Library Discussion Panel Part I

Interview 1. The Library Interview Series is a set of interviews with a variety of personnel involved with the planning and building of the new Jerry Falwell Library building. The building’s history and planning are discussed as well as the history of the library in general. The recordings were made just before the opening of the new building in early 2014. Lowell Walters; Carl Merat; Abigail Sattler; Greg Smit

Mosaic Genome Architecture of the Anopheles gambiae Species Complex

Attempts over the last three decades to reconstruct the phylogenetic history of the Anopheles gambiae species complex have been important for developing better strategies to control malaria transmission.We used fingerprint genotyping data from 414 field-collected female mosquitoes at 42 microsatellite loci to infer the evolutionary relationships of four species in the A. gambiae complex, the two major malaria vectors A. gambiae sensu stricto (A. gambiae s.s.) and A. arabiensis, as well as two minor vectors, A. merus and A. melas.We identify six taxonomic units, including a clear separation of West and East Africa A. gambiae s.s. S molecular forms. We show that the phylogenetic relationships vary widely between different genomic regions, thus demonstrating the mosaic nature of the genome of these species. The two major malaria vectors are closely related and closer to A. merus than to A. melas at the genome-wide level, which is also true if only autosomes are considered. However, within the Xag inversion region of the X chromosome, the M and two S molecular forms are most similar to A. merus. Near the X centromere, outside the Xag region, the two S forms are highly dissimilar to the other taxa. Furthermore, our data suggest that the centromeric region of chromosome 3 is a strong discriminator between the major and minor malaria vectors.Although further studies are needed to elucidate the basis of the phylogenetic variation among the different regions of the genome, the preponderance of sympatric admixtures among taxa strongly favor introgression of different genomic regions between species, rather than lineage sorting of ancestral polymorphism, as a possible mechanism

Multi-species population indices for sets of species including rare, disappearing or newly occurring species

NI is funded by Natural Environment Research Council award NE/R016429/1 as part of the UK-SCAPE programme delivering National Capability.Multi-species indices (MSI) are widely used as ecological indicators and as instruments to inform environmental policies. Many of these indices combine species-specific estimates of relative population sizes using the geometric mean. Because the geometric mean is not defined when values of zero occur, usually only commoner species are included in MSIs and zero values are replaced by a small non-zero value. The latter can exhibit an arbitrary influence on the geometric mean MSI. Here, we show how the compound Poisson and the negative binomial model can be used in such cases to obtain an MSI that has similar features to the geometric mean, including weighting halving and doubling of a species’ population equally. In contrast to the geometric mean, these two statistical models can handle zero values in population sizes and thus accommodate newly occurring and temporarily or permanently disappearing species in the MSI. We compare the MSIs obtained by the two statistical models with the geometric mean MSI and measure sensitivity to changes in evenness and to population trends in rare and abundant species. Additionally, we outline sources of uncertainty and discuss how to measure them. We found that, in contrast to the geometric mean and the negative binomial MSI, the compound Poisson MSI is less sensitive to changes in evenness when total abundance is constant. Further, we found that the compound Poisson model can be influenced more than the other two methods by trends of species showing a low interannual variance. The negative binomial MSI is less sensitive to trends in rare species compared with the other two methods, and similarly sensitive to trends in abundant species as the geometric mean. While the two new MSIs have the advantage that they are not arbitrarily influenced by rare, newly appearing and disappearing species, both do not weight all species equally. We recommend replacing the geometric mean MSI with either compound Poisson or negative binomial when there are species with a population size of zero in some years having a strong influence on the geometric mean MSI. Further, we recommend providing additional information alongside the MSIs. For example, it is particularly important to give an evenness index in addition to the compound Poisson MSI and to indicate the number of disappearing and newly occurring species alongside the negative binomial MSI.Publisher PDFPeer reviewe

Immunoassay Urine Drug Testing among Patients Receiving Opioids at a Safety-Net Palliative Medicine Clinic

BACKGROUND: Few studies have examined the use of immunoassay urine drug testing of cancer patients in palliative care clinics. OBJECTIVES: We examined the frequency of immunoassay urine drug test (UDT) abnormalities and the factors associated with aberrancy at a safety-net hospital palliative medicine clinic. METHODS: A retrospective review of the electronic medical records of consecutive eligible patients seen at the outpatient palliative medicine clinic in a resource-limited safety-net hospital system was conducted between 1 September 2015 and 31 December 2020. We collected longitudinal data on patient demographics, UDT findings, and potential predictors of aberrant results. RESULTS: Of the 913 patients in the study, 500 (55%) underwent UDT testing, with 455 (50%) having the testing within the first three visits. Among those tested within the first three visits, 125 (27%) had aberrant UDT results; 44 (35%) of these 125 patients were positive for cocaine. In a multivariable regression model analysis of predictors for aberrant UDT within the first three visits, non-Hispanic White race (odds ratio (OR) = 2.13; 95% confidence interval (CI): 1.03-4.38; CONCLUSION: Despite limitations of immunoassay UDT, it was able to detect aberrant drug-taking behaviors in a significant number of patients seen at a safety-net hospital palliative care clinic, including cocaine use. These findings support universal UDT monitoring and utility of immunoassay-based UDT in resource-limited settings

Adherence to Opioid Patient Prescriber Agreements at a Safety Net Hospital

Patient prescriber agreements, also known as opioid contracts or opioid treatment agreements, have been recommended as a strategy for mitigating non-medical opioid use (NMOU). The purpose of our study was to characterize the proportion of patients with PPAs, the rate of non-adherence, and clinical predictors for PPA completion and non-adherence. This retrospective study covered consecutive cancer patients seen at a palliative care clinic at a safety net hospital between 1 September 2015 and 31 December 2019. We included patients 18 years or older with cancer diagnoses who received opioids. We collected patient characteristics at consultation and information regarding PPA. The primary purpose was to determine the frequency and predictors of patients with a PPA and non-adherence to PPAs. Descriptive statistics and multivariable logistic regression models were used for the analysis. The survey covered 905 patients having a mean age of 55 (range 18-93), of whom 474 (52%) were female, 423 (47%) were Hispanic, 603 (67%) were single, and 814 (90%) had advanced cancer. Of patients surveyed, 484 (54%) had a PPA, and 50 (10%) of these did not adhere to their PPA. In multivariable analysis, PPAs were associated with younger age (odds ratio [OR] 1.44

The thymocyte-specific RNA-binding protein Arpp21 provides TCR repertoire diversity by binding to the 3'-UTR and promoting Rag1 mRNA expression

The regulation of thymocyte development by RNA-binding proteins (RBPs) is largely unexplored. We identify 642 RBPs in the thymus and focus on Arpp21, which shows selective and dynamic expression in early thymocytes. Arpp21 is downregulated in response to T cell receptor (TCR) and Ca2+ signals. Downregulation requires Stim1/Stim2 and CaMK4 expression and involves Arpp21 protein phosphorylation, polyubiquitination and proteasomal degradation. Arpp21 directly binds RNA through its R3H domain, with a preference for uridine-rich motifs, promoting the expression of target mRNAs. Analysis of the Arpp21-bound transcriptome reveals strong interactions with the Rag1 3 '-UTR. Arpp21-deficient thymocytes show reduced Rag1 expression, delayed TCR rearrangement and a less diverse TCR repertoire. This phenotype is recapitulated in Rag1 3 '-UTR mutant mice harboring a deletion of the Arpp21 response region. These findings show how thymocyte-specific Arpp21 promotes Rag1 expression to enable TCR repertoire diversity until signals from the TCR terminate Arpp21 and Rag1 activities

Covariation in population trends and demography reveals targets for conservation action

Wildlife conservation policies directed at common and widespread, but declining, species are difficult to design and implement effectively, as multiple environmental changes are likely to contribute to population declines. Conservation actions ultimately aim to influence demographic rates, but targeting actions towards feasible improvements in these is challenging in widespread species with ranges that encompass a wide range of environmental conditions. Across Europe, sharp declines in the abundance of migratory landbirds have driven international calls for action, but actions that could feasibly contribute to population recovery have yet to be identified. Targeted actions to improve conditions on poor-quality sites could be an effective approach, but only if local conditions consistently influence local demography and hence population trends. Using long-term measures of abundance and demography of breeding birds at survey sites across Europe, we show that co-occurring species with differing migration behaviours have similar directions of local population trends and magnitudes of productivity, but not survival rates. Targeted actions to boost local productivity within Europe, alongside large-scale (non-targeted) environmental protection across non-breeding ranges, could therefore help address the urgent need to halt migrant landbird declines. Such demographic routes to recovery are likely to be increasingly needed to address global wildlife declines.Peer reviewe

Ecological and genetic relationships of the Forest-M form among chromosomal and molecular forms of the malaria vector Anopheles gambiae sensu stricto

<p>Abstract</p> <p>Background</p> <p><it>Anopheles gambiae sensu stricto</it>, one of the principal vectors of malaria, has been divided into two subspecific groups, known as the M and S molecular forms. Recent studies suggest that the M form found in Cameroon is genetically distinct from the M form found in Mali and elsewhere in West Africa, suggesting further subdivision within that form.</p> <p>Methods</p> <p>Chromosomal, microsatellite and geographic/ecological evidence are synthesized to identify sources of genetic polymorphism among chromosomal and molecular forms of the malaria vector <it>Anopheles gambiae s.s</it>.</p> <p>Results</p> <p>Cytogenetically the Forest M form is characterized as carrying the standard chromosome arrangement for six major chromosomal inversions, namely 2La, 2Rj, 2Rb, 2Rc, 2Rd, and 2Ru. Bayesian clustering analysis based on molecular form and chromosome inversion polymorphisms as well as microsatellites describe the Forest M form as a distinct population relative to the West African M form (Mopti-M form) and the S form. The Forest-M form was the most highly diverged of the <it>An. gambiae s.s</it>. groups based on microsatellite markers. The prevalence of the Forest M form was highly correlated with precipitation, suggesting that this form prefers much wetter environments than the Mopti-M form.</p> <p>Conclusion</p> <p>Chromosome inversions, microsatellite allele frequencies and habitat preference all indicate that the Forest M form of <it>An. gambiae </it>is genetically distinct from the other recognized forms within the taxon <it>Anopheles gambiae sensu stricto</it>. Since this study covers limited regions of Cameroon, the possibility of gene flow between the Forest-M form and Mopti-M form cannot be rejected. However, association studies of important phenotypes, such as insecticide resistance and refractoriness against malaria parasites, should take into consideration this complex population structure.</p