No / Farming transformed societies globally. Yet, despite more than a century of research, there is little consensus on the speed or completeness of this fundamental change and, consequently, on its principal drivers. For Northern Europe, the debate has often centered on the rich archaeological record of the Western Baltic, but even here it is unclear how quickly or completely people abandoned wild terrestrial and marine resources after the introduction of domesticated plants and animals at approximately 4000 calibrated years B.C. Ceramic containers are found ubiquitously on these sites and contain remarkably well-preserved lipids derived from the original use of the vessel. Reconstructing culinary practices from this ceramic record can contribute to longstanding debates concerning the origins of farming. Here we present data on the molecular and isotopic characteristics of lipids extracted from 133 ceramic vessels and 100 carbonized surface residues dating to immediately before and after the first evidence of domesticated animals and plants in the Western Baltic. The presence of specific lipid biomarkers, notably omega-(o-alkylphenyl)alkanoic acids, and the isotopic composition of individual n-alkanoic acids clearly show that a significant proportion ( approximately 20%) of ceramic vessels with lipids preserved continued to be used for processing marine and freshwater resources across the transition to agriculture in this region. Although changes in pottery use are immediately evident, our data challenge the popular notions that economies were completely transformed with the arrival of farming and that Neolithic pottery was exclusively associated with produce from domesticated animals and plants.

No / RATIONALE: The carbon isotopic characterisation of ruminant lipids associated with ceramic vessels has been crucial for elucidating the origins and changing nature of pastoral economies. delta(13)C values of fatty acids extracted from potsherds are commonly compared with those from the dairy and carcass fats of modern domesticated animals to determine vessel use. However, the processing of wild ruminant products in pottery, such as deer, is rarely considered despite the presence of several different species on many prehistoric sites. To address this issue, the carbon isotope range of fatty acids from a number of red deer (Cervus elaphus) tissues, a species commonly encountered in the European archaeological record, was investigated. METHODS: Lipids were extracted from 10 modern red deer tissues obtained from the Slowinski National Park (Poland). Fatty acids were fractionated, methylated and analysed by gas chromatography/combustion/isotope ratio mass spectrometry (GCCIRMS). The delta(13)C values of n-octadecanoic acid and n-hexadecanoic acid, and the difference between these values (Delta(13)C), were compared with those from previously published ruminant fats. RESULTS: Nine of the ten deer carcass fats measured have Delta(13)C values of less than -3.3 per thousand, the threshold previously used for classifying dairy products. Despite considerable overlap, dairy fats from domesticated ruminants with Delta(13)C values less than -4.3 per thousand are still distinguishable. CONCLUSIONS: The finding has implications for evaluating pottery use and early pastoralism. The processing of deer tissues and our revised criteria should be considered, especially where there is other archaeological evidence for their consumption.

No / Pottery was a hunter-gatherer innovation that first emerged in East Asia between 20,000 and 12,000 calibrated years before present (cal bp), towards the end of the Late Pleistocene epoch, a period of time when humans were adjusting to changing climates and new environments. Ceramic container technologies were one of a range of late glacial adaptations that were pivotal to structuring subsequent cultural trajectories in different regions of the world, but the reasons for their emergence and widespread uptake are poorly understood. The first ceramic containers must have provided prehistoric hunter-gatherers with attractive new strategies for processing and consuming foodstuffs, but virtually nothing is known of how early pots were used. Here we report the chemical analysis of food residues associated with Late Pleistocene pottery, focusing on one of the best-studied prehistoric ceramic sequences in the world, the Japanese Jomon. We demonstrate that lipids can be recovered reliably from charred surface deposits adhering to pottery dating from about 15,000 to 11,800 cal bp (the Incipient Jomon period), the oldest pottery so far investigated, and that in most cases these organic compounds are unequivocally derived from processing freshwater and marine organisms. Stable isotope data support the lipid evidence and suggest that most of the 101 charred deposits analysed, from across the major islands of Japan, were derived from high-trophic-level aquatic food. Productive aquatic ecotones were heavily exploited by late glacial foragers, perhaps providing an initial impetus for investment in ceramic container technology, and paving the way for further intensification of pottery use by hunter-gatherers in the early Holocene epoch. Now that we have shown that it is possible to analyse organic residues from some of the world's earliest ceramic vessels, the subsequent development of this critical technology can be clarified through further widespread testing of hunter-gatherer pottery from later periods.

No / The molecular identity of ion channels which confer PCO(2)/pH sensitivity in the brain is unclear. Heteromeric Kir4.1/Kir5.1 channels are highly sensitive to inhibition by intracellular pH and are widely expressed in several brainstem nuclei involved in cardiorespiratory control, including the locus coeruleus. This has therefore led to a proposed role for these channels in neuronal CO(2) chemosensitivity. To examine this, we generated mutant mice lacking the Kir5.1 (Kcnj16) gene. We show that although locus coeruleus neurons from Kcnj16((+/+)) mice rapidly respond to cytoplasmic alkalinization and acidification, those from Kcnj16((-/-)) mice display a dramatically reduced and delayed response. These results identify Kir5.1 as an important determinant of PCO(2)/pH sensitivity in locus coeruleus neurons and suggest that Kir5.1 may be involved in the response to hypercapnic acidosis.

No / OBJECTIVE: To describe the growth pattern from birth to 2 years of UK-born white British and Pakistani infants. DESIGN: Birth cohort. SETTING: Bradford, UK. PARTICIPANTS: 314 white British boys, 383 Pakistani boys, 328 white British girls and 409 Pakistani girls. MAIN OUTCOME MEASURES: Weight and length trajectories based on repeat measurements from birth to 2 years. RESULTS: Linear spline multilevel models for weight and length with knot points at 4 and 9 months fitted the data well. At birth Pakistani boys were 210 g lighter (95% CI -290 to -120) and 0.5 cm shorter (-1.04 to 0.02) and Pakistani girls were 180 g lighter (-260 to -100) and 0.5 cm shorter (-0.91 to -0.03) than white British boys and girls, respectively. Pakistani infants gained length faster than white British infants between 0 and 4 months (+0.3 cm/month (0.1 to 0.5) for boys and +0.4 cm/month (0.2 to 0.6) for girls) and gained more weight per month between 9 and 24 months (+10 g/month (0 to 30) for boys and +30 g/month (20 to 40) for girls). Adjustment for maternal height attenuated ethnic differences in weight and length at birth, but not in postnatal growth. Adjustment for other confounders did not explain differences in any outcomes. CONCLUSIONS: Pakistani infants were lighter and had shorter predicted mean length at birth than white British infants, but gained weight and length quicker in infancy. By age 2 years both ethnic groups had similar weight, but Pakistani infants were on average taller than white British infants.

No / Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders that often progress to chemotherapy-resistant secondary acute myeloid leukemia (sAML). We used whole-genome sequencing to perform an unbiased comprehensive screen to discover the somatic mutations in a sample from an individual with sAML and genotyped the loci containing these mutations in the matched MDS sample. Here we show that a missense mutation affecting the serine at codon 34 (Ser34) in U2AF1 was recurrently present in 13 out of 150 (8.7%) subjects with de novo MDS, and we found suggestive evidence of an increased risk of progression to sAML associated with this mutation. U2AF1 is a U2 auxiliary factor protein that recognizes the AG splice acceptor dinucleotide at the 3' end of introns, and the alterations in U2AF1 are located in highly conserved zinc fingers of this protein. Mutant U2AF1 promotes enhanced splicing and exon skipping in reporter assays in vitro. This previously unidentified, recurrent mutation in U2AF1 implicates altered pre-mRNA splicing as a potential mechanism for MDS pathogenesis.

No / The hTREX complex mediates cellular bulk mRNA nuclear export by recruiting the nuclear export factor, TAP, via a direct interaction with the export adaptor, Aly. Intriguingly however, depletion of Aly only leads to a modest reduction in cellular mRNA nuclear export, suggesting the existence of additional mRNA nuclear export adaptor proteins. In order to efficiently export Kaposi's sarcoma-associated herpesvirus (KSHV) intronless mRNAs from the nucleus, the KSHV ORF57 protein recruits hTREX onto viral intronless mRNAs allowing access to the TAP-mediated export pathway. Similarly however, depletion of Aly only leads to a modest reduction in the nuclear export of KSHV intronless mRNAs. Herein, we identify a novel interaction between ORF57 and the cellular protein, UIF. We provide the first evidence that the ORF57-UIF interaction enables the recruitment of hTREX and TAP to KSHV intronless mRNAs in Aly-depleted cells. Strikingly, depletion of both Aly and UIF inhibits the formation of an ORF57-mediated nuclear export competent ribonucleoprotein particle and consequently prevents ORF57-mediated mRNA nuclear export and KSHV protein production. Importantly, these findings highlight that redundancy exists in the eukaryotic system for certain hTREX components involved in the mRNA nuclear export of intronless KSHV mRNAs.

No / OBJECTIVES: Legislation and health policy enabling nurses and pharmacists to prescribe a comprehensive range of medicines has been in place in the UK since 2006. Our objective was to evaluate the clinical appropriateness of prescribing by these professionals. METHODS: A modified version of the Medication Appropriateness Index (MAI) was used by 10 medical, seven pharmacist and three nurse independent raters to evaluate a sample of 100 audio-recorded consultations in which a medicine was prescribed by a nurse or pharmacist. Raters were current prescribers with recognized experience in prescribing. Consultations were recorded in nine clinical practice settings in England. RESULTS: Raters' analysis indicated that, in the majority of instances, nurses and pharmacists were prescribing clinically appropriately on all of the ten MAI criteria (indication, effectiveness, dosage, directions, practicality, drug-drug interaction, drug-disease interaction, duplication, duration, cost). Highest mean 'inappropriate' ratings were given for correct directions (nurses 12%; pharmacists 11%) and the cost of the drug prescribed (nurses 16% pharmacists 22%). Analysis of raters' qualitative comments identified two main themes: positive views on the overall safety and effectiveness of prescribing episodes; and potential for improvement in nurses' and pharmacists' history-taking, assessment and diagnosis skills. CONCLUSIONS: Nurses and pharmacists are generally making clinically appropriate prescribing decisions. Decisions about the cost of drugs prescribed and assessment and diagnostic skills are areas for quality improvement.

No / We explore the relative utility of shape from shading and binocular disparity for depth perception. Ray-traced images either featured a smooth surface illuminated from above (shading-only) or were defined by small dots (disparity-only). Observers judged which of a pair of smoothly curved convex objects had most depth. The shading cue was around half as reliable as the rich disparity information for depth discrimination. Shading- and disparity-defined cues where combined by placing dots in the stimulus image, superimposed upon the shaded surface, resulting in veridical shading and binocular disparity. Independently varying the depth delivered by each channel allowed creation of conflicting disparity-defined and shading-defined depth. We manipulated the reliability of the disparity information by adding disparity noise. As noise levels in the disparity channel were increased, perceived depths and variances shifted toward those of the now more reliable shading cue. Several different models of cue combination were applied to the data. Perceived depths and variances were well predicted by a classic maximum likelihood estimator (MLE) model of cue integration, for all but one observer. We discuss the extent to which MLE is the most parsimonious model to account for observer performance.

No / In a visual search experiment, the subject must find a target item hidden in a display of other items, and their performance is measured by their reaction time (RT). Here I look at how visual search reaction times are correlated with past reaction times. Target-absent RTs (i.e. RTs to displays that have no target) are strongly correlated with past target-absent RTs and, treated as a time series, have a 1/f power spectrum. Target-present RTs, on the other hand, are effectively uncorrelated with past RTs. A model for visual search is presented which generates search RTs with this pattern of correlations and power spectra. In the model, search is conducted by matching search items up with "categorizers," which take a certain time to categorize each item as target or distractor; the RT is the sum of categorization times. The categorizers are drawn at random from a pool of active categorizers. After each search, some of the categorizers in the active pool are replaced with categorizers drawn from a larger population of unused categorizers. The categorizers that are not replaced are responsible for the RT correlations and the 1/f power spectrum.