Use of Compliant Interbody Force Sensing Grafts to Compare Load Sharing Properties of Unidirectional and Bidirectional Multilevel Dynamic Translational Anterior Cervical Plates

INTRODUCTION: Pseudoarthrosis is a relatively rare complication following anterior cervical arthrodesis, and is felt to be related to stress shielding. To address this, dynamic anterior cervical plates have emerged to maintain load sharing as an arthodesis matures. Dynamic plates can translate bidirectionally (allow translation in compressive and tensile loads), or unidirectionally (allow translation in compression, but maintain its position under tensile loads). The objective of this study was to compare the graft load mechanics between three plated conditions during settling using compliant interbody load cells: A static (fixed, non-moving) plate, a unidirectional multi-level translational plate design, and a bidirectional two-level translational plate design. METHODS: Six fresh human cadaveric cervical spines (C2-T1) were procured and mounted in a programmable testing apparatus and tested in flexion-extension, left-right lateral bending, and left-right axial rotation under displacement control to a load limit of 3.0 Nm or 30 degrees of motion. Four different spine conditions were evaluated: the harvested (H) condition and three types of instrumented conditions containing two-level discectomy and graft at C4-C5 and C5-C6: a unidirectional translational plate, a bidirectional translational plate, and a rigid static plate. Compliant force sensing grafts were placed in the discectomized regions prior to plate application that permitted up to 2mm of deformation during compressive loading. The ATLANTIS® Translational cervical plating system (Medtronic Spinal and Biologics, Memphis, TN) was used for the plated spine conditions with fixed-angle screws. Measurements included vertebral motion, applied load and moment, and graft loads. Normalized flexibility data, motion data, and graft load data were compared using a one-way Repeated Measures ANOVA (p\u3c0.05) and SNK tests. RESULTS: A significant reduction in flexion+extension motion occurred at the operated levels of all instrumented spines compared to the harvested spine. The normalized flexion+extension motion for the unidirectional plate was significantly less than the bidirectional plate. During flexion, the unidirectional plate shortened an average of 2 mm (1 mm per level). Once shortened, a significant increase in the baseline graft preload occurred. CONCLUSION: In this study, a compliant interbody load cell was developed and used to determine the graft load properties of three different anterior cervical plate designs: static, unidirectional and bidirectional translational. Both translational plates demonstrated better load-sharing properties than the static plate. The results showed that the unidirectional plate had less motion in flexion/extension, while maintaining a more continuous graft loading than the bidirectional plate. Also, the ratchet mechanism of unidirectional translational plate was validated in the study, where the plate was able to translate under compressive load and maintain its position under tension when ratcheted. The ability to limit motion and maintain compression with a unidirectional dynamic plate may have improved rates of fusion; however, this will need to be evaluated further in an in vivo and/or clinical model

Younger Dryas glaciers and climate in the Mourne Mountains, Northern Ireland

Here, we present evidence to suggest that the Mourne Mountains, Northern Ireland, were last occupied by glaciers during the Younger Dryas Stadial. The margins of these glaciers are marked by moraines, chronologically constrained to the Younger Dryas by Schmidt hammer exposure dating. Reconstructions indicate that these glaciers had equilibrium-line altitudes (ELAs) ranging from 356 ± 33 m (a.s.l.) to 570 ± 9 m (a.s.l.), with a mean of 475 ± 36 m (a.s.l.). ELAs rise from west to east, probably reflecting the contribution of windblown snow and ice to the accumulation of Younger Dryas glaciers in the western Mournes. Taking this into consideration, a mean ‘climatic’ ELA of 529 ± 4 m (a.s.l.) is calculated for the mountains as a whole. Assuming a mean annual sea level air temperature of −8 °C, and an annual temperature range of 34 °C, degree-day modelling suggests that during the Younger Dryas, accumulation at the ‘climatic’ ELA of glaciers in the Mournes was 846–990 mm a−1. This suggests increased aridity, relative to present, and is consistent with other parts of NW Europe, where reduced precipitation alongside notable cooling is thought to reflect increased North Atlantic sea ice extent during the Younger Dryas.</p

Survey Mode Effects on Valuation of Environmental Goods

This article evaluates the effect of the choice of survey recruitment mode on the value of water quality in lakes, rivers, and streams. Four different modes are compared: bringing respondents to one central location after phone recruitment, mall intercepts in two states, national phone-mail survey, and an Internet survey with a national, probability-based panel. The modes differ in terms of the representativeness of the samples, non-response rates, sample selection effects, and consistency of responses. The article also shows that the estimated value of water quality can differ substantially depending on the survey mode. The national Internet panel has the most desirable properties with respect to performance on the four important survey dimensions of interest

FY17 Report Summaries of Five Completed Center Innovation Fund (CIF) Projects for the Highlights/Abstract Section of the FY 2018 CIF Annual Report

The Center Innovation Fund Annual Report for FY18 is an annual report for Space Technology Mission Directorate (STMD) Leadership, STMD Principle Technologists, and Center Innovation Fund Management. Attached is the Highlights/Abstract section of this annual report, which is the only section to be shared outside of NASA. Contributors were asked not to include any SBU information for these report summaries

Locations and patterns of meiotic recombination in two-generation pedigrees

<p>Abstract</p> <p>Background</p> <p>Meiotic crossovers are the major mechanism by which haplotypes are shuffled to generate genetic diversity. Previously available methods for the genome-wide, high-resolution identification of meiotic crossover sites are limited by the laborious nature of the assay (as in sperm typing).</p> <p>Methods</p> <p>Several methods have been introduced to identify crossovers using high density single nucleotide polymorphism (SNP) array technologies, although programs are not widely available to implement such analyses.</p> <p>Results</p> <p>Here we present a two-generation "reverse pedigree analysis" method (analyzing the genotypes of two children relative to each parent) and a web-accessible tool to determine and visualize inheritance differences among siblings and crossover locations on each parental gamete. This approach is complementary to existing methods and uses informative markers which provide high resolution for locating meiotic crossover sites. We introduce a segmentation algorithm to identify crossover sites, and used a synthetic data set to determine that the segmentation algorithm specificity was 92% and sensitivity was 89%. The use of reverse pedigrees allows the inference of crossover locations on the X chromosome in a maternal gamete through analysis of two sons and their father. We further analyzed genotypes from eight multiplex autism families, observing a 1.462 maternal to paternal recombination ratio and no significant differences between affected and unaffected children. Meiotic recombination results from pediSNP can also be used to identify haplotypes that are shared by probands within a pedigree, as we demonstrated with a multiplex autism family.</p> <p>Conclusion</p> <p>Using "reverse pedigrees" and defining unique sets of genotype markers within pedigree data, we introduce a method that identifies inherited allelic differences and meiotic crossovers. We implemented the method in the pediSNP software program, and we applied it to several data sets. This approach uses data from two generations to identify crossover sites, facilitating studies of recombination in disease. pediSNP is available online at <url>http://pevsnerlab.kennedykrieger.org/pediSNP</url>.</p

Precision grid and hand motion for accurate needle insertion in brachytherapy

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98741/1/MPH004749.pd

A phylum-level phylogenetic classification of zygomycete fungi based on genome-scale data

Zygomycete fungi were classified as a single phylum, Zygomycota, based on sexual reproduction by zygospores, frequent asexual reproduction by sporangia, absence of multicellular sporocarps, and production of coenocytic hyphae, all with some exceptions. Molecular phylogenies based on one or a few genes did not support the monophyly of the phylum, however, and the phylum was subsequently abandoned. Here we present phylogenetic analyses of a genome-scale data set for 46 taxa, including 25 zygomycetes and 192 proteins, and we demonstrate that zygomycetes comprise two major clades that form a paraphyletic grade. A formal phylogenetic classification is proposed herein and includes two phyla, six subphyla, four classes and 16 orders. On the basis of these results, the phyla Mucoromycota and Zoopagomycota are circumscribed. Zoopagomycota comprises Entomophtoromycotina, Kickxellomycotina and Zoopagomycotina; it constitutes the earliest diverging lineage of zygomycetes and contains species that are primarily parasites and pathogens of small animals (e.g. amoeba, insects, etc.) and other fungi, i.e. mycoparasites. Mucoromycota comprises Glomeromycotina, Mortierellomycotina, and Mucoromycotina and is sister to Dikarya. It is the more derived clade of zygomycetes and mainly consists of mycorrhizal fungi, root endophytes, and decomposers of plant material. Evolution of trophic modes, morphology, and analysis of genome-scale data are discussed

Social Cognition in Alzheimer's Disease: A Separate Construct Contributing to Dependence

The extent to which social cognitive changes reflect a discrete constellation of symptoms dissociable from general cognitive changes in Alzheimer's disease (AD) is unclear. Moreover, whether social cognitive symptoms contribute to disease severity and progression is unknown. The current multicenter study investigated cross-sectional and longitudinal associations between social cognition measured with six items from the Blessed Dementia Rating Scale, general cognition, and dependence in 517 participants with probable AD. Participants were monitored every 6 months for 5.5 years. Results from multivariate latent growth curve models adjusted for sex, age, education, depression, and recruitment site revealed that social cognition and general cognition were unrelated cross-sectionally and throughout time. However, baseline levels of each were related independently to dependence, and change values of each were related independently to change in dependence. These findings highlight the separability of social and general cognition in AD. Results underscore the relevance of considering social cognition when modeling disease and estimating clinical outcomes related to patient disability

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

A novel Alzheimer disease locus located near the gene encoding tau protein

This is the author accepted manuscript. The final version is available from the publisher via the DOI in this recordAPOE ε4, the most significant genetic risk factor for Alzheimer disease (AD), may mask effects of other loci. We re-analyzed genome-wide association study (GWAS) data from the International Genomics of Alzheimer's Project (IGAP) Consortium in APOE ε4+ (10 352 cases and 9207 controls) and APOE ε4- (7184 cases and 26 968 controls) subgroups as well as in the total sample testing for interaction between a single-nucleotide polymorphism (SNP) and APOE ε4 status. Suggestive associations (P<1 × 10-4) in stage 1 were evaluated in an independent sample (stage 2) containing 4203 subjects (APOE ε4+: 1250 cases and 536 controls; APOE ε4-: 718 cases and 1699 controls). Among APOE ε4- subjects, novel genome-wide significant (GWS) association was observed with 17 SNPs (all between KANSL1 and LRRC37A on chromosome 17 near MAPT) in a meta-analysis of the stage 1 and stage 2 data sets (best SNP, rs2732703, P=5·8 × 10-9). Conditional analysis revealed that rs2732703 accounted for association signals in the entire 100-kilobase region that includes MAPT. Except for previously identified AD loci showing stronger association in APOE ε4+ subjects (CR1 and CLU) or APOE ε4- subjects (MS4A6A/MS4A4A/MS4A6E), no other SNPs were significantly associated with AD in a specific APOE genotype subgroup. In addition, the finding in the stage 1 sample that AD risk is significantly influenced by the interaction of APOE with rs1595014 in TMEM106B (P=1·6 × 10-7) is noteworthy, because TMEM106B variants have previously been associated with risk of frontotemporal dementia. Expression quantitative trait locus analysis revealed that rs113986870, one of the GWS SNPs near rs2732703, is significantly associated with four KANSL1 probes that target transcription of the first translated exon and an untranslated exon in hippocampus (P≤1.3 × 10-8), frontal cortex (P≤1.3 × 10-9) and temporal cortex (P≤1.2 × 10-11). Rs113986870 is also strongly associated with a MAPT probe that targets transcription of alternatively spliced exon 3 in frontal cortex (P=9.2 × 10-6) and temporal cortex (P=2.6 × 10-6). Our APOE-stratified GWAS is the first to show GWS association for AD with SNPs in the chromosome 17q21.31 region. Replication of this finding in independent samples is needed to verify that SNPs in this region have significantly stronger effects on AD risk in persons lacking APOE ε4 compared with persons carrying this allele, and if this is found to hold, further examination of this region and studies aimed at deciphering the mechanism(s) are warranted