Clemson University’s Teacher Learning Progression Program: Personalized Advanced Credentials for Teachers

This chapter provides an overview of Clemson University\u27s Teacher Learning Progression program, which offers participating middle school science, technology, engineering, and/or mathematics (STEM) teachers with personalized advanced credentials. In contrast to typical professional development (PD) approaches, this program identifies individualized pathways for PD based on teachers\u27 unique interests and needs and offers PD options through the use of a “recommender system”—a system providing context-specific recommendations to guide teachers toward the identification of preferred PD pathways and content. In this chapter, the authors introduce the program and highlight (1) the data collection and instrumentation needed to make personalized PD recommendations, (2) the recommender system, and (3) the personalized advanced credential options. The authors also discuss lessons learned through initial stages of project implementation and consider future directions for the use of recommender systems to support teacher PD, considering both research and applied implications and settings

Radiostereometric Evaluation of Tendon Elongation After Distal Biceps Repair.

BACKGROUND: Operative repair of distal biceps tendon ruptures has shown successful outcomes. However, little is known about the amount of tendon or repair site lengthening after repair. PURPOSE/HYPOTHESIS: The purpose of this study was to evaluate distal biceps tendon repair via intratendinous radiostereometric analysis to analyze tendon lengthening at different time intervals of healing. The hypothesis was that there is significant lengthening after repair. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Eleven patients with distal biceps ruptures requiring operative repair were recruited. During repair, two 2-mm tantalum beads with laser-etched holes were sutured to the distal biceps tendon. Beads were evaluated via computed tomography scans immediately postoperatively and at 16 weeks. Radiographs were obtained at time 0 and then at 4, 8, and 16 weeks postoperatively. Measurements were made using the button-to-bead and bead-to-bead distances to assess repair site elongation as well as tendon elongation over time. After final follow-up, patients filled out the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire and underwent ultrasound to confirm the integrity of the tendon. RESULTS: Ten patients had complete ruptures, with 1 having a partial rupture that underwent completion of the tear and subsequent repair. All patients showed statistically significant lengthening after surgery. The mean amount of tendon lengthening after surgery was 22.8 mm (range, 11.2-30.9 mm; P \u3c .05), and the repair site lengthened a mean 17.0 mm (range, 9.6-30.6 mm; P \u3c .05) from surgery to final follow-up. The greatest change in lengthening was noted between time 0 and week 4 (mean, 11.3 mm; P \u3c .05), with the least amount of lengthening between weeks 8 and 16 (mean, 2.6 mm; P \u3c .05). The mean DASH score was 11.2. Final ultrasound evaluations found all tendons to be in continuity. CONCLUSION: All patients undergoing distal biceps tendon repair have significant elongation after surgery, with the greatest amount of lengthening seen in the early postoperative period

Computer delivery of gesture therapy for people with severe aphasia

Background: Using gesture as a compensatory communication strategy may be challenging for people with severe aphasia. Therapy can improve skills with gesture, at least in elicitation tasks, but gains ar often modest. Raising the treatment dose with technology might improve outcomes. Aims: This feasibility study developed a computer gesture therapy tool (GeST), and piloted it with nine people who have severe aphasia. It aimed to determine whether practice with GeST would improve gesture production and/or spoken naming. It also explored whether GeST encouraged independent practice and was easy to use. Methods & Procedures: Pilot participants had 6 weeks practice with GeST, flanked by pre- and post-therapy tests of gesture and word production. Usability was explored through interviews and structured observations, and the amount of time spent in the programme was monitored. Outcomes & Results: Scores on the gesture test were evaluated by 36 independent raters. Recognition scores for gestures practised with the tool improved significantly after therapy and the gain was maintained. However, gains were small and only occurred on items that were practised with regular therapist support. There was no generalisation to unpractised gestures and no effect on spoken naming. Usability results were positive. Participants undertook an average of 64.4 practice sessions with GeST, and the average session length was just under 14 minutes. Conclusions: GeST was proved to be easy and enjoyable to use and had some effect on participants’ gesturing skills. Increasing the magnitude of gains would be desirable. The effect on everyday communication needs to be explored

Dietary Cholesterol Promotes Adipocyte Hypertrophy and Adipose Tissue Inflammation in Visceral, But Not Subcutaneous, Fat in Monkeys

Objective—Excessive caloric intake is associated with obesity and adipose tissue dysfunction. However, the role of dietary cholesterol in this process is unknown. The aim of this study was to determine whether increasing dietary cholesterol intake alters adipose tissue cholesterol content, adipocyte size, and endocrine function in nonhuman primates. Approach and Results—Age-matched, male African Green monkeys (n=5 per group) were assigned to one of three diets containing 0.002 (Lo), 0.2 (Med) or 0.4 (Hi) mg cholesterol/Kcal. After 10 weeks of diet feeding, animals were euthanized for adipose tissue, liver, and plasma collection. With increasing dietary cholesterol, free cholesterol (FC) content and adipocyte size increased in a step-wise manner in visceral, but not subcutaneous fat, with a significant association between visceral adipocyte size and FC content (r2=0.298; n=15; p=0.035). In visceral fat, dietary cholesterol intake was associated with: 1) increased pro-inflammatory gene expression and macrophage recruitment, 2) decreased expression of genes involved in cholesterol biosynthesis and lipoprotein uptake, and 3) increased expression of proteins involved in FC efflux. Conclusions—Increasing dietary cholesterol selectively increases visceral fat adipocyte size, FC and macrophage content, and proinflammatory gene expression in nonhuman primates

Waning efficacy in a long-term AAV-mediated gene therapy study in the murine model of Krabbe disease

Neonatal AAV9-gene therapy of the lysosomal enzyme galactosylceramidase (GALC) significantly ameliorates central and peripheral neuropathology, prolongs survival, and largely normalizes motor deficits in Twitcher mice. Despite these therapeutic milestones, new observations identified the presence of multiple small focal demyelinating areas in the brain after 6-8 months. These lesions are in stark contrast to the diffuse, global demyelination that affects the brain of naive Twitcher mice. Late-onset lesions exhibited lysosomal alterations with reduced expression of GALC and increased psychosine levels. Furthermore, we found that lesions were closely associated with the extravasation of plasma fibrinogen and activation of the fibrinogen-BMP-SMAD-GFAP gliotic response. Extravasation of fibrinogen correlated with tight junction disruptions of the vasculature within the lesioned areas. The lesions were surrounded by normal appearing white matter. Our study shows that the dysregulation of therapeutic GALC was likely driven by the exhaustion of therapeutic AAV episomal DNA within the lesions, paralleling the presence of proliferating oligodendrocyte progenitors and glia. We believe that this is the first demonstration of diminishing expression in vivo from an AAV gene therapy vector with detrimental effects in the brain of a lysosomal storage disease animal model. The development of this phenotype linking localized loss of GALC activity with relapsing neuropathology in the adult brain of neonatally AAV-gene therapy-treated Twitcher mice identifies and alerts to possible late-onset reductions of AAV efficacy, with implications to other genetic leukodystrophies

Acute Sterol O-Acyltransferase 2 (SOAT2) Knockdown Rapidly Mobilizes Hepatic Cholesterol for Fecal Excretion

The primary risk factor for atherosclerotic cardiovascular disease is LDL cholesterol, which can be reduced by increasing cholesterol excretion from the body. Fecal cholesterol excretion can be driven by a hepatobiliary as well as a non-biliary pathway known as transintestinal cholesterol efflux (TICE). We previously showed that chronic knockdown of the hepatic cholesterol esterifying enzyme sterol O-acyltransferase 2 (SOAT2) increased fecal cholesterol loss via TICE. To elucidate the initial events that stimulate TICE, C57Bl/6 mice were fed a high cholesterol diet to induce hepatic cholesterol accumulation and were then treated for 1 or 2 weeks with an antisense oligonucleotide targeting SOAT2. Within 2 weeks of hepatic SOAT2 knockdown (SOAT2HKD), the concentration of cholesteryl ester in the liver was reduced by 70% without a reciprocal increase in hepatic free cholesterol. The rapid mobilization of hepatic cholesterol stores resulted in a ∼ 2-fold increase in fecal neutral sterol loss but no change in biliary cholesterol concentration. Acute SOAT2HKD increased plasma cholesterol carried primarily in lipoproteins enriched in apoB and apoE. Collectively, our data suggest that acutely reducing SOAT2 causes hepatic cholesterol to be swiftly mobilized and packaged onto nascent lipoproteins that feed cholesterol into the TICE pathway for fecal excretion

Reduction of VLDL Secretion Decreases Cholesterol Excretion in Niemann-Pick C1-Like 1 Hepatic Transgenic Mice

An effective way to reduce LDL cholesterol, the primary risk factor of atherosclerotic cardiovascular disease, is to increase cholesterol excretion from the body. Our group and others have recently found that cholesterol excretion can be facilitated by both hepatobiliary and transintestinal pathways. However, the lipoprotein that moves cholesterol through the plasma to the small intestine for transintestinal cholesterol efflux (TICE) is unknown. To test the hypothesis that hepatic very low-density lipoproteins (VLDL) support TICE, antisense oligonucleotides (ASO) were used to knockdown hepatic expression of microsomal triglyceride transfer protein (MTP), which is necessary for VLDL assembly. While maintained on a high cholesterol diet, Niemann-Pick C1-like 1 hepatic transgenic (L1Tg) mice, which predominantly excrete cholesterol via TICE, and wild type (WT) littermates were treated with control ASO or MTP ASO. In both WT and L1Tg mice, MTP ASO decreased VLDL triglyceride (TG) and cholesterol secretion. Regardless of treatment, L1Tg mice had reduced biliary cholesterol compared to WT mice. However, only L1Tg mice treated with MTP ASO had reduced fecal cholesterol excretion. Based upon these findings, we conclude that VLDL or a byproduct such as LDL can move cholesterol from the liver to the small intestine for TICE

DNA Testing Reveals the Putative Identity of JB55, a 19th Century Vampire Buried in Griswold, Connecticut

In 1990 in Griswold, Connecticut, archaeologists excavated a burial found in a "skull and crossbones" orientation. The lid of the 19th century coffin had brass tacks that spelled "JB55", the initials of the person lying there and age at death. JB55 had evidence of chronic pulmonary infection, perhaps tuberculosis. It is possible that JB55 was deemed a vampire due to his disease, and therefore had to be "killed" by mutilating his corpse. In an attempt to reveal the identity of JB55, DNA testing was performed. Ancestry informative single nucleotide polymorphism (SNP) analysis using the Precision ID Ancestry Panel indicated European ancestry. A full Y-chromosomal short tandem repeat (Y-STR) profile was obtained, belonging to haplogroup R1b. When the Y-STR profile was searched in the publicly accessible FamilyTreeDNA R1b Project website, the two closest matches had the surname "Barber". A search of historical records led to a death notice mentioning John Barber, whose son Nathan Barber was buried in Griswold in 1826. The description of Nathan Barber closely fits the burial of "NB13," found near JB55. By applying modern forensic DNA tools to a historical mystery, the identity of JB55 as John Barber, the 19th century Connecticut vampire, has been revealed

Development of (6 R)-2-Nitro-6-[4-(trifluoromethoxy)phenoxy]-6,7-dihydro-5 H-imidazo[2,1- b][1,3]oxazine (DNDI-8219): A New Lead for Visceral Leishmaniasis.

Discovery of the potent antileishmanial effects of antitubercular 6-nitro-2,3-dihydroimidazo[2,1- b][1,3]oxazoles and 7-substituted 2-nitro-5,6-dihydroimidazo[2,1- b][1,3]oxazines stimulated the examination of further scaffolds (e.g., 2-nitro-5,6,7,8-tetrahydroimidazo[2,1- b][1,3]oxazepines), but the results for these seemed less attractive. Following the screening of a 900-compound pretomanid analogue library, several hits with more suitable potency, solubility, and microsomal stability were identified, and the superior efficacy of newly synthesized 6 R enantiomers with phenylpyridine-based side chains was established through head-to-head assessments in a Leishmania donovani mouse model. Two such leads ( R-84 and R-89) displayed promising activity in the more stringent Leishmania infantum hamster model but were unexpectedly found to be potent inhibitors of hERG. An extensive structure-activity relationship investigation pinpointed two compounds ( R-6 and pyridine R-136) with better solubility and pharmacokinetic properties that also provided excellent oral efficacy in the same hamster model (>97% parasite clearance at 25 mg/kg, twice daily) and exhibited minimal hERG inhibition. Additional profiling earmarked R-6 as the favored backup development candidate

Evidence for Color Dichotomy in the Primordial Neptunian Trojan Population

In the current model of early Solar System evolution, the stable members of the Jovian and Neptunian Trojan populations were captured into resonance from the leftover reservoir of planetesimals during the outward migration of the giant planets. As a result, both Jovian and Neptunian Trojans share a common origin with the primordial disk population, whose other surviving members constitute today's trans-Neptunian object (TNO) populations. The cold classical TNOs are ultra-red, while the dynamically excited "hot" population of TNOs contains a mixture of ultra-red and blue objects. In contrast, Jovian and Neptunian Trojans are observed to be blue. While the absence of ultra-red Jovian Trojans can be readily explained by the sublimation of volatile material from their surfaces due to the high flux of solar radiation at 5AU, the lack of ultra-red Neptunian Trojans presents both a puzzle and a challenge to formation models. In this work we report the discovery by the Dark Energy Survey (DES) of two new dynamically stable L4 Neptunian Trojans,2013 VX30 and 2014 UU240, both with inclinations i >30 degrees, making them the highest-inclination known stable Neptunian Trojans. We have measured the colors of these and three other dynamically stable Neptunian Trojans previously observed by DES, and find that 2013 VX30 is ultra-red, the first such Neptunian Trojan in its class. As such, 2013 VX30 may be a "missing link" between the Trojan and TNO populations. Using a simulation of the DES TNO detection efficiency, we find that there are 162 +/- 73 Trojans with Hr < 10 at the L4 Lagrange point of Neptune. Moreover, the blue-to-red Neptunian Trojan population ratio should be higher than 17:1. Based on this result, we discuss the possible origin of the ultra-red Neptunian Trojan population and its implications for the formation history of Neptunian Trojans