Using normative modelling to detect disease progression in mild cognitive impairment and Alzheimer’s disease in a cross-sectional multi-cohort study

Abstract Normative modelling is an emerging method for quantifying how individuals deviate from the healthy populational pattern. Several machine learning models have been implemented to develop normative models to investigate brain disorders, including regression, support vector machines and Gaussian process models. With the advance of deep learning technology, the use of deep neural networks has also been proposed. In this study, we assessed normative models based on deep autoencoders using structural neuroimaging data from patients with Alzheimer’s disease (n = 206) and mild cognitive impairment (n = 354). We first trained the autoencoder on an independent dataset (UK Biobank dataset) with 11,034 healthy controls. Then, we estimated how each patient deviated from this norm and established which brain regions were associated to this deviation. Finally, we compared the performance of our normative model against traditional classifiers. As expected, we found that patients exhibited deviations according to the severity of their clinical condition. The model identified medial temporal regions, including the hippocampus, and the ventricular system as critical regions for the calculation of the deviation score. Overall, the normative model had comparable cross-cohort generalizability to traditional classifiers. To promote open science, we are making all scripts and the trained models available to the wider research community

Assessing the association between hypoxia during craniofacial development and oral clefts

Objectives: To evaluate the association between hypoxia during embryo development and oral clefts in an animal model, and to evaluate the association between polymorphisms in the HIF-1A gene with oral clefts in human families. Material and Methods: The study with the animal model used zebrafish embryos at 8 hours post-fertilization submitted to 30% and 50% hypoxia for 24 hours. At 5 days post-fertilization, the larvae were fixed. The cartilage structures were stained to evaluate craniofacial phenotypes. The family-based association study included 148 Brazilian nuclear families with oral clefts. The association between the genetic polymorphisms rs2301113 and rs2057482 in HIF-1A with oral clefts was tested. We used real time PCR genotyping approach. ANOVA with Tukey's post-test was used to compare means. The transmission/disequilibrium test was used to analyze the distortion of the inheritance of alleles from parents to their affected offspring. Results: For the hypoxic animal model, the anterior portion of the ethmoid plate presented a gap in the anterior edge, forming a cleft. The hypoxia level was associated with the severity of the phenotype (p<0.0001). For the families, there was no under-transmitted allele among the affected progeny (p>0.05). Conclusion: Hypoxia is involved in the oral cleft etiology, however, polymorphisms in HIF-1A are not associated with oral clefts in humans

Contribution of ULF Wave Activity to the Global Recovery of the Outer Radiation Belt During the Passage of a High-Speed Solar Wind Stream Observed in September 2014

Energy coupling between the solar wind and the Earth's magnetosphere can affect the electron population in the outer radiation belt. However, the precise role of different internal and external mechanisms that leads to changes of the relativistic electron population is not entirely known. This paper describes how ultralow frequency (ULF) wave activity during the passage of Alfvénic solar wind streams contributes to the global recovery of the relativistic electron population in the outer radiation belt. To investigate the contribution of the ULF waves, we searched the Van Allen Probes data for a period in which we can clearly distinguish the enhancement of electron fluxes from the background. We found that the global recovery that started on 22 September 2014, which coincides with the corotating interaction region preceding a high-speed stream and the occurrence of persistent substorm activity, provides an excellent scenario to explore the contribution of ULF waves. To support our analyses, we employed ground- and space-based observational data and global magnetohydrodynamic simulations and calculated the ULF wave radial diffusion coefficients employing an empirical model. Observations show a gradual increase of electron fluxes in the outer radiation belt and a concomitant enhancement of ULF activity that spreads from higher to lower L-shells. Magnetohydrodynamic simulation results agree with observed ULF wave activity in the magnetotail, which leads to both fast and Alfvén modes in the magnetospheric nightside sector. The observations agree with the empirical model and are confirmed by phase space density calculations for this global recovery period

Monitoring SARS-CoV-2 seroprevalence over time among pregnant women admitted to delivery units: Suitability for surveillance.

OBJECTIVES: To determine SARS-CoV-2 seroprevalence over time and risk factors among pregnant women at delivery in São Paulo, Brazil; and to evaluate the suitability of pregnant women as a sentinel population for SARS-CoV-2 serosurveillance. METHODS: Unselected consecutive pregnant women presenting at the labor ward of a single large hospital between July 20th 2020 to February 21st 2021 were enrolled and tested for SARS-CoV-2 serology using two assays: the rapid chromatic Wondfo One Step (for total IgA and IgG detection) and Roche Elecsys assay (detecting anti-nucleoprotein [N] IgG). SARS-CoV-2 seroprevalence was computed as smooth spline function over time with 95% confidence intervals (CI). Risk factors were evaluated for positivity by each assay. We compared timepoint seroprevalence by the two assays with four concomitant community household surveys (HHS), in which the Roche assay was used, to determine the sensitivity and relevance of the pregnant women population as sentinel population. RESULTS: Overall SARS-CoV-2 seroprevalence was 28.9% (221/763) by Roche and 17.9% (137/763) by Wondfo. Reported symptoms experienced during pregnancy were all significantly correlated with being SARS-CoV-2 seropositive at delivery with any assay (with odds-ratios ranging from 3.0 [95% CI: 2.1-4.3] for coryza to 22.8 [95% CI: 12.3-46.6] for ageusia). Seropositivity by either assay was high in women at delivery in the early period of the pandemic (June 2020), compared with seropositivity in women from the concomitant HHS: 44.1% (95% CI: 21.8-66.4) for Roche, 54.1% (30.9-78.5) for Wondfo, versus 11.4% (95% CI: 9.2-13.6) for HHS. For later periods (October 2020 and January 2021), the seropositivity in women at delivery measured by Roche corresponded well with the prevalence found among women in the HHS using the same assay, whilst prevalence measured by Wondfo dropped. CONCLUSIONS: Women at delivery represent a highly exposed and readily accessible population for sentinel surveillance of emerging infections such as SARS-CoV-2

Vertical transmission of SARS-CoV2 during pregnancy: A high-risk cohort.

OBJECTIVE: Identify the potential for and risk factors of SARS-CoV-2 vertical transmission. METHODS: Symptomatic pregnant women with COVID-19 diagnosis in whom PCR for SARS-CoV-2 was performed at delivery using maternal serum and at least one of the biological samples: cord blood (CB), amniotic fluid (AF), colostrum and/or oropharyngeal swab (OPS) of the neonate. The association of parameters with maternal, AF and/or CB positivity and the influence of SARS-CoV-2 positivity in AF and/or CB on neonatal outcomes were investigated. RESULTS: Overall 73.4% (80/109) were admitted in hospital due to COVID-19, 22.9% needed intensive care and there were four maternal deaths. Positive RT-PCR for SARS-CoV-2 was observed in 14.7% of maternal blood, 13.9% of AF, 6.7% of CB, 2.1% of colostrum and 3.7% of OPS samples. The interval between COVID-19 symptoms and delivery was inversely associated with SARS-CoV-2 positivity in the maternal blood (p = 0.002) and in the AF and/or CB (p = 0.049). Maternal viremia was associated with positivity for SARS-CoV-2 in AF and/or CB (p = 0.001). SARS-CoV-2 positivity in the compartments was not associated with neonatal outcomes. CONCLUSION: Vertical transmission is possible in pregnant women with COVID-19 and a shorter interval between maternal symptoms and delivery is an influencing factor

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection