ARCHAEOLOGICAL HERITAGE AS A CATALYST FOR PUBLIC ENGAGEMENT, RURAL REJUVENATION, AND RETHINKING OUR SHARED PAST: PERSPECTIVES FROM A QUARTER CENTURY OF COMMUNITY ARCHAEOLOGY IN NEWFOUNDLAND AND LABRADOR

Archaeological research in Canada’s easternmost province has enjoyed a long and evolving history of community partnerships. This is due, in part, to Memorial University’s unique mandate, as well as the Department of Archaeology’s strong commitment to working with individuals and organizations where excavations are conducted. Three case studies from Newfoundland and Labrador shed light on the motivations, experiences, challenges, and outcomes that community–university research partnerships can foster, and demonstrate that archaeology has the potential to make valuable local contributions.A pesquisa arqueológica na província mais oriental do Canadá se beneficiou de uma longa e expansível história de parcerias com as comunidades. Tal deve-se, em parte, ao mandato excepcional da Memorial University, assim como ao engajamento forte do departamento de arqueologia em trabalhar com indivíduos e organizações locais durante escavações. A partir de três casos de estudos da província de Terra Nova e Labrador, este artigo revela as motivações, as experiências, os desafios, como os resultados que podem surgir das parcerias comunidade-universidade, e atesta do potencial da arqueologia em contribuir localmente de forma vantajosamente.La recherche archéologique dans la province canadienne située le plus à l’Est du pays a longtemps profité d’une histoire de partenariats avec les communautés qui a su évoluer dans le temps. Cela s’explique, en partie, par le mandat exceptionnel de la Memorial University, ainsi que par l’engagement prononcé du département d’archéologie pour travailler avec les individus et les organisations locales lors des excavations. À partir de trois études de cas de Terre-Neuve et Labrador, cet article met en lumière les motivations, les expériences, les défis, et les résultats que les partenariats communauté–université peuvent générer, et démontre le potentiel de la discipline archéologique à réaliser des contributions importantes au niveau local

Sex matters: Otolith shape and genomic variation in deacon rockfish (Sebastes diaconus)

Little is known about intraspecific variation within the deacon rockfish (Sebastes di‐ aconus), a recently described species found in the northeast Pacific Ocean. We in‐ vestigated population structure among fish sampled from two nearshore reefs (Siletz Reef and Seal Rock) and one offshore site (Stonewall Bank) within a 15,000 neutral loci, whether analyzed independently or classified into nearshore and offshore groups. Male and females were readily distinguished using genetic data and 92 outlier loci were as‐ sociated with sex, potentially indicating differential selection between males and fe‐ males. Morphometric results indicated that there was significant secondary sexual dimorphism in otolith shape, but further sampling is required to disentangle potential confounding influence of age. This study is the first step toward understanding in‐ traspecific variation within the deacon rockfish and the potential management impli‐ cations. Since differentiation among the three sample sites was small, we consider the results to be suggestive of a single stock. However, future studies should evalu‐ ate how the stock is affected by differences in sex, age, and gene flow between the nearshore and offshore environments

Archaeological evidence of resource utilisation of the great whales over the past two millennia: A systematic review protocol

Archaeological faunal remains provide key insights into human societies in the past, alongside information on previous resource utilisation and exploitation of wildlife populations. The great whales (Mysticete and sperm whales) were hunted unsustainably throughout the 16th - 20th centuries (herein defined as the modern period) leading to large population declines and variable recovery patterns among species. Humans have utilised whales as a resource through carcass scavenging for millennia; however, increasing local and regional ethnographic and archaeological evidence suggests that, prior to the modern period, hunting of the great whales was more common than previously thought; impacts of earlier hunting pressures on the population ecology of many whale species remains relatively unknown. Hunting guided by traditional ecological knowledge may have been sustainable and likely originated in societies that also incorporated opportunistic use of stranded individuals. The collation of georeferenced zooarchaeological data of the great whales between the 1st - 20th centuries CE worldwide will provide insight into the timescale and distribution of resource utilisation of the great whales and how this varied within and between societies, and may have changed over time. By comparing regions of known resource utilisation and breeding and feeding grounds of current-day whale populations, this information will subsequently be used to infer regions where whale populations were possibly lost or extirpated prior to detailed historical records. This systematic review protocol also provides a template for archaeologists, ecologists, and historians interested in using faunal remains to infer historical ecology and resource use of wild animal populations. The transparency of our data collection approach provides opportunities for reproducibility and comparability with future datasets

C17 Prevents Inflammatory Arthritis and Associated Joint Destruction in Mice

C17 was first described about ten years ago as a gene expressed in CD34+ cells. A more recent study has suggested a role for C17 in chondrogenesis and development of cartilage. However, based on sequence analysis, we believe that C17 has homology to IL-2 and hence we present the hypothesis that C17 is a cytokine possessing immune-regulatory properties. We provide evidence that C17 is a secreted protein preferentially expressed in chondrocytes, hence in cartilage-rich tissues. Systemic expression of C17 in vivo reduces disease in a collagen antibody-induced arthritis model in mice (CAIA). Joint protection is evident by delayed disease onset, minimal edema, bone protection and absence of diverse histological features of disease. Expression of genes typically associated with acute joint inflammation and erosion of cartilage or bone is blunted in the presence of C17. Consistent with the observed reduction in bone erosion, we demonstrate reduced levels of RANKL in the paws and sera of mice over-expressing C17. Administration of C17 at the peak of disease, however, had no effect on disease progression, indicating that C17's immune-regulatory activity must be most prominent prior to or at the onset of severe joint inflammation. Based on this data we propose C17 as a cytokine that s contributes to immune homeostasis systemically or in a tissue-specific manner in the joint

Rising statin use and effect on ischemic stroke outcome

BACKGROUND: Statins (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) have neuroprotective effects in experimental stroke models and are commonly prescribed in clinical practice. The aim of this study was to determine if patients taking statins before hospital admission for stroke had an improved clinical outcome. METHODS: This was an observational study of 436 patients admitted to the National Institutes of Health Suburban Hospital Stroke Program between July 2000 and December 2002. Self-reported risk factors for stroke were obtained on admission. Stroke severity was determined by the admission National Institutes of Health Stroke Scale score. Good outcome was defined as a Rankin score < 2 at discharge. Statistical analyses used univariate and multivariate logistic regression models. RESULTS: There were 436 patients with a final diagnosis of ischemic stroke; statin data were available for 433 of them. A total of 95/433 (22%) of patients were taking a statin when they were admitted, rising from 16% in 2000 to 26% in 2002. Fifty-one percent of patients taking statins had a good outcome compared to 38% of patients not taking statins (p = 0.03). After adjustment for confounding factors, statin pretreatment was associated with a 2.9 odds (95% CI: 1.2–6.7) of a good outcome at the time of hospital discharge. CONCLUSIONS: The proportion of patients taking statins when they are admitted with stroke is rising rapidly. Statin pretreatment was significantly associated with an improved functional outcome at discharge. This finding could support the early initiation of statin therapy after stroke

Neurodevelopmental and Epilepsy Phenotypes in Individuals With Missense Variants in the Voltage-Sensing and Pore Domains of KCNH5

Background and Objectives KCNH5 encodes the voltage-gated potassium channel EAG2/Kv10.2. We aimed to delineate the neurodevelopmental and epilepsy phenotypic spectrum associated with de novo KCNH5 variants.Methods We screened 893 individuals with developmental and epileptic encephalopathies for KCNH5 variants using targeted or exome sequencing. Additional individuals with KCNH5 variants were identified through an international collaboration. Clinical history, EEG, and imaging data were analyzed; seizure types and epilepsy syndromes were classified. We included 3 previously published individuals including additional phenotypic details.Results We report a cohort of 17 patients, including 9 with a recurrent de novo missense variant p.Arg327His, 4 with a recurrent missense variant p.Arg333His, and 4 additional novel missense variants. All variants were located in or near the functionally critical voltage-sensing or pore domains, absent in the general population, and classified as pathogenic or likely pathogenic using the American College of Medical Genetics and Genomics criteria. All individuals presented with epilepsy with a median seizure onset at 6 months. They had a wide range of seizure types, including focal and generalized seizures. Cognitive outcomes ranged from normal intellect to profound impairment. Individuals with the recurrent p.Arg333His variant had a self-limited drug-responsive focal or generalized epilepsy and normal intellect, whereas the recurrent p.Arg327His variant was associated with infantile-onset DEE. Two individuals with variants in the pore domain were more severely affected, with a neonatal-onset movement disorder, early-infantile DEE, profound disability, and childhood death.Discussion We describe a cohort of 17 individuals with pathogenic or likely pathogenic missense variants in the voltage-sensing and pore domains of Kv10.2, including 14 previously unreported individuals. We present evidence for a putative emerging genotype-phenotype correlation with a spectrum of epilepsy and cognitive outcomes. Overall, we expand the role of EAG proteins in human disease and establish KCNH5 as implicated in a spectrum of neurodevelopmental disorders and epilepsy.</p

Asymmetrical Gene Flow in a Hybrid Zone of Hawaiian Schiedea (Caryophyllaceae) Species with Contrasting Mating Systems

Asymmetrical gene flow, which has frequently been documented in naturally occurring hybrid zones, can result from various genetic and demographic factors. Understanding these factors is important for determining the ecological conditions that permitted hybridization and the evolutionary potential inherent in hybrids. Here, we characterized morphological, nuclear, and chloroplast variation in a putative hybrid zone between Schiedea menziesii and S. salicaria, endemic Hawaiian species with contrasting breeding systems. Schiedea menziesii is hermaphroditic with moderate selfing; S. salicaria is gynodioecious and wind-pollinated, with partially selfing hermaphrodites and largely outcrossed females. We tested three hypotheses: 1) putative hybrids were derived from natural crosses between S. menziesii and S. salicaria, 2) gene flow via pollen is unidirectional from S. salicaria to S. menziesii and 3) in the hybrid zone, traits associated with wind pollination would be favored as a result of pollen-swamping by S. salicaria. Schiedea menziesii and S. salicaria have distinct morphologies and chloroplast genomes but are less differentiated at the nuclear loci. Hybrids are most similar to S. menziesii at chloroplast loci, exhibit nuclear allele frequencies in common with both parental species, and resemble S. salicaria in pollen production and pollen size, traits important to wind pollination. Additionally, unlike S. menziesii, the hybrid zone contains many females, suggesting that the nuclear gene responsible for male sterility in S. salicaria has been transferred to hybrid plants. Continued selection of nuclear genes in the hybrid zone may result in a population that resembles S. salicaria, but retains chloroplast lineage(s) of S. menziesii

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice