The spiral wave frequency effect in atrial fibrillation.

A spiral wavefront (WF), generated by a cardiac rotor that drifts between surface electrodes during atrial fibrillation, exhibits frequency changes inconsistent with classical Doppler effect (CDE) phenomena. Recent clinical studies reveal three repeatedly observed events--1) side-dependent frequency changes across the path of the rotor, 2) one additional WF strike on the higher frequency side, and 3) a reversal of WF strike sequence--which constitute a diametrical property of spinning WF sources. A linear ray model is first used to reveal and develop the diametrical phenomena. Mathematical models of an Archimedean spiral and a spiral generated by the diffusion equation are developed and compared. Each formulation predicts the diametrical property that CDE does not capture and illuminates the occurrence of a strong side and weak side with respect to the rotor path. Whereas CDE exhibits higher and lower frequencies from approaching and receding sources of WFs, respectively, spiral rotors generate higher and lower frequencies on opposite sides of the migration path. This motivates the reconsideration of mapping and ablation strategies that have traditionally been based on identifying sites of the dominant frequency. While this research aims to characterize the path of a spiral rotor during atrial fibrillation accurately, the results are applicable in other fields of science and engineering in which rotating spiral waves occur.

A longitudinal evaluation of personalized intrinsic network topography and cognitive decline in Parkinson's disease.

Resting state functional magnetic resonance imaging (R-fMRI) offers insight into how synchrony within and between brain networks is altered in disease states. Individual and disease-related variability in intrinsic connectivity networks may influence our interpretation of R-fMRI data. We used a personalized approach designed to account for individual variation in the spatial location of correlation maxima to evaluate R-fMRI differences between Parkinson's disease (PD) patients who showed cognitive decline, those who remained cognitively stable and cognitively stable controls. We compared fMRI data from these participant groups, studied at baseline and 18 months later, using both network-based statistics (NBS) and calculations of mean inter- and intra-network connectivity within pre-defined functional networks. The NBS analysis showed that PD participants who remained cognitively stable showed exclusively (at baseline) or predominantly (at follow-up) increased intra-network connectivity, whereas decliners showed exclusively reduced intra-network and inter- (ventral attention and default mode) connectivity, in comparison with the control group. Evaluation of mean connectivity between all regions of interest (ROIs) within a priori networks showed that decliners had consistently reduced inter-network connectivity for ventral attention, somatomotor, visual and striatal networks and reduced intra-network connectivity for ventral attention network to striatum and cerebellum. These findings suggest that specific functional connectivity covariance patterns differentiate PD cognitive subtypes and may predict cognitive decline. Further, increased intra and inter-network synchrony may support cognitive function in the face of PD-related network disruptions.

Barriers and Facilitators Impacting Lung Cancer Screening Uptake Among Black Veterans: A Qualitative Study.

BACKGROUND: Racial disparities in lung cancer screening (LCS) are well established. Black Veterans are among those at the highest risk for developing lung cancer but are less likely to complete LCS. We sought to identify barriers and facilitators to LCS uptake among Black Veterans. PATIENTS AND METHODS: A qualitative study using semistructured interviews was conducted with 32 Black Veterans to assess for barriers, facilitators, and contextual factors for LCS and strategies to improve screening. Veterans were purposively sampled by age, sex, and LCS participation status (ie, patients who received a low-dose CT [LDCT], patients who contacted the screening program but did not receive an LDCT, and patients who did not connect with the screening program nor receive an LDCT). Interview guides were developed using the Theoretical Domains Framework and Health Belief Model. Data were analyzed using rapid qualitative analysis. RESULTS: Barriers of LCS uptake among Black Veterans include self-reported low LCS knowledge and poor memory, attention, and decision processes associated with the centralized LCS process. Facilitators of LCS uptake among Black Veterans include social/professional role; identity and social influences; perceived susceptibility, threat, and consequences due to smoking status and military or occupational exposures; emotion, behavioral regulation, and intentions; and high trust in providers. Environmental context and resources (eg, transportation) and race and racism serve as contextual factors that did not emerge as having a major impact on LCS uptake. Strategies to improve LCS uptake included increased social messaging surrounding LCS, various forms of information dissemination, LCS reminders, balanced and repeated shared decision-making discussions, and streamlined referrals. CONCLUSIONS: We identified addressable barriers and facilitators for LCS uptake among Black Veterans that can help focus efforts to improve disparities in screening. Future studies should explore provider perspectives and test interventions to improve equity in LCS.

Systematic Literature Review of Health-Related Quality-of-Life Measures for Caregivers of Older Adult Trauma Patients.

INTRODUCTION: As the older adult population increases, hospitals treat more older adults with injuries. After leaving, these patients suffer from decreased mobility and independence, relying on care from others. Family members often assume this responsibility, mostly informally and unpaid. Caregivers of other older adult populations have increased stress and decreased caregiver-related quality of life (CRQoL). Validated CRQoL measures are essential to capture their unique experiences. Our objective was to review existing CRQoL measures and their validity in caregivers of older adult trauma patients. METHODS: A professional librarian searched published literature from the inception of databases through August 12, 2022 in MEDLINE (via PubMed), Embase (via Elsevier), and CINAHL Complete (via EBSCO). We identified 1063 unique studies of CRQoL in caregivers for adults with injury and performed a systematic review following COnsensus-based Standards for the selection of health Measurement Instruments guidelines for CRQoL measures. RESULTS: From the 66 studies included, we identified 54 health-related quality-of-life measures and 60 domains capturing caregiver-centered concerns. The majority (83%) of measures included six or fewer CRQoL content domains. Six measures were used in caregivers of older adults with single-system injuries. There were no validated CRQoL measures among caregivers of older adult trauma patients with multisystem injuries. CONCLUSIONS: While many measures exist to assess healthcare-related quality of life, few, if any, adequately assess concerns among caregivers of older adult trauma patients. We found that CRQoL domains, including mental health, emotional health, social functioning, and relationships, are most commonly assessed among caregivers. Future measures should focus on reliability and validity in this specific population to guide interventions.

Using in vivo functional and structural connectivity to predict chronic stroke aphasia deficits.

Focal brain damage caused by stroke can result in aphasia and advances in cognitive neuroscience suggest that impairment may be associated with network-level disorder rather than just circumscribed cortical damage. Several studies have shown meaningful relationships between brain-behaviour using lesions; however, only a handful of studies have incorporated in vivo structural and functional connectivity. Patients with chronic post-stroke aphasia were assessed with structural (n = 68) and functional (n = 39) MRI to assess whether predicting performance can be improved with multiple modalities and if additional variance can be explained compared to lesion models alone. These neural measurements were used to construct models to predict four key language-cognitive factors: (i) phonology; (ii) semantics; (iii) executive function; and (iv) fluency. Our results showed that each factor (except executive ability) could be significantly related to each neural measurement alone; however, structural and functional connectivity models did not explain additional variance above the lesion models. We did find evidence that the structural and functional predictors may be linked to the core lesion sites. First, the predictive functional connectivity features were found to be located within functional resting-state networks identified in healthy controls, suggesting that the result might reflect functionally specific reorganization (damage to a node within a network can result in disruption to the entire network). Second, predictive structural connectivity features were located within core lesion sites, suggesting that multimodal information may be redundant in prediction modelling. In addition, we observed that the optimum sparsity within the regularized regression models differed for each behavioural component and across different imaging features, suggesting that future studies should consider optimizing hyperparameters related to sparsity per target. Together, the results indicate that the observed network-level disruption was predicted by the lesion alone and does not significantly improve model performance in predicting the profile of language impairment.

Bipartite functional fractionation within the neural system for social cognition supports the psychological continuity of self versus other.

Research of social neuroscience establishes that regions in the brain's default-mode network (DN) and semantic network (SN) are engaged by socio-cognitive tasks. Research of the human connectome shows that DN and SN regions are both situated at the transmodal end of a cortical gradient but differ in their loci along this gradient. Here we integrated these 2 bodies of research, used the psychological continuity of self versus other as a "test-case," and used functional magnetic resonance imaging to investigate whether these 2 networks would encode social concepts differently. We found a robust dissociation between the DN and SN-while both networks contained sufficient information for decoding broad-stroke distinction of social categories, the DN carried more generalizable information for cross-classifying across social distance and emotive valence than did the SN. We also found that the overarching distinction of self versus other was a principal divider of the representational space while social distance was an auxiliary factor (subdivision, nested within the principal dimension), and this representational landscape was more manifested in the DN than in the SN. Taken together, our findings demonstrate how insights from connectome research can benefit social neuroscience and have implications for clarifying the 2 networks' differential contributions to social cognition.

Trajectories of Palliative Care Needs in the ICU and Long-Term Psychological Distress Symptoms.

OBJECTIVES: While palliative care needs are assumed to improve during ICU care, few empiric data exist on need trajectories or their impact on long-term outcomes. We aimed to describe trajectories of palliative care needs during ICU care and to determine if changes in needs over 1 week was associated with similar changes in psychological distress symptoms at 3 months. DESIGN: Prospective cohort study. SETTING: Six adult medical and surgical ICUs. PARTICIPANTS: Patients receiving mechanical ventilation for greater than or equal to 2 days and their family members. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the 13-item Needs at the End-of-Life Screening Tool (NEST; total score range 0-130) completed by family members at baseline, 3, and 7 days. The Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Post-Traumatic Stress Scale (PTSS) were completed at baseline and 3 months. General linear models were used to estimate differences in distress symptoms by change in need (NEST improvement ≥ 10 points or not). One-hundred fifty-nine family members participated (median age, 54.0 yr [interquartile range (IQR), 44.0-63.0 yr], 125 [78.6%] female, 54 [34.0%] African American). At 7 days, 53 (33%) a serious level of overall need and 35 (22%) ranked greater than or equal to 1 individual need at the highest severity level. NEST scores improved greater than or equal to 10 points in only 47 (30%). Median NEST scores were 22 (IQR, 12-40) at baseline and 19 (IQR, 9-37) at 7 days (change, -2.0; IQR, -11.0 to 5.0; p = 0.12). There were no differences in PHQ-9, GAD-7, or PTSS change scores by change in NEST score (all p > 0.15). CONCLUSIONS: Serious palliative care needs were common and persistent among families during ICU care. Improvement in needs was not associated with less psychological distress at 3 months. Serious needs may be commonly underrecognized in current practice.

Factors Associated With Triage Decisions in Older Adult Trauma Patients: Impact on Mortality and Morbidity.

INTRODUCTION: As medical advances have significantly increased the life expectancy among older adults, the number of older patients requiring trauma care has risen proportionately. Nevertheless, it is unclear among this growing population which sociodemographic and economic factors are associated with decisions to triage and transfer to level I/II centers. This study aims to assess for any association between patient sociodemographic characteristics, triage decisions, and outcomes during acute trauma care presentations. METHODS: The National Trauma Data Bank was queried for patients aged 65 and older with an injury severity score > 15 between the years 2007 to 2017. Factors associated with subsequent levels of triage on presentation were assessed using multivariate logistic regression, and associations of levels of triage with outcomes of mortality, morbidity, and hospital length of stay are examined using logistic and linear regression models. RESULTS: Triage of 210,310 older adult trauma patients showed significant findings. American Indian patients had higher odds of being transferred to level I/II centers, while Asian, Black, and Native Hawaiian patients had lower odds of being transferred to level I/II centers when compared to Caucasian patients (P < 0.001). Regarding insurance, self-pay (uninsured) patients were less likely to be transferred to a higher level of care; however, this was also demonstrated in private insurance holders (P < 0.001). Caucasian patients had significantly higher odds of mortality, with Black patients (odds ratio [OR] 0.80 [0.75, 0.85]) and American Indian patients (OR 0.87 [0.72, 1.04]) having significantly lower odds (P < 0.001). Compared to government insurance, private insurance holders (OR 0.82 [0.80, 0.85]) also had significantly lower odds of mortality, while higher odds among self-pay were observed (OR 1.75 [1.62, 1.90]), (P < 0.001). CONCLUSIONS: Access to insurance is associated with triage decisions involving older adults sustaining trauma, with lower access increasing mortality risk. Factors such as race and gender were less likely to be associated with triage decisions. However, due to this study's retrospective design, further prospective analysis is necessary to fully assess the decisions that influence trauma triage decisions in this patient population.

Digital solutions and the future of recovery after critical illness.

PURPOSE OF REVIEW: Digital technologies may address known physical and psychological barriers to recovery experienced by intensive care survivors following hospital discharge and provide solutions to care fragmentation and unmet needs. The review highlights recent examples of digital technologies designed to support recovery of survivors of critically illness. RECENT FINDINGS: Despite proliferation of digital technologies supporting health in the community, there are relatively few examples for intensive care survivors. Those we identified included web-based, app-based or telemedicine-informed recovery clinics or pathways offering services, including informational resources, care planning and navigation support, medication reconciliation, and recovery goal setting. Digital interventions supporting psychological recovery included apps providing adaptive coping skills training, mindfulness, and cognitive behavioural therapy. Efficacy data are limited, although feasibility and acceptability have been established for some. Challenges include difficulties identifying participants most likely to benefit and delivery in a format easily accessible to all, with digital exclusion a resultant risk. SUMMARY: Digital interventions supporting recovery comprise web or app-based recovery clinics or pathways and digital delivery of psychological interventions. Understanding of efficacy is relatively nascent, although several studies demonstrate feasibility and acceptability. Future research is needed but should be mindful of the risk of digital exclusion.

Neighborhood socioeconomic deprivation, healthcare access, and 30-day mortality and readmission after sepsis or critical illness: findings from a nationwide study.

BACKGROUND: To determine if neighborhood socioeconomic deprivation independently predicts 30-day mortality and readmission for patients with sepsis or critical illness after adjusting for individual poverty, demographics, comorbidity burden, access to healthcare, and characteristics of treating healthcare facilities. METHODS: We performed a nationwide study of United States Medicare beneficiaries from 2017 to 2019. We identified hospitalized patients with severe sepsis and patients requiring prolonged mechanical ventilation, tracheostomy, or extracorporeal membrane oxygenation (ECMO) through Diagnosis Related Groups (DRGs). We estimated the association between neighborhood socioeconomic deprivation, measured by the Area Deprivation Index (ADI), and 30-day mortality and unplanned readmission using logistic regression models with restricted cubic splines. We sequentially adjusted for demographics, individual poverty, and medical comorbidities, access to healthcare services; and characteristics of treating healthcare facilities. RESULTS: A total of 1,526,405 admissions were included in the mortality analysis and 1,354,548 were included in the readmission analysis. After full adjustment, 30-day mortality for patients was higher for those from most-deprived neighborhoods (ADI 100) compared to least deprived neighborhoods (ADI 1) for patients with severe sepsis (OR 1.35 95% [CI 1.29-1.42]) or with prolonged mechanical ventilation with or without sepsis (OR 1.42 [95% CI 1.31, 1.54]). This association was linear and dose dependent. However, neighborhood socioeconomic deprivation was not associated with 30-day unplanned readmission for patients with severe sepsis and was inversely associated with readmission for patients requiring prolonged mechanical ventilation with or without sepsis. CONCLUSIONS: A strong association between neighborhood socioeconomic deprivation and 30-day mortality for critically ill patients is not explained by differences in individual poverty, demographics, measured baseline medical risk, access to healthcare resources, or characteristics of treating hospitals.

Infant-directed speech does not always involve exaggerated vowel distinctions: Evidence from Danish.

This study compared the acoustic properties of 26 (100% female, 100% monolingual) Danish caregivers' spontaneous speech addressed to their 11- to 24-month-old infants (infant-directed speech, IDS) and an adult experimenter (adult-directed speech, ADS). The data were collected between 2016 and 2018 in Aarhus, Denmark. Prosodic properties of Danish IDS conformed to cross-linguistic patterns, with a higher pitch, greater pitch variability, and slower articulation rate than ADS. However, an acoustic analysis of vocalic properties revealed that Danish IDS had a reduced or similar vowel space, higher within-vowel variability, raised formants, and lower degree of vowel discriminability compared to ADS. None of the measures, except articulation rate, showed age-related differences. These results push for future research to conduct theory-driven comparisons across languages with distinct phonological systems.

Palliative Care Early in the Care Continuum among Patients with Serious Respiratory Illness: An Official ATS/AAHPM/HPNA/SWHPN Policy Statement.

Background: Patients with serious respiratory illness and their caregivers suffer considerable burdens, and palliative care is a fundamental right for anyone who needs it. However, the overwhelming majority of patients do not receive timely palliative care before the end of life, despite robust evidence for improved outcomes. Goals: This policy statement by the American Thoracic Society (ATS) and partnering societies advocates for improved integration of high-quality palliative care early in the care continuum for patients with serious respiratory illness and their caregivers and provides clinicians and policymakers with a framework to accomplish this. Methods: An international and interprofessional expert committee, including patients and caregivers, achieved consensus across a diverse working group representing pulmonary-critical care, palliative care, bioethics, health law and policy, geriatrics, nursing, physiotherapy, social work, pharmacy, patient advocacy, psychology, and sociology. Results: The committee developed fundamental values, principles, and policy recommendations for integrating palliative care in serious respiratory illness care across seven domains: 1) delivery models, 2) comprehensive symptom assessment and management, 3) advance care planning and goals of care discussions, 4) caregiver support, 5) health disparities, 6) mass casualty events and emergency preparedness, and 7) research priorities. The recommendations encourage timely integration of palliative care, promote innovative primary and secondary or specialist palliative care delivery models, and advocate for research and policy initiatives to improve the availability and quality of palliative care for patients and their caregivers. Conclusions: This multisociety policy statement establishes a framework for early palliative care in serious respiratory illness and provides guidance for pulmonary-critical care clinicians and policymakers for its proactive integration.

Gap detection responses modelled using the Hill equation in adults with well-controlled HIV.

OBJECTIVE: This study's objective was determining whether gap detection deficits are present in a longstanding cohort of people living with HIV (PLWH) compared to those living without HIV (PLWOH) using a new gap detection modelling technique (i.e. fitting gap responses using the Hill equation and analysing the individual gap detection resulting curves with non-linear statistics). This approach provides a measure of both gap threshold and the steepness of the gap length/correct detection relationship. DESIGN: The relationship between the correct identification rate at each gap length was modelled using the Hill equation. Results were analysed using a nonlinear mixed-effect regression model. STUDY SAMPLE: 45 PLWH (age range 41-78) and 39 PLWOH (age range 38-79) were enrolled and completed gap detection testing. RESULTS: The likelihood ratio statistic comparing the full regression model with the HIV effects to the null model, assuming one population curve for both groups, was highly significant (p < 0.001), suggesting a less precise relationship between gap length and correct detection in PLWH. CONCLUSIONS: PLWH showed degraded gap detection ability compared to PLWOH, likely due to central nervous system effects of HIV infection or treatment. The Hill equation provided a new approach for modelling gap detection ability.

Child-oriented word associations improve models of early word learning.

How words are associated within the linguistic environment conveys semantic content; however, different contexts induce different linguistic patterns. For instance, it is well known that adults speak differently to children than to other adults. We present results from a new word association study in which adult participants were instructed to produce either unconstrained or child-oriented responses to each cue, where cues included 672 nouns, verbs, adjectives, and other word forms from the McArthur-Bates Communicative Development Inventory (CDI; Fenson et al., 2006). Child-oriented responses consisted of higher frequency words with fewer letters, earlier ages of acquisition, and higher contextual diversity. Furthermore, the correlations among the responses generated for each pair of cues differed between unconstrained (adult-oriented) and child-oriented responses, suggesting that child-oriented associations imply different semantic structure. A comparison of growth models guided by a semantic network structure revealed that child-oriented associations are more predictive of early lexical growth. Additionally, relative to a growth model based on a corpus of naturalistic child-directed speech, the child-oriented associations explain added unique variance to lexical growth. Thus, these new child-oriented word association norms provide novel insight into the semantic context of young children and early lexical development.

Interpretations of meaningful and ambiguous hand gestures in autistic and non-autistic adults: A norming study.

Gestures are ubiquitous in human communication, and a growing but inconsistent body of research suggests that people with autism spectrum disorder (ASD) may process co-speech gestures differently from neurotypical individuals. To facilitate research on this topic, we created a database of 162 gesture videos that have been normed for comprehensibility by both autistic and non-autistic raters. These videos portray an actor performing silent gestures that range from highly meaningful (e.g., iconic gestures) to ambiguous or meaningless. Each video was rated for meaningfulness and given a one-word descriptor by 40 autistic and 40 non-autistic adults, and analyses were conducted to assess the level of within- and across-group agreement. Across gestures, the meaningfulness ratings provided by raters with and without ASD correlated at r > 0.90, indicating a very high level of agreement. Overall, autistic raters produced a more diverse set of verbal labels for each gesture than did non-autistic raters. However, measures of within-gesture semantic similarity among the responses provided by each group did not differ, suggesting that increased variability within the ASD group may have occurred at the lexical rather than semantic level. This study is the first to compare gesture naming between autistic and non-autistic individuals, and the resulting dataset is the first gesture stimulus set for which both groups were equally represented in the norming process. This database also has broad applicability to other areas of research related to gesture processing and comprehension. The video database and accompanying norming data are available on the Open Science Framework.

Finding Distributed Needles in Neural Haystacks.

The human cortex encodes information in complex networks that can be anatomically dispersed and variable in their microstructure across individuals. Using simulations with neural network models, we show that contemporary statistical methods for functional brain imaging-including univariate contrast, searchlight multivariate pattern classification, and whole-brain decoding with L1 or L2 regularization-each have critical and complementary blind spots under these conditions. We then introduce the sparse-overlapping-sets (SOS) LASSO-a whole-brain multivariate approach that exploits structured sparsity to find network-distributed information-and show in simulation that it captures the advantages of other approaches while avoiding their limitations. When applied to fMRI data to find neural responses that discriminate visually presented faces from other visual stimuli, each method yields a different result, but existing approaches all support the canonical view that face perception engages localized areas in posterior occipital and temporal regions. In contrast, SOS LASSO uncovers a network spanning all four lobes of the brain. The result cannot reflect spurious selection of out-of-system areas because decoding accuracy remains exceedingly high even when canonical face and place systems are removed from the dataset. When used to discriminate visual scenes from other stimuli, the same approach reveals a localized signal consistent with other methods-illustrating that SOS LASSO can detect both widely distributed and localized representational structure. Thus, structured sparsity can provide an unbiased method for testing claims of functional localization. For faces and possibly other domains, such decoding may reveal representations more widely distributed than previously suspected.SIGNIFICANCE STATEMENT Brain systems represent information as patterns of activation over neural populations connected in networks that can be widely distributed anatomically, variable across individuals, and intermingled with other networks. We show that four widespread statistical approaches to functional brain imaging have critical blind spots in this scenario and use simulations with neural network models to illustrate why. We then introduce a new approach designed specifically to find radically distributed representations in neural networks. In simulation and in fMRI data collected in the well studied domain of face perception, the new approach discovers extensive signal missed by the other methods-suggesting that prior functional imaging work may have significantly underestimated the degree to which neurocognitive representations are distributed and variable across individuals.

Stem Cell-based therapies for COVID-19-related acute respiratory distress syndrome.

As the number of confirmed cases and resulting death toll of the COVID-19 pandemic continue to increase around the globe - especially with the emergence of new mutations of the SARS-CoV-2 virus in addition to the known alpha, beta, gamma, delta and omicron variants - tremendous efforts continue to be dedicated to the development of interventive therapeutics to mitigate infective symptoms or post-viral sequelae in individuals for which vaccines are not accessible, viable or effective in the prevention of illness. Many of these investigations aim to target the associated acute respiratory distress syndrome, or ARDS, which induces damage to lung epithelia and other physiologic systems and is associated with progression in severe cases. Recently, stem cell-based therapies have demonstrated preliminary efficacy against ARDS based on a number of preclinical and preliminary human safety studies, and based on promising outcomes are now being evaluated in phase II clinical trials for ARDS. A number of candidate stem cell therapies have been found to exhibit low immunogenicity, coupled with inherent tropism to injury sites. In recent studies, these have demonstrated the ability to modulate suppression of pro-inflammatory cytokine signals such as those characterizing COVID-19-associated ARDS. Present translational studies are aiming to optimize the safety, efficacy and delivery to fully validate stem cell-based strategies targeting COVID-19 associated ARDS for viable clinical application.

Proliferation in the developing intestine is regulated by the endosomal protein Endotubin.

During postnatal intestinal development, the intestinal epithelium is highly proliferative, and this proliferation is regulated by signaling in the intervillous and crypt regions. This signaling is primarily mediated by Wnt, and requires membrane trafficking. However, the mechanisms by which membrane trafficking regulates signaling during this developmental phase are largely unknown. Endotubin (EDTB, MAMDC4) is an endosomal protein that is highly expressed in the apical endocytic complex (AEC) of villus enterocytes during fetal and postnatal development, and knockout of EDTB results in defective formation of the AEC and giant lysosome. Further, knockout of EDTB in cell lines results in decreased proliferation. However, the role of EDTB in proliferation during the development of the intestine is unknown. Using Villin-CreERT2 in EDTBfl/fl mice, we deleted EDTB in the intestine in the early postnatal period, or in enteroids in vitro after isolation of intervillous cells. Loss of EDTB results in decreased proliferation in the developing intestinal epithelium and decreased ability to form enteroids. EDTB is present in cells that contain the stem cell markers LGR5 and OLFM4, indicating that it is expressed in the proliferative compartment. Further, using immunoblot analysis and TCF/LEF-GFP mice as a reporter of Wnt activity, we find that knockout of EDTB results in decreased Wnt signaling. Our results show that EDTB is essential for normal proliferation during the early stages of intestinal development and suggest that this effect is through modulation of Wnt signaling.

Warming in the land of the midnight sun: breeding birds may suffer greater heat stress at high- versus low-Arctic sites.

Rising global temperatures are expected to increase reproductive costs for wildlife as greater thermoregulatory demands interfere with reproductive activities. However, predicting the temperatures at which reproductive performance is negatively impacted remains a significant hurdle. Using a thermoregulatory polygon approach, we derived a reproductive threshold temperature for an Arctic songbird-the snow bunting (Plectrophenax nivalis). We defined this threshold as the temperature at which individuals must reduce activity to suboptimal levels (i.e. less than four-time basal metabolic rate) to sustain nestling provisioning and avoid overheating. We then compared this threshold to operative temperatures recorded at high (82° N) and low (64° N) Arctic sites to estimate how heat constraints translate into site-specific impacts on sustained activity level. We predict buntings would become behaviourally constrained at operative temperatures above 11.7°C, whereupon they must reduce provisioning rates to avoid overheating. Low-Arctic sites had larger fluctuations in solar radiation, consistently producing daily periods when operative temperatures exceeded 11.7°C. However, high-latitude birds faced entire, consecutive days when parents would be unable to sustain required provisioning rates. These data indicate that Arctic warming is probably already disrupting the breeding performance of cold-specialist birds and suggests counterintuitive and severe negative impacts of warming at higher latitude breeding locations.

A systematic review and Bayesian meta-analysis of the development of turn taking in adult-child vocal interactions.

Fluent conversation requires temporal organization between conversational exchanges. By performing a systematic review and Bayesian multi-level meta-analysis, we map the trajectory of infants' turn-taking abilities over the course of early development (0 to 70 months). We synthesize the evidence from 26 studies (78 estimates from 429 unique infants, of which at least 152 are female) reporting response latencies in infant-adult dyadic interactions. The data were collected between 1975 and 2019, exclusively in North America and Europe. Infants took on average circa 1 s to respond, and the evidence of changes in response over time was inconclusive. Infants' response latencies are related to those of their adult conversational partners: an increase of 1 s in adult response latency (e.g., 400 to 1400 ms) would be related to an increase of over 1 s in infant response latency (from 600 to 1857 ms). These results highlight the dynamic reciprocity involved in the temporal organization of turn-taking. Based on these results, we provide recommendations for future avenues of enquiry: studies should analyze how turn-by-turn exchanges develop on a longitudinal timescale, with rich assessment of infants' linguistic and social development.