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Abstract Introduction Dimethyl fumarate (DMF) has demonstrated a favorable benefit–risk profile in patients with relapsing–remitting multiple sclerosis (RRMS) in clinical and real-world studies. The ESTEEM study (NCT02047097) was conducted to assess the long-term safety and effectiveness of delayed-release DMF in patients with relapsing forms of MS in routine clinical practice. We report final outcomes from ESTEEM with up to 6.5 years of follow-up. Methods Patients newly prescribed DMF were recruited from 393 sites globally. The primary objective was to assess the incidence and type of serious adverse events (SAEs) and adverse events (AEs) leading to discontinuation of DMF. Secondary objectives included assessment of DMF effectiveness on annualized relapse rate (ARR) and patient-reported outcomes (PROs). Results Overall, 5124 patients received ≥ 1 dose of DMF. The mean (standard deviation [SD]) age at enrollment was 40.0 (11.2) years; 74% of patients were female. Patients received DMF for a mean (SD) duration of 31.0 (22.7) months. Primary reasons for discontinuation were AEs (n = 1237; 24%); the most common were gastrointestinal AEs (n = 469; 9%), blood and lymphatic disorders (n = 218; 4%), and vascular disorders (n = 200; 4%). SAEs occurred in 391 (8%) patients, most commonly infections and infestations (n = 102; 2%). Adjusted ARR declined by 90% (95% confidence interval [CI]: 90–91%; p

Abstract Introduction Treatment persistence and adherence are essential for achieving therapeutic goals in patients with multiple sclerosis (MS). OroSEP is an independent patient-support program (PSP) in France for patients with relapsing–remitting MS (RRMS) receiving oral disease-modifying therapies. Methods TEC-ADHERE (NCT04221191; 08/19/2019–09/15/2022) was a prospective, non-interventional, phase 4 study to assess the effect of OroSEP on persistence and adherence to dimethyl fumarate (DMF; Tecfidera™) in patients with RRMS. Outcomes were compared for patients in OroSEP versus non-OroSEP patients who received their neurologists’ standard of care (SoC). Patients initiated DMF at month 0 (M0); follow-up visits occurred at M3 and M6. Primary outcome was persistence at M6. Secondary outcomes included persistence at M1 and M3, adherence at M6 (Girerd questionnaire), anxiety (Generalized Anxiety Disorder Assessment), patient satisfaction at M6 (Treatment Satisfaction Questionnaire for Medication), patient and neurologist satisfaction with OroSEP participation, and adverse events (AEs). Results Per-protocol population included 341 patients (OroSEP, n = 135; SoC, n = 206). Persistence was similar for OroSEP vs SoC (M6, 75.9% vs 76.6%; M1, 96.0% vs 92.4%; M3, 85.5% vs 89.0%). At M6, mean adherence was higher for OroSEP (5.4) vs SoC (4.7; p

Mitxelenak (1981) euskalki guztiek abiapuntua v.-vi. mendeetan kokatu beharreko éuscaro batean zutela proposatu zuenetik, oparoa izan da EBZ honen ezaugarriak berreraikitzen jardun duten ekarpenak. Lan honetan, Hualderen (2015: 131) diagrama ezagunetik abiatuz, auzi honen kanpoko aspektuei ekingo zaie. Elementu historikoen eta linguistikoen korrelazioen bidez, EBZa eta MEZa prozesu historikoekiko loturak ezartzeko saio bat egingo da. EBZa eta akitanieraren arteko harremana ere eztabaidatuko da.

The integration of Wide Bandgap (WBG) semiconductors has enhanced the performance of switching power supplies in terms of both efficiency and power density. However, the fast-switching dynamics of these devices, particularly in Gallium Nitride (GaN) semiconductors, amplify the impact of parasitic elements in the circuit, demanding new methods and tools in power converter design. To address this problem, a multi-objective design method for a GaN-based isolated DC-DC converter is presented, complemented by an analytical Double Pulse Test (DPT) model. This method is applied to select the optimal components and switching frequency for a push-pull converter, resulting in the design of a GaN-based step-up DC-DC converter. The analytical estimations for power losses and overvoltage are validated through a GaN-based push-pull prototype. The design achieves an efficiency of 93% under nominal conditions, with a power density of 2.23 W/cm3, and a total component cost of 17.5 € for the magnetics, capacitors, and semiconductors. This approach not only demonstrates significant improvement in terms of efficiency, volume, and cost compared to silicon-based isolated DC-DC converters but also offers a promising design methodology to improve isolated DC-DC converters in modern power conversion applications.

The railway industry is continuously evolving, necessitating the development of more intricate and dependable software algorithms. To meet these requirements, the creation of new validation tools has become increasingly crucial, with a specific focus on Hardware-In-the-Loop (HIL) simulations. HIL simulations are invaluable during the product development process as they improve system resilience, performance, and overall product value. This study details the design of a HIL platform that can validate the software created for the Traction Control Unit (TCU) of a complex traction system. By producing real interfaces in real-time, this platform offers a practical simulation environment for examining the TCU software. The HIL platform built in this research provides comprehensive test coverage of the TCU software, a feat that is often unattainable through on-train testing. Moreover, the platform provides greater tuning and debugging capabilities, allowing for a virtual certification of the TCU software, which can offer greater security and assurances of success when encountering official tests. Thus, this paper demonstrates how profitable a HIL platform that models the whole traction system can be in order to debug and certificate its TCU software.

The increase in agricultural data has created a need for developing tools that can manage, share, and visualise this information, while also being accessible to farmers. The use of different technical languages, varying needs, and differing objectives for the tools being developed and used creates a gap between technology developers and farmers, leading to inefficient information transfer. Consequently, interfaces are often poorly adapted to the real needs of end-users and lack essential functionality. This white paper aims to propose a User-Centred Design methodology in order to address the challenges encountered in creating interfaces for shared agricultural Data Space Ecosystems. The proposed methodology, an adaptation of ISO 9241:210-2019, highlights the importance of user participation at various stages of the interface design cycle for the creation of user-adaptive technologies.

Diabetic cardiomyopathy (DCM) is a major complication of type 2 diabetes mellitus (T2DM) that leads to significant morbidity and mortality. The alteration in the signaling mechanism in diabetes leading to cardiomyopathy remains unclear. The purpose of this study is to investigate the role of tauopathy in myocardial dysfunction observed in T2DM. In that regard, diabetic Sprague Dawley rats were treated with intraperitoneal injections of lithium chloride (LiCl), inhibiting tau phosphorylation. Cardiac function was evaluated, and molecular markers of myocardial fibrosis and the TGF-β signaling were analyzed. T2DM rats exhibited a decline in ejection fraction and fractional shortening that revealed cardiac function abnormalities and increased myocardial fibrosis. These changes were associated with tau hyperphosphorylation. Treating diabetic rats with LiCl attenuated cardiac fibrosis and improved myocardial function. Inhibition of GSK-3β leads to the suppression of tau phosphorylation, which is associated with a decrease in TGF-β expression and regulation of the pro-inflammatory markers, suggesting that tau hyperphosphorylation is parallelly associated with fibrosis and inflammation in the diabetic heart. Our findings provide evidence of a possible role of tau hyperphosphorylation in the pathogenesis of DCM through the activation of TGF-β and by inducing inflammation. Targeting the inhibition of tau phosphorylation may offer novel therapeutic approaches to reduce DCM burden in T2DM patients.

En este informe se tratan los aspectos lingüísticos de la mano de Irulegi, y a la vez se contextualiza en su ámbito «vascónico» y en su relación con el euskera histórico. La inscripción debe contener gramática en una lengua no indoeuropea. Sin embargo, dejando a un lado el s.o.r.i.o.n inicial (probablemente compuesto de dos palabras paleoeuskéricas), para ningún otro elemento puede asegurarse una filiación paleoeuskérica. Se defiende también que, incluso aunque la mano de Irulegi estuviera en paleoeuskera, la documentación bajoimperial apunta a una discontinuidad entre cualquier lengua prerromana hablada en el territorio vascónico y el euskera histórico que emerge en la Alta Edad Media.

Sr. Editor: Se presenta el caso de un paciente de 57 años con antecedentes de radiación torácica en la adolescencia por un linfoma de Hodgkin torácico. Presenta además enfermedad pulmonar intersticial no filiada y bocio endotorácico con desplazamiento traqueal que condiciona una vía aérea difícil. En 2014 se le diagnosticó un síndrome coronario crónico y se le realizó revascularización percutánea completa en la coronaria derecha. Los ecocardiogramas mostraron estenosis aórtica mitral grave secundaria a calcificación valvular sin estigmas de enfermedad reumática, con función sistólica conservada e hipertensión pulmonar grave. El paciente desarrolló progresivamente clínica de insuficiencia cardiaca, por lo que se indicó una sustitución valvular aórtica. Ante la evidencia de aorta de porcelana, se decidió el implante percutáneo de una prótesis aórtica (TAVI), modelo Edwards SAPIEN 23 mm (Edwards Lifescience, Estados Unidos) por acceso femoral bajo sedación profunda. No hubo complicaciones al alta. En seguimiento en consulta de valvulopatías, su disnea fue empeorando (clase III de la New York Heart Association [NYHA]). Las pruebas complementarias confirmaron la progresión de la estenosis mitral. Mediante ecocardiograma transtorácico (ETT) y transesofágico (ETE) se visualizó una calcificación anular mitral extensa que condicionaba estenosis mitral grave (gradiente medio de 15 mmHg), sin insuficiencia, ventrículo derecho ligeramente dilatado con...

To the Editor, This is the case of a 57-year-old man with a past medical history of thoracic radiation in his adolescence in the context of Hodgkin’s lymphoma. The patient also has unclassified interstitial lung disease and endothoracic goitre with tracheal displacement creating a difficult airway. Back in 2014, the patient was diagnosed with chronic coronary syndrome and complete percutaneous revascularization of right coronary artery was achieved. The echocardiograms revealed the presence of severe mitral valve stenosis due to valve calcification without signs of rheumatic disease, preserved systolic function, and severe pulmonary hypertension. The patient started showing progressive signs of heart failure, and aortic valve replacement was indicated. Given the evidence of porcelain aorta, transcatheter aortic valve implantation (TAVI) was decided using a 23 mm Edwards SAPIEN valve (Edwards Lifesciences, United States) under deep sedation via femoral access. No complications were reported at discharge. Follow-up in the valve clinic showed progressive worsening of dyspnea (New York Heart Association [NYHA] class III). Additional tests confirmed the progression of mitral stenosis. The transthoracic (TTE) and transesophageal (TEE) echocardiography confirmed the presence of extensive mitral annular calcification (MAC) causing severe mitral stenosis (mean gradient, 15 mmHg) without regurgitation, mild right ventricular dilatation with preserved function, and...

Prosthetic joint infections are considered difficult to treat they needing aggressive surgery and long antimicrobial treatments. However, the exact duration of these therapies has been established empirically. In the last years, several studies have explored the possibility of reducing the length of treatment in this setting, with conflicting results. In this narrative review, we critically appraise the published evidence, considering the different surgical approaches (implant retention [DAIR] and one-step and two-step exchange procedures) separately. In patients managed with DAIR, usually treated for at least 12 weeks, a large, randomized trial failed to show that 6 weeks were non-inferior. However, another randomized clinical trial supports the use of 8 weeks, as long as the surgical conditions are favorable and antibiotics with good antibiofilm activity can be administered. In patients managed with a two-step exchange procedure, usually treated during 6 weeks, a randomized clinical trial showed the efficacy of a 4-week course of antimicrobials. Also, the use of local antibiotics may allow the use of even shorter treatments. Finally, in the case of one-step exchange procedures, there is a trend towards reducing the length of therapy, and the largest randomized clinical trial supports the use of 6 weeks of therapy.

ABSTRACT: Objectives: To investigate the impact of the time-to-positivity of blood cultures (TTP) on 30-day mortality in patients with Pseudomonas aeruginosa bacteremia. Methods: All nonduplicated episodes of P. aeruginosa monomicrobial bacteremia in adult patients from January 2013 to February 2020 were analysed. Epidemiological and clinical data were collected. TTP of blood cultures for P. aeruginosa isolates was automatically recorded. Multivariate analysis identified factors predicting 30-day overall mortality. Results: A total of 328 patients were identified. The median TTP for P. aeruginosa isolates was 15 h (interquartile range [IQR] 12–18 h). All multidrug-resistant and extensively drug-resistant (MDR/XDR) episodes were positive within the first 36 h. The 30-day mortality rate was 32.3%. The best cut-off value of the TTP for predicting mortality was 16 h (area under the receiver operating characteristic curve 0.62, 95% confidence interval [CI] 0.56–0.67, P = 0.001). The 30-day mortality rate was significantly higher in the TTP ≤16 h group (41.0% vs. 19.5%, P < 0.001). In a multivariate analysis, severe neutropenia (adjusted odds ratio [aOR] 2.67, 95% CI 1.4–5.09, P = 0.002), septic shock (aOR 3.21, 95% CI 1.57–5.89, P < 0.001), respiratory source (aOR 4.37, 95% CI 2.24–8.52, P < 0.001), nosocomial acquisition (aOR 1.99, 95% CI 1.06–3.71, P = 0.030), TTP ≤16 h (aOR 2.27, 95% CI 2.12–4.25, P = 0.010), and MDR/XDR phenotype (aOR 2.54, 95% CI 1.38–4.67, P = 0.002) were independently associated with 30-day mortality. Conclusions: A short TTP (≤16 h) was independently associated with increased 30-day mortality. After local validation, this routinely available microbiological parameter might be useful for guiding empirical antipseudomonal therapies and supporting the close monitoring of patients with P. aeruginosa bacteremia.

Abstract Aggregated community-scale data could be harnessed to provide insights into the disparate impacts of managed power outages, burst pipes, and food inaccessibility during extreme weather events. During the winter storm that brought historically low temperatures, snow, and ice to the entire state of Texas in February 2021, Texas power-generating plant operators resorted to rolling blackouts to prevent collapse of the power grid when power demand overwhelmed supply. To reveal the disparate impact of managed power outages on vulnerable subpopulations in Harris County, Texas, which encompasses the city of Houston, we collected and analyzed community-scale big data using statistical and trend classification analyses. The results highlight the spatial and temporal patterns of impacts on vulnerable subpopulations in Harris County. The findings show a significant disparity in the extent and duration of power outages experienced by low-income and minority groups, suggesting the existence of inequality in the management and implementation of the power outage. Also, the extent of burst pipes and disrupted food access, as a proxy for storm impact, were more severe for low-income and minority groups. Insights provided by the results could form a basis from which infrastructure operators might enhance social equality during managed service disruptions in such events. The results and findings demonstrate the value of community-scale big data sources for rapid impact assessment in the aftermath of extreme weather events.

Detecting faults and anomalies in real-time industrial systems is a challenge due to the difficulty of sufficiently covering an industrial system’s complexity. Today, Industry 4.0 makes it possible to tackle these problems through emerging technologies such as the Internet of Things and Machine Learning. This paper proposes a hybrid machine-learning ensemble real-time anomaly-detection pipeline that combines three Machine Learning models–Local Outlier Factor, One-Class Support Vector Machine, and Autoencoder–, through a weighted average to improve anomaly detection. The ensemble model was tested with three air-blowing machines obtaining a ${F}_{{1}}$ -score value of 0.904, 0.890, and 0.887, respectively. The results of the ensemble model showed improved performance metrics concerning the individual metrics. A novelty of this model is that it consists of two stages inspired by a standard industrial system: i) a manufacturing stage and ii) an operation stage.

Summary: The synapsis of DNA ends is a critical step for the repair of double-strand breaks by non-homologous end joining (NHEJ). This is performed by a multicomponent protein complex assembled around Ku70-Ku80 heterodimers and regulated by accessory factors, including long non-coding RNAs, through poorly understood mechanisms. Here, we use magnetic tweezers to investigate the contributions of core NHEJ proteins and APLF and lncRNA NIHCOLE to DNA synapsis. APLF stabilizes DNA end bridging and, together with Ku70-Ku80, establishes a minimal complex that supports DNA synapsis for several minutes under piconewton forces. We find the C-terminal acidic region of APLF to be critical for bridging. NIHCOLE increases the dwell time of the synapses by Ku70-Ku80 and APLF. This effect is further enhanced by a small and structured RNA domain within NIHCOLE. We propose a model where Ku70-Ku80 can simultaneously bind DNA, APLF, and structured RNAs to promote the stable joining of DNA ends.

DivIVA, GpsB, FilP, and Scy are all involved in bacterial cell division. They have been reported to interact with each other, and although they have been the subject of considerable research interest, not much is known about the molecular basis for their biological activity. Although they show great variability in taxonomic occurrence, phenotypic profile, and molecular properties, we find that they nevertheless share a conserved N-terminal sequence motif, which points to a common evolutionary origin. The motif always occurs N-terminally to a coiled-coil helix that mediates dimerization. We define the motif and coiled coil jointly as a new domain, which we name DivIVA-like. In a large-scale survey of this domain in the protein sequence database, we identify a new family of proteins potentially involved in cell division, whose members, unlike all other DivIVA-like proteins, have between 2 and 8 copies of the domain in tandem. AlphaFold models indicate that the domains in these proteins assemble within a single chain, therefore not mediating dimerization.

Microalgae are among the most suitable sources of new protein ingredients and bioactive compounds, although their cost-effective production still remains a developmental bottleneck. Heterotrophic growth has advantages, such as higher productivity and non-dependence on light and CO2, but it has not yet been fully implemented. The aim of this study was to increase the biomass and protein of Chlorella protothecoides in heterotrophic conditions using expired fruit and vegetable juices (FVJ) and to compare the results to those obtained using a modified Bristol (MB) medium. The initial amounts of sugars (15 g L−1) and yeast extract (8 g L−1) led to the highest protein production (43%) and protein yield (5.2 g L−1) in trials using 1 L bottles. Bioreactor trials using FVJ resulted in a similar biomass productivity (2.94 g L−1 d−1) compared to MB (3.04 g L−1 d−1) and in enhanced polyunsaturated fatty acid content; nonetheless, a lower amount of essential amino acids (EAA) was obtained. Biomass was further processed by ultra-high-pressure homogenisation for protein concentration and residual pellet production. The protein extracts showed significant increases in EAA (11.8% and 26% increase in MB and FVJ, respectively). Residual biomass showed potential as a source of lutein and antimicrobial compounds. The results indicate that FVJ is a promising source of nutrients for the heterotrophic production of C. protothecoides, and that the extracts obtained present nutritional profiles and bioactivities of potential interest.

In this paper, a short history of Basque anthroponymy is made, starting from Antiquity and going through the Roman period, the Middle Ages, the Modern Age and the Contemporary Age. For each of these periods, the stock of the most frequent person names is presented, by synthesizing a variety of works by other authors, who in turn depend on the kind of sources that we have for each period. As in other parts of Europe, an autochthonous repertoire of anthroponyms dominates until the 11th century, either of Aquitanian/Basque etymology or borrowed (mainly from Romance), but deep-rooted in the Basque-speaking areas and particularly in the Kingdom of Pamplona. From the 11th century, the centralizing reforms undertaken by the Catholic Church brought about a gradual substitution of those ancient person names by some others taken from saints, evangelists, characters of the New Testament, a tendency brought to the extreme by the previsions fostered by the Council of Trent. However, as any other European language, Basque developed vernacular versions of these names, as well as an ample array of hypocoristic variants, in which the autochtonous processes of the language such as suffixation, palatalization, etc., are profusely employed. As against some previous accounts of Basque anthroponymy, which have focused exclusively on the analysis of separate anthroponymic units (basically idionyms and patronyms), this paper aims at a global description of the anthroponymic system, considering also social aspects like the development of naming structures as a whole (e.g. idionym + patronym + toponym), and the motivation for giving children particular names (according to relatives, ancestors, patron saints, calendars…).

Automotive Original Equipment Manufacturers (OEMs) require varying levels of functionalities and model details at different phases of the electric vehicles (EV) development process, with a trade-off between accuracy and execution time. This article proposes a scalable modelling approach depending on the multi-objective targets between model functionalities, accuracy and execution time. In this article, four different fidelity levels of modelling approaches are described based on the model functionalities, accuracy and execution time. The highest error observed between the low fidelity (LoFi) map-based model and the high fidelity (HiFi) physics-based model is 5.04%; while, the simulation time of the LoFi model is ~104 times faster than corresponding one of the HiFi model. A detailed comparison of all characteristics between multi-fidelity models is demonstrated in this paper. Furthermore, a dSPACE SCALEXIO Hardware-in-the-Loop (HiL) testbench, equipped with a minimal latency of 18 μ sec, is used for real-time (RT) model implementation of the EV's HV DC/DC converter. The performance of the entire HiL setup is compared with the Model-in-the-Loop (MiL) setup and the highest RMSE is limited to 0.54 among the HiL and MiL results. Moreover, the accuracy (95.7%) of the passive component loss estimation is verified through the Finite Element Method (FEM) software model. Finally, the experimental results of a full-scale 30-kW SiC DC/DC converter prototype are presented to validate the accuracy and correlation between multi-fidelity models. It has been observed that the efficiency deviation between the hardware prototype and multi-fidelity models is less than 1.25% at full load. Furthermore, the SiC Interleaved Bidirectional Converter (IBC) prototype achieves a high efficiency of 98.4% at rated load condition.

La presente obra navega entre dos conceptos —la heterotopía y la utopía— en el contexto de la posmetrópolis. La heterotopía, tal y como explican en el prefacio los coeditores, ha atraído una innegable atención en el ámbito de las ciencias sociales desde que Foucault trasladara el concepto del ámbito médico al espacial (Foucault, 1994: 752-763). Frente al no espacio de la utopía y su carácter ideal y regulador, las heterotopías serían lugares reales, en los que la diferencia se manifiesta al invertir y subvertir aquellos órdenes que configuran nuestros espacios cotidianos. Siendo uno de estos lugares cotidianos la ciudad, y atendiendo a las posibilidades emancipatorias y reactivas que pronto se asociaron a lo heterotópico, cabe preguntarse por el estado actual de las heterotopías urbanas: ¿son las heterotopías actuales, como registra el título de la obra, utopías liberales? León Casero y Urabayen ofrecen en el prefacio un amplio panorama al respecto.

Background Global malaria mortality estimates are hindered by the low reliability of the verbal autopsy (VA) and the clinical records, the most common sources of information used to estimate malaria-specific mortality. We aimed to determine the accuracy of these tools, as well as of the minimally invasive autopsy (MIA), a needle-based postmortem sampling method, to identify malaria-specific mortality in a large series of deceased patients from Mozambique, using complete autopsy as the gold standard.Methods Observational study that included 264 deaths, occurring at a tertiary level hospital in Mozambique, from 1 November 2013 to 31 March 2015 (17 months-long period). Clinical data were abstracted, a computer coded VA was completed using the clinical data as source of information, and an MIA followed by a complete autopsy were performed. Screening for malaria infection was conducted postmortem to all participants using molecular and histological techniques (PCR and immunohistochemistry).Findings Malaria infection was considered the cause of death in 6/264 (2.3%) cases: 2/54 children (3.7%, both less than 5 years old) and 4/57 (7.0%) maternal deaths. The sensitivity and specificity of the VA, the clinical data and the MIA to identify malaria-specific deaths were 33.3% and 96.1%, 66.7% and 96.1%, and 100% and 100%, respectively. In addition, malaria was identified as a possible contributor in 14 additional patients who died of other diseases. These cases were also accurately identified by the MIA (sensitivity 82.4%, specificity 100%).Interpretation The high sensitivity and specificity of the MIA in identifying malaria may help to improve current estimates of malaria-specific mortality in endemic areas.

Lan honetan, euskararen lerrokadura morfologiko ergatiboaren sorrera ikertzen da. Hau eragin zuen prozesua akitaniera eta latinarekiko kontaktuaren hasiera baino lehenago kokatu behar dugu, aitzineuskararen uneren batean. Trask-en (1977) proposamenari jarraikiz, onartuko da orainaldiko joskeretako eta lehenaldi/irrealiseko joskera askotako aditz jokatu iragankorren hasierako slot-a P-ak (= Patient) okupatzen duenez, “today’s morphology is yesterday’s syntax” Givón-en printzipioa (adib. nator < *ni da-tor) aplikatuz aditz jokatu iragankorrok predikatu pasiboetatik datozela (adib. nakus ‘nakusa’ < *ni da-kus ‘ni ikusia naiz’). Aurrekoa onartzeak euskal hizkuntzalaritzaren arazo morfologiko eta sintaktiko klasiko batzuei konponbide bat eskain diezaieke, hala nola ergatibitate hautsia, izen-deklinabideko -k marka ergatiboaren sorrera, jatorri ez-izenordainezkoko -t eta -k komunztadura marken sorrera, eta aditu gehienek onarturiko AVO > AOV osagai-hurrenkeraren aldaketa.

The emergence of ceftazidime/avibactam (CZA) resistance among Guiana extended-spectrum β-lactamase (GES)-producing Pseudomonas aeruginosa isolates has rarely been described. Herein, we analyze the phenotypic and genomic characterization of CZA resistance in different GES-producing P. aeruginosa isolates that emerged in our institution. A subset of nine CZA-resistant P. aeruginosa isolates was analyzed and compared with thirteen CZA-susceptible isolates by whole-genome sequencing (WGS). All CZA-resistant isolates belonged to the ST235 clone and O11 serotype. A variety of GES enzymes were detected: GES-20 (55.6%, 5/9), GES-5 (22.2%, 2/9), GES-1 (11.1%, 1/9), and GES-7 (11.1%, 1/9). WGS revealed the presence of two mutations within the blaGES-20 gene comprising two single-nucleotide substitutions, which caused aspartic acid/serine and leucine/premature stop codon amino acid changes at positions 165 (D165S) and 237 (L237X), respectively. No major differences in the mutational resistome (AmpC, OprD porin, and MexAB-OprM efflux pump-encoding genes) were found among CZA-resistant and CZA-susceptible isolates. None of the mutations that have been previously demonstrated to cause CZA resistance were observed. Different mutations within the blaGES-20 gene were documented in CZA-resistant GES-producing P. aeruginosa isolates belonging to the ST235 clone in our institution. Although further analysis should be performed, according to our results, other resistance mechanisms might be involved in CZA resistance.

Due to the presence of various traffic calming measures (TCM) and traffic lights in urban areas, the speed of vehicles is maintained low. Nevertheless, a problem arises in the frontier between urban and non-urban areas because drivers must adapt their speed and behavior to new conditions. This risk becomes even greater in rural roads that penetrate small villages without a bypass and with a short urban segment, since drivers do not normally speed down in these segments. Various measures can be installed, but traffic lights that turn red if the speed limit is exceeded is not usually considered as a TCM in the literature. Therefore, this paper aims to analyze the efficiency of traffic lights turning red in case of exceeding speed limit. The village of Ábalos in Spain was selected for this research, with an urban area of 630 m and this type of traffic lights in both directions. Results showed that drivers do not respect the speed limit - and hence, the red light - when they are placed separately. However, if they are placed next to a crosswalk, their effect is increased. Consequently, it is recommended to place these traffic lights with a crosswalk to reinforce the efficiency of both TCMs.

The spread of pandemics such as COVID-19 is strongly linked to human activities. The objective of this article is to specify and examine early indicators of disease spread risk in cities during the initial stages of outbreak based on patterns of human activities obtained from digital trace data. In this study, the Venables distance (Dv) and the activity density (Da) are used to quantify and evaluate human activities for 193 United States counties, whose cumulative number of confirmed cases was greater than 100 as of March 31, 2020. Venables distance provides a measure of the agglomeration of the level of human activities based on the average distance of human activities across a city or a county (less distance could lead to a greater contact risk). Activity density provides a measure of level of overall activity level in a county or a city (more activity could lead to a greater risk). Accordingly, Pearson correlation analysis is used to examine the relationship between the two human activity indicators and the basic reproduction number in the following weeks. The results show statistically significant correlations between the indicators of human activities and the basic reproduction number in all counties, as well as a significant leader-follower relationship (time lag) between them. The results also show one to two weeks’ lag between the change in activity indicators and the decrease in the basic reproduction number. This result implies that the human activity indicators provide effective early indicators for the spread risk of the pandemic during the early stages of the outbreak. Hence, the results could be used by the authorities to proactively assess the risk of disease spread by monitoring the daily Venables distance and activity density in a proactive manner.

Nous rapportons le cas clinique d´un patient de 58 ans qui présentait des céphalées depuis 3 mois dont les investigations paracliniques ont permis de poser le diagnostic d´hémosidérose du système nerveux centrale et son association rare avec un macro-adénome hypophysaire.

In this second and last part of the article about the grammatical number in Basque, it is discussed what the state of affairs in prehistorical periods may have been like, taking historical data as a starting point. In Point 3, the different sectors of the morphology are analised in successive subpoints: nouns, demonstratives, indefinite pronouns, personal pronouns and verbal morphs. In the first two of them, the problem of the origin of the plural is described in detail, listing pros and cons of each possible interpretation. In 3.4, several formal similarities between some personal pronouns and certain plural morphs are pointed out, and in 3.5 the pronominal origin of the verbal marks of person are analised from the point of view of the category of grammatical number. In Point 4, the conclusion reached –i.e., the absence of grammatical number in old Basque, except for 1st and 2nd person pronouns– is confronted with the implicational hierarchy about number put forward by typological research.

In this paper, an attempt is made to set out the Aquitanian anthroponymic data in an intergenerational layout, i.e. indicating all the kinship sequences between father and/or mother and individual deducible from inscriptions. To begin with, the analized corpus and the employed methodology are explained, as well as the formalisms used in the exposition of the data to indicate that some aspects are not certain or are doubtful, either in the reading or in the establishment of kinship relationships (Section 2). Then, all the bigenerational sequences are expounded in four tables designed according to linguistic criteria, in order to visualise in which cases the anthroponymic Aquinatity is lost —or recovered— from one generation to the following (Section 3). Next, the same data are put in the opposite direction (father and/or mother → individual), also displaying them geographically (Section 4). Finally, the familiar groups are expounded which are inferable from the cases in which there are trigenerational sequences (Section 5). Over the work, several observations are made about the general procedure of Aquitanians to choose names.

In this paper, an attempt is made to set out the Aquitanian anthroponymic data in an intergenerational layout, i.e. indicating all the kinship sequences between father and/or mother and individual deducible from inscriptions. To begin with, the analized corpus and the employed methodology are explained, as well as the formalisms used in the exposition of the data to indicate that some aspects are not certain or are doubtful, either in the reading or in the establishment of kinship relationships (Section 2). Then, all the bigenerational sequences are expounded in four tables designed according to linguistic criteria, in order to visualise in which cases the anthroponymic Aquinatity is lost —or recovered— from one generation to the following (Section 3). Next, the same data are put in the opposite direction (father and/or mother → individual), also displaying them geographically (Section 4). Finally, the familiar groups are expounded which are inferable from the cases in which there are trigenerational sequences (Section 5). Over the work, several observations are made about the general procedure of Aquitanians to choose names.

In the system of the Statute of Autonomy, even though foral bodies have kept for themselves the traditional power regarding administrative and revenues issues, the competence in Private law matters, with an undoubted foral standing, has implicitly been allocated to the autonomic common body for its preservation, modification and development, although as a matter of fact it was also materialized by the historic territories. For that matter, the competences attributed in the field of Private law have been implemented by the Basque legislator by means of irrigations in different areas of competences and with the use of the competence of «civil legislation», distinctly, has been postponed with punctual territorial articulations. It is time to approach the process of promoting the Basque Civil Law in a systematic way, a task to be steered by the new committee for Civil law as facilitator and advisory body of the Basque Parliament and government.

When we talk about the human right to science, many may think that we are speaking about a new right, recently created to face the challenges that science and technology generate in our society of the 21st century. However, the right to science is already enshrined in the Universal Declaration of Human Rights (1948) and in the International Covenant on Economic, Social and Cultural Rights (1966). We can find it even earlier in the inter-American regional system, particularly, in the Charter of the Organization of American States (1948) and in the American Declaration of the Rights and Duties of Man (1948). Few know that, in fact, the Latin American countries in general and Chile in particular played a crucial role in the universal recognition of this right. The first part of the article explains the history of the right to science and its international legal recognition. In a second chapter, we will study its current institutional situation within the United Nations and, finally, in the third chapter, we will analyze the characteristics of this right, its normative content, elements and type of obligations that it creates.

Introduction: El traumatismo craneoencefálico (TCE) en ancianos supone un alto impacto asistencial y económico en los servicios de urgencias. En el Hospital Universitario Basurto (HUB) origina aproximadamente el 15% de las consultas quirúrgico-traumatológicas. La caída es la principal causa y la medicación/polifarmacia uno de los principales factores de riesgo modificable. Policy context and objective: En un estudio desarrollado en Urgencias del HUB sobre 859 pacientes atendidos por TCE durante un año, 90% fueron causados por caídas. El 72% estaban polimedicados, 82% tomaba algún medicamento crónico asociado a riesgo de caídas (benzodiacepinas, opioides…) y 62% alguno incluido en criterios STOPP. Casi 60% tomaba anticoagulantes/antiagregantes, lo que aumenta la morbilidad, prolongando la estancia hospitalaria. Simultáneamente, en los Centros de Atención Primaria (AP) de la Organización Sanitaria Integrada Bilbao-Basurto se desplegó, el “Programa para la Valoración Integral del mayor polimedicado (BiE-Kronikoak)” que contempla la revisión de la medicación en ancianos polimedicados, la valoración de factores de fragilidad y otros predictores de discapacidad y morbimortalidad. La confluencia de ambas circunstancias proporcionó una oportunidad para la integración asistencial. El objetivo del presente trabajo es diseñar e implantar un programa de coordinación para garantizar la continuidad asistencial a la población diana, que implica una cita prioritaria desde Urgencias en consulta de AP para revisar la medicación y realizar los cambios oportunos para prevenir/minimizar el riesgo de caídas y reingresos. Targeted population: Pacientes >75 años polimedicados (> 5 medicamentos crónicos) que acuden a urgencias del HUB por haber sufrido un TCE tras caída. Se excluyen pacientes residenciados. Highlights: Presentamos un proyecto multidisciplinar de integración que implica médicos, farmacéuticos y enfermería de urgencias y AP, apoyado por los mandos de la organización, que garantiza la continuidad asistencial. El funcionamiento del circuito se pilotó durante 3 meses resultando que, de 153 pacientes susceptibles de derivación desde Urgencias a la consulta de AP, solo 33 fueron citados y de ellos el 20% fueron atendidos. Esto permitió identificar sus puntos débiles y rediseñarlo. Los resultados de esta revisión serán presentados en el Congreso. Comments on transferability: El envejecimiento de la población y la polimedicación son realidades que afectan a todas las organizaciones sanitarias de los países desarrollados. Las caídas son causa frecuente de discapacidad y muerte en los ancianos. A menudo los medicamentos juegan un papel importante. La experiencia con los ancianos atendidos por TCE podría extrapolarse a otros motivos de ingreso tras caída (fracturas de cadera, etc), en los que una intervención coordinada sobre los factores de riesgo sería igualmente importante. Conclusions(key findings, discussion, lessons learned): La coordinación entre el Servicio de Urgencias hospitalario y AP facilita el cuidado integral de los ancianos polimedicados con riesgo de caídas. El buen funcionamiento del programa exige un líder, motivación constante de los participantes, implicación de los mandos y apoyo informático que simplifique las tareas. El diseño inicial del circuito presenta puntos débiles que hacen que un número importante de pacientes susceptibles de intervención no sean citados en AP, lo que ha obligado a un nuevo planteamiento, cuya efectividad se está evaluando actualmente.

Coffee Leaf Rust (CLR) is a fungal epidemic disease that has been affecting coffee trees around the world since the 1980s. The early diagnosis of CLR would contribute strategically to minimize the impact on the crops and, therefore, protect the farmers’ profitability. In this research, a cyber-physical data-collection system was developed, by integrating Remote Sensing and Wireless Sensor Networks, to gather data, during the development of the CLR, on a test bench coffee-crop. The system is capable of automatically collecting, structuring, and locally and remotely storing reliable multi-type data from different field sensors, Red-Green-Blue (RGB) and multi-spectral cameras (RE and RGN). In addition, a data-visualization dashboard was implemented to monitor the data-collection routines in real-time. The operation of the data collection system allowed to create a three-month size dataset that can be used to train CLR diagnosis machine learning models. This result validates that the designed system can collect, store, and transfer reliable data of a test bench coffee-crop towards CLR diagnosis.

The purpose of this paper is to identify two inconsistencies that are found in the third chapter of Marx's Das Kapital, dedicated to the study of credit. In the first one Marx states that the distinction between commercial and bank credit is only nominal, but he resorts to it in order to provide an explanation for the nineteenth century crisis in England, thus implying that the distinction was not only nominal, but real. The second inconsistency is noticed between Marx’s statement that real and money capital move in opposite directions during the trade cycle (with-out an explanation of how it is possible), and the second book of The Capital where Marx states that capital in the form of money and real capital must move in the same directions during the business cycle

Agricultural activity has always been threatened by the presence of pests and diseases that prevent the proper development of crops and negatively affect the economy of farmers. One of these pests is Coffee Leaf Rust (CLR), which is a fungal epidemic disease that affects coffee trees and causes massive defoliation. As an example, this disease has been affecting coffee trees in Colombia (the third largest producer of coffee worldwide) since the 1980s, leading to devastating losses between 70% and 80% of the harvest. Failure to detect pathogens at an early stage can result in infestations that cause massive destruction of plantations and significantly damage the commercial value of the products. The most common way to detect this disease is by walking through the crop and performing a human visual inspection. As a result of this problem, different research studies have proven that technological methods can help to identify these pathogens. Our contribution is an experiment that includes a CLR development stage diagnostic model in the Coffea arabica, Caturra variety, scale crop through the technological integration of remote sensing (through drone capable multispectral cameras), wireless sensor networks (multisensor approach), and Deep Learning (DL) techniques. Our diagnostic model achieved an F1-score of 0.775. The analysis of the results revealed a p-value of 0.231, which indicated that the difference between the disease diagnosis made employing a visual inspection and through the proposed technological integration was not statistically significant. The above shows that both methods were significantly similar to diagnose the disease.

The management of forests and the forest policy are presently based on enviromental and sustainability criteria which are addressed to the decisions regarding the exploitation of the main natural resource of the territory. Because of it, in the framework of the whole territorial planning, the planning by the participation of all the public and private agents that operate within the agrarian, forest and herding field becomes an essential instrument of the guidelines that guaratee the management which using ideally the forest nowadays give that same social and economic value to the future generations.

There is a clear need for a public domain data set of road networks with high special accuracy and global coverage for a range of applications. The Global Roads Open Access Data Set (gROADS), version 1, is a first step in that direction. gROADS relies on data from a wide range of sources and was developed using a range of methods. Traditionally, map development was highly centralized and controlled by government agencies due to the high cost or required expertise and technology. In the past decade, however, high resolution satellite imagery and global positioning system (GPS) technologies have come into wide use, and there has been significant innovation in web services, such that a number of new methods to develop geospatial information have emerged, including automated and semi-automated road extraction from satellite/aerial imagery and crowdsourcing. In this paper we review the data sources, methods, and pros and cons of a range of road data development methods: heads-up digitizing, automated/semi-automated extraction from remote sensing imagery, GPS technology, crowdsourcing, and compiling existing data sets. We also consider the implications for each method in the production of open data.

With the increasing demand for electric vehicles, the requirements of the market are changing ever faster. Therefore, there is a need to improve the electric car’s design time, where simulations could be an appropriate tool for this task. In this paper, the modeling and simulation of an inverter for an electric vehicle are presented. Four different modeling approaches are proposed, depending on the required simulation speed and accuracy in each case. In addition, these models can provide up to 150 different electric modeling and three different thermal modeling variants. Therefore, in total, there were 450 different electrical and thermal variants. These variants are easily selectable and usable and offer different options to calculate the electrical parameters of the inverter. Finally, the speed and accuracy of the different models were compared and the obtained results presented.

OBJECTIVES/SPECIFIC AIMS: The primary objective of this research is to determine whether being hand-reared, and deprived of early maternal interaction, will affect telomere length in orphaned kittens. The secondary goal is to examine how early maternal separation impacts the health, growth and behavior of orphaned kittens. METHODS/STUDY POPULATION: Kittens were fostered through local rescue groups and shelters. We collected blood samples from 42 orphaned kittens during the first week of their lives. Due to high mortality of this population, we obtained a second blood sample at eight weeks of age from only 30 of these kittens. We collected blood samples from 12 control kittens raised with mothers at during the first and eighth weeks of life. Blood samples are currently being processed with real time quantitative PCR (qPCR) by the Real-time PCR Research and Diagnostics Core Facility at the UC Davis School of Veterinary Medicine (SVM). This includes RNA extraction, cDNA synthesis, Reference Gene Validation, and qPCR analysis. Relative telomere length (RTL) will be calculated by comparing the average telomere abundance across three samples cells with that of a reference gene (single copy number) for each sample. The resulting T/S ratio (telomere to single copy) is proportional to the average telomere length. If T/S = 1, then telomere length in the sample and the reference are the same. RESULTS/ANTICIPATED RESULTS: Because telomeres show the fastest rate of shortening early in life, we predict that maternal separation will increase the rate of telomere shortening in kittens. We also predict that the telomeres of orphaned kittens will be shorter at both one week and eight weeks of age, compared to controls. DISCUSSION/SIGNIFICANCE OF IMPACT: This study will increase our understanding of early life adversity, a finding that can translate to other mammals. It will inform the practice of fostering neonatal kittens, and illuminate whether these kittens might be at higher risk than mother-reared kittens for health problems (which could be investigated in future studies). If significant telomere shortening occurs between collection periods, then future studies can take more frequent blood samples to determine what stages of early development are potentially most sensitive. If differences between groups are found, this will establish a protocol for several future research projects, such as testing whether these detrimental effects can be mitigated by environmental enrichment via activation of telomerase. Telomerase is an enzyme that appears to counteract some shortening of telomeres, and is activated by several external factors, including exercise. Thus, a logical follow up study would be developing and testing age-specific and appropriate enrichments that may activate telomerase and reduce telomere loss. Physical contact, whether human, mother, or siblings, is another possible source of telomerase activation in young kittens. Future studies also could quantify the effects of different sources of physical contact on telomere shortening. Finally, a positive finding would establish a need for longitudinal studies of the effects of early weaning on feline health and behavior and whether differences in early-life telomere lengths predict health and longevity of cats.

In this second and last part of the article about the grammatical number in Basque, it is discussed what the state of affairs in prehistorical periods may have been like, taking historical data as a starting point. In Point 3, the different sectors of the morphology are analised in successive subpoints: nouns, demonstratives, indefinite pronouns, personal pronouns and verbal morphs. In the first two of them, the problem of the origin of the plural is described in detail, listing pros and cons of each possible interpretation. In 3.4, several formal similarities between some personal pronouns and certain plural morphs are pointed out, and in 3.5 the pronominal origin of the verbal marks of person are analised from the point of view of the category of grammatical number. In Point 4, the conclusion reached –i.e., the absence of grammatical number in old Basque, except for 1st and 2nd person pronouns– is confronted with the implicational hierarchy about number put forward by typological research.

This is the first half of an article in which all sectors of Basque morpho - logy with some overt opposition for grammatical number are synchronically and diachronically analyzed. This opposition presents different values across lexical categories: sg. / pl. / indef. on nouns (etxe-a, etxe-ak, etxe), sg. / pl. on demonstratives (hau / hau-ek), indef. on interrogative/relative and indefinite pronouns (zenbait etxe), sg. / pl. on personal pronouns (ni / gu), and sg. / pl. on the personal marks of verbs (na-bil / ga-bil-tza, da-bil / da-bil-tza, da-kar-t / da-kar-gu, da-kar / da-kar-tza, da-kar / da-kar-te...). This half includes two points. In Point 1, the expressions of these categories in modern standard Basque are analyzed. In Point 2, these expressions are discussed dialectally and historically, in order to track their historical evolution as far as it is possible.

Palladium-catalyzed dehydrogenative coupling is an efficient synthetic strategy for the construction of quinoline scaffolds, a privileged structure and prevalent motif in many natural and biologically active products, in particular in marine alkaloids. Thus, quinolines and 1,2-dihydroquinolines can be selectively obtained in moderate-to-good yields via intramolecular C–H alkenylation reactions, by choosing the reaction conditions. This methodology provides a direct method for the construction of this type of quinoline through an efficient and atom economical procedure, and constitutes significant advance over the existing procedures that require preactivated reaction partners.

Índice• El modelo conceptual • Aplicación del modelo como herramienta metodológica para medir la sustentabilidad • Bibliografía Resumen Se propone un modelo conceptual de la sustentabilidad, en el ánimo de establecer una herramienta operativa que permita medirla. Propone tres categorías de análisis: lo económico, lo social y lo territorial, donde la sustentabilidad sería la relación armónica entre estos tres objetivos y se cruzan ellos con los aspectos de lugar, actos y formas que caracterizan los espacios urbanos. Se genera una matriz de doble entrada, donde los cruces apuntan a los conceptos de tamaño, residencia, organización, aptitud, equipamiento, categoría, configuración, ordenamiento y relaciones. La sustentabilidad general queda definida por el volumen del cubo constituido por los vectores equidad, eficiencia y habitabilidad; la sustentabilidad urbanística por los vectores del cubo lugar, forma y acto. Seleccionando indicadores relevantes para los nueve cruces señalados, es posible establecer mediciones de la sustentabilidad entre distintos lugares o evoluciones en el tiempo. Abstract We propose a conceptual model of sustainability, in the minds of establishing an operational tool that allows measurement. It proposes three different categories: economic, social and territorial, where sustainability would be a harmonious relationship between these three objectives and they intersect with issues of place, events and forms that characterize urban areas. It generates an array of double entry, where the crosses point to the concepts of size, residence, organization, skills, equipment, status, configuration, management and relationships. The overall sustainability is defined by the volume of the cube formed by the vectors equity efficiency and livability, urban sustainability by the vectors of the cube place, form and action. Selecting relevant indicators for the nine crosses reported, it is possible to establish measures of sustainability between different places or changes over time.

Lan honetan Koldo Mitxelenaren euskara zaharraren berreraiketa fonologikotik abiatuz, ‘Aitzin-Euskara Zaharra’ izenda dezakegun eta Mitxelenarena baino garai zaharrago bati dagokion hizkuntzaren aitzin-sistema fonologikoa berreraikitzen saiatzen gara. Horretarako, Joseba Lakarrak azken urteotan euskararen erro zahar disilabikoen azterketa morfo-fonologiko zein etimologikoan burutu dituen aurrerakuntzetan oinarritzen gara. Alde batetik, erro disilabiko horiek garai zaharrago batean bi erro monosilabikoez osaturiko egitura perifrastikoak izan zirela onartzen dugu. Beste alde batetik, azterketa honek barne-berreraiketa fonologikorako bidea urratzen duelakoan gaude, elementu monosilabiko hauek testuinguru fonetikoaren arabera erakusten dituzten formen arteko txandaketen erkaketak forma zaharrak nolakoak ziren zehazten lagun diezagukeelarik.

In this article, a thorough criticism of the main issues concerning the Basque accentuation is performed. In point 1, a synchronic description of the different Basque accentual types as described in Michelena (1972) and Hualde (1997) is carried out. Type I corresponds to western varieties (specially V and G.) and is characterized by the presence of certain accentually marked roots and morphemes, like the plural suffix. Type II corresponds to the Northeastern corner of the Basque-speaking territory (Suletin. and Roncalese dialects) and its main feature is that the stress (witch is clearly intensive) falls nearly regularly on the penultimate syllable in the bulk of the lexikon. Type III corresponds roughly to High Navarrese (AN) and is a derivation of Type II by means of a tendency towards the «columnization» of the accent throughtout the paradigm. Type IV is still operative in the low part ofthe Bidasoa valley and according to it most word are stressed on the second syllable from the beginning. Point 2 is an explanation of the different attempts to reconstruct the common accent. In particular, we discuss the proposals made by Martinet (1950, 1955) (accent on the first syllable), Michelena (1958) (accent on the second syllable) and Hualde (1993) (phrase-final accent with no word-level prominence). In point 3, we discuss all the elements that are relevant in the diachronic analysis. Thus, we argue that Lakarra's (1995) theory of the root provides support for the accent-on-second theory, since some etymologies proposed by him seem to suggest that in some bisyllabic roots the first element has lost some phonic substance, whereas the second remains untouched which may imply pretonic position of the former (*han-ker "wicked animal" > aker "billy goat"). Finally, in point 4 we sketch out how the chronological development from that commmon accent system to the historical types may have taken place.