2,951 research outputs found

    The Importance of Spatial Data to Open - Access National Archaeological Databases and the Development of Paleodemography Research

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    With generous support from the National Science Foundation, we have spent the past four years developing an archaeological radiocarbon database for the United States. Here, we highlight the importance of spatial data for open-access, national-scale archaeological databases and the development of paleodemography research. We propose a new method for analyzing radiocarbon time series in the context of paleoclimate models. This method forces us to confront one of the central challenges to realizing the full potential of national-scale databases: the quality of the spatial data accompanying radiocarbon dates. We seek to open a national discussion on the use of spatial data in open-source archaeological databases

    RNA-seq reveals post-transcriptional regulation of Drosophila insulin-like peptide dilp8 and the neuropeptide-like precursor Nplp2 by the exoribonuclease Pacman/XRN1

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    Ribonucleases are critically important in many cellular and developmental processes and defects in their expression are associated with human disease. Pacman/XRN1 is a highly conserved cytoplasmic exoribonuclease which degrades RNAs in a 5' - 3' direction. In Drosophila, null mutations in pacman result in small imaginal discs, a delay in onset of pupariation and lethality during the early pupal stage. In this paper, we have used RNA-seq in a genome-wide search for mRNAs misregulated in pacman null wing imaginal discs. Only 4.2% of genes are misregulated ±>2-fold in pacman null mutants compared to controls, in line with previous work showing that Pacman has specificity for particular mRNAs. Further analysis of the most upregulated mRNAs showed that Pacman post-transcriptionally regulates the expression of the secreted insulin-like peptide Dilp8. Dilp8 is related to human IGF-1, and has been shown to co-ordinate tissue growth with developmental timing in Drosophila. The increased expression of Dilp8 is consistent with the developmental delay seen in pacman null mutants. Our analysis, together with our previous results, show that the normal role of this exoribonuclease in imaginal discs is to suppress the expression of transcripts that are crucial in apoptosis and growth control during normal development

    The relationship between the development of general offending and intimate partner violence perpetration in young adulthood

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    This study examined how patterns in general offending relate to the occurrence of and likelihood of persistence in intimate partner violence (IPV) perpetration in young adulthood. The study used longitudinal data from the cohort of 18 year olds from the Project on Human Development in Chicago Neighborhoods study. Self-reported offending was measured in all three waves, and data on IPV were collected in Waves 1 and 3. Group-based trajectory modeling identified three distinct general offending trajectory groups: non-offenders, low-rate offenders, and high-rate offenders. The majority of respondents engaged in psychological IPV perpetration, and half of all young adults reported physical IPV, but prevalence rates decreased over the waves. Binary logistic regression analyses showed that those involved in offending, especially those who showed a diverse offending pattern, were at increased risk of perpetrating psychological and (severe) physical IPV, as well as to show persistence in the different forms of IPV perpetration. The findings highlight an important overlap between general crime and IPV perpetration. In recognition that IPV is often part of a broader pattern of antisocial behavior, interventions should focus on interrupting the criminal careers of all young offenders to reduce the prevalence and harms of IPV

    Studying Effects of Primary Care Physicians and Patients on the Trade-Off Between Charges for Primary Care and Specialty Care Using a Hierarchical Multivariate Two-Part Model

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    Objective. To examine effects of primary care physicians (PCPs) and patients on the association between charges for primary care and specialty care in a point-of-service (POS) health plan. Data Source. Claims from 1996 for 3,308 adult male POS plan members, each of whom was assigned to one of the 50 family practitioner-PCPs with the largest POS plan member-loads. Study Design. A hierarchical multivariate two-part model was fitted using a Gibbs sampler to estimate PCPs\u27 effects on patients\u27 annual charges for two types of services, primary care and specialty care, the associations among PCPs\u27 effects, and within-patient associations between charges for the two services. Adjusted Clinical Groups (ACGs) were used to adjust for case-mix. Principal Findings. PCPs with higher case-mix adjusted rates of specialist use were less likely to see their patients at least once during the year (estimated correlation: –.40; 95% CI: –.71, –.008) and provided fewer services to patients that they saw (estimated correlation: –.53; 95% CI: –.77, –.21). Ten of 11 PCPs whose case-mix adjusted effects on primary care charges were significantly less than or greater than zero (p \u3c .05) had estimated, case-mix adjusted effects on specialty care charges that were of opposite sign (but not significantly different than zero). After adjustment for ACG and PCP effects, the within-patient, estimated odds ratio for any use of primary care given any use of specialty care was .57 (95% CI: .45, .73). Conclusions. PCPs and patients contributed independently to a trade-off between utilization of primary care and specialty care. The trade-off appeared to partially offset significant differences in the amount of care provided by PCPs. These findings were possible because we employed a hierarchical multivariate model rather than separate univariate models

    A Hierarchical Multivariate Two-Part Model for Profiling Providers\u27 Effects on Healthcare Charges

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    Procedures for analyzing and comparing healthcare providers\u27 effects on health services delivery and outcomes have been referred to as provider profiling. In a typical profiling procedure, patient-level responses are measured for clusters of patients treated by providers that in turn, can be regarded as statistically exchangeable. Thus, a hierarchical model naturally represents the structure of the data. When provider effects on multiple responses are profiled, a multivariate model rather than a series of univariate models, can capture associations among responses at both the provider and patient levels. When responses are in the form of charges for healthcare services and sampled patients include non-users of services, charge variables are a mix of zeros and highly-skewed positive values that present a modeling challenge. For analysis of regressor effects on charges for a single service, a frequently used approach is a two-part model (Duan, Manning, Morris, and Newhouse 1983) that combines logistic or probit regression on any use of the service and linear regression on the log of positive charges given use of the service. Here, we extend the two-part model to the case of charges for multiple services, using a log-linear model and a general multivariate log-normal model, and employ the resultant multivariate two-part model as the within-provider component of a hierarchical model. The log-linear likelihood is reparameterized as proposed by Fitzmaurice and Laird (1993), so that regressor effects on any use of each service are marginal with respect to any use of other services. The general multivariate log-normal likelihood is constructed in such a way that variances of log of positive charges for each service are provider-specific but correlations between log of positive charges for different services are uniform across providers. A data augmentation step is included in the Gibbs sampler used to fit the hierarchical model, in order to accommodate the fact that values of log of positive charges are undefined for unused service. We apply this hierarchical, multivariate, two-part model to analyze the effects of primary care physicians on their patients\u27 annual charges for two services, primary care and specialty care. Along the way, we also demonstrate an approach for incorporating prior information about the effects of patient morbidity on response variables, to improve the accuracy of provider profiles that are based on patient samples of limited size

    The extinct, giant giraffid Sivatherium giganteum: skeletal reconstruction and body mass estimation

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    Sivatherium giganteum is an extinct giraffid from the Plio–Pleistocene boundary of the Himalayan foothills. To date, there has been no rigorous skeletal reconstruction of this unusual mammal. Historical and contemporary accounts anecdotally state that Sivatherium rivalled the African elephant in terms of its body mass, but this statement has never been tested. Here, we present a three-dimensional composite skeletal reconstruction and calculate a representative body mass estimate for this species using a volumetric method. We find that the estimated adult body mass of 1246 kg (857—1812 kg range) does not approach that of an African elephant, but confirms that Sivatherium was certainly a large giraffid, and may have been the largest ruminant mammal that has ever existed. We contrast this volumetric estimate with a bivariate scaling estimate derived from Sivatherium's humeral circumference and find that there is a discrepancy between the two. The difference implies that the humeral circumference of Sivatherium is greater than expected for an animal of this size, and we speculate this may be linked to a cranial shift in centre of mass

    MyosinVa and dynamic actin oppose minus-end directed microtubule motors to drive anterograde melanosome transport

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    The intracellular transport of organelles and vesicles is thought to utilise both microtubules and actin filaments, which mediate long and short-range transport, respectively. Melanosomes, synthesised in melanocytes, are a convenient model organelle to study intracellular transport, since they are visible using brightfield microscopy. They are believed to be transported from the perinuclear area to the actin cortex along microtubules, and then captured by the myosin-Va/melanophilin/Rab27a complex which traffics them along actin filaments to the plasma membrane. In contrast, data presented here demonstrate that anterograde melanosome transport relies only upon the actin cytoskeleton. Myosin-Va null melanocytes were used to test the importance of microtubules and actin on long-range organelle transport. In these cells, melanosomes cluster around the perinuclear area, but disperse into peripheral dendrites upon reintroduction of the myosin-Va gene. When this assay was repeated in the absence of microtubules, melanosomes still dispersed indicating that microtubule-based motors are not necessary for long-range anterograde trafficking. However, depolymerising F-actin, or freezing actin dynamics with latrunculin A or jasplakinolide inhibited the dispersion of pigment granules in myosin-Va null cells melanocytes and induced a clustered phenotype in WT melanocytes. This effect was abolished if microtubules were absent, suggesting that microtubules are only required for retrograde transport whilst dynamic actin is essential for anterograde melanosome transport. Moreover, when Kif5B was forcibly recruited to the melanosome membrane via an inducible dimerisation system, the melanosomes dispersed abnormally. An siRNA knockdown screen of over 120 actin binding proteins identified several proteins including formin-1, Arpc1b, cofilin-1, gamma-actin and spire1/2, which appear to be necessary for maintaining peripherally dispersed melanosomes. This evidence further underlines the importance of the actin cytoskeleton, rather than the microtubule network as previously thought, for the anterograde trafficking of melanosomes
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