Teaching Apparel Pattern Completion through Instructional Scaffolding

Similar to the scaffolding used in construction to support workers as they work on a specific task, instructional scaffolds are temporary support structures faculty put in place to assist students accomplish new tasks and concepts they could not typically achieve on their own

Patterns of Amygdala Region Pathology in LATE-NC: Subtypes that Differ with Regard to TDP-43 Histopathology, Genetic Risk Factors, and Comorbid Pathologies

Transactive response (TAR) DNA-binding protein 43 kDa (TDP-43) pathology is a hallmark of limbic-predominant agerelated TDP-43 encephalopathy (LATE). The amygdala is afected early in the evolution of LATE neuropathologic change (LATE-NC), and heterogeneity of LATE-NC in amygdala has previously been observed. However, much remains to be learned about how LATE-NC originates and progresses in the brain. To address this, we assessed TDP-43 and other pathologies in the amygdala region of 184 autopsied subjects (median age=85 years), blinded to clinical diagnoses, other neuropathologic diagnoses, and risk genotype information. As previously described, LATE-NC was associated with older age at death, cognitive impairment, and the TMEM106B risk allele. Pathologically, LATE-NC was associated with comorbid hippocampal sclerosis (HS), myelin loss, and vascular disease in white matter (WM). Unbiased hierarchical clustering of TDP-43 inclusion morphologies revealed discernable subtypes of LATE-NC with distinct clinical, genetic, and pathologic associations. The most common patterns were: Pattern 1, with lamina II TDP-43+processes and preinclusion pathology in cortices of the amygdala region, and frequent LATE-NC Stage 3 with HS; Pattern 2, previously described as type-β, with neurofbrillary tangle-like TDP-43 neuronal cytoplasmic inclusions (NCIs), high Alzheimer’s disease neuropathologic change (ADNC), frequent APOE ε4, and usually LATE-NC Stage 2; Pattern 3, with round NCIs and thick neurites in amygdala, younger age at death, and often comorbid Lewy body disease; and Pattern 4 (the most common pattern), with tortuous TDP43 processes in subpial and WM regions, low ADNC, rare HS, and lower dementia probability. TDP-43 pathology with features of patterns 1 and 2 were often comorbid in the same brains. Early and mild TDP-43 pathology was often best described to be localized in the “amygdala region” rather than the amygdala proper. There were also important shared attributes across patterns. For example, all four patterns were associated with the TMEM106B risk allele. Each pattern also demonstrated the potential to progress to higher LATE-NC stages with confuent anatomical and pathological patterns, and to contribute to dementia. Although LATE-NC showed distinct patterns of initiation in amygdala region, there was also apparent shared genetic risk and convergent pathways of clinico-pathological evolution

A Collaborative Clearinghouse for Data Management Training and Education Resources

Objective: The main objectives of this breakout session are for the Data Management Training (DMT) Clearinghouse team to: 1) introduce the Clearinghouse and its current design and implementation, 2) solicit submissions to its learning resource inventory, and 3) collect feedback upon its web interface and future development. Features of the Clearinghouse that will be demonstrated include how to search and browse its inventory as well as submit a learning resource to the Clearinghouse using the LRMI (Learning Resource Metadata Initiative) metadata format. The team will also share the roadmap for the Clearinghouse’s upcoming features. In order to provide feedback regarding the Clearinghouse’s usability, the team will invite the session attendees to test the Clearinghouse’s services and will encourage comments to guide its future development. Setting/Participants/Resources: Since the DMT Clearinghouse is entirely accessible via the web, in order to demonstrate the Clearinghouse successfully, a reliable (and preferably free of charge) internet connection, and an overhead projecting capability will need to be available to the presenter. It would also be very useful for the attendees of the session to have access to the same internet connection, so that if they desire, the attendees can follow along with the steps of the demonstration, and contribute to the Clearinghouse inventory. The main presenter will plan to bring her own laptop with built-in standard HDMI and USB ports. As a result, it will be helpful if a HDMI or USB cable could also be provided for the presenter to connect her laptop to the projecting equipment. Method: Many research organizations, government agencies, and academic institutions have been developing excellent learning resources in order to support and meet the needs for data management training. However, these learning resources are often hosted on various websites and spread across various scientific domains. Consequently, these resources can be difficult to locate, especially by those who are not already familiar with the creators/authors. This is a barrier to the use and reuse of these resources, and can have significant impact on the promotion and propagation of best practices for data management. To address this need within the Earth sciences, the U.S. Geological Survey’s (USGS) Community for Data Integration (CDI), the Federation of Earth Science Information Partners (ESIP), and the Data Observation Network for Earth (DataONE) have collaborated to create a web-based Clearinghouse1 for collecting data management learning resources that are focused on the Earth sciences. The initial seed funding for the effort was provided by a grant received from the USGS CDI earlier in 2016, and ESIP’s Drupal site provided the hosting infrastructure for the Clearinghouse. Members from the USGS, DataONE, ESIP’s Data Stewardship Committee and its Data Management Training Working Group, Knowledge Motifs LLC, as well as Blue Dot Lab met regularly between April and October, 2016 in order to discuss, create, and implement the content structure and infrastructure components necessary to build the current revision of the Clearinghouse. 1. http://dmtclearinghouse.esipfed.org Results: As a registry of information about the educational resources on topics related to research data management (initially focused on Earth sciences), the Clearinghouse serves as a centralized location for searching or browsing an inventory of these learning resources. Currently, the Clearinghouse offers search and browse functionality that is open to all, and submission of information about educational resources by login with a free ESIP account. To assist with discoverability, the learning resources are described using Learning Resource Metadata Initiative (LRMI) schema. Additionally, the resources may be associated with the steps of data and research life cycles, such as the USGS CDI’s Science Support Framework2 and DataONE’s Data Life Cycle3. Leveraging the team’s collective experience in creating, presenting and distributing data management learning resources, the Clearinghouse included the learning resources from USGS, ESIP, and DataONE as its initial inventory, but is expanding to resources from NASA and others. Crowdsourcing is currently the main mechanism for sustaining the Clearinghouse. Going forward, in addition to the built-in workflow to allow anyone from the public to submit descriptive information about the data management learning resources that s/he wishes to share, future capabilities will be added to enable contributions to review, edit, and rank the submissions, as desired. 2. https://my.usgs.gov/confluence/display/cdi/CDI+Science+Support+Framework3. https://www.dataone.org/data-life-cycle Discussion/Conclusion: The DMT Clearinghouse team was successful in completing the initial development phase as scheduled for the first six months of its funding, including some informal usability testing of the interface. The team aims to continue to develop and enhance the Clearinghouse’s capabilities, including the evaluation of its usability, through collaboration with additional communities, and if feasible, adding the capability for bulk-loading of learning resources. Being able to present the Clearinghouse at the eScience Symposium would not only allow those who are involved with or would like to learn about data management to leverage the Clearinghouse’s resources, but also connect those who would like to contribute to the project with the Clearinghouse team. Ultimately, the Clearinghouse is designed so that the resources from its inventory could be used in a variety of data management training and education environments. By exposing the Clearinghouse to diverse users and communities, the Clearinghouse team can better assess how the Clearinghouse can be updated and what technological enhancements to pursue in the future in order to improve our support of research data management training needs

Genomics and CSF Analyses Implicate Thyroid Hormone in Hippocampal Sclerosis of Aging

We report evidence of a novel pathogenetic mechanism in which thyroid hormone dysregulation contributes to dementia in elderly persons. Two single nucleotide polymorphisms (SNPs) on chromosome 12p12 were the initial foci of our study: rs704180 and rs73069071. These SNPs were identified by separate research groups as risk alleles for non-Alzheimer’s neurodegeneration. We found that the rs73069071 risk genotype was associated with hippocampal sclerosis (HS) pathology among people with the rs704180 risk genotype (National Alzheimer’s Coordinating Center/Alzheimer’s Disease Genetic Consortium data; n = 2113, including 241 autopsy-confirmed HS cases). Furthermore, both rs704180 and rs73069071 risk genotypes were associated with widespread brain atrophy visualized by MRI (Alzheimer’s Disease Neuroimaging Initiative data; n = 1239). In human brain samples from the Braineac database, both rs704180 and rs73069071 risk genotypes were associated with variation in expression of ABCC9, a gene which encodes a metabolic sensor protein in astrocytes. The rs73069071 risk genotype was also associated with altered expression of a nearby astrocyte-expressed gene, SLCO1C1. Analyses of human brain gene expression databases indicated that the chromosome 12p12 locus may regulate particular astrocyte-expressed genes induced by the active form of thyroid hormone, triiodothyronine (T3). This is informative biologically, because the SLCO1C1 protein transports thyroid hormone into astrocytes from blood. Guided by the genomic data, we tested the hypothesis that altered thyroid hormone levels could be detected in cerebrospinal fluid (CSF) obtained from persons with HS pathology. Total T3 levels in CSF were elevated in HS cases (p \u3c 0.04 in two separately analyzed groups), but not in Alzheimer’s disease cases, relative to controls. No change was detected in the serum levels of thyroid hormone (T3 or T4) in a subsample of HS cases prior to death. We conclude that brain thyroid hormone perturbation is a potential pathogenetic factor in HS that may also provide the basis for a novel CSF-based clinical biomarker

Amygdala and Ventrolateral Prefrontal Cortex Function during Anticipated Peer Evaluation in Pediatric Social Anxiety

1. Context. Amygdala and ventrolateral prefrontal cortex dysfunction manifests in adolescents with anxiety disorders when they view negatively-valenced stimuli in threatening contexts. Such fear-circuitry dysfunction may also manifest when anticipated social evaluation leads socially anxious adolescents to misperceive peers as threatening. 2. Objective. To determine whether photographs of negatively-evaluated smiling peers, viewed during anticipated evaluation, engage the amygdala and ventrolateral prefrontal cortex differentially in adolescents with and without social anxiety. 3. Design. Case-control study. 4. Setting. Government clinical research institute. 5. Participants. Fourteen adolescents with anxiety disorders associated with marked social concerns and 14 diagnosis-free adolescents, matched on sex, age, IQ, and socio-economic status. 6. Main Outcome Measure(s). Blood oxygenation level-dependent signal measured with event-related functional magnetic resonance imaging. Before and during neuroimaging scans, participants anticipating social evaluation completed peer- and self-appraisals. Event-related analyses were tailored to participants’ ratings of specific peers. 7. Results. Participants classified 40 pictures of same-age peers as ones they wanted to engage or not engage with for a social interaction. Anxious adolescents showed greater amygdala activation than healthy adolescents when anticipating evaluation from peers rated as undesired for an interaction. Viewing undesired peers engaged stronger positive amygdala-ventrolateral-prefrontal-cortex connectivity in anxious vs. healthy adolescents. 8. Conclusions. Anticipating social evaluation from negatively-perceived peers modulates amygdala and ventrolateral prefrontal cortex engagement differentially in anxious and healthy 3 adolescents. Amygdala and ventrolateral prefrontal cortex abnormalities in adolescent anxiety disorders are heightened in specific contexts of potential peer evaluation

Challenges and Considerations Related to Studying Dementia in Blacks/African Americans

Blacks/African Americans have been reported to be ~2–4 times more likely to develop clinical Alzheimer’s disease (AD) compared to Whites. Unfortunately, study design challenges (e.g., recruitment bias), racism, mistrust of healthcare providers and biomedical researchers, confounders related to socioeconomic status, and other sources of bias are often ignored when interpreting differences in human subjects categorized by race. Failure to account for these factors can lead to misinterpretation of results, reification of race as biology, discrimination, and missed or delayed diagnoses. Here we provide a selected historical background, discuss challenges, present opportunities, and suggest considerations for studying health outcomes among racial/ethnic groups. We encourage neuroscientists to consider shifting away from using biologic determination to interpret data, and work instead toward a paradigm of incorporating both biological and socio-environmental factors known to affect health outcomes with the goal of understanding and improving dementia treatments for Blacks/African Americans and other underserved populations

iPSCORE: A Resource of 222 iPSC Lines Enabling Functional Characterization of Genetic Variation across a Variety of Cell Types.

Large-scale collections of induced pluripotent stem cells (iPSCs) could serve as powerful model systems for examining how genetic variation affects biology and disease. Here we describe the iPSCORE resource: a collection of systematically derived and characterized iPSC lines from 222 ethnically diverse individuals that allows for both familial and association-based genetic studies. iPSCORE lines are pluripotent with high genomic integrity (no or low numbers of somatic copy-number variants) as determined using high-throughput RNA-sequencing and genotyping arrays, respectively. Using iPSCs from a family of individuals, we show that iPSC-derived cardiomyocytes demonstrate gene expression patterns that cluster by genetic background, and can be used to examine variants associated with physiological and disease phenotypes. The iPSCORE collection contains representative individuals for risk and non-risk alleles for 95% of SNPs associated with human phenotypes through genome-wide association studies. Our study demonstrates the utility of iPSCORE for examining how genetic variants influence molecular and physiological traits in iPSCs and derived cell lines

Possible Fruit Protein Effects on Primate Communities in Madagascar and the Neotropics

The ecological factors contributing to the evolution of tropical vertebrate communities are still poorly understood. Primate communities of the tropical Americas have fewer folivorous but more frugivorous genera than tropical regions of the Old World and especially many more frugivorous genera than Madagascar. Reasons for this phenomenon are largely unexplored. We developed the hypothesis that Neotropical fruits have higher protein concentrations than fruits from Madagascar and that the higher representation of frugivorous genera in the Neotropics is linked to high protein concentrations in fruits. Low fruit protein concentrations in Madagascar would restrict the evolution of frugivores in Malagasy communities.We reviewed the literature for nitrogen concentrations in fruits from the Neotropics and from Madagascar, and analyzed fruits from an additional six sites in the Neotropics and six sites in Madagascar. Fruits from the Neotropical sites contain significantly more nitrogen than fruits from the Madagascar sites. Nitrogen concentrations in New World fruits are above the concentrations to satisfy nitrogen requirements of primates, while they are at the lower end or below the concentrations to cover primate protein needs in Madagascar.Fruits at most sites in the Neotropics contain enough protein to satisfy the protein needs of primates. Thus, selection pressure to develop new adaptations for foods that are difficult to digest (such as leaves) may have been lower in the Neotropics than in Madagascar. The low nitrogen concentrations in fruits from Madagascar may contribute to the almost complete absence of frugivorous primate species on this island

Risk of Incident Clinical Diagnosis of Alzheimer\u27s Disease-Type Dementia Attributable to Pathology-Confirmed Vascular Disease

INTRODUCTION: The presence of cerebrovascular pathology may increase the risk of clinical diagnosis of Alzheimer\u27s disease (AD). METHODS: We examined excess risk of incident clinical diagnosis of AD (probable and possible AD) posed by the presence of lacunes and large infarcts beyond AD pathology using data from the Statistical Modeling of Aging and Risk of Transition study, a consortium of longitudinal cohort studies with more than 2000 autopsies. We created six mutually exclusive pathology patterns combining three levels of AD pathology (low, moderate, or high AD pathology) and two levels of vascular pathology (without lacunes and large infarcts or with lacunes and/or large infarcts). RESULTS: The coexistence of lacunes and large infarcts results in higher likelihood of clinical diagnosis of AD only when AD pathology burden is low. DISCUSSION: Our results reinforce the diagnostic importance of AD pathology in clinical AD. Further harmonization of assessment approaches for vascular pathologies is required

Characterizing college science instruction: The Three-Dimensional Learning Observation Protocol

The importance of improving STEM education is of perennial interest, and to this end, the education community needs ways to characterize transformation efforts. Three-dimensional learning (3DL) is one such approach to transformation, in which core ideas of the discipline, scientific practices, and crosscutting concepts are combined to support student development of disciplinary expertise. We have previously reported on an approach to the characterization of assessments, the Three-Dimensional Learning Assessment Protocol (3D-LAP), that can be used to identify whether assessments have the potential to engage students in 3DL. Here we present the development of a companion, the Three-Dimensional Learning Observation Protocol (3D-LOP), an observation protocol that can reliably distinguish between instruction that has potential for engagement with 3DL and instruction that does not. The 3D-LOP goes beyond other observation protocols, because it is intended not only to characterize the pedagogical approaches being used in the instructional environment, but also to identify whether students are being asked to engage with scientific practices, core ideas, and crosscutting concepts. We demonstrate herein that the 3D-LOP can be used reliably to code for the presence of 3DL; further, we present data that show the utility of the 3D-LOP in differentiating between instruction that has the potential to promote 3DL from instruction that does not. Our team plans to continue using this protocol to evaluate outcomes of instructional transformation projects. We also propose that the 3D-LOP can be used to support practitioners in developing curricular materials and selecting instructional strategies to promote engagement in three-dimensional instruction