Building a Landscape History and Occupational Chronology at Čḯxwicən, a Coastal Village on the Strait of Juan de Fuca, Washington State, U.S.A

Geoarchaeological analysis at Čḯxwicən, an ancestral Klallam village near Port Angeles in northwestern Washington State, U.S.A., highlights the resilience of coastal foragers and their connection to place. Ancestral Klallam peoples occupied ever-changing beach and spit landforms growing within the shelter of Ediz Hook on the Strait of Juan de Fuca (SJDF) for 2700 years. Geoarchaeological methods were employed to define seven chronostratigraphic zones that chronologically structure the cultural deposits and allow them to be correlated to a sequence of beach development and to markers for tsunami that overtopped the site. Initial habitation prior to 1750 BP utilized a narrow beach against the bluff, then expanded with the prograding beach ridges, which grew north to create a lagoon. Stabilization of beach ridges after 1300 and 1000 BP was followed in each case by construction of a plank house, one of which was occupied for 800 years, and the other for 500 years. Inundation of the site, as indicated by erosional channels, backwash deposits, and structural collapse, occurred five times, and can be correlated with documented Cascadia Subduction Zone plate boundary megathrust earthquake events. The resilience of the households, who re-occupied the houses soon after the events, is striking, particularly the rebuilding of one house after it collapsed around 600BP

Late Holocene Tsunami Deposits at Salt Creek, Washington, USA

We interpret two thin sand layers in the estuarine marsh at Salt Creek, on the southern shore of the Strait of Juan de Fuca, as the products of tsunamis propagated by earthquakes at the Cascadia subduction zone. The sand layers extend for about 60 m along the left bank of the creek about 800 m from the mouth, and can be traced to the base of a nearby upland area. One layer is exposed in the creek bank about 400 m further upstream, but they are only patchily distributed in the rest of the central area of the marsh. Both layers contain brackish-marine epipsammic diatoms. The lower sand layer marks a sharp contact between intertidal peaty mud and overlying mud, perhaps reflecting modest coseismic subsidence in association with tsunami deposition, but little or no change in the bracketing sediment occurs in association with the upper sand layer. The ages of the sand layers are not closely constrained, but were most likely deposited by tsunamis generated by great earthquakes at the Cascadia subduction zone about 1650 and 1300 years ago. The Cascadia great earthquake of AD1700 may have induced slight subsidence in the marsh, but no tsunami deposit was detected at the inferred contact. The absence of deposits from the marsh immediately inland of the 4 m-high barrier beach indicates that the largest tsunamis in the late Holocene at this site have not overtopped the barrier, which suggests that these tsunamis were likely only 2-3 m high

The Čḯxwicən Project of Northwest Washington State, U.S.A.: Opportunity Lost, Opportunity Found

Čḯxwicən (pronounced ch-WHEET-son) is a 2700 year-old ancestral village of the Lower Elwha Klallam Tribe (LEKT), located on the northwest coast of Washington State, U.S.A. The Čḯxwicən project has scientific values that broadly contribute to research in human ecodynamics and maritime foragers, given the scale of the project, excavation methods, and enormous quantities of faunal materials recovered. The village holds great significance to the LEKT as their traditional village, which includes a sacred burial ground. The project began under challenging circumstances, when the village was inadvertently encountered during a construction project, incurring huge political, social and financial costs. Commitment by the LEKT and Čḯxwicən scholars and other partners turned an “opportunity lost” into an “opportunity found.” This paper provides background to this remarkable site and project goals that guided the Čḯxwicən research project. The Special Issue papers showcase project results, including reflections by tribal members. Overall, the project shows the potential for archaeology and heritage to support reconciliation between tribes and archaeologists and broader society

Characteristics and Outcomes of Patients with Vasoplegic Versus Tissue Dysoxic Septic Shock

Background: The current consensus definition of septic shock requires hypotension after adequate fluid challenge or vasopressor requirement. Some patients with septic shock present with hypotension and hyperlactatemia greater than 2 mmol/L (tissue dysoxic shock), whereas others have hypotension alone with normal lactate (vasoplegic shock). Objective: The objective of this study was to determine differences in outcomes of patients with tissue dysoxic versus vasoplegic septic shock. Methods: This was a secondary analysis of a large, multicenter randomized controlled trial. Inclusion criteria were suspected infection, two or more systemic inflammatory response criteria, and systolic blood pressure less than 90 mmHg after a fluid bolus. Patients were categorized by presence of vasoplegic or tissue dysoxic shock. Demographics and Sequential Organ Failure Assessment scores were evaluated between the groups. The primary outcome was in-hospital mortality. Results: A total of 247 patients were included, 90 patients with vasoplegic shock and 157 with tissue dysoxic shock. There were no significant differences in age, race, or sex between the vasoplegic and tissue dysoxic shock groups. The group with vasoplegic shock had a lower initial Sequential Organ Failure Assessment score than did the group with tissue dysoxic shock (5.5 vs. 7.0 points; P = 0.0002). The primary outcome of in-hospital mortality occurred in 8 (9%) of 90 patients with vasoplegic shock compared with 41 (26%) of 157 in the group with tissue dysoxic shock (proportion difference, 17%; 95% confidence interval, 7%–26%; P < 0.0001; log-rank test P = 0.02). After adjusting for confounders, tissue dysoxic shock remained an independent predictor of in-hospital mortality. Conclusions: In this analysis of patients with septic shock, we found a significant difference in in-hospital mortality between patients with vasoplegic versus tissue dysoxic septic shock. These findings suggest a need to consider these differences when designing future studies of septic shock therapies

A subset of NSAIDs lower amyloidogenic Aβ42 independently of cyclooxygenase activity

Epidemiological studies have documented a reduced prevalence of Alzheimer's disease among users of nonsteroidal anti-inflammatory drugs (NSAIDs). It has been proposed that NSAIDs exert their beneficial effects in part by reducing neurotoxic inflammatory responses in the brain, although this mechanism has not been proved. Here we report that the NSAIDs ibuprofen, indomethacin and sulindac sulphide preferentially decrease the highly amyloidogenic Aβ42 peptide (the 42-residue isoform of the amyloid-β peptide) produced from a variety of cultured cells by as much as 80%. This effect was not seen in all NSAIDs and seems not to be mediated by inhibition of cyclooxygenase (COX) activity, the principal pharmacological target of NSAIDs. Furthermore, short-term administration of ibuprofen to mice that produce mutant β-amyloid precursor protein (APP) lowered their brain levels of Aβ42. In cultured cells, the decrease in Aβ42 secretion was accompanied by an increase in the Aβ(1–38) isoform, indicating that NSAIDs subtly alter γ-secretase activity without significantly perturbing other APP processing pathways or Notch cleavage. Our findings suggest that NSAIDs directly affect amyloid pathology in the brain by reducing Aβ42 peptide levels independently of COX activity and that this Aβ42-lowering activity could be optimized to selectively target the pathogenic Aβ42 species

B Cells Migrate into Remote Brain Areas and Support Neurogenesis and Functional Recovery after Focal Stroke in Mice

Lymphocytes infiltrate the stroke core and penumbra and often exacerbate cellular injury. B cells, however, are lymphocytes that do not contribute to acute pathology but can support recovery. B cell adoptive transfer to mice reduced infarct volumes 3 and 7 d after transient middle cerebral artery occlusion (tMCAo), independent of changing immune populations in recipient mice. Testing a direct neurotrophic effect, B cells cocultured with mixed cortical cells protected neurons and maintained dendritic arborization after oxygen-glucose deprivation. Whole-brain volumetric serial two-photon tomography (STPT) and a custom-developed image analysis pipeline visualized and quantified poststroke B cell diapedesis throughout the brain, including remote areas supporting functional recovery. Stroke induced significant bilateral B cell diapedesis into remote brain regions regulating motor and cognitive functions and neurogenesis (e.g., dentate gyrus, hypothalamus, olfactory areas, cerebellum) in the whole-brain datasets. To confirm a mechanistic role for B cells in functional recovery, rituximab was given to human CD20+ (hCD20+) transgenic mice to continuously deplete hCD20+-expressing B cells following tMCAo. These mice experienced delayed motor recovery, impaired spatial memory, and increased anxiety through 8 wk poststroke compared to wild type (WT) littermates also receiving rituximab. B cell depletion reduced stroke-induced hippocampal neurogenesis and cell survival. Thus, B cell diapedesis occurred in areas remote to the infarct that mediated motor and cognitive recovery. Understanding the role of B cells in neuronal health and disease-based plasticity is critical for developing effective immune-based therapies for protection against diseases that involve recruitment of peripheral immune cells into the injured brain

Novel Use of Surveillance Data to Detect HIV-Infected Persons with Sustained High Viral Load and Durable Virologic Suppression in New York City

Background: Monitoring of the uptake and efficacy of ART in a population often relies on cross-sectional data, providing limited information that could be used to design specific targeted intervention programs. Using repeated measures of viral load (VL) surveillance data, we aimed to estimate and characterize the proportion of persons living with HIV/AIDS (PLWHA) in New York City (NYC) with sustained high VL (SHVL) and durably suppressed VL (DSVL). Methods/Principal Findings: Retrospective cohort study of all persons reported to the NYC HIV Surveillance Registry who were alive and $12 years old by the end of 2005 and who had$2 VL tests in 2006 and 2007. SHVL and DSVL were defined as PLWHA with 2 consecutive VLs $100,000 copies/mL and PLWHA with all VLs #400 copies/mL, respectively. Logistic regression models using generalized estimating equations were used to model the association between SHVL and covariates. There were 56,836 PLWHA, of whom 7 % had SHVL and 38 % had DSVL. Compared to those without SHVL, persons with SHVL were more likely to be younger, black and have injection drug use (IDU) risk. PLWHA with SHVL were more likely to die by 2007 and be younger by nearly ten years, on average. Conclusions/Significance: Nearly 60 % of PLWHA in 2005 had multiple VLs, of whom almost 40 % had DSVL, suggesting successful ART uptake. A small proportion had SHVL, representing groups known to have suboptimal engagement in care. This group should be targeted for additional outreach to reduce morbidity and secondary transmission. Measures based o

Border Insecurity: Reading Transnational Environments in Jim Lynch’s Border Songs

This article applies an eco-critical approach to contemporary American fiction about the Canada-US border, examining Jim Lynch’s portrayal of the British Columbia-Washington borderlands in his 2009 novel Border Songs. It argues that studying transnational environmental actors in border texts—in this case, marijuana, human migrants, and migratory birds—helps illuminate the contingency of political boundaries, problems of scale, and discourses of risk and security in cross-border regions after 9/11. Further, it suggests that widening the analysis of trans-border activity to include environmental phenomena productively troubles concepts of nature and regional belonging in an era of climate change and economic globalization. Cet article propose une lecture écocritique de la fiction étatsunienne contemporaine portant sur la frontière entre le Canada et les États-Unis, en étudiant le portrait donné par Jim Lynch de la région frontalière entre la Colombie-Britannique et Washington dans son roman Border Songs, paru en 2009. L’article soutient que l’étude, dans les textes sur la frontière, des acteurs environnementaux transnationaux – dans ce cas-ci, la marijuana, les migrants humains et les oiseaux migratoires – jette un jour nouveau sur la contingence des limites territoriales politiques, des problèmes d’échelle et des discours sur le risque et la sécurité des régions transfrontalières après les évènements du 11 septembre 2001. Il suggère également qu’en élargissant l’analyse de l’activité transfrontalière pour y inclure les phénomènes environnementaux, on brouille de façon productive les concepts de nature et d’appartenance régionale d’une époque marquée par les changements climatiques et la mondialisation de l’économie