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Variation in coat color is a prominent feature in carnivores, thought to be shaped by environmental factors. As new traits could allow populations to occupy novel niches and habitats, color polymorphism may be maintained by balancing selection. Consequently, color polymorphic species may speciate more rapidly and can give rise to monomorphic daughter species. We thus predicted that, within the Carnivora, (i) speciation rate is higher in polymorphic lineages, (ii) divergence between color polymorphic lineages is more recent, and (iii) within closely related groups, polymorphic lineages are ancestral and monomorphic lineages derived. We also tested whether accelerated speciation rates relate to niche breadth, measured by the number of occupied habitats and range size. We collected data of 48 polymorphic and 192 monomorphic carnivore species, and assessed speciation rates using phylogenetic comparative methods. We found that polymorphic carnivores had higher speciation rates (λ1 = 0.29, SD = 0.13) than monomorphic species (λ0 = 0.053, SD = 0.044). Hidden and quantitative state speciation and extinction models inferred that color polymorphism was the main contributing factor, and that niche breadth was not of influence. Therefore, other selective forces than spatial niche segregation, such as predator-prey coevolution, may contribute to color polymorphism in wild carnivores. [ABSTRACT FROM AUTHOR]

Causation is a core feature of human cognition and language. How children learn about intricate causal meanings is yet unresolved. Here, we focus on how children learn verbs that express causation. Such verbs, known as lexical causatives (e.g., break and raise), lack explicit morphosyntactic markers indicating causation, thus requiring that the child generalizes the causal meaning from the context. The language addressed to children presumably plays a crucial role in this learning process. Hence, we tested whether adults adapt their use of lexical causatives to children when talking to them in day‐to‐day interactions. We analyzed naturalistic longitudinal data from 12 children in the Manchester corpus (spanning from 20 to 36 months of age). To detect semantic generalization, we employed a network approach with semantics learned from cross‐situational contexts. Our results show an increasing trend in the expansion of causative semantics, observable in both child speech and child‐directed speech. Adults consistently maintain somewhat more intricate causative semantic networks compared to children. However, both groups display evolving patterns. Around 28–30 months of age, children undergo a reduction in the degree of causative generalization, followed by a slightly time‐lagged adjustment by adults in their speech directed to children. These findings substantiate adults' adaptation in child‐directed speech, extending to semantics. They highlight child‐directed speech as a highly adaptive and subconscious teaching tool that facilitates the dynamic processes of language acquisition. [ABSTRACT FROM AUTHOR]

Background: Pruritus is a symptom profoundly impairing patients' quality of life (QoL). It is a common symptom in chronic heart failure (CHF) patients of yet unknown nature. The aim of this study was to evaluate the risk factors of pruritus in CHF patients. Methods: For this monocentric, prospective cohort study, CHF patients were recruited and CHF symptoms, comorbidities and drug intake were assessed using a structured report. Additionally, a questionnaire evaluated pruritus symptoms. Detailed medical histories including laboratory test results were retrieved from patient files for all participants. Results: We evaluated data from 550 CHF patients. Of those, 25.3% reported pruritus to occur frequently (3–5 times per week), often (1–2 times per week) or daily. Patients of higher NYHA classes (NYHA III + IV) experienced significantly more pruritus (31.2%) than lower NYHA classes (NYHA I + II) (21.1%, p = 0.024). Patients with pruritus reported disproportionately often concomitant stasis dermatitis (p = 0.026) and chronic lung disease (p = 0.014). Other parameters reflecting cardiac, liver, kidney and thyroid function, as well as medical therapies showed no significant differences between patients with and without pruritus. In the multivariate logistic regression analysis, only NYHA class (p = 0.016, OR 1.55, 95% confidence interval (CI): [1.09; 2.20]) and elevated leukocyte count (p = 0.007, OR 1.11, CI [1.03; 1.21]) remained significantly associated with pruritus in CHF patients. Conclusions: NYHA class is an independent predictor for pruritus in CHF patients. Besides NYHA class, leukocyte count was also associated with increased pruritus. Pruritus may impair QoL in CHF patients and should thus be included in the assessment of those patients. We suggest that providing best care for CHF patients can be achieved through an interdisciplinary approach of cardiologists and dermatologists and should include a pruritus assessment. [ABSTRACT FROM AUTHOR]

The study explores the relationship between anti-rubella IgG serum levels and the risk of SARS-CoV-2 breakthrough infections. Lower anti-rubella IgG levels were associated with an increased risk of breakthrough infections, indicating a potential predictive value for identifying individuals at risk. These findings suggest that assessing anti-rubella IgG levels could help determine the need for additional SARS-CoV-2 vaccinations and may serve as an indicator of vaccine efficacy beyond SARS-CoV-2. The study was conducted with a diverse group of participants and adhered to ethical guidelines, providing valuable insights for personalized prevention strategies. [Extracted from the article]

Humor is an important component of children's learning and development. Yet, the cognitive mechanisms that underlie humor recognition in children have not been well-researched. In this pre-registered study, we asked whether (1) 4- to 5-year-old children recognize and categorize amisfortunate situation as funny only if the victims show a funny bewildered face (slapstick humor), and not a painful or angry expression, (2) this ability increases with age, (3) it is associated with children's Theory of Mind (ToM) abilities, (4) it is related to the ability to recognize facial emotional expressions. In an online experiment platform, children (N = 61, Mage = 53 months) were asked to point to the funny picture between a funny and an affective picture. Then, children were asked to point to the happy, sad, fearful, or angry face among four faces displaying these emotions. Children's ToM was assessed using the Children's Social Understanding Scale (CSUS), which was filled out online by parents. Results showed that from the earliest age onward, the predicted probability of humor recognition exceeded the chance level. Only ToM but not age was a significant predictor. Children with higher ToM scores showed better humor recognition. We found no evidence for a relation between children's humor recognition and their recognition of any emotion (happy, sad, fearful, or angry). Our findings suggest that 4-5-year-old children recognize facial emotional expressions and slapstick humor, although these abilities seem unrelated. Instead, children's understanding of mental states appears to play a role in their recognition of slapstick humor. [ABSTRACT FROM AUTHOR]

To provide the current student generation with an innovative online learning method, podcasts with science fiction short stories are introduced to marketing education. Findings from neurology and psychology point to positive effects of storytelling for gaining knowledge and developing interpersonal skills. Science fiction stories challenge common conceptions and enable students to engage with upcoming marketing issues in creative ways. An overview of eight marketing related science fiction stories is provided that are available for download as open access podcasts, with 23 more management and economics podcast stories available in the online appendix. To show how science fiction podcasts can be implemented in class, one of the stories is discussed in more detail. Further suggestions for implementation and possible challenges are outlined. [ABSTRACT FROM AUTHOR]

The marine cyanobacterium Prochlorococcus is a main contributor to global photosynthesis, whilst being limited by iron availability. Cyanobacterial genomes generally encode two different types of FutA iron-binding proteins: periplasmic FutA2 ABC transporter subunits bind Fe(III), while cytosolic FutA1 binds Fe(II). Owing to their small size and their economized genome Prochlorococcus ecotypes typically possess a single futA gene. How the encoded FutA protein might bind different Fe oxidation states was previously unknown. Here, we use structural biology techniques at room temperature to probe the dynamic behavior of FutA. Neutron diffraction confirmed four negatively charged tyrosinates, that together with a neutral water molecule coordinate iron in trigonal bipyramidal geometry. Positioning of the positively charged Arg103 side chain in the second coordination shell yields an overall charge-neutral Fe(III) binding state in structures determined by neutron diffraction and serial femtosecond crystallography. Conventional rotation X-ray crystallography using a home source revealed X-ray-induced photoreduction of the iron center with observation of the Fe(II) binding state; here, an additional positioning of the Arg203 side chain in the second coordination shell maintained an overall charge neutral Fe(II) binding site. Dose series using serial synchrotron crystallography and an XFEL X-ray pump-probe approach capture the transition between Fe(III) and Fe(II) states, revealing how Arg203 operates as a switch to accommodate the different iron oxidation states. This switching ability of the Prochlorococcus FutA protein may reflect ecological adaptation by genome streamlining and loss of specialized FutA proteins. [ABSTRACT FROM AUTHOR]

Interoception, the perception of internal bodily signals, is fundamental to our sense of self. Even though theoretical accounts suggest an important role for interoception in the development of the self, empirical investigations are limited, particularly in infancy. Previous studies used preferential‐looking paradigms to assess the detection of sensorimotor and multisensory contingencies in infancy, usually related to proprioception and touch. So far, only one recent study reported that infants discriminated between audiovisual stimuli presented synchronously or asynchronously with their heartbeat. This discrimination was related to the amplitude of the infant's heartbeat evoked potentials (HEP), a neural correlate of interoception. In the current study, we measured looking preferences between synchronous and asynchronous visuocardiac (bimodal), and audiovisuocardiac (trimodal) stimuli as well as the HEP in conditions of different emotional contexts and with different degrees of self‐relatedness in a mirror‐like setup. While the infants preferred trimodal to bimodal stimuli, we did not observe the predicted differences between synchronous and asynchronous stimulation. Furthermore, the HEP was not modulated by emotional context or self‐relatedness. These findings do not support previously published results and highlight the need for further studies on the early development of interoception in relation to the development of the self. Interoception has recently been discussed as fundamental in the development of the sense of self. Here, we report findings that are not in line with previous evidence of the presence of interoceptive sensitivity in infants, both at a behavioral and neurophysiological level. The study contributes to closing the currently existing gap in theoretical discussions on the development of interoception and the empirical evidence thereof. [ABSTRACT FROM AUTHOR]

Knee range of motion and patient-reported outcome measures (PROMs) are often used as screening tools to assess the severity of knee osteoarthritis and guide the decision to refer patients to an arthroplasty clinic. However, there is little understanding regarding the correlation between these factors. Thus, the purpose of this study was to determine the correlation between patient-reported clinical function measured with the Oxford Knee Score (OKS), pain assessed using the visual analog scale (VAS), knee range of motion (ROM), and characteristic radiographic features in patients with advanced osteoarthritis of the knee. A prospective analysis of a consecutive series of 138 patients with advanced unilateral osteoarthritis (OA) of the knee was performed. The severity of radiographic OA was classified according to the most commonly used Kellgren and Lawrence classification (K&L). Spearman's rank correlation analysis and multiple linear regression analysis were performed. The OKS was used as a dependent variable and was adjusted for pain, ROM, and nine standardized radiographic parameters on multiple views of the tibiofemoral and patellofemoral joint. OKS and pain correlated weakly with the K&L grade (r = −0.289; p = 0.001; r = 0.258; p = 0.002). K&L grade and the degree of patellofemoral joint space narrowing were identified as independent factors being associated with a poorer OKS (coefficient −4.528, p = 0.021; coefficient −2.211, p = 0.038). Slightly worse results were identified for OKS and pain in patients with K&L grade 4 osteoarthritis compared to patients with K&L grade 3 osteoarthritis (∆OKS 5.5 points, p < 0.001; ∆VAS 1.7 points, p = 0.003). There was no significant difference for passive range of motion between patients with K&L grade 3 or 4. When counseling patients with advanced knee osteoarthritis who may be eligible for knee arthroplasty, it is essential to give primary consideration to pain levels and self-reported limitations experienced during daily activities. Relying solely on knee ROM and PROMs is not an effective screening method for guiding the decision to refer patients to an arthroplasty clinic. [ABSTRACT FROM AUTHOR]

Introduction: In adults, allergic reactions to insect stings are among the most frequent causes of anaphylaxis, a potentially life-threatening condition. Recurrent anaphylaxis following vespid stings may be prevented by allergen immunotherapy (AIT). The aim of this study was to evaluate the benefit of measuring venom-induced wheal area in intracutaneous skin tests (ICT), in comparison to various serological and clinical parameters, for the diagnosis of severe vespid venom allergy and during follow-up of AIT. Methods: We conducted a monocentric, retrospective evaluation of 170 patients undergoing AIT against vespid venoms. We scanned ICT wheals at baseline and at three time points after AIT initiation and measured wheal area using objective data analysis software. Results: We found that ICT histamine-induced and venom-induced wheal areas did not correlate. In addition, the venom-induced wheal area was independent from the minimal venom concentration required to elicit a wheal in an ICT and all other parameters. No correlation was found between wheal area and the severity of anaphylaxis. Wheal area standardized to the application of 0.1 μg/mL venom inversely correlated with anaphylaxis severity and positively correlated with venom-specific IgE levels. During AIT, mean areas of venom-induced wheals did not change. In contrast, venom-specific IgG and IgG4 levels, and the minimal venom concentration required to induce a positive ICT result increased, while the venom wheal area standardized to 0.1 μg/mL venom application and specific IgE levels decreased over time. Conclusion: Wheal area evaluation did not provide additional information over specific IgE analysis. We therefore recommend that ICTs are used only as a secondary measure for confirming serological test results. [ABSTRACT FROM AUTHOR]

The article presents a neuroscience research study on the understanding of how sensory and contextual effects on pain are processed in the brain. Topics include the influence of sensory information on local brain oscillations and the exclusive influence of expectations on interregional connectivity; and sensory effects primarily affect local brain activity, while expectations impact the communication between different brain regions in processing sensory and contextual aspects of pain.

The innate immune system detects pathogens via germline-encoded receptors that bind to conserved pathogen ligands called pathogen-associated molecular patterns (PAMPs). Here we consider an additional strategy of pathogen sensing called effector-triggered immunity (ETI). ETI involves detection of pathogen-encoded virulence factors, also called effectors. Pathogens produce effectors to manipulate hosts to create a replicative niche and/or block host immunity. Unlike PAMPs, effectors are often diverse and rapidly evolving and can thus be unsuitable targets for direct detection by germline-encoded receptors. Effectors are instead often sensed indirectly via detection of their virulence activities. ETI is a viable strategy for pathogen sensing and is used across diverse phyla, including plants, but the molecular mechanisms of ETI are complex compared to simple receptor/ligand-based PAMP detection. Here we survey the mechanisms and functions of ETI, with a particular focus on emerging insights from animal studies. We suggest that many examples of ETI may remain to be discovered, hiding in plain sight throughout immunology. [ABSTRACT FROM AUTHOR]

Context. The presence of radioactive 26Al at 1.8MeV reveals an ongoing process of nucleosynthesis in the Milky Way. Diffuse emission from its decay can be measured with gamma-ray telescopes in space. The intensity, line shape, and spatial distribution of the 26Al emission allow for studies of these nucleosynthesis sources. The line parameters trace massive-star feedback in the interstellar medium thanks to its 1 My lifetime. Aims. We aim to expand upon previous studies of the 26Al emission in the Milky Way, using all available gamma-ray data, including single and double events collected with SPI on INTEGRAL from 2003 until 2020. Methods. We applied improved spectral response and background as evaluated from tracing spectral details over the entire mission. The exposure for the Galactic 26Al emission was enhanced using all event types measured within SPI. We redetermined the intensity of Galactic 26Al emission across the entire sky, through maximum likelihood fits of simulated and model-built sky distributions to SPI spectra for single and for double detector hits. Results. We found an all-sky flux of (1.84±0.03)×10-3 ph cm-2 s-1 in the 1.809 MeV line from 26Al, determined via fitting to sky distributions from previous observations with COMPTEL. Significant emission from higher latitudes indicates an origin from nearby massive-star groups and superbubbles, which is also supported by a bottom-up population synthesis model. The line centroid is found at (1809.83±0.04 keV), while the line broadening from source kinematics integrated over the sky is (0.62±0.3) keV (FWHM). [ABSTRACT FROM AUTHOR]

Diffuse 1-ray line emission traces freshly produced radioisotopes in the interstellar gas, providing a unique perspective on the entire Galactic cycle of matter from nucleosynthesis in massive stars to their ejection and mixing in the interstellar medium (ISM). We aim to construct a model of nucleosynthesis ejecta on a galactic scale that is specifically tailored to complement the physically most important and empirically accessible features of 1ray measurements in the MeV range, in particular for decay 1 rays such as 26Al, 60Fe, or 44Ti. Based on properties of massive star groups, we developed a Population SYnthesis COde (PSYCO), which can instantiate galaxy models quickly and based on many different parameter configurations, such as the star formation rate (SFR), density profiles, or stellar evolution models. As a result, we obtain model maps of nucleosynthesis ejecta in the Galaxy which incorporate the population synthesis calculations of individual massive star groups. Based on a variety of stellar evolution models, supernova (SN) explodabilities, and density distributions, we find that the measured 26Al distribution from INTEGRAL/SPI can be explained by a Galaxy-wide population synthesis model with a SFR of 4-8 M yr-1 and a spiral-arm-dominated density profile with a scale height of at least 700 pc. Our model requires that most massive stars indeed undergo a SN explosion. This corresponds to a SN rate in the Milky Way of 1.8-2.8 per century, with quasi-persistent 26Al and 60Fe masses of 1.2-2.4 Mand 1-6 M, respectively. Comparing the simulated morphologies to SPI data suggests that a frequent merging of superbubbles may take place in the Galaxy, and that an unknown yet strong foreground emission at 1.8MeV could be present. [ABSTRACT FROM AUTHOR]

The innate immune system employs two different strategies to detect pathogens: first, it recognizes microbial components as ligands of pattern recognition receptors (pattern-triggered immunity [PTI]), and second, it detects the activities of pathogen-encoded effectors (effector-triggered immunity [ETI]). Recently, these pathogen-centric concepts were expanded to include sensing of self-derived signals during cellular distress or damage (damage-triggered immunity [DTI]). This extension relied on broadening the PTI model to include damage-associated molecular patterns (DAMPs). However, applying the pattern recognition framework of PTI to DTI overlooks the critical role of sterile activation of ETI pathways. We argue that both PTI and ETI pathways are prone to erroneous detection of self, which is largely attributable to 'friendly fire' rather than protective immune activation. This erroneous activation is inherent to the trade-off between sensitivity and specificity of immune sensing and might be tolerated because its detrimental effects emerge late in life, a phenomenon known as antagonistic pleiotropy. [ABSTRACT FROM AUTHOR]

Today, a vast number of tools exist to measure development in early childhood in a variety of domains such as cognition, language, or motor, cognition. These tools vary in different aspects. Either children are examined by a trained experimenter, or caregivers fill out questionnaires. The tools are applied in the controlled setting of a laboratory or in the children's natural environment. While these tools provide a detailed picture of the current state of children's development, they are at the same time subject to several constraints. Furthermore, the measurement of an individual child's change of different skills over time requires not only one measurement but high-density longitudinal assessments. These assessments are time-consuming, and the breadth of developmental domains assessed remains limited. In this paper, we present a novel tool to assess the development of skills in different domains, a smartphone-based developmental diary app (the kleineWeltentdecker App, henceforth referred to as the APP (The German expression "kleine Weltentdecker" can be translated as "young world explorers".)). By using the APP, caregivers can track changes in their children's skills during development. Here, we report the construction and validation of the questionnaires embedded in the APP as well as the technical details. Empirical validations with children of different age groups confirmed the robustness of the different measures implemented in the APP. In addition, we report preliminary findings, for example, on children's communicative development by using existing APP data. This substantiates the validity of the assessment. With the APP, we put a portable tool for the longitudinal documentation of individual children's development in every caregiver's pocket, worldwide. [ABSTRACT FROM AUTHOR]

Introduction: This study aims to compare cup inclination achieved (1) Using two orientation guides, whilst using the same 3-point pelvic positioner and (2) Using two types of pelvic positioners, whilst measuring intra-operative cup inclination with an inclinometer. Materials and methods: This is a prospective, diagnostic cohort study of a consecutive series of 150 THAs performed through a posterior approach. Two types of 3-point pelvic positioners were used (Stulberg and modified Capello Hip Positioners) and the cup was positioned freehand using one of two orientation guides (mechanical guide or digital inclinometer). Intra-operative inclination was recorded, radiographic cup inclination and anteversion were measured from radiographs. The differences in inclination due to pelvic position (ΔPelvicPosition) and orientation definitions (ΔDefinition) were calculated. Target radiographic inclination and anteversion was 40/20° ± 10°. Results: There was no difference in radiographic cup inclination/ (p = 0.63) using a mechanical guide or digital inclinometer. However, differences were seen in ΔPelvicPosition between the positioners ((Stulberg: 0° ± 5 vs. Capello: 3° ± 6); p = 0.011). Intra-operative inclination at implantation was different between positioners and this led to equivalent cases within inclination/anteversion targets (Stulberg:84%, Capello:80%; p = 0.48). Conclusions: With the pelvis securely positioned with 3-point supports, optimum cup orientation can be achieved with both alignment guides and inclinometer. Non-optimal cup inclinations were seen when intra-operative inclinations were above 40° and below 32°, or the ΔPelvicPosition was excessive (> 15°; n = 2). We would thus recommend that the intra-operative cup inclination should be centered strictly between 30° and 35° relative to the floor. Small differences exist between different type of pelvic positioners that surgeons need to be aware off and account for. [ABSTRACT FROM AUTHOR]

Given the unprecedented rates of global warming, widespread shifts in species' distributions are anticipated to play a key role for their survival. Yet, current conservation policies often allocate priority to native species and their typical habitats, thereby preserving historic conditions rather than preparing for future species distributions. Policy initiatives aimed at halting biodiversity loss, such as the EU 2030 Biodiversity Strategy, could provide an opportunity to proactively integrate species' future distributions into conservation objectives on an international scale, for example, by encouraging management actions that allow for species migration along projected paths of dispersal. Acknowledging climate‐tracking species as a conceptually distinct phenomenon, we qualitatively analyzed to which extent the EU 2030 Biodiversity Strategy and the legal framework it is embedded in, such as the Draft Note on Designation Criteria (ENV.D.3/JC) and the Framework for Blue and Green Infrastructure (SWD/2019/193), integrated climate‐trackers into their conservation objectives. We found that the Biodiversity Strategy did not explicitly incorporate future patterns of species distributions into conservation planning but emphasized the maintenance of historical community compositions and species distributions. While the commitments in these legal documents to nature restoration will certainly be helpful for biodiversity conservation today and after 2030, it may miss the chance to be a more comprehensive conservation policy. [ABSTRACT FROM AUTHOR]

In the last 2 years, several studies investigated the immunological responses to SARS-CoV-2 infections and/or COVID-19 vaccinations,1-6 but long-term immunological effects in response to different vaccination combinations are poorly defined. In this regard, vaccination regimes including BNT162b2 elicit strong immune responses with a more rapid decline, whereas vector-based vaccinations yield lower and comparably stable immunological effects. For the groups with BNT162b2 as a second vaccination, anti-spike-RBD-IgG was negatively associated with the days elapsed since the second vaccination (Figure 1C, left panel) suggesting higher antibody dynamics for vaccination regimes including BNT162b2. [Extracted from the article]

Background: Homologous and heterologous SARS‐CoV‐2 vaccinations yield different spike protein‐directed humoral and cellular immune responses. This study aimed to explore their currently unknown interdependencies. Methods: COV‐ADAPT is a prospective, observational cohort study of 417 healthcare workers who received vaccination with homologous ChAdOx1 nCoV‐19, homologous BNT162b2 or with heterologous ChAdOx1 nCoV‐19/BNT162b2. We assessed humoral (anti‐spike‐RBD‐IgG, neutralizing antibodies, and avidity) and cellular (spike‐induced T‐cell interferon‐γ release) immune responses in blood samples up to 2 weeks before (T1) and 2–12 weeks following secondary immunization (T2). Results: Initial vaccination with ChAdOx1 nCoV‐19 resulted in lower anti‐spike‐RBD‐IgG compared with BNT162b2 (70 ± 114 vs. 226 ± 279 BAU/ml, p <.01) at T1. Booster vaccination with BNT162b2 proved superior to ChAdOx1 nCoV‐19 at T2 (anti‐spike‐RBD‐IgG: ChAdOx1 nCoV‐19/BNT162b2 2387 ± 1627 and homologous BNT162b2 3202 ± 2184 vs. homologous ChAdOx1 nCoV‐19 413 ± 461 BAU/ml, both p <.001; spike‐induced T‐cell interferon‐γ release: ChAdOx1 nCoV‐19/BNT162b2 5069 ± 6733 and homologous BNT162b2 4880 ± 7570 vs. homologous ChAdOx1 nCoV‐19 1152 ± 2243 mIU/ml, both p <.001). No significant differences were detected between BNT162b2‐boostered groups at T2. For ChAdOx1 nCoV‐19, no booster effect on T‐cell activation could be observed. We found associations between anti‐spike‐RBD‐IgG levels (ChAdOx1 nCoV‐19/BNT162b2 and homologous BNT162b2) and T‐cell responses (homologous ChAdOx1 nCoV‐19 and ChAdOx1 nCoV‐19/BNT162b2) from T1 to T2. Additionally, anti‐spike‐RBD‐IgG and T‐cell response were linked at both time points (all groups combined). All regimes yielded neutralizing antibodies and increased antibody avidity at T2. Conclusions: Interdependencies between humoral and cellular immune responses differ between common SARS‐CoV‐2 vaccination regimes. T‐cell activation is unlikely to compensate for poor humoral responses. [ABSTRACT FROM AUTHOR]

Keywords: decision support; diagnostic error; quality improvement EN decision support diagnostic error quality improvement 241 249 9 05/12/22 20220501 NES 220501 Introduction Diagnostic error is a frequent health care problem [[1]], [[2]], [[3]], [[4]] with major medical [[4]], [[5]], [[6]], legal [[7]], [[8]], [[9]] and economic consequences [[10]]. In the second dataset, 11 students only provided a diagnosis in five out of six cases, resulting in 109 out of 120 pairs of diagnoses being available for analysis. Three trained raters independently classified the pair of ER admittance diagnosis and internal medicine discharge diagnosis as either similar or discrepant, based on a previously validated scheme [[37]]. These are missed opportunities in diagnosis that did not result in patient harm, those that did (an entity he consequently terms "preventable diagnostic harm"), and delayed/wrong diagnosis without clear evidence of a missed opportunity, either with or without resulting harm [[18]]. [Extracted from the article]

Background: The presence of hip osteoarthritis is associated with abnormal spinopelvic characteristics. This study aimed to determine whether the preoperative, pathological spinopelvic characteristics normalize at 1 year after total hip arthroplasty (THA).Methods: This was a prospective, longitudinal, case-control, matched cohort study. Forty-seven patients undergoing THA underwent preoperative and 1-year postoperative assessments. This group was matched with regard to age, sex, and body mass index with 47 controls (volunteers) with well-functioning hips. All participants underwent clinical and radiographic assessments including lateral radiographs in standing, relaxed-seated, and deep-flexed-seated positions. Spinopelvic characteristics included change in lumbar lordosis (ΔLL), change in pelvic tilt (ΔPT), and hip flexion (change in pelvic-femoral angle, ΔPFA) when moving from a standing position to either of the seated positions. Spinopelvic hypermobility was defined as ΔPT > 30° between the standing and upright-seated positions.Results: Patients who underwent THA, compared with the control group, preoperatively demonstrated less mean change in hip flexion (ΔPFA, -54.8° ± 17.1° compared with -68.5° ± 9.5°; p < 0.001), greater mean change in pelvic tilt (ΔPT, 22.0° ± 13.5° compared with 12.7° ± 8.1°; p < 0.001), and greater mean lumbar movement (ΔLL, -22.7° ± 15.5° compared with -15.4° ± 10.9°; p = 0.015) transitioning from a standing position to an upright-seated position. After THA, these differences were no longer present between the THA group and the control group: the mean postoperative changes were -65.8° ± 12.5° (p = 0.256) for ΔPFA, 14.3° ± 9.5° (p = 0.429) for ΔPT, and -15.3° ± 10.6° (p = 0.966) for ΔLL. The higher prevalence of spinopelvic hypermobility in the THA group compared with the control group that was observed preoperatively (21% compared with 0%; p = 0.009) was no longer present after THA (6% compared with 0%; p = 0.194). Similar results were found moving from a standing position to a deep-seated position after THA.Conclusions: Preoperative spinopelvic characteristics that contribute to abnormal mechanics can normalize after THA following improvement in hip flexion. This leads to patients having the expected hip, pelvic, and spinal flexion as demographically matched controls, thus potentially eliminating abnormal mechanics that contribute to the development or exacerbation of hip-spine syndrome.Level Of Evidence: Therapeutic Level II. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Spinopelvic mobility affects outcome after THA. Whether the sacro‐femoral‐pubic (SFP) angle, measured on AP radiographs, can be reliably used to estimate pelvic tilt (PT) in hip osteoarthritis patients is unknown. This study aimed to (1) validate the use of the SFP angle in the calculation of PT from AP radiographs, and (2) identify individual patient factors affecting the estimation of PT. A cohort of 100 patients awaiting THA for end‐stage hip osteoarthritis was prospectively studied. AP and lateral radiographs, taken in the standing and relaxed‐seated positions were evaluated for spinopelvic measurements (SFP, PT, and pelvic incidence [PI]). To validate the SFP angle, estimated PT values using the formula [PT = 75°‐SFP] were compared to the true, measured values from the lateral radiographs. Despite good agreement for the estimated and true PT (16.2 ± 5.9° vs. 15.5 ± 8.6°; p =.315), a significantly poorer agreement could be found between the two methods at high or low values of PT. Patient‐specific PI correlated with the difference between the two measurement methods (Pearson's r = −0.644; p <.001). However, the change in SFP angle equaled approximately the change in pelvic tilt (∆PT = 2°−∆SFP; Pearson's r = −0.934; p <.001). Absolute values for the sagittal PT should not be estimated from AP pelvic radiographs in patients awaiting total hip arthroplasty. However, the relative change in PT between different positions equals approximately the change in SFP angle. This may allow functional cup orientation after THA to be determined between different postures from an AP radiograph of the pelvis. The SFP angle has moderate accuracy in determining a patient's pelvic tilt; however, it can accurately determine a patient's change in pelvic tilt in different positions. [ABSTRACT FROM AUTHOR]

The perception of pain is shaped by somatosensory information about threat. However, pain is also influenced by an individual's expectations. Such expectations can result in clinically relevant modulations and abnormalities of pain. In the brain, sensory information, expectations (predictions), and discrepancies thereof (prediction errors) are signaled by an extended network of brain areas which generate evoked potentials and oscillatory responses at different latencies and frequencies. However, a comprehensive picture of how evoked and oscillatory brain responses signal sensory information, predictions, and prediction errors in the processing of pain is lacking so far. Here, we therefore applied brief painful stimuli to 48 healthy human participants and independently modulated sensory information (stimulus intensity) and expectations of pain intensity while measuring brain activity using electroencephalography (EEG). Pain ratings confirmed that pain intensity was shaped by both sensory information and expectations. In contrast, Bayesian analyses revealed that stimulus-induced EEG responses at different latencies (the N1, N2, and P2 components) and frequencies (alpha, beta, and gamma oscillations) were shaped by sensory information but not by expectations. Expectations, however, shaped alpha and beta oscillations before the painful stimuli. These findings indicate that commonly analyzed EEG responses to painful stimuli are more involved in signaling sensory information than in signaling expectations or mismatches of sensory information and expectations. Moreover, they indicate that the effects of expectations on pain are served by brain mechanisms which differ from those conveying effects of sensory information on pain. [ABSTRACT FROM AUTHOR]

The Integrator was originally discovered as a specialized 3'-end processing endonuclease complex required for maturation of RNA polymerase II (RNAPII)-dependent small nuclear RNAs (snRNAs). Since its discovery, Integrator's spectrum of substrates was significantly expanded to include non-polyadenylated long noncoding RNAs (lncRNA), enhancer RNAs (eRNAs), telomerase RNA (tertRNA), several Herpesvirus transcripts, and messenger RNAs (mRNAs). Recently emerging transcriptome-wide studies reveled an important role of the Integrator in protein-coding genes, where it contributes to gene expression regulation through promoter-proximal transcription attenuation. These new functional data are complemented by several structures of Integrator modules and higher-order complexes, providing mechanistic insights into Integrator-mediated processing events. In this work, we summarize recent progress in our understanding of the structure and function of the Integrator complex. [ABSTRACT FROM AUTHOR]

Little is known about the parenting style of male couples who become fathers via surrogacy, adoption or fostering. In a European study, 35 gay fathers and 33 heterosexual fathers answered questionnaires with respect to their parenting style with their first-born child, temperament characteristics of that child, and their own personality. The results indicate that gay fathers show higher levels of warmth and cooperation with their partner than heterosexual fathers. Gay fathers also reported less irritation if their first-born child displayed a negative temperament. No differences in the parenting style were found with respect to the sex of their child. Our results contribute to the limited empirical research about same-sex male parents and parenting style. [ABSTRACT FROM AUTHOR]

An inherent component of tool‐use actions is the transformation of the user's operating movement into the desired effect. In this study, the relevance of this transformation for young children's learning of tool‐use actions was investigated. Sixty‐four children at the age of 27–30 months learned to use levers which either simply extended (compatible transformation) or reversed (incompatible transformation) their operating movements. Data revealed a compatibility effect as well as transfer effects originating from the two different types of transformations. Furthermore, results suggest that young children's tool‐use learning is not a uniform process, but has to be regarded individually depending on the type of transformation. [ABSTRACT FROM AUTHOR]

TNF is a highly pro-inflammatory cytokine that contributes not only to the regulation of immune responses but also to the development of severe inflammatory diseases. TNF is synthesized as a transmembrane protein, which is further matured via proteolytic cleavage by metalloproteases such as ADAM17, a process known as shedding. At present, TNF is mainly detected by measuring the precursor or the mature cytokine of bulk cell populations by techniques such as ELISA or immunoblotting. However, these methods do not provide information on the exact timing and extent of TNF cleavage at single-cell resolution and they do not allow the live visualization of shedding events. Here, we generated C-tag TNF as a genetically encoded reporter to study TNF shedding at the single-cell level. The functionality of the C-tag TNF reporter is based on the exposure of a cryptic epitope on the C terminus of the transmembrane portion of pro-TNF on cleavage. In both denatured and nondenatured samples, this epitope can be detected by a nanobody in a highly sensitive and specific manner only upon TNF shedding. As such, C-tag TNF can successfully be used for the detection of TNF cleavage in flow cytometry and live-cell imaging applications. We furthermore demonstrate its applicability in a forward genetic screen geared toward the identification of genetic regulators of TNF maturation. In summary, the C-tag TNF reporter can be employed to gain novel insights into the complex regulation of ADAM-dependent TNF shedding. [ABSTRACT FROM AUTHOR]

The ability to infer mental and affective states of others is crucial for social functioning. This ability, denoted as Theory of Mind (ToM), develops rapidly during childhood, yet results on its development across adolescence and into young adulthood are rare. In the present study, we tested the two‐component model, measuring age‐related changes in social‐perceptual and social‐cognitive ToM in a sample of 267 participants between 11 and 25 years of age. Additionally, we measured language, reasoning, and inhibitory control as major covariates. Participants inferred mental states from non‐verbal cues in a social‐perceptual task (Eye Test) and from stories with faux pas in a social‐cognitive task (Faux Pas Test). Results showed substantial improvement across adolescence in both ToM measures and in the covariates. Analysis with linear mixed models (LMM) revealed specific age‐related growth for the social‐perceptual component, while the age‐related increase of the social‐cognitive component fully aligned with the increase of the covariates. These results support the distinction between ToM components and indicate that adolescence is a crucial period for developing social‐perceptual ToM abilities. Statement of contributionWhat is already known on this subject?To date, much research has been dedicated to Theory of Mind (ToM) development in early and middle childhood. However, only a few studies have examined development of ToM in adolescence.Studies so far suggest age‐related differences in ToM between adolescents and young adults.What this study addsThe study offers several methodological advantages including a large sample size with a continuous distribution of age (age 11–25) and the use of a comprehensive test battery to assess ToM and covariates (language, executive functions, reasoning).The results provide evidence for asymmetries in the development of two ToM components (social‐perceptual and social‐cognitive; the two‐component account) across the studied age range:the social perceptual component showed specific development, while the age‐related increase of the social‐cognitive component fully aligned with increase of the covariates.Adolescence is a crucial period for developing social‐perceptual ToM abilities. [ABSTRACT FROM AUTHOR]

Pain is a complex phenomenon that is served by neural oscillations and connectivity involving different brain areas and frequencies. Here, we aimed to systematically and comprehensively assess the pattern of neural oscillations and connectivity characterizing the state of tonic experimental pain in humans. To this end, we applied 10‐min heat pain stimuli consecutively to the right and left hand of 39 healthy participants and recorded electroencephalography. We systematically analyzed global and local measures of oscillatory brain activity, connectivity, and graph theory‐based network measures during tonic pain and compared them to a nonpainful control condition. Local measures showed suppressions of oscillatory activity at alpha frequencies together with stronger connectivity at alpha and beta frequencies in sensorimotor areas during tonic pain. Furthermore, sensorimotor areas contralateral to stimulation showed significantly increased connectivity to a common area in the medial prefrontal cortex at alpha frequencies. Together, these observations indicate that the state of tonic experimental pain is associated with a sensorimotor‐prefrontal network connected at alpha frequencies. These findings represent a step further toward understanding the brain mechanisms underlying long‐lasting pain states in health and disease. [ABSTRACT FROM AUTHOR]

• Laughter and humour are important elements of social and cognitive development. • Previous research suggested that humans may not be the only species that "laughs". • We discuss possible common roots of human and animal humour. • Humour and humour-like behaviour can reveal cognitive and social development. • The SPeCies Perspective frames humour based on social, physiological, and cognitive factors. This mini-review discusses the existing evidence on various forms of humour and humour-like behaviour in non-human animals, combining ontogenetic and phylogenetic perspectives. The first section describes humour-like behaviours, from the simplest to the most complex form (from laughing, tickling, joking, and chasing to ToM humour). In the second section, we propose the SPeCies (Social, Physiological, and Cognitive) Perspective, which frames the various types of humour based on Social motivation, Physiological state, and Cognitive skills. Finally, in the third section, we discuss future directions for further development. [ABSTRACT FROM AUTHOR]

Chronic pain is a common and severely disabling disease whose treatment is often unsatisfactory. Insights into the brain mechanisms of chronic pain promise to advance the understanding of the underlying pathophysiology and might help to develop disease markers and novel treatments. Here, we systematically exploited the potential of electroencephalography to determine abnormalities of brain function during the resting state in chronic pain. To this end, we performed state-of-the-art analyses of oscillatory brain activity, brain connectivity, and brain networks in 101 patients of either sex suffering from chronic pain. The results show that global and local measures of brain activity did not differ between chronic pain patients and a healthy control group. However, we observed significantly increased connectivity at theta (4-8 Hz) and gamma (>60 Hz) frequencies in frontal brain areas as well as global network reorganization at gamma frequencies in chronic pain patients. Furthermore, a machine learning algorithm could differentiate between patients and healthy controls with an above-chance accuracy of 57%, mostly based on frontal connectivity. These results suggest that increased theta and gamma synchrony in frontal brain areas are involved in the pathophysiology of chronic pain. Although substantial challenges concerning the reproducibility of the findings and the accuracy, specificity, and validity of potential electroencephalography-based disease markers remain to be overcome, our study indicates that abnormal frontal synchrony at theta and gamma frequencies might be promising targets for noninvasive brain stimulation and/or neurofeedback approaches. [ABSTRACT FROM AUTHOR]

Abstract Language that describes actions, for instance verbs, can help to predict future actions of conspecifics in social interactions. Language and action are therefore interrelated. This interrelation has been described on a behavioral level for adults and toddlers. Furthermore, in adults, the sensorimotor system is involved in this interrelation. However, little is known about the early interrelation on the neural level at the onset of verb acquisition. In the present study, we examined the role of the sensorimotor system during the processing of acoustically presented verbs that describe dynamic actions and visually presented actions in toddlers, who are in the earliest stage of expressive language development. The activity of the sensorimotor system, in particular the suppression of the mu rhythm, was measured by means of electroencephalography (EEG). Results showed a significant suppression of the mu rhythm during both the processing of action verbs and observed actions, but not during the processing of pseudoverbs. This suggests that the sensorimotor system is already involved in the processing of action and language early in life. Highlights • Action and language processing are interrelated in adults and toddlers. • The sensorimotor system is involved in action and verb processing in adults. • We assessed the sensorimotor system's role in verb processing early in development. • We found that toddlers show sensorimotor activity for action and verb processing. [ABSTRACT FROM AUTHOR]

Background: Cementless stems demonstrate excellent long-term survival, but little is known about the long-term survival rate of the stem after isolated cup revision. The aim of the present retrospective cohort study was to determine the long-term survival rate of cementless stems retained after prior cup revision.Methods: We reviewed the clinical and radiographic results of 119 total hip arthroplasties (THAs) utilizing a cementless, grit-blasted, tapered titanium femoral stem that were performed in 113 patients between January 1985 and December 1989. The mean age at the time of the primary THA was 52 years (range, 16 to 74 years) and the mean time between primary THA and cup revision was 13 years (standard deviation [SD], 6 years; range, 0 to 30 years). At the time of the latest follow-up, no patient was lost to follow-up, 36 patients representing 37 hips had died, and 11 hips in 11 patients had required stem revision. The mean follow-up was 13 years following cup revision (SD, 6 years; range, 0 to 28 years). A competing risk analysis was performed to estimate the survival of the stem after isolated cup revision, with death being the competing risk factor.Results: At 20 years after cup revision, the survival rate of retained stems was 89% (95% confidence interval [CI], 79% to 94%) for the end point of stem revision for any reason and 97% (95% CI, 91% to 99%) for the end point of stem revision for aseptic loosening.Conclusions: The long-term survival of cementless stems retained after cup revision was excellent. Well-fixed cementless stems should be retained during cup revision for aseptic loosening.Level Of Evidence: Level IV. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Chronic pain is a major health care issue characterized by ongoing pain and a variety of sensory, cognitive, and affective abnormalities. The neural basis of chronic pain is still not completely understood. Previous work has implicated prefrontal brain areas in chronic pain. Furthermore, prefrontal neuronal oscillations at gamma frequencies (60–90 Hz) have been shown to reflect the perceived intensity of longer lasting experimental pain in healthy human participants. In contrast, noxious stimulus intensity has been related to alpha (8–13 Hz) and beta (14–29 Hz) oscillations in sensorimotor areas. However, it is not fully understood how the intensity of ongoing pain as the key symptom of chronic pain is represented in the human brain. Here, we asked 31 chronic back pain patients to continuously rate their ongoing pain while simultaneously recording electroencephalography (EEG). Time–frequency analyses revealed a positive association between ongoing pain intensity and prefrontal beta and gamma oscillations. No association was found between pain and alpha or beta oscillations in sensorimotor areas. These findings indicate that ongoing pain as the key symptom of chronic pain is reflected by neuronal oscillations implicated in the subjective perception of longer lasting pain rather than by neuronal oscillations related to the processing of objective nociceptive input. The findings, thus, support a dissociation of pain intensity from nociceptive processing in chronic back pain patients. Furthermore, although possible confounds by muscle activity have to be taken into account, they might be useful for defining a neurophysiological marker of ongoing pain in the human brain. [ABSTRACT FROM AUTHOR]

The article focuses on how cells protect themselves from self-damage caused by interferon-stimulated genes (ISGs), specifically guanylate-binding proteins (GBPs), in response to interferon-g (IFN-g) stimulation, and how the kinase PIM1 controls GBP1 activity to prevent cellular damage while maintaining its antimicrobial function in human macrophages.

Implant failure and periprosthetic fractures because of periprosthetic bone loss are a major concern in total hip arthroplasty (THA). Hardly any clinical data exist on the long-term evolution of bone mineral density (BMD) around uncemented femoral implants. The question to address is whether relevant bone loss continues into third decade around well-fixed uncemented femoral implants. BMD around stable uncemented straight titanium femoral implants was assessed in a longitudinal cohort study. We included 142 hips of 128 patients and measured the development of the periprosthetic BMD using dual-energy X-ray absorptiometry. The baseline measurement was 12 years (t1) after the implantation of an uncemented femoral stem. Follow-up-measurements were performed at 17 (t2) and at 21 years (t3) after primary THA. The regions of interest (ROI) were selected conforming to Gruen et al. We acquired complete data including three consecutive measurements (t1, t2, t3) for 42 patients (49 hips). Performing radiographic evaluation at t1, t2 and t3, we found a regular bone-implant interface present in all cases. Significant decrease in BMD could be shown in ROI 1 (p = 0.0001; − 7.8%), 4 (p = 0.024; − 2.4%), 6 (p = 0.001; − 5.5%) and 7 (p < 0.0001; − 11.7%) between t1 and t3 and in ROI 1 (p = 0.002; − 3.7%), 2 (p = 0.046; − 3.6%), 4 (p = 0.002; − 2.7%) and 7 (p < 0.0001; − 8.0%) between t2 and t3. There were significant differences in overall bone density (netavg) between t1 and t3 (p = 0.001; − 3.6%) and between t2 and t3 (p = 0.020; − 2.1%). The data indicate clinically relevant changes of BMD especially in the proximal Gruen zones in the long-term after uncemented THA. Loss of periprosthetic BMD might be a risk factor for periprosthetic fractures. [ABSTRACT FROM AUTHOR]

NLRP3 is the most studied inflammasome sensor due to its crucial involvement in sterile and infection-triggered inflammation. Although its molecular mode of activation remains to be defined, it is well established that low intracellular potassium concentrations result in its activation. This functionality allows the classical NLRP3 pathway to serve as a highly sensitive, but non-specific surveillance mechanism responding to any type of perturbation that breaches plasma membrane integrity and the associated potassium gradient across the membrane. Here, we review our current knowledge on potassium efflux-dependent NLRP3 activation, with a special focus on how major cell death programs are rendered pro-inflammatory by secondary NLRP3 activation. Apart from the “alternative inflammasome” as the major exception to the rule, this connection explains the fundamental importance of NLRP3 in cell death-associated inflammation and firmly establishes NLRP3 as a principal surveillance mechanism of cellular integrity. [ABSTRACT FROM AUTHOR]

Children from the age of 3 years understand social norms as such and enforce these norms in interactions with others. Differences in parental and institutional education across cultures make it likely that children receive divergent information about how to act in cases of norm violations. In the current study, we investigated whether cultural values are associated with the ways in which children react to norm violations. We tested 80 bicultural 3-year-olds with a norm enforcement paradigm and analyzed their reactions to norm violations. The reactions were correlated to the children’s parental cultural values using the Global Leadership and Organizational Behavior Effectiveness (GLOBE) scales, and these results show that parental culture was associated with children’s reactions to norm violations. The three strongest correlations were found for institutional collectivism, performance orientation, and assertiveness. [ABSTRACT FROM AUTHOR]

Pain serves the protection of the body by translating noxious stimulus information into a subjective percept and protective responses. Such protective responses rely on autonomic responses that allocate energy resources to protective functions. However, the precise relationship between objective stimulus intensity, subjective pain intensity, autonomic responses, and brain activity is not fully clear yet. Here, we addressed this question by continuously recording pain ratings, skin conductance, heart rate, and electroencephalography during tonic noxious heat stimulation of the hand in 39 healthy human subjects. The results confirmed that pain intensity dissociates from stimulus intensity during 10 minutes of noxious stimulation. Furthermore, skin conductance measures were significantly related to stimulus intensity but not to pain intensity. Correspondingly, skin conductance measures were significantly related to alpha and beta oscillations in contralateral sensorimotor cortex, which have been shown to encode stimulus intensity rather than pain intensity. No significant relationships were found between heart rate and stimulus intensity or pain intensity. The findings were consistent for stimulation of the left and the right hands. These results suggest that sympathetic autonomic responses to noxious stimuli in part directly result from nociceptive rather than from perceptual processes. Beyond, these observations support concepts of pain and emotions in which sensory, motor, and autonomic components are partially independent processes that together shape emotional and painful experiences. [ABSTRACT FROM AUTHOR]

The turbulent asymptotic suction boundary layer is studied using a one-dimensional turbulence (ODT) model. ODT is a fully resolved, unsteady stochastic simulation technique. While flow properties reside on a one-dimensional domain, turbulent advection is represented using mapping events whose occurrences are governed by a random process. Due to its reduced spatial dimensionality, ODT achieves major cost reductions compared to three-dimensional (3D) simulations. A comparison to recent direct numerical simulation (DNS) data at moderate Reynolds number (Re=u∞/v0= 333, whereu∞andv0are the free stream and suction velocity, respectively) suggests that the ODT model is capable of reproducing several velocity statistics, i.e. mean velocity and turbulent kinetic energy budgets, while peak turbulent stresses are under-estimated by ODT. Variation of the Reynolds number in the rangeRe∈ [333,400,500,1000] shows that ODT can reproduce various trends observed as a result of increased suction in turbulent asymptotic suction boundary layers, i.e. the reduction of Reynolds stresses and enhanced skin friction. While up toRe= 500 our results can be directly compared to recent LES data, the simulation atRe= 1000 is currently not feasible through full 3D simulations, hence ODT may assist the design of future DNS or LES simulations at larger Reynolds numbers. [ABSTRACT FROM AUTHOR]

Noxious stimuli induce physiological processes which commonly translate into pain. However, under certain conditions, pain intensity can substantially dissociate from stimulus intensity, e.g. during longer-lasting pain in chronic pain syndromes. How stimulus intensity and pain intensity are differentially represented in the human brain is, however, not yet fully understood. We therefore used electroencephalography (EEG) to investigate the cerebral representation of noxious stimulus intensity and pain intensity during 10 min of painful heat stimulation in 39 healthy human participants. Time courses of objective stimulus intensity and subjective pain ratings indicated a dissociation of both measures. EEG data showed that stimulus intensity was encoded by decreases of neuronal oscillations at alpha and beta frequencies in sensorimotor areas. In contrast, pain intensity was encoded by gamma oscillations in the medial prefrontal cortex. Contrasting right versus left hand stimulation revealed that the encoding of stimulus intensity in contralateral sensorimotor areas depended on the stimulation side. In contrast, a conjunction analysis of right and left hand stimulation revealed that the encoding of pain in the medial prefrontal cortex was independent of the side of stimulation. Thus, the translation of noxious stimulus intensity into pain is associated with a change from a spatially specific representation of stimulus intensity by alpha and beta oscillations in sensorimotor areas to a spatially independent representation of pain by gamma oscillations in brain areas related to cognitive and affective-motivational processes. These findings extend the understanding of the brain mechanisms of nociception and pain and their dissociations during longer-lasting pain as a key symptom of chronic pain syndromes. [ABSTRACT FROM AUTHOR]

Classical modes of NLRP3 activation entail a priming step that enables its activation (signal 1) and a potassium efflux-dependent activation signal (signal 2) that triggers pyroptosome formation and pyroptosis, a lytic cell death necessary for IL-1β release. Opposing to that, human monocytes engage an alternative NLRP3 inflammasome pathway in response to LPS that proceeds in the absence of signal 2 activation and enables IL-1β secretion without pyroptosis. This specifically relies on Caspase-8 to propagate signaling to NLRP3, leading to inflammasome activation in absence of pyroptosome formation. Here, we summarize the current knowledge about alternative inflammasome activation, discuss potential extensions of this signaling entity beyond LPS-dependent activation, speculate about its role in tissue homeostasis and sterile inflammation and highlight the implications of pyroptosis-independent IL-1β secretion. [ABSTRACT FROM AUTHOR]

• This study investigated goal focus with a multi-method approach. • We tested a large sample across a wide age range from 14 to 87 years. • We found no support for a generalized goal focus or systematic age differences. • Instead, goal focus seems to differ between goals and methods. • We discuss implications for goal-related research in general. Goals are cognitive representations of means-ends relations that reflect what a person wants to approach or avoid. Previous research has demonstrated that the relative salience of the means and ends (i.e., goal focus) differs across adulthood. Due to inconsistent findings in recent studies, this study systematically investigated the convergence of goal focus across different dimensions (i.e., goal content, complexity, type, i.e., hypothetical vs. personal goals, and method of assessment) and its relation to age. To this end, we conducted a multimethod online study (N = 773) across an age range from 14 to 87 years. The results provide little support for the convergence of goal focus across different assessment methods and systematic associations with age. We discuss the implications of these findings for goal research. [ABSTRACT FROM AUTHOR]

The anticipation of the forthcoming behaviour of social interaction partners is a useful ability supporting interaction and communication between social partners. Associations and prediction based on the production system (in line with views that listeners use the production system covertly to anticipate what the other person might be likely to say) are two potential factors, which have been proposed to be involved in anticipatory language processing. We examined the influence of both factors on the degree to which listeners predict upcoming linguistic input. Are listeners more likely to predictbookas an appropriate continuation of the sentence “The boy reads a”, based on the strength of the association between the wordsreadandbook(strong association) andreadandletter(weak association)? Do more proficient producers predict more? What is the interplay of these two influences on prediction? The results suggest that associations influence language-mediated anticipatory eye gaze in two-year-olds and adults only when two thematically appropriate target objects compete for overt attention but not when these objects are presented separately. Furthermore, children's prediction abilities are strongly related to their language production skills when appropriate target objects are presented separately but not when presented together. Both influences on prediction in language processing thus appear to be context dependent. We conclude that multiple factors simultaneously influence listeners’ anticipation of upcoming linguistic input and that only such a dynamic approach to prediction can capture listeners’ prowess at predictive language processing. [ABSTRACT FROM PUBLISHER]

Recent experimental evidence and theoretical models suggest that an integration of exteroceptive and interoceptive signals underlies several key aspects of the bodily self. While it has been shown that self-attribution of both the hand and the full-body are altered by conflicting extero-exteroceptive (e.g. visuo-tactile) and extero-interoceptive (e.g. visuo-cardiac) information, no study has thus far investigated whether self-attribution of the face might be altered by visuo-cardiac stimulation similarly to visuo-tactile stimulation. In three independent groups of participants we presented ambiguous (i.e. morphed with a stranger's face) self-faces flashing synchronously or asynchronously with the participants’ heartbeat. We then measured the subjective percentages of self-face attribution of morphed stimuli. To control for a potential effect of visuo-cardiac synchrony on familiarity, a task assessing the attribution of a familiar face was introduced. Moreover, different durations of visuo-cardiac flashing and different degrees of asynchronicity were used. Based on previous studies showing that synchronous visuo-cardiac stimulation generally increases self-attribution of the full-body and the hand, and that synchronous visuo-tactile stimulation increases self-face attribution, we predicted higher self-face attribution during the synchronous visuo-cardiac flashing of the morphed stimuli. In contrast to this hypothesis, the results showed no difference between synchronous and asynchronous stimulation on self-face attribution in any of the three studies. We thus conclude that visuo-cardiac synchrony does not boost self-attribution of the face as it does that of hand and full-body. [ABSTRACT FROM AUTHOR]

The goal of the present study was to test the influence of the spatial and temporal dynamics of observed manual actions on infants' action prediction. Twelve-month-old infants were presented with reach-and-transport actions performed by a human agent. Movement distance, duration, and - resulting from the two - movement velocity were systematically varied. Action prediction was measured via the latency of gaze arrival at target in relation to agent's hand. The results showed a general effect of all parameters on the infants' perception of goal-directed actions: Infants were more likely to predict the action goal the longer the movement distance was, the longer the movement duration was, and the slower the movement velocity was. In addition, they were more likely to predict the goal of a reaching than a transport action. The present findings extent previous findings by showing that infants are not only sensitive to differences in distances, durations, and velocities at early age but that these factors have a strong impact on the prediction of the goal of observed actions. [ABSTRACT FROM AUTHOR]

Summary Interleukin-1β (IL-1β) is a cytokine whose bioactivity is controlled by activation of the inflammasome. However, in response to lipopolysaccharide, human monocytes secrete IL-1β independently of classical inflammasome stimuli. Here, we report that this constituted a species-specific response that is not observed in the murine system. Indeed, in human monocytes, lipopolysaccharide triggered an “alternative inflammasome” that relied on NLRP3-ASC-caspase-1 signaling, yet was devoid of any classical inflammasome characteristics including pyroptosome formation, pyroptosis induction, and K + efflux dependency. Genetic dissection of the underlying signaling pathway in a monocyte transdifferentiation system revealed that alternative inflammasome activation was propagated by TLR4-TRIF-RIPK1-FADD-CASP8 signaling upstream of NLRP3. Importantly, involvement of this signaling cascade was limited to alternative inflammasome activation and did not extend to classical NLRP3 activation. Because alternative inflammasome activation embraces both sensitivity and promiscuity of TLR4, we propose a pivotal role for this signaling cascade in TLR4-driven, IL-1β-mediated immune responses and immunopathology in humans. [ABSTRACT FROM AUTHOR]

African floodplains are an excellent example of coupled human–natural systems because they exhibit strong interactions among multiple social, ecological, and hydrological systems. The intra-annual and interannual variations in seasonal flooding have direct and indirect impacts on ecosystems and human lives and livelihoods. Coupled human and natural system (CHANS) is a broad conceptual framework that is used to study systems in which human and natural components interact. While there are other conceptual frameworks to study social-ecological systems, the CHANS framework offers a clear way of studying the interactions, called couplings, between human and natural systems. Core features of the framework are the following: human and natural systems are analytically separated; focus is on processes within and couplings between systems; and the goal is to build an integrative, quantitative model of the coupled system. This paper explains the conceptual framework of coupled systems, using the case study of the Logone floodplain in Cameroon. We compare the CHANS framework with other frameworks that have been used to study the same floodplain, and argue for its usefulness in the study of African floodplains. [ABSTRACT FROM PUBLISHER]