ceramic having MPB-like properties of d33 = 453 pC/N, tan δ = 0.017, TC = 340 °C, and Ec = 9.3 kV/cm, which was observed to be similar to commercial ‘soft’ PZT-5A1.

This study aimed to examine the physical activity levels of the eligible students to study at the Faculty of Sports Sciences in the current academic year. A total of 200 students participated in the research as a result of the removal of the erroneous questionnaires from the questionnaires applied to 224 students who were eligible to attend the Faculty of Sports Sciences. The "International Physical Activity Questionnaire (IPAQ) short form was applied to the participants. While there was no significant difference according to the gender and body mass index variables values of the students who were entitled to study (p>0.05), a significant difference was found according to the sports branches, sports experience, and the departments they attend (p

Through our study, we studied the perception of the students of an economic faculty speciality which are at the end of their studies and who will soon become economists, and their attitude towards the cryptocurrencies. Their contacts inside or outside the university led to their professional development because they brought to their attention the widening of the sphere of finance through the prism of a new concept that appeared fifteen years ago, that of cryptocurrency. The main scope of the paper is to understand how students currently relate to cryptocurrencies, after going through all the subjects in the curriculum of their economic specialization. The methodology will involve the use of a structured interview. Important results of our study will be related to the fact that the female students interviewed, who, unlike almost all of the female students, are or say that they will be involved in trading cryptocurrencies in the near future and to the fact that an important part of their information regarding the cryptocurrencies is obtained from outside the faculty. We will recommend, knowing the current situation of the interviewed students, to the teachers who teach various disciplines in the specialization of which the interviewed students are part of that they could try, in the situation where the taught subjects allow it, to offer to the students who will come in the following years additional information about the cryptocurrencies.

Experimental models of a clinical, pathophysiological context are used to understand molecular mechanisms and develop novel therapies. Previous studies revealed better outcomes for spinal cord injury chronic ethanol-consuming patients. This study evaluated cellular and molecular changes in a model mimicking spinal cord injury (hypoxic stress induced by treatment with deferoxamine or cobalt chloride) in chronic ethanol-consuming patients (ethanol-exposed neural cultures (SK-N-SH)) in order to explain the clinical paradigm of better outcomes for spinal cord injury chronic ethanol-consuming patients. The results show that long-term ethanol exposure has a cytotoxic effect, inducing apoptosis. At 24 h after the induction of hypoxic stress (by deferoxamine or cobalt chloride treatments), reduced ROS in long-term ethanol-exposed SK-N-SH cells was observed, which might be due to an adaptation to stressful conditions. In addition, the HIF-1α protein level was increased after hypoxic treatment of long-term ethanol-exposed cells, inducing fluctuations in its target metabolic enzymes proportionally with treatment intensity. The wound healing assay demonstrated that the cells recovered after stress conditions, showing that the ethanol-exposed cells that passed the acute step had the same proliferation profile as the cells unexposed to ethanol. Deferoxamine-treated cells displayed higher proliferative activity than the control cells in the proliferation–migration assay, emphasizing the neuroprotective effect. Cells have overcome the critical point of the alcohol-induced traumatic impact and adapted to ethanol (a chronic phenomenon), sustaining the regeneration process. However, further experiments are needed to ensure recovery efficiency is more effective in chronic ethanol exposure.

Purpose Data was obtained from students from 39 universities in 24 countries, part of a large experiential exercise, X-Culture, who worked remotely in cross-cultural teams to solve business problems. The purpose of this study is to develop and test, using structural equation modeling, a conceptual model that identifies the determinants of satisfaction with teamwork. Design/methodology/approach Data was obtained from participants, students from universities from 39 universities in 24 countries, in a large experiential exercise, X-Culture, who worked remotely in cross-cultural teams to solve business problems. A conceptual model that identifies determinants of satisfaction with teamwork was developed and tested using structural equation modeling. Findings Satisfaction with teamwork is related to cultural intelligence (CQ), team identity and team climate. Interestingly, CQ of individual team members does not directly impact satisfaction with teamwork. Team identification and team climate, variables that require personal engagement and goodwill, mediate the effects of CQ on satisfaction. Originality/value Results suggest that team identification and team climate are important antecedents and explanatory mechanisms for developing satisfaction with teamwork. Having culturally intelligent team members is a necessary, but insufficient condition for satisfying teamwork. Therefore, to increase satisfaction with global virtual teamwork, teams need more than simply culturally intelligent team members. Increased satisfaction requires that team members identify with their team and develop a favorable team climate. The authors suggest education recommendations for global virtual teams.

The current global changes bring to the fore the importance of the innovation and digital transformation for economic development. Under the previous assumption, an objective evaluation of the economic growth discrepancies, considering the digitalization process, is required. The main goal of the present research is to analyse the economic growth of the European countries, based to the digitalization process, by using an input-output method. Under these circumstances, a Data Envelopment Analysis (DEA) was performed, considering the digitalization dimensions of DESI Index as input and the economic growth (annual %) as output. Based on the proposed model, the results highlighted the bidirectional relationship between economic growth and digitalization. Consistent with the research results, the European countries can be divided in two main categories: the efficient and the inefficient. On one hand, we can find the relatively efficient European states in terms of achieving the economic growth through digitalization (Ireland, Romania, Croatia and Greece). On the other hand, there is a numerous list of the inefficient ones, including important countries like Finland, Germany or France. Obviously, a remarkable aspect related to their situation is that, considering the national available inputs, an output maximization will be possible. According to the proposed model, the efficient countries can serve as peers or optimal benchmarks for solving the issue of relative inefficiency, by adapting and implementing their good practices.

Although noise from large fans has been extensively studied by the scientific community, few experimental studies have been performed on small-scale fans, where aerodynamic effects due to low Reynolds numbers needs be taken into account. For this reason, some preliminary experimental investigations have been carried out on cooling fans for automotive applications. The experimental campaign has been focused on the characterization of the flow outlet first, using a static Pitot on a 5.5-inch five-bladed fan, with and without its protective grid. After this preliminary phase, simultaneous measurements of velocity with hot-wire anemometry (HWA) and pressure fluctuations with microphones have been also carried out, the HWA probe being located downstream and two microphones positioned in the nearfield and far-field of the fan. The fan has been also studied at different working conditions, varying the rotational speed and applying specific fine grids at the intake, in order to well reproduce the presence of the cooler. Analyses in the time and frequency domain have been performed on the measured data, including cross-correlation between pressure and velocity signals, in order to find the main driving mechanisms that are related to the noise generation.

Efficient cloning techniques are a requirement for synthetic biology. This study provides a simplified cloning method based on Golden Gate Assembly that can be used for rapid vector construction. The building of multiple expression vectors with customizable modules is achieved in a timely manner with minimal hands-on time by removing unnecessary steps in the workflow. The authors constructed a total of 21 mammalian episomal expression vectors and conducted a fluorescence expression comparison for different regulatory region combinations post-transfection in HEK293T and HEPG2 cells. Screening revealed that using the EF-1α promoter in combination with the bovine growth hormone polyadenylation sequence seemed to perform best in the types of cells tested compared with other variants.

Growing interest in electric propulsion, together with the increased deployment of unmanned aerial vehicles, results in the consequent need for a clear understanding of the physical phenomena under propeller interactions which represent a primary noise source in multi-rotor configurations. To this purpose, the effect of rotor-to-rotor interactions of a twin pusher propeller configuration at static thrust conditions was experimentally investigated through aerodynamic and aeroacoustic measurement campaigns. The propellers tested refer to the APC-8x45MR rotor with an 8 inches diameter. The aerodynamics and aeroacoustics of several configurations were investigated using PIV technique, Pitot tube acquisitions, and microphone measurements performed in an anechoic environment. The propeller speed was varied within a typical range in the applications for both co-rotating and counter-rotating layouts. To define critical relative positions, many tip-to-tip separation distances were considered highlighting the general effects. Owing to the deformation exhibited by the rotor wakes due to their proximity, the pressure and velocity signals were conditioned to inspect the driving mechanisms responsible for the noise emission. Results provide a deeper insight into the physics involved and show different types of interaction effects on the fluid-dynamic field as a function of the propeller position, allowing the identification of the main critical configurations.

Background:Patient-reported outcome measures are commonly used to evaluate the effectiveness of treatments. CHD remains the most common congenital malformation. There has been a gradual shift in evaluating the outcome of surgery for CHD from mortality to morbidity and now to self-reported outcomes.Aims:We aimed to review studies assessing patient-reported outcome measures as a useful marker of outcome for patients, both children and adults, who underwent surgery for CHD.Methods:A systematic database search was conducted of original articles that explored the application of patient-reported outcome measures in the CHD surgical setting in PubMed and SCOPUS from inception to February 2022.Results:Our search yielded 1511 papers, of which six studies were included in this review after screening abstract and full-text, with a total sample size of 5734 patients. The main areas of discussion were the utility of patient-reported outcome measures, determinants of patient-reported outcome measures, and the need for a congenital cardiac surgery-specific patient-reported outcome measure for paediatric patients and their parents/guardians and adult patients.Conclusion:This systematic review reports the use of patient-reported outcome measures to be a useful indicator to gain insight into the patients’ perspective to provide holistic and patient-centred management. However, further studies are required to assess the utility of patient-reported outcome measures in a congenital cardiac surgical setting.

Macroalgal cultures are currently of great interest worldwide. Although along the Romanian Black Sea coast, there is no tradition in this sense, currently, a major interest in developing this direction exists, taking into consideration that the overexploitation of wild seaweed resources involves the disturbance of the marine environment, with implications that can sometimes be irreversible. Porphyra and Pyropia species (also known as nori algae) are considered the world’s most valuable mariculture algal products due to their high nutritional value and multiple active principles, considered unique representatives of marine algae. Considering these aspects, attention was focused on the only nori species from the Romanian Black Sea coast, namely, Pyropia leucosticta. The species was cultivated in controlled laboratory conditions for 5.5 months by manipulating its reproductive elements. The aim was to establish a simple, low-cost method by avoiding the complicated conchocelis phase of the species; therefore, reproduction and further species development were achieved by collecting the released neutral spores and isolating them in culture vessels, ensuring, at the same time, proper nutrient conditions, using sterile enriched seawater and mimicking ambient conditions. At the end of the experiment, specimens of almost 80−90 mm were obtained, making this method suitable for obtaining ex situ P. leucosticta blades on the Romanian Black Sea shore.

Traditionally, when making white wines, the musts are subjected to clarification and settling, even those from harvests in perfect phytosanitary condition. The increasingly perfected technical and technological procedures, involved in the operation of clarifying and deburring the musts, lead to the total removal of undesirable impurities, but also of the small fragments of skins and core, the only carriers of varietal aromas specific to each variety. In such situations, wines lacking fruitiness, aromatic "expressiveness" and varietal typicality result. In order to avoid such inconveniences, recently investigations have been intensified on the topic of improving white winemaking technologies, showing that the pellicular maceration is particularly appropriate, especially when the grapes are, at the time of harvesting, in a perfect state phytosanitary and are well matured. By applying pellicular maceration, notable results are obtained in the vinification of semi-aromatic (Sauvignon) and aromatic (Muscat Ottonel) grapes, but significant improvements were also obtained when using grapes of "neutral" aromatic varieties, such as those belonging to the Chardonnay variety.

Point-of-care ultrasonography (POCUS) is an established tool in the management of hypotensive patients in the emergency department (ED). We compared the diagnostic accuracy of a POCUS protocol versus standard assessment without POCUS in patients with undifferentiated hypotension.This was an international, multicenter randomized controlled trial included three EDs in North America and three in South Africa from September 2012 to December 2016. Hypotensive patients were randomized to early POCUS protocol plus standard care (POCUS group) or standard care without POCUS (control group). Initial and secondary diagnoses were recorded at 0 and 60 min. The main outcome was measures of diagnostic accuracy of a POCUS protocol in differentiating between cardiogenic and non-cardiogenic shock. Secondary outcomes were diagnostic performance for shock sub-types, as well as changes in perceived category of shock and overall diagnosis.Follow-up was completed for 270 of 273 patients. For cardiogenic shock, the POCUS-based diagnostic approach (POCUS) performed similarly to the non-POCUS approach (control) for specificity [95.5% (89.9-98.5) vs.93.8% (87.7-97.5)]; positive likelihood ratio (17.92 vs 14.80); negative likelihood ratio (0.21 vs 0.09) and diagnostic odds ratio (85.6 vs 166.57), with a similar overall diagnostic accuracy between the two approaches [93.7% (88-97.2) vs 93.6% (87.8-97.2)]. Diagnostic performance measures were similar across sub-categories of shock.This is the first randomized controlled trial to compare diagnostic performance of a POCUS protocol to standard care without POCUS in undifferentiated hypotensive ED patients. POCUS performed well diagnostically in undifferentiated hypotensive patients, especially as a rule-in test; however, performance did not differ meaningfully from standard assessment.RéSUMé: OBJECTIF: L'échographie au point d'intervention (POCUS) est un outil bien établi dans la gestion des patients hypotendus dans le service des urgences. Nous avons comparé la précision diagnostique d'un protocole POCUS par rapport à une évaluation standard sans POCUS chez des patients présentant une hypotension indifférenciée. MéTHODES: Il s'agissait d'un essai contrôlé randomisé international multicentrique incluant 3 services d'urgence en Amérique du Nord et 3 en Afrique du Sud de septembre 2012 à décembre 2016. Les patients hypotenseurs ont été répartis par randomisation selon le protocole POCUS précoce plus les soins standard (groupe POCUS) ou les soins standard sans POCUS (groupe témoin). Les diagnostics initiaux et secondaires ont été enregistrés à 0 et 60 minutes. Le principal résultat était la mesure de la précision diagnostique d'un protocole POCUS pour différencier le choc cardiogénique du choc non cardiogénique. Les résultats secondaires étaient la performance diagnostique pour les sous-types de chocs, ainsi que les changements dans la perception de la catégorie de choc et du diagnostic global. RéSULTATS: Le suivi a été complété pour 270 des 273 patients. Pour le choc cardiogénique, l'approche diagnostique basée sur le POCUS (POCUS) a donné des résultats similaires à l'approche non-POCUS (Contrôle) pour la spécificité (95,5 % (89,9–98,5) vs 93,8 % (87,7–97,5)) ; Rapport de vraisemblance positif (17,92 vs 14,80) ; Le rapport de vraisemblance négatif (0,21 vs 0,09) et le rapport de cotes diagnostiques (85,6 vs 166,57), avec une précision diagnostique globale similaire entre les deux approches (93,7 % (88–97,2) vs 93,6 % (87,8–97,2). Les mesures de performance diagnostique étaient similaires dans toutes les sous-catégories de choc. CONCLUSION: Il s'agit du premier essai contrôlé randomisé visant à comparer la performance diagnostique d'un protocole POCUS aux soins standard sans POCUS chez des patients hypotendus indifférenciés aux urgences. La POCUS a donné de bons résultats diagnostiques chez les patients hypotendus indifférenciés, surtout en tant que test de référence ; cependant, les performances ne diffèrent pas de manière significative de l'évaluation standard.

Our paper examines the manner in which public opinion is affected by public communication in a very specific situation. The conflict in Ukraine has been on everyone’s mind for the last three months not only due to its unreasonableness but also due to the Ukrainians mastery of communicating to the public, be it national or international. As the conflict has grown stronger in its intensity so has the public communication on the Ukrainian side which took any given chance to address the international political scene through President Volodymyr Zelenski’s speeches in front of numerous Parliaments. While scrutinising the Ukrainian manner of communicating information and asking for humanitarian, financial and military aid, we will also inspect the manner in which the Russian side communicates. We will look into the effect that these addresses have had on the public opinion. The theoretical background of the paper includes the views on public opinion of Gabriel Tarde, Pierre Zémor’s definition of public communication as well as Jürgen Habermas’ communicative theory. These theories will assist us in our research to demonstrate which side communicates the better and which has the ability to use cultural references that support their message. Our paper studies an ongoing military conflict, i.e. the data that we have included so far could be interpreted differently later.

Interplanetary space missions require spacecraft autonomy in order to fulfill the mission objective. The fault detection and isolation (FDI) system increases the level of autonomy and can ensure the safety of the spacecraft by detecting and isolating potential faults before they become critical. The proposed FDI system is based on an innovative bank of SMOs (sliding mode observers), designed for different fault scenarios cases. The FDI system design aims to detect and isolate actuators and measurement units’ faults used by the satellite control system and considers the nonlinear model of the satellite dynamics. This approach gives the possibility of fault reconstruction based on the information provided by an equivalent injection signal, allowing to reconstruct external perturbances and faults. The SMO chattering phenomenon is avoided by using the pseudo-sliding function, being a linear approximation of the signum function, which gives the possibility of using the equivalent injection signal for fault reconstruction purposes. The proposed fault reconstruction methodology is illustrated by a case study for a 6U Cubesat.

Considering the debates regarding population migration from rural areas, the purpose of this study is to analyze socio-economic indicators to identify the main challenges of rural areas in Romania as well as to identify solutions to ensure the development of the Romanian rural environment. Our research aims to present the socioeconomic consequences of the rural population's migration by analyzing indicators such as the population by domicile by residence, the average age of the population by domicile, the flow of internal urban and rural migration, the population activity rate, the employed population per economic activities, and the total average monthly income obtained by a rural person. In addition, at the end of the study, a Pearson correlation was made with the help of the SPSS software, which identified the link between income from agriculture and the number of people working in agriculture. The results obtained indicated that while the number of people employed in agriculture, forestry, and fishing is decreasing, the average total income from agriculture is increasing. On the other hand, the migration of the population from the rural area to the urban area is on average about 82 thousand people and the rural population is in a continuous decrease, while the average age registered in the rural area is higher compared to the average age registered in urban areas.

There are several choices for the correction of complex transposition of the great arteries and double outlet right ventricle not amenable to the Rastelli-type surgery, but outcome data are limited to small series. This study aims to report results after the aortic root translocation and en bloc rotation of the outflow tract procedures.This is a retrospective, multicentric, observational study. Clinical, anatomy, procedural, and detailed follow-up data (median, 4.43 years) were collected.A total of 70 patients (62.9% male; median age, 1 year; range 4 days to 12.4 years) were included: n = 43 in the aortic root translocation group and n = 27 in the en bloc rotation group. Those in the aortic root translocation group were older (P = .01) and more likely to have had previous procedures (P .0001), but cardiac anatomy was similar in both groups. Aortic root translocation and en bloc rotation early mortality (30 days) was similar (4.7% vs 3.7%, P = .8). Late survival and freedom from any cardiac reintervention were 92.7% and 16.9% at 15 years overall, respectively. Freedom from right ventricular outflow tract/conduit reintervention was better in the en bloc rotation group than in the aortic root translocation group (100% vs 24.5%, P = .0003), but more patients in the en bloc rotation group had moderate (or worse) aortic valve regurgitation during follow-up (16% vs 2.6%, P = .07).Both aortic root translocation and en bloc rotation are valuable surgical options for the treatment of complex transposition of the great arteries and double outlet right ventricle. In the en bloc rotation group, there was better freedom from right ventricular outflow tract reinterventions, but a higher probability of aortic valve regurgitation. Identifying the main driving forces for these observed differences requires further study of these procedures.

Clearance of jaundice (CoJ) is the first key objective of Kasai portoenterostomy (KPE) for biliary atresia (BA) and its achievement is by far the best index of long-term prognosis. We sought to identify the reasons for failure [subsequent liver transplant (LT)] in this cohort.Review of single-center prospective BA database. Successful KPE was defined by achieving a postoperative bilirubin of ≤20 µmol/L. Pre-KPE and post-KPE variables were identified together with a multivariate logistic regression model to identify those observable at 3 months post-KPE. Data are quoted as median (range). A P value of ≤0.05 was significant.One hundred thirty-five infants underwent KPE between January 2012 and December 2018, of which 90 (67%) achieved CoJ. From these 20 (22%) (Cohort A) underwent LT with the remainder continuing with native liver (Cohort B) (median follow-up of 4.15 years). There was no difference in age at KPE (P = 0.41), APRi (aspartate aminotransferase-to-platelet ratio) (P = 0.07), associated anomalies (P = 0.7), and cytomegalovirus status (P = 0.7) between the 2 groups. Postoperatively, both cholangitis [any episode, 18/20 (90%) vs 15/70 (21%); P0.0001] and portal hypertension (PHT) [gastrointestinal (GI) bleed, 10/20 (50%) vs 2/70 (2.8%); P0.0001] were significantly more common in cohort A. Univariate analysis showed that the most significant predictive values at 3 months for LT by 2 years were high APRi, bilirubin, international normalized ratio, and ultrasound (US)-detected ascites with multivariate logistic modeling confirming these variables with predictive values of r2 = 0.79, AUROC = 0.98.Failure is not preordained at KPE but due to recurrent cholangitis and/or symptoms of PHT.

Liver transplant recipients (LTRs) frequently develop biliary complications, and endoscopy is crucial for their subsequent management. Recently, single-operator video cholangioscopy (SOVC) with digital imaging quality was introduced. This study evaluated the utility of digital SOVC for the management of biliary complications in LTRs.This observational study retrospectively analyzed all LTRs undergoing digital SOVC between 2015 and 2019 at a tertiary referral center. Endpoints included the assessment of biliary strictures, performance of selective guidewire passage across biliary strictures, and diagnosis and treatment of biliary stone disease.In total, 79 digital SOVCs performed in 50 LTRs were identified. Fifty-eight percent of the procedures were performed for biliary stricture assessment, and using visual signs or guided biopsies, SOVC excluded malignancy in all cases (100%). Of all the examinations, 29.1% (23/79) were performed solely because of a previous failure of conventional endoscopic methods to pass a guidewire across a biliary stricture. Using SOVC, guidewire passage was successfully performed in 73.9% of these examinations, enabling subsequent endoscopic therapy. Furthermore, biliary stones were found in 16.5% (13/79) of the examinations. In 38.5% of these cases, standard fluoroscopy failed to detect stones, which were only visualized using digital SOVC. Biliary stone treatment was successful in 92% (12/13) of the examinations. Complications occurred in 11.4% of all SOVCs. No procedure-associated mortalities were observed.Digital SOVC is effective and safe for the endoscopic management of biliary complications in LTRs and offers unique diagnostic and therapeutic opportunities that strongly impact the clinical course in selected cases.

The purpose of this paper is to evaluate the behaviour of 3D printed honeycomb structures under low velocity impact loading for their use in energy absorption applications. Additive manufacturing technologies are part of a growing field that represents high interest for industries such as aerospace, automotive and naval. This paper aims to determine the mechanical properties of a 3D printed polymer - Polylactic Acid (PLA) manufactured by FDM (Fused Deposition Modelling) technology. In this regard, first the material is characterized by low velocity impact dynamic experimental tests. A finite Element Analysis (FEA) is performed in LS-Dyna software in order to validate the results. The samples were manufactured by varying the infill percent to investigate the influence of different parameters on a batch of samples for every configuration. The 3D CAD modelling for impact tests samples were performed in Catia V5. Among wide range of cellular structures, honeycomb non-auxetic hexagonal cell pattern was selected in this study, assuring high strength/weight ratio. The amount of energy absorbed during the impact, the failure and degradation of the impacted specimens were monitored, following the analysis of experimental and numerical data. A fair agreement was obtained between experimental and numerical results, showing that honeycomb developed lightweight structures exhibits a proper energy absorption capacity, with a mechanism of release similar to metal or composite materials honeycombs.

Corruption is one of the plagues of the modern world that is characteristic especially of the economic, administrative, and political areas. The history of civilization shows us that this phenomenon has existed in the world since the beginning. Still, depending on the era and the measures taken against it, it was more or less developed. From an economic perspective, it is considered to be particularly harmful because it constitutes an obstacle to the healthy, prosperous, and fair development of a nation. In our era, the phenomenon of globalization has acquired very strong valences, unfortunately, and corruption has acquired an impressive development, ripping the fruits of global deepening, especially now that we are also talking about corruption manifested across borders when it affects or is promoted by multinational companies. Of course, the phenomenon of corruption cannot be completely eradicated and there is no country in the world that can boast of such a performance, but firm measures are needed to limit and stop it. Romania has been dealing with this phenomenon for a long time, and the legislative measures, the political will and the pressures of the European institutions should aim, in the medium term, to reduce it. The present article evokes the terminological aspects of the phenomenon of corruption, analyzing its causes and possible solutions, but also a perspective of mathematical modeling of its progression. The study’s novelty is given by the deepening of the corruption phenomenon in light of the opportunities offered by the new paradigm of the globalization phenomenon.

Item does not contain fulltext BACKGROUND: Etrolizumab is a gut-targeted anti-β7 integrin monoclonal antibody. In a previous phase 2 induction study, etrolizumab significantly improved clinical remission versus placebo in patients with moderately to severely active ulcerative colitis. We aimed to compare the safety and efficacy of etrolizumab with infliximab in patients with moderately to severely active ulcerative colitis. METHODS: We conducted a randomised, double-blind, double-dummy, parallel-group, phase 3 study (GARDENIA) across 114 treatment centres worldwide. We included adults (age 18-80 years) with moderately to severely active ulcerative colitis (Mayo Clinic total score [MCS] of 6-12 with an endoscopic subscore of ≥2, a rectal bleeding subscore of ≥1, and a stool frequency subscore of ≥1) who were naive to tumour necrosis factor inhibitors. Patients were required to have had an established diagnosis of ulcerative colitis for at least 3 months, corroborated by both clinical and endoscopic evidence, and evidence of disease extending at least 20 cm from the anal verge. Participants were randomly assigned (1:1) to receive subcutaneous etrolizumab 105 mg once every 4 weeks or intravenous infliximab 5 mg/kg at 0, 2, and 6 weeks and every 8 weeks thereafter for 52 weeks. Randomisation was stratified by baseline concomitant treatment with corticosteroids, concomitant treatment with immunosuppressants, and baseline disease activity. All participants and study site personnel were masked to treatment assignment. The primary endpoint was the proportion of patients who had both clinical response at week 10 (MCS ≥3-point decrease and ≥30% reduction from baseline, plus ≥1-point decrease in rectal bleeding subscore or absolute rectal bleeding score of 0 or 1) and clinical remission at week 54 (MCS ≤2, with individual subscores ≤1); efficacy was analysed using a modified intention-to-treat population (all randomised patients who received at least one dose of study drug). GARDENIA was designed to show superiority of etrolizumab over infliximab for the primary endpoint. This trial is registered with ClinicalTrials.gov, NCT02136069, and is now closed to recruitment. FINDINGS: Between Dec 24, 2014, and June 23, 2020, 730 patients were screened for eligibility and 397 were enrolled and randomly assigned to etrolizumab (n=199) or infliximab (n=198). 95 (48%) patients in the etrolizumab group and 103 (52%) in the infliximab group completed the study through week 54. At week 54, 37 (18·6%) of 199 patients in the etrolizumab group and 39 (19·7%) of 198 in the infliximab group met the primary endpoint (adjusted treatment difference -0·9% [95% CI -8·7 to 6·8]; p=0·81). The number of patients reporting one or more adverse events was similar between treatment groups (154 [77%] of 199 in the etrolizumab group and 151 [76%] of 198 in the infliximab group); the most common adverse event in both groups was ulcerative colitis (55 [28%] patients in the etrolizumab group and 43 [22%] in the infliximab group). More patients in the etrolizumab group reported serious adverse events (including serious infections) than did those in the infliximab group (32 [16%] vs 20 [10%]); the most common serious adverse event was ulcerative colitis (12 [6%] and 11 [6%]). There was one death during follow-up, in the infliximab group due to a pulmonary embolism, which was not considered to be related to study treatment. INTERPRETATION: To our knowledge, this trial is the first phase 3 maintenance study in moderately to severely active ulcerative colitis to use infliximab as an active comparator. Although the study did not show statistical superiority for the primary endpoint, etrolizumab performed similarly to infliximab from a clinical viewpoint. FUNDING: F Hoffmann-La Roche.

Copyright © 2022 The Authors. This is an open access article under the CC BY-NC-ND license. Peer review under responsibility of International Federation of Automatic Control. Systems with elements linked via a communication network are vulnerable to communication problems and attacks of malicious agents, with potentially harmful consequences for performance and stability. This paper proposes a stochastic Model Predictive Control (MPC) scheme to deal with two different sources of uncertainties simultaneously, namely, packet losses and external disturbances. In particular, the controller deals with packet losses using a tree-based approach and is robustified against external disturbances using a multiple scenario approach. Finally, the algorithm performance is compared via simulation with other MPC alternatives and a feedback control law.

ispartof: Forever Young: Celebrating 50 years of the World Heritage Convention pages:11-13 ispartof: vol:I pages:11-13 status: published

The intrathecally administered antisense oligonucleotide tofersen reduces synthesis of the superoxide dismutase 1 (SOD1) protein and is being studied in patients with amyotrophic lateral sclerosis (ALS) associated with mutations in SOD1 (SOD1 ALS).In this phase 3 trial, we randomly assigned adults with SOD1 ALS in a 2:1 ratio to receive eight doses of tofersen (100 mg) or placebo over a period of 24 weeks. The primary end point was the change from baseline to week 28 in the total score on the ALS Functional Rating Scale-Revised (ALSFRS-R; range, 0 to 48, with higher scores indicating better function) among participants predicted to have faster-progressing disease. Secondary end points included changes in the total concentration of SOD1 protein in cerebrospinal fluid (CSF), in the concentration of neurofilament light chains in plasma, in slow vital capacity, and in handheld dynamometry in 16 muscles. A combined analysis of the randomized component of the trial and its open-label extension at 52 weeks compared the results in participants who started tofersen at trial entry (early-start cohort) with those in participants who switched from placebo to the drug at week 28 (delayed-start cohort).A total of 72 participants received tofersen (39 predicted to have faster progression), and 36 received placebo (21 predicted to have faster progression). Tofersen led to greater reductions in concentrations of SOD1 in CSF and of neurofilament light chains in plasma than placebo. In the faster-progression subgroup (primary analysis), the change to week 28 in the ALSFRS-R score was -6.98 with tofersen and -8.14 with placebo (difference, 1.2 points; 95% confidence interval [CI], -3.2 to 5.5; P = 0.97). Results for secondary clinical end points did not differ significantly between the two groups. A total of 95 participants (88%) entered the open-label extension. At 52 weeks, the change in the ALSFRS-R score was -6.0 in the early-start cohort and -9.5 in the delayed-start cohort (difference, 3.5 points; 95% CI, 0.4 to 6.7); non-multiplicity-adjusted differences favoring early-start tofersen were seen for other end points. Lumbar puncture-related adverse events were common. Neurologic serious adverse events occurred in 7% of tofersen recipients.In persons with SOD1 ALS, tofersen reduced concentrations of SOD1 in CSF and of neurofilament light chains in plasma over 28 weeks but did not improve clinical end points and was associated with adverse events. The potential effects of earlier as compared with delayed initiation of tofersen are being further evaluated in the extension phase. (Funded by Biogen; VALOR and OLE ClinicalTrials.gov numbers, NCT02623699 and NCT03070119; EudraCT numbers, 2015-004098-33 and 2016-003225-41.).

The emergence of trust and solidarity is arguably foundational for economic development and social order. Yet many studies, often survey-based, document large disparities in general trust and social cohesion between countries. Can mutual trust and solidarity arise between people even in areas of low general trust, or do national cultural contexts block such connections? We report an experimental investigation of the dynamic between national environments and local social interactions, specifically those embedded in social exchange. Results of our experiments conducted in the United States and Romania, societies marked by relatively high and low general trust, respectively, show that while national context impacts the level of relational trust formed within dyads, only this emergent relational trust affects dyadic solidarity in both societies. Importantly, burgeoning solidarity has persistent consequences for future exchanges and subsequent solidarity, thus experimentally demonstrating critical linkages between macro- and micro-level precursors to social order.

Background and aim. Modern society is experiencing an accelerated increase in the number of elderly people, to the detriment of children and young adults, in the context of declining birth rates, high adult mortality and increasing life expectancy due to advances in medicine. Cardiovascular diseases are becoming more common in the general population, representing the leading cause of death, being responsible for a third of the total number of deaths worldwide, and heart failure is the most common cause of hospitalization in patients over 65 years. Depression is one of the most common mental illnesses, presents different clinical pictures, which vary from person to person and in relation to age, being shown that there are somatic disorders due to depression, including cardiovascular disease. Materials and method. We studied 127 patients hospitalized in the Geriatrics Department of the Calarasi County Emergency Hospital, diagnosed with heart failure (HF), being divided into 2 groups: the first group, which included 63 patients with heart failure with mildly reduced ejection fraction and the second, which included 64 patients with heart failure with preserved ejection fraction. Results. The main risk factor present in the studied patients was dyslipidemia, which is present in 90% of patients with a mildly ejection fraction and in 88% of patients with a preserved ejection fraction. Hypertension was also present in 75% of patients in the first group and in 63% of those in the second group. Depression was present in 67% of patients with mildly reduced ejection fraction and in 64% of those with preserved ejection fraction. The degree of depression was higher among women, 11% of those with HF with mildly reduced ejection fraction and 14% of those with preserved ejection fraction had major depression. The degree of depression increases with age, patients over 80 years presented predominantly moderate-severe depression (41% of patients in the first group, and 50% in the second). Patients with NYHA class III heart failure had predominantly moderate-to-severe depression: 50% of patients with mildly reduced ejection fraction and 67% of those with preserved ejection fraction. Conclusion. Depression is an important independent risk factor for heart failure in the elderly patients. Due to the fact that the symptoms of the two pathologies are often similar, the diagnosis of depression can be difficult to make, which is why it should be investigated in all patients with heart failure. It is important to understand the peculiarities of the polypathology of the elderly, which often poses problems for the diagnosis and treatment of the clinician.