Transregional Slave Networks of the Northern Arc, 700–900 C.E.:

Thesis advisor: Robin FlemingThis dissertation charts the movement of slaves from Western Europe, through Scandinavia, and into the frontiers of the Caliphate, a movement which took shape in the early 700s and flourished into the late 800s. The victims of this movement are well attested in texts from either end of their journey, and the movement of everyday things allows us to trace the itineraries they followed. Necklace beads—produced in the east, carried to the north, and worn in the west—serve as proxies for human traffic that traveled the same routes in opposite directions. Attention to this traffic overcomes four impasses—between regional particularism and interregional connectivity; between attention to exchange and focus on production; between privileging textual or material evidence; and between definitions of slavery that obscure practices of enslavement. The introduction outlines problems of studying medieval slavery with regard to transregional approaches to the Middle Ages, the transition to serfdom, and the use of material evidence. Chapter One gathers narrative texts previously dealt with anecdotally to establish patterns for the Viking-Age slave trade, with eastward traffic thriving by the late 800s. Chapter Two confirms these patterns by graphically comparing viking violence to reports of captive taking in the annals and archival documents of Ireland, Francia, and Anglo-Saxon England. Chapter Three investigates how viking captive taking impacted Western societies and the creation of written records in Carolingian Europe. Chapter Four turns to the material record, using beads to trace the intensity and flow of human traffic that fed from early viking violence. Chapter Five establishes a corresponding demand for slaves in the ʿAbbāsid Caliphate through Arabic archival, legal, historical, and geographic texts. The conclusion places this research in the context of global history. By spanning periods, regions, and disciplines, this dissertation brings to focus people who crossed boundaries unwillingly, but whose movements contributed to epochal change.Thesis (PhD) — Boston College, 2019.Submitted to: Boston College. Graduate School of Arts and Sciences.Discipline: History

Identification of genetic variants associated with Huntington's disease progression: a genome-wide association study

Background Huntington's disease is caused by a CAG repeat expansion in the huntingtin gene, HTT. Age at onset has been used as a quantitative phenotype in genetic analysis looking for Huntington's disease modifiers, but is hard to define and not always available. Therefore, we aimed to generate a novel measure of disease progression and to identify genetic markers associated with this progression measure. Methods We generated a progression score on the basis of principal component analysis of prospectively acquired longitudinal changes in motor, cognitive, and imaging measures in the 218 indivduals in the TRACK-HD cohort of Huntington's disease gene mutation carriers (data collected 2008–11). We generated a parallel progression score using data from 1773 previously genotyped participants from the European Huntington's Disease Network REGISTRY study of Huntington's disease mutation carriers (data collected 2003–13). We did a genome-wide association analyses in terms of progression for 216 TRACK-HD participants and 1773 REGISTRY participants, then a meta-analysis of these results was undertaken. Findings Longitudinal motor, cognitive, and imaging scores were correlated with each other in TRACK-HD participants, justifying use of a single, cross-domain measure of disease progression in both studies. The TRACK-HD and REGISTRY progression measures were correlated with each other (r=0·674), and with age at onset (TRACK-HD, r=0·315; REGISTRY, r=0·234). The meta-analysis of progression in TRACK-HD and REGISTRY gave a genome-wide significant signal (p=1·12 × 10−10) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2. The genes in this locus were associated with progression in TRACK-HD (MSH3 p=2·94 × 10−8 DHFR p=8·37 × 10−7 MTRNR2L2 p=2·15 × 10−9) and to a lesser extent in REGISTRY (MSH3 p=9·36 × 10−4 DHFR p=8·45 × 10−4 MTRNR2L2 p=1·20 × 10−3). The lead single nucleotide polymorphism (SNP) in TRACK-HD (rs557874766) was genome-wide significant in the meta-analysis (p=1·58 × 10−8), and encodes an aminoacid change (Pro67Ala) in MSH3. In TRACK-HD, each copy of the minor allele at this SNP was associated with a 0·4 units per year (95% CI 0·16–0·66) reduction in the rate of change of the Unified Huntington's Disease Rating Scale (UHDRS) Total Motor Score, and a reduction of 0·12 units per year (95% CI 0·06–0·18) in the rate of change of UHDRS Total Functional Capacity score. These associations remained significant after adjusting for age of onset. Interpretation The multidomain progression measure in TRACK-HD was associated with a functional variant that was genome-wide significant in our meta-analysis. The association in only 216 participants implies that the progression measure is a sensitive reflection of disease burden, that the effect size at this locus is large, or both. Knockout of Msh3 reduces somatic expansion in Huntington's disease mouse models, suggesting this mechanism as an area for future therapeutic investigation

Viking-Age Bead Classification System (Callmer 1977)

This spreadsheet presents the classification system commonly used for the beads and necklaces of Viking-Age Scandinavia (ca. 800-1000 C.E.). This system was first published by Johan Callmer in 1977 and is now out of print; it is made available here with the author's permission. The creator of this spreadsheet (Matthew Delvaux) has updated terminology to conform to current usage, reorganized the system to make it more accessible for researchers, and integrated chronological information wherever possible to aid in the classification and interpretation of new finds. Preliminary notes, including important deviations from Callmer's original system, are presented in the sheet labeled "Remarks." This is followed by a sheet labeled "System," which defines the properties used to describe Viking-Age beads, including both Callmer's original descriptions and the revised terminology used throughout the spreadsheet. "Beads" provides a searchable and sortable table of bead types, with chronological information derived from Callmer's assemblages in the right-hand columns. "Assemblages" presents information on the necklaces Callmer used for his analysis. "Bead Groups" lists the classification system that Callmer developed to sort these assemblages, including the number of assemblages he assigned to each group. "Bead Periods" offers summary information for each bead period, derived from Callmer's assemblage inventories and how he sorted these assemblages into chronological groups

Ofatumumab versus Teriflunomide in Multiple Sclerosis

BACKGROUND: Ofatumumab, a subcutaneous anti-CD20 monoclonal antibody, selectively depletes B cells. Teriflunomide, an oral inhibitor of pyrimidine synthesis, reduces T-cell and B-cell activation. The relative effects of these two drugs in patients with multiple sclerosis are not known. METHODS: In two double-blind, double-dummy, phase 3 trials, we randomly assigned patients with relapsing multiple sclerosis to receive subcutaneous ofatumumab (20 mg every 4 weeks after 20-mg loading doses at days 1, 7, and 14) or oral teriflunomide (14 mg daily) for up to 30 months. The primary end point was the annualized relapse rate. Secondary end points included disability worsening confirmed at 3 months or 6 months, disability improvement confirmed at 6 months, the number of gadolinium-enhancing lesions per T1-weighted magnetic resonance imaging (MRI) scan, the annualized rate of new or enlarging lesions on T2-weighted MRI, serum neurofilament light chain levels at month 3, and change in brain volume. RESULTS: Overall, 946 patients were assigned to receive ofatumumab and 936 to receive teriflunomide; the median follow-up was 1.6 years. The annualized relapse rates in the ofatumumab and teriflunomide groups were 0.11 and 0.22, respectively, in trial 1 (difference, -0.11; 95% confidence interval [CI], -0.16 to -0.06; P<0.001) and 0.10 and 0.25 in trial 2 (difference, -0.15; 95% CI, -0.20 to -0.09; P<0.001). In the pooled trials, the percentage of patients with disability worsening confirmed at 3 months was 10.9% with ofatumumab and 15.0% with teriflunomide (hazard ratio, 0.66; P = 0.002); the percentage with disability worsening confirmed at 6 months was 8.1% and 12.0%, respectively (hazard ratio, 0.68; P = 0.01); and the percentage with disability improvement confirmed at 6 months was 11.0% and 8.1% (hazard ratio, 1.35; P = 0.09). The number of gadolinium-enhancing lesions per T1-weighted MRI scan, the annualized rate of lesions on T2-weighted MRI, and serum neurofilament light chain levels, but not the change in brain volume, were in the same direction as the primary end point. Injection-related reactions occurred in 20.2% in the ofatumumab group and in 15.0% in the teriflunomide group (placebo injections). Serious infections occurred in 2.5% and 1.8% of the patients in the respective groups. CONCLUSIONS: Among patients with multiple sclerosis, ofatumumab was associated with lower annualized relapse rates than teriflunomide. (Funded by Novartis; ASCLEPIOS I and II ClinicalTrials.gov numbers, NCT02792218 and NCT02792231.)