Adolescent Social Outcomes Declined During COVID-19: Evidence From Bangladesh, Jordan, And Ethiopia.

Although adolescents have been less susceptible to COVID-19-related morbidity and mortality than older people, the social containment policies put in place to curb the disease constrained their ability to thrive. This study explored changes in adolescent outcomes during the COVID-19 pandemic, particularly among vulnerable adolescents, focusing on education, economic participation, early marriage, self-reported health, and food security. We investigated the role of governmental and nongovernmental cash and food aid in mitigating negative effects. Using panel data collected both before (2017-20) and at two points during (2020-21) the pandemic on more than 7,000 adolescents from Bangladesh, Jordan, and Ethiopia, we found evidence of worsening outcomes across all measures except self-reported health. Declines were generally worse for more vulnerable adolescents. There is little evidence that aid mitigated negative impacts for adolescents in general or for vulnerable adolescents in particular. This research highlights the need for greater focus on developing social protection that is responsive to the multifaceted needs of adolescents.

Adverse maternal, fetal, and newborn outcomes among pregnant women with SARS-CoV-2 infection: an individual participant data meta-analysis.

INTRODUCTION: Despite a growing body of research on the risks of SARS-CoV-2 infection during pregnancy, there is continued controversy given heterogeneity in the quality and design of published studies. METHODS: We screened ongoing studies in our sequential, prospective meta-analysis. We pooled individual participant data to estimate the absolute and relative risk (RR) of adverse outcomes among pregnant women with SARS-CoV-2 infection, compared with confirmed negative pregnancies. We evaluated the risk of bias using a modified Newcastle-Ottawa Scale. RESULTS: We screened 137 studies and included 12 studies in 12 countries involving 13 136 pregnant women.Pregnant women with SARS-CoV-2 infection-as compared with uninfected pregnant women-were at significantly increased risk of maternal mortality (10 studies; n=1490; RR 7.68, 95% CI 1.70 to 34.61); admission to intensive care unit (8 studies; n=6660; RR 3.81, 95% CI 2.03 to 7.17); receiving mechanical ventilation (7 studies; n=4887; RR 15.23, 95% CI 4.32 to 53.71); receiving any critical care (7 studies; n=4735; RR 5.48, 95% CI 2.57 to 11.72); and being diagnosed with pneumonia (6 studies; n=4573; RR 23.46, 95% CI 3.03 to 181.39) and thromboembolic disease (8 studies; n=5146; RR 5.50, 95% CI 1.12 to 27.12).Neonates born to women with SARS-CoV-2 infection were more likely to be admitted to a neonatal care unit after birth (7 studies; n=7637; RR 1.86, 95% CI 1.12 to 3.08); be born preterm (7 studies; n=6233; RR 1.71, 95% CI 1.28 to 2.29) or moderately preterm (7 studies; n=6071; RR 2.92, 95% CI 1.88 to 4.54); and to be born low birth weight (12 studies; n=11 930; RR 1.19, 95% CI 1.02 to 1.40). Infection was not linked to stillbirth. Studies were generally at low or moderate risk of bias. CONCLUSIONS: This analysis indicates that SARS-CoV-2 infection at any time during pregnancy increases the risk of maternal death, severe maternal morbidities and neonatal morbidity, but not stillbirth or intrauterine growth restriction. As more data become available, we will update these findings per the published protocol.

Clinical risk factors of adverse outcomes among women with COVID-19 in the pregnancy and postpartum period: a sequential, prospective meta-analysis.

OBJECTIVE: This sequential, prospective meta-analysis sought to identify risk factors among pregnant and postpartum women with COVID-19 for adverse outcomes related to disease severity, maternal morbidities, neonatal mortality and morbidity, and adverse birth outcomes. DATA SOURCES: We prospectively invited study investigators to join the sequential, prospective meta-analysis via professional research networks beginning in March 2020. STUDY ELIGIBILITY CRITERIA: Eligible studies included those recruiting at least 25 consecutive cases of COVID-19 in pregnancy within a defined catchment area. METHODS: We included individual patient data from 21 participating studies. Data quality was assessed, and harmonized variables for risk factors and outcomes were constructed. Duplicate cases were removed. Pooled estimates for the absolute and relative risk of adverse outcomes comparing those with and without each risk factor were generated using a 2-stage meta-analysis. RESULTS: We collected data from 33 countries and territories, including 21,977 cases of SARS-CoV-2 infection in pregnancy or postpartum. We found that women with comorbidities (preexisting diabetes mellitus, hypertension, cardiovascular disease) vs those without were at higher risk for COVID-19 severity and adverse pregnancy outcomes (fetal death, preterm birth, low birthweight). Participants with COVID-19 and HIV were 1.74 times (95% confidence interval, 1.12-2.71) more likely to be admitted to the intensive care unit. Pregnant women who were underweight before pregnancy were at higher risk of intensive care unit admission (relative risk, 5.53; 95% confidence interval, 2.27-13.44), ventilation (relative risk, 9.36; 95% confidence interval, 3.87-22.63), and pregnancy-related death (relative risk, 14.10; 95% confidence interval, 2.83-70.36). Prepregnancy obesity was also a risk factor for severe COVID-19 outcomes including intensive care unit admission (relative risk, 1.81; 95% confidence interval, 1.26-2.60), ventilation (relative risk, 2.05; 95% confidence interval, 1.20-3.51), any critical care (relative risk, 1.89; 95% confidence interval, 1.28-2.77), and pneumonia (relative risk, 1.66; 95% confidence interval, 1.18-2.33). Anemic pregnant women with COVID-19 also had increased risk of intensive care unit admission (relative risk, 1.63; 95% confidence interval, 1.25-2.11) and death (relative risk, 2.36; 95% confidence interval, 1.15-4.81). CONCLUSION: We found that pregnant women with comorbidities including diabetes mellitus, hypertension, and cardiovascular disease were at increased risk for severe COVID-19-related outcomes, maternal morbidities, and adverse birth outcomes. We also identified several less commonly known risk factors, including HIV infection, prepregnancy underweight, and anemia. Although pregnant women are already considered a high-risk population, special priority for prevention and treatment should be given to pregnant women with these additional risk factors.

COVID-19 and the gendered impacts on adolescent wellbeing: Evidence from a cross-sectional study of locally adapted measures in Ethiopia, Jordan, and Palestine.

Background: The COVID-19 pandemic and associated policy responses have interrupted services, increased financial stress, and driven social isolation, with acute impacts for adolescents. This study explores relationships between gender, COVID-19 vulnerability, social protection, and adolescent wellbeing in three diverse contexts: Ethiopia, Jordan, and Palestine. Methods: This study presents findings from a quantitative phone survey with adolescents in Ethiopia, Jordan, and Palestine (n = 5752) on household-level vulnerability to COVID-19-related shocks, household-level social protection (cash transfers or food aid), and locally adapted outcome measures designed to capture the gendered impacts of COVID-19 (collected between November 22, 2020 and February 25, 2021). We examine the relationship between each outcome and household-level COVID-19 vulnerability and social protection (and their interaction) using multivariate regressions, adjusting for adolescent and household characteristics. Findings: For all adolescents, increased vulnerability to COVID-19-related shocks is associated with worse outcomes for resilient coping and time spent on domestic tasks and care work. Across samples, girls spent over two additional hours on domestic and care work compared to boys. Girls in more vulnerable households experienced greater gendered constraints on behaviour. We find no association between receipt of social protection and adolescent wellbeing, and find that it only moderates the effect of COVID-19 vulnerability for less vulnerable households. Disability status, being out of school, and experiencing child marriage are also associated with adverse outcomes. Interpretation: Our study highlights that the pandemic has exacerbated underlying gender inequalities across adolescents in three very different settings, and that existing social safety nets are not adequate to fully address these impacts, particularly for the most vulnerable. Funding: This work was supported by UK aid through a grant from the Foreign, Commonwealth & Development Office to the Gender and Adolescence: Global Evidence (GAGE) longitudinal research study; the EMERGE project (Bill & Melinda Gates Foundation grants: OPP1163682 and INV018007; PI Anita Raj) and the World Health Organization (WHO) Regional Office for the Eastern Mediterranean.

Protocol for a sequential, prospective meta-analysis to describe coronavirus disease 2019 (COVID-19) in the pregnancy and postpartum periods.

We urgently need answers to basic epidemiological questions regarding SARS-CoV-2 infection in pregnant and postpartum women and its effect on their newborns. While many national registries, health facilities, and research groups are collecting relevant data, we need a collaborative and methodologically rigorous approach to better combine these data and address knowledge gaps, especially those related to rare outcomes. We propose that using a sequential, prospective meta-analysis (PMA) is the best approach to generate data for policy- and practice-oriented guidelines. As the pandemic evolves, additional studies identified retrospectively by the steering committee or through living systematic reviews will be invited to participate in this PMA. Investigators can contribute to the PMA by either submitting individual patient data or running standardized code to generate aggregate data estimates. For the primary analysis, we will pool data using two-stage meta-analysis methods. The meta-analyses will be updated as additional data accrue in each contributing study and as additional studies meet study-specific time or data accrual thresholds for sharing. At the time of publication, investigators of 25 studies, including more than 76,000 pregnancies, in 41 countries had agreed to share data for this analysis. Among the included studies, 12 have a contemporaneous comparison group of pregnancies without COVID-19, and four studies include a comparison group of non-pregnant women of reproductive age with COVID-19. Protocols and updates will be maintained publicly. Results will be shared with key stakeholders, including the World Health Organization (WHO) Maternal, Newborn, Child, and Adolescent Health (MNCAH) Research Working Group. Data contributors will share results with local stakeholders. Scientific publications will be published in open-access journals on an ongoing basis.

Compounding inequalities: Adolescent psychosocial wellbeing and resilience among refugee and host communities in Jordan during the COVID-19 pandemic.

PURPOSE: The COVID-19 pandemic and associated risk-mitigation strategies have altered the social contexts in which adolescents in low- and middle-income countries live. Little is known, however, about the impacts of the pandemic on displaced populations, and how those impacts differ by gender and life stage. We investigate the extent to which the pandemic has compounded pre-existing social inequalities among adolescents in Jordan, and the role support structures play in promoting resilience. METHODS: Our analysis leverages longitudinal quantitative survey data and in-depth qualitative interviews, collected before and after the onset of COVID-19, with over 3,000 Syrian refugees, stateless Palestinians and vulnerable Jordanians, living in camps, host communities and informal tented settlements. We utilize mixed-methods analysis combining multivariate regression with deductive qualitative tools to evaluate pandemic impacts and associated policy responses on adolescent wellbeing and mental health, at three and nine months after the pandemic onset. We also explore the role of support systems at individual, household, community, and policy levels. FINDINGS: We find the pandemic has resulted in severe economic and service disruptions with far-reaching and heterogenous effects on adolescent wellbeing. Nine months into the pandemic, 19.3% of adolescents in the sample presented with symptoms of moderate-to severe depression, with small signs of improvement (3.2 percentage points [pp], p<0.001). Two thirds of adolescents reported household stress had increased during the pandemic, especially for Syrian adolescents in host communities (10.7pp higher than any other group, p<0.001). Social connectedness was particularly low for girls, who were 13.4 percentage points (p<0.001) more likely than boys to have had no interaction with friends in the past 7 days. Adolescent programming shows signs of being protective, particularly for girls, who were 8.8 percentage points (p<0.01) more likely to have a trusted friend than their peers who were not participating in programming. CONCLUSIONS: Pre-existing social inequalities among refugee adolescents affected by forced displacement have been compounded during the COVID-19 pandemic, with related disruptions to services and social networks. To achieve Sustainable Development Goal targets to support healthy and empowered development in adolescence and early adulthood requires interventions that target the urgent needs of the most vulnerable adolescents while addressing population-level root causes and determinants of psychosocial wellbeing and resilience for all adolescent girls and boys.

The use of a book club to promote biomedical trainee professional development.

Professional development for biomedical doctoral and postdoctoral trainees is vital, especially due to the increase in individuals pursuing non-faculty career paths. We created a professional development-focused discussion group between trainees and faculty/staff by utilizing a book club format in which monthly small group meetings occurred over an 8-month period. A pre- and post-survey consisting of Likert and free-response questions was completed by participants. Results demonstrated that after the book club, trainees: 1) were more knowledgeable about a variety of career paths; 2) had improved awareness of their interests in relation to their career; 3) were more knowledgeable of their transferrable skills; 4) were more comfortable engaging with their PI and completing/updating an Individual Development Plan; 5) were more likely to find mentors in addition to their PI to address career specific needs; and 6) were more likely to seek opportunities to conduct informational interviews or experiential learning. Additionally, we found that faculty/staff: 1) were more knowledgeable about careers outside of academia; 2) had greater consideration for their mentee's values and interests in relation to their career; 3) had a better understanding of their mentee's transferable skills; and 4) were more comfortable engaging with their mentee about their career path and addressing an Individual Development Plan. Overall, we found that the utilization of a book club consisting of trainees and faculty/staff as a professional development tool was beneficial for both groups of participants, and this format is feasible for use in biomedical education professional development.

Intersecting barriers to adolescents' educational access during COVID-19: Exploring the role of gender, disability and poverty.

This article explores the social determinants of adolescents' access to education during the COVID-19 pandemic in three diverse urban contexts in Bangladesh, Ethiopia and Jordan. It provides novel empirical data from the Gender and Adolescence: Global Evidence longitudinal study, drawing on phone surveys (4441), qualitative interviews with adolescents aged 12-19 years (500), and key informant interviews conducted between April and October 2020. Findings highlight that the pandemic is compounding pre-existing vulnerabilities to educational disadvantage, and that gender, poverty and disability are intersecting to deepen social inequalities. The paper concludes by reflecting on policy implications for inclusive distance education in emergencies.

Volitional control of single-electrode high gamma local field potentials by people with paralysis.

Intracortical brain-computer interfaces (BCIs) can enable individuals to control effectors, such as a computer cursor, by directly decoding the user's movement intentions from action potentials and local field potentials (LFPs) recorded within the motor cortex. However, the accuracy and complexity of effector control achieved with such "biomimetic" BCIs will depend on the degree to which the intended movements used to elicit control modulate the neural activity. In particular, channels that do not record distinguishable action potentials and only record LFP modulations may be of limited use for BCI control. In contrast, a biofeedback approach may surpass these limitations by letting the participants generate new control signals and learn strategies that improve the volitional control of signals used for effector control. Here, we show that, by using a biofeedback paradigm, three individuals with tetraplegia achieved volitional control of gamma LFPs (40-400 Hz) recorded by a single microelectrode implanted in the precentral gyrus. Control was improved over a pair of consecutive sessions up to 3 days apart. In all but one session, the channel used to achieve control lacked distinguishable action potentials. Our results indicate that biofeedback LFP-based BCIs may potentially contribute to the neural modulation necessary to obtain reliable and useful control of effectors. NEW & NOTEWORTHY Our study demonstrates that people with tetraplegia can volitionally control individual high-gamma local-field potential (LFP) channels recorded from the motor cortex, and that this control can be improved using biofeedback. Motor cortical LFP signals are thought to be both informative and stable intracortical signals and, thus, of importance for future brain-computer interfaces.

Hematopoietic and neural crest defects in zebrafish shoc2 mutants: a novel vertebrate model for Noonan-like syndrome.

The extracellular signal-related kinase 1 and 2 (ERK1/2) pathway is a highly conserved signaling cascade with numerous essential functions in development. The scaffold protein Shoc2 amplifies the activity of the ERK1/2 pathway and is an essential modulator of a variety of signaling inputs. Germline mutations in Shoc2 are associated with the human developmental disease known as the Noonan-like syndrome with loose anagen hair. Clinical manifestations of this disease include congenital heart defects, developmental delays, distinctive facial abnormalities, reduced growth and cognitive deficits along with hair anomalies. The many molecular details of pathogenesis of the Noonan-like syndrome and related developmental disorders, cumulatively called RASopathies, remain poorly understood. Mouse knockouts for Shoc2 are embryonic lethal, emphasizing the need for additional animal models to study the role of Shoc2 in embryonic development. Here, we characterize a zebrafish shoc2 mutant, and show that Shoc2 is essential for development, and that its loss is detrimental for the development of the neural crest and for hematopoiesis. The zebrafish model of the Noonan-like syndrome described here provides a novel system for the study of structure-function analyses and for genetic screens in a tractable vertebrate system.

Watch, Imagine, Attempt: Motor Cortex Single-Unit Activity Reveals Context-Dependent Movement Encoding in Humans With Tetraplegia.

Planning and performing volitional movement engages widespread networks in the human brain, with motor cortex considered critical to the performance of skilled limb actions. Motor cortex is also engaged when actions are observed or imagined, but the manner in which ensembles of neurons represent these volitional states (VoSs) is unknown. Here we provide direct demonstration that observing, imagining or attempting action activates shared neural ensembles in human motor cortex. Two individuals with tetraplegia (due to brainstem stroke or amyotrophic lateral sclerosis, ALS) were verbally instructed to watch, imagine, or attempt reaching actions displayed on a computer screen. Neural activity in the precentral gyrus incorporated information about both cognitive state and movement kinematics; the three conditions presented overlapping but unique, statistically distinct activity patterns. These findings demonstrate that individual neurons in human motor cortex reflect information related to sensory inputs and VoS in addition to movement features, and are a key part of a broader network linking perception and cognition to action.

Stable long-term BCI-enabled communication in ALS and locked-in syndrome using LFP signals.

Restoring communication for people with locked-in syndrome remains a challenging clinical problem without a reliable solution. Recent studies have shown that people with paralysis can use brain-computer interfaces (BCIs) based on intracortical spiking activity to efficiently type messages. However, due to neuronal signal instability, most intracortical BCIs have required frequent calibration and continuous assistance of skilled engineers to maintain performance. Here, an individual with locked-in syndrome due to brain stem stroke and an individual with tetraplegia secondary to amyotrophic lateral sclerosis (ALS) used a simple communication BCI based on intracortical local field potentials (LFPs) for 76 and 138 days, respectively, without recalibration and without significant loss of performance. BCI spelling rates of 3.07 and 6.88 correct characters/minute allowed the participants to type messages and write emails. Our results indicate that people with locked-in syndrome could soon use a slow but reliable LFP-based BCI for everyday communication without ongoing intervention from a technician or caregiver. NEW & NOTEWORTHY This study demonstrates, for the first time, stable repeated use of an intracortical brain-computer interface by people with tetraplegia over up to four and a half months. The approach uses local field potentials (LFPs), signals that may be more stable than neuronal action potentials, to decode participants' commands. Throughout the several months of evaluation, the decoder remained unchanged; thus no technical interventions were required to maintain consistent brain-computer interface operation.

Virtual typing by people with tetraplegia using a self-calibrating intracortical brain-computer interface.

Brain-computer interfaces (BCIs) promise to restore independence for people with severe motor disabilities by translating decoded neural activity directly into the control of a computer. However, recorded neural signals are not stationary (that is, can change over time), degrading the quality of decoding. Requiring users to pause what they are doing whenever signals change to perform decoder recalibration routines is time-consuming and impractical for everyday use of BCIs. We demonstrate that signal nonstationarity in an intracortical BCI can be mitigated automatically in software, enabling long periods (hours to days) of self-paced point-and-click typing by people with tetraplegia, without degradation in neural control. Three key innovations were included in our approach: tracking the statistics of the neural activity during self-timed pauses in neural control, velocity bias correction during neural control, and periodically recalibrating the decoder using data acquired during typing by mapping neural activity to movement intentions that are inferred retrospectively based on the user's self-selected targets. These methods, which can be extended to a variety of neurally controlled applications, advance the potential for intracortical BCIs to help restore independent communication and assistive device control for people with paralysis.

Reprint of "Non-causal spike filtering improves decoding of movement intention for intracortical BCIs".

BACKGROUND: Multiple types of neural signals are available for controlling assistive devices through brain-computer interfaces (BCIs). Intracortically recorded spiking neural signals are attractive for BCIs because they can in principle provide greater fidelity of encoded information compared to electrocorticographic (ECoG) signals and electroencephalograms (EEGs). Recent reports show that the information content of these spiking neural signals can be reliably extracted simply by causally band-pass filtering the recorded extracellular voltage signals and then applying a spike detection threshold, without relying on "sorting" action potentials. NEW METHOD: We show that replacing the causal filter with an equivalent non-causal filter increases the information content extracted from the extracellular spiking signal and improves decoding of intended movement direction. This method can be used for real-time BCI applications by using a 4ms lag between recording and filtering neural signals. RESULTS: Across 18 sessions from two people with tetraplegia enrolled in the BrainGate2 pilot clinical trial, we found that threshold crossing events extracted using this non-causal filtering method were significantly more informative of each participant's intended cursor kinematics compared to threshold crossing events derived from causally filtered signals. This new method decreased the mean angular error between the intended and decoded cursor direction by 9.7° for participant S3, who was implanted 5.4 years prior to this study, and by 3.5° for participant T2, who was implanted 3 months prior to this study. CONCLUSIONS: Non-causally filtering neural signals prior to extracting threshold crossing events may be a simple yet effective way to condition intracortically recorded neural activity for direct control of external devices through BCIs.

Neural Point-and-Click Communication by a Person With Incomplete Locked-In Syndrome.

A goal of brain-computer interface research is to develop fast and reliable means of communication for individuals with paralysis and anarthria. We evaluated the ability of an individual with incomplete locked-in syndrome enrolled in the BrainGate Neural Interface System pilot clinical trial to communicate using neural point-and-click control. A general-purpose interface was developed to provide control of a computer cursor in tandem with one of two on-screen virtual keyboards. The novel BrainGate Radial Keyboard was compared to a standard QWERTY keyboard in a balanced copy-spelling task. The Radial Keyboard yielded a significant improvement in typing accuracy and speed-enabling typing rates over 10 correct characters per minute. The participant used this interface to communicate face-to-face with research staff by using text-to-speech conversion, and remotely using an internet chat application. This study demonstrates the first use of an intracortical brain-computer interface for neural point-and-click communication by an individual with incomplete locked-in syndrome.

Non-causal spike filtering improves decoding of movement intention for intracortical BCIs.

BACKGROUND: Multiple types of neural signals are available for controlling assistive devices through brain-computer interfaces (BCIs). Intracortically recorded spiking neural signals are attractive for BCIs because they can in principle provide greater fidelity of encoded information compared to electrocorticographic (ECoG) signals and electroencephalograms (EEGs). Recent reports show that the information content of these spiking neural signals can be reliably extracted simply by causally band-pass filtering the recorded extracellular voltage signals and then applying a spike detection threshold, without relying on "sorting" action potentials. NEW METHOD: We show that replacing the causal filter with an equivalent non-causal filter increases the information content extracted from the extracellular spiking signal and improves decoding of intended movement direction. This method can be used for real-time BCI applications by using a 4ms lag between recording and filtering neural signals. RESULTS: Across 18 sessions from two people with tetraplegia enrolled in the BrainGate2 pilot clinical trial, we found that threshold crossing events extracted using this non-causal filtering method were significantly more informative of each participant's intended cursor kinematics compared to threshold crossing events derived from causally filtered signals. This new method decreased the mean angular error between the intended and decoded cursor direction by 9.7° for participant S3, who was implanted 5.4 years prior to this study, and by 3.5° for participant T2, who was implanted 3 months prior to this study. CONCLUSIONS: Non-causally filtering neural signals prior to extracting threshold crossing events may be a simple yet effective way to condition intracortically recorded neural activity for direct control of external devices through BCIs.

Age-related changes in niche cells influence hematopoietic stem cell function.

In a recent issue of Nature, Mayack et al. (2010) use young and old parabiotic mice to show that systemic signals from the young parabiont rejuvenate hematopoietic stem cell function via the microenvironmental niche.

CG dinucleotide clustering is a species-specific property of the genome.

Cytosines at cytosine-guanine (CG) dinucleotides are the near-exclusive target of DNA methyltransferases in mammalian genomes. Spontaneous deamination of methylcytosine to thymine makes methylated cytosines unusually susceptible to mutation and consequent depletion. The loci where CG dinucleotides remain relatively enriched, presumably due to their unmethylated status during the germ cell cycle, have been referred to as CpG islands. Currently, CpG islands are solely defined by base compositional criteria, allowing annotation of any sequenced genome. Using a novel bioinformatic approach, we show that CG clusters can be identified as an inherent property of genomic sequence without imposing a base compositional a priori assumption. We also show that the CG clusters co-localize in the human genome with hypomethylated loci and annotated transcription start sites to a greater extent than annotations produced by prior CpG island definitions. Moreover, this new approach allows CG clusters to be identified in a species-specific manner, revealing a degree of orthologous conservation that is not revealed by current base compositional approaches. Finally, our approach is able to identify methylating genomes (such as Takifugu rubripes) that lack CG clustering entirely, in which it is inappropriate to annotate CpG islands or CG clusters.