58 research outputs found

    Archaeology of marronage in the Caribbean Antilles

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    The archaeological study of maroons in the Caribbean Antilles presents both opportunities and challenges. On small islands, runaways had few places where they could seek refuge from slavery and elude capture for long periods of time. Consequently, such sites were occupied briefly and have been difficult to locate and identify. The Greater Antilles (Cuba, Jamaica, Hispaniola, and Puerto Rico) had both short-term refuge sites and long-term settlements comparable to quilombos. Archaeologists have been most successful in their investigations maroons in Cuba and Jamaica. In Hispaniola, where I am working at the present, only a few cave sites and one presumed maniel (the local term for a long-term maroon settlements) have been studied. In this paper, I provide an overview of the archaeological study of maroons on the Caribbean Islands and my preliminary research to locate El Maniel de Ocoa, a major settlement of slave runaways for over a hundred years during 1500s-1660s.  O estudo arqueolĂłgico de maroons nas Antilhas do Caribe apresenta oportunidades e desafios. Em pequenas ilhas, os fugitivos tinham poucos lugares onde podiam buscar refĂșgio da escravidĂŁo e iludir a captura por longos perĂ­odos de tempo. Consequentemente, esses sĂ­tios foram ocupados brevemente e tĂȘm sido difĂ­ceis de localizar e identificar. As Grandes Antilhas (Cuba, Jamaica, Hispaniola e Porto Rico) possuĂ­am locais de refĂșgio de curto prazo e assentamentos de longo prazo comparĂĄveis aos quilombos. Os arqueĂłlogos foram mais bem-sucedidos em suas investigaçÔes de maroons em Cuba e na Jamaica. Em Hispaniola, onde estou trabalhando no momento, apenas alguns locais de cavernas e um suposto maniel (o termo local para um assentamento maroon de longo prazo) foram estudados. Neste artigo, forneço uma visĂŁo geral do estudo arqueolĂłgico de marrons nas Ilhas do Caribe e minha pesquisa preliminar para localizar El Maniel de Ocoa, um importante assentamento de fugitivos de escravos por mais de cem anos, entre 1500 e 1660

    Subprime and predatory lending in rural America: mortgage lending practices that can trap low-income rural people

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    This brief examines predatory mortgage loans and the harmful impact they have on rural homeowners and their communities. The report finds that minorities and low-income people are more likely to fall victim to higher-cost loans. The brief includes recommendations for policy changes at the state and federal levels, as well as advice on identifying and avoiding predatory loans

    Pharmacokinetic evaluation of the PNC disassembler metarrestin in wild-type and Pdx1-Cre;LSL-KrasG12D/+;Tp53R172H/+ (KPC) mice, a genetically engineered model of pancreatic cancer

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    This work is licensed under a Creative Commons Attribution 4.0 International License.Purpose Metarrestin is a first-in-class small molecule clinical candidate capable of disrupting the perinucleolar compartment, a subnuclear structure unique to metastatic cancer cells. This study aims to define the pharmacokinetic (PK) profile of metarrestin and the pharmacokinetic/pharmacodynamic relationship of metarrestin-regulated markers. Methods PK studies included the administration of single or multiple dose of metarrestin at 3, 10, or 25 mg/kg via intravenous (IV) injection, gavage (PO) or with chow to wild-type C57BL/6 mice and KPC mice bearing autochthonous pancreatic tumors. Metarrestin concentrations were analyzed by UPLC–MS/MS. Pharmacodynamic assays included mRNA expression profiling by RNA-seq and qRT-PCR for KPC mice. Results Metarrestin had a moderate plasma clearance of 48 mL/min/kg and a large volume of distribution of 17 L/kg at 3 mg/kg IV in C57BL/6 mice. The oral bioavailability after single-dose (SD) treatment was > 80%. In KPC mice treated with SD 25 mg/kg PO, plasma AUC0–∞ of 14400 ng h/mL, Cmax of 810 ng/mL and half-life (t1/2) of 8.5 h were observed. At 24 h after SD of 25 mg/kg PO, the intratumor concentration of metarrestin was high with a mean value of 6.2 ”g/g tissue (or 13 ”M), well above the cell-based IC50 of 0.4 ”M. At multiple dose (MD) 25 mg/kg/day PO in KPC mice, mean tissue/plasma AUC0–24h ratio for tumor, spleen and liver was 37, 30 and 31, respectively. There was a good linear relationship of dosage to AUC0–24h and C24h. AUC0–24h MD to AUC0–24h SD ratios ranged from two for liver to five for tumor indicating additional accumulation in tumors. Dose-dependent normalization of FOXA1 and FOXO6 mRNA expression was observed in KPC tumors. Conclusions Metarrestin is an effective therapeutic candidate with a favorable PK profile achieving excellent intratumor tissue levels in a disease with known poor drug delivery.Intramural Research Program (IRP) of the NIHNational Cancer InstituteCenter for Cancer Research (ZIA BC 011267

    Can Orchards Help Connect Mediterranean Ecosystems? Animal Movement Data Alter Conservation Priorities

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    As natural habitats become fragmented by human activities, animals must increasingly move through human-dominated systems, particularly agricultural landscapes. Mapping areas important for animal movement has therefore become a key part of conservation planning. Models of landscape connectivity are often parameterized using expert opinion and seldom distinguish between the risks and barriers presented by different crop types. Recent research, however, suggests different crop types, such as row crops and orchards, differ in the degree to which they facilitate or impede species movements. Like many mammalian carnivores, bobcats (Lynx rufus) are sensitive to fragmentation and loss of connectivity between habitat patches. We investigated how distinguishing between different agricultural land covers might change conclusions about the relative conservation importance of different land uses in a Mediterranean ecosystem. Bobcats moved relatively quickly in row crops but relatively slowly in orchards, at rates similar to those in natural habitats of woodlands and scrub. We found that parameterizing a connectivity model using empirical data on bobcat movements in agricultural lands and other land covers, instead of parameterizing the model using habitat suitability indices based on expert opinion, altered locations of predicted animal movement routes. These results emphasize that differentiating between types of agriculture can alter conservation planning outcomes

    Mundos mesclados, espaços segregados: cultura material, mestiçagem e segmentação no sítio Aldeia em Santarém (PA)

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    This article discusses the processes of cultural exchange between Portuguese, Portuguese-Brazilian, Amerindians, and mestizos based on the analysis of the material culture from households of SantarĂ©m (PA), occupied during the eighteenth and nineteenth centuries,. Although these social groups manipulated material culture aiming to express different values, related to hierarchy, social segmentation, and affirmation of identities, ambiguity also characterizes these assemblages. This material ambiguity informs about the mixtures of both practices and cultural references that brought about the building of a mestizo society.Com base na anĂĄlise da cultura material proveniente de unidades domĂ©sticas do nĂșcleo urbano de SantarĂ©m (PA), ocupadas nos sĂ©culos XVIII e XIX, o presente artigo discute os processos de trocas culturais entre portugueses, luso-brasileiros, indĂ­genas e mestiços. Embora esses grupos sociais tenham manipulado a cultura material visando expressar diferentes valores, relacionados Ă  hierarquia, segmentação social e afirmação de identidades, a ambigĂŒidade Ă© uma caracterĂ­stica das amostras analisadas, informando sobre as misturas de prĂĄticas e de referenciais culturais que levaram Ă  construção de uma sociedade mestiça

    Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

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    Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

    SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

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    Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

    Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

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    IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570
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