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Face processing relies on predictive processes driven by low spatial frequencies (LSF) that convey coarse information prior to fine information conveyed by high spatial frequencies. However, autistic individuals might have atypical predictive processes, contributing to facial processing difficulties. This may be more normalized in autistic females, who often exhibit better socio-communicational abilities than males. We hypothesized that autistic females would display a more typical coarse-to-fine processing for socio-emotional stimuli compared to autistic males. To test this hypothesis, we asked adult participants (44 autistic, 51 non-autistic) to detect fearful faces among neutral faces, filtered in two orders: from coarse-to-fine (CtF) and from fine-to-coarse (FtC). Results show lower d' values and longer reaction times for fearful detection in autism compared to non-autistic (NA) individuals, regardless of the filtering order. Both groups presented shorter P100 latency after CtF compared to FtC, and larger amplitude for N170 after FtC compared to CtF. However, autistic participants presented a reduced difference in source activity between CtF and FtC in the fusiform. There was also a more spatially spread activation pattern in autistic females compared to NA females. Finally, females had faster P100 and N170 latencies, as well as larger occipital activation for FtC sequences than males, irrespective of the group. Overall, the results do not suggest impaired predictive processes from LSF in autism despite behavioral differences in fear detection. However, they do indicate reduced brain modulation by spatial frequency in autism. In addition, the findings highlight sex differences that warrant consideration in understanding autistic females.
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This work aims to assess the surface coupling of molecularly imprinted polymers (MIP) on carbon adsorbents produced from spent brewery grain, namely biochar (BC) and activated carbon (AC), as a strategy to improve selectivity and the adsorptive removal of the antibiotic sulfamethoxazole (SMX) from water. BC and AC were produced by microwave-assisted pyrolysis, and MIP was obtained by fast bulk polymerization. Two different methodologies were used for the molecular imprinting of BC and AC, the resulting materials being tested for SMX adsorption. Then, after selecting the most favourable molecular imprinting methodology, different mass ratios of MIP:BC or MIP:AC were used to produce and evaluate eight different materials. Molecular imprinting was shown to significantly improve the performance of BC for the target application, and one of the produced composites (MIP1-BC-s(1:3)) was selected for further kinetic and equilibrium studies and comparison with individual MIP and BC. The kinetic behaviour was properly described by both the pseudo-first and pseudo-second order models. Regarding equilibrium isotherms, they fitted the Freundlich and Langmuir models, with MIP1-BC-s(1:3) reaching a maximum adsorption capacity (qm) of 25 ± 1 µmol g-1, 19 % higher than BC. In comparison with other seven pharmaceuticals, the adsorption of SMX onto MIP1-BC-s(1:3) was remarkably higher, as for the specific recognition of this antibiotic by the coupled MIP. The pH study evidenced that SMX removal was higher under acidic conditions. Regeneration experiments showed that MIP1-BC-s(1:3) provided good adsorption performance, which was stable during five regeneration-reutilization cycles. Overall, this study has demonstrated that coupling with MIP may be a suitable strategy to improve the adsorption properties and performance of biochar for antibiotics removal from water, increasing its suitability for practical applications.
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Gulls commonly rely on human-generated waste as their primary food source, contributing to the spread of antibiotic-resistant bacteria and their resistance genes, both locally and globally. Our understanding of this process remains incomplete, particularly in relation to its potential interaction with surrounding soil and water. We studied the lesser black-backed gull, Larus fuscus, as a model to examine the spatial variation of faecal bacterial communities, antibiotic resistance genes (ARGs), and mobile genetic elements (MGEs) and its relationship with the surrounding water and soil. We conducted sampling campaigns within a connectivity network of different flocks of gulls moving across functional units (FUs), each of which represents a module of highly interconnected patches of habitats used for roosting and feeding. The FUs vary in habitat use, with some gulls using more polluted sites (notably landfills), while others prefer more natural environments (e.g., wetlands or beaches). Faecal bacterial communities in gulls from flocks that visit and spend more time in landfills exhibited higher richness and diversity. The faecal microbiota showed a high compositional overlap with bacterial communities in soil. The overlap was greater when compared to landfill (11%) than to wetland soils (6%), and much lower when compared to bacterial communities in surrounding water (2% and 1% for landfill and wetland water, respectively). The relative abundance of ARGs and MGEs were similar between FUs, with variations observed only for specific families of ARGs and MGEs. When exploring the faecal carriage of ARGs and MGEs in bird faeces relative to soil and water compartments, gull faeces were enriched in ARGs classified as High-Risk. Our results shed light on the complex dynamics of antibiotic resistance spread in wild bird populations, providing insights into the interactions among gull movement and feeding behavior, habitat characteristics, and the dissemination of antibiotic resistance determinants across environmental reservoirs.
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Functional analysis in mouse models is necessary to establish the involvement of a set of genetic variations in tumor development. A modeling platform to facilitate and cost-effectively analyze the role of multiple genes in carcinogenesis would be valuable. Here, we present an innovative strategy for lung mutagenesis using CRISPR/Cas9 ribonucleoproteins delivered via cationic polymers. This approach allows the simultaneous inactivation of multiple genes. We validate the effectiveness of this system by targeting a group of tumor suppressor genes, specifically Rb1, Rbl1, Pten, and Trp53, which were chosen for their potential to cause lung tumors, namely small cell lung carcinoma (SCLC). Tumors with histologic and transcriptomic features of human SCLC emerged after intratracheal administration of CRISPR/polymer nanoparticles. These tumors carried loss-of-function mutations in all four tumor suppressor genes at the targeted positions. These findings were reproduced in two different pure genetic backgrounds. We provide a proof of principle for simplified modeling of lung tumorigenesis to facilitate functional testing of potential cancer-related genes.
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Sistemas CRISPR-Cas , Neoplasias Pulmonares , Mutagênese , PTEN Fosfo-Hidrolase , Carcinoma de Pequenas Células do Pulmão , Proteína Supressora de Tumor p53 , Animais , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Camundongos , PTEN Fosfo-Hidrolase/genética , Proteína Supressora de Tumor p53/genética , Carcinoma de Pequenas Células do Pulmão/genética , Carcinoma de Pequenas Células do Pulmão/patologia , Humanos , Modelos Animais de Doenças , Proteína p107 Retinoblastoma-Like/genética , Proteína p107 Retinoblastoma-Like/metabolismo , Proteína do Retinoblastoma/genética , Proteína do Retinoblastoma/metabolismo , Edição de Genes/métodosRESUMO
A new interactive quantum zero-knowledge protocol for identity authentication implementable in currently available quantum cryptographic devices is proposed and demonstrated. The protocol design involves a verifier and a prover knowing a pre-shared secret, and the acceptance or rejection of the proof is determined by the quantum bit error rate. It has been implemented in modified Quantum Key Distribution devices executing two fundamental cases. In the first case, all players are honest, while in the second case, one of the users is a malicious player. We demonstrate an increase of the quantum bit error rate around 25% in the latter case compared to the case of honesty. The protocol has also been validated for distances from a back-to-back setup to more than 60 km between verifier and prover. The security and robustness of the protocol has been analysed, demonstrating its completeness, soundness and zero-knowledge properties.
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Contextual cues and emotional states carry expectations and biases that are used to attribute meaning to what we see. In addition, emotional states, such as anxiety, shape our visual systems, increasing overall, and particularly threat-related, sensitivity. It remains unclear, however, how anxiety interacts with additional cues when categorising sensory input. This is especially important in social scenarios where ambiguous gestures are commonplace, thus requiring the integration of cues for a proper interpretation. To this end, we decided to assess how states of anxiety might bias the perception of potentially aggressive social interactions, and how external cues are incorporated in this process. Participants (N = 71) were tasked with signalling the presence of aggression in ambiguous social interactions. Simultaneously, an observer (facial expression) reacted (by showing an emotional expression) to this interaction. Importantly, participants performed this task under safety and threat of shock conditions. Decision measures and eye-tracking data were collected. Our results showed that threat of shock did not affect sensitivity nor criterion when detecting aggressive interactions. The same pattern was observed for response times. Drift diffusion modelling analysis, however, suggested quicker evidence accumulation when under threat. Finally, dwell times over the observer were higher when under threat, indicating a possible association between anxiety states and a bias towards potentially threat-related indicators. Future probing into this topic remains a necessity to better explain the current findings.
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One of the less recognized effects of anxiety lies in perception alterations caused by how one weighs both sensory evidence and contextual cues. Here, we investigated how anxiety affects our ability to use social cues to anticipate the others' actions. We adapted a paradigm to assess expectations in social scenarios, whereby participants were asked to identify the presence of agents therein, while supported by contextual cues from another agent. Participants (N = 66) underwent this task under safe and threat-of-shock conditions. We extracted both criterion and sensitivity measures as well as gaze data. Our analysis showed that whilst the type of action had the expected effect, threat-of-shock had no effect over criterion and sensitivity. Although showing similar dwell times, gaze exploration of the contextual cue was associated with shorter fixation durations whilst participants were under threat. Our findings suggest that anxiety does not appear to influence the use of expectations in social scenarios.
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Antecipação Psicológica , Ansiedade , Humanos , Masculino , Feminino , Adulto , Ansiedade/psicologia , Adulto Jovem , Sinais (Psicologia) , Percepção Visual/fisiologiaRESUMO
Autism spectrum disorders (ASDs) are known to present sex-specific differences. At the same time, understanding how maternal behaviours are affected by pathogenic mutations is crucial to translate research efforts since rearing may recursively modulate neurodevelopment phenotype of the progeny. In this work, we focused on the effects of Gprasp2 deletion in females and its impact in progeny care and development. Female mice, wild-type (WT), Gprasp2+/- (HET) or Gprasp2-/- (KO) mutants and their progeny were used and behavioural paradigms targeting anxiety, memory, maternal care, and other social behaviours were performed. Analysis of communication was carried out through daily recordings of ultrasonic vocalizations in isolated pups and cross-fostering experiments were performed to understand the effect of maternal genotype in pup development. We found that Gprasp2-/- females presented striking impairments in social and working memory. Females also showed disruptions in maternal care, as well as physiological and molecular alterations in the reproductive system and hypothalamus, such as the structure of the mammary gland and the expression levels of oxytocin receptor (OxtR) in nulliparous versus primiparous females. We observed alterations in pup communication, particularly a reduced number of calls in Gprasp2 KO pups, which resulted from an interaction effect of the dam and pup genotype. Cross-fostering mutant pups with wild-type dams rescued some of the early defects shown in vocalizations, however, this effect was not bidirectional, as rearing WT pups with Gprasp2-/- dams was not sufficient to induce significant phenotypical alterations. Our results suggest Gprasp2 mutations perturb social and working memory in a sex-independent manner, but impact female-specific behaviours towards progeny care, female physiology, and gene expression. These changes in mutant dams contribute to a disruption in early stages of progeny development. More generally, our results highlight the need to better understand GxE interactions in the context of ASDs, when female behaviour may present a contributing factor in postnatal neurodevelopmental trajectory.
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Comportamento Materno , Camundongos Knockout , Comportamento Social , Animais , Comportamento Materno/fisiologia , Feminino , Camundongos , Masculino , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Comportamento Animal , Receptores de Ocitocina/genética , Transtorno do Espectro Autista/genética , Vocalização Animal/fisiologia , Deleção de GenesRESUMO
Anxiety shifts visual attention and perceptual mechanisms, preparing oneself to detect potentially threatening information more rapidly. Despite being demonstrated for threat-related social stimuli, such as fearful expressions, it remains unexplored if these effects encompass other social cues of danger, such as aggressive gestures/actions. To this end, we recruited a total of 65 participants and asked them to identify, as quickly and accurately as possible, potentially aggressive actions depicted by an agent. By introducing and manipulating the occurrence of electric shocks, we induced safe and threatening conditions. In addition, the association between electric shocks and aggression was also manipulated. Our result showed that participants have improved sensitivity, with no changes to criterion, when detecting aggressive gestures during threat compared to safe conditions. Furthermore, drift diffusion model analysis showed that under threat participants exhibited faster evidence accumulation toward the correct perceptual decision. Lastly, the relationship between threat source and aggression appeared to not impact any of the effects described above. Overall, our results indicate that the benefits gained from states of anxiety, such as increased sensitivity toward threat and greater evidence accumulation, are transposable to social stimuli capable of signaling danger other than facial expressions.
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Agressão , Medo , Humanos , Agressão/psicologia , Masculino , Feminino , Adulto Jovem , Adulto , Ansiedade/psicologia , Percepção Social , Atenção , Expressão Facial , Sinais (Psicologia) , EletrochoqueRESUMO
Given experience in cluttered but stable visual environments, our eye-movements form stereotyped routines that sample task-relevant locations, while not mixing-up routines between similar task-settings. Both dopamine signaling and mindfulness have been posited as factors that influence the formation of such routines, yet quantification of their impact remains to be tested in healthy humans. Over two sessions, participants searched through grids of doors to find hidden targets, using a gaze-contingent display. Within each session, door scenes appeared in either one of two colors, with each color signaling a differing set of likely target locations. We derived measures for how well target locations were learned (target-accuracy), how routine were sets of eye-movements (stereotypy), and the extent of interference between the two scenes (setting-accuracy). Participants completed two sessions, where they were administered either levodopa (dopamine precursor) or placebo (vitamin C), under double-blind counterbalanced conditions. Dopamine and trait mindfulness (assessed by questionnaire) interacted to influence both target-accuracy and stereotypy. Increasing dopamine improved accuracy and reduced stereotypy for high mindfulness scorers, but induced the opposite pattern for low mindfulness scorers. Dopamine also disrupted setting-accuracy invariant to mindfulness. Our findings show that mindfulness modulates the impact of dopamine on the target-accuracy and stereotypy of eye-movement routines, whereas increasing dopamine promotes interference between task-settings, regardless of mindfulness. These findings provide a link between non-human and human models regarding the influence of dopamine on the formation of task-relevant eye-movement routines and provide novel insights into behavior-trait factors that modulate the use of experience when building adaptive repertoires.
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Dopamina , Atenção Plena , Humanos , Masculino , Feminino , Adulto , Adulto Jovem , Dopamina/metabolismo , Levodopa/farmacologia , Levodopa/administração & dosagem , Método Duplo-Cego , Movimentos Oculares/fisiologia , Percepção Visual/fisiologia , Dopaminérgicos/farmacologia , Atenção/fisiologia , Desempenho Psicomotor/fisiologiaRESUMO
This scoping review identified contemporary stigma-reduction studies across US health-care settings. Despite the significance of this problem, only 3 intervention studies were identified in the past 5 years. These studies highlight the value of intervening during formative training experiences and the importance of including interprofessional health-care providers in interventions. The findings relate to the novel approaches (eg, virtual patient simulations) that are used in interventions. The importance of using a participatory approach to intervention design is noted. Critical gaps in human immunodeficiency virus (HIV) stigma measurement and the lack of interventions are identified, laying a foundation for future programs and research.
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Infecções por HIV , Estigma Social , Humanos , Infecções por HIV/psicologia , Estados Unidos , Pessoal de Saúde/psicologiaRESUMO
New pyridine-based chalcones 4a-h and pyrazolines 5a-h (N-acetyl), 6a-h (N-phenyl), and 7a-h (N-4-chlorophenyl) were synthesized and evaluated by the National Cancer Institute (NCI) against 60 different human cancer cell lines. Pyrazolines 6a, 6c-h, and 7a-h satisfied the pre-determined threshold inhibition criteria, obtaining that compounds 6c and 6f exhibited high antiproliferative activity, reaching submicromolar GI50 values from 0.38 to 0.45 µM, respectively. Moreover, compound 7g (4-CH3) exhibited the highest cytostatic activity of these series against different cancer cell lines from leukemia, nonsmall cell lung, colon, ovarian, renal, and prostate cancer, with LC50 values ranging from 5.41 to 8.35 µM, showing better cytotoxic activity than doxorubicin. Furthermore, the compounds were tested for antibacterial and antiplasmodial activities. Chalcone 4c was the most active with minimal inhibitory concentration (MIC) = 2 µg/mL against methicillin-resistant Staphylococcus aureus (MRSA), while the pyrazoline 6h showed a MIC = 8 µg/mL against Neisseria gonorrhoeae. For anti-Plasmodium falciparum activity, the chalcones display higher activity with EC50 values ranging from 10.26 to 10.94 µg/mL. Docking studies were conducted against relevant proteins from P. falciparum, exhibiting the minimum binding energy with plasmepsin II. In vivo toxicity assay in Galleria mellonella suggests that most compounds are low or nontoxic.
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Antibacterianos , Antimaláricos , Antineoplásicos , Chalconas , Testes de Sensibilidade Microbiana , Plasmodium falciparum , Pirazóis , Piridinas , Humanos , Antineoplásicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/química , Chalconas/farmacologia , Chalconas/síntese química , Chalconas/química , Antibacterianos/farmacologia , Antibacterianos/síntese química , Antibacterianos/química , Linhagem Celular Tumoral , Relação Estrutura-Atividade , Plasmodium falciparum/efeitos dos fármacos , Pirazóis/farmacologia , Pirazóis/química , Pirazóis/síntese química , Piridinas/farmacologia , Piridinas/química , Piridinas/síntese química , Antimaláricos/farmacologia , Antimaláricos/síntese química , Antimaláricos/química , Simulação de Acoplamento Molecular , Ensaios de Seleção de Medicamentos Antitumorais , Proliferação de Células/efeitos dos fármacos , Estrutura Molecular , Animais , Relação Dose-Resposta a Droga , Neisseria gonorrhoeae/efeitos dos fármacosRESUMO
The Banff Working Group on Liver Allograft Pathology met in September 2022. Participants included hepatologists, surgeons, pathologists, immunologists, and histocompatibility specialists. Presentations and discussions focused on the evaluation of long-term allograft health, including noninvasive and tissue monitoring, immunosuppression optimization, and long-term structural changes. Potential revision of the rejection classification scheme to better accommodate and communicate late T cell-mediated rejection patterns and related structural changes, such as nodular regenerative hyperplasia, were discussed. Improved stratification of long-term maintenance immunosuppression to match the heterogeneity of patient settings will be central to improving long-term patient survival. Such personalized therapeutics are in turn contingent on a better understanding and monitoring of allograft status within a rational decision-making approach, likely to be facilitated in implementation with emerging decision-support tools. Proposed revisions to rejection classification emerging from the meeting include the incorporation of interface hepatitis and fibrosis staging. These will be opened to online testing, modified accordingly, and subject to consensus discussion leading up to the next Banff conference.
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Rejeição de Enxerto , Transplante de Fígado , Humanos , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/patologia , Sobrevivência de Enxerto , AloenxertosRESUMO
IntroduccioÌn: La adolescencia es la etapa clave en la adquisicioÌn de haÌbitos y conductas adictivas que perduran toda la vida. Existe un modelo de consumo juvenil de drogas, legales e ilegales, como forma de relacioÌn social, uso recreativo y realizacioÌn personal. El policonsumo no debe ser visto como un rito de transicioÌn, sino como un problema de salud puÌblica. Objetivos: Se estudioÌ la prevalencia de consumo de sustancias adictivas y de medicamentos en 520 alumnos, entre 15 y 18 anÌos, de Escuelas PuÌblicas secundarias de la ciudad de BahiÌa Blanca. Asimismo, caracteriza el marco familiar, haÌbitos y costumbres de los estudiantes. Grupos estudiados: El 55% de los alumnos encuestados pertenece al sexo femenino y un 36% tiene doble escolaridad. Resultados: Los resultados indican que el 24% de los alumnos manifiesta fumar y un 85% tomar alcohol, de los cuales el 62% llegoÌ a la borrachera. El 25% consume drogas, 96% corresponde a marihuana, 8% cocaiÌna y 7% eÌxtasis. El 76% declara automedicarse y un 27% considera riesgosa esta praÌctica. El 84% convive con ambos padres y un 51% no posee materias desaprobadas. Un 35% de los joÌvenes no realiza deporte, el 46% estudia otro idioma y un 39% tiene como haÌbito la lectura. El 25% de los alumnos que reconocen tener actividad sexual no utilizaron ninguÌn meÌtodo de proteccioÌn. Conclusiones: Los resultados de la encuesta exponen la magnitud del problema y sumado a la baja edad de los estudiantes, derivan en muÌltiples consecuencias adversas. Este panorama constituye un desafiÌo para el meÌdico que, junto con la familia, docentes y especialistas, pueden actuar en aspectos preventivos, diagnoÌsticos y terapeÌuticos.
Introduction: Adolescence is the key stage in the acquisition of habits and addictive behaviors that last a lifetime. There is a pattern of youth drug use, both legal and illegal, as a form of social interaction, recreational use and personal fulfilment. Polydrug use should not be seen as a rite of passage, but as a public health problem. Objetive: This paper studies the prevalence of substance and drug use in 520 students, aged 15-18, from public secondary schools in the city of BahiÌa Blanca. It also characterizes the family background, habits and customs of the students. Gropus: 55% of the students surveyed were female and 36% of them had double schooling. Results: The results indicate that 24% of the students report smoking and 85% drinking alcohol, of which 62% became drunk. 25% use drugs, 96% marijuana, 8% cocaine and 7% ecstasy. 76% declare that they self-medicate and 27% consider this practice risky. 84% live with both parents and 51% do not have failed subjects in the report card. 35% of those surveyed do not practice sport, 46% study another language and 39% have reading as a habit. 25% of students who admit to sexual activity did not use any method of protection. Conclusions: The results of the survey expose the magnitude of the pro- blem and, coupled with the low age of the students, lead to multiple adverse consequences. This panorama constitutes a challenge for the doctor who, together with the family, teachers and specialists, can act in preventive, diagnostic and therapeutic aspects.
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Uso Indevido de Medicamentos , Automedicação , Saúde do Estudante , Transtornos Relacionados ao Uso de SubstânciasRESUMO
Stable visual perception, while we are moving, depends on complex interactions between multiple brain regions. We report a patient with damage to the right occipital and temporal lobes who presented with a visual disturbance of inward movement of roadside buildings towards the centre of his visual field, that occurred only when he moved forward on his motorbike. We describe this phenomenon as "self-motion induced environmental kinetopsia". Additionally, he was identified to have another illusion, in which objects displayed on the screen, appeared to pop out of the background. Here, we describe the clinical phenomena and the behavioural tasks specifically designed to document and measure this altered visual experience. Using the methods of lesion mapping and lesion network mapping we were able to demonstrate disrupted functional connectivity in the areas that process flow-parsing such as V3A and V6 that may underpin self-motion induced environmental kinetopsia. Moreover, we suggest that altered connectivity to the regions that process environmental frames of reference such as retrosplenial cortex (RSC) might explain the pop-out illusion. Our case adds novel and convergent lesion-based evidence to the role of these brain regions in visual processing.
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Ilusões , Percepção de Movimento , Masculino , Humanos , Mapeamento Encefálico/métodos , Imageamento por Ressonância Magnética/métodos , Estimulação LuminosaRESUMO
A novel combination of Butyric and Valeric acid glycerol esters with oregano oil in a dry powder form was evaluated for performance improvements in broilers. The dosing regimen (500 g/Ton feed in starter and grower; 250 g/Ton in finisher feed) was considered low compared to conventional practices using non-esterified Butyric and Valeric short-chain fatty acids (SCFA). Six trials were conducted at various trial facilities in Italy, United Kingdom, Spain, and Poland. Supplemented broilers weighed significantly more than the control birds at 28 days of age (+3.4%; 1459 g vs. 1412 g; p = 0.0006) and at 42 days of age (+2.5%; 2834 g vs. 2763 g; p = 0.0030). Supplementation significantly reduced mortality from 1.9% to 0.8% during the finisher phase (from 29 to 42 days of age); however, average mortality was 3.2% for the whole 42-day growth period and was not affected. Further, supplemented broilers grew more (66.4 vs. 64.5 g/day; p = 0.0005), ate more feed (104.7 vs. 103.1 g/day; p = 0.0473), converted feed significantly more efficiently (1.58 vs. 1.60; p = 0.0072), leading to better EPEF value (410 vs. 389; p = 0.0006) than the control broilers. Meta-analysed trial performance data for novel SCFA formulations such as these are not commonly available, and serve to facilitate efficacy determination from an end-user perspective. The use of short- and medium-chain fatty acid esters in optimal low-dose combinations to reliably augment gut health and performance appears promising in commercial broiler production, and may lead to further improvements in industry practices and reduced antibiotic use.
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Adaptive behaviours depend on dynamically updating internal representations of the world based on the ever-changing environmental contingencies. People with a substance use disorder (pSUD) show maladaptive behaviours with high persistence in drug-taking, despite severe negative consequences. We recently proposed a salience misattribution model for addiction (SMMA; Kalhan et al., 2021), arguing that pSUD have aberrations in their updating processes where drug cues are misattributed as strong predictors of positive outcomes, but weaker predictors of negative outcomes. We also argued that conversely, non-drug cues are misattributed as weak predictors of positive outcomes, but stronger predictors of negative outcomes. We tested these hypotheses using a multi-cue reversal learning task, with reversals in whether drug or non-drug cues are relevant in predicting the outcome (monetary win or loss). We show that people with a tobacco use disorder (pTUD), do form misaligned internal representations. We found that pTUD updated less towards learning the drug cue's relevance in predicting a loss. Further, when neither drug nor non-drug cue predicted a win, pTUD updated more towards the drug cue being relevant predictors of that win. Our Bayesian belief updating model revealed that pTUD had a low estimated likelihood of non-drug cues being predictors of wins, compared to drug cues, which drove the misaligned updating. Overall, several hypotheses of the SMMA were supported, but not all. Our results implicate that strengthening the non-drug cue association with positive outcomes may help restore the misaligned internal representation in pTUD, and offers a quantifiable, computational account of these updating processes.
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Tabagismo , Humanos , Sinais (Psicologia) , Teorema de Bayes , Aprendizagem , Adaptação PsicológicaRESUMO
OBJECTIVES: Pathologists interpreting kidney allograft biopsies using the Banff system usually start by recording component scores (eg, i, t, cg) using histopathologic criteria committed to memory. Component scores are then melded into diagnoses using the same manual/mental processes. This approach to complex Banff rules during routine sign-out produces a lack of fidelity and needs improvement. METHODS: We constructed a web-based "smart template" (software-assisted sign-out) system that uniquely starts with upstream Banff-defined additional diagnostic parameters (eg, infection) and histopathologic criteria (eg, percent interstitial inflammation) collectively referred to as feeder data that is then translated into component scores and integrated into final diagnoses using software-encoded decision trees. RESULTS: Software-assisted sign-out enables pathologists to (1) accurately and uniformly apply Banff rules, thereby eliminating human inconsistencies (present in 25% of the cohort); (2) document areas of improvement; (3) show improved correlation with function; (4) examine t-Distributed Stochastic Neighbor Embedding clustering for diagnosis stratification; and (5) ready upstream incorporation of artificial intelligence-assisted scoring of biopsies. CONCLUSIONS: Compared with the legacy approach, software-assisted sign-out improves Banff accuracy and fidelity, more closely correlates with kidney function, is practical for routine clinical work and translational research studies, facilitates downstream integration with nonpathology data, and readies biopsy scoring for artificial intelligence algorithms.
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Transplante de Rim , Software , Humanos , Biópsia , Rim/patologia , Aloenxertos/patologia , Rejeição de Enxerto/patologia , Rejeição de Enxerto/diagnósticoRESUMO
Neuroimaging research requires purpose-built analysis software, which is challenging to install and may produce different results across computing environments. The community-oriented, open-source Neurodesk platform ( https://www.neurodesk.org/ ) harnesses a comprehensive and growing suite of neuroimaging software containers. Neurodesk includes a browser-accessible virtual desktop, command-line interface and computational notebook compatibility, allowing for accessible, flexible, portable and fully reproducible neuroimaging analysis on personal workstations, high-performance computers and the cloud.