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In this letter, the authors carry out a judicious application of the 2-D method of moments (MoM) to the analysis of the scattering of plane waves by infinite conducting cylinders in the case where the cylinders show two orthogonal planes of mirror symmetry. In particular, the original MoM scattering problem is replaced by four new MoM scattering problems in which the two mirror symmetry planes behave as perfect electric conductors and/or perfect magnetic conductors. The current densities of the four new MoM problems only have to be obtained in one quarter of the cylinders cross section, and therefore, the number of MoM matrix entries in each new problem is one-sixteenth the number of MoM matrix entries in the original problem, which makes it possible to reduce the CPU time required for the solution of the original problem to roughly one-fourth. Results are generated for cylinders where the cross section is a rectangle, a rhombus, an ellipse, and an ogive, the one-quarter CPU time reduction being confirmed in all cases.

Transformers achieve great performance on Visual Question Answering (VQA). However, their systematic generalization capabilities, i.e., handling novel combinations of known concepts, is unclear. We reveal that Neural Module Networks (NMNs), i.e., question-specific compositions of modules that tackle a sub-task, achieve better or similar systematic generalization performance than the conventional Transformers, even though NMNs’ modules are CNN-based. In order to address this shortcoming of Transformers with respect to NMNs, in this paper we investigate whether and how modularity can bring benefits to Transformers. Namely, we introduce Transformer Module Network (TMN), a novel NMN based on compositions of Transformer modules. TMNs achieve state-of-the-art systematic generalization performance in three VQA datasets, improving more than 30% over standard Transformers for novel compositions of sub-tasks. We show that not only the module composition but also the module specialization for each sub-task are the key of such performance gain.

Introduction:The ribonuclease (RNase) A superfamily encodes cationic antimicrobial proteins with potent microbicidal activity toward uropathogenic bacteria. Ribonuclease 6 (RNase6) is an evolutionarily conserved, leukocyte-derived antimicrobial peptide with potent microbicidal activity toward uropathogenic Escherichia coli(UPEC), the most common cause of bacterial urinary tract infections (UTIs). In this study, we generated Rnase6-deficient mice to investigate the hypothesis that endogenous RNase 6 limits host susceptibility to UTI. Methods:We generated a Rnase6EGFPknock-in allele to identify cellular sources of Rnase6and determine the consequences of homozygous Rnase6deletion on antimicrobial activity and UTI susceptibility. Results:We identified monocytes and macrophages as the primary cellular sources of Rnase6in bladders and kidneys of Rnase6EGFP/+mice. Rnase6deficiency (i.e., Rnase6EGFP/EGFP) resulted in increased upper urinary tract UPEC burden during experimental UTI, compared to Rnase6+/+controls. UPEC displayed increased intracellular survival in Rnase6-deficient macrophages. Conclusion:Our findings establish that RNase6prevents pyelonephritis by promoting intracellular UPEC killing in monocytes and macrophages and reinforce the overarching contributions of endogenous antimicrobial RNase A proteins to host UTI defense.

Heterostructures, composed of semiconducting transition-metal dichalcogenides (TMDC) and magnetic van-der-Waals materials, offer exciting prospects for the manipulation of the TMDC valley properties via proximity interaction with the magnetic material. We show that the atomic proximity of monolayer MoSe2and the antiferromagnetic van-der-Waals crystal CrSBr leads to an unexpected breaking of time-reversal symmetry, with originally perpendicular spin directions in both materials. The observed effect can be traced back to a proximity-induced exchange interaction via first-principles calculations. The resulting spin splitting in MoSe2is determined experimentally and theoretically to be on the order of a few meV. Moreover, we find a more than 2 orders of magnitude longer valley lifetime of spin-polarized charge carriers in the heterostructure, as compared to monolayer MoSe2/SiO2, driven by a Mott transition in the type-III band-aligned heterostructure.

Introduction: Although several studies report that the robotic approach is more costly than laparoscopy, the cost-effectiveness of robotic distal pancreatectomy (RDP) over laparoscopic distal pancreatectomy (LDP) is still an issue. Methods: This study is an observational, multicenter, national prospective study (ROBOCOSTES). Results: During the study period, 80 procedures from 14 Spanish centres were analyzed. Conclusions: The RDP procedure in the Spanish healthcare system appears more cost-effective than the LDP.

La alta incidencia de la enfermedad nodular tiroidea ha hecho que crezca la preocupación sobre el manejo terapéutico de los nódulos tiroideos benignos. El desarrollo de técnicas mínimamente invasivas (TMI) supone una alternativa a la cirugía con una baja tasa de complicaciones. Nuestro objetivo es evaluar la eficacia y el impacto sobre la calidad de vida relacionada con la salud (CVRS) del tratamiento mediante inyección percutánea de etanol (IPE) de los nódulos tiroideos sintomáticos, quísticos y mixtos de predominio quístico (componente quístico >50%) tratados en la unidad de alta resolución (UARNT) del Hospital Verge de la Cinta.

Los recién nacidos que no alcanzan un peso acorde con su edad gestacional y sexo se pueden clasificar de distintos modos. En este artículo se definen los conceptos de pequeño para la edad gestacional (PEG) y crecimiento intrauterino reducido, así como las causas que las determinan con el objetivo de consensuar las definiciones en este tipo de pacientes que puedan ser susceptibles de tratamiento con hormona de crecimiento a lo largo de su infancia, así como de desarrollar enfermedad endocrinológica en la pubertad y en la edad adulta. La mayoría de los niños PEG experimentan un crecimiento recuperador espontáneo que suele completarse a los 2 años. En los PEG que no lo realizan, el tratamiento con hormona de crecimiento humana recombinante es efectivo, aumentando su talla adulta. Los PEG con crecimiento recuperador rápido y marcado en peso tienen mayor riesgo de desarrollar adrenarquia precoz, pubertad adelantada, síndrome del ovario poliquístico (niñas), resistencia a la insulina y obesidad; predisponiendo al desarrollo de diabetes tipo 2 y síndrome metabólico en la edad adulta. La condición de PEG puede afectar diferentes áreas del neurodesarrollo y manifestarse éstas en diferentes etapas de la vida; los PEG con crecimiento recuperador espontáneo tienen mejor pronóstico neurológico. Los posibles riesgos descritos asociados a la condición de PEG hacen imperativo la adecuada caracterización de estos pacientes al nacimiento, que permitirá su seguimiento prospectivo y la detección precoz de alteraciones.

abstract:Despite the growing interest in the economic backgrounds of mps in Western Europe, the evolution of working-class numerical representation before 1945 has not been systematically studied. Using data from England and Wales (1832–1944), Germany (1871–1930), and Norway (1906–1936), the authors show both that working-class mps were elected when barriers were lowered and that almost all working-class parliamentarians were affiliated with socialist parties. The authors further probe the conditions that determined the electoral success of workers using data about all candidates, constituencies’ occupational profile, and unionization in Norway between 1906 and 1936. They find that socialist parties nominated workers either in relatively uncompetitive elections in which unionization was high or in competitive races in which the party’s victory was possible but not guaranteed. Using information about mps in Germany and England and Wales, the authors find similar patterns. The article discusses the implications for research about democratization, the rise of social democracy, and the numerical representation of workers.

Two ultimately thin vanadium-rich 2D materials based on VS2are created via molecular beam epitaxy and investigated using scanning tunneling microscopy, X-ray photoemission spectroscopy, and density functional theory (DFT) calculations. The controlled synthesis of stoichiometric single-layer VS2or either of the two vanadium-rich materials is achieved by varying the sample coverage and sulfur pressure during annealing. Through annealing of small stoichiometric single-layer VS2islands without S pressure, S-vacancies spontaneously order in 1D arrays, giving rise to patterned adsorption. Via the comparison of DFT calculations with scanning tunneling microscopy data, the atomic structure of the S-depleted phase, with a stoichiometry of V4S7, is determined. By depositing larger amounts of vanadium and sulfur, which are subsequently annealed in a S-rich atmosphere, self-intercalated ultimately thin V5S8-derived layers are obtained, which host 2 × 2 V-layers between sheets of VS2. We provide atomic models for the thinnest V5S8-derived structures. Finally, we use scanning tunneling spectroscopy to investigate the charge density wave observed in the 2D V5S8-derived islands.

The advent of twist engineering in two-dimensional crystals enables the design of van der Waals heterostructures with emergent properties. In the case of magnets, this approach can afford artificial antiferromagnets with tailored spin arrangements. Here we fabricate an orthogonally twisted bilayer by twisting two CrSBr ferromagnetic monolayers with an easy-axis in-plane spin anisotropy by 90°. The magnetotransport properties reveal multistep magnetization switching with a magnetic hysteresis opening, which is absent in the pristine case. By tuning the magnetic field, we modulate the remanent state and coercivity and select between hysteretic and non-hysteretic magnetoresistance scenarios. This complexity pinpoints spin anisotropy as a key aspect in twisted magnetic superlattices. Our results highlight control over the magnetic properties in van der Waals heterostructures, leading to a variety of field-induced phenomena and opening a fruitful playground for creating desired magnetic symmetries and manipulating non-collinear magnetic configurations.

Alzheimer’s disease is the leading cause of dementia worldwide, but the cellular pathways that underlie its pathological progression across brain regions remain poorly understood1–3. Here we report a single-cell transcriptomic atlas of six different brain regions in the aged human brain, covering 1.3 million cells from 283 post-mortem human brain samples across 48 individuals with and without Alzheimer’s disease. We identify 76 cell types, including region-specific subtypes of astrocytes and excitatory neurons and an inhibitory interneuron population unique to the thalamus and distinct from canonical inhibitory subclasses. We identify vulnerable populations of excitatory and inhibitory neurons that are depleted in specific brain regions in Alzheimer’s disease, and provide evidence that the Reelin signalling pathway is involved in modulating the vulnerability of these neurons. We develop a scalable method for discovering gene modules, which we use to identify cell-type-specific and region-specific modules that are altered in Alzheimer’s disease and to annotate transcriptomic differences associated with diverse pathological variables. We identify an astrocyte program that is associated with cognitive resilience to Alzheimer’s disease pathology, tying choline metabolism and polyamine biosynthesis in astrocytes to preserved cognitive function late in life. Together, our study develops a regional atlas of the ageing human brain and provides insights into cellular vulnerability, response and resilience to Alzheimer’s disease pathology.

Culturally relevant evidence-based interventions for Spanish speaking Latinx care partners are needed to address negative outcomes often associated with caregiver burden. Problem Solving Training (PST), an evidence-based, problem-solving skills training intervention with a person-centered approach is optimal for adaptation to other languages and cultures. Our objective was to culturally adapt PST to Descubriendo Soluciones Juntos (DSJ) for Spanish-speaking Latinx care partners of adults with neurological disorders through and iterative process of translation and language validation and input from therapists and Spanish-speaking Latinx care partners engaged in the intervention. Three primarily Spanish-speaking care partners completed a single-group, pre-post-test design pilot study of DSJ, comprising six one-on-one sessions delivered via telephone or videoconference and baseline and post-intervention measures of caregiver burden, depressive symptoms, and positive aspects of caregiving. Iterative cultural adaptation occurred in concordance with Marsiglia and Booth’s (Res Soc Work Pract 25:423–432, 2015) roadmap for cultural adaptation. Process-based and content-based adaptations are described, resulting in a final protocol for DSJ that maintains the core components of PST. All participants were satisfied with DSJ and reported positive changes in caregiver burden, positive aspects of caregiving, and/or relationship quality with their care recipient. PST/DSJ is a bicultural problem-solving intervention with potential to provide much needed evidence-based support to Spanish-speaking Latinx care partners.

In this paper a detailed life cycle analysis of a freestanding cooking appliance is presented. The work provided data collection (life cycle inventory) for a specific model of a freestanding cooker manufactured and used in the US market. Impact assessment was done using a dedicated software tool (i.e., SimaPro) to identify the most impacting life cycle phases as well as critical items that characterize each phase. Environmental impact results highlighted how the most critical aspect is related to product use due to the large consumption of electric energy, especially in a market characterized by a grid mix with a low percentage of renewable energy. The large volumes of the oven cavity and the adoption of traditional technology (e.g., electric radiant resistance) are also relevant contributions to the environmental impacts of the use phase. With respect to the manufacturing phase, the use of some specific materials in all the cooking appliances was the main reason for the highest impact, on top of these materials are the electronic components followed by metallic components which can be either made from stainless steel or carbon steel. In addition, the outcome of this work allows comparing this appliance to other cooking appliances available in the market, providing interesting insights in the development of eco-design actions.

Product design plays a key role in supporting the principles of circular economy and sustainability by improving the repair and disassembly capabilities of products. The EN4555X standard series provides a framework and a set of indicators to evaluate these aspects for energy-related products. This paper focuses on applying the RSS (Repair Scoring System) introduced by the EN45554 standard to kitchen ventilation systems (T-shape cooker hood models). The study investigates the reliability of the repairability index by examining the impact of assumptions made during its assessment, particularly focusing on the data and parameters used for calculations. The methodology involves four key steps: identification of index parameters, experimental analysis, sensitivity analysis (SA) through data variation, and result interpretation. The experimental analysis involves computing the RSS index for the chosen range hoods, encompassing a SA developed by varying index’s parameters. Results illustrate that introducing consistent parameter variations across models leads to changes in the Disassemblability Index. However, these alterations remain consistent across all cases, preserving the overall product ranking. Nonetheless, the study also indicates that altering parameter weights may lead to changes in product rankings within the repairability score. This highlights the importance of employing uniform weights within the same product category. In conclusion, this study underscores the importance of employing consistent methodologies and weights to uphold the reliability of repairability indexes when assessing product repairability.

Remanufacturing, a beacon of economic and ecological alignment, hinges on disassembly’s complexity. As both manual and robotic approaches face challenges, systems in which human and robots can work iteratively offer adaptable solutions, curbing the required system flexibility at acceptable capital expenditure. However, today no metrics exist to evaluate the ease of disassembly of product designs when considering a combination of manual and robotic disassembly Therefore, this study extends the existing ease of Disassembly Metric (e-DiM) for designers, policymakers, and recyclers in anticipation of the industrialization of human-robot cooperative disassembly systems. For the development of such a metric the expected limitations of robotic disassembly systems are first discussed based on prior research. Subsequently, a set of criteria are presented to define which operations can be performed successfully in a flexible system. Finally, the Robotic ease of Disassembly metric (Re-DiM) is introduced, which serves to comprehensively evaluate both manual and robotic disassembly times. To validate Re-DiM’s applicability, the ease of both manual and robotic disassembly is evaluated for all critical components of a robotic vacuum cleaner. The presented case study highlights today’s robotic disassembly challenges, underscoring also the relevance of novel design for robotic disassembly approaches.

The mechanical properties of a commercially available hot-melt adhesive (HMA) have been studied under different environmental and loading conditions. To date, disassembly analyses including triggering features, design parameters, and time have not been fully investigated in the literature. In this study, experimental parametric studies have been performed on single lap joints considering the geometric features of the joint and a combination of thermo-mechanical effects. Disassembly time has been assessed through experimental analysis, considering variations in geometry, the use of alternative heat sources and different load conditions. Use of a heat gun as the heat source was found to lead to the highest variation in disassembly time compared to a static climatic chamber (i.e., industrial oven). In relation to the joint geometry, the disassembly time was mostly affected by the overlap length rather than the type or thickness of the base material. The outcomes of this study will drive the design of adhesive joints in mechanical applications, providing design-for-disassembly guidelines for the development of reversible joints employing hot-melt adhesives.

In this article, we present an efficient implementation of the spectral-domain method of moments (SD-MoM) for the analysis of periodic multilayered structures in the case where asymmetric rooftop basis functions defined in a nonuniform mesh are used. This mesh only needs to be generated in the bounding rectangle that encloses the electric or magnetic current to be discretized. The slowly convergent double infinite summations involved in the MoM matrix entries are computed by means of four 2-D nonuniform fast Fourier transforms (NUFFT-2D), and the singularities and quasi-singularities appearing in the spectral functions that are subjected to the NUFFT-2D are skipped by rearranging terms and introducing eight additional 1-D NUFFTs (NUFFT-1D). The code implementing the NUFFT-accelerated SD-MoM approach has been used to analyze the cells of frequency-selective surfaces (FSSs) and reflectarray antennas (RAs). We have found that the proposed NUFFT-accelerated SD-MoM can be up to three orders of magnitude faster than the brute-force SD-MoM (direct summation of the truncated series) and around two orders of magnitude faster than commercial software CST.

Genetic variants associated with complex traits are primarily noncoding, and their effects on gene-regulatory activity remain largely uncharacterized. To address this, we profile epigenomic variation of histone mark H3K27ac across 387 brain, heart, muscle and lung samples from Genotype-Tissue Expression (GTEx). We annotate 282 k active regulatory elements (AREs) with tissue-specific activity patterns. We identify 2,436 sex-biased AREs and 5,397 genetically influenced AREs associated with 130 k genetic variants (haQTLs) across tissues. We integrate genetic and epigenomic variation to provide mechanistic insights for disease-associated loci from 55 genome-wide association studies (GWAS), by revealing candidate tissues of action, driver SNPs and impacted AREs. Lastly, we build ARE–gene linking scores based on genetics (gLink scores) and demonstrate their unique ability to prioritize SNP–ARE–gene circuits. Overall, our epigenomic datasets, computational integration and mechanistic predictions provide valuable resources and important insights for understanding the molecular basis of human diseases/traits such as schizophrenia.

This communication proves that the analysis of the scattering by a mirror-symmetric multilayered periodic structure (MPS) can be replaced by the analysis of the scattering by two semi-structures with half the size in which the symmetry plane behaves either as a perfect magnetic conductor (PMC) or as a perfect electric conductor (PEC). The proof is based on the reflection properties of the electric and magnetic fields through PMCs and PECs, and it is valid for arbitrary oblique incidence. As an application of this concept, the spectral-domain method of moments (SD-MoM) is reformulated to deal with MPSs limited by PMCs and PECs, and it is used in the design of a mirror-symmetric multilayered linear polarization (LP)-to-circular polarization (CP) converter. The results obtained with SD-MoM are validated by comparison with commercial software CST. Numerical simulations show that the CPU time required by both SD-MoM and CST in the analysis of half the LP-to-CP converter limited by PMC and PEC is between 30% and 42% smaller than that required by the analysis of the complete LP-to-CP converter, which shows the numerical advantage gained in exploiting the symmetry when it is present.

The van der Waals semiconductor metamagnet CrSBr offers an ideal platform for studying the interplay between optical and magnetic properties in the two-dimensional limit. Here, we carried out an exhaustive optical characterization of this material by means of temperature- and magnetic-field-dependent photoluminescence (PL) on flakes of different thicknesses down to the monolayer. We found a characteristic emission peak that is quenched upon switching the ferromagnetic layers from an antiparallel to a parallel configuration and exhibits a temperature dependence different from that of the peaks commonly ascribed to excitons. The contribution of this peak to the PL is boosted around 30–40 K, coinciding with the hidden order magnetic transition temperature. Our findings reveal the connection between the optical and magnetic properties via the ionization of magnetic donor vacancies. This behavior enables a useful tool for the optical reading of the magnetic states in atomically thin layers of CrSBr and shows the potential of the design of 2D heterostructures with magnetic and excitonic properties.

The crystal structure of the CH3NH3PbBr3perovskite has been investigated under high-pressure conditions by synchrotron-based powder X-ray diffraction. We found that after the previously reported phase transitions in CH3NH3PbBr3(Pm3̅m→Im3̅→Pmn21), which occur below 2 GPa, there is a third transition to a crystalline phase at 4.6 GPa. This transition is reported here for the first time contradicting previous studies, which reported amorphization of CH3NH3PbBr3between 2.3 and 4.6 GPa. Our X-ray diffraction measurements show that CH3NH3PbBr3remains crystalline up to at least 7.6 GPa, the highest pressure covered by experiments. The new high-pressure phase is also described by the space group Pmn21; however, the transition involves abrupt changes in the unit-cell parameters and a 3% decrease of the unit-cell volume. Our conclusions are confirmed by optical-absorption experiments, by visual observations, and by the fact that pressure-induced changes up to 10 GPa are reversible. The optical studies also allow for the determination of the pressure dependence of the band-gap energy, which is discussed using the structural information obtained from X-ray diffraction.

Preferred crystallographic orientation in polycrystalline films is desirable for efficient charge carrier transport in metal halide perovskites and semiconductors. However, the mechanisms that determine the preferred orientation of halide perovskites are still not well understood. In this work, we investigate crystallographic orientation in lead bromide perovskites. We show that the solvent of the precursor solution and organic A-site cation strongly affect the preferred orientation of the deposited perovskite thin films. Specifically, we show that the solvent, dimethylsulfoxide, influences the early stages of crystallization and induces preferred orientation in the deposited films by preventing colloidal particle interactions. Additionally, the methylammonium A-site cation induces a higher degree of preferred orientation than the formamidinium counterpart. We use density functional theory to show that the lower surface energy of the (100) plane facets in methylammonium-based perovskites, compared to the (110) planes, is the reason for the higher degree of preferred orientation. In contrast, the surface energy of the (100) and (110) facets is similar for formamidinium-based perovskites, leading to lower degree of preferred orientation. Furthermore, we show that different A-site cations do not significantly affect ion diffusion in bromine-based perovskite solar cells but impact ion density and accumulation, leading to increased hysteresis. Our work highlights the interplay between the solvent and organic A-site cation which determine crystallographic orientation and plays a critical role in the electronic properties and ionic migration of solar cells.

The poem "Patria Archipelago" by Leo Boix and Alexandra Lytton Regalado is presented. First Line: And then the time came to be inside; Last Line: the way a pebble ripples into still water.

The tongue facilitates vital activities such as swallowing. Swallowing difficulties (dysphagia) are common in the elderly and in many adult-onset neuromuscular diseases. In oculopharyngeal muscular dystrophy (OPMD), dysphagia is often the first symptom. OPMD is an autosomal dominant myopathy caused by a trinucleotide expansion mutation in the gene encoding PABPN1. The expanded PABPN1 forms insoluble nuclear aggregates that reduce the levels of the soluble form. Clinical tongue involvement in OPMD has been documented but is poorly understood.

To analyse the differences in pharmacokinetic and clinical parameters (bleeding rates and joint health) before and after switching from standard half-life factor VIII (FVIII) to extended half-life pegylated FVIII in patients with severe/moderate haemophilia A on prophylaxis, 1 year before and after the switch in real-life.

•Fatigue is experienced by more than 80% of people with multiple sclerosis.•Patient reported outcomes are used to measure fatigue. However, they have significant limitations in terms of validity and reliability.•This study is the first systematic review to assess the psychometric properties of all patient-reported outcomes specific to fatigue in people with multiple sclerosis.•Patient-reported outcomes are the best way to understand patient perceptions, so it is important to follow current standards when developing these instruments to ensure their correct use and interpretability.

In this brief, glide symmetry is applied to design common-mode rejection filters based on defected ground structures with bandstop response. To this aim, complementary split-ring resonators are chosen as the basic components for common-mode rejection. To illustrate the advantages of using glide symmetry, three implementations are studied and compared. The results reveal that glide symmetry offers the best performance in terms of common-mode rejection level and fractional bandwidth. Furthermore, glide symmetry barely affects the integrity of the differential mode. A prototype of each of the considered symmetries has been designed, simulated, and tested for practical validation. Good agreement is observed between the simulated and measured results, experimentally demonstrating the advantages of glide symmetry.

Let Rbe a commutative Noetherian ring of prime characteristic p. The main goal of this paper is to study in some detail when {p∈Spec(R):FEpis finitely generated as a ring over its degree zero piece}is an open set in the Zariski topology, where FEpdenotes the Frobenius algebra attached to the injective hull of the residue field of Rp.We show that this is true when Ris a Stanley–Reisner ring; moreover, in this case, we explicitly compute its closed complement, providing an algorithmic method for doing so.

Treatment failure occurs in about 25% of patients with methicillin-susceptible Staphylococcusaureus(MSSA) bacteremia. We assessed whether cloxacillin plus fosfomycin achieves better treatment success than cloxacillin alone in hospitalized adults with MSSA bacteremia. We conducted a multicenter, open-label, phase III–IV superiority randomized clinical trial. We randomly assigned patients (1:1) to receive 2 g of intravenous cloxacillin alone every 4 h or with 3 g of intravenous fosfomycin every 6 h for the initial 7 days. The primary endpoint was treatment success at day 7, a composite endpoint with the following criteria: patient alive, stable or with improved quick Sequential Organ Failure Assessment score, afebrile and with negative blood cultures for MSSA, adjudicated by an independent committee blinded to treatment allocation. We randomized 215 patients, of whom 105 received cloxacillin plus fosfomycin and 110 received cloxacillin alone. We analyzed the primary endpoint with the intention-to-treat approach in 214 patients who received at least 1 day of treatment. Treatment success at day 7 after randomization was achieved in 83 (79.8%) of 104 patients receiving combination treatment versus 82 (74.5%) of 110 patients receiving monotherapy (risk difference 5.3%; 95% confidence interval (CI), –5.95–16.48). Secondary endpoints, including mortality and adverse events, were similar in the two groups except for persistent bacteremia at day 3, which was less common in the combination arm. In a prespecified interim analysis, the independent committee recommended stopping recruitment for futility prior to meeting the planned randomization of 366 patients. Cloxacillin plus fosfomycin did not achieve better treatment success at day 7 of therapy than cloxacillin alone in MSSA bacteremia. Further trials should consider the intrinsic heterogeneity of the infection by using a more personalized approach. ClinicalTrials.gov registration: NCT03959345.

•El cribado del cáncer de próstata en nuestro medio consiste en la determinación de PSA y práctica de tacto rectal en pacientes de alto riesgo, con esperanza de vida de más de 15 años y siempre que accedan previamente informados de las consecuencias de ser diagnosticados.•Las consecuencias del cribado sistemático más importantes son el sobrediagnóstico y el sobretratamiento, que se combaten mediante pruebas diagnósticas y terapéuticas adecuadas a una cuidadosa evaluación de riesgo de cancer clínicamente significativo.•La resonancia magnética de próstata no es una prueba diagnóstica de cribado.•La resonancia magnética y la clasificación PI-RADS v2 ayudan a identificar pacientes en los que es necesario practicar biopsia prostática diagnóstica.

In the last years, new standards (e.g., the EN4555X series) and indices (i.e., RSS, eDiM,) have been published to include repairability aspects in product design. These indices are very useful in the design phase to characterize the product and to understand the ability of products to be repaired, reused, upgraded, and recycled. However, the way how these indices have been developed presents some issues that can lead to a wrong assessment/evaluation and result interpretation. This work analyses the main shortcomings encountered in the assessment of the disassembly index in the RSS score providing useful guidelines to improve them. The study has been carried out based on a set of laboratory tests and results analysis performed on cooking appliances (e.g., ovens, hobs, hoods). Nine issues related to the disassembly index have been highlighted including a focus on the impacted parameters. The work provides a useful base to enhance the studies related to product disassembly for repairability as well as to update the standard related to repairability and to make use of this index in the early phase of product design.

Nowadays, household appliance manufacturers shall adapt their engineering methods and tools to meet environmental concerns. Despite the environmental assessment of products and services is usually carried out based on Life Cycle Assessment (LCA) standardized approach (e.g., ISO14040/14044), numerous assumptions are up to practitioners’ discretion, such as functional unit, system boundaries, or allocation method. These choices may lead to a results discrepancy between equivalent studies, even if similar products are considered. The goal of this work is to present a method for determining appropriate metrics (indices) that enable designers to compare the findings of LCA analysis carried out in the context of home appliances. The indices refer to the cooker hoods family and they were developed through a systematic literature review. LCA studies carried out from 2006 to 2022 were the basis for the identification of design features and parameters that allow the normalization of results retrieved in different studies. These features served as the basis for the indices formulation, enabling an accurate comparison of appliances from the same family. The application of these indices, according to the results, makes LCA evaluations of cooker hood models with different performances and design factors comparable. Finally, the same approach can be adopted to create a framework and a useful guide to conduct future LCA studies for other household appliance families with the aim to provide a normalization basis to compare product design alternatives.

•The CLL15 signature, based on the expression of genes associated with microenvironment signaling, predicts early progression in CLL.•The predictive power of the CLL15 signature is independent of the IGHVmutational status and IPS-E CLL score.

Several gene expression profiles with a strong correlation with patient outcomes have been previously described in chronic lymphocytic leukemia (CLL), although their applicability as biomarkers in clinical practice has been particularly limited. Here we describe the training and validation of a gene expression signature for predicting early progression in patients with CLL based on the analysis of 200 genes related to microenvironment signaling on the NanoString platform. In the training cohort (n = 154), the CLL15 assay containing a 15-gene signature was associated with the time to first treatment (TtFT) (hazard ratio [HR], 2.83; 95% CI, 2.17-3.68; P < .001). The prognostic value of the CLL15 score (HR, 1.71; 95% CI, 1.15-2.52; P = .007) was further confirmed in an external independent validation cohort (n = 112). Notably, the CLL15 score improved the prognostic capacity over IGHV mutational status and the International Prognostic Score for asymptomatic early-stage (IPS-E) CLL. In multivariate analysis, the CLL15 score (HR, 1.83; 95% CI, 1.32-2.56; P < .001) and the IPS-E CLL (HR, 2.23; 95% CI, 1.59-3.12; P < .001) were independently associated with TtFT. The newly developed and validated CLL15 assay successfully translated previous gene signatures such as the microenvironment signaling into a new gene expression–based assay with prognostic implications in CLL.

The high-pressure crystal structure evolution of CH3NH3PbBr3(MAPbBr3) perovskite has been investigated by single-crystal X-ray diffraction and synchrotron-based powder X-ray diffraction. Single-crystal X-ray diffraction reveals that the crystal structure of MAPbBr3undergoes two phase transitions following the space-group sequence: Pm3̅m→ Im3̅ → Pmn21, unveiling the occurrence of a nonpolar/polar transition (Im3̅ → Pmn21). The transitions take place at around 0.8 and 1.8 GPa, respectively. This result contradicts the previously reported phase transition sequence: Pm3̅m→ Im3̅ →Pnma. In this work, the crystal structures of each of the three phases are determined from single-crystal X-ray diffraction analysis, which is later supported by Rietveld refinement of powder X-ray diffraction patterns. The pressure dependence of the crystal lattice parameters and unit-cell volumes are determined from the two aforementioned techniques, as well as the bulk moduli for each phase. The bandgap behavior of MAPbBr3has been studied up to around 4 GPa, by means of single-crystal optical absorption experiments. The evolution of the bandgap has been well explained using the pressure dependence of the Pb–Br bond distance and Pb–Br–Pb angles as determined from single-crystal X-ray diffraction experiments.

Metal halide perovskite nanocrystals can display excellent light-emission properties, leveraging the chemical versatility of this family of materials. However, using these features in functional films is an elusive task due to aggregation and material-instability problems. Using a metal-organic host matrix based on a sol-gel approach allows for a controlled in situcrystallization of perovskite nanocrystals with extremely low-demanding fabrication methods. As a result, this ambient annealing-free process generates high-performance nanocomposite thin films with photoluminescence quantum yield (PLQY) >80% with outstanding ambient and mechanical stability. The crystallization dynamics determining the final nanoparticle size, and thus the emission properties, can be adjusted in detail through the ambient exposure and precursor concentration.

Hydrogenated graphene (H-Gr) is an extensively studied system not only because of its capabilities as a simplified model system for hydrocarbon chemistry but also because hydrogenation is a compelling method for Gr functionalization. However, knowledge of how H-Gr interacts with molecules at higher pressures and ambient conditions is lacking. Here we present experimental and theoretical evidence that room temperature O2exposure at millibar pressures leads to preferential removal of H dimers on H-functionalized graphene, leaving H clusters on the surface. Our density functional theory (DFT) analysis shows that the removal of H dimers is the result of water or hydrogen peroxide formation. For water formation, we show that the two H atoms in the dimer motif attack one end of the physisorbed O2molecule. Moreover, by comparing the reaction pathways in a vacuum with the ones on free-standing graphene and on the graphene/Ir(111) system, we find that the main role of graphene is to arrange the H atoms in geometrical positions, which facilitates the activation of the O═O double bond.

Whether thrombectomy alone is equally as effective as intravenous alteplase plus thrombectomy remains controversial. We aimed to determine whether thrombectomy alone would be non-inferior to intravenous alteplase plus thrombectomy in patients presenting with acute ischaemic stroke.

Mounting evidence suggests that antimicrobial peptides and proteins (AMPs) belonging to the RNase A superfamily have a critical role in defending the bladder and kidney from bacterial infection. RNase 6 has been identified as a potent, leukocyte-derived AMP, but its impact on urinary tract infection (UTI) in vivo has not been demonstrated. To test the functional role of human RNase 6, we generated RNASE6transgenic mice and studied their susceptibility to experimental UTI. In addition, we generated bone marrow-derived macrophages to study the impact of RNase 6 on antimicrobial activity within a cellular context. When subjected to experimental UTI, RNASE6transgenic mice developed reduced uropathogenic Escherichia coli(UPEC) burden, mucosal injury, and inflammation compared to non-transgenic controls. Monocytes and macrophages were the predominant cellular sources of RNase 6 during UTI, and RNASE6transgenic macrophages were more proficient at intracellular UPEC killing than non-transgenic controls. Altogether, our findings indicate a protective role for human RNase 6 during experimental UTI.

One of the main aspects to increase the useful life of ErP and reduce waste generation is the product repairability. Key factors in assessing the ability to repair a product are the ease of disassembly, and the use of repairability indexes (i.e., eDiM, French repairability index, RSS, etc.). The goal of this paper is to retrieve eco-design guidelines analyzing the product repairability of target components belonging to four different types of electric ovens. The analysis adopts as baseline the report of the Joint Research Centre and the European standard EN 45554. Results provide interesting insights concerning the identification of disassembly issues and the mitigation of these hotspots through eco-design guidelines retrieved by the analysis of repairability.

Traditional assembly processes such as screw fastening and riveting are increasingly being replaced by new processes such as adhesive bonding. Life cycle performance including fatigue and durability are critical, for which surface activation techniques are often used with the aim of improving both mechanical and life cycle performance. Within this context, the present paper aims to investigate the life cycle performance of adhesive bonding in relation to engineering polymers considering four surface pre-treatments: mechanical, chemical, plasma, and laser activation. The work focuses on two key aspects: (i) mechanical characterization of fatigue performance by assessing the useful life of joints, and (ii) environmental analysis through Life Cycle Assessment (LCA). The outcome of this study provides important insight into the development of laser and plasma technologies as sustainable surface activation methods for polymer joining methods. The substitution of traditional joining methods (i.e., bolting, riveting) with adhesive bonding will allow reductions in overall product weight to be achieved.

•A human relevant POP mixture was injected into the allantois of the chicken egg.•Different POPs reached the chicken embryo brain at varying speed and concentrations.•Brain concentrations were in the same range as measured in humans.•Measured concentrations could be fitted to specific pharmacokinetic models.•Chicken embryo is a novel model to study toxicological endpoints.

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ABSTRACTOwing to the recent outbreak of Coronavirus Disease of 2019 (COVID-19), it is urgent to develop effective and safe drugs to treat the present pandemic and prevent other viral infections that might come in the future. Proteins from our own innate immune system can serve as ideal sources of novel drug candidates thanks to their safety and immune regulation versatility. Some host defense RNases equipped with antiviral activity have been reported over time. Here, we try to summarize the currently available information on human RNases that can target viral pathogens, with special focus on enveloped single-stranded RNA (ssRNA) viruses. Overall, host RNases can fight viruses by a combined multifaceted strategy, including the enzymatic target of the viral genome, recognition of virus unique patterns, immune modulation, control of stress granule formation, and induction of autophagy/apoptosis pathways. The review also includes a detailed description of representative enveloped ssRNA viruses and their strategies to interact with the host and evade immune recognition. For comparative purposes, we also provide an exhaustive revision of the currently approved or experimental antiviral drugs. Finally, we sum up the current perspectives of drug development to achieve successful eradication of viral infections.