The Fallacy of Using Administrative Data in Assessing the Effectiveness of Food Fortification. Comment on: "Folic Acid Fortification and Neural Tube Defect Risk: Analysis of the Food Fortification Initiative Dataset. Nutrients 2020, 12, 247".

Our objective in this comment is to highlight several limitations in an ecological research study that was published in Nutrients by Murphy and Westmark (2020) in January 2020. The study used data from the Food Fortification Initiative (FFI) website, and applying an ecological study design, made an error of "ecologic fallacy" in concluding that "national fortification with folic acid is not associated with a significant decrease in the prevalence of neural tube defects (NTDs) at the population level". We list study limitations that led to their erroneous conclusions, stemming from incorrect considerations regarding NTD prevalence, the average grain availability for a country, the fortification coverage in a country, the population reach of fortified foods within a country, and the absence of the consideration of fortification type (voluntary vs. mandatory), country-specific policies on elective terminations for NTD-affected pregnancies, stillbirth proportions among those with NTDs, and fortification implementation. FFI data are derived from many sources and intended for fortification advocacy, not for hypothesis testing. The flawed study by Murphy & Westmark (2020) in Nutrients promotes a confusing and incorrect message to stakeholders, misguides policy makers, and hinders progress in global NTD prevention through a cost-effective, safe, and effective intervention: the mandatory large-scale folic acid fortification of staple foods

How Mistimed and Unwanted Pregnancies Affect Timing of Antenatal Care Initiation in three Districts in Tanzania

Early antenatal care (ANC) initiation is a doorway to early detection and management of potential complications associated with pregnancy. Although the literature reports various factors associated with ANC initiation such as parity and age, pregnancy intentions is yet to be recognized as a possible predictor of timing of ANC initiation. Data originate from a cross-sectional household survey on health behaviour and service utilization patterns. The survey was conducted in 2011 in Rufiji, Kilombero and Ulanga districts in Tanzania on 910 women of reproductive age who had given birth in the past two years. ANC initiation was considered to be early only if it occurred in the first trimester of pregnancy gestation. A recently completed pregnancy was defined as mistimed if a woman wanted it later, and if she did not want it at all the pregnancy was termed as unwanted. Chisquare was used to test for associations and multinomial logistic regression was conducted to examine how mistimed and unwanted pregnancies affect timing of ANC initiation. Although 49.3% of the women intended to become pregnant, 50.7% (34.9% mistimed and 15.8% unwanted) became pregnant unintentionally. While ANC initiation in the 1st trimester was 18.5%, so was 71.7% and 9.9% in the 2nd and 3rd trimesters respectively. Multivariate analysis revealed that ANC initiation in the 2nd trimester was 1.68 (95% CI 1.10‒2.58) and 2.00 (95% CI 1.05‒3.82) times more likely for mistimed and unwanted pregnancies respectively compared to intended pregnancies. These estimates rose to 2.81 (95% CI 1.41‒5.59) and 4.10 (95% CI 1.68‒10.00) respectively in the 3rd trimester. We controlled for gravidity, age, education, household wealth, marital status, religion, district of residence and travel time to a health facility. Late ANC initiation is a significant maternal and child health consequence of mistimed and unwanted pregnancies in Tanzania. Women should be empowered to delay or avoid pregnancies whenever they need to do so. Appropriate counseling to women, especially those who happen to conceive unintentionally is needed to minimize the possibility of delaying ANC initiation.\u

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Environmentalism, pre-environmentalism, and public policy

In the last decade, thousands of new grassroots groups have formed to oppose environmental pollution on the basis that it endangers their health. These groups have revitalized the environmental movement and enlarged its membership well beyond the middle class. Scientists, however, have been unable to corroborate these groups' claims that exposure to pollutants has caused their diseases. For policy analysts this situation appears to pose a choice between democracy and science. It needn't. Instead of evaluating the grassroots groups from the perspective of science, it is possible to evaluate science from the perspective of environmentalism. This paper argues that environmental epidemiology reflects ‘pre-environmentalist’ assumptions about nature and that new ideas about nature advanced by the environmental movement could change the way scientists collect and interpret data.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45449/1/11077_2005_Article_BF01006494.pd

Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis

Multifactorial mechanisms underlying late-onset Alzheimer's disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD–abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system's integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions

Quantitative 18F-AV1451 Brain Tau PET Imaging in Cognitively Normal Older Adults, Mild Cognitive Impairment, and Alzheimer's Disease Patients

Recent developments of tau Positron Emission Tomography (PET) allows assessment of regional neurofibrillary tangles (NFTs) deposition in human brain. Among the tau PET molecular probes, 18F-AV1451 is characterized by high selectivity for pathologic tau aggregates over amyloid plaques, limited non-specific binding in white and gray matter, and confined off-target binding. The objectives of the study are (1) to quantitatively characterize regional brain tau deposition measured by 18F-AV1451 PET in cognitively normal older adults (CN), mild cognitive impairment (MCI), and AD participants; (2) to evaluate the correlations between cerebrospinal fluid (CSF) biomarkers or Mini-Mental State Examination (MMSE) and 18F-AV1451 PET standardized uptake value ratio (SUVR); and (3) to evaluate the partial volume effects on 18F-AV1451 brain uptake.Methods: The study included total 115 participants (CN = 49, MCI = 58, and AD = 8) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed 18F-AV1451 PET images, structural MRIs, and demographic and clinical assessments were downloaded from the ADNI database. A reblurred Van Cittertiteration method was used for voxelwise partial volume correction (PVC) on PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. The parametric images of 18F-AV1451 SUVR relative to cerebellum were calculated. The ROI SUVR measurements from PVC and non-PVC SUVR images were compared. The correlation between ROI 18F-AV1451 SUVR and the measurements of MMSE, CSF total tau (t-tau), and phosphorylated tau (p-tau) were also assessed.Results:18F-AV1451 prominently specific binding was found in the amygdala, entorhinal cortex, parahippocampus, fusiform, posterior cingulate, temporal, parietal, and frontal brain regions. Most regional SUVRs showed significantly higher uptake of 18F-AV1451 in AD than MCI and CN participants. SUVRs of small regions like amygdala, entorhinal cortex and parahippocampus were statistically improved by PVC in all groups (p < 0.01). Although there was an increasing tendency of 18F-AV-1451 SUVRs in MCI group compared with CN group, no significant difference of 18F-AV1451 deposition was found between CN and MCI brains with or without PVC (p > 0.05). Declined MMSE score was observed with increasing 18F-AV1451 binding in amygdala, entorhinal cortex, parahippocampus, and fusiform. CSF p-tau was positively correlated with 18F-AV1451 deposition. PVC improved the results of 18F-AV-1451 tau deposition and correlation studies in small brain regions.Conclusion: The typical deposition of 18F-AV1451 tau PET imaging in AD brain was found in amygdala, entorhinal cortex, fusiform and parahippocampus, and these regions were strongly associated with cognitive impairment and CSF biomarkers. Although more deposition was observed in MCI group, the 18F-AV-1451 PET imaging could not differentiate the MCI patients from CN population. More tau deposition related to decreased MMSE score and increased level of CSF p-tau, especially in ROIs of amygdala, entorhinal cortex and parahippocampus. PVC did improve the results of tau deposition and correlation studies in small brain regions and suggest to be routinely used in 18F-AV1451 tau PET quantification