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Abstract Background Suicide has become a first-order public health concern, especially following the negative impact of COVID-19 on the mental health of the general population. Few studies have analysed the effects of early psychotherapeutic interventions on subjects who have attempted suicide, and even fewer have focused on those hospitalized in non-psychiatric units after a Medically Serious Suicide Attempt (MSSA). The main aim of this study is to describe the protocol designed to evaluate the effectiveness of individual psychological treatment for patients hospitalized after an MSSA. The secondary objectives of the study are: (1) to evaluate the impact on quality of life and other psychosocial variables of patients with a recent MSSA who receive early psychological intervention; (2) to analyse the biological, psychological, and clinical impact of early psychotherapeutic treatment on subjects hospitalized after an MSSA. Methods A longitudinal randomised controlled trial will be conducted with patients over 16 years of age admitted to two general hospitals. The case intervention group will enrol for 8-sessions of individual psychotherapy, Suicide Attempts Multi-component Intervention Treatment (SAMIT), combining Dialectical Behaviour Therapy (DBT), Mentalization-Based Therapy (MBT), and Narrative approaches, while the control group will receive a treatment-as-usual intervention (TAU). Longitudinal assessment will be conducted at baseline (before treatment), post-treatment, and 3, 6, and 12 months after. The main outcome variable will be re-attempting suicide during follow-up. Discussion Some psychotherapeutic interventions, usually implemented in outpatient, have proven to be effective in preventing suicidal behaviours. The combination of some of these may be a powerful treatment for preventing future SA in patients hospitalised after an MSSA, which is the most severely suicidal subgroup. Moreover, assessment of the biological, clinical and psychometric impact of this new intervention on patients during the first year after the attempt may help understand some of the multi-level factors associated with the effectiveness of psychotherapeutic interventions in MSSAs. The prevalence of high suicide rates requires the design of effective psychological interventions for their prevention, and also in order to design new pharmacological and psychological treatments. Trial registration ClinicalTrials.gov ID: NCT06238414. Date of registration: 1st February 2024, final update is protocol version 3.0, 19th March 2024.

Abstract The cellular prion protein (PrPC) plays many roles in the developing and adult brain. In addition, PrPC binds to several amyloids in oligomeric and prefibrillar forms and may act as a putative receptor of abnormal misfolded protein species. The role of PrPC in tau seeding and spreading is not known. In the present study, we have inoculated well-characterized sarkosyl-insoluble fractions of sporadic Alzheimer’s disease (sAD) into the brain of adult wild-type mice (Prnp +/+), Prnp 0/0 (ZH3 strain) mice, and mice over-expressing the secreted form of PrPC lacking their GPI anchor (Tg44 strain). Phospho-tau (ptau) seeding and spreading involving neurons and oligodendrocytes were observed three and six months after inoculation. 3Rtau and 4Rtau deposits from the host tau, as revealed by inoculating Mapt 0/0 mice and by using specific anti-mouse and anti-human tau antibodies suggest modulation of exon 10 splicing of the host mouse Mapt gene elicited by exogenous sAD-tau. However, no tau seeding and spreading differences were observed among Prnp genotypes. Our results show that PrPC does not affect tau seeding and spreading in vivo.

Abstract The goal of the current study was to develop a pig model to investigate oxidative stress with a low negative impact on piglet welfare. Four independent trials (A, B, C, and D) were performed using a single intraperitoneal shot of lipopolysaccharide (LPS) as an immune challenge, aiming to assess the minimal LPS dose for piglets of different age to trigger a measurable acute oxidative stress response in healthy animals. In trial A, piglets received an LPS dose of 25 µg/KgBW at 41 days post-weaning (p.w.). In trial B, piglets received 25 µg/KgBW of LPS at 28 days p.w., in trials C And D, piglets were injected with 50 µg/KgBW of LPS at 21 days p.w., respectively. Piglets were randomly allocated either to the T1) Control group with saline solution (Ctrl), or T2) LPS challenge (LPS). The oxidative stress response was measured through the enzymatic activity of glutathione peroxidase (GPx), glutathione-S-transferase (GST), superoxide dismutase (SOD), and catalase (CAT), in both plasma and intestinal tissues. Intestinal gene expression of oxidative stress and inflammatory markers was assessed. Discomfort behaviors (panting, prostration, trembling, and vomits) were also recorded. Plasmatic and intestinal oxidative stress response was inconsistent across the four trials even when the dose and pig age were similar, possibly due to individual variability. Relative gene expression differences of anti-inflammatory cytokines (IL10), oxidation precursor (iNOS), and antioxidant markers (GPx4, MnSOD, and CAT) were detected between Ctrl and LPS treatment (P

Abstract Despite showing the greatest primate diversity on the planet, genomic studies on Amazonian primates show very little representation in the literature. With 48 geolocalized high coverage whole genomes from wild uakari monkeys, we present the first population-level study on platyrrhines using whole genome data. In a very restricted range of the Amazon rainforest, eight uakari species (Cacajao genus) have been described and categorized into the bald and black uakari groups, based on phenotypic and ecological differences. Despite a slight habitat overlap, we show that posterior to their split 0.92 Mya, bald and black uakaris have remained independent, without gene flow. Nowadays, these two groups present distinct genetic diversity and group-specific variation linked to pathogens. We propose differing hydrology patterns and effectiveness of geographic barriers have modulated the intra-group connectivity and structure of bald and black uakari populations. With this work we have explored the effects of the Amazon rainforest’s dynamism on wild primates’ genetics and increased the representation of platyrrhine genomes, thus opening the door to future research on the complexity and diversity of primate genomics.

Abstract The orphan G protein-coupled receptor 37 (GPR37), widely associated with Parkinson’s disease (PD), undergoes proteolytic processing under physiological conditions. The N-terminus domain is proteolyzed by a disintegrin and metalloproteinase 10 (ADAM-10), which generates various membrane receptor forms and ectodomain shedding (ecto-GPR37) in the extracellular environment. We investigated the processing and density of GPR37 in several neurodegenerative conditions, including Lewy body disease (LBD), multiple system atrophy (MSA), corticobasal degeneration (CBD), progressive supranuclear palsy (PSP), and Alzheimer’s disease (AD). The presence of ecto-GPR37 peptides in the cerebrospinal fluid (CSF) of PD, MSA, CBD and PSP patients was assessed through an in-house nanoluciferase-based immunoassay. This study identified increased receptor processing in early-stage LBD within the PFC and striatum, key brain areas in neurodegeneration. In MSA only the 52 kDa form of GPR37 appeared in the striatum. This form was also significantly elevated in the striatum of AD necropsies. On the contrary, GPR37 processing remained unchanged in the brains of CBD and PSP patients. Furthermore, while CSF ecto-GPR37 increased in PD patients, its levels remained unchanged in MSA, CBD, and PSP subjects. Importantly, patients with PD with rapid progression of the disease did not have elevated ecto-GPR37 in the CSF, while those with slow progression showed a significant increase, suggesting a possible prognostic use of ecto-GPR37 in PD. This research underscores the distinctive processing and density patterns of GPR37 in neurodegenerative diseases, providing crucial insights into its potential role as an indicator of PD progression rates.

Abstract Determining the extent to which the perceptual world can be recovered from language is a longstanding problem in philosophy and cognitive science. We show that state-of-the-art large language models can unlock new insights into this problem by providing a lower bound on the amount of perceptual information that can be extracted from language. Specifically, we elicit pairwise similarity judgments from GPT models across six psychophysical datasets. We show that the judgments are significantly correlated with human data across all domains, recovering well-known representations like the color wheel and pitch spiral. Surprisingly, we find that a model (GPT-4) co-trained on vision and language does not necessarily lead to improvements specific to the visual modality, and provides highly correlated predictions with human data irrespective of whether direct visual input is provided or purely textual descriptors. To study the impact of specific languages, we also apply the models to a multilingual color-naming task. We find that GPT-4 replicates cross-linguistic variation in English and Russian illuminating the interaction of language and perception.

To automate surgical (sub-)tasks in robotic surgery, the knowledge of the exact pose of the instrument is mandatory. The application of Optical Coherence Tomography (OCT) to the problem of pose measurement appears promising due to its advantages of 3D imaging and micron-scale resolution. To investigate this, 175 image sequences of the EndoWrist Round Tip Scissor Tool were acquired with an OCT system. The images differ in the opening angles of the scissor blades and the rotation angles of the entire instrument about its central axis. These image sequences were further processed through computer vision methods of the individual images followed by point cloud generation. For pose estimation, an Iterative Closest Point algorithm was implemented to register the acquired point clouds to reference point clouds created from the instrument CAD file. The implemented algorithm was able to determine the opening angle with an overall error of 2∘ ± 1.3∘ and the rotation angle with a standard deviation between several runs of 0.6∘ ±2.8∘. However, the overall processing time of (39 ± 17)s on a standard PC leaves room for further investigations.

ABSTRACT Purpose: To validate the Barcelona magnetic resonance imaging predictive model (BCN-MRI PM) in men with pre-biopsy multiparametric MRI (mpMRI) reported with the Prostate Imaging Reporting and Data System (PI-RADS) v2.1, followed by transrectal and transperineal prostate biopsies. Materials and Methods: Prospective analysis of 3,264 men with PSA >3.0 ng/mL and/or abnormal digital rectal examination who were referred to ten participant centers in the csPCa early detection program of Catalonia (Spain), between 2021 and 2023. MpMRI was reported with the PI-RADS v2.1, and 2- to 4-core MRI-transrectal ultrasound (TRUS) fusion-targeted biopsy of suspected lesions and/or 12-core systematic biopsy were conducted. 2,295 (70.3%) individuals were referred to six centers for transrectal prostate biopsies, while 969 (39.7%) were referred to four centers for transperineal prostate biopsies. CsPCa was classified whenever the International Society of Urologic Pathology grade group was 2 or higher. Results: CsPCa was detected in 41% of transrectal prostate biopsies and in 45.9% of transperineal prostate biopsies (p

Abstract During the last decades, effective pain reduction and early mobilization were identified as the central priorities in therapy of insufficiency fractures of the pelvis. For operative treatment minimally-invasive stabilization techniques are favored. While there is consensus on the significance of sufficient dorsal stabilization the role of additional fixation of the anterior fracture component stays under discussion. Within the present study we developed an internal ring fixator system (RingFix) with the question whether an in-itself-closed construct can improve stability of the entire ring structure. RingFix was evaluated on an osteoporotic bone model with a standardized FFP IIIc fracture within an established biomechanical setup regarding its primary stabilization potential. Further, it was compared to transiliac–transsacral screw fixation with and without stabilization of the anterior fracture component. The transiliac–transsacral fixation with separate screw fixation of the anterior fracture showed significantly higher stability than the RingFix and the transiliac–transsacral screw fixation without anterior stabilization. Our results show that stabilization of the anterior fracture component relevantly improves the stability of the entire ring construct. As a bridging stabilizer, RingFix shows biomechanical advantages over an isolated dorsal fracture fixation, but inferior results than direct stabilization of the single fracture components.

Background and objective: The depth of the prostate-specific antigen (PSA) decline after androgen receptor pathway inhibitor (ARPI) treatment combined with androgen deprivation therapy for patients with metastatic hormone-sensitive prostate cancer (mHSPC) may affect prognosis. The primary objective in our study was the correlation between the PSA response at 3 mo and radiologic progression-free survival (rPFS) at 24 mo. Three groups were defined according to the PSA decline: complete response (PSA ≤0.02 ng/ml), partial response (PSA >0.02 and ≤0.2 ng/ml), and incomplete response (PSA >0.2 ng/ml). Secondary objectives were correlation between the PSA response at 3 mo and overall survival, and the development of a model predicting complete PSA response. Methods: We conducted a retrospective multicenter study of patients with mHSPC treated with apalutamide from May 2018 to September 2023 registered in the Real-World Evidence APA registry across 20 centers. Key findings and limitations: We included 633 patients with mHSPC. The median age at diagnosis was 68 yr (interquartile range [IQR] 63–75) and median PSA was 16 ng/ml (IQR 7.5–64). Some 63% of the short had low-volume disease, 51% had de novo disease, 48% had recurrent disease. At 3 mo, 27% had a complete response, 42% a partial response, and 31% an incomplete response, with corresponding rRFS rates at 24 mo of 92%, 86%, and 63%. According to the predictive model, a complete PSA response at 3 mo was associated with the use of next-generation imaging and PSA

Abstract Jaundice affects almost all neonates in their first days of life and is caused by the accumulation of bilirubin. Although the core biochemistry of bilirubin metabolism is well understood, it is not clear why some neonates experience more severe jaundice and require treatment with phototherapy. Here, we present the first genome-wide association study of neonatal jaundice to date in nearly 30,000 parent-offspring trios from Norway (cases ≈ 2000). The alternate allele of a common missense variant affecting the sequence of UGT1A4 reduces the susceptibility to jaundice five-fold, which replicated in separate cohorts of neonates of African American and European ancestries. eQTL colocalization analyses indicate that the association may be driven by regulation of UGT1A1 in the intestines, but not in the liver. Our results reveal marked differences in the genetic variants involved in neonatal jaundice compared to those regulating bilirubin levels in adults, suggesting distinct genetic mechanisms for the same biological pathways.

Quality control of programs for detection of significant prostate cancer (sPCa) could be defined by the correlation between observed and reference 95% confidence intervals (CIs) for Prostate Imaging-Reporting and Data System (PI-RADS) categories. We used the area under the receiver operating characteristic curve (AUC) for the Barcelona magnetic resonance imaging (MRI) predictive model to screen the quality of ten participant centers in the sPCa opportunistic early detection program in Catalonia. We set an AUC of 3.0 ng/ml and/or a suspicious digital rectal examination who underwent multiparametric MRI and two- to four-core targeted biopsies of PI-RADS ≥3 lesions and/or 12-core systematic biopsy, AUC values ranged from 0.527 to 0.914 and were

Abstract Giant barocaloric effects were recently reported for spin-crossover materials. The volume change in these materials suggests that the transition can be influenced by uniaxial stress, and give rise to giant elastocaloric properties. However, no measurements of the elastocaloric properties in these compounds have been reported so far. Here, we demonstrated the existence of elastocaloric effects associated with the spin-crossover transition. We dissolved particles of ([Fe(L)2](BF4)2, [L=2,6di(pyrazol-1-yl)pyridine]) into a polymeric matrix. We showed that the application of tensile uniaxial stress to a composite film resulted in a significant elastocaloric effect. The elastocaloric effect in this compound required lower applied stress than for other prototype elastocaloric materials. Additionally, this phenomenon occurred for low values of strain, leading to coefficient of performance of the material being one order of magnitude larger than that of other elastocaloric materials. We believe that spin-crossover materials are a good alternative to be implemented in eco-friendly refrigerators based on elastocaloric effects.

Abstract We present numerical solutions in a one-dimensional setting of quantum master equations that have been recently derived. We focus on the dynamics of a single heavy quark-antiquark pair in a Quark-Gluon Plasma in thermal equilibrium, in the so-called quantum Brownian regime where the temperature of the plasma is large in comparison with the spacing between the energy levels of the Q Q ¯ $$ Q\overline{Q} $$ system. The one-dimensional potential used in the calculations has been adjusted so as to produce numbers that are relevant for the phenomenology of the charmonium. The equations are solved using different initial states and medium configurations. Various temperature regimes are studied and the effects of screening and collisions thoroughly analyzed. Technical features of the equations are analyzed. The contributions of the different operators that control the evolution are discussed as a function of the temperature. Some phenomenological consequences are addressed.

Abstract Huntington’s disease (HD) is a neurological disorder caused by a CAG expansion in the Huntingtin gene (HTT). HD pathology mostly affects striatal medium-sized spiny neurons and results in an altered cortico-striatal function. Recent studies report that motor skill learning, and cortico-striatal stimulation attenuate the neuropathology in HD, resulting in an amelioration of some motor and cognitive functions. During physical training, extracellular vesicles (EVs) are released in many tissues, including the brain, as a potential means for inter-tissue communication. To investigate how motor skill learning, involving acute physical training, modulates EVs crosstalk between cells in the striatum, we trained wild-type (WT) and R6/1 mice, the latter with motor and cognitive deficits, on the accelerating rotarod test, and we isolated their striatal EVs. EVs from R6/1 mice presented alterations in the small exosome population when compared to WT. Proteomic analyses revealed that striatal R6/1 EVs recapitulated signaling and energy deficiencies present in HD. Motor skill learning in R6/1 mice restored the amount of EVs and their protein content in comparison to naïve R6/1 mice. Furthermore, motor skill learning modulated crucial pathways in metabolism and neurodegeneration. All these data provide new insights into the pathogenesis of HD and put striatal EVs in the spotlight to understand the signaling and metabolic alterations in neurodegenerative diseases. Moreover, our results suggest that motor learning is a crucial modulator of cell-to-cell communication in the striatum.

Abstract We use complex systems science to explore the emergent behavioral patterns that typify eusocial species, using collective ant foraging as a paradigmatic example. Our particular aim is to provide a methodology to quantify how the collective orchestration of foraging provides functional advantages to ant colonies. For this, we combine (i) a purpose-built experimental arena replicating ant foraging across realistic spatial and temporal scales, and (ii) a set of analytical tools, grounded in information theory and spin-glass approaches, to explore the resulting data. This combined approach yields computational replicas of the colonies; these are high-dimensional models that store the experimental foraging patterns through a training process, and are then able to generate statistically similar patterns, in an analogous way to machine learning tools. These in silico models are then used to explore the colony performance under different resource availability scenarios. Our findings highlight how replicas of the colonies trained under constant and predictable experimental food conditions exhibit heightened foraging efficiencies, manifested in reduced times for food discovery and gathering, and accelerated transmission of information under similar conditions. However, these same replicas demonstrate a lack of resilience when faced with new foraging conditions. Conversely, replicas of colonies trained under fluctuating and uncertain food conditions reveal lower efficiencies at specific environments but increased resilience to shifts in food location.

Over the past decades, health care systems have significantly evolved due to aging populations, chronic diseases, and higher-quality care expectations. Concurrently with the added health care needs, information and communications technology advancements have transformed health care delivery. Technologies such as telemedicine, electronic health records, and mobile health apps promise enhanced accessibility, efficiency, and patient outcomes, leading to more personalized, data-driven care. However, organizational, political, and cultural barriers and the fragmented approach to health information management are challenging the integration of these technologies to effectively support health care delivery. This fragmentation collides with the need for integrated care pathways that focus on holistic health and wellness. Catalonia (northeast Spain), a region of 8 million people with universal health care coverage and a single public health insurer but highly heterogeneous health care service providers, has experienced outstanding digitalization and integration of health information over the past 25 years, when the first transition from paper to digital support occurred. This Viewpoint describes the implementation of health ITs at a system level, discusses the hits and misses encountered in this journey, and frames this regional implementation within the global context. We present the architectures and use trends of the health information platforms over time. This provides insightful information that can be used by other systems worldwide in the never-ending transformation of health care structure and services.

Espinoza Lolas, Ricardo (2023) Psychoanalysis for Intersectional Humanity. Sade Reloaded Oxon/New York: Routledge, 162 p. ISBN 9781032440392

Long-range axonal projections of diverse classes of neocortical excitatory neurons likely contribute to brain-wide interactions processing sensory, cognitive and motor signals. Here, we performed light-sheet imaging of fluorescently labeled axons from genetically defined neurons located in posterior primary somatosensory barrel cortex and supplemental somatosensory cortex. We used convolutional networks to segment axon-containing voxels and quantified their distribution within the Allen Mouse Brain Atlas Common Coordinate Framework. Axonal density was analyzed for different classes of glutamatergic neurons using transgenic mouse lines selectively expressing Cre recombinase in layer 2/3 intratelencephalic projection neurons (Rasgrf2-dCre), layer 4 intratelencephalic projection neurons (Scnn1a-Cre), layer 5 intratelencephalic projection neurons (Tlx3-Cre), layer 5 pyramidal tract projection neurons (Sim1-Cre), layer 5 projection neurons (Rbp4-Cre), and layer 6 corticothalamic neurons (Ntsr1-Cre). We found distinct axonal projections from the different neuronal classes to many downstream brain areas, which were largely similar for primary and supplementary somatosensory cortices. Functional connectivity maps obtained from optogenetic activation of sensory cortex and wide-field imaging revealed topographically organized evoked activity in frontal cortex with neurons located more laterally in somatosensory cortex signaling to more anteriorly located regions in motor cortex, consistent with the anatomical projections. The current methodology therefore appears to quantify brain-wide axonal innervation patterns supporting brain-wide signaling.

Background & Aims: Etiologic factor removal (ER) drives recompensation and improves portal hypertension in cirrhosis. Esophageal varices (EV) and portosystemic shunts (PSS) have been found in patients despite hepatic venous pressure gradient (HVPG) dropping below 10 mmHg after ER, questioning HVPG accuracy in reflecting true portal pressure in the setting of ER. We aim to evaluate the correlation of HVPG with direct portal pressure (DPP) in patients with persistence of EV after ER despite HVPG

Background: A more sustainable diet with fewer animal-based products has a lower ecological impact but might lead to a lower protein quantity and quality. The extent to which shifting to more plant-based diets impacts the adequacy of protein intake in older adults needs to be studied. Objectives: We simulated how a transition towards a more plant-based diet (flexitarian, pescetarian, vegetarian, or vegan) affects protein availability in the diets of older adults. Setting: Community. Participants: Data from the Dutch National Food Consumption Survey 2019–2021 of community-dwelling older adults (n = 607) was used Measurements: Food consumption data was collected via two 24 -h dietary recalls per participant. Protein availability was expressed as total protein, digestible protein, and utilizable protein (based on digestibility corrected amino acid score) intake. The percentage below estimated average requirements (EAR) for utilizable protein was assessed using an adjusted EAR. Results: Compared to the original diet (∼62% animal-based), utilizable protein intake decreased by about 5% in the flexitarian, pescetarian and vegetarian scenarios. In the vegan scenario, both total protein intake and utilizable protein were lower, leading to nearly 50% less utilizable protein compared to the original diet. In the original diet, the protein intake of 7.5% of men and 11.1% of women did not meet the EAR. This slightly increased in the flexitarian, pescetarian, and vegetarian scenarios. In the vegan scenario, 83.3% (both genders) had a protein intake below EAR. Conclusions: Replacing animal-based protein sources with plant-based food products in older adults reduces both protein quantity and quality, albeit minimally in non-vegan plant-rich diets. In a vegan scenario, the risk of an inadequate protein intake is imminent.

Background: Along with the ageing of society, the absolute prevalence of age-related diseases is expected to rise, leading to a substantial burden on healthcare systems and society. Thus, there is an urgent need to promote healthy ageing. As opposed to chronological age, biological age was introduced to accurately represent the ageing process, as it considers physiological deterioration that is linked to morbidity and mortality risk. Furthermore, biological age responds to various factors, including nutritional factors, which have the potential to mitigate the risk of age-related diseases. As a result, a promising biomarker of biological age known as the epigenetic clock has emerged as a suitable measure to investigate the direct relations between nutritional factors and ageing, thereby identifying potential intervention targets to improve healthy ageing. Methods: In this study, we analysed data from 3,969 postmenopausal women from the Women's Health Initiative to identify nutrients that are associated with the rate of ageing by using an accurate measure of biological age called the PhenoAge epigenetic clock. We used Copula Graphical Models, a data-driven exploratory analysis tool, to identify direct relationships between nutrient intake and age-acceleration, while correcting for every variable in the dataset. Results: We revealed that increased dietary intakes of coumestrol, beta-carotene and arachidic acid were associated with decelerated epigenetic ageing. In contrast, increased intakes of added sugar, gondoic acid, behenic acid, arachidonic acid, vitamin A and ash were associated with accelerated epigenetic ageing in postmenopausal women. Conclusion: Our study discovered direct relations between nutrients and epigenetic ageing, revealing promising areas for follow-up studies to determine the magnitude and causality of our estimated diet-epigenetic relationships.

Participatory Planning and Evaluation (CPPE), an approach to community participation and empowerment developed from the work of Rifkin, LaveracK, Pérez, and others. More than just a methodology, CPPE is an approach which encourages comprehensive analysis and participation by various actors at local, regional, and national level in the planning and evaluation of health actions. CPPE has its roots in the 1980s, when an international team of researchers from the Institutes of Tropical Medicine in Antwerp (ITM-Belgium) and Amsterdam (KIT-Netherlands) developed a framework of comprehensive participatory evaluation for nutritional improvement programs. Following its initial application in the Philippines, further work extended the evaluation approach to planning. CPPE was gradually refined with the support of research teams in Indonesia, the Philippines, and Brazil as they applied it in different contexts and projects. Since 2008 projects have been carried out in Cuba to analyze the possibilities offered by CPPE for increasing community participation in health. This article illustrates the rationale and tools employed in CPPE through our experience in Cuba in the urban municipalities of Centro Habana and Las Tunas and in a rural community in the mountains of Cumanayagua. We discuss key methodological components, the conditions needed for the success of CPPE, and potential differences between the Cuban experience and the possible application of CPPE in other contexts.

Regrouping practices are frequent in pig production, altering hierarchy and triggering aggressive behaviors. The present study aimed to investigate the physiological responses of piglets to an experimental model designed to induce stress through systematic social mixing in two trials. In Trial A, a total of 144 crossbred piglets (25 days postweaning) housed in one room within 36 pens (four piglets/pen) were used and randomly assigned to either a control group (piglets maintained in their pen, Ctrl-A) or a social challenge group (piglets mixed, SC-A). In Trial B, the same number of animals (33 days postweaning) and crossbreed line was used, and each piglet was assigned either to a control group (Ctrl-B) or a social challenge group (SC-B) in two independent rooms (rooms Ctrl and SC, 12 pens/ room, six piglets/pen). The social challenge consisted of daily moves of three out of four pen mates and five out of six pen mates, for Trials A and B, respectively. In the Ctrl groups, all piglets stayed in their original pen. Before the 1st mixing day and at the end of the 3rd mixing day, saliva (cortisol concentration) and blood (cortisol concentration changes, hemogram, and immunologic activation) samples were collected from two random piglets per pen. Skin lesion scores of all piglets were also recorded on the front, middle, and rear body regions. In Trial A, the total skin lesions score was higher in the SC-A group compared to the Ctrl-A group after the social challenge (0.53 vs. 0.17; p

Background: The recent shift toward increased plant-based protein consumption has necessitated the development of new tools to evaluate the quality and quantity of protein in meals, especially given the changing dietary guidelines and the adoption of plant-centric menus in healthcare and other settings. Objectives: To develop and test the feasibility of the meal protein quality score (MPQS), a novel metric that assesses the protein quality and quantity in meals based on essential amino acid (EAA) content, digestibility, and requirements, with a focus on optimizing protein intake for vulnerable populations, particularly older adults. Methods: The MPQS integrates digestibility-adjusted EAA intake with total protein consumed in a meal, which, together with the EAA requirements, provides a score from 0 to 100 to reflect EAA coverage adequacy. The score was tested for feasibility by applying it to recipe data from real-life hospital meals and to dietary data from the [New Dietary Strategies Addressing the Specific Needs of Elderly Population for Healthy Aging in Europe] NU-AGE trial, involving detailed 7-d food records from 252 nonvegan participants analyzed over multiple meal moments. Results: The analyses revealed that the higher the content of plant protein in a meal, the lower the meal protein quality. Also, breakfast meals scored lowest on protein quality, mainly due to low contents of protein overall, and of lysine and methionine. The MPQS effectively highlighted the difference in protein quality between plant-based and animal-based meals, and across different meal types. Conclusions: The MPQS appears to be a practical tool that facilitates the assessment of meal-based protein quality. The MPQS can be used to guide dietary transitions toward plant-rich diets, ensuring that such shifts do not compromise protein adequacy for at-risk populations. The score allows for guidance in meal planning, leading to improvements in plant-rich meal formulation to meet both individual and public health nutritional needs.

Abstract is missing (Short communication)

Abstract Healthcare fraud, waste and abuse are costly problems that have huge impact on society. Traditional approaches to identify non-compliant claims rely on auditing strategies requiring trained professionals, or on machine learning methods requiring labelled data and possibly lacking interpretability. We present Clais, a collaborative artificial intelligence system for claims analysis. Clais automatically extracts human-interpretable rules from healthcare policy documents (0.72 F1-score), and it enables professionals to edit and validate the extracted rules through an intuitive user interface. Clais executes the rules on claim records to identify non-compliance: on this task Clais significantly outperforms two baseline machine learning models, and its median F1-score is 1.0 (IQR = 0.83 to 1.0) when executing the extracted rules, and 1.0 (IQR = 1.0 to 1.0) when executing the same rules after human curation. Professionals confirm through a user study the usefulness of Clais in making their workflow simpler and more effective.

Abstract Differentiation between leukocyte subtypes like monocytes and lymphocytes is essential for cell therapy and research applications. To guarantee the cost-effective delivery of functional cells in cell therapies, billions of cells must be processed in a limited time. Yet, the sorting rates of commercial cell sorters are not high enough to reach the required yield. Process parallelization by using multiple instruments increases variability and production cost. A compact solution with higher throughput can be provided by multichannel flow cytometers combining fluidics and optics on-chip. In this work, we present a micro-flow cytometer with monolithically integrated photonics and fluidics and demonstrate that both the illumination of cells, as well as the collection of scattered light, can be realized using photonic integrated circuits. Our device is the first with sufficient resolution for the discrimination of lymphocytes and monocytes. Innovations in microfabrication have enabled complete integration of miniaturized photonic components and fluidics in a CMOS-compatible wafer stack. In combination with external optics, the device is ready for the collection of fluorescence using the on-chip excitation.

Abstract SLC22A10 is an orphan transporter with unknown substrates and function. The goal of this study is to elucidate its substrate specificity and functional characteristics. In contrast to orthologs from great apes, human SLC22A10, tagged with green fluorescent protein, is not expressed on the plasma membrane. Cells expressing great ape SLC22A10 orthologs exhibit significant accumulation of estradiol-17β-glucuronide, unlike those expressing human SLC22A10. Sequence alignments reveal a proline at position 220 in humans, which is a leucine in great apes. Replacing proline with leucine in SLC22A10-P220L restores plasma membrane localization and uptake function. Neanderthal and Denisovan genomes show proline at position 220, akin to modern humans, indicating functional loss during hominin evolution. Human SLC22A10 is a unitary pseudogene due to a fixed missense mutation, P220, while in great apes, its orthologs transport sex steroid conjugates. Characterizing SLC22A10 across species sheds light on its biological role, influencing organism development and steroid homeostasis.

We describe how a direct combination of an axicon and a lens can represent a simple and efficient beam-shaping solution for laser material processing applications. We produce high-angle pseudo-Bessel micro-beams at 1550 nm, which would be difficult to produce by other methods. Combined with appropriate stretching of femtosecond pulses, we access optimized conditions inside semiconductors allowing us to develop high-aspect-ratio refractive-index writing methods. Using ultrafast microscopy techniques, we characterize the delivered local intensities and the triggered ionization dynamics inside silicon with 200-fs and 50-ps pulses. While similar plasma densities are produced in both cases, we show that repeated picosecond irradiation induces permanent modifications spontaneously growing shot-after-shot in the direction of the laser beam from front-surface damage to the back side of irradiated silicon wafers. The conditions for direct microexplosion and microchannel drilling similar to those today demonstrated for dielectrics still remain inaccessible. Nonetheless, this work evidences higher energy densities than those previously achieved in semiconductors and a novel percussion writing modality to create structures in silicon with aspect ratios exceeding ~700 without any motion of the beam. The estimated transient change of conductivity and measured ionization fronts at near luminal speed along the observed microplasma channels support the vision of vertical electrical connections optically controllable at GHz repetition rates. The permanent silicon modifications obtained by percussion writing are light-guiding structures according to a measured positive refractive index change exceeding 10−2. These findings open the door to unique monolithic solutions for electrical and optical through-silicon-vias which are key elements for vertical interconnections in 3D chip stacks.

Abstract We revisit the Next-to-Leading Order (two-loop) contributions to the Anomalous Dimensions of ∆F = 1 four-quark operators in QCD. We devise a test for anomalous dimensions, that we regard as of general interest, and by means of which we detect a problem in the results available in the literature. Deconstructing the steps leading to the available result, we identify the source of the problem, which is related to the operator known as Q 11. We show how to fix the problem and provide the corrected anomalous dimensions. With the insight of our findings, we propose an alternative approach to the one used in the literature which does not suffer from the identified disease, and which confirms our corrected results. We assess the numerical impact of our corrections, which happens to be in the ballpark of 5% in certain entries of the evolution matrix. Our results are important for the correct resummation of Next-to-Leading Logarithms in analyses of physics beyond the Standard Model in ∆F = 1 processes, such as the decays of Kaons and B-mesons.

Purpose: To relate the prostate volume category (PVC) assessed with digital rectal examination (DRE)—small, median, and large—and the prostate volumes (PVs) assessed with magnetic resonance imaging (MRI) and transrectal ultrasound (TRUS). To compare the clinically significant prostate cancer (csPCa) discrimination ability of two predictive models based on DREPVC and MRI-PV. Materials and Methods: A prospective trial of 2,090 men with prostate-specific antigen >3 ng/mL and/or PCa suspicious DRE were prospectively recruited in 10 centers from Catalonia (Spain), between 2021 and 2022, in whom DRE-PVC was assessed. Pre-biopsy MRI, and 12-core TRUS-random biopsy was always performed after 2- to 6-core TRUS-fusion targeted biopsy of prostate imaging-report and data system >3 lesions. In 370 men (17.7%) the DRE-PVC was unconclusive. Among the 1,720 men finally analyzed the csPCa (grade group >2) detection was 42.4%. Results: The median (interquartile range) of TRUS and MRI-PVs of small prostates were 33 mL (19–37 mL) and 35 mL (23–30 mL), p=0.410; in median prostates they were 51 mL (38–58 mL) and 55 mL (48–63 mL) respectively, p

Abstract Identifying key patterns of tactics implemented by rival teams, and developing effective responses, lies at the heart of modern football. However, doing so algorithmically remains an open research challenge. To address this unmet need, we propose TacticAI, an AI football tactics assistant developed and evaluated in close collaboration with domain experts from Liverpool FC. We focus on analysing corner kicks, as they offer coaches the most direct opportunities for interventions and improvements. TacticAI incorporates both a predictive and a generative component, allowing the coaches to effectively sample and explore alternative player setups for each corner kick routine and to select those with the highest predicted likelihood of success. We validate TacticAI on a number of relevant benchmark tasks: predicting receivers and shot attempts and recommending player position adjustments. The utility of TacticAI is validated by a qualitative study conducted with football domain experts at Liverpool FC. We show that TacticAI’s model suggestions are not only indistinguishable from real tactics, but also favoured over existing tactics 90% of the time, and that TacticAI offers an effective corner kick retrieval system. TacticAI achieves these results despite the limited availability of gold-standard data, achieving data efficiency through geometric deep learning.

Abstract Background Lithuania, a Baltic country in the European Union, can be characterized by high alcohol consumption and attributable burden. The aim of this contribution is to estimate the mortality burden due to alcohol use for the past two decades based on different relative risk functions, identify trends, and analyse the associations of alcohol-attributable burden with alcohol control policies and life expectancy. Methods The standard methodology used by the World Health Organization for estimating alcohol-attributable mortality was employed to generate mortality rates for alcohol-attributable mortality, standardized for Lithuania’s 2021 population distribution. Joinpoint analysis, T-tests, correlations, and regression analyses including meta-regressions were used to describe trends and associations. Results Age-standardized alcohol-attributable mortality was high in Lithuania during the two decades between 2001 and 2021, irrespective of which relative risks were used for the estimates. Overall, there was a downward trend, mainly in males, which was associated with four years of intensive implementation of alcohol control policies in 2008, 2009, 2017, and 2018. For the remaining years, the rates of alcohol-attributable mortality were stagnant. Among males, the correlations between alcohol-attributable mortality and life expectancy were 0.90 and 0.76 for Russian and global relative risks respectively, and regression analyses indicated a significant association between changes in alcohol-attributable mortality and life expectancy, after controlling for gross domestic product. Conclusions Male mortality and life expectancy in Lithuania were closely linked to alcohol-attributable mortality and markedly associated with strong alcohol control policies. Further implementation of such policies is predicted to lead to further improvements in life expectancy.

Abstract Data on the SARS-CoV-2 infection among primary health care workers (PHCWs) are scarce but essential to reflect on policy regarding prevention and control measures. We assessed the prevalence of PHCWs who have been infected by SARS-CoV-2 in comparison with modeling from the general population in metropolitan France, and associated factors. A cross-sectional study was conducted among general practitioners (GPs), pediatricians, dental and pharmacy workers in primary care between May and August 2021. Participants volunteered to provide a dried-blood spot for SARS-CoV-2 antibody assessment and completed a questionnaire. The primary outcome was defined as the detection of infection-induced antibodies (anti-nucleocapsid IgG, and for non-vaccinees: anti-Spike IgG and neutralizing antibodies) or previous self-reported infection (positive RT-qPCR or antigenic test, or positive ELISA test before vaccination). Estimates were adjusted using weights for representativeness and compared with prediction from the general population. Poisson regressions were used to quantify associated factors. The analysis included 1612 PHCWs. Weighted prevalences were: 31.7% (95% CI 27.5–36.0) for GPs, 28.7% (95% CI 24.4–33.0) for pediatricians, 25.2% (95% CI 20.6–31.0) for dentists, and 25.5% (95% CI 18.2–34.0) for pharmacists. Estimates were compatible with model predictions for the general population. PHCWs more likely to be infected were: GPs compared to pharmacist assistants (adjusted prevalence ratio [aPR] = 2.26; CI 95% 1.01–5.07), those living in Île-de-France (aPR = 1.53; CI 95% 1.14–2.05), South-East (aPR = 1.57; CI 95% 1.19–2.08), North-East (aPR = 1.81; CI 95% 1.38–2.37), and those having an unprotected contact with a COVID-19 case within the household (aPR = 1.48; CI 95% 1.22–1.80). Occupational factors were not associated with infection. In conclusion, the risk of SARS-CoV-2 exposure for PHCWs was more likely to have occurred in the community rather than at their workplace.

The value of hospital care to patients is expressed as a combination of reduced healthcare costs, fewer medical complications, and improved patient satisfaction. Few studies highlight the value hospitals provide to their patients through hip replacement surgery.This study aims to define a methodology for inter-hospital comparison purposes that can assess the value of hip replacement management to patients by using indicators of costs, medical complications, and patient outcomes.We identified medical complications and costs from medico-administrative data collected by three hospitals. We associated a Disability Adjusted Life Years (DALYs) impact with medical complications, readmissions (within 30 days), and hospital mortality. Costs were analysed from a social security perspective. Patient outcomes were collected through a questionnaire-based survey after hip surgery. To compare the three hospitals, we created a composite indicator by standardizing each dependent variable and combining a weighting of importance provided by patients.This study analysed 342 hospital stays. The mean (standard deviation) number of DALYs per stay was estimated to be more than 0.0028 (0.016) for a mean (standard deviation) cost of €4,834 (€3,665). The composite indicator allowed hospitals to be ranked and areas for improvement to be identified. In our case mix, Hospital 3 is the lowest-ranked hospital, with excessively high costs and a relatively low level of satisfaction compared to the others.The simultaneous evaluation of medical complications, patient outcomes, and costs is a prerequisite for quality improvement efforts by managers and practitioners. In our opinion, this experiment, which sought to estimate the value hospitals bring to patients, may be viewed as the first step towards value-based purchasing in Belgium.

Introduction Heart failure (HF) is a chronic condition associated with substantial mortality and hospitalisation, resulting in costly inpatient visits. The healthcare systems of several countries, including Vietnam, experience considerable difficulty in dealing with the enormous fiscal burden presented by HF. This study aims to analyse the direct medical costs associated with HF inpatient treatment from the hospital perspective.Materials and methods This study retrospectively analysed the electronic medical records of patients diagnosed with HF from 2018 to 2021 at Military Hospital 175 in Vietnam. The sample consisted of 906 hospitalised patients (mean age: 71.2 ± 14.1 years). The financial impact of HF was assessed by examining the direct medical expenses incurred by the healthcare system, and the costs of pharmaceutical categories used in treatment were explored.Results The cumulative economic burden of HF from 2018 to 2021 was US$1,068,870, with annual costs ranging from US$201,670 to US$443,831. Health insurance covered 72.7% of these costs. Medications and infusions, and medical supplies accounted for the largest expenses, at 29.8% and 22.1%, respectively. The medication HF group accounted for 13.01% of these expenses, of which the costliest medications included nitrates (2.57%), angiotensin II receptor blockers (0.51%), ivabradine (0.39%), diuretics (0.24%), and mineralocorticoid receptor antagonists (0.23%). Comorbidities and the length of hospital stay significantly influenced annual treatment costs.Conclusion The study reveals that HF significantly impacts Vietnam’s healthcare system and citizens, requiring a comprehensive understanding of its financial implications and efficient management of medical resources for those diagnosed. This study highlights the substantial economic burden of HF on Vietnam’s healthcare system, with medication costs, particularly antithrombotic drugs, representing the largest expense. Most healthcare costs were covered by health insurance, and expenses were significantly influenced by comorbidity and length of hospital stay. These findings can inform healthcare policy, resource allocation and optimise management strategies in Vietnam.

Abstract Solid‐state methods for cooling and heating promise a sustainable alternative to current compression cycles of greenhouse gases and inefficient fuel‐burning heaters. Barocaloric effects (BCE) driven by hydrostatic pressure (p) are especially encouraging in terms of large adiabatic temperature changes (|ΔT| ≈ 10 K) and isothermal entropy changes (|ΔS| ≈ 100 J K−1 kg−1). However, BCE typically require large pressure shifts due to irreversibility issues, and sizeable |ΔT| and |ΔS| seldom are realized in a same material. Here, the existence of colossal and reversible BCE in LiCB11H12 is demonstrated near its order‐disorder phase transition at ≈380 K. Specifically, for Δp ≈ 0.23 (0.10) GPa, |ΔSrev| = 280 (200) J K−1 kg−1 and |ΔTrev| = 32 (10) K are measured, which individually rival with state‐of‐the‐art BCE figures. Furthermore, pressure shifts of the order of 0.1 GPa yield huge reversible barocaloric strengths of ≈2 J K−1 kg−1 MPa−1. Molecular dynamics simulations are performed to quantify the role of lattice vibrations, molecular reorientations, and ion diffusion on the disclosed BCE. Interestingly, lattice vibrations are found to contribute the most to |ΔS| while the diffusion of lithium ions, despite adding up only slightly to the entropy change, is crucial in enabling the molecular order–disorder phase transition.

Polymer-cationic mediated gene delivery is a well-stablished strategy of transient gene expression (TGE) in mammalian cell cultures. Nonetheless, its industrial implementation is hindered by the phenomenon known as cell density effect (CDE) that limits the cell density at which cultures can be efficiently transfected. The rise in personalized medicine and multiple cell and gene therapy approaches based on TGE, make more relevant to understand how to circumvent the CDE. A rational study upon DNA/PEI complex formation, stability and delivery during transfection of HEK293 cell cultures has been conducted, providing insights on the mechanisms for polyplexes uptake at low cell density and disruption at high cell density. DNA/PEI polyplexes were physiochemically characterized by coupling X-ray spectroscopy, confocal microscopy, cryo-transmission electron microscopy (TEM) and nuclear magnetic resonance (NMR). Our results showed that the ionic strength of polyplexes significantly increased upon their addition to exhausted media. This was reverted by depleting extracellular vesicles (EVs) from the media. The increase in ionic strength led to polyplex aggregation and prevented efficient cell transfection which could be counterbalanced by implementing a simple media replacement (MR) step before transfection. Inhibiting and labeling specific cell-surface proteoglycans (PGs) species revealed different roles of PGs in polyplexes uptake. Importantly, the polyplexes uptake process seemed to be triggered by a coalescence phenomenon of HSPG like glypican-4 around polyplex entry points. Ultimately, this study provides new insights into PEI-based cell transfection methodologies, enabling to enhance transient transfection and mitigate the cell density effect (CDE).

Summary: Vascular plants are exceptional among eukaryotes due to their outstanding genome size diversity which ranges ∼2,400-fold, including the largest genome so far recorded in the angiosperm Paris japonica (148.89 Gbp/1C). Despite available data showing that giant genomes are restricted across the Tree of Life, the biological limits to genome size expansion remain to be established. Here, we report the discovery of an even larger eukaryotic genome in Tmesipteris oblanceolata, a New Caledonian fork fern. At 160.45 Gbp/1C, this record-breaking genome challenges current understanding and opens new avenues to explore the evolutionary dynamics of genomic gigantism.

IntroductionThe field of Medicines Development faces a continuous need for educational evolution to match the interdisciplinary and global nature of the pharmaceutical industry. This paper discusses the outcomes of a 7-year collaboration between King’s College London and the Global Medicines Development Professionals (GMDP) Academy, which aimed to address this need through a blended e-learning program.MethodsThe collaboration developed a comprehensive curriculum based on the PharmaTrain syllabus, delivered through a combination of asynchronous and synchronous e-learning methods. The program targeted a diverse range of professionals serving in areas related to Medical Affairs.ResultsOver seven annual cohorts, 682 participants from eighty-six countries were enrolled in the program. The program’s effectiveness was assessed using Kirkpatrick’s model, showing elevated levels of satisfaction (over 4.0 on a five-point scale), suggesting significant gains in competence at the cognitive level and leveraged performance. Notably, 70% of responding alumni reported significant improvement in their functions, corroborated by 30% of their supervisors. The further long-term impact of the program on their respective organization has not been established.DiscussionThe GMDP Academy’s program has significantly contributed to life-long learning in Medicines Development, addressing educational gaps and fostering interdisciplinary collaboration. Its success highlights the importance of continuous education in keeping pace with the industry’s evolving demands and underscores the potential of blended learning in achieving educational objectives in pharmaceutical medicine.

As the fifth generation (5G) mobile communication systems are commercially deployed, they bring new services, enhance user experiences, and offer various opportunities to different industries. Despite its advancements, 5G encounters several challenges. To tackle these issues, global industrial, academic, and standards organizations are actively researching on sixth generation (6G) wireless communication systems. 6G networks are envisioned as a transformative shift in the interactions between the physical, digital, and human realms, paving the way for a pervasive human-centered cyber-physical world. 6G is positioned to be a platform that offers communication and beyond communication services considering both performance and value centric technological development approaches. In this paper, we present the way forward towards the design of 6G endto-end (E2E) system as a consolidated view of leading industry stakeholders and academia in the European level 6G flagship project Hexa-X-II. We discuss the key challenges with 5G and how 6G is expected to tackle those by introducing new technological innovations and supporting novel use case requirements. We provide a comprehensive methodology for the design of a 6G E2E system including ten principles, a blueprint, and a structured design process. The architecture design principles prioritize environmental sustainability, digital inclusiveness, and trustworthiness, considering their impact on the 6G E2E system. The blueprint is described corresponding to the infrastructure, network centric application, and application layers, as well as the pervasive functionalities and the relevant technological innovations. Following the design principles and the system blueprint, the design process is demonstrated as two-way approaches (i.e., 1) key performance and value indicators based design process. 2) top-down versus bottom-up alignment process) through the lens of a collaborative robot use case. Through this use case, a special attention is given to the technological enablers that cover management and orchestration functionalities and their 6G enhancement to go beyond the limitations characterizing the previous network generation. In addition, virtual modelling aspects related to digital twining and simulations for 6G E2E system design are also discussed.

Background: Dermoscopy is a non-invasive method of evaluating disorders of the skin. Dermoscopy of hair and scalp disorders termed trichoscopy is useful in assessing scalp disorders with alopecia. Aim and Objectives: The aim of the study was to evaluate trichoscopic features of common scalp disorders with alopecia. The primary objective was to identify distinctive features of these disorders while the secondary objective was to formulate a simplified algorithm to arrive at a diagnosis. Material and Methods: A descriptive, cross sectional study of common scalp disorders with alopecia was conducted over a period of 2 years at a tertiary care centre. Two hundred cases were enrolled after obtaining approval of ethics committee and informed consent of patients. A detailed history was taken and general physical and dermatological examination carried out. Trichoscopic evaluation was carried out using Heine Delta 20T dermatoscope. Results: Common scalp disorders with alopecia included male pattern androgenetic alopecia (20.5%), alopecia areata (19.5%), telogen effluvium (12.5%) and female pattern hair loss (10.5%) and their trichoscopic features were tabulated. On the basis of trichoscopic features, an algorithm for rapid diagnosis was formulated. Conclusion: Common scalp disorders with alopecia have characteristic trichoscopic signs. A simplified algorithm formulated from the study may help in rapid diagnosis.

Research on vehicle-to-everything (V2X) is attracting significant attention nowadays, driven by the recent advances in beyond-5G (B5G) networks and the multi-access edge computing (MEC) paradigm. However, the inherent heterogeneity of B5G combined with the security vulnerabilities of MEC infrastructure in dynamic V2X scenarios introduces unprecedented challenges. Efficient resource and security management in multi-domain V2X environments is vital, especially with the growing threat of distributed denial-of-service (DDoS) attacks against critical V2X services within MEC. Our approach employs the zero-touch network and service management (ZSM) standard, integrating autonomous security into end-to-end (E2E) slicing management. We consider an entire 5G network, including vehicular user equipment, radio access networks, MEC, and core components, in the presence of DDoS targeting V2X services. Our framework complies with security service-level agreements (SSLAs) and policies, autonomously deploying and interconnecting security sub-slices across domains. Security requirements are continuously monitored and, upon DDoS detection, our framework reacts with a coordinated E2E strategy. The strategy mitigates DDoS at the MEC and deploys countermeasures in neighboring domains. Performance assessment reveals effective DDoS detection and mitigation with low latency, aligned with the mission-critical nature of certain V2X services. This work is part of ETSI ZSM PoC “security SLA assurance in 5G network slices”.

Implementing a compact optical integrated circuit by utilizing subwavelength plasmonic devices requires the design of compact and efficient photonic to plasmonic mode converters. Especially for plasmonic multiple-input devices such as logic gates that require multiple converters, the footprint can be largely penalized by the photonic waveguides, which should be considered in the design. In this work, we simulate and benchmark five photonic to plasmonic mode converter topologies for the application of multiple-input plasmonic devices. Our design includes both directional and end coupling schemes of plasmonic waveguide and Si photonic waveguides of wire and slot configurations. We optimize the performance of the converters considering the pitch mismatch between the photonic and plasmonic waveguides, the total footprint, and mode conversion efficiency.

Abstract Objective Peripheral arterial disease (PAD) is a manifestation of atherosclerosis that affects the lower extremities and afflicts more than 200 million people worldwide. Because of limited resources, the need to provide quality care associated with cost control is essential for health policies. Our study concerns an interhospital comparison among seventeen Belgian hospitals that integrates the weighting of quality indicators and the costs of care, from the hospital perspective, for a patient with this pathology in 2018. Methods The disability-adjusted life years (DALYs) were calculated by adding the number of years of life lost due to premature death and the number of years of life lost due to disability for each in-hospital stay. The DALY impact was interpreted according to patient safety indicators. We compared the hospitals using the adjusted values ​​of costs and DALYs for their case mix index, obtained by relating the observed value to the predicted value obtained by linear regression. Results We studied 2,437 patients and recorded a total of 560.1 DALYs in hospitals. The in-hospital cost average [standard deviation (SD)] was €8,673 (€10,893). Our model identified the hospitals whose observed values were higher than predicted; six needed to reduce the costs and impacts of DALYs, six needed to improve one of the two factors, and four seemed to have good results. The average cost (SD) for the worst performing hospitals amounted to €27,803 (€28,358). Conclusions Studying the costs of treatment according to patient safety indicators permits us to evaluate the entire chain of care using a comparable unit of measurement.

Abstract The association between Attention Deficit Hyperactivity Disorder (ADHD) and low-grade inflammation has been explored in children but rarely in adults. Inflammation is characteristic of some, but not all, patients with ADHD and might be influenced by ADHD medication but also lifestyle factors including nutrition, smoking, and stress. It is also still unclear if any specific symptoms are related to inflammation. Therefore, we assessed 96 inflammatory proteins in a deeply phenotyped cohort of 126 adult ADHD participants with a stable medication status using OLINK technology. A data-based, unsupervised hierarchical clustering method could identify two distinct biotypes within the 126 ADHD participants based on their inflammatory profile: a higher inflammatory potential (HIP) and a lower inflammatory protein potential (LIP) group. Biological processes that differed strongest between groups were related to the NF-κB pathway, chemokine signaling, IL-17 signaling, metabolic alterations, and chemokine attraction. A comparison of sample characteristics revealed that the HIP group was more likely to have higher levels of chronic stress (p

Abstract Many epidemiological models and algorithms are used to fit the parameters of a given epidemic curve. On many occasions, fitting algorithms are interleaved with the actual epidemic models, which yields combinations of model-parameters that are hard to compare among themselves. Here, we provide a model-agnostic framework for epidemic parameter fitting that can (fairly) compare different epidemic models without jeopardizing the quality of the fitted parameters. Briefly, we have developed a Python framework that expects a Python function (epidemic model) and epidemic data and performs parameter fitting using automatic configuration. Our framework is capable of fitting parameters for any type of epidemic model, as long as it is provided as a Python function (or even in a different programming language). Moreover, we provide the code for different types of models, as well as the implementation of 4 concrete models with data to fit them. Documentation, code and examples can be found at https://ulog.udl.cat/static/doc/epidemic-gga/html/index.html .