A multilab study of bilingual infants: Exploring the preference for infant-directed speech

From the earliest months of life, infants prefer listening to and learn better from infant-directed speech (IDS) than adult-directed speech (ADS). Yet, IDS differs within communities, across languages, and across cultures, both in form and in prevalence. This large-scale, multi-site study used the diversity of bilingual infant experiences to explore the impact of different types of linguistic experience on infants’ IDS preference. As part of the multi-lab ManyBabies project, we compared lab-matched samples of 333 bilingual and 385 monolingual infants’ preference for North-American English IDS (cf. ManyBabies Consortium, in press (MB1)), tested in 17 labs in 7 countries. Those infants were tested in two age groups: 6–9 months (the younger sample) and 12–15 months (the older sample). We found that bilingual and monolingual infants both preferred IDS to ADS, and did not differ in terms of the overall magnitude of this preference. However, amongst bilingual infants who were acquiring North-American English (NAE) as a native language, greater exposure to NAE was associated with a stronger IDS preference, extending the previous finding from MB1 that monolinguals learning NAE as a native language showed a stronger preference than infants unexposed to NAE. Together, our findings indicate that IDS preference likely makes a similar contribution to monolingual and bilingual development, and that infants are exquisitely sensitive to the nature and frequency of different types of language input in their early environments

The present and future status of heavy neutral leptons

The existence of nonzero neutrino masses points to the likely existence of multiple Standard Model neutral fermions. When such states are heavy enough that they cannot be produced in oscillations, they are referred to as heavy neutral leptons (HNLs). In this white paper, we discuss the present experimental status of HNLs including colliders, beta decay, accelerators, as well as astrophysical and cosmological impacts. We discuss the importance of continuing to search for HNLs, and its potential impact on our understanding of key fundamental questions, and additionally we outline the future prospects for next-generation future experiments or upcoming accelerator run scenarios

Impact of common cardio-metabolic risk factors on fatal and non-fatal cardiovascular disease in Latin America and the Caribbean: an individual-level pooled analysis of 31 cohort studies

Background: Estimates of the burden of cardio-metabolic risk factors in Latin America and the Caribbean (LAC) rely on relative risks (RRs) from non-LAC countries. Whether these RRs apply to LAC remains un- known. Methods: We pooled LAC cohorts. We estimated RRs per unit of exposure to body mass index (BMI), systolic blood pressure (SBP), fasting plasma glucose (FPG), total cholesterol (TC) and non-HDL cholesterol on fatal (31 cohorts, n = 168,287) and non-fatal (13 cohorts, n = 27,554) cardiovascular diseases, adjusting for regression dilution bias. We used these RRs and national data on mean risk factor levels to estimate the number of cardiovascular deaths attributable to non-optimal levels of each risk factor. Results: Our RRs for SBP, FPG and TC were like those observed in cohorts conducted in high-income countries; however, for BMI, our RRs were consistently smaller in people below 75 years of age. Across risk factors, we observed smaller RRs among older ages. Non-optimal SBP was responsible for the largest number of attributable cardiovascular deaths ranging from 38 per 10 0,0 0 0 women and 54 men in Peru, to 261 (Dominica, women) and 282 (Guyana, men). For non-HDL cholesterol, the lowest attributable rate was for women in Peru (21) and men in Guatemala (25), and the largest in men (158) and women (142) from Guyana. Interpretation: RRs for BMI from studies conducted in high-income countries may overestimate disease burden metrics in LAC; conversely, RRs for SBP, FPG and TC from LAC cohorts are similar to those esti- mated from cohorts in high-income countries

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Background: Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. // Methods: We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung's disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. // Findings: We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung's disease) from 264 hospitals (89 in high-income countries, 166 in middle-income countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in low-income countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. // Interpretation: Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between low-income, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

A multilab study of bilingual infants: Exploring the preference for infant-directed speech

From the earliest months of life, infants prefer listening to and learn better from infant-directed speech (IDS) compared with adult-directed speech (ADS). Yet IDS differs within communities, across languages, and across cultures, both in form and in prevalence. This large-scale, multisite study used the diversity of bilingual infant experiences to explore the impact of different types of linguistic experience on infants’ IDS preference. As part of the multilab ManyBabies 1 project, we compared preference for North American English (NAE) IDS in lab-matched samples of 333 bilingual and 384 monolingual infants tested in 17 labs in seven countries. The tested infants were in two age groups: 6 to 9 months and 12 to 15 months. We found that bilingual and monolingual infants both preferred IDS to ADS, and the two groups did not differ in terms of the overall magnitude of this preference. However, among bilingual infants who were acquiring NAE as a native language, greater exposure to NAE was associated with a stronger IDS preference. These findings extend the previous finding from ManyBabies 1 that monolinguals learning NAE as a native language showed a stronger IDS preference than infants unexposed to NAE. Together, our findings indicate that IDS preference likely makes similar contributions to monolingual and bilingual development, and that infants are exquisitely sensitive to the nature and frequency of different types of language input in their early environments

FTY720 (fingolimod) modulates the severity of viral-induced encephalomyelitis and demyelination

BACKGROUND: FTY720 (fingolimod) is the first oral drug approved by the Food and Drug Administration for treatment of patients with the relapsing-remitting form of the human demyelinating disease multiple sclerosis. Evidence suggests that the therapeutic benefit of FTY720 occurs by preventing the egress of lymphocytes from lymph nodes thereby inhibiting the infiltration of disease-causing lymphocytes into the central nervous system (CNS). We hypothesized that FTY720 treatment would affect lymphocyte migration to the CNS and influence disease severity in a mouse model of viral-induced neurologic disease. METHODS: Mice were infected intracranially with the neurotropic JHM strain of mouse hepatitis virus. Infected animals were treated with increasing doses (1, 3 and 10 mg/kg) of FTY720 and morbidity and mortality recorded. Infiltration of inflammatory virus-specific T cells (tetramer staining) into the CNS of FTY720-treated mice was determined using flow cytometry. The effects of FTY720 treatment on virus-specific T cell proliferation, cytokine production and cytolytic activity were also determined. The severity of neuroinflammation and demyelination in FTY720-treated mice was examined by flow cytometry and histopathologically, respectively, in the spinal cords of the mice. RESULTS: Administration of FTY720 to JHMV-infected mice resulted in increased clinical disease severity and mortality. These results correlated with impaired ability to control viral replication (P < 0.05) within the CNS at days 7 and 14 post-infection, which was associated with diminished accumulation of virus-specific CD4+ and CD8+ T cells (P < 0.05) into the CNS. Reduced neuroinflammation in FTY720-treated mice correlated with increased retention of T lymphocytes within draining cervical lymph nodes (P < 0.05). Treatment with FTY720 did not affect virus-specific T cell proliferation, expression of IFN-γ, TNF-α or cytolytic activity. FTY720-treated mice exhibited a reduction in the severity of demyelination associated with dampened neuroinflammation. CONCLUSION: These findings indicate that FTY720 mutes effective anti-viral immune responses through impacting migration and accumulation of virus-specific T cells within the CNS during acute viral-induced encephalomyelitis. FTY720 treatment reduces the severity of neuroinflammatory-mediated demyelination by restricting the access of disease-causing lymphocytes into the CNS but is not associated with viral recrudescence in this model

The present and future status of heavy neutral leptons

The existence of nonzero neutrino masses points to the likely existence of multiple Standard Model neutral fermions. When such states are heavy enough that they cannot be produced in oscillations, they are referred to as heavy neutral leptons (HNLs). In this white paper, we discuss the present experimental status of HNLs including colliders, beta decay, accelerators, as well as astrophysical and cosmological impacts. We discuss the importance of continuing to search for HNLs, and its potential impact on our understanding of key fundamental questions, and additionally we outline the future prospects for next-generation future experiments or upcoming accelerator run scenarios.Peer reviewe

Impact of common cardio-metabolic risk factors on fatal and non-fatal cardiovascular disease in Latin America and the Caribbean: an individual-level pooled analysis of 31 cohort studies

Background: Estimates of the burden of cardio-metabolic risk factors in Latin America and the Caribbean (LAC) rely on relative risks (RRs) from non-LAC countries. Whether these RRs apply to LAC remains un- known. Methods: We pooled LAC cohorts. We estimated RRs per unit of exposure to body mass index (BMI), systolic blood pressure (SBP), fasting plasma glucose (FPG), total cholesterol (TC) and non-HDL cholesterol on fatal (31 cohorts, n = 168,287) and non-fatal (13 cohorts, n = 27,554) cardiovascular diseases, adjusting for regression dilution bias. We used these RRs and national data on mean risk factor levels to estimate the number of cardiovascular deaths attributable to non-optimal levels of each risk factor. Results: Our RRs for SBP, FPG and TC were like those observed in cohorts conducted in high-income countries; however, for BMI, our RRs were consistently smaller in people below 75 years of age. Across risk factors, we observed smaller RRs among older ages. Non-optimal SBP was responsible for the largest number of attributable cardiovascular deaths ranging from 38 per 10 0,0 0 0 women and 54 men in Peru, to 261 (Dominica, women) and 282 (Guyana, men). For non-HDL cholesterol, the lowest attributable rate was for women in Peru (21) and men in Guatemala (25), and the largest in men (158) and women (142) from Guyana. Interpretation: RRs for BMI from studies conducted in high-income countries may overestimate disease burden metrics in LAC; conversely, RRs for SBP, FPG and TC from LAC cohorts are similar to those esti- mated from cohorts in high-income countries