Report of the Ad Hoc Committee on Bibliographic Control of Electronic Serials

Report of the Ad Hoc Committee on Bibliographic Control of Electronic Serials of the University of Rhode Island Libraries. Recommends six policies related to the bibliographic control of electronic journals. The charge to the committee was as follows: The Ad Hoc Committee on the Bibliographic Control of Electronic Serials will review present library practice for the handling of electronic serials from the point of order, through invoicing, payment and cataloging in the HELIN system and on the library\u27s home page. It will review the process for the continuing management of the bibliographic record for accuracy, currency, and quality. The committee will consider the process for paid subscriptions, free subscriptions, type of access points, consortia implications, branch implications, and any other issues which are uncovered during the committee\u27s deliberations

The interplay of type I and type II interferons in murine autoimmune cholangitis as a basis for sex-biased autoimmunity

We have reported on a murine model of autoimmune cholangitis, generated by altering the AU-rich element (ARE) by deletion of the interferon gamma (IFN-γ) 3\u27 untranslated region (coined ARE-Del−/−), that has striking similarities to human primary biliary cholangitis (PBC) with female predominance. Previously, we suggested that the sex bias of autoimmune cholangitis was secondary to intense and sustained type I and II IFN signaling. Based on this thesis, and to define the mechanisms that lead to portal inflammation, we specifically addressed the hypothesis that type I IFNs are the driver of this disease. To accomplish these goals, we crossed ARE-Del−/− mice with IFN type I receptor alpha chain (Ifnar1) knockout mice. We report herein that loss of type I IFN receptor signaling in the double construct of ARE-Del−/− Ifnar1−/− mice dramatically reduces liver pathology and abrogated sex bias. More importantly, female ARE-Del−/− mice have an increased number of germinal center (GC) B cells as well as abnormal follicular formation, sites which have been implicated in loss of tolerance. Deletion of type I IFN signaling in ARE-Del−/− Ifnar1−/− mice corrects these GC abnormalities, including abnormal follicular structure. Conclusion: Our data implicate type I IFN signaling as a necessary component of the sex bias of this murine model of autoimmune cholangitis. Importantly these data suggest that drugs that target the type I IFN signaling pathway would have potential benefit in the earlier stages of PBC. (Hepatology 2018;67:1408-1419)

Deweyan tools for inquiry and the epistemological context of critical pedagogy

This article develops the notion of resistance as articulated in the literature of critical pedagogy as being both culturally sponsored and cognitively manifested. To do so, the authors draw upon John Dewey\u27s conception of tools for inquiry. Dewey provides a way to conceptualize student resistance not as a form of willful disputation, but instead as a function of socialization into cultural models of thought that actively truncate inquiry. In other words, resistance can be construed as the cognitive and emotive dimensions of the ongoing failure of institutions to provide ideas that help individuals both recognize social problems and imagine possible solutions. Focusing on Dewey\u27s epistemological framework, specifically tools for inquiry, provides a way to grasp this problem. It also affords some innovative solutions; for instance, it helps conceive of possible links between the regular curriculum and the study of specific social justice issues, a relationship that is often under-examined. The aims of critical pedagogy depend upon students developing dexterity with the conceptual tools they use to make meaning of the evidence they confront; these are background skills that the regular curriculum can be made to serve even outside social justice-focused curricula. Furthermore, the article concludes that because such inquiry involves the exploration and potential revision of students\u27 world-ordering beliefs, developing flexibility in how one thinks may be better achieved within academic subjects and topics that are not so intimately connected to students\u27 current social lives, especially where students may be directly implicated

Defining Ecological Drought for the Twenty-First Century

THE RISING RISK OF DROUGHT. Droughts of the twenty-first century are characterized by hotter temperatures, longer duration, and greater spatial extent, and are increasingly exacerbated by human demands for water. This situation increases the vulnerability of ecosystems to drought, including a rise in drought-driven tree mortality globally (Allen et al. 2015) and anticipated ecosystem transformations from one state to another—for example, forest to a shrubland (Jiang et al. 2013). When a drought drives changes within ecosystems, there can be a ripple effect through human communities that depend on those ecosystems for critical goods and services (Millar and Stephenson 2015). For example, the “Millennium Drought” (2002–10) in Australia caused unanticipated losses to key services provided by hydrological ecosystems in the Murray–Darling basin—including air quality regulation, waste treatment, erosion prevention, and recreation. The costs of these losses exceeded AUD $800 million, as resources were spent to replace these services and adapt to new drought-impacted ecosystems (Banerjee et al. 2013). Despite the high costs to both nature and people, current drought research, management, and policy perspectives often fail to evaluate how drought affects ecosystems and the “natural capital” they provide to human communities. Integrating these human and natural dimensions of drought is an essential step toward addressing the rising risk of drought in the twenty-first century

nab-Paclitaxel–Based Therapy in Underserved Patient Populations: The ABOUND.PS2 Study in Patients With NSCLC and a Performance Status of 2

IntroductionThe phase II ABOUND.PS2 study (NCT02289456) assessed safety/tolerability of a first-line modified nab-paclitaxel/carboplatin regimen for patients with advanced non-small cell lung cancer (NSCLC) and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 2.MethodsChemotherapy-naive patients with stage IIIB/IV NSCLC and ECOG PS 2 received four cycles of nab-paclitaxel 100 mg/m2 days 1 and 8 plus carboplatin area under the curve 5 day 1 q3w (induction). Patients without progression received nab-paclitaxel monotherapy (100 mg/m2 days 1 and 8 q3w) until progression/unacceptable toxicity. Primary endpoint: percentage of patients discontinuing induction due to treatment-emergent adverse events (TEAEs).Results11/40 treated patients (27.5%; 95% CI, 14.60–43.89) discontinued chemotherapy induction due to TEAEs; 16/40 (40.0%) continued nab-paclitaxel monotherapy. Median progression-free and overall survival were 4.4 (95% CI, 2.99–7.00) and 7.7 (95% CI, 4.93–13.17) months. Grade 3/4 TEAEs during induction included neutropenia (22.5%), anemia (17.5%), thrombocytopenia (5.0%), and peripheral neuropathy (2.5%).ConclusionThis nab-paclitaxel–based regimen was tolerable in patients with advanced NSCLC and ECOG PS 2, with efficacy comparable to historical chemotherapy data

Discovery of common and rare genetic risk variants for colorectal cancer.

To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.Goncalo R Abecasis has received compensation from 23andMe and Helix. He is currently an employee of Regeneron Pharmaceuticals. Heather Hampel performs collaborative research with Ambry Genetics, InVitae Genetics, and Myriad Genetic Laboratories, Inc., is on the scientific advisory board for InVitae Genetics and Genome Medical, and has stock in Genome Medical. Rachel Pearlman has participated in collaborative funded research with Myriad Genetics Laboratories and Invitae Genetics but has no financial competitive interest

Genetic architectures of proximal and distal colorectal cancer are partly distinct.

OBJECTIVE: An understanding of the etiologic heterogeneity of colorectal cancer (CRC) is critical for improving precision prevention, including individualized screening recommendations and the discovery of novel drug targets and repurposable drug candidates for chemoprevention. Known differences in molecular characteristics and environmental risk factors among tumors arising in different locations of the colorectum suggest partly distinct mechanisms of carcinogenesis. The extent to which the contribution of inherited genetic risk factors for CRC differs by anatomical subsite of the primary tumor has not been examined. DESIGN: To identify new anatomical subsite-specific risk loci, we performed genome-wide association study (GWAS) meta-analyses including data of 48 214 CRC cases and 64 159 controls of European ancestry. We characterised effect heterogeneity at CRC risk loci using multinomial modelling. RESULTS: We identified 13 loci that reached genome-wide significance (p<5×10-8) and that were not reported by previous GWASs for overall CRC risk. Multiple lines of evidence support candidate genes at several of these loci. We detected substantial heterogeneity between anatomical subsites. Just over half (61) of 109 known and new risk variants showed no evidence for heterogeneity. In contrast, 22 variants showed association with distal CRC (including rectal cancer), but no evidence for association or an attenuated association with proximal CRC. For two loci, there was strong evidence for effects confined to proximal colon cancer. CONCLUSION: Genetic architectures of proximal and distal CRC are partly distinct. Studies of risk factors and mechanisms of carcinogenesis, and precision prevention strategies should take into consideration the anatomical subsite of the tumour

Heterogeneity of soil nutrients and subsurface biota in a dryland ecosystem

Dryland ecosystems have long been considered to have a highly heterogeneous distribution of nutrients and soil biota, with greater concentrations of both in soils under plants relative to interspace soils. We examined the distribution of soil resources in two plant communities (dominated by either the shrub Coleogyne ramosissima or the grass Stipa hymenoides) at two locations. Interspace soils were covered either by early successional biological soil crusts (BSCs) or by later successional BSCs (dominated by nitrogen (N)-fixing cyanobacteria and lichens). For each of the 8 plant type×crust type×locations, we sampled the stem, dripline, and 3 interspace distances around each of 3 plants. Soil analyses revealed that only available potassium (Kav) and ammonium concentrations were consistently greater under plants (7 of 8 sites and 6 of 8 sites, respectively). Nitrate and iron (Fe) were greater under plants at 4 sites, while all other nutrients were greater under plants at less than 50% of the sites. In contrast, calcium, copper, clay, phosphorus (P), and zinc were often greater in the interspace than under the plants. Soil microbial biomass was always greater under the plant compared to the interspace. The community composition of N-fixing bacteria was highly variable, with no distinguishable patterns among microsites. Bacterivorous nematodes and rotifers were consistently more abundant under plants (8 and 7 sites, respectively), and fungivorous and omnivorous nematodes were greater under plants at 5 of the 8 sites. Abundance of other soil biota was greater under plants at less than 50% of the sites, but highly correlated with the availability of N, P, Kav, and Fe. Unlike other ecosystems, the soil biota was only infrequently correlated with organic matter. Lack of plant-driven heterogeneity in soils of this ecosystem is likely due to (1) interspace soils covered with BSCs, (2) little incorporation of above-ground plant litter into soils, and/or (3) root deployment patterns