Wrapped in Meaning: Chumash Cache Caves

A large number of dry caves scattered across the mountainous Santa Barbara backcountry, in south-central California, have yielded a unique collection of indigenous artefacts. The xeric environmental conditions in these caves have resulted in exceptional preservation of perishable materials; and the assemblage contains items such as wooden bullroarers, feather bands, deer bone whistles, basketry and curated plant materials. A significant proportion of this material appears to have been deposited in the colonial period (AD 1769 – late 19th century). This region was occupied primarily by the indigenous Chumash people, semi-sedentary hunter-gatherers who were characterised by their complex political organisation, diverse subsistence base, and rich ceremonial tradition. Indigenous life was plunged into turmoil from AD 1769 when the Spanish missionisation programme heralded the start of the colonial period. Over the next hundred years Spanish, Mexican and Anglo-American colonisers dramatically changed the economic, political and ecological landscape of south-central California. The majority of archaeological studies pertaining to the Chumash have focused on the prehistoric period. Most previous colonial-period studies have concentrated on the missions and closely adjacent indigenous sites where colonial influence was strongest. The study of cache caves and their artefacts provides a novel opportunity to explore indigenous practices during the turbulent colonial period within the more autonomous context of the Santa Barbara hinterland. This thesis provides the first collation of all the data relating to cache cave sites and their associated artefacts in the Santa Barbara hinterland. This information has been used to provide a basic chronological and geographic framework, and in turn, to propose models for indigenous caching practices in the Santa Barbara hinterland. These caching models are explored in terms of value systems in order to consider processes of indigenous resistance and acculturation during the colonial period

CD4 enumeration technologies: a systematic review of test performance for determining eligibility for antiretroviral therapy.

BACKGROUND: Measurement of CD4+ T-lymphocytes (CD4) is a crucial parameter in the management of HIV patients, particularly in determining eligibility to initiate antiretroviral treatment (ART). A number of technologies exist for CD4 enumeration, with considerable variation in cost, complexity, and operational requirements. We conducted a systematic review of the performance of technologies for CD4 enumeration. METHODS AND FINDINGS: Studies were identified by searching electronic databases MEDLINE and EMBASE using a pre-defined search strategy. Data on test accuracy and precision included bias and limits of agreement with a reference standard, and misclassification probabilities around CD4 thresholds of 200 and 350 cells/μl over a clinically relevant range. The secondary outcome measure was test imprecision, expressed as % coefficient of variation. Thirty-two studies evaluating 15 CD4 technologies were included, of which less than half presented data on bias and misclassification compared to the same reference technology. At CD4 counts 350 cells/μl, bias ranged from -70.7 to +47 cells/μl, compared to the BD FACSCount as a reference technology. Misclassification around the threshold of 350 cells/μl ranged from 1-29% for upward classification, resulting in under-treatment, and 7-68% for downward classification resulting in overtreatment. Less than half of these studies reported within laboratory precision or reproducibility of the CD4 values obtained. CONCLUSIONS: A wide range of bias and percent misclassification around treatment thresholds were reported on the CD4 enumeration technologies included in this review, with few studies reporting assay precision. The lack of standardised methodology on test evaluation, including the use of different reference standards, is a barrier to assessing relative assay performance and could hinder the introduction of new point-of-care assays in countries where they are most needed

Cleavage of Stalled Forks by Fission Yeast Mus81/Eme1 in Absence of DNA Replication Checkpoint

During replication arrest, the DNA replication checkpoint plays a crucial role in the stabilization of the replisome at stalled forks, thus preventing the collapse of active forks and the formation of aberrant DNA structures. How this checkpoint acts to preserve the integrity of replication structures at stalled fork is poorly understood. In Schizosaccharomyces pombe, the DNA replication checkpoint kinase Cds1 negatively regulates the structure-specific endonuclease Mus81/Eme1 to preserve genomic integrity when replication is perturbed. Here, we report that, in response to hydroxyurea (HU) treatment, the replication checkpoint prevents S-phase–specific DNA breakage resulting from Mus81 nuclease activity. However, loss of Mus81 regulation by Cds1 is not sufficient to produce HU-induced DNA breaks. Our results suggest that unscheduled cleavage of stalled forks by Mus81 is permitted when the replisome is not stabilized by the replication checkpoint. We also show that HU-induced DNA breaks are partially dependent on the Rqh1 helicase, the fission yeast homologue of BLM, but are independent of its helicase activity. This suggests that efficient cleavage of stalled forks by Mus81 requires Rqh1. Finally, we identified an interplay between Mus81 activity at stalled forks and the Chk1-dependent DNA damage checkpoint during S-phase when replication forks have collapsed