Early pragmatic expectations in human infancy.

There is no room for pragmatic expectations about communicative interactions in core cognition. Spelke takes the combinatorial power of the human language faculty to overcome the limits of core cognition. The question is: Why should the combinatorial power of the human language faculty support infants' pragmatic expectations not merely about speech, but also about nonverbal communicative interactions?

On the murky dissociation between expression and communication.

The authors present an ambitious attempt to outline the gradual evolution of the cognitive foundations of ostensive communication. We focus on three problematic aspects of the distinction between expression and communication: ambiguity in the distinction's central principle of "complementary mechanisms," inconsistencies in the application of the distinction across taxa, and the dismissal of mentalizing in nonhuman primates.

Variability of signal sequences in turn-taking exchanges induces agency attribution in 10.5-mo-olds.

Infants' sensitivity to contingent reactivity as an indicator of intentional agency has been demonstrated by numerous referential gaze-following studies. Here we propose that variability of signal sequences in a turn-taking exchange provides an informative cue for infants to recognize interactions that may involve communicative information transfer between agents. Our experiment demonstrates that based on the abstract structural cue of variability of exchanged signal sequences, 10.5-mo-olds gaze-followed an entity's subsequent object-orienting action to fixate the same object. This gaze-following effect did not depend on the specific acoustic features of the sound signals produced. However, no orientation following to target was induced when the exchanged signal sequences were identical, or when only a single entity produced the variable sound sequences. These results demonstrate infants' early sensitivity to detect signal variability in turn-taking interactions as a relevant feature of communicative information transfer, which induces them to attribute intentional agency and communicative abilities to the participating entities. However, when no variability was present in the exchanged signals, or when the variable signal sequences were produced by a single entity alone, infants showed no evidence of attributing agency. In sum, we argue that perceiving contingent turn-taking exchange of variable signal sequences induce 10.5-mo-old preverbal infants to recognize such interactions as potentially involving communicative information transmission and attribute agency to the participating entities even if both the entities and the signals they produce are unfamiliar to them.

If you presume relevance, you don't need a bifocal lens.

We argue for a relevance-guided learning mechanism to account for both innovative reproduction and faithful imitation by focusing on the role of communication in knowledge transmission. Unlike bifocal stance theory, this mechanism does not require a strict divide between instrumental and ritual-like actions, and the goals they respectively fulfill (material vs. social/affiliative), to account for flexibility in action interpretation and reproduction.

Acquiring sub-efficient and efficient variants of novel means by integrating information from multiple social models in preschoolers.

Sub-efficient action routines often represent culture-specific conventional forms of actions that belong to the repertoire of cultural knowledge shared by a social group. Children readily acquire such sub-efficient routines from social demonstrations and often preserve them in their action repertoire despite encountering more efficient alternatives. This suggests that they can treat sub-efficient conventional forms and their efficient alternatives in a context-sensitive selective manner. We hypothesized that children may rely on their sensitivity to differentiate speakers of their own language versus a foreign language as an informative cue indicating whether the model belongs to their own cultural community and the action modeled represents shared cultural knowledge. We assessed preschoolers' imitation following two different demonstrations. The first model demonstrated a sub-efficient action sequence, whereas the second model presented a more efficient alternative to obtain the same goal. We varied whether the children had heard the models speak their own language or a foreign language before their nonverbal action demonstrations. We found that 4-year-olds adopted the second model's efficient alternative, but only when she spoke their own language. However, they disregarded the efficient alternative if it was presented by a foreign-language speaker and continued to perform the sub-efficient routine they initially acquired. Therefore, 4-year-olds employed the cue of shared language to optimize acquiring and maintaining culturally shared sub-efficient action routines by selectively updating their action repertoire relying on their language-based evaluation of the demonstrator's culture-specific competence. In contrast, 5- and 6-year-olds adopted the efficient alternative independently of the demonstrator's language. Possible reasons for this developmental trend are discussed.

Fourteen-month-old infants track the language comprehension of communicative partners.

Infants employ sophisticated mechanisms to acquire their first language, including some that rely on taking the perspective of adults as speakers or listeners. When do infants first show awareness of what other people understand? We tested 14-month-old infants in two experiments measuring event-related potentials. In Experiment 1, we established that infants produce the N400 effect, a brain signature of semantic violations, in a live object naming paradigm in the presence of an adult observer. In Experiment 2, we induced false beliefs about the labeled objects in the adult observer to test whether infants keep track of the other person's comprehension. The results revealed that infants reacted to the semantic incongruity heard by the other as if they encountered it themselves: they exhibited an N400-like response, even though labels were congruous from their perspective. This finding demonstrates that infants track the linguistic understanding of social partners.

Seeing behind the surface: communicative demonstration boosts category disambiguation in 12-month-olds.

In their first years, infants acquire an incredible amount of information regarding the objects present in their environment. While often it is not clear what specific information should be prioritized in encoding from the many characteristics of an object, different types of object representations facilitate different types of generalizations. We tested the hypotheses that 1-year-old infants distinctively represent familiar objects as exemplars of their kind, and that ostensive communication plays a role in determining kind membership for ambiguous objects. In the training phase of our experiment, infants were exposed to movies displaying an agent sorting objects from two categories (cups and plates) into two locations (left or right). Afterwards, different groups of infants saw either an ostensive or a non-ostensive demonstration performed by the agent, revealing that a new object that looked like a plate can be transformed into a cup. A third group of infants experienced no demonstration regarding the new object. During test, infants were presented with the ambiguous object in the plate format, and we measured generalization by coding anticipatory looks to the plate or the cup side. While infants looked equally often towards the two sides when the demonstration was non-ostensive, and more often to the plate side when there was no demonstration, they performed more anticipatory eye movements to the cup side when the demonstration was ostensive. Thus, ostensive demonstration likely highlighted the hidden dispositional properties of the target object as kind-relevant, guiding infants' categorization of the foldable cup as a cup, despite it looking like a plate. These results suggest that infants likely encode familiar objects as exemplars of their kind and that ostensive communication can play a crucial role in disambiguating what kind an object belongs to, even when this requires disregarding salient surface features.

To what adaptive problems is human teaching a solution?

We welcome Kline's systematic overview of teaching from a functional evolutionary perspective. However, Kline's framework does not provide satisfying characterization of the adaptive problems driving the evolution of teaching through communication found in humans, where the key function is better characterized in terms of licensing inferences to opaque generic content than in terms of overcoming shortages of access and attention.

Better Together: 14-Month-Old Infants Expect Agents to Cooperate.

Humans engage in cooperative activities from early on and the breadth of human cooperation is unparalleled. Human preference for cooperation might reflect cognitive and motivational mechanisms that drive engagement in cooperative activities. Here we investigate early indices of humans' cooperative abilities and test whether 14-month-old infants expect agents to prefer cooperative over individual goal achievement. Three groups of infants saw videos of agents facing a choice between two actions that led to identical rewards but differed in the individual costs. Our results show that, in line with prior research, infants expect agents to make instrumentally rational choices and prefer the less costly of two individual action alternatives. In contrast, when one of the action alternatives is cooperative, infants expect agents to choose cooperation over individual action, even though the cooperative action demands more effort from each agent to achieve the same outcome. Finally, we do not find evidence that infants expect agents to choose the less costly alternative when both options entail cooperative action. Combined, these results indicate an ontogenetically early expectation of cooperation, and raise interesting implications and questions regarding the nature of infants' representations of cooperative actions and their utility.

Communicating shared knowledge in infancy.

Object-directed emotion expressions provide two types of information: They can convey the expressers' person-specific subjective disposition toward objects, or they can be used communicatively as referential symbolic devices to convey culturally shared valence-related knowledge about referents that can be generalized to other individuals. By presenting object-directed emotion expressions in communicative versus noncommunicative contexts, we demonstrated that 18-month-olds can flexibly assign either a person-centered interpretation or an object-centered interpretation to referential emotion displays. When addressed by ostensive signals of communication, infants generalized their object-centered interpretation of the emotion display to other individuals as well, whereas in the noncommunicative emotion-expression context, they attributed to the emoting agent a person-specific subjective dispositional attitude without generalizing this attribution as relevant to other individuals. The findings indicate that, as proposed by natural pedagogy theory, infants are prepared to learn shared cultural knowledge from nonverbal communicative demonstrations addressed to them at a remarkably early age.

Beyond rational imitation: learning arbitrary means actions from communicative demonstrations.

The principle of rationality has been invoked to explain that infants expect agents to perform the most efficient means action to attain a goal. It has also been demonstrated that infants take into account the efficiency of observed actions to achieve a goal outcome when deciding whether to reenact a specific behavior or not. It is puzzling, however, that they also tend to imitate an apparently suboptimal unfamiliar action even when they can bring about the same outcome more efficiently by applying a more rational action alternative available to them. We propose that this apparently paradoxical behavior is explained by infants' interpretation of action demonstrations as communicative manifestations of novel and culturally relevant means actions to be acquired, and we present empirical evidence supporting this proposal. In Experiment 1, we found that 14-month-olds reenacted novel arbitrary means actions only following a communicative demonstration. Experiment 2 showed that infants' inclination to reproduce communicatively manifested novel actions is restricted to behaviors they can construe as goal-directed instrumental acts. The study also provides evidence that infants' reenactment of the demonstrated novel actions reflects epistemic motives rather than purely social motives. We argue that ostensive communication enables infants to represent the teleological structure of novel actions even when the causal relations between means and end are cognitively opaque and apparently violate the efficiency expectation derived from the principle of rationality. This new account of imitative learning of novel means shows how the teleological stance and natural pedagogy--two separate cognitive adaptations to interpret instrumental versus communicative actions--are integrated as a system for learning socially constituted instrumental knowledge in humans.

[Detailed methodological recommendations for the treatment of Clostridium difficile-associated diarrhea with faecal transplantation]. / Módszertani ajánlás a Clostridium difficile fertozéshez asszociált hasmenés széklettranszplantációval történo kezeléséhez.

The incidence of Clostridium difficile associated enteral disease shows dramatic increase worldwide, with appallingly high treatment costs, mortality figures, recurrence rates and treatment refractoriness. It is not surprising, that there is significant interest in the development and introduction of alternative therapeutic strategies. Among these only stool transplantation (or faecal bacteriotherapy) is gaining international acceptance due to its excellent cure rate (≈92%), low recurrence rate (≈6%), safety and cost-effectiveness. Unfortunately faecal transplantation is not available for most patients, although based on promising international results, its introduction into the routine clinical practice is well justified and widely expected. The authors would like to facilitate this process, by presenting a detailed faecal transplantation protocol prepared in their Institution based on the available literature and clinical rationality. Officially accepted national methodological guidelines will need to be issued in the future, founded on the expert opinion of relevant professional societies and upcoming advances in this field.

Neural mechanisms of understanding rational actions: middle temporal gyrus activation by contextual violation.

Performing goal-directed actions toward an object in accordance with contextual constraints, such as the presence or absence of an obstacle, has been widely used as a paradigm for assessing the capacity of infants or nonhuman primates to evaluate the rationality of others' actions. Here, we have used this paradigm in a functional magnetic resonance imaging experiment to visualize the cortical regions involved in the assessment of action rationality while controlling for visual differences in the displays and directly correlating magnetic resonance activity with rationality ratings. Bilateral middle temporal gyrus (MTG) regions, anterior to extrastriate body area and the human middle temporal complex, were involved in the visual evaluation of action rationality. These MTG regions are embedded in the superior temporal sulcus regions processing the kinematics of observed actions. Our results suggest that rationality is assessed initially by purely visual computations, combining the kinematics of the action with the physical constraints of the environmental context. The MTG region seems to be sensitive to the contingent relationship between a goal-directed biological action and its relevant environmental constraints, showing increased activity when the expected pattern of rational goal attainment is violated.

[Successful treatment of life-threatening, treatment resistant Clostridium difficile infection associated pseudomembranous colitis with faecal transplantation]. / Életet veszélyezteto, terápiarefrakter Clostridium difficile fertozés okozta pseudomembranosus colitis sikeres kezelése széklettranszplantációval.

Due to world-wide spread of hypervirulent and antibiotic resistant Clostridium difficile strains, the incidence of these infections are dramatically increasing in Hungary with appalling mortality and recurrence rates. Authors present a case of a 59-year-old patient who developed a severe, relapsing pseudomembranous colitis after antibiotic treatment. Life-threatening symptoms of fulminant colitis were successfully treated with prolonged administration of metronidazole and vancomycin, careful supportive therapy and weeks of intensive care. However, a well-documented, severe relapse developed within a week and this time faecal bacteriotherapy was performed. This treatment resulted in a complete cure without any further antibiotic treatment. In relation to this life-saving faecal transplantation, methodology and indications are briefly discussed. In addition, microbiological issues, epidemiological data and threats associated with antibiotic treatment of Clostridium difficile infections are also covered. Finally, relevant professional societies are urged to prepare a national protocol for faecal transplantation, which could allow introduction of this valuable, cost-effective procedure into the routine clinical practice.

The newborn brain is sensitive to the communicative function of language.

Recent studies demonstrated neural systems in bilateral fronto-temporal brain areas in newborns specialized to extract linguistic structure from speech. We hypothesized that these mechanisms show additional sensitivity when identically structured different pseudowords are used communicatively in a turn-taking exchange by two speakers. In an fNIRS experiment newborns heard pseudowords sharing ABB repetition structure in three conditions: two voices turn-takingly exchanged different pseudowords (Communicative); the different pseudowords were produced by a (Single Speaker); two voices turn-takingly repeated identical pseudowords (Echoing). Here we show that left fronto-temporal regions (including Broca's area) responded more to the Communicative than the other conditions. The results demonstrate that newborns' left hemisphere brain areas show additional activation when various pseudowords sharing identical structure are exchanged in turn-taking alternation by two speakers. This indicates that language processing brain areas at birth are not only sensitive to the structure but to the functional use of language: communicative information transmission. Newborns appear to be equipped not only with innate systems to identify the structural properties of language but to identify its use, communication itself, that is, information exchange between third party social agents-even outside of the mother-infant dyad.

Influenza as a threat to cardiovascular health and the role of vaccination in risk reduction / Az influenza mint kardiológiai rizikótényezo és a vakcináció szerepe a kockázat csökkentésében

The different types of cardiovascular diseases, including coronary heart disease, cardiac arrhythmias and heart failure are highly prevalent in the society. Cardiovascular diseases are the leading cause of mortality. Although the influenza is forced out from the mainstream of thinking nowadays because of the ongoing SARS-CoV-2 pandemic, it still has its serious epidemiological significance. The seasonal influenza epidemic often contributes to mortality mainly, but not exclusively among old, multi-morbid patients. There are a vast number of scientific publications and evidence which prove and emphasize the synergic health-destroying and mortality-increasing effect of co-existing cardiovascular disease and influenza. Moreover, the beneficial effect of vaccination against influenza infection and its major role in prevention is also well documented. The SARS-CoV-2 pandemic enforces the importance of influenza vaccination because both viruses can lead to severe or often fatal disease, especially among old and frail patients. In addition, the younger population can be far more vulnerable against the novel coronavirus in the case of a co-existing influenza infection. International guidelines recommend influenza vaccination for patients having heart disease, like for other high-risk populations. Despite the nationally reimbursed, cost-free vaccines, the influenza vaccination rate of the society is still low not just in Hungary but also internationally. The authors review the effect of influenza infection on heart diseases, and draw attention to the role of influenza vaccination in decreasing cardiovascular morbidity and mortality.

Semantic systems are mentalistically activated for and by social partners.

A recently discovered electrophysiological response, the social N400, suggests that we use our language system to track how social partners comprehend language. Listeners show an increased N400 response, when themselves not, only a communicative partner experiences a semantic incongruity. Does the N400 reflect purely semantic or mentalistic computations as well? Do we attribute language comprehension to communicative partners using our semantic systems? In five electrophysiological experiments we identified two subcomponents of the social N400. First, we manipulated the presence-absence of an Observer during object naming: the semantic memory system was activated by the presence of a social partner in addition to semantic predictions for the self. Next, we induced a false belief-and a consequent miscomprehension-in the Observer. Participants showed the social N400, over and above the social presence effect, to labels that were incongruent for the Observer, even though they were congruent for them. This effect appeared only if participants received explicit instructions to track the comprehension of the Observer. These findings suggest that the semantic systems of the brain are not merely sensitive to social information and contribute to the attribution of comprehension, but they appear to be mentalistic in nature.

Dutogliptin in Combination with Filgrastim in Early Recovery Post-Myocardial Infarction-The REC-DUT-002 Trial.

Patients with acute myocardial infarction are at high risk for developing heart failure due to scar development. Although regenerative approaches are evolving, consistent clinical benefits have not yet been reported. Treatment with dutogliptin, a second-generation DPP-4 inhibitor, in co-administration with filgrastim (G-CSF) has been shown to enhance endogenous repair mechanisms in experimental models. The REC-DUT-002 trial was a phase 2, multicenter, double-blind placebo-controlled trial which explored the safety, tolerability, and efficacy of dutogliptin and filgrastim in patients with ST-elevation Myocardial Infarction (STEMI). Patients (n = 47, 56.1 ± 10.7 years, 29% female) with STEMI, reduced left ventricular ejection fraction (EF ≤ 45%) and successful revascularization following primary PCI were randomized to receive either study treatment or matching placebo. Cardiac magnetic resonance imaging (cMRI) was performed within 72 h post-PCI and repeated after 3 months. The study was closed out early due to the SARS-CoV-2 pandemic. There was no statistically significant difference between the groups with respect to serious adverse events (SAE). Predefined mean changes within cMRI-derived functional and structural parameters from baseline to 90 days did not differ between placebo and treatment (left ventricular end-diastolic volume: +13.7 mL vs. +15.7 mL; LV-EF: +5.7% vs. +5.9%). Improvement in cardiac tissue health over time was noted in both groups: full-width at half-maximum late gadolinium enhancement (FWHM LGE) mass (placebo: -12.7 g, treatment: -19.9 g; p = 0.23). Concomitant treatment was well tolerated, and no safety issues were detected. Based on the results, the FDA and EMA have already approved an adequately powered large outcome trial.

Immunological response and temporal associations in myocarditis after COVID-19 vaccination using cardiac magnetic resonance imaging: An amplified T-cell response at the heart of it?

Introduction: Although myocarditis after anti-SARS-CoV-2 vaccination is increasingly recognized, we have little data regarding the course of the disease and, consequently, the imaging findings, including the tissue-specific features. The purpose of this study is to describe the clinical, immunological, and cardiac magnetic resonance (CMR) features of myocarditis after COVID-19 immunization in the acute phase and during follow-up. We aimed to compare the trajectory of the disease to myocarditis cases unrelated to COVID-19. Methods: We assembled a CMR-based registry of potentially COVID-19 vaccination-related myocarditis cases. All patients who experienced new-onset chest pain and troponin elevation after COVID-19 vaccination and imaging confirming the clinical suspicion of acute myocarditis were enrolled in our study. Participants underwent routine laboratory testing and testing of their humoral and cellular immune response to COVID-19 vaccination. Clinical and CMR follow-up was performed after 3-6 months. We included two separate, sex- and age-matched control groups: (1) individuals with myocarditis unrelated to COVID-19 infection or vaccination confirmed by CMR and (2) volunteers with similar immunological exposure to SARS-CoV-2 compared to our group of interest (no difference in the number of doses, types and the time since anti-SARS-CoV-2 vaccination and no difference in anti-nucleocapsid levels). Results: We report 16 CMR-confirmed cases of myocarditis presenting (mean ± SD) 4 ± 2 days after administration of the anti-SARS-CoV-2 vaccine (male patients, 22 ± 7 years), frequently with predisposing factors such as immune-mediated disease and previous myocarditis. We found that 75% received mRNA vaccines, and 25% received vector vaccines. During follow-up, CMR metrics depicting myocardial injury, including oedema and necrosis, decreased or completely disappeared. There was no difference regarding the CMR metrics between myocarditis after immunization and myocarditis unrelated to COVID-19. We found an increased T-cell response among myocarditis patients compared to matched controls (p < 0.01), while there was no difference in the humoral immune response. Conclusion: In our cohort, myocarditis occurred after both mRNA and vector anti-SARS-CoV-2 vaccination, frequently in individuals with predisposing factors. Upon follow-up, the myocardial injury had healed. Notably, an amplified cellular immune response was found in acute myocarditis cases occurring 4 days after COVID-19 vaccination.

A Randomized, double-blind, dose ranging clinical trial of intravenous FDY-5301 in acute STEMI patients undergoing primary PCI.

BACKGROUND: Ischemia-reperfusion injury remains a major clinical problem in patients with ST-elevation myocardial infarction (STEMI), leading to myocardial damage despite early reperfusion by primary percutaneous coronary intervention (PPCI). There are no effective therapies to limit ischemia-reperfusion injury, which is caused by multiple pathways activated by rapid tissue reoxygenation and the generation of reactive oxygen species (ROS). FDY-5301 contains sodium iodide, a ubiquitous inorganic halide and elemental reducing agent that can act as a catalytic anti-peroxidant. We tested the feasibility, safety and potential utility of FDY-5301 as a treatment to limit ischemia-reperfusion injury, in patients with first-time STEMI undergoing emergency PPCI. METHODS: STEMI patients (n = 120, median 62 years) presenting within 12 h of chest pain onset were randomized at 20 PPCI centers, in a double blind Phase 2 clinical trial, to receive FDY-5301 (0.5, 1.0 or 2.0 mg/kg) or placebo prior to reperfusion, to evaluate the feasibility endpoints. Participants underwent continuous ECG monitoring for 14 days after PPCI to address pre-specified cardiac arrhythmia safety end points and cardiac magnetic resonance imaging (MRI) at 72 h and at 3 months to assess exploratory efficacy end points. RESULTS: Intravenous FDY-5301 was delivered before re-opening of the infarct-related artery in 97% participants and increased plasma iodide levels ~1000-fold within 2 min. There was no significant increase in the primary safety end point of incidence of cardiac arrhythmias of concern. MRI at 3 months revealed median final infarct sizes in placebo vs. 2.0 mg/kg FDY-5301-treated patients of 14.9% vs. 8.5%, and LV ejection fractions of 53.9% vs. 63.2%, respectively, although the study was not powered to detect statistical significance. In patients receiving FDY-5301, there was a significant reduction in the levels of MPO, MMP2 and NTproBNP after PPCI, but no reduction with placebo. CONCLUSIONS: Intravenous FDY-5301, delivered immediately prior to PPCI in acute STEMI, is feasible, safe, and shows potential efficacy. A larger trial is justified to test the effects of FDY-5301 on acute ischemia-reperfusion injury and clinical outcomes. CLINICAL TRIAL REGISTRATION: CT.govNCT03470441; EudraCT 2017-000047-41.