The time of arrival of people in Australia is an unresolved question. It is relevant to debates about when modern humans first dispersed out of Africa and when their descendants incorporated genetic ...material from Neanderthals, Denisovans and possibly other hominins. Humans have also been implicated in the extinction of Australia's megafauna. Here we report the results of new excavations conducted at Madjedbebe, a rock shelter in northern Australia. Artefacts in primary depositional context are concentrated in three dense bands, with the stratigraphic integrity of the deposit demonstrated by artefact refits and by optical dating and other analyses of the sediments. Human occupation began around 65,000 years ago, with a distinctive stone tool assemblage including grinding stones, ground ochres, reflective additives and ground-edge hatchet heads. This evidence sets a new minimum age for the arrival of humans in Australia, the dispersal of modern humans out of Africa, and the subsequent interactions of modern humans with Neanderthals and Denisovans.
This paper links new firm survival with growth, with a focus on the patterns in firms' growth paths. We theorise a Gambler's Ruin framework by arguing that new firm performance is best modelled as a ...random walk process, but that survival is nonrandom and depends primarily on the stock of accumulated resources. A firm's resources are either there when the business begins or are generated by successful periods — ‘wins’. The empirical section tracks, over six years, the sales and survival/non-survival of 6247 UK start-ups which all began trading in the same quarter of 2004. We do not find strong evidence in favour of a taxonomy of growth paths, because we observe that every possible growth path seems to occur with roughly equal probability. However, we observe that growth paths influence subsequent survival. Controlling for lagged size, we observe that longer lags of growth, and even start-up size, have significant effects on survival.
► We investigate the growth and survival of nascent businesses by analyzing their bank records. ► We do not find strong evidence in favour of a taxonomy of growth paths. ► Every possible growth path seems to occur with roughly equal probability. ► We observe that survival depends on the business' growth path. ► Even when controlling for lagged size, lagged growth has significant effects on survival.
Enteroendocrine cells (EECs) produce hormones such as glucagon-like peptide 1 and peptide YY that regulate food absorption, insulin secretion, and appetite. Based on the success of glucagon-like ...peptide 1-based therapies for type 2 diabetes and obesity, EECs are themselves the focus of drug discovery programs to enhance gut hormone secretion. The aim of this study was to identify the transcriptome and peptidome of human EECs and to provide a cross-species comparison between humans and mice. By RNA sequencing of human EECs purified by flow cytometry after cell fixation and staining, we present a first transcriptomic analysis of human EEC populations and demonstrate a strong correlation with murine counterparts. RNA sequencing was deep enough to enable identification of low-abundance transcripts such as G-protein-coupled receptors and ion channels, revealing expression in human EECs of G-protein-coupled receptors previously found to play roles in postprandial nutrient detection. With liquid chromatography-tandem mass spectrometry, we profiled the gradients of peptide hormones along the human and mouse gut, including their sequences and posttranslational modifications. The transcriptomic and peptidomic profiles of human and mouse EECs and cross-species comparison will be valuable tools for drug discovery programs and for understanding human metabolism and the endocrine impacts of bariatric surgery.
Abstract We propose a new set of priorities for quality management in primary care, acknowledging that payers and regulators likely will continue to insist on reporting numerical quality metrics. ...Primary care practices have been described as complex adaptive systems. Traditional quality improvement processes applied to linear mechanical systems, such as isolated single-disease care, are inappropriate for nonlinear, complex adaptive systems, such as primary care, because of differences in care processes, outcome goals, and the validity of summative quality scorecards. Our priorities for primary care quality management include patient-centered reporting; quality goals not based on rigid targets; metrics that capture avoidance of excessive testing or treatment; attributes of primary care associated with better outcomes and lower costs; less emphasis on patient satisfaction scores; patient-centered outcomes, such as days of avoidable disability; and peer-led qualitative reviews of patterns of care, practice infrastructure, and intrapractice relationships.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
The single grain optically stimulated luminescence (OSL) chronology for the sedimentary deposit at Diepkloof Rockshelter, reported by Jacobs et al. (2008c), has recently been critiqued and several ...reasons proposed for why the OSL ages for the Intermediate and Early Howieson's Poort (HP) and Still Bay (SB) techno-complexes might be inaccurate. Tribolo et al. (2013) presented a series of OSL and thermoluminescence (TL) ages that were in agreement with each other, but, for some part of the sequence at least, were much older than the OSL chronology of Jacobs et al. (2008c). In this paper, we have tested the criticisms of Tribolo et al. (2013) and colleagues related to both the equivalent dose (De) estimates and the beta dose rates by performing a series of targeted experiments, combined with updates and re-assessments of our error calculations. We show that the De estimates are stable over a range of alternative measurement conditions and also over time. We also demonstrate the reproducibility of our measurement procedures for the beta dose rates, and their accuracy tested against a range of independently obtained estimates. We show that, for the stratigraphic units (SUs) where there are major discrepancies in age between Jacobs et al. (2008c) and Tribolo et al. (2013)—notably the Intermediate HP and Early HP—and for which both studies had single grain OSL ages, the estimation of potassium (K) in the sediment surrounding the dated grains is critical. We provide new and updated De and dose rate estimates, and final ages which we compare with our previous age estimates and those of Tribolo et al. (2013). The differences in the size of the errors associated with the ages reported in the two independent studies are also addressed. We can show that our ages are robust and consistent with the original chronology, but we cannot satisfactorily explain why the TL and OSL ages provided by Tribolo et al. (2013) might be wrong. So, the dating conundrum at Diepkloof Rockshelter remains. As a result, we caution against the development of HP and SB age models based on only one of the chronologies for this site. At this stage, extrapolation of the Tribolo et al. (2013) chronology to a re-interpretation of the southern African MSA would appear to be premature, especially as the ages do not differ systematically between the two studies and as differences between TL and OSL ages are not an issue at other sites in southern Africa where both dating methods have been applied. Further work is needed to resolve the question of the Diepkloof chronology.
•We report improved single grain OSL ages for the MSA layers at Diepkloof, South Africa.•We report a series of internal checks of equivalent dose and beta dose rate.•We propose a new method for estimating beta dose rate errors from GM-25-5 beta counting.•We compare our new ages with those published previously by us and others.•We explore causes for remaining discrepancies between alternative chronologies.
The Altai region of Siberia was inhabited for parts of the Pleistocene by at least two groups of archaic hominins-Denisovans and Neanderthals. Denisova Cave, uniquely, contains stratified deposits ...that preserve skeletal and genetic evidence of both hominins, artefacts made from stone and other materials, and a range of animal and plant remains. The previous site chronology is based largely on radiocarbon ages for fragments of bone and charcoal that are up to 50,000 years old; older ages of equivocal reliability have been estimated from thermoluminescence and palaeomagnetic analyses of sediments, and genetic analyses of hominin DNA. Here we describe the stratigraphic sequences in Denisova Cave, establish a chronology for the Pleistocene deposits and associated remains from optical dating of the cave sediments, and reconstruct the environmental context of hominin occupation of the site from around 300,000 to 20,000 years ago.
The peopling of Sahul (the combined continent of Australia and New Guinea) represents the earliest continental migration and settlement event of solely anatomically modern humans, but its patterns ...and ecological drivers remain largely conceptual in the current literature. We present an advanced stochastic-ecological model to test the relative support for scenarios describing where and when the first humans entered Sahul, and their most probable routes of early settlement. The model supports a dominant entry via the northwest Sahul Shelf first, potentially followed by a second entry through New Guinea, with initial entry most consistent with 50,000 or 75,000 years ago based on comparison with bias-corrected archaeological map layers. The model's emergent properties predict that peopling of the entire continent occurred rapidly across all ecological environments within 156-208 human generations (4368-5599 years) and at a plausible rate of 0.71-0.92 km year
. More broadly, our methods and approaches can readily inform other global migration debates, with results supporting an exit of anatomically modern humans from Africa 63,000-90,000 years ago, and the peopling of Eurasia in as little as 12,000-15,000 years via inland routes.
The Arabian Peninsula is a key region for understanding hominin dispersals and the effect of climate change on prehistoric demography, although little information on these topics is presently ...available owing to the poor preservation of archaeological sites in this desert environment. Here, we describe the discovery of three stratified and buried archaeological sites in the Nefud Desert, which includes the oldest dated occupation for the region. The stone tool assemblages are identified as a Middle Palaeolithic industry that includes Levallois manufacturing methods and the production of tools on flakes. Hominin occupations correspond with humid periods, particularly Marine Isotope Stages 7 and 5 of the Late Pleistocene. The Middle Palaeolithic occupations were situated along the Jubbah palaeolake-shores, in a grassland setting with some trees. Populations procured different raw materials across the lake region to manufacture stone tools, using the implements to process plants and animals. To reach the Jubbah palaeolake, Middle Palaeolithic populations travelled into the ameliorated Nefud Desert interior, possibly gaining access from multiple directions, either using routes from the north and west (the Levant and the Sinai), the north (the Mesopotamian plains and the Euphrates basin), or the east (the Persian Gulf). The Jubbah stone tool assemblages have their own suite of technological characters, but have types reminiscent of both African Middle Stone Age and Levantine Middle Palaeolithic industries. Comparative inter-regional analysis of core technology indicates morphological similarities with the Levantine Tabun C assemblage, associated with human fossils controversially identified as either Neanderthals or Homo sapiens.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Bariatric surgery is widely used to treat obesity and improves type 2 diabetes beyond expectations from the degree of weight loss. Elevated post-prandial concentrations of glucagon-like peptide 1 ...(GLP-1), peptide YY (PYY), and insulin are widely reported, but the importance of GLP-1 in post-bariatric physiology remains debated. Here, we show that GLP-1 is a major driver of insulin secretion after bariatric surgery, as demonstrated by blocking GLP-1 receptors (GLP1Rs) post-gastrectomy in lean humans using Exendin-9 or in mice using an anti-GLP1R antibody. Transcriptomics and peptidomics analyses revealed that human and mouse enteroendocrine cells were unaltered post-surgery; instead, we found that elevated plasma GLP-1 and PYY correlated with increased nutrient delivery to the distal gut in mice. We conclude that increased GLP-1 secretion after bariatric surgery arises from rapid nutrient delivery to the distal gut and is a key driver of enhanced insulin secretion.
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•Increased postprandial GLP-1 triggers higher insulin levels after bariatric surgery•Bariatric surgery does not change enteroendocrine cell identity or hormone content•Increased nutrient flow to the distal gut after surgery enhances GLP-1 secretion
Bariatric surgery is associated with enhanced postprandial gut hormone release, particularly of GLP-1, which increases insulin secretion and glucose clearance. Larraufie et al. show that higher gut hormone levels are due not to changes in enteroendocrine cell characteristics or tissue hormone content but to altered flow of nutrients that stimulates more distal enteroendocrine cells.
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