Different in different ways: A network-analysis approach to voice and prosody in Autism Spectrum Disorder.

The current study investigated whether the difficulty in finding group differences in prosody between speakers with autism spectrum disorder (ASD) and neurotypical (NT) speakers might be explained by identifying different acoustic profiles of speakers which, while still perceived as atypical, might be characterized by different acoustic qualities. We modelled the speech from a selection of speakers (N = 26), with and without ASD, as a network of nodes defined by acoustic features. We used a community-detection algorithm to identify clusters of speakers who were acoustically similar and compared these clusters with atypicality ratings by naïve and expert human raters. Results identified three clusters: one primarily composed of speakers with ASD, one of mostly NT speakers, and one comprised of an even mixture of ASD and NT speakers. The human raters were highly reliable at distinguishing speakers with and without ASD, regardless of which cluster the speaker was in. These results suggest that community-detection methods using a network approach may complement commonly-employed human ratings to improve our understanding of the intonation profiles in ASD.

Genomic surveillance reveals dynamic shifts in the connectivity of COVID-19 epidemics.

The maturation of genomic surveillance in the past decade has enabled tracking of the emergence and spread of epidemics at an unprecedented level. During the COVID-19 pandemic, for example, genomic data revealed that local epidemics varied considerably in the frequency of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage importation and persistence, likely due to a combination of COVID-19 restrictions and changing connectivity. Here, we show that local COVID-19 epidemics are driven by regional transmission, including across international boundaries, but can become increasingly connected to distant locations following the relaxation of public health interventions. By integrating genomic, mobility, and epidemiological data, we find abundant transmission occurring between both adjacent and distant locations, supported by dynamic mobility patterns. We find that changing connectivity significantly influences local COVID-19 incidence. Our findings demonstrate a complex meaning of "local" when investigating connected epidemics and emphasize the importance of collaborative interventions for pandemic prevention and mitigation.

Estimating the effects of COVID-19 on essential health services utilization in Uganda and Bangladesh using data from routine health information systems.

Background: Since March 2020, the coronavirus disease 2019 (COVID-19) pandemic has been a major shock to health systems across the world. We examined national usage patterns for selected basic, essential health services, before and during the COVID-19 pandemic in Uganda and Bangladesh, to determine whether COVID-19 affected reporting of service utilization and the use of health services in each country. Methods: We used routine health information system data since January 2017 to analyze reporting and service utilization patterns for a variety of health services. Using time series models to replicate pre-COVID-19 trajectories over time we estimated what levels would have been observed if COVID-19 had not occurred during the pandemic months, starting in March 2020. The difference between the observed and predicted levels is the COVID-19 effect on health services. Results: The time trend models for Uganda and Bangladesh closely replicated the levels and trajectories of service utilization during the 38 months prior to the COVID-19 pandemic. Our results indicate that COVID-19 had severe effects across all services, particularly during the first months of the pandemic, but COVID-19 impacts on health services and subsequent recovery varied by service type. In general, recovery to expected levels was slow and incomplete across the most affected services. Conclusion: Our analytical approach based on national information system data could be very useful as a form of surveillance for health services disruptions from any cause leading to rapid responses from health service managers and policymakers.

Doxorubicin Changes the Spatial Organization of the Genome around Active Promoters.

In this study, we delve into the impact of genotoxic anticancer drug treatment on the chromatin structure of human cells, with a particular focus on the effects of doxorubicin. Using Hi-C, ChIP-seq, and RNA-seq, we explore the changes in chromatin architecture brought about by doxorubicin and ICRF193. Our results indicate that physiologically relevant doses of doxorubicin lead to a local reduction in Hi-C interactions in certain genomic regions that contain active promoters, with changes in chromatin architecture occurring independently of Top2 inhibition, cell cycle arrest, and differential gene expression. Inside the regions with decreased interactions, we detected redistribution of RAD21 around the peaks of H3K27 acetylation. Our study also revealed a common structural pattern in the regions with altered architecture, characterized by two large domains separated from each other. Additionally, doxorubicin was found to increase CTCF binding in H3K27 acetylated regions. Furthermore, we discovered that Top2-dependent chemotherapy causes changes in the distance decay of Hi-C contacts, which are driven by direct and indirect inhibitors. Our proposed model suggests that doxorubicin-induced DSBs cause cohesin redistribution, which leads to increased insulation on actively transcribed TAD boundaries. Our findings underscore the significant impact of genotoxic anticancer treatment on the chromatin structure of the human genome.

Early developmental plasticity enables the induction of an intermediate extraembryonic cell state.

Two fundamental elements of pre-implantation embryogenesis are cells' intrinsic self-organization program and their developmental plasticity, which allows embryos to compensate for alterations in cell position and number; yet, these elements are still poorly understood. To be able to decipher these features, we established culture conditions that enable the two fates of blastocysts' extraembryonic lineages-the primitive endoderm and the trophectoderm-to coexist. This plasticity emerges following the mechanisms of the first lineage segregation in the mouse embryo, and it manifests as an extended potential for extraembryonic chimerism during the pre-implantation embryogenesis. Moreover, this shared state enables robust assembly into higher-order blastocyst-like structures, thus combining both the cell fate plasticity and self-organization features of the early extraembryonic lineages.

Association of State Child Abuse Policies and Mandated Reporting Policies With Prenatal and Postpartum Care Among Women Who Engaged in Substance Use During Pregnancy.

Importance: Some states have implemented policies that consider substance use during pregnancy as child abuse and require mandated reporting of substance use during pregnancy. Implications of these policies for health care receipt among pregnant people who engage in substance use are unknown. Objective: To examine the association of state child abuse policies and mandated reporting policies with prenatal and postpartum care among women who engaged in substance use during pregnancy. Design, Setting, and Participants: In this cross-sectional study, data from the 2016-2019 Pregnancy Risk Assessment Monitoring System survey were analyzed. The study population included 4155 women from 23 states who reported substance use during pregnancy. Data were analyzed between August and November 2021. Exposures: Delivery in a state with a child abuse policy only (n = 6), a mandated reporting policy only (n = 4), both policies (n = 7), or neither policy (n = 5). One state switched from a mandated reporting policy only to having both policies. Main Outcomes and Measures: Month of gestation at prenatal care initiation (ie, months 1-10, with a higher number of months indicating later initiation), receipt of adequate prenatal care, and receipt of a postpartum health care visit 4 to 6 weeks after delivery. Sample characteristics were calculated using unweighted frequencies and weighted percentages and means. Associations of state policies with the outcomes were examined using generalized linear regression with generalized estimating equations, adjusting for potential confounders and accounting for the complex sampling design of the Pregnancy Risk Assessment Monitoring System survey. Results: The study sample included 4155 women who reported substance use during pregnancy; 33.9% of these women delivered in states with a child abuse policy only, 16.4% in states with a mandated reporting policy only, 32.9% in states with both policies, and 16.8% in states with neither policy. Overall, 14.7% of women were Black, 69.0% were White, and 64.6% were aged 18 to 29 years at delivery. Women who delivered in states with a child abuse policy only, mandated reporting policy only, or both policies initiated prenatal care at a later month of gestation (ß = 0.44 [95% CI, 0.10-0.78], 0.32 [95% CI, 0.04-0.59], and 0.40 [95% CI, 0.09-0.72], respectively) and had a lower likelihood of adequate prenatal care (risk ratio, 0.85 [95% CI, 0.79-0.91], 0.94 [95% CI, 0.87-1.01], and 0.95 [95% CI, 0.89-1.03], respectively) and a postpartum health care visit (risk ratio, 0.89 [95% CI, 0.82-0.96], 0.89 [95% CI, 0.80-0.98], and 0.92 [95% CI, 0.83-1.02], respectively) compared with women who delivered in states with neither policy. Conclusions and Relevance: The results indicate that state child abuse policies and mandated reporting policies are associated with reduced receipt of prenatal and postpartum care among women who engage in substance use during pregnancy.

Wastewater sequencing reveals early cryptic SARS-CoV-2 variant transmission.

As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing and/or sequencing capacity, which can also introduce biases1-3. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing4,5. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We developed and deployed improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detected emerging variants of concern up to 14 days earlier in wastewater samples, and identified multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission.

Real-time Feedback to Improve HIV Treatment Adherence in Pregnant and Postpartum Women in Uganda: A Randomized Controlled Trial.

We assessed an intervention aimed at improving adherence to antiretroviral therapy (ART) among pregnant and postpartum women living with HIV (PPWLH). We randomized 133 pregnant women initiating ART in Uganda to receive text reminders generated by real time-enabled electronic monitors and data-informed counseling through 3 months postpartum (PPM3) or standard care. Intention-to-treat analyses found low adherence levels and no intervention impact. Proportions achieving ≥95% adherence in PPM3 were 16.4% vs. 9.1% (t = -1.14, p = 0.26) in intervention vs. comparison groups, respectively; 30.9% vs. 29.1% achieved ≥80% adherence. Additional analyses found significant adherence declines after delivery, and no effect on disease progression (CD4-cell count, viral load), though treatment interruptions were significantly fewer in intervention participants. Per-protocol analyses encompassing participants who used adherence monitors as designed experienced better outcomes, suggesting potential benefit for some PPWLH. The study was registered on ClinicalTrials.Gov (NCT02396394).

Association of prenatal substance use with prenatal and postpartum care: Evidence from the Pregnancy Risk Assessment Monitoring System, 2016-2019.

The objective of this study was to build on existing qualitative research to estimate the association of prenatal substance use with prenatal and postpartum care. We used data from the 2016-2019 Pregnancy Risk Assessment Monitoring System for 9 states. We conducted adjusted linear regression to compare month of gestation of first prenatal visit and adjusted logistic regression to compare receipt of adequate prenatal care and a postpartum healthcare visit among women who reported prenatal use of any opioids, prescription opioids, marijuana, and illicit drugs to those who did not report use of each substance. Women who reported prenatal use of any opioids (Risk Difference(RD) = 0.16; 95% Confidence Interval (CI) = 0.04, 0.28), prescription opioids (RD = 0.16; 95% CI = 0.04, 0.28), marijuana (RD = 0.25; 95% CI = 0.10, 0.41) and illicit drugs (RD = 0.52; 95% CI = 0.09, 0.95) initiated prenatal care later than those who did not report use of each substance. Women who reported prenatal use of any opioid (Odds Ratio (OR) = 0.82; 95% CI = 0.68, 1.00), prescription opioids (OR = 0.84; 95% CI = 0.69, 1.02), marijuana (OR = 0.59; 95% CI = 0.48, 0.73) and illicit drugs (OR = 0.29; 95% CI = 0.20, 0.42) were less likely to receive adequate prenatal care. Women who reported prenatal use of any opioid (OR = 0.82, 95% CI = 0.65, 1.04), prescription opioids (OR = 0.83; 95% CI = 0.66, 1.05), marijuana (OR = 0.65; 95% CI = 0.51, 0.82) and illicit drugs (OR = 0.47; 95% CI = 0.30, 0.72) had a lower likelihood of a postpartum visit than those who did not report use of each substance. Results indicate potential intervention points for pregnant women who use substances.

Wastewater sequencing uncovers early, cryptic SARS-CoV-2 variant transmission.

As SARS-CoV-2 continues to spread and evolve, detecting emerging variants early is critical for public health interventions. Inferring lineage prevalence by clinical testing is infeasible at scale, especially in areas with limited resources, participation, or testing/sequencing capacity, which can also introduce biases. SARS-CoV-2 RNA concentration in wastewater successfully tracks regional infection dynamics and provides less biased abundance estimates than clinical testing. Tracking virus genomic sequences in wastewater would improve community prevalence estimates and detect emerging variants. However, two factors limit wastewater-based genomic surveillance: low-quality sequence data and inability to estimate relative lineage abundance in mixed samples. Here, we resolve these critical issues to perform a high-resolution, 295-day wastewater and clinical sequencing effort, in the controlled environment of a large university campus and the broader context of the surrounding county. We develop and deploy improved virus concentration protocols and deconvolution software that fully resolve multiple virus strains from wastewater. We detect emerging variants of concern up to 14 days earlier in wastewater samples, and identify multiple instances of virus spread not captured by clinical genomic surveillance. Our study provides a scalable solution for wastewater genomic surveillance that allows early detection of SARS-CoV-2 variants and identification of cryptic transmission.

Emerging mechanisms and dynamics of three-dimensional genome organisation at zygotic genome activation.

The genome of an early embryo undergoes significant remodelling at the epigenetic, transcriptional, and structural levels. New technological developments have made it possible to study 3D genome organisation in the zygote and early embryo of many different species. Recent studies in human embryos, zebrafish, medaka, and Xenopus have revealed that, similar to previous results in mouse and Drosophila, the zygotic genome is unstructured prior to zygotic genome activation. While these studies show that topologically associating domains are established coincident with zygotic genome activation across species, other 3D genome structures have more varied timing. Here, we review recent studies examining the timing and mechanisms of establishment of 3D genome organisation in the early embryo, and discuss similarities and differences between species. Investigating the establishment of 3D chromatin conformation in early embryos has the potential to reveal novel mechanisms of 3D genome organisation.

Ronin governs the metabolic capacity of the embryonic lineage for post-implantation development.

During implantation, the murine embryo transitions from a "quiet" into an active metabolic/proliferative state, which kick-starts the growth and morphogenesis of the post-implantation conceptus. Such transition is also required for embryonic stem cells to be established from mouse blastocysts, but the factors regulating this process are poorly understood. Here, we show that Ronin plays a critical role in the process by enabling active energy production, and the loss of Ronin results in the establishment of a reversible quiescent state in which naïve pluripotency is promoted. In addition, Ronin fine-tunes the expression of genes that encode ribosomal proteins and is required for proper tissue-scale organisation of the pluripotent lineage during the transition from blastocyst to egg cylinder stage. Thus, Ronin function is essential for governing the metabolic capacity so that it can support the pluripotent lineage's high-energy demands for cell proliferation and morphogenesis.

Trends in cesarean section rates in private and public facilities in rural eastern Maharashtra, India from 2010-2017.

INTRODUCTION: Rates of cesarean sections (CS) have increased dramatically over the past two decades in India. This increase has been disproportionately high in private facilities, but little is known about the drivers of the CS rate increase and how they vary over time and geographically. METHODS: Women enrolled in the Nagpur, India site of the Global Network for Women's and Children's Health Research Maternal and Neonatal Health Registry, who delivered in a health facility with CS capability were included in this study. The trend in CS rates from 2010 to 2017 in public and private facilities were assessed and displayed by subdistrict. Multivariable generalized estimating equations models were used to assess the association of delivering in private versus public facilities with having a CS, adjusting for known risk factors. RESULTS: CS rates increased substantially between 2010 and 2017 at both public and private facilities. The odds of having a CS at a private facility were 40% higher than at a public facility after adjusting for other known risk factors. CS rates had unequal spatial distributions at the subdistrict level. DISCUSSION: Our study findings contribute to the knowledge of increasing CS rates in both public and private facilities in India. Maps of the spatial distribution of subdistrict-based CS rates are helpful in understanding patterns of CS deliveries, but more investigation as to why clusters of high CS rates have formed in warranted.

Independence of chromatin conformation and gene regulation during Drosophila dorsoventral patterning.

The relationship between chromatin organization and gene regulation remains unclear. While disruption of chromatin domains and domain boundaries can lead to misexpression of developmental genes, acute depletion of regulators of genome organization has a relatively small effect on gene expression. It is therefore uncertain whether gene expression and chromatin state drive chromatin organization or whether changes in chromatin organization facilitate cell-type-specific activation of gene expression. Here, using the dorsoventral patterning of the Drosophila melanogaster embryo as a model system, we provide evidence for the independence of chromatin organization and dorsoventral gene expression. We define tissue-specific enhancers and link them to expression patterns using single-cell RNA-seq. Surprisingly, despite tissue-specific chromatin states and gene expression, chromatin organization is largely maintained across tissues. Our results indicate that tissue-specific chromatin conformation is not necessary for tissue-specific gene expression but rather acts as a scaffold facilitating gene expression when enhancers become active.

Tracking nonliteral language processing using audiovisual scenarios.

Recognizing sarcasm and jocularity during face-to-face communication requires the integration of verbal, paralinguistic, and nonverbal cues, yet most previous research on nonliteral language processing has been carried out using written or static stimuli. In the current study, we examined the processing of dynamic literal and nonliteral intentions using eye tracking. Participants (N = 37) viewed short, ecologically valid video vignettes and were asked to identify the speakers' intention. Participants had greater difficulty identifying jocular statements as insincere in comparison to sarcastic statements and spent significantly more time looking at faces during nonliteral versus literal social interactions. Finally, participants took longer to shift their attention from one talker to the other talker during interactions that conveyed literal positive intentions compared with jocular and literal negative intentions. These findings currently support the Standard Pragmatic Model and the Parallel-Constraint-Satisfaction Model of nonliteral language processing. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Alternative Immunization Clinics to Improve Vaccination Access during the COVID-19 Pandemic.

The United States declared a national emergency on March 13, 2020, in response to the rapidly spreading COVID-19 pandemic after all 50 states reported laboratory-confirmed cases.1 The demand for ambulatory medical care in the US fell by almost 60% and immunization encounters at Walter Reed National Military Medical Center decreased by 76% as patients became concerned about the risk of coronavirus exposure within a clinic or hospital setting.2 Our vaccination initiatives aimed to increase our pediatric and adult immunization rates through offering two alternative immunization platforms aimed to reduce patient concerns about COVID exposure.

Childhood Trauma, Gender Inequitable Attitudes, Alcohol Use and Multiple Sexual Partners: Correlates of Intimate Partner Violence in Northern Tanzania.

Intimate partner violence (IPV), including physical, sexual, emotional, and economic violence, has profound immediate and long-term effects on individuals and communities worldwide. To date, few studies have focused on couples' reporting of IPV. The aim of this article is to present the results of a survey of couples' reporting of IPV and the individual, interpersonal, and social correlates of IPV in northern Tanzania. Four hundred fifty couples from Karatu District, Tanzania, completed a questionnaire measuring attitudes on gender norms and relations, men's experience of childhood trauma, and men's perpetration and women's experience of IPV. We found high levels of acceptance and experience of IPV: 72% of men justified a husband's perpetration of IPV, and 54% of men and 76% of women said that a woman should tolerate violence to keep her family together. The majority of women had ever experienced IPV (77.8%), and 73.6% and 69% had experienced IPV in the past 12 and 3 months, respectively. Men were significantly less likely to report that they had committed IPV: 63.6% ever, 48.9% in the past 12 months, and 46.2% in the past 3 months. Multivariate logistic regression found that younger men, men who reported gender inequitable attitudes, childhood trauma, multiple sexual partners, and alcohol use were significantly more likely to report IPV perpetration in the past 3 months. Younger women, and women with low levels of education and reported food shortages were significantly more likely to report IPV in the past 3 months. These results indicate that social and individual acceptance and justification of IPV are common. Experience of violence persists over time in many relationships. This study demonstrates the need for interventions that address individual-, interpersonal-, and community-level determinants of IPV, including attitudes regarding gender equity, exposure to violence as children and intergenerational violence, lack of education, and poverty.

Seasonal trends and maternal characteristics as predictors of maternal undernutrition and low birthweight in Eastern Maharashtra, India.

Few studies have assessed whether women and infants in rural and peri-urban communities in South Asia experience seasonal fluctuations in nutritional status; however, a handful of studies have documented seasonal variability in risk factors for undernutrition including food availability, physical activity and infections. We used data from the Maternal and Newborn Health (MNH) registry, a population-based pregnancy and birth registry in Eastern Maharashtra, India, to analyse seasonal trends in birthweight and maternal nutritional status-body mass index (BMI) and haemoglobin-in the first trimester of pregnancy. We plotted monthly and seasonal trends in birthweight, and maternal BMI and haemoglobin, and used multivariable regression models to identify seasonal and maternal characteristics that predicted each outcome. Between October 2014 and January 2018, MNH included 29,253 livebirths with recorded birthweight. BMI was assessed in 15,252 women less than 12 weeks of gestation and haemoglobin in 18,278 women less than 13 weeks of gestation. Maternal characteristics (age, education, parity and height) were significantly associated with nutritional status; however, there were minimal seasonal fluctuations in birthweight or maternal nutrition. There were significant secular trends in maternal haemoglobin; between 2014 and 2018, the prevalence of maternal anaemia decreased from 91% to 79% and moderate or severe anaemia from 53% to 37%. The prevalence of maternal underweight (45.3%) and overweight (9.8%) and low birthweight (19.1%) remained relatively constant over the study period. Our findings highlight that in some rural and peri-urban areas in South Asia, tackling systemic drivers of malnutrition may be more effective than targeted interventions based on season.