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ObjectivesFlorbetapir F 18 PET can image amyloid-β (Aβ) aggregates in the brains of living subjects. We prospectively evaluated the prognostic utility of detecting Aβ pathology using florbetapir PET in subjects at risk for progressive cognitive decline.MethodsA total of 151 subjects who previously participated in a multicenter florbetapir PET imaging study were recruited for longitudinal assessment. Subjects included 51 with recently diagnosed mild cognitive impairment (MCI), 69 cognitively normal controls (CN), and 31 with clinically diagnosed Alzheimer disease dementia (AD). PET images were visually scored as positive (Aβ+) or negative (Aβ-) for pathologic levels of β-amyloid aggregation, blind to diagnostic classification. Cerebral to cerebellar standardized uptake value ratios (SUVr) were determined from the baseline PET images. Subjects were followed for 18 months to evaluate changes in cognition and diagnostic status. Analysis of covariance and correlation analyses were conducted to evaluate the association between baseline PET amyloid status and subsequent cognitive decline.ResultsIn both MCI and CN, baseline Aβ+ scans were associated with greater clinical worsening on the Alzheimer's Disease Assessment Scale-Cognitive subscale (ADAS-Cog (p < 0.01) and Clinical Dementia Rating-sum of boxes (CDR-SB) (p < 0.02). In MCI Aβ+ scans were also associated with greater decline in memory, Digit Symbol Substitution (DSS), and Mini-Mental State Examination (MMSE) (p < 0.05). In MCI, higher baseline SUVr similarly correlated with greater subsequent decline on the ADAS-Cog (p < 0.01), CDR-SB (p < 0.03), a memory measure, DSS, and MMSE (p < 0.05). Aβ+ MCI tended to convert to AD dementia at a higher rate than Aβ- subjects (p < 0.10).ConclusionsFlorbetapir PET may help identify individuals at increased risk for progressive cognitive decline.

Objective:To investigate predictors of missing data in a longitudinal study of Alzheimer disease (AD).Methods:The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a clinic-based, multicenter, longitudinal study with blood, CSF, PET, and MRI scans repeatedly measured in 229 participants with normal cognition (NC), 397 with mild cognitive impairment (MCI), and 193 with mild AD during 2005–2007. We used univariate and multivariable logistic regression models to examine the associations between baseline demographic/clinical features and loss of biomarker follow-ups in ADNI.Results:CSF studies tended to recruit and retain patients with MCI with more AD-like features, including lower levels of baseline CSF Aβ42. Depression was the major predictor for MCI dropouts, while family history of AD kept more patients with AD enrolled in PET and MRI studies. Poor cognitive performance was associated with loss of follow-up in most biomarker studies, even among NC participants. The presence of vascular risk factors seemed more critical than cognitive function for predicting dropouts in AD.Conclusion:The missing data are not missing completely at random in ADNI and likely conditional on certain features in addition to cognitive function. Missing data predictors vary across biomarkers and even MCI and AD groups do not share the same missing data pattern. Understanding the missing data structure may help in the design of future longitudinal studies and clinical trials in AD.

Despite the availability of many treatment options, depressive disorders remain a global public health problem. Even in affluent nations, 70% of reported cases either do not receive the recommended level of treatment or do not get treated at all, and this percentage does not reflect cases of depression that go unreported due to lack of access to health care, stigma, or other reasons. In developing countries, the World Health Organization estimates that

Background The potential for machine learning to disrupt the medical profession is the subject of ongoing debate within biomedical informatics. Objective This study aimed to explore psychiatrists’ opinions about the potential impact innovations in artificial intelligence and machine learning on psychiatric practice Methods In Spring 2019, we conducted a web-based survey of 791 psychiatrists from 22 countries worldwide. The survey measured opinions about the likelihood future technology would fully replace physicians in performing ten key psychiatric tasks. This study involved qualitative descriptive analysis of written responses (“comments”) to three open-ended questions in the survey. Results Comments were classified into four major categories in relation to the impact of future technology on: (1) patient-psychiatrist interactions; (2) the quality of patient medical care; (3) the profession of psychiatry; and (4) health systems. Overwhelmingly, psychiatrists were skeptical that technology could replace human empathy. Many predicted that ‘man and machine’ would increasingly collaborate in undertaking clinical decisions, with mixed opinions about the benefits and harms of such an arrangement. Participants were optimistic that technology might improve efficiencies and access to care, and reduce costs. Ethical and regulatory considerations received limited attention. Conclusions This study presents timely information on psychiatrists’ views about the scope of artificial intelligence and machine learning on psychiatric practice. Psychiatrists expressed divergent views about the value and impact of future technology with worrying omissions about practice guidelines, and ethical and regulatory issues.

Poor health care-seeking behaviour, access to services and availability of service delivery have implications for the health of the community. This study explored the perceptions, practices and challenges related to maternal and neonatal care in the teagarden community in Bangladesh. The study also identified service gaps and problems prevalent in teagarden health facilities. A qualitative study was conducted in five teagardens in the Moulvibazar district of Bangladesh. Six focus group discussions (FGDs) were completed with individuals from the teagarden community, and twelve in-depth interviews (IDIs) were performed with health facility staff working in those teagarden facilities. Misconceptions and harmful traditional practices were found to exist among the families in the teagardens, restricting them from accessing quality health care. Pregnant women are not aware of antenatal care, and deliveries are being conducted at home by untrained birth attendants. Unhygienic and harmful postnatal practices are used. Teagarden health facilities are not well equipped or prepared to provide good care. Inequities exist within the teagarden communities, with unregistered workers having even poorer access to care. Improvement of the quality of maternal health care for this marginalised community is needed to progress maternal health.

Abstract PM2.5, or fine particulate matter, is a category of air pollutant consisting of particles with effective aerodynamic diameter equal to or less than 2.5 μm. These particles have been linked to human health impacts as well as regional haze, visibility, and climate change issues. Due to cost and space restrictions, the U.S. Environmental Protection Agency monitoring network remains spatially sparse. To increase the spatial resolution of monitoring, previous studies have used satellite data to estimate ground‐level PM concentrations, despite these estimates being associated with moderate to large uncertainties when relating a column measure of aerosol (aerosol optical depth) with surface measurements. To this end, we discuss a low‐cost air quality monitor (LCAQM) network deployed in California. In this study, we present an application of LCAQM and satellite data for quantifying the impact of wildfires in California during October 2017. The impacts of fires on PM2.5 concentration at varying temporal (hourly, daily, and weekly) and spatial (local to regional) scales have been evaluated. Comparison between low‐cost air quality sensors and reference‐grade air quality instruments shows expected performance with moderate to high uncertainties. The LCAQM measurements, in the absence of federal equivalent method data, were also found to be very useful in developing statistical models to convert aerosol optical depth into PM2.5 with performance of satellite‐derived PM2.5, similar to that obtained using the federal equivalent method data. This paper also highlights challenges associated with both LCAQM and satellite‐based PM2.5 measurements, which require further investigation and research.

Abstract Sex differences in Alzheimer’s disease (AD) biology and progression are not yet fully characterized. The goal of this study is to examine the effect of sex on cognitive progression in subjects with high likelihood of mild cognitive impairment (MCI) due to Alzheimer’s and followed up to 10 years in the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Cerebrospinal fluid total-tau and amyloid-beta (Aβ42) ratio values were used to sub-classify 559 MCI subjects (216 females, 343 males) as having “high” or “low” likelihood for MCI due to Alzheimer’s. Data were analyzed using mixed-effects models incorporating all follow-ups. The worsening from baseline in Alzheimer’s Disease Assessment Scale-Cognitive score (mean, SD) (9 ± 12) in subjects with high likelihood of MCI due to Alzheimer’s was markedly greater than that in subjects with low likelihood (1 ± 6, p

This paper describes the development and validation of a science teacher leadership instrument modeled on the seven domains of the Teacher Leader Model (TLM) Standards (The Teacher Leadership Exploratory Consortium, 2011). Instrument development was part of National Science Foundation--funded Mathematics and Science Partnership (MSP) program that aimed to develop science teacher leaders through the use of Project-Based Science (PBS) in the context of renewable energy. Ratings of professional development sessions presented by teacher leaders to their peers were analyzed to assess whether the instrument could be used to measure teacher leadership in this context. The resulting TLM Standards Instrument is presented as a valid instrument to observe the development and assessment of teacher leadership.

Abstract The heterogeneity of Alzheimer’s disease contributes to the high failure rate of prior clinical trials. We analyzed 5-year longitudinal outcomes and biomarker data from 562 subjects with mild cognitive impairment (MCI) from two national studies (ADNI) using a novel multilayer clustering algorithm. The algorithm identified homogenous clusters of MCI subjects with markedly different prognostic cognitive trajectories. A cluster of 240 rapid decliners had 2-fold greater atrophy and progressed to dementia at almost 5 times the rate of a cluster of 184 slow decliners. A classifier for identifying rapid decliners in one study showed high sensitivity and specificity in the second study. Characterizing subgroups of at risk subjects, with diverse prognostic outcomes, may provide novel mechanistic insights and facilitate clinical trials of drugs to delay the onset of AD.

Abstract Background Refugees and host nationals who accessed antiretroviral therapy (ART) in a remote refugee camp in Kakuma, Kenya (2011–2013) were compared on outcome measures that included viral suppression and adherence to ART. Methods This study used a repeated cross-sectional design (Round One and Round Two). All adults (≥18 years) receiving care from the refugee camp clinic and taking antiretroviral therapy (ART) for ≥30 days were invited to participate. Adherence was measured by self-report and monthly pharmacy refills. Whole blood was measured on dried blood spots. HIV-1 RNA was quantified and treatment failures were submitted for drug resistance testing. A remedial intervention was implemented in response to baseline testing. The primary outcome was viral load

Abstract Background To address family planning for crisis-affected communities, in 2011 and 2012, the United Nations High Commissioner for Refugees and the Women’s Refugee Commission undertook a multi-country assessment to document knowledge of family planning, beliefs and practices of refugees, and the state of service provision in the select refugee settings of Cox’s Bazar, Bangladesh; Ali Addeh, Djibouti; Amman, Jordan; Eastleigh, Kenya; Kuala Lumpur, Malaysia; and Nakivale, Uganda. Methods The studies employed mixed methods: a household survey, facility assessments, in-depth interviews, and focus group discussions. Results Findings on awareness and demand for family planning, availability, accessibility, and quality of services showed that adult women aged 20–29 years were significantly more likely to be aware, to have ever used, or are currently using a modern method as compared to adolescent girls aged 15–19 years. Facility assessments showed limited availability of certain methods, especially long-acting and permanent methods. Despite availability, in all sites, focus group discussion participants—especially adolescents—reported many accessibility-related barriers to using existing services, including distant service delivery points, cost of transport, lack of knowledge about different types of methods, misinformation and misconceptions, religious opposition, cultural factors, language barriers with providers, and provider biases. Conclusion Based on gaps, partners to the study developed short and long-term recommendations around improving service availability, accessibility, and quality. There remains a need to scale up support for refugees, particularly around adolescent access to family planning services.

Abstract Introduction The growing public threat of Alzheimer's disease (AD) has raised the urgency to quantify the degree of cognitive decline during the conversion process of mild cognitive impairment (MCI) to AD and its underlying genetic pathway. The aim of this article was to test genetic common variants associated with accelerated cognitive decline after the conversion of MCI to AD. Methods In 583 subjects with MCI enrolled in the Alzheimer's Disease Neuroimaging Initiative (ADNI; ADNI‐1, ADNI‐Go, and ADNI‐2), 245 MCI participants converted to AD at follow‐up. We tested the interaction effects between individual single‐nucleotide polymorphisms and AD diagnosis trajectory on the longitudinal Alzheimer's Disease Assessment Scale‐Cognition scores. Results Our findings reveal six genes, including BDH1, ST6GAL1, RAB20, PDS5B, ADARB2, and SPSB1, which are directly or indirectly related to MCI conversion to AD. Discussion This genome‐wide association study sheds light on a genetic mechanism of longitudinal cognitive changes during the transition period from MCI to AD.

Background: Periodontitis and atherosclerosis represent a chronic inflammatory process. The incidence of periodontitis in cardiac patients with atherosclerosis is a well-established fact. The role of viruses in the etiopathogenesis of both has been proposed. Aim: The aim of the study was to evaluate the prevalence of Torque Teno virus (TTV), Epstein–Barr virus (EBV), and cytomegalovirus (CMV) in cardiac patients with atherosclerosis and coexisting chronic periodontitis (CP). Materials and Methods: Thirty patients (17 males and 13 females) with atherosclerotic plaques and coexisting periodontitis were recruited for this cross-sectional study. Viral DNA was extracted from the subgingival and atheromatous plaque. The presence of CMV, EBV, and TTV in the plaque samples was identified using polymerase chain reaction. The collected data were statistically analyzed for the prevalence of the viruses and Chi-squared test was performed to find out its association with atheroma and CP. Results: The prevalence of CMV, EBV, and TTV in atheromatous plaque was 63.3%, 56.7%, and 46.7%, respectively, as compared to rates of 80%, 63.3%, and 53.3% in subgingival plaque. Results also indicated no significant association of CMV, EBV, and TTV in both samples (P = 0.08, 0.346, and 0.261, respectively). Conclusions: There was no significant association of CMV, EBV, and TTV between subgingival and atheromatous plaque. The prevalence of CMV, EBV, and TTV was high in atheromatous plaque. TTV was isolated from more than 50% of participants in atheromatous plaque, which is a significant finding.

Background. Maximum sealing ability or adhesion of endodontic sealers can be achieved after effective removal of the smear layer. Endodontic irrigants assist in adequate removal of the smear layer, improving the retention mechanism. The aim of this study was to evaluate the effect of two different root canal irrigation solutions (5.25% NaOCl followed by 17% EDTA and QMix) on the apical sealing ability of two different root canal sealers (MTA Fillapex and Adseal). Methods. Forty-six single-canal teeth were divided into 4 experimental groups of 10 teeth each and a positive and negative group of 3 teeth each. The root canals were prepared using step-back technique. The teeth in groups 1 and 2 were irrigated with 5.25% NaOCl followed by 17% EDTA and the teeth in groups 3 and 4 were irrigated with QMix. Finally all the teeth were flushed with sterile saline and dried using paper points. Obturation was accomplished by gutta-percha using lateral condensation technique. MTA Fillapex sealer was used in groups 1 and 3 whereas Adseal was used in groups 2 and 4. Dye penetration method was used to evaluate apical leakage. Data were analyzed with Kruskal-Wallis and Mann-Whitney U tests using SPSS 14. Statistical significance was set at P < 0.05. Results. Group 3 showed maximum amount of apical leakage (3.7±0.3 mm) whereas group 2 exhibited the least amount of apical leakage (2.1 ± 0.4 mm) among all the experimental groups. Significant differences were found in the amount of apical leakage between all the groups (P = 0.00001). Conclusion. Within the limitations of this study, 5.25% sodium hypochlorite followed by 17% EDTA and Adseal resulted in the best apical seal.

Alzheimer's disease (AD), including its mild cognitive impairment (MCI) phase that may or may not progress into the AD, is the most ordinary form of dementia. It is extremely important to correctly identify patients during the MCI stage because this is the phase where AD may or may not develop. Thus, it is crucial to predict outcomes during this phase. Thus far, many researchers have worked on only using a single modality of a biomarker for the diagnosis of AD or MCI. Although recent studies show that a combination of one or more different biomarkers may provide complementary information for the diagnosis, it also increases the classification accuracy distinguishing between different groups. In this paper, we propose a novel machine learning-based framework to discriminate subjects with AD or MCI utilizing a combination of four different biomarkers: fluorodeoxyglucose positron emission tomography (FDG-PET), structural magnetic resonance imaging (sMRI), cerebrospinal fluid (CSF) protein levels, and Apolipoprotein-E (APOE) genotype. The Alzheimer's Disease Neuroimaging Initiative (ADNI) baseline dataset was used in this study. In total, there were 158 subjects for whom all four modalities of biomarker were available. Of the 158 subjects, 38 subjects were in the AD group, 82 subjects were in MCI groups (including 46 in MCIc [MCI converted; conversion to AD within 24 months of time period], and 36 in MCIs [MCI stable; no conversion to AD within 24 months of time period]), and the remaining 38 subjects were in the healthy control (HC) group. For each image, we extracted 246 regions of interest (as features) using the Brainnetome template image and NiftyReg toolbox, and later we combined these features with three CSF and two APOE genotype features obtained from the ADNI website for each subject using early fusion technique. Here, a different kernel-based multiclass support vector machine (SVM) classifier with a grid-search method was applied. Before passing the obtained features to the classifier, we have used truncated singular value decomposition (Truncated SVD) dimensionality reduction technique to reduce high dimensional features into a lower-dimensional feature. As a result, our combined method achieved an area under the receiver operating characteristic (AU-ROC) curve of 98.33, 93.59, 96.83, 94.64, 96.43, and 95.24% for AD vs. HC, MCIs vs. MCIc, AD vs. MCIs, AD vs. MCIc, HC vs. MCIc, and HC vs. MCIs subjects which are high relative to single modality results and other state-of-the-art approaches. Moreover, combined multimodal methods have improved the classification performance over the unimodal classification.

Introduction Mild cognitive impairment (MCI) is common in older adults and represents a high-risk group for progression to Alzheimer’s disease (AD). Medication trials in MCI have generally failed, but new discoveries with brain plasticity in ageing have led to the study of cognitive training as a potential treatment to improve cognitive abilities. Computerised cognitive training (CCT) involves computerised cognitive exercises that target specific cognitive abilities and neural networks to potentially improve cognitive functioning through neuroplasticity.Methods and analysis In a two-site study (New York State Psychiatric Institute/Columbia University Medical Center and Duke University Medical Center), we will randomise 100 patients with MCI (Wechsler Memory Scale-III Logical Memory II score 0–11; Folstein Mini Mental State Examination ≥23) to home-based CCT (suite of exercises: memory, matching, spatial recognition, processing speed) or a home-based active control condition (computerised crossword puzzle training (CPT)) with 12 weeks of intensive training followed by regular booster sessions up to 78 weeks. All patients will receive standard neuropsychological and functional assessments in clinic as well as structural/functional brain MRI scans at study entry and endpoint. We will test if CCT, versus CPT, leads to improved cognitive functioning, transfers to functional ability and tasks of everyday life and impacts hippocampal volume changes and changes in the default mode network of the brain measured by resting-state functional MRI.Ethics and dissemination The study will be conducted following ethics approval and written informed consent will be obtained from all subjects. Study results will be disseminated via publication, clinicaltrials.gov, media and conference presentations. This will be the first controlled long-term trial to evaluate the effects of home-based CCT versus computerised CPT on cognitive abilities and functional measures and neural outcomes as determined by MRI indices in patients with MCI. Positive results from trial may support further development of home-based CCT.Trial registration number ClinicalTrials.gov identifier (NCT03205709).

Mild cognitive impairment (MCI) is a transitional state between the cognitive changes in normal aging and Alzheimer’s disease (AD), which induces abnormalities in specific brain regions. Previous studies showed that paired helical filaments Tau (PHF-Tau) protein is a potential pathogenic protein which may cause abnormal brain function and structure in MCI and AD patients. However, the understanding of the PHF-Tau protein network in MCI patients is limited. In this study, 225 subjects with PHF-Tau Positron Emission Tomography (PET) images were divided into four groups based on whether they carried Apolipoprotein E ε4 (APOE 4) or abnormal cerebrospinal fluid Total-Tau (CSF T-Tau). They are two important pathogenic factors that might cause cognitive function impairment. The four groups were: individuals harboring CSF T-Tau pathology but no APOE 4 (APOE 4−T+); APOE 4 carriers with normal CSF T-Tau (APOE 4+T−); APOE 4 carriers with abnormal CSF T-Tau (APOE 4+T+); and APOE 4 noncarriers with abnormal CSF T-Tau (APOE 4−T−). We explored the topological organization of PHF-Tau networks in these four groups and calculated five kinds of network properties: clustering coefficient, shortest path length, Q value of modularity, nodal centrality and degree. Our findings showed that compared with APOE 4−T− group, the other three groups showed different alterations in the clustering coefficient, shortest path length, Q value of modularity, nodal centrality and degree. Simultaneously, voxel-level analysis was conducted and the results showed that compared with APOE 4−T− group, the other three groups were found increased PHF-Tau distribution in some brain regions. For APOE 4+T+ group, positive correlation was found between the value of PHF-Tau distribution in altered regions and Functional Assessment Questionnaire (FAQ) score. Our results indicated that the effects of APOE 4 and abnormal CSF T-Tau may induce abnormalities of PHF-Tau protein and APOE 4 has a greater impact on PHF-Tau than abnormal CSF T-Tau. Our results may be particularly helpful in uncovering the pathophysiology underlying the cognitive dysfunction in MCI patients.

BackgroundNon-invasive brain stimulation (NIBS) has been widely used to treat mild cognitive impairment (MCI). However, there exists no consensus on the best stimulation sites.ObjectiveTo explore potential stimulation locations for NIBS treatment in patients with MCI, combining meta- and resting state functional connectivity (rsFC) analyses.MethodsThe meta-analysis was conducted to identify brain regions associated with MCI. Regions of interest (ROIs) were extracted based on this meta-analysis. The rsFC analysis was applied to 45 MCI patients to determine brain surface regions that are functionally connected with the above ROIs.ResultsWe found that the dorsolateral prefrontal cortex (DLPFC) and inferior frontal gyrus (IFG) were the overlapping brain regions between our results and those of previous studies. In addition, we recommend that the temporoparietal junction (including the angular gyrus), which was found in both the meta- and rsFC analysis, should be considered in NIBS treatment of MCI. Furthermore, the bilateral orbital prefrontal gyrus, inferior temporal gyrus, medial superior frontal gyrus, and right inferior occipital gyrus may be potential brain stimulation sites for NIBS treatment of MCI.ConclusionOur results provide several potential sites for NIBS, such as the DLFPC and IFG, and may shed light on the locations of NIBS sites in the treatment of patients with MCI.

Sport participation is an important part of the development of children and adolescents in the United States. Due to the popularity of sport-related films, coaches, athletic trainers, and parents have used these films to both educate and motivate pediatric athletes. The objective of this study was to develop a discussion guide template based on common positive and negative themes depicted in sport-related films, and demonstrate the application of this discussion guide template to a select number of sport-related films released from 2014 to 2018. A discussion guide template (“SPORTS ARE FUN”) was developed by the co-investigators, reflecting common themes of “ S portsmanship, P articipation for All, O bstacles, R elationships, T eamwork, S etting Realistic Goals, A cademics, R esponsibility, E xercise/Nutrition/Rest/Drugs/Performance Enhancing Drugs, F un, U nrelenting Spirit, and “ N o Pain, No Gain.” The authors hope that pediatric health care providers, athletic coaches/staff, and parents can utilize this discussion guide template in the education and development of children and adolescents who participate in sports.

Collecting multiple modalities of neuroimaging data on the same subject is increasingly becoming the norm in clinical practice and research. Fusing multiple modalities to find related patterns is a challenge in neuroimaging analysis. Canonical correlation analysis (CCA) is commonly used as a symmetric data fusion technique to find related patterns among multiple modalities. In CCA-based data fusion, principal component analysis (PCA) is frequently applied as a preprocessing step to reduce data dimension followed by CCA on dimension-reduced data. PCA, however, does not differentiate between informative voxels from non-informative voxels in the dimension reduction step. Sparse PCA (sPCA) extends traditional PCA by adding sparse regularization that assigns zero weights to non-informative voxels. In this study, sPCA is incorporated into CCA-based fusion analysis and applied on neuroimaging data. A cross-validation method is developed and validated to optimize the parameters in sPCA. Different simulations are carried out to evaluate the improvement by introducing sparsity constraint to PCA. Four fusion methods including sPCA+CCA, PCA+CCA, parallel ICA and sparse CCA were applied on structural and functional magnetic resonance imaging data of mild cognitive impairment subjects and normal controls. Our results indicate that sPCA significantly can reduce the impact of non-informative voxels and lead to improved statistical power in uncovering disease-related patterns by a fusion analysis.

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.

IntroductionPrevious studies evaluating the association between clinically diagnosed Alzheimer's disease (AD) and age-related macular degeneration (AMD) have generated conflicting results. This study is the first to assess whether AMD prevalence is higher in AD patients than non-AD controls by using histopathology to definitively diagnose AD.MethodsThis was a retrospective case-control study utilizing diagnostic information extracted from autopsy reports of patients age 75 and above, including 115 with a neuropathological diagnosis of AD and 57 age-matched normal controls.ResultsThe rate of AMD was not significantly higher in AD cases (53.0%) than in controls (59.6%) (z = 0.820, p = 0.794). AMD severity as determined by Sarks score was similar between AD patients and controls (χ2 = 2.96, p = 0.706). There was also no significant association between Braak stage of AD severity and AMD (χ2 = 4.55, p = 0.602).DiscussionNo significant effect of AD diagnosis or pathologic severity on AMD comorbidity was found, suggesting that any shared mechanisms between AMD and AD may be nondeterministic.

School closures during pandemics raise important concerns for children and adolescents. Our aim is synthesizing available data on the impact of school closure during the coronavirus disease 2019 (COVID-19) pandemic on child and adolescent health globally. We conducted a rapid systematic review by searching PubMed, Embase, and Google Scholar for any study published between January and September 2020. We included a total of ten primary studies. COVID-19-related school closure was associated with a significant decline in the number of hospital admissions and pediatric emergency department visits. However, a number of children and adolescents lost access to school-based healthcare services, special services for children with disabilities, and nutrition programs. A greater risk of widening educational disparities due to lack of support and resources for remote learning were also reported among poorer families and children with disabilities. School closure also contributed to increased anxiety and loneliness in young people and child stress, sadness, frustration, indiscipline, and hyperactivity. The longer the duration of school closure and reduction of daily physical activity, the higher was the predicted increase of Body Mass Index and childhood obesity prevalence. There is a need to identify children and adolescents at higher risk of learning and mental health impairments and support them during school closures.

Objective: To directly compare the effect of incident age 68+ traumatic brain injury (TBI) on the risk of diagnosis of clinical Alzheimer's disease (AD) in the general population of older adults, and between male veterans and nonveterans; to assess how this effect changes with time since TBI. Setting and Participants: Community-dwelling traditional Medicare beneficiaries 68 years or older from the Health and Retirement Study (HRS). Design: Fine-Gray models combined with inverse-probability weighting were used to identify associations between incident TBI, post-TBI duration, and TBI treatment intensity, with a diagnosis of clinical AD dementia. The study included 16 829 older adults followed over the 1991-2015 period. For analyses of veteran-specific risks, 4281 veteran males and 3093 nonveteran males were identified. Analysis of veteran females was unfeasible due to the age structure of the population. Information on occurrence(s) of TBI, and onset of AD and risk-related comorbidities was constructed from individual-level HRS-linked Medicare claim records while demographic and socioeconomic risk factors were based on the survey data. Results: Later-life TBI was strongly associated with increased clinical AD risk in the full sample (pseudo-hazard ratio [HR]: 3.22; 95% confidence interval [CI]: 2.57-4.05) and in veteran/nonveteran males (HR: 5.31; CI: 3.42-7.94), especially those requiring high-intensity/duration care (HR: 1.58; CI: 1.29-1.91). Effect magnitude decreased with time following TBI (HR: 0.72: CI: 0.68-0.80). Conclusion: Later-life TBI was strongly associated with increased AD risk, especially in those requiring high-intensity/duration care. Effect magnitude decreased with time following TBI. Univariate analysis showed no differences in AD risk between veterans and nonveterans, while the protective effect associated with veteran status in Fine-Gray models was largely due to differences in demographics, socioeconomics, and morbidity. Future longitudinal studies incorporating diagnostic procedures and documentation quantifying lifetime TBI events are necessary to uncover pathophysiological mediating and/or moderating mechanisms between TBI and AD. [ABSTRACT FROM AUTHOR]

Machined surface quality and integrity affect the corrosion performance of AZ31 magnesium composites. These novel materials are preferred for temporary orthopedic and vascular implants. In this paper, the drilling performance of AZ31-magnesium reinforced with hollow alumina microsphere syntactic foam under LN2 cryogenic, dry, and Almag® Oil is presented. Cutting tests were conducted using TiAlN physical vapor deposition (PVD) coated multilayer carbide and K10 uncoated carbide twist drills. AZ31 magnesium matrices were reinforced with hollow alumina ceramic microspheres with varying volume fractions (5%, 10%, 15%) and average bubble sizes. Experimental results showed that the drilling thrust forces increased by 250% with increasing feed rate (0.05 to 0.6 mm/tooth) and 46% with the increasing volume fraction of alumina microspheres (5% to 15%). Cryogenic machining generated 45% higher thrust forces compared to dry and wet machining. The higher the volume fraction and the finer the average size of hollow microspheres, the higher were the thrust forces. Cryogenic machining (0.42 µm) produced a 75% improvement in surface roughness (Ra) values compared to wet machining (1.84 µm) with minimal subsurface machining-induced defects. Surface quality deteriorated by 129% with an increasing volume fraction of alumina microspheres (0.61 µm to 1.4 µm). Burr height reduction of 53% was achieved with cryogenic machining (60 µm) compared to dry machining (130 µm). Overall, compared to dry and wet machining methods, cryogenic drilling can be employed for the machining of AZ31 magnesium syntactic foams to achieve good surface quality and integrity.

Abstract Virus‐induced gene silencing (VIGS) is an important forward and reverse genetics method for the study of gene function in many plant species, especially Nicotiana benthamiana. However, despite the widespread use of VIGS, a searchable database compiling the phenotypes observed with this method is lacking. Such a database would allow researchers to know the phenotype associated with the silencing of a large number of individual genes without experimentation. We have developed a VIGS phenomics and functional genomics database (VPGD) that has DNA sequence information derived from over 4,000 N. benthamiana VIGS clones along with the associated silencing phenotype for approximately 1,300 genes. The VPGD has a built‐in BLAST search feature that provides silencing phenotype information of specific genes. In addition, a keyword‐based search function could be used to find a specific phenotype of interest with the corresponding gene, including its Gene Ontology descriptions. Query gene sequences from other plant species that have not been used for VIGS can also be searched for their homologs and silencing phenotype in N. benthamiana. VPGD is useful for identifying gene function not only in N. benthamiana but also in related Solanaceae plants such as tomato and potato. The database is accessible at http://vigs.noble.org.

Background: Prompt and efficient identification, referral of pregnancy related complications and emergencies are key factors to the reduction of maternal and newborn morbidity and mortality. As a response to this critical need, a midwifery led continuum of reproductive health care was introduced in five teagardens in the Sylhet division, Bangladesh during 2016. Within this intervention, professional midwives provided reproductive healthcare to pregnant teagarden women in the community. This study evaluates the effect of the referral of pregnancy related complications. Methods: A qualitative case study design by reviewing records retrospectively was used to explore the effect of deploying midwives on referrals of pregnancy related complications from the selected teagardens to the referral health facilities in Moulvibazar district of the Sylhet division during 2016. In depth analyses was also performed on 15 randomly selected cases to understand the facts behind the referral. Results: Out of a total population of 450 pregnant women identified by the midwives, 72 complicated mothers were referred from the five teagardens to the facilities. 76.4% of mothers were referred to conduct delivery at facilities, and 31.1% of them were referred with the complication of prolonged labour. Other major complications were pre-eclampsia (17.8%), retention of the placenta with post-partum hemorrhage (11.1%) and premature rupture of the membrane (8.9%). About 60% of complicated mothers were referred to the primary health care centre, and among them 14% of mothers were delivered by caesarean section. 94% deliveries resulted in livebirths and only 6% were stillbirths. Conclusions: This study reveals that early detection of pregnancy complications by skilled professionals and timely referral to a facility is beneficial in saving the majority of baby’s as well as mother’s lives in resource-poor teagardens with a considerable access barrier to health facilities.