Remembering the Best Interest of the Child in Child Custody Disputes between a Natural Parent and a Third Party - Grant v. Martin

Symposium - The Judicial Selectio

The Role of Slp-76 Phosphotyrosines in TCR Signal Transduction and T Cell Differentiation

The cytosolic adapter protein src homology 2(SH2) domain-containing leukocyte phosphoprotein of 76 kDa (SLP-76) lacks enzymatic activity but nucleates a multi-molecular signaling complex that links early T cell receptor (TCR)-induced phosphorylation events into multiple downstream signaling pathways. The N-terminus of SLP-76 contains three tyrosines at residues 112,128 and 145 that are phosphorylated following TCR ligation and, although the mechanisms are not entirely clear, they are required for optimal TCR signal transduction. TCR signals are required for T cell proliferation, cytokine production, and effector and memory differentiation. The experiments described in this dissertation have first tested the biochemical mechanisms by which the SLP-76 tyrosines transmit signals and second tested how alterations in the TCR signals transmitted through SLP-76 tyrosines influence T cell differentiation and effector function. Experiments were performed using two genomic knock-in (KI) mice that express tyrosine to phenylalanine mutations at residue 145 (Y145F) or 112 and 128 together (Y112/128F). Using biochemistry-, flow cytometry- and microscopy-based approaches we show that mutations in the tyrosines of SLP-76 result in graded defects in TCR-induced signals and function depending on the tyrosine(s) affected. Surprisingly, localization of SH2 domain containing effector proteins to mutant SLP-76-nucleated signaling complexes was not lost and therefore could not account for the observed signaling defects. Infection of SLP-76 KI mice with lymphocytic choriomeningitis virus (LCMV) resulted in normal CD8 expansion but graded enhancement of memory differentiation consistent with a model in which weaker TCR signals preferentially promote memory versus effector differentiation. Furthermore CD8+ effector and memory KI T cells failed to produce appropriate cytokine upon antigen restimulation. Similarly, in vitro polarized KI Th17 and Th2 cells failed to produce IL17a and IL4, respectively, following TCR restimulation. Taken together our data show that SLP-76 tyrosines are essential for optimal TCR signal transduction and, moreover, TCR signals sufficient to promote T cell differentiation are different than those required to elicit inflammatory cytokine production

Low-latency Science Exploration of Planetary Bodies: a Demonstration Using ISS in Support of Mars Human Exploration

We summarize a proposed experiment to use the International Space Station to formally examine the application and validation of low-latency telepresence for surface exploration from space as an alternative, precursor, or potentially as an adjunct to astronaut "boots on the ground." The approach is to develop and propose controlled experiments, which build upon previous field studies and which will assess the effects of different latencies (0 to 500 msec), task complexity, and alternate forms of feedback to the operator. These experiments serve as an example of a pathfinder for NASA's roadmap of missions to Mars with low-latency telerobotic exploration as a precursor to astronaut's landing on the surface to conduct geological tasks

Fibromyalgia Syndrome Care of Iraq- and Afghanistan-Deployed Veterans in Veterans Health Administration

Little is known regarding fibromyalgia syndrome (FMS) care among Operation Iraqi Freedom/Operation Enduring Freedom/Operation New Dawn (OIF/OEF/OND) Veterans. Current recommendations include interdisciplinary, teambased combined care approaches and limited opioid use. In this study of OIF/OEF/OND Veterans who accessed Veterans Health Administration services between 2002 and 2012, we hypothesized that combined care (defined as at least 4 primary care visits/yr with visits to mental health and/or rheumatology) versus/yr only would be associated with lower risk of at least 2 opioid prescriptions 12 mo following an FMS diagnosis. Using generalized linear models with a loglink, the Poisson family, and robust standard errors, we estimated risk ratios (RRs) and 95% confidence intervals (CIs). We found that 1% of Veterans had at least 2 FMS diagnoses (International Classification of Diseases-9th Revision-Clinical Modification code 729.1) or at least 1 FMS diagnosis by rheumatology. Veterans with (vs without) FMS were more likely to be female, older, Hispanic, and never/currently married. Combined primary, mental health, and rheumatology care was associated with at least 2 opioid prescriptions (RR [95% CI] for males 2.2 [1.1–4.4] and females 2.8 [0.4–18.6]). Also, combined care was associated with at least 2 nonopioid painrelated prescriptions, a practice supported by evidence-based clinical practice guidelines. In tandem, these results provide mixed evidence of benefit of combined care for FMS. Future studies of healthcare encounter characteristics, care coordination, and benefits for Veterans with FMS are needed

Community Collaboration to Implement a Vaccination Clinic in Rural Areas

Primary care has delivered more vaccinations to people in the US than any other healthcare organization or entity. Patients seek vaccine advice from their primary care clinician, and this is no different for the COVID-19 vaccine. While mass COVID-19 vaccination sites are a critical piece of the greater public health strategy to immunize our communities, reaching older, underserved, and vaccine adverse communities will require engaging primary care and leveraging the trusting relationships practices establish with communities. Oregon Health & Science University Family Medicine Health Center, Scappoose, OR, collaborated with our rural county health department to establish a mass vaccination site at our clinic building. Based on our experience, we also developed a toolkit for decision-makers and implementers of vaccine clinics, designed to be a “vaccination clinic in a box,” that could be replicated in, and tailored to, many types of settings.http://deepblue.lib.umich.edu/bitstream/2027.42/167008/1/Annals_COVID Vaccine Toolkit_FINAL DRAFT_rev for online pub_3.25.21_PP.pdfDescription of Annals_COVID Vaccine Toolkit_FINAL DRAFT_rev for online pub_3.25.21_PP.pdf : Main ArticleSEL

Techno–ecological synergies of solar energy for global sustainability

The strategic engineering of solar energy technologies—from individual rooftop modules to large solar energy power plants—can confer significant synergistic outcomes across industrial and ecological boundaries. Here, we propose techno–ecological synergy (TES), a framework for engineering mutually beneficial relationships between technological and ecological systems, as an approach to augment the sustainability of solar energy across a diverse suite of recipient environments, including land, food, water, and built-up systems. We provide a conceptual model and framework to describe 16 TESs of solar energy and characterize 20 potential techno–ecological synergistic outcomes of their use. For each solar energy TES, we also introduce metrics and illustrative assessments to demonstrate techno–ecological potential across multiple dimensions. The numerous applications of TES to solar energy technologies are unique among energy systems and represent a powerful frontier in sustainable engineering to minimize unintended consequences on nature associated with a rapid energy transition

Fine Mapping of the Bsr1 Barley Stripe Mosaic Virus Resistance Gene in the Model Grass Brachypodium distachyon

The ND18 strain of Barley stripe mosaic virus (BSMV) infects several lines of Brachypodium distachyon, a recently developed model system for genomics research in cereals. Among the inbred lines tested, Bd3-1 is highly resistant at 20 to 25°C, whereas Bd21 is susceptible and infection results in an intense mosaic phenotype accompanied by high levels of replicating virus. We generated an F6∶7 recombinant inbred line (RIL) population from a cross between Bd3-1 and Bd21 and used the RILs, and an F2 population of a second Bd21 × Bd3-1 cross to evaluate the inheritance of resistance. The results indicate that resistance segregates as expected for a single dominant gene, which we have designated Barley stripe mosaic virus resistance 1 (Bsr1). We constructed a genetic linkage map of the RIL population using SNP markers to map this gene to within 705 Kb of the distal end of the top of chromosome 3. Additional CAPS and Indel markers were used to fine map Bsr1 to a 23 Kb interval containing five putative genes. Our study demonstrates the power of using RILs to rapidly map the genetic determinants of BSMV resistance in Brachypodium. Moreover, the RILs and their associated genetic map, when combined with the complete genomic sequence of Brachypodium, provide new resources for genetic analyses of many other traits

Developing a manually annotated clinical document corpus to identify phenotypic information for inflammatory bowel disease

<p>Abstract</p> <p>Background</p> <p>Natural Language Processing (NLP) systems can be used for specific Information Extraction (IE) tasks such as extracting phenotypic data from the electronic medical record (EMR). These data are useful for translational research and are often found only in free text clinical notes. A key required step for IE is the manual annotation of clinical corpora and the creation of a reference standard for (1) training and validation tasks and (2) to focus and clarify NLP system requirements. These tasks are time consuming, expensive, and require considerable effort on the part of human reviewers.</p> <p>Methods</p> <p>Using a set of clinical documents from the VA EMR for a particular use case of interest we identify specific challenges and present several opportunities for annotation tasks. We demonstrate specific methods using an open source annotation tool, a customized annotation schema, and a corpus of clinical documents for patients known to have a diagnosis of Inflammatory Bowel Disease (IBD). We report clinician annotator agreement at the document, concept, and concept attribute level. We estimate concept yield in terms of annotated concepts within specific note sections and document types.</p> <p>Results</p> <p>Annotator agreement at the document level for documents that contained concepts of interest for IBD using estimated Kappa statistic (95% CI) was very high at 0.87 (0.82, 0.93). At the concept level, F-measure ranged from 0.61 to 0.83. However, agreement varied greatly at the specific concept attribute level. For this particular use case (IBD), clinical documents producing the highest concept yield per document included GI clinic notes and primary care notes. Within the various types of notes, the highest concept yield was in sections representing patient assessment and history of presenting illness. Ancillary service documents and family history and plan note sections produced the lowest concept yield.</p> <p>Conclusion</p> <p>Challenges include defining and building appropriate annotation schemas, adequately training clinician annotators, and determining the appropriate level of information to be annotated. Opportunities include narrowing the focus of information extraction to use case specific note types and sections, especially in cases where NLP systems will be used to extract information from large repositories of electronic clinical note documents.</p

The requirements for natural Th17 cell development are distinct from those of conventional Th17 cells

A distinct population of Th17 cells develops in the thymus with innate immune cell characteristics, different selection requirements, and skewed TCR gene usage compared with peripheral Th17 cells