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In previously reported retrospective studies, high tumor RNA disruption during neoadjuvant chemotherapy predicted for post-treatment pathologic complete response (pCR) and improved disease-free survival at definitive surgery for primary early breast cancer. The BREVITY (Breast Cancer Response Evaluation for Individualized Therapy) prospective clinical trial (NCT03524430) seeks to validate these prior findings. Here we report training set (Phase I) findings, including determination of RNA disruption index (RDI) cut points for outcome prediction in the subsequent validation set (Phase II; 454 patients). In 80 patients of the training set, maximum tumor RDI values for biopsies obtained during neoadjuvant chemotherapy were significantly higher in pCR responders than in patients without pCR post-treatment (P 1⁄4 .008). Moreover, maximum tumor RDI values ≤3.7 during treatment predicted for a lack of pCR at surgery (negative predictive value 1⁄4 93.3%). These findings support the prospect that on-treatment tumor RNA disruption assessments may effectively predict post-surgery outcome, possibly permitting treatment optimization.

Histone deacetylases (HDACs) are enzymes pivotal for histone modification (i.e. acetylation marks removal), chromatin accessibility and gene expression regulation. Class I HDACs (including HDAC1, 2, 3, 8) are ubiquitously expressed and they often participate in multi-molecular protein complexes. To date, three neurodevelopmental disorders caused by mutations in genes encoding for HDACs (HDAC4, HDAC6 and HDAC8) and thus belonging to the group of chromatinopathies, have been described. We performed whole exome sequencing (WES) for a patient (#249) clinically diagnosed with the chromatinopathy Rubinstein-Taybi syndrome (RSTS) but negative for mutations in RSTS genes, identifying a de novo frameshift variant in HDAC2 gene. We then investigated its molecular effects in lymphoblastoid cell lines (LCLs) derived from the patient compared to LCLs from healthy donors (HD). As the variant was predicted to be likely pathogenetic and to affect the sequence of nuclear localization signal, we performed immunocytochemistry and lysates fractionation, observing a nuclear mis-localization of HDAC2 compared to HD LCLs. In addition, HDAC2 total protein abundance resulted altered in patient, and we found that newly identified variant in HDAC2 affects also acetylation levels, with significant difference in acetylation pattern among patient #249, HD and RSTS cells and in expression of a known molecular target. Remarkably, RNA-seq performed on #249, HD and RSTS cells shows differentially expressed genes (DEGs) common to #249 and RSTS. Interestingly, our reported patient was clinically diagnosed with RSTS, a chromatinopathy which known causative genes encode for enzymes antagonizing HDACs. These results support the role of HDAC2 as causative gene for chromatinopathies, strengthening the genotype-phenotype correlations in this relevant group of disorders.

Nanoparticles' (NPs) permeation through cell membranes, whether it happens via passive or active transport, is an essential initial step for their cellular internalization. The NPs' surface coating impacts the way they translocate through the lipid bilayer and the spontaneity of the process. Understanding the molecular details of NPs' interaction with cell membranes allows the design of nanosystems with optimal characteristics for crossing the lipid bilayer: computer simulations are a powerful tool for this purpose. In this work, we have performed coarse-grained molecular dynamics simulations and free energy calculations on spherical titanium dioxide NPs conjugated with polymer chains of different chemical compositions. We have demonstrated that the hydrophobic/hydrophilic character of the chains, more than the nature of their terminal group, plays a crucial role in determining the NPs' interaction with the lipid bilayer and the thermodynamic spontaneity of NPs' translocation from water to the membrane. We envision that this computational work will be helpful to the experimental community in terms of the rational design of NPs for efficient cell membrane permeation.By coarse-grained molecular dynamics simulations, we have unveiled that nanoparticles coated with mixed hydrophobic/hydrophilic polymer chains spontaneously penetrate lipid membranes, unlike those covered with chains of hydrophilic character only.

Introduction: We assessed clinical and laboratory parameters associated with early recurrence of febrile seizure in patients presenting at the Emergency Department with a first episode. Methods: Case series of patients admitted to the emergency department with the first episode of febrile seizure for ten consecutive years. Exclusion criteria were focal features and prolonged duration (>15 min). Results: We included 693 patients, 284 (41%) female. Median age of 20 (IQR 15–27) months. Fifty-two (8%) patients had a recurrence within 24 h. At univariate analysis, patients with recurrent seizures had higher use of antipyretics (88% vs. 74%, P = 0.03, OR 2.6, 95% CI: 1.1–7.7), higher median maximal body temperature (39.3 °C, IQR 38.9–39.9, vs. 38.9, IQR 38.4–39.3, P < 0.001, OR 2.3, 95% CI: 1.5–2.6) and presented with a lower proportion of respiratory tract infections (54% vs. 70%, P = 0.02) compared to patients without recurrence. A maximal body temperature equal to or higher than 39 °C was associated with a higher recurrence (11% vs. 4%, P < 0.001, OR 2.9, 95% CI: 1.6–5.6). Hyponatremia was not associated with a risk of recurrence. The multivariate analysis confirmed a direct association with body temperature (OR 2.3, 95% CI: 1.5–3.7, P < 0.001), and an inverse association with respiratory tract infections (OR 0.4, 95% CI: 0.2–0.9, P = 0.01), while antipyretic use was not correlated (OR 1.9, 95% CI: 0.8–5.2, P = 0.2). Conclusions: High body temperature and respiratory tract infections were (directly and inversely) associated with recurrences. Consideration of these conditions might help for anticipating the probability of recurrence.

Auditability allows to track all the read operations performed on a register. It abstracts the need of data owners to control access to their data, tracking who read which information. This work considers possible formalizations of auditing and their ramification for the possibility of providing it. The natural definition is to require a linearization of all write, read and audit operations together (atomic auditing). The paper shows that atomic auditing is a powerful tool, as it can be used to solve consensus. The number of processes that can solve consensus using atomic audit depends on the number of processes that can read or audit the register. If there is a single reader or a single auditor (the writer), then consensus can be solved among two processes. If multiple readers and auditors are possible, then consensus can be solved among the same number of processes. This means that strong synchronization primitives are needed to support atomic auditing. We give implementations of atomic audit when there are either multiple readers or multiple auditors (but not both) using primitives with consensus number 2 (swap and fetch&add). When there are multiple readers and multiple auditors, the implementation uses compare&swap. These findings motivate a weaker definition, in which audit operations are not linearized together with read and write operations (regular auditing). We prove that regular auditing can be implemented from ordinary reads and writes on atomic registers.

IntroductionInternet Gaming Disorder (IGD) according to DSM-5 is a behavioral addiction needing additional study. IGD in youth is correlated with anxiety, depression, attention problems, interpersonal problems, social phobia, behavior problems and low academic achievement. The aim of the present research is to contribute to the understanding of the disorder, by providing preliminary data on the factorial structure of the IGD Questionnaire in the Italian version.Participants612 Italian students (323 females), mean of age = 13.94 (SD = 2.44). Instruments: a survey comprising IGD Questionnaire, Internet Addiction Test (IAT), Children's Coping Strategies Checklist (CCSC-R1), Assessment of Interpersonal Relations (AIR), and Child Behavior Checklist (CBCL).Results15.2% of participants showed a sub-clinical IGD and 2.1% met the full diagnostic criteria. Participants with IGD showed lower scores in interpersonal relationships, worse coping strategies and higher scores in externalization. The factorial structure of the IGD Questionnaire highlights 4 factors ("addiction", "gaming as coping", "impaired control" and "negative outcomes") that explain 52.14% of the variance. A single-factor solution was also tested and results seem to be coherent with the four-factor solution, explaining less variance.ConclusionsIGD is a complex clinical condition that can be thought both as a single-factored and as a multi-faceted condition.

Leímos con gran interés el artículo de López-Pintor et al. (https://ojs.sanidad.gob.es/index.php/resp/article/view/323) sobre la relación entre el valor Cycle Threshold (CT) de la reacción en cadena de la polimerasa (PCR) inicial de pacientes con COVID-19 y la persistencia de la infección. Desde finales de 2019, la COVID-19 estalló rápidamente en todo el mundo, provocando una pandemia que ha planteado serios desafíos a la comunidad médica. Para detener la propagación del virus, los funcionarios de salud han aplicado una serie de medidas extraordinarias de Salud Pública, incluida la cuarentena de las personas que estuvieron expuestas a la COVID-19. Sin embargo, la duración óptima de la cuarentena sigue siendo un tema de debate, dados los hallazgos sobre los resultados positivos de las pruebas de PCR para el SARS-CoV-2 durante muchas semanas. Por lo tanto, la identificación de factores que predicen pruebas negativas podría ser útil para optimizar las medidas de prevención y control de infecciones, particularmente en vista del esfuerzo mundial actual para acortar la duración del aislamiento.

En este proyecto utiliza el huerto didáctico de la Facultad de Educación-Centro de Formación del Profesorado de la UCM como una herramienta para trabajar la educación para la sostenibilidad a través de actividades orientadas a atender la diversidad del alumnado y favorecer la integración, con estudiantes de los Grados de Maestro de Educación Infantil y Educación Primaria. La Educación Ambiental es clave en la formación inicial de maestros, quienes tendrán la responsabilidad de educar a los futuros gestores de una sociedad que afronta grandes retos ambientales a nivel global. Sin embargo, esta disciplina presenta muchas carencias en la formación inicial de maestros, donde no existe ninguna asignatura obligatoria con contenidos específicos en Educación para la Sostenibilidad y donde, además, raramente se trabaja de manera trasversal a lo largo de los estudios del Grado de Maestro. Por otro lado, un reto que tendrán que afrontar los futuros maestros en las aulas es atender la diversidad de su alumnado y favorecer la integración de los estudiantes en las dinámicas de trabajo. El huerto didáctico es un espacio que ofrece importantes beneficios a los estudiantes de los Grados en Maestro en este sentido, permitiendo trabajar de manera manipulativa, vivencial, colaborativa y globalizadora contenidos de diferentes áreas del currículo escolar en un contexto diferente al aula muy propicio para trabajar aspectos relacionados con la integración y la atención a la diversidad. Desde su creación en 2014, el huerto didáctico de la Facultad de Educación ha crecido curso tras curso debido al éxito que ha tenido entre todos los miembros de la comunidad universitaria, docentes, PAS y estudiantes, quienes cada año realizan allí las prácticas académicas de diversas asignaturas. El trabajo que presenta este proyecto está ligado de manera oficial a la formación académica de los estudiantes de la Facultad de Educación a través de las prácticas de distintas asignaturas del Departamento de Did

This dissertation is a study of how government actions can impact the macroeconomy under different circumstances. In Chapter 1, I examine the impacts from political conflict and violence in several empirical frameworks. Using generalized least squares, I find that higher levels of magnitude of violence lead to lower growth, investment, and standards of living. This result is further confirmed after running two-stage least squares regressions to address the concern of reverse correlation. I also apply a panel vector-autoregression (VAR) model to study the cross-country economic effects of a shock to the magnitude of political violence in three groups of countries that have had turbulent conflicts in the late 20th century. Findings from the panel VARs show that cross-country effects from a political violence shock are most significant when the countries share characteristics directly related to the cause of the conflict. In Chapter 2 and 3, I pivot towards studying how the behavioral feature, "myopia", affects government policy in the U.S. economy. Chapter 2 investigates the impact of fiscal policy on economic stimulation within the context of agents who exhibit partial myopia, implying that households and firms are less forward-looking and attentive towards future events. This deviation from perfect rationality impacts the marginal propensity to consume, ultimately challenging the theory of Ricardian Equivalence. To address this, I emphasize the importance of introducing partially myopic agents into a new Keynesian model with hand-to-mouth consumers. I estimate the model using Bayesian MCMC methods to fit U.S. time series data between 1984-2019 under both determinacy and indeterminacacy. Under determinacy, partially myopic agents may result in higher fiscal multipliers but significantly crowd out private investment. Furthermore, the estimated myopia parameter is 0.86, which is in alignment with Gabaix (2020). However, the data suggets a preference for an indeterminat

The healthy lifestyle index (HLI), defined as the unweighted sum of individual lifestyle components, was used to investigate the combined role of lifestyle factors on health-related outcomes. We introduced weighted outcome-specific versions of the HLI, where individual lifestyle components were weighted according to their associations with disease outcomes. Within the European Prospective Investigation into Cancer and Nutrition (EPIC), we examined the association between the standard and the outcome-specific HLIs and the risk of T2D, CVD, cancer, and all-cause premature mortality. Estimates of the hazard ratios (HRs), the Harrell’s C-index and the population attributable fractions (PAFs) were compared. For T2D, the HR for 1-SD increase of the standard and T2D-specific HLI were 0.66 (95% CI: 0.64, 0.67) and 0.43 (0.42, 0.44), respectively, and the C-index were 0.63 (0.62, 0.64) and 0.72 (0.72, 0.73). Similar, yet less pronounced differences in HR and C-index were observed for standard and outcome-specific estimates for cancer, CVD and all-cause mortality. PAF estimates for mortality before age 80 were 57% (55%, 58%) and 33% (32%, 34%) for standard and mortality-specific HLI, respectively. The use of outcome-specific HLI could improve the assessment of the role of lifestyle factors on disease outcomes, thus enhancing the definition of public health recommendations.

Importance: Vascular disease is a treatable contributor to dementia risk, but the role of specific markers remains unclear, making prevention strategies uncertain. Objective: To investigate the causal association between white matter hyperintensity (WMH) burden, clinical stroke, blood pressure (BP), and dementia risk, while accounting for potential epidemiologic biases. Design, Setting, and Participants: This study first examined the association of genetically determined WMH burden, stroke, and BP levels with Alzheimer disease (AD) in a 2-sample mendelian randomization (2SMR) framework. Second, using population-based studies (1979-2018) with prospective dementia surveillance, the genetic association of WMH, stroke, and BP with incident all-cause dementia was examined. Data analysis was performed from July 26, 2020, through July 24, 2022. Exposures: Genetically determined WMH burden and BP levels, as well as genetic liability to stroke derived from genome-wide association studies (GWASs) in European ancestry populations. Main Outcomes and Measures: The association of genetic instruments for WMH, stroke, and BP with dementia was studied using GWASs of AD (defined clinically and additionally meta-analyzed including both clinically diagnosed AD and AD defined based on parental history [AD-meta]) for 2SMR and incident all-cause dementia for longitudinal analyses. Results: In 2SMR (summary statistics-based) analyses using AD GWASs with up to 75 024 AD cases (mean [SD] age at AD onset, 75.5 [4.4] years; 56.9% women), larger WMH burden showed evidence for a causal association with increased risk of AD (odds ratio [OR], 1.43; 95% CI, 1.10-1.86; P = .007, per unit increase in WMH risk alleles) and AD-meta (OR, 1.19; 95% CI, 1.06-1.34; P = .008), after accounting for pulse pressure for the former. Blood pressure traits showed evidence for a protective association with AD, with evidence for confounding by shared genetic instruments. In the longitudinal (individual-level data

Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in either of two genes (CREBBP, EP300) which encode for the proteins CBP and p300, which both have a function in transcription regulation and histone acetylation. As a group of international experts and national support groups dedicated to the syndrome, we realised that marked heterogeneity currently exists in clinical and molecular diagnostic approaches and care practices in various parts of the world. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria for types of RTS (RTS1: CREBBP; RTS2: EP300), molecular investigations, long-term management of various particular physical and behavioural issues and care planning. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimisation of diagnostics and care.

Early life microbiota encompasses of a large percentage of Bifidobacterium, while it is not sufficiently understood how the Bifidobacterium population develops after infant’s birth. Current study investigated the longitudinal changes in Bifidobacterium population during the first two years of life in 196 term born infants (1,654 samples) using 16S rRNA-23S rRNA internal transcribed spacer (ITS) sequence analysis. Throughout the first two years of life, Bifidobacterium breve, Bifidobacterium longum subsp. longum and Bifidobacterium adolescentis were most dominant and prevalent in the Bifidobacterium population, while B. breve had the highest relative abundance and prevalence during the first week of life and it was taken over by B. longum subsp. longum around two years after birth. Sampling time points, early antibiotic(s) exposure (effect only measurable within a month after birth), delivery mode (effect still detectable two-months after birth) and feeding mode (effect lasted until six months after birth), significantly contributed to the overall variation in the bifidobacterial population. From six months onwards, introducing of solid food and cessation of breastfeeding were accompanied with drastic changes in the composition in bifidobacterial population. Altogether, current study confirmed the effect of potential contributors to the longitudinal changes within the bifidobacterial population during the first two years of life.

Mesomodels for masonry and historical structures typically focus on regular bond masonry, for which the geometrical description and the discretization are straightforward. The present contribution leverages image segmentation tools on acquired images of real historic masonry assemblies. The geometrical information of the mortar joints is lumped on null-thickness interface descriptions by exploiting the notion of medial axis, a concept from the field of image processing. A kinematic limit analysis problem is solved by formulating the problem statement as a linear programming problem, with the assumption of infinitely strong and rigid blocks. This technique is applied to analyze the homogenized failure behaviour of a representative volume element (RVE-) window, which corresponds to a representative portion of the historical masonry arrangement used to derive the overall mechanical properties and behaviour of the entire assembly. Based on successful image acquisition and segmentation, this approach computes homogenized failure envelopes in the stress space with the corresponding failure mechanisms with unparalleled computational efficiency, providing a streamlined pathway from image-based input to homogenization. Results in terms of homogenized failure envelopes in the stress space and the corresponding failure mechanisms are critically commented on., info:eu-repo/semantics/published

The article focuses on Tanta gente, Mariana (1959) with the aim of analysing the ways in which the author, through the trajectories of the protagonists, contributes to designing a geography of subalternity feminine. Both the space and its inhabitants are mirrors of a hostile context that confines these women inexorably out of place. The eponymous novel and “A Menina Arminda”, in particular, provide a reflection on the deaf revolt of all those women who, escaping the pre-established paths, refuse to conform to the roles of wives, mothers and good housewives.

This study aims to explore strategies and methods that Swedish teachers use to motivate middle-school students to read literature. By distributing qualitative surveys to teachers, we seek to gain a deeper understanding of how Swedish teachers motivate their students to engage with literature in the classroom. The study is centered around two main research questions: First, what strategies and methods do teachers use to raise 7–9 students interested in reading literature? Second, what challenges and opportunities do these strategies and methods present? The results show that effective strategies include allocating sufficient time for reading, choosing texts that match the students’ own life experiences and providing the opportunity to choose what to read autonomously. Challenges include not having enough resources and dealing with different interests among students. However, there are opportunities to improve teaching by using a variety of interesting materials. This study highlights how important teachers are when it comes to creating a lively and welcoming space for reading that motivate students to involve and learn more.

This paper examines the relationship between language, (in)visibility, and (im)mobility in racialized spaces, focusing on Finnish, Somali, and Arabic speakers in Sweden. Using a theoretical framework based on hegemonic whiteness and intersectionality, the study explores how multilingual practices and subjectivities intersect with race, religion, gender, and class to shape social visibility and mobility. The research draws on linguistic ethnographic data, including interviews, linguistic landscape documentation, and an analysis of the media discourse. The study finds that while Finnish speakers have become invisible due to assimilation policies, Somali and Arabic speakers are hypervisible in Swedish public spaces and discourse, although Arabic speakers are sometimes, and in relation to other migrants, nearing Swedish whiteness. However, all three languages and their speakers are constrained by a white normativity that reproduces inequality. The paper challenges simplistic notions of mobility/immobility and visibility/invisibility in the context of a changing racial order in Sweden, where whiteness serves as a binary sorting mechanism that perpetuates inequality. Overall, this research sheds light on the complex entanglement of language, visibility, and mobility in white spaces and contributes to a more nuanced understanding of the intersectional dynamics of race and language.

Fisheries can have profound impacts on co-occurring species exposed to incidental capture, particularly those with life history traits that make them vulnerable to elevated mortality levels. Fisheries spatial management holds substantial potential to balance socioeconomic benefits and costs to threatened bycatch species. This study analyzed observer program data for a western Pacific Ocean tuna purse seine fishery to estimate the effect of the spatial and temporal distribution of fishing on catch rates of target and at-risk species by fitting spatially-explicit generalised additive multilevel regression models within a Bayesian inference framework. Mean field prediction surfaces defined catch rate hotspots for principal market tunas, silky sharks, rays and whale sharks, informing the development of candidate area-based management strategies. Due to sample size limitations, odontocete and marine turtle catch geospatial patterns were summarized using 2D hexagonal binning of mean catch rates. Effort could be focused in two areas within core fishing grounds in the Solomon and Bismark Seas to reduce overlap with hotspots for silky sharks, rays and whale sharks without affecting target catch. Effort could also be shifted outside of core fishing grounds to zones with higher target tuna catch rates that would also reduce overlap with hotspots for at-risk species. However, two tuna warmspots overlapped silky and whale shark warmspots. Sparse and small marine turtle and whale shark hotspots occurred across the fishing grounds. Research on the economic and operational viability of alternative spatial management strategies is a priority. A small subset of sets had disproportionately large odontocete captures. Real time fleet communication and move-on rules and avoiding sets on dolphin schools might reduce odontocete catch rates. Management of informative operational predictors such as set association type and mesh size present additional opportunities to balance catch rates of

Rubinstein-Taybi syndrome (RTS) is an archetypical genetic syndrome that is characterised by intellectual disability, well-defined facial features, distal limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in either of two genes (CREBBP, EP300) which encode for the proteins CBP and p300, which both have a function in transcription regulation and histone acetylation. As a group of international experts and national support groups dedicated to the syndrome, we realised that marked heterogeneity currently exists in clinical and molecular diagnostic approaches and care practices in various parts of the world. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria for types of RTS (RTS1: CREBBP; RTS2: EP300), molecular investigations, long-term management of various particular physical and behavioural issues and care planning. The recommendations as presented here will need to be evaluated for improvements to allow for continued optimisation of diagnostics and care.

La tecnologia CRISPR/Cas9 rappresenta un ottimo strumento per effettuare modifiche target all¿interno del genoma, consentendo la disattivazione del gene di interesse. In questo lavoro è stata testata tale tecnologia su embrioni somatici di castagno, silenziando il gene della fitoene desaturasi la cui mutazione dà origine ad un fenotipo albino. I risultati hanno mostrato una buona efficienza di editing, di circa il 60%. Il costrutto CRISPR/Cas9 è stato anche testato sotto forma di ribonucleoproteina in protoplasti isolati da calli embriogenici. Sono stati isolati 4.500.000 protoplasti/mL (91% vitali) e trasfettati con il complesso ribonucleoproteico contenente l¿RNA guida (gRNA) disegnato sul gene della fitoene. I risultati hanno mostrato un¿efficienza di editing del 15-20%, paragonabile ai dati bibliografici

The CRISPR/Cas9 ribonucleoprotein (RNP)-mediated technology represents a fascinating tool for modifying gene expression or mutagenesis as this system allows for obtaining transgene-free plants, avoiding exogenous DNA integration. Holm oak (Quercus ilex) has an important social, economic, and ecological role in the Mediterranean climate zones of Western Europe and North Africa and is severely affected by oak decline syndrome. Here we report the first example of the application of the CRISPR/Cas9-RNP technology in holm oak. Firstly, we evaluated the protoplast isolation from both in vitro leaves and proembryogenic masses. Proembryogenic masses represented the best material to get high protoplast yield (11 x 106 protoplasts/ml) and viability. Secondly, the protoplast transfection ability was evaluated through a vector expressing green fluorescence protein as marker gene of transfection, reaching a transfection percentage of 62% after 24 hours. CRISPR/Cas9 RNPs were successfully delivered into protoplasts resulting in 5.6% ± 0.5% editing efficiency at phytoene desaturase (pds) target genomic region. Protoplasts were then cultured in semisolid media and, after 45 days in culture, developed embryogenic calli were observed in a Murashige and Skoog media with half concentration of NH4NO3 and KNO3 supplemented with 0.1 mg/L benzylaminopurine and 0.1 mg/L 2,4-dichlorophenoxyacetic acid.

Extensive research has focused on numerical methods for analysing regularly stacked masonry, yet the comprehension of load transfer mechanisms in irregular masonry remains lacking. In this context, the present contribution aims to propose a modelling pathway able to extract Representative Volume Elements directly from images of historic masonry, and to determine their failure envelope in the stress space and the corresponding failure mechanisms. To achieve this, recently developed image segmentation tools are combined with distance fields-based morphing procedures and a medial axis extraction technique, effectively lumping mortar joints onto a zero-thickness interfaces geometrical representation, which allows for building efficient models. By identifying intersection points between multiple inclusions, the geometry can be further simplified. This geometry representation obtained from real segmented images serves as the main input to a tailored block-based kinematic limit analysis procedure, formulated and solved as a linear programming problem. Morphed blocks are assumed to be infinitely strong and rigid, therefore failure can only occur at the common interfaces between adjacent blocks. Based on these tools, failure envelopes in the homogenised stress space and their corresponding failure mechanisms can be obtained at unparalleled speeds. Simplified geometries yield similar results with enhanced computational efficiency, especially given larger Representative Volume Elements. The procedure will be illustrated on examples of real historic masonry structures., info:eu-repo/semantics/inPress

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation., Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8 and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5 and DCC), synaptic structure and function genes (for example, PCLO, NCAM1 and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3 and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

Learned image compression codecs have recently achieved impressive compression performances surpassing the most efficient image coding architectures. However, most approaches are trained to minimize rate and distortion which often leads to unsatisfactory visual results at low bitrates since perceptual metrics are not taken into account. In this paper, we show that conditional diffusion models can lead to promising results in the generative compression task when used as a decoder, and that, given a compressed representation, they allow creating new tradeoff points between distortion and perception at the decoder side based on the sampling method.

Ensuring Conditional Independence (CI) constraints is pivotal for the development of fair and trustworthy machine learning models. In this paper, we introduce \sys, a framework that harnesses optimal transport theory for data repair under CI constraints. Optimal transport theory provides a rigorous framework for measuring the discrepancy between probability distributions, thereby ensuring control over data utility. We formulate the data repair problem concerning CIs as a Quadratically Constrained Linear Program (QCLP) and propose an alternating method for its solution. However, this approach faces scalability issues due to the computational cost associated with computing optimal transport distances, such as the Wasserstein distance. To overcome these scalability challenges, we reframe our problem as a regularized optimization problem, enabling us to develop an iterative algorithm inspired by Sinkhorn's matrix scaling algorithm, which efficiently addresses high-dimensional and large-scale data. Through extensive experiments, we demonstrate the efficacy and efficiency of our proposed methods, showcasing their practical utility in real-world data cleaning and preprocessing tasks. Furthermore, we provide comparisons with traditional approaches, highlighting the superiority of our techniques in terms of preserving data utility while ensuring adherence to the desired CI constraints.

Relaxing the sequential specification of a shared object is a way to obtain an implementation with better performance compared to implementing the original specification. We apply this approach to the Counter object, under the assumption that the number of times the Counter is incremented in any execution is at most a known bound $m$. We consider the $k$-multiplicative-accurate Counter object, where each read operation returns an approximate value that is within a multiplicative factor $k$ of the accurate value. More specifically, a read is allowed to return an approximate value $x$ of the number $v$ of increments previously applied to the counter such that $v/k \le x \le vk$. We present three algorithms to implement this object in a wait-free linearizable manner in the shared memory model using read-write registers. All the algorithms have read operations whose worst-case step complexity improves exponentially on that for an exact $m$-bounded counter (which in turn improves exponentially on that for an exact unbounded counter). Two of the algorithms have read step complexity that is asymptotically optimal. The algorithms differ in their requirements on $k$, step complexity of the increment operation, and space complexity., Comment: 26 pages, to be published in SIROCCO 2024 proceedings

LoRaWAN is a wireless technology that enables high-density deployments of IoT devices. Designed for Low Power Wide Area Networks (LPWAN), LoRaWAN employs large cells to service a potentially extremely high number of devices. The technology enforces a centralized architecture, directing all data generated by the devices to a single network server for data processing. End-to-end encryption is used to guarantee the confidentiality and security of data. In this demo, we present \edgelora, a system architecture designed to incorporate edge processing in LoRaWAN without compromising security and confidentiality of data. \edgelora maintains backward compatibility and addresses scalability issues arising from handling large amounts of data sourced from a diverse range of devices. The demo provides evidence on the advantages in terms of reduced latency, lower network bandwidth requirements, higher scalability, and improved security and privacy resulting from the application of the Edge processing paradigm to LoRaWAN., Comment: This paper is a pre-print version of the conference paper that has been accepted to ACM MobiCom 2023: Proceedings of the 29th Annual International Conference on Mobile Computing and Networking

Authors’ contributions IC, CMGB, JIR, SG, JMR, SD, and AM conceived and designed the study. NM, LR, IGD, JS, and ABC conducted the laboratory work. NM, AC, CMGB, and JIR collected and processed the biological samples. ABC developed the DNA extraction protocol. CM, MM, and MV performed the library preparation for NGS and the DNA sequencing. NM, CM, BS, MM, and MV analyzed the 16S data and the metagenomic data. JS, LR, JMR, and IC analyzed the NMR data. CMGB and JIR recruited the subjects. NM, MV, IC, SD, and AM prepared the figures and tables and wrote the manuscript. All authors read and approved the final manuscript., Background: The microbial populations of the human intestinal tract and their relationship to specific diseases have been extensively studied during the last decade. However, the characterization of the human bile microbiota as a whole has been hampered by difficulties in accessing biological samples and the lack of adequate methodologies to assess molecular studies. Although a few reports have described the biliary microbiota in some hepatobiliary diseases, the bile microbiota of healthy individuals has not been described. With this in mind, the goal of the present study was to generate fundamental knowledge on the composition and activity of the human bile microbiota, as well as establishing its potential relationship with human bile-related disorders. Results: Human bile samples from the gallbladder of individuals from a control group, without any record of hepatobiliary disorder, were obtained from liver donors during liver transplantation surgery. A bile DNA extraction method was optimized together with a quantitative PCR (qPCR) assay for determining the bacterial load. This allows the selection of samples to perform functional metagenomic analysis. Bile samples from the gallbladder of individuals suffering from lithiasis were collected during gallbladder resection and the microbial profiles assessed, using a 16S rRNA gene-based sequencing analysis, and compared with those of the control group. Additionally, the metabolic profile of the samples was analyzed by nuclear magnetic resonance (NMR). We detected, for the first time, bacterial communities in gallbladder samples of individuals without any hepatobiliary pathology. In the biliary microecosystem, the main bacterial phyla were represented by Firmicutes, Bacteroidetes, Actinobacteria, and Proteobacteria. Significant differences in the relative abundance of different taxa of both groups were found. Sequences belonging to the family Propionibacteriaceae were more abundant in bile samples from control subjects, Ministerio de Economía, Comercio y Empresa, Sección Deptal. de Farmacia Galénica y Tecnología Alimentaria (Veterinaria), Fac. de Veterinaria, TRUE, pub

Depto. de Relaciones Internacionales e Historia Global, Fac. de Ciencias Políticas y Sociología, TRUE, pub

We define and study a new structural parameter for directed graphs, which we call \emph{ear anonymity}. Our parameter aims to generalize the useful properties of \emph{funnels} to larger digraph classes. In particular, funnels are exactly the acyclic digraphs with ear anonymity one. We prove that computing the ear anonymity of a digraph is \NP/-hard and that it can be solved in $O(m(n + m))$-time on acyclic digraphs (where \(n\) is the number of vertices and \(m\) is the number of arcs in the input digraph). It remains open where exactly in the polynomial hierarchy the problem of computing ear anonymity lies, however for a related problem we manage to show $\Sigma_2^p$-completeness.

Background: Nordic walking (NW) has several potential benefits for individuals with cardiovascular disease (CV), type 2 diabetes, and obesity/overweight. It improves cardiovascular health, including exercise capacity and blood pressure control. It enhances glycemic control and insulin sensitivity in diabetes. It aids in weight management and body composition improvement. NW offers additional advantages such as improved muscular strength, joint mobility, physical activity levels, and psychological well-being. Methods: This open-label study with three arms will aim to evaluate the efficacy, safety, and adherence to exercise prescription in obese/overweight diabetic patients with CV complications. The primary objective will be to assess the CV performance of participants after a 6- and 12-month follow-up period, following a 3-month NW intervention, compared with standard rehabilitation (SR) and cardiological counseling (control group, CG) training lasting 3 months. Results: The results of the study will provide valuable insights into the comparative effectiveness of a NW intervention versus SR and CG training in improving cardiovascular performance in obese/overweight diabetic patients with CV complications. Additionally, safety and adherence data will help inform the feasibility and sustainability of the exercise prescription over an extended period. Conclusions: These findings may have implications for the development of tailored exercise programs for this specific patient population, with the aim of optimizing cardiovascular health outcomes.

BackgroundThe transition from in-hospital intravenous administration to subcutaneous therapies to treat inflammatory bowel disease (IBD) can raise some concerns among patients due to the self-administration concerns, the management of potential side effects and the overall worries related to a change of treatment. This study aimed at evaluating patients' opinion about the switch from intravenous to subcutaneous formulations and their knowledge on new available therapeutic options.MethodsWe conducted a survey using a questionnaire prepared by a team of gastroenterologists and nurses working at the IBD unit. It consists of 31 items and has been divided into four sections: descriptive, commitment, knowledge and passage mode opinion. The questions were formulated in Italian and conceived according to daily consultations with patients in everyday practice, without any previous piloting or specific medical literature reference. The survey was administered to consecutive IBD patients in intravenous biological treatment; patients currently or previously treated with subcutaneous therapy were excluded.ResultsFour hundred questionnaires were distributed to participants. As many as 311 patients (77.7%) completed the survey, while the remaining were excluded from the analysis; 155 (49.8%) patients were favorable to switch from intravenous to subcutaneous therapy, while only 78 (25.1%) disagreed. In univariate and multi-variate analysis, the approval rate for home therapy was significantly associated with the distance from the IBD center and work/family/personal commitments. Surprisingly, only a quarter of the IBD patients knew that almost all available therapeutic agents have a subcutaneous administration route. Regarding patients' opinion on the efficacy of subcutaneous administration of biological agents compared to intravenous drugs, 194 (63%) had no definite idea, while 44 (14%) believed that the effectiveness could be reduced.ConclusionThe transition from in-hospital to su

Mental illness remains one of the most critical public health issues, with a significant gap between the available mental health support and patient needs. Many mental health professionals highlight a disconnect between their training and real-world patient interactions, leaving some trainees feeling unprepared and potentially affecting their early career success. In this paper, we propose PATIENT-{\Psi}, a novel patient simulation framework for cognitive behavior therapy (CBT) training. To build PATIENT-{\Psi}, we constructed diverse patient profiles and their corresponding cognitive models based on CBT principles, and then used large language models (LLMs) programmed with the patient cognitive models to act as a simulated therapy patient. We propose an interactive training scheme, PATIENT-{\Psi}-TRAINER, for mental health trainees to practice a key skill in CBT -- formulating the cognitive model of the patient -- through role-playing a therapy session with PATIENT-{\Psi}. To evaluate PATIENT-{\Psi}, we conducted a user study of 4 mental health trainees and 10 experts. The results demonstrate that practice using PATIENT-{\Psi}-TRAINER greatly enhances the perceived skill acquisition and confidence of the trainees beyond existing forms of training such as textbooks, videos, and role-play with non-patients. Based on the experts' perceptions, PATIENT-{\Psi} is perceived to be closer to real patient interactions than GPT-4, and PATIENT-{\Psi}-TRAINER holds strong promise to improve trainee competencies. Our pioneering patient simulation training framework, using LLMs, holds great potential to enhance and advance mental health training, ultimately leading to improved patient care and outcomes. We will release all our data, code, and the training platform., Comment: Work in progress