Weak and pleiotropy robust sex-stratified Mendelian randomization in the one sample and two sample settings.

BACKGROUND: Mendelian randomization (MR) leverages genetic data as an instrumental variable to provide estimates for the causal effect of an exposure X on a health outcome Y that is robust to confounding. Unfortunately, horizontal pleiotropy-the direct association of a genetic variant with multiple phenotypes-is highly prevalent and can easily render a genetic variant an invalid instrument. METHODS: Building on existing work, we propose a simple method for leveraging sex-specific genetic associations to perform weak and pleiotropy-robust MR analysis. This is achieved by constructing an MR estimator in which pleiotropy is perfectly removed by cancellation, while placing it within the powerful machinery of the robust adjusted profile score (MR-RAPS) method. Pleiotropy cancellation has the attractive property that it removes heterogeneity and therefore justifies a statistically efficient fixed effects model. We extend the method from the typical two-sample summary-data MR setting to the one-sample setting by adapting the technique of Collider-Correction. Simulation studies and applied examples are used to assess how the sex-stratified MR-RAPS estimator performs against other common approaches. RESULTS: The sex-stratified MR-RAPS method is shown to be robust to pleiotropy even in cases where all genetic variants violated the standard Instrument Strength Independent of Direct Effect assumption. In some cases where the strength of the pleiotropic effect additionally varied by sex (and so perfect cancellation was not achieved), over-dispersed MR-RAPS implementations can still consistently estimate the true causal effect. In applied analyses, we investigate the causal effect of waist-hip ratio (WHR), an important marker of central obesity, on a range of downstream traits. While the conventional approaches suggested paradoxical links between WHR and height and body mass index, the sex-stratified approach obtained a more realistic null effect. Nonzero effects were also detected for systolic and diastolic blood pressure as well as high-density and low-density lipoprotein cholesterol. DISCUSSION: We provide a simple but attractive method for weak and pleiotropy robust causal estimation of sexually dimorphic traits on downstream outcomes, by combining several existing approaches in a novel fashion.

Updating predictions in a complex repertoire of actions and its neural representation.

Even though actions we observe in everyday life seem to unfold in a continuous manner, they are automatically divided into meaningful chunks, that are single actions or segments, which provide information for the formation and updating of internal predictive models. Specifically, boundaries between actions constitute a hub for predictive processing since the prediction of the current action comes to an end and calls for updating of predictions for the next action. In the current study, we investigated neural processes which characterize such boundaries using a repertoire of complex action sequences with a predefined probabilistic structure. Action sequences consisted of actions that started with the hand touching an object (T) and ended with the hand releasing the object (U). These action boundaries were determined using an automatic computer vision algorithm. Participants trained all action sequences by imitating demo videos. Subsequently, they returned for an fMRI session during which the original action sequences were presented in addition to slightly modified versions thereof. Participants completed a post-fMRI memory test to assess the retention of original action sequences. The exchange of individual actions, and thus a violation of action prediction, resulted in increased activation of the action observation network and the anterior insula. At U events, marking the end of an action, increased brain activation in supplementary motor area, striatum, and lingual gyrus was indicative of the retrieval of the previously encoded action repertoire. As expected, brain activation at U events also reflected the predefined probabilistic branching structure of the action repertoire. At T events, marking the beginning of the next action, midline and hippocampal regions were recruited, reflecting the selected prediction of the unfolding action segment. In conclusion, our findings contribute to a better understanding of the various cerebral processes characterizing prediction during the observation of complex action repertoires.

Comprehensive investigation of predictive processing: A cross- and within-cognitive domains fMRI meta-analytic approach.

Predictive processing (PP) stands as a predominant theoretical framework in neuroscience. While some efforts have been made to frame PP within a cognitive domain-general network perspective, suggesting the existence of a "prediction network," these studies have primarily focused on specific cognitive domains or functions. The question of whether a domain-general predictive network that encompasses all well-established cognitive domains exists remains unanswered. The present meta-analysis aims to address this gap by testing the hypothesis that PP relies on a large-scale network spanning across cognitive domains, supporting PP as a unified account toward a more integrated approach to neuroscience. The Activation Likelihood Estimation meta-analytic approach was employed, along with Meta-Analytic Connectivity Mapping, conjunction analysis, and behavioral decoding techniques. The analyses focused on prediction incongruency and prediction congruency, two conditions likely reflective of core phenomena of PP. Additionally, the analysis focused on a prediction phenomena-independent dimension, regardless of prediction incongruency and congruency. These analyses were first applied to each cognitive domain considered (cognitive control, attention, motor, language, social cognition). Then, all cognitive domains were collapsed into a single, cross-domain dimension, encompassing a total of 252 experiments. Results pertaining to prediction incongruency rely on a defined network across cognitive domains, while prediction congruency results exhibited less overall activation and slightly more variability across cognitive domains. The converging patterns of activation across prediction phenomena and cognitive domains highlight the role of several brain hubs unfolding within an organized large-scale network (Dynamic Prediction Network), mainly encompassing bilateral insula, frontal gyri, claustrum, parietal lobules, and temporal gyri. Additionally, the crucial role played at a cross-domain, multimodal level by the anterior insula, as evidenced by the conjunction and Meta-Analytic Connectivity Mapping analyses, places it as the major hub of the Dynamic Prediction Network. Results support the hypothesis that PP relies on a domain-general, large-scale network within whose regions PP units are likely to operate, depending on the context and environmental demands. The wide array of regions within the Dynamic Prediction Network seamlessly integrate context- and stimulus-dependent predictive computations, thereby contributing to the adaptive updating of the brain's models of the inner and external world.

Preexposure to one social threat alters responses to another social threat: Behavioral and electrophysiological evidence.

A recent Cyberball study has indicated that the experience of loss of control can affect how people process subsequent social exclusion. This "preexposure effect" supports the idea of a common cognitive system involved in the processing of different types of social threats. To test the validity of this assumption in the current study, we reversed the sequence of the preexposure setup. We measured the effects of social exclusion on the subsequent processing of loss of control utilizing event-related brain potentials (ERPs) and self-reports. In the control group (CG, n = 26), the transition to loss of control elicited significant increases in both the P3 amplitude and the self-reported negative mood. Replicating the results of the previous preexposure study, these effects were significantly reduced by the preexposure to an independent social threat (here: social exclusion). In contrast to previous findings, these effects were not modulated by the discontinuation (EG1disc, n = 25) or continuation (EG2cont, n = 24) of the preexposure threat. Given that the P3 effect is related to the violation of subjective expectations, these results support the notion that preexposure to a specific social threat has widespread effects on the individuals' expectancy of upcoming social participation and control.

Adaptation of the BaAl4 Type to Small Cations: The Case of NaGa4.

Single-phase NaGa4 samples were prepared by annealing stoichiometric element mixtures at 200 °C, 300 °C, and 450 °C in closed tantalum ampoules. No compositional homogeneity range was detected. While single crystals annealed at 200 °C feature a fully ordered crystal structure, a crystal annealed at 300 °C reveals a defect with mutual exchange of Na atoms and Ga2 dumbbells. The structure motif caused by the violation of translational symmetry resembles the CeMg2Si2 type of structure. The NaGa4 structure constitutes a branch of the BaAl4 type distinguished by a notably high c/a ratio (space group I4/mmm; a = 4.2261(1) Å, c = 11.2633(6) Å, c/a = 2.67). This distortion enables the adaption of the BaAl4-type to small cations, when the further shortening of the apical-apical distance d(Ga-Ga) is not possible any more. Therefore, NaGa4 offers an adaption alternative to the monoclinic distortion observed in the CaGa4 and YbGa4. Conductivity measurements validate the metallic behavior anticipated by NMR measurements in earlier studies.

Pictorial depth cues elicit the perception of tridimensionality in dogs.

The perception of tridimensionality is elicited by binocular disparity, motion parallax, and monocular or pictorial cues. The perception of tridimensionality arising from pictorial cues has been investigated in several non-human animal species. Although dogs can use and discriminate bidimensional images, to date there is no evidence of dogs' ability to perceive tridimensionality in pictures and/or through pictorial cues. The aim of the present study was to assess the perception of tridimensionality in dogs elicited by two pictorial cues: linear perspective and shading. Thirty-two dogs were presented with a tridimensional stimulus (i.e., a ball) rolling onto a planar surface until eventually falling into a hole (control condition) or until reaching and rolling over an illusory hole (test condition). The illusory hole corresponded to the bidimensional pictorial representation of the real hole, in which the pictorial cues of shading and linear perspective created the impression of tridimensionality. In a violation of expectation paradigm, dogs showed a longer looking time at the scene in which the unexpected situation of a ball rolling over an illusory hole occurred. The surprise reaction observed in the test condition suggests that the pictorial cues of shading and linear perspective in the bidimensional image of the hole were able to elicit the perception of tridimensionality in dogs.

Experimental perspectives on the matter-antimatter asymmetry puzzle: developments in electron EDM and [Formula: see text] experiments.

In the search for clues to the matter-antimatter puzzle, experiments with atoms or molecules play a particular role. These systems allow measurements with very high precision, as demonstrated by the unprecedented limits down to [Formula: see text] e cm on electron EDM using molecular ions, and relative measurements at the level of [Formula: see text] in spectroscopy of antihydrogen atoms. Building on these impressive measurements, new experimental directions offer potential for drastic improvements. We review here some of the new perspectives in those fields and their associated prospects for new physics searches. This article is part of the theme issue 'The particle-gravity frontier'.

Pornography Use and the Acceptance of Gender Norm Violation in a School Context.

Although media effect studies have quite extensively investigated the association between pornography use and gendered attitudes, some questions remain. The present study aimed to address two of these questions by exploring how gendered attitudes and gender beliefs may be influenced by gender typicality and pornography use. First, the literature has not yet accounted for individual differences based on gender typicality. Second, the influence of pornography use on gender beliefs going beyond pornography's script application is understudied. This online cross-sectional study (N = 1,440, Mage = 23.86, SD = 4.79) contributes to the field by investigating the indirect association between pornography use and acceptance of gender norm violation through gendered attitudes and the moderating role of gender typicality. Acceptance of gender norm violation was measured via vignettes describing a school context in which a teacher and a student violated gender norms. Findings indicated that gendered attitudes negatively relate to the acceptance of gender norm violation. Moreover, compared to women, men's pornography use indirectly relates to lower acceptance rates through gendered attitudes. Additionally, for men, specific levels of gender typicality and atypicality form a strengthening and buffering role, respectively. This applies to the association between pornography use and gendered attitudes as well as to the indirect relationship of pornography use with acceptance of gender norm violation. These findings suggest that pornography use may also affect gender beliefs that are unrelated to the scripts present in pornography. Future studies should take into account the type of preferred pornography and unravel the specific impact of women's pornography use.

Out of sight, not out of mind: New pupillometric evidence on object permanence in a sample of 10- and 12-month-old German infants.

Findings on the emergence and interpretation of early object representation in the first year of life diverge widely between designs that employ looking times versus action-based measures. As a promising new approach, pupillometry has produced evidence for object permanence at 18 months of age, but not younger as of yet. In the current study, we (re)investigated object permanence following occlusion events in a pupillometric violation-of-expectation paradigm optimized for younger infants. During each trial, infants observed a toy object's occlusion and prompt reveal in the expected condition or its absence in the unexpected condition. Across two experiments, we show that 10- and 12-month-old infants' (total N = 82) pupils dilate in response to unexpected object disappearances relative to expected appearances. Control analyses revealed no differences between the scenes before the experimental manipulation, excluding perceptual interpretations. We further report an age-dependent effect of condition on pupil responses, with unexpected outcomes triggering greater pupil dilation in the older group. These results provide positive pupillometric evidence in support of object permanence in the context of a violation-of-expectation paradigm at 10 and 12 months of age.

Development and psychometric evaluation of the Violation Appraisal Measure (VAM).

Mental contamination refers to feelings of dirtiness and/or urges to wash that arise without direct contact with a contaminant. Cognitive models propose that this results from "serious, negative misappraisals of perceived violations". However, the specific violation misappraisals most relevant to mental contamination have yet to be established empirically, in part due to the lack of a comprehensive validated inventory of violation appraisals. Therefore, this study's aim was to develop and validate such a measure. Items for the new Violation Appraisal Measure (VAM) were developed from qualitative interviews, theoretical models, and previous empirical work. An Exploratory Factor Analysis was conducted in a sample of (n = 300) undergraduate participants, which revealed a four-factor structure: Responsibility/Self-Blame, Permanence, Mistrust, and Self-Worth. The VAM showed excellent internal consistency (α = 0.90), good convergent (r = .50 to .64) and adequate divergent (r = -.01 to .46) validity and was predictive of mental contamination symptoms over and above existing related appraisal measures, ΔF(1,289) = 29.35, p < .001, ΔR2 = 0.06. A Confirmatory Factor Analysis in a second sample of (n = 300) undergraduate students confirmed strong model fit for the four-factor structure of the VAM. The development of the VAM is an important contribution to the search for empirically based cognitive mechanisms in mental contamination and other violation-related sequelae.

Risk Factors for Multiple Violations of Protective Orders in Intimate Partner Violence Against Women.

This study examined 1,134 cases of violence against women in intimate partner relationships with violations of protective orders in a monitoring period of up to 15 months. The dynamics of time and violence were analyzed in the cases of multiple violation versus one-time violation, with the objective of identifying and thus neutralizing the risk factors for this type of recidivism. The results showed that early violation, serious physical violence, death threats, as well as jealousy, harassment, and control are related to multiple violation. This article discusses the results in comparison with other research and proposes measures to avoid revictimizations.

Traditional socio-cultural practices and early pregnancies in Togo: Between social norms and violation of adolescent rights.

This article shows how certain traditional socio-cultural practices that influence the root causes of teenage pregnancy violate the rights of adolescents. The data came from the action-research entitled "Multisectoral and transformative approaches to rites and initiations for adolescent sexual and reproductive health rights", conducted by the Togolese Association for Family Welfare (ATBEF) in May 2022. The option is made for a qualitative approach. The information collected was recorded on dictaphones and then transcribed from the local languages of collection into French. Content analysis was used to write the research report. The results reveal that these practices, which are still prevalent in the localities of the study, and which exert pressure on adolescent girls, are also products of violations of many girls' rights.

Cet article montre en quoi certaines pratiques socio-culturelles traditionnelles qui influencent les causes profondes de la survenue des grossesses chez les adolescentes, constituent une violation des droits de ces dernières. Les données proviennent de la recherche action titrée « Approches multisectorielles et transformatrices des rites et initiations pour les droits en santé sexuelle et de la reproduction des adolescentes ¼, menée par l'Association Togolaise pour le Bien-Etre Familial (ATBEF) en mai 2022. L'option est faite pour une approche qualitative. Les informations collectées ont été enregistrées sur dictaphones puis transcrites des langues locales de collecte vers le français. L'analyse de contenu a été utilisée pour la rédaction du rapport de recherche. Les résultats révèlent que ces pratiques encore prégnantes dans les localités de l'étude et qui exercent des pressions sur les adolescentes, sont aussi des produits des violations de nombreux droits des filles.

The Interplay between Tunneling and Parity Violation in Chiral Molecules.

In this review, the concepts of quantum tunneling and parity violation are introduced in the context of chiral molecules. A particle moving in a double well potential provides a good model to study the behavior of chiral molecules, where the left well and right well represent the L and R enantiomers, respectively. If the model considers the quantum behavior of matter, the concept of quantum tunneling emerges, giving place to stereomutation dynamics between left- and right-handed chiral molecules. Parity-violating interactions, like the electroweak one, can be also considered, making possible the existence of an energy difference between the L and R enantiomers, the so-called parity-violating energy difference (PVED). Here we provide a brief account of some theoretical methods usually employed to calculate this PVED, also commenting on relevant experiments devoted to experimentally detect the aforementioned PVED in chiral molecules. Finally, we comment on some ways of solving the so-called Hund's paradox, with emphasis on mean-field theory and decoherence.

Analytic Formulae for T Violation in Neutrino Oscillations.

Recently, a concept known as µTRISTAN, which involves the acceleration of µ+, has been proposed. This initiative has led to considerations of a new design for a neutrino factory. Additionally, leveraging the polarization of µ+, measurements of T violation in neutrino oscillations are also being explored. In this paper, we present analytical expressions for T violation in neutrino oscillations within the framework of standard three-flavor neutrino oscillations, a scenario involving nonstandard interactions, and a case of unitarity violation. We point out that examining the energy spectrum of T violation may be useful for probing new physics effects.

Optimizing Distributions for Associated Entropic Vectors via Generative Convolutional Neural Networks.

The complete characterization of the almost-entropic region yields rate regions for network coding problems. However, this characterization is difficult and open. In this paper, we propose a novel algorithm to determine whether an arbitrary vector in the entropy space is entropic or not, by parameterizing and generating probability mass functions by neural networks. Given a target vector, the algorithm minimizes the normalized distance between the target vector and the generated entropic vector by training the neural network. The algorithm reveals the entropic nature of the target vector, and obtains the underlying distribution, accordingly. The proposed algorithm was further implemented with convolutional neural networks, which naturally fit the structure of joint probability mass functions, and accelerate the algorithm with GPUs. Empirical results demonstrate improved normalized distances and convergence performances compared with prior works. We also conducted optimizations of the Ingleton score and Ingleton violation index, where a new lower bound of the Ingleton violation index was obtained. An inner bound of the almost-entropic region with four random variables was constructed with the proposed method, presenting the current best inner bound measured by the volume ratio. The potential of a computer-aided approach to construct achievable schemes for network coding problems using the proposed method is discussed.

Experiencing Surprise: The Temporal Dynamics of Its Impact on Memory.

To efficiently process information, the brain shifts between encoding and retrieval states, prioritizing bottom-up or top-down processing accordingly. Expectation violation before or during learning has been shown to trigger an adaptive encoding mechanism, resulting in better memory for unexpected events. Using fMRI, we explored (1) whether this encoding mechanism is also triggered during retrieval, and if so, (2) what the temporal dynamics of its mnemonic consequences are. Male and female participants studied object images, then, with new objects, they learned a contingency between a cue and a semantic category. Rule-abiding (expected) and violating (unexpected) targets and similar foils were used at test. We found interactions between previous and current similar events' expectation, such that when an expected event followed a similar but unexpected event, its performance was boosted, underpinned by activation in the hippocampus, midbrain, and occipital cortex. In contrast, a sequence of two unexpected similar events also triggered occipital engagement; however, this did not enhance memory performance. Taken together, our findings suggest that when the goal is to retrieve, encountering surprising events engages an encoding mechanism, supported by bottom-up processing, that may enhance memory for future related events.SIGNIFICANCE STATEMENT Optimizing the balance between new learning and the retrieval of existing knowledge is an ongoing process, at the core of human cognition. Previous research into memory encoding suggests experiencing surprise leads to the prioritization of the learning of new memories, forming an adaptive encoding mechanism. We examined whether this mechanism is also engaged when the current goal is to retrieve information. Our results demonstrate that an expectation-driven shift toward an encoding state, supported by enhanced perceptual processing, is beneficial for the correct identification of subsequent expected similar events. These findings have important implications for our understanding of the temporal dynamics of the adaptive encoding of information into memory.

Theµ-τreflection symmetry of Majorana neutrinos.

The observed pattern of lepton flavor mixing and CP violation strongly indicates the possible existence of a simple flavor symmetry in the neutrino sector-the effective Majorana neutrino mass term keeps invariant when the three left-handed neutrino fields transform asνeL→(νeL)c,νµL→(ντL)candντL→(νµL)c. A direct application of such aµ-τreflection symmetry to the canonical seesaw mechanism can help a lot to constrain the flavor textures of active and sterile Majorana neutrinos. The present article is intended to summarize the latest progress made in exploring the properties of this minimal flavor symmetry, its translational and rotational extensions, its soft breaking effects via radiative corrections from a superhigh energy scale to the electroweak scale, and its various phenomenological implications.

Conflicts in Mitochondrial Phylogenomics of Branchiopoda, with the First Complete Mitogenome of Laevicaudata (Crustacea: Branchiopoda).

Conflicting phylogenetic signals are pervasive across genomes. The potential impact of such systematic biases may be reduced by phylogenetic approaches accommodating for heterogeneity or by the exclusive use of homoplastic sites in the datasets. Here, we present the complete mitogenome of Lynceus grossipedia as the first representative of the suborder Laevicaudata. We employed a phylogenomic approach on the mitogenomic datasets representing all major branchiopod groups to identify the presence of conflicts and concordance across the phylogeny. We found pervasive phylogenetic conflicts at the base of Diplostraca. The homogeneity of the substitution pattern tests and posterior predictive tests revealed a high degree of compositional heterogeneity among branchiopod mitogenomes at both the nucleotide and amino acid levels, which biased the phylogenetic inference. Our results suggest that Laevicaudata as the basal clade of Phyllopoda was most likely an artifact caused by compositional heterogeneity and conflicting phylogenetic signal. We demonstrated that the exclusive use of homoplastic site methods combining the application of site-heterogeneous models produced correct phylogenetic estimates of the higher-level relationships among branchiopods.

Amygdala-frontoparietal effective connectivity in creativity and humor processing.

Although both creativity and humor elicit experiences of surprise followed by appreciation, it remains unknown whether shared or distinct patterns of effective connectivity are involved in their processing. The present fMRI study used dynamic causal modeling and parametrical empirical Bayes analysis to examine the effective connectivity between the amygdala and frontoparietal network during two-stage creativity and humor processing. We examined processing during the setup and punch line stages for creativity and humor, including typical forms (alternate uses for creativity and incongruity-resolution humor), atypical forms (aesthetic uses for creativity and nonsense humor), and baseline forms. Our focus was on the mesolimbic pathway during the punch line stage. We found that the amygdala plays a key role in expectation violation and appreciation. Broadly, amygdala-to-IFG connectivity was important for evaluating typical and atypical forms of both creativity and humor, while amygdala-to-precuneus connectivity was involved in evaluating typical forms. Amygdala-to-IFG connectivity was involved in the expectation violation to resolution stage of processing for typical and atypical forms of creativity and humor. Amygdala-to-precuneus connectivity was involved in processing the novelty and usefulness of typical forms of creativity (alternate uses) and understanding others' intentions in typical forms of humor (incongruity-resolution). Interestingly, VTA-to-amygdala connectivity was involved in processing the appreciation of both typical (incongruity-resolution humor) and atypical (nonsense humor) forms of humor while amygdala-to-VTA connectivity was involved in processing the appreciation of atypical (aesthetic uses) forms of creativity. Altogether, these findings suggest that the amygdala and frontoparietal circuitry are critical for creativity and humor processing.

Dogs' expectations about occlusion events: from expectancy violation to exploration.

Previous research on human infants has shown that violations of basic physical regularities can stimulate exploration, which may represent a type of hypothesis testing aimed at acquiring knowledge about new causal relationships. In this study, we examined whether a similar connection between expectancy violation and exploration exists in nonhuman animals. Specifically, we investigated how dogs react to expectancy violations in the context of occlusion events. Throughout three experiments, dogs exhibited longer looking times at expectancy-inconsistent events than at consistent ones. This finding was further supported by pupil size analyses in the first two eye-tracking experiments. Our results suggest that dogs expect objects to reappear when they are not obstructed by a screen and consider the size of the occluding screen in relation to the occluded object. In Experiment 3, expectancy violations increased the dogs' exploration of the target object, similar to the findings with human infants. We conclude that expectancy violations can provide learning opportunities for nonhuman animals as well.