Beringia and the global dispersal of modern humans.

Until recently, the settlement of the Americas seemed largely divorced from the out-of-Africa dispersal of anatomically modern humans, which began at least 50,000 years ago. Native Americans were thought to represent a small subset of the Eurasian population that migrated to the Western Hemisphere less than 15,000 years ago. Archeological discoveries since 2000 reveal, however, that Homo sapiens occupied the high-latitude region between Northeast Asia and northwest North America (that is, Beringia) before 30,000 years ago and the Last Glacial Maximum (LGM). The settlement of Beringia now appears to have been part of modern human dispersal in northern Eurasia. A 2007 model, the Beringian Standstill Hypothesis, which is based on analysis of mitochondrial DNA (mtDNA) in living people, derives Native Americans from a population that occupied Beringia during the LGM. The model suggests a parallel between ancestral Native Americans and modern human populations that retreated to refugia in other parts of the world during the arid LGM. It is supported by evidence of comparatively mild climates and rich biota in south-central Beringia at this time (30,000-15,000 years ago). These and other developments suggest that the settlement of the Americas may be integrated with the global dispersal of modern humans.

A comparative study of ancient sedimentary DNA, pollen and macrofossils from permafrost sediments of northern Siberia reveals long-term vegetational stability.

Although ancient DNA from sediments (sedaDNA) has been used to investigate past ecosystems, the approach has never been directly compared with the traditional methods of pollen and macrofossil analysis. We conducted a comparative survey of 18 ancient permafrost samples spanning the Late Pleistocene (46-12.5 thousand years ago), from the Taymyr Peninsula in northern Siberia. The results show that pollen, macrofossils and sedaDNA are complementary rather than overlapping and, in combination, reveal more detailed information on plant palaeocommunities than can be achieved by each individual approach. SedaDNA and macrofossils share greater overlap in plant identifications than with pollen, suggesting that sedaDNA is local in origin. These two proxies also permit identification to lower taxonomic levels than pollen, enabling investigation into temporal changes in species composition and the determination of indicator species to describe environmental changes. Combining data from all three proxies reveals an area continually dominated by a mosaic vegetation of tundra-steppe, pioneer and wet-indicator plants. Such vegetational stability is unexpected, given the severe climate changes taking place in the Northern Hemisphere during this time, with changes in average annual temperatures of >22 °C. This may explain the abundance of ice-age mammals such as horse and bison in Taymyr Peninsula during the Pleistocene and why it acted as a refugium for the last mainland woolly mammoth. Our finding reveals the benefits of combining sedaDNA, pollen and macrofossil for palaeovegetational reconstruction and adds to the increasing evidence suggesting large areas of the Northern Hemisphere remained ecologically stable during the Late Pleistocene.

A new terrestrial palaeoenvironmental record from the Bering Land Bridge and context for human dispersal.

Palaeoenvironmental records from the now-submerged Bering Land Bridge (BLB) covering the Last Glacial Maximum (LGM) to the present are needed to document changing environments and connections with the dispersal of humans into North America. Moreover, terrestrially based records of environmental changes are needed in close proximity to the re-establishment of circulation between Pacific and Atlantic Oceans following the end of the last glaciation to test palaeo-climate models for the high latitudes. We present the first terrestrial temperature and hydrologic reconstructions from the LGM to the present from the BLB's south-central margin. We find that the timing of the earliest unequivocal human dispersals into Alaska, based on archaeological evidence, corresponds with a shift to warmer/wetter conditions on the BLB between 14 700 and 13 500 years ago associated with the early Bølling/Allerød interstadial (BA). These environmental changes could have provided the impetus for eastward human dispersal at that time, from Western or central Beringia after a protracted human population standstill. Our data indicate substantial climate-induced environmental changes on the BLB since the LGM, which would potentially have had significant influences on megafaunal and human biogeography in the region.

Neutrophil CD64 is an improved indicator of infection or sepsis in emergency department patients.

CONTEXT: Sepsis, affecting millions of individuals annually with an associated high mortality rate, is among the top 10 causes of death. In addition, improvements in diagnostic tests for detecting and monitoring sepsis and infection have been limited in the last 25 years. Neutrophil CD64 expression has been proposed as an improved diagnostic test for the evaluation of infection and sepsis. OBJECTIVE: To evaluate the diagnostic performance of a quantitative flow cytometric assay for leukocyte CD64 expression in comparison with the standard tests for infection/sepsis in an ambulatory care setting. DESIGN: Prospective analysis of 100 blood samples from patients from an emergency department setting in a 965-bed tertiary care suburban community hospital was performed for neutrophil CD64 expression, C-reactive protein, erythrocyte sedimentation rate, and complete blood count. The laboratory findings were compared with a clinical score for the likelihood of infection/sepsis, which was obtained by a blinded retrospective chart review. RESULTS: The diagnostic performance, as gauged by the clinical score, varied with neutrophil CD64 (sensitivity 87.9%, specificity 71.2%, efficiency 76.8%) and outperformed C-reactive protein (sensitivity 88.2%, specificity 59.4%, efficiency 69.4%), absolute neutrophil count (sensitivity 60.0%, specificity 50.8%, efficiency 53.8%), myeloid left shift (sensitivity 68.2%, specificity 76.3%, efficiency 73.3%), and sedimentation rate (sensitivity 50.0%, specificity 65.5%, efficiency 61.0%). CONCLUSION: Neutrophil CD64 expression quantitation provides improved diagnostic detection of infection/sepsis compared with the standard diagnostic tests used in current medical practice.

Comparison of neutrophil CD64 expression, manual myeloid immaturity counts, and automated hematology analyzer flags as indicators of infection or sepsis.

There is a clear need for improved indicators of infection or sepsis to increase the sensitivity and specificity of both diagnosis and therapeutic monitoring. One of the effects of inflammatory cytokines on the innate immune response is the rapid up-regulation of CD64 expression on the neutrophil membrane. We and others have hypothesized that the measurement of neutrophil CD64 expression might represent an improved diagnostic indicator of infection and sepsis. In this study we assessed the relative ability of flow cytometric neutrophil CD64 measurements, neutrophil counts, myeloid immaturity differential counts, and flagging on an automated hematology analyzer to correlate with the presence of infection, as determined by a retrospective clinical scoring system of infection or sepsis. A total of 160 blood samples were randomly selected to derive equal proportions of the 3 categories of flags on a Coulter STKS blood counter that indicate the presence of a myeloid left shift. The patients for these samples were scored by retrospective chart review and placed into 4 groups on the basis of likelihood of infection, sepsis, or severe tissue injury. Neutrophil CD64 expression demonstrated a superior sensitivity (94.1%), specificity (84.9%), and positive predictive likelihood ratio (6.24), compared with neutrophil counts (sensitivity, 79.4%; specificity, 46.8%; positive predictive likelihood ratio, 1.49), band counts (sensitivity, 87.5%; specificity, 43.5%; positive predictive likelihood ratio, 1.55), myeloid immaturity fraction (sensitivity, 94.6%; specificity, 84.5%; positive predictive likelihood ratio, 2.12), and flagging on an automated hematology analyzer (sensitivity, 94.1%; specificity, 40.5%; positive predictive likelihood ratio, 1.58). Relative to the other laboratory parameters, the neutrophil CD64 parameter also provided the best separation of the 4 clinical groups. The findings indicate that neutrophil CD64 expression as determined by quantitative flow cytometry is an improved diagnostic indicator of infection/sepsis relative to current laboratory indicators of relative or absolute myeloid cell counts or hematology analyzer flagging algorithms.