Prevalence of preterm, low birthweight, and small for gestational age delivery after breast cancer diagnosis: a population-based study

Abstract Background Black-white disparities in breast cancer incidence rates and birth outcomes raise concerns about potential disparities in the reproductive health of premenopausal breast cancer survivors. We examined the prevalence of preterm birth (PTB), low birthweight (LBW), and small for gestational age (SGA) by breast cancer history and effect modification by race. Methods We analyzed linked North Carolina birth records and Central Cancer Registry files from 1990 to 2009 (n = 2,325,229). We used multivariable negative log-binomial regression to calculate prevalence ratios (PRs) and 95% confidence intervals (CIs) for the association between breast cancer history and PTB, LBW, and SGA. Results Of 1,912,269 eligible births, 512 births were to mothers with a previous breast cancer diagnosis history. Average age at breast cancer diagnosis was 31.8 years (SD = 4.7). Mean time from diagnosis to delivery was 3.3 years (SD = 2.8). After multivariable adjustment, the PR was 1.67 (95% CI, 1.42–1.97) for PTB, 1.50 (95% CI, 1.23–1.84) for LBW, and 1.30 (95% CI, 1.05–1.61) for SGA comparing women with a breast cancer history to the general population. Among black mothers, the PRs associated with breast cancer history for PTB, LBW, and SGA were 1.31 (95% CI, 1.00–1.72), 1.49 (95% CI, 1.14–1.94), and 1.44 (95% CI, 1.11–1.87), respectively. The corresponding PRs among white mothers were 2.06 (95% CI, 1.67–2.54), 1.53 (95% CI, 1.12–2.08), and 1.10 (95% CI, 0.77–1.58), respectively. The interaction between breast cancer history and race was statistically significant for associations with PTB, but not for LBW or SGA. Conclusions In our data, women with a breast cancer history were at higher risk of delivering a PTB, LBW, or SGA infant, especially if they received chemotherapy or gave birth within 2 years of their breast cancer diagnosis date

MedFTs’ Role in the Recruitment and Retention of a Diverse Physician Population: A Conceptual Model

Recruitment and retention of a diverse physician population across stages of medical education is essential for the success of the healthcare system. MedFTs have a unique role to play in advocacy and intervention related to the recruitment and retention of these physicians at all stages of their education and career. As MedFTs expand their influence in healthcare systems, they must ground into their fundamental theories, like systems theory and the Four World View, all while advancing in their professional competencies to attune their skills and those whom they are entrusted in training. The conceptual model, MedFTs’ Role in the Recruitment and Retention of a Diverse Physician Population, provides a framework for MedFTs to use their influence to enact change related to diversity and equity in the healthcare system. In addition, the model provides avenues for intervention and advocacy on the part of the MedFT related to each of the four worlds and their specific role(s) in the health care

Community-Guided Focus Group Analysis to Examine Cancer Disparities

Accountability for Cancer Care through Undoing Racism and Equity (ACCURE) is a systems-change intervention addressing disparities in treatment initiation and completion and outcomes for early stage Black and White breast and lung cancer patients. Using a community-based participatory research approach, ACCURE is guided by a diverse partnership involving academic researchers, a non-profit community-based organization, its affiliated broader-based community coalition, and providers and staff from two cancer centers

Expanding the Reach of an Evidence-Based, System-Level, Racial Equity Intervention: Translating ACCURE to the Maternal Healthcare and Education Systems

The abundance of literature documenting the impact of racism on health disparities requires additional theoretical, statistical, and conceptual contributions to illustrate how anti-racist interventions can be an important strategy to reduce racial inequities and improve population health. Accountability for Cancer Care through Undoing Racism and Equity (ACCURE) was an NIH-funded intervention that utilized an antiracism lens and community-based participatory research (CBPR) approaches to address Black-White disparities in cancer treatment completion. ACCURE emphasized change at the institutional level of healthcare systems through two primary principles of antiracism organizing: transparency and accountability. ACCURE was successful in eliminating the treatment completion disparity and improved completion rates for breast and lung cancer for all participants in the study. The structural nature of the ACCURE intervention creates an opportunity for applications in other health outcomes, as well as within educational institutions that represent social determinants of health. We are focusing on the maternal healthcare and K-12 education systems in particular because of the dire racial inequities faced by pregnant people and school-aged children. In this article, we hypothesize cross-systems translation of a system-level intervention exploring how key characteristics of ACCURE can be implemented in different institutions. Using core elements of ACCURE (i.e., community partners, milestone tracker, navigator, champion, and racial equity training), we present a framework that extends ACCURE's approach to the maternal healthcare and K-12 school systems. This framework provides practical, evidence-based antiracism strategies that can be applied and evaluated in other systems to address widespread structural inequities

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

The impact of PICALM genetic variations on reserve capacity of posterior cingulate in AD continuum

Phosphatidylinositolbinding clathrin assembly protein (PICALM) gene is one novel genetic player associated with late-onset Alzheimer’s disease (LOAD), based on recent genome wide association studies (GWAS). However, how it affects AD occurrence is still unknown. Brain reserve hypothesis highlights the tolerant capacities of brain as a passive means to fight against neurodegenerations. Here, we took the baseline volume and/or thickness of LOAD-associated brain regions as proxies of brain reserve capacities and investigated whether PICALM genetic variations can influence the baseline reserve capacities and the longitudinal atrophy rate of these specific regions using data from Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset. In mixed population, we found that brain region significantly affected by PICALM genetic variations was majorly restricted to posterior cingulate. In sub-population analysis, we found that one PICALM variation (C allele of rs642949) was associated with larger baseline thickness of posterior cingulate in health. We found seven variations in health and two variations (rs543293 and rs592297) in individuals with mild cognitive impairment were associated with slower atrophy rate of posterior cingulate. Our study provided preliminary evidences supporting that PICALM variations render protections by facilitating reserve capacities of posterior cingulate in non-demented elderly

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

Schizophrenia-associated somatic copy-number variants from 12,834 cases reveal recurrent NRXN1 and ABCB11 disruptions

While germline copy-number variants (CNVs) contribute to schizophrenia (SCZ) risk, the contribution of somatic CNVs (sCNVs)—present in some but not all cells—remains unknown. We identified sCNVs using blood-derived genotype arrays from 12,834 SCZ cases and 11,648 controls, filtering sCNVs at loci recurrently mutated in clonal blood disorders. Likely early-developmental sCNVs were more common in cases (0.91%) than controls (0.51%, p = 2.68e−4), with recurrent somatic deletions of exons 1–5 of the NRXN1 gene in five SCZ cases. Hi-C maps revealed ectopic, allele-specific loops forming between a potential cryptic promoter and non-coding cis-regulatory elements upon 5′ deletions in NRXN1. We also observed recurrent intragenic deletions of ABCB11, encoding a transporter implicated in anti-psychotic response, in five treatment-resistant SCZ cases and showed that ABCB11 is specifically enriched in neurons forming mesocortical and mesolimbic dopaminergic projections. Our results indicate potential roles of sCNVs in SCZ risk

Conversion Discriminative Analysis on Mild Cognitive Impairment Using Multiple Cortical Features from MR Images

Neuroimaging measurements derived from magnetic resonance imaging provide important information required for detecting changes related to the progression of mild cognitive impairment (MCI). Cortical features and changes play a crucial role in revealing unique anatomical patterns of brain regions, and further differentiate MCI patients from normal states. Four cortical features, namely, gray matter volume, cortical thickness, surface area, and mean curvature, were explored for discriminative analysis among three groups including the stable MCI (sMCI), the converted MCI (cMCI), and the normal control (NC) groups. In this study, 158 subjects (72 NC, 46 sMCI, and 40 cMCI) were selected from the Alzheimer's Disease Neuroimaging Initiative. A sparse-constrained regression model based on the l2-1-norm was introduced to reduce the feature dimensionality and retrieve essential features for the discrimination of the three groups by using a support vector machine (SVM). An optimized strategy of feature addition based on the weight of each feature was adopted for the SVM classifier in order to achieve the best classification performance. The baseline cortical features combined with the longitudinal measurements for 2 years of follow-up data yielded prominent classification results. In particular, the cortical thickness produced a classification with 98.84% accuracy, 97.5% sensitivity, and 100% specificity for the sMCI–cMCI comparison; 92.37% accuracy, 84.78% sensitivity, and 97.22% specificity for the cMCI–NC comparison; and 93.75% accuracy, 92.5% sensitivity, and 94.44% specificity for the sMCI–NC comparison. The best performances obtained by the SVM classifier using the essential features were 5–40% more than those using all of the retained features. The feasibility of the cortical features for the recognition of anatomical patterns was certified; thus, the proposed method has the potential to improve the clinical diagnosis of sub-types of MCI and predict the risk of its conversion to Alzheimer's disease

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