Termination of Afferent Axons in Macaque Striate Cortex

We used horseradish peroxidase (HRP) to orthogradely label afferent axons in macaque striate cortex. Of the 38 axons that we recovered, nine were recorded intracellularly before being filled with HRP. Light microscope and computer reconstructions of filled processes reveal highly stereotyped patterns of arborization and suggest that there are at least five discrete populations of lateral geniculate nucleus (LGN) afferent axon: (1) those to layer 4Cβ, which have extremely circumscribed, dense terminal fields (small branches of which occasionally intrude into 4Cα) but which have not been shown to project to other laminae; (2) afferents to layer 4A, which in some cases send fine ascending collaterals into layer 2-3 and which do not, apparently, send collaterals to other laminae; (3) afferents to layer 1, which are fine, extend over large distances horizontally, and send collaterals to layer 6A; (4) afferents to the lower two-thirds of layer 4Cα, which have few or no collaterals in layer 6; and (5) afferents to the upper half of layer 4Cα, which have arborizing collaterals in layer 6B. Of the nine axons that were recorded intracellularly, those with projections to layer 4Cβ (two axons) and to layer 1 (one axon) had color-selective properties, whereas those (six axons) which arborized in 4Cα all had transient, broad band and highly contrast-sensitive receptive fields. These properties are consistent with derivations from somata in the parvocellular and magnocellular divisions of the LGN, respectively. Afferents to 4Cα were found to cover approximately 6 times as much surface area as afferents to 4Cβ. The preterminal trunks of all axons were found to follow tortuous paths through the neuropil-paths that may derive from axon segregation during development. The wide ranging, patchy distributions of single afferents in 4Cα suggest that individual 4Cα axons supply more than one ocular dominance stripe. In one case where the terminal arborization of a 4Cα axon was mapped against the transneuronally determined pattern of ocular dominance, three separate patches of terminal boutons were indeed found to coincide with the bands of one eye

Thiazolidinedione use and ulcerative colitis-related flares: An exploratory analysis of administrative data:

Recent animal studies and clinical trials suggest that thiazolidinediones, a class of oral antidiabetic agents, are efficacious in reducing inflammation, yet no studies have evaluated their effectiveness in preventing flares. We examined the association between thiazolidinedione use and ulcerative colitis (UC)-related flares

Adenomatous Polyposis Coli (APC) Is Required for Normal Development of Skin and Thymus

The tumor suppressor gene Apc (adenomatous polyposis coli) is a member of the Wnt signaling pathway that is involved in development and tumorigenesis. Heterozygous knockout mice for Apc have a tumor predisposition phenotype and homozygosity leads to embryonic lethality. To understand the role of Apc in development we generated a floxed allele. These mice were mated with a strain carrying Cre recombinase under the control of the human Keratin 14 (K14) promoter, which is active in basal cells of epidermis and other stratified epithelia. Mice homozygous for the floxed allele that also carry the K14-cre transgene were viable but had stunted growth and died before weaning. Histological and immunochemical examinations revealed that K14-cre–mediated Apc loss resulted in aberrant growth in many ectodermally derived squamous epithelia, including hair follicles, teeth, and oral and corneal epithelia. In addition, squamous metaplasia was observed in various epithelial-derived tissues, including the thymus. The aberrant growth of hair follicles and other appendages as well as the thymic abnormalities in K14-cre; Apc(CKO/CKO) mice suggest the Apc gene is crucial in embryonic cells to specify epithelial cell fates in organs that require epithelial–mesenchymal interactions for their development

IPS-1 Is Essential for the Control of West Nile Virus Infection and Immunity

The innate immune response is essential for controlling West Nile virus (WNV) infection but how this response is propagated and regulates adaptive immunity in vivo are not defined. Herein, we show that IPS-1, the central adaptor protein to RIG-I-like receptor (RLR) signaling, is essential for triggering of innate immunity and for effective development and regulation of adaptive immunity against pathogenic WNV. IPS-1−/− mice exhibited increased susceptibility to WNV infection marked by enhanced viral replication and dissemination with early viral entry into the CNS. Infection of cultured bone-marrow (BM) derived dendritic cells (DCs), macrophages (Macs), and primary cortical neurons showed that the IPS-1-dependent RLR signaling was essential for triggering IFN defenses and controlling virus replication in these key target cells of infection. Intriguingly, infected IPS-1−/− mice displayed uncontrolled inflammation that included elevated systemic type I IFN, proinflammatory cytokine and chemokine responses, increased numbers of inflammatory DCs, enhanced humoral responses marked by complete loss of virus neutralization activity, and increased numbers of virus-specific CD8+ T cells and non-specific immune cell proliferation in the periphery and in the CNS. This uncontrolled inflammatory response was associated with a lack of regulatory T cell expansion that normally occurs during acute WNV infection. Thus, the enhanced inflammatory response in the absence of IPS-1 was coupled with a failure to protect against WNV infection. Our data define an innate/adaptive immune interface mediated through IPS-1-dependent RLR signaling that regulates the quantity, quality, and balance of the immune response to WNV infection

DETERMINANTS OF ADJUVANT OXALIPLATIN RECEIPT AMONG OLDER STAGE II AND III COLORECTAL CANCER PATIENTS

Controversy exists regarding adjuvant oxaliplatin treatment among older stage II and III colorectal cancer (CRC) patients. We sought to identify patient/tumor, physician, hospital, and geographic factors associated with oxaliplatin use among older patients

230 Th normalization: new insights on an essential tool for quantifying sedimentary fluxes in the modern and quaternary ocean

© The Author(s), 2020. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Costa, K. M., Hayes, C. T., Anderson, R. F., Pavia, F. J., Bausch, A., Deng, F., Dutay, J., Geibert, W., Heinze, C., Henderson, G., Hillaire-Marcel, C., Hoffmann, S., Jaccard, S. L., Jacobel, A. W., Kienast, S. S., Kipp, L., Lerner, P., Lippold, J., Lund, D., Marcantonio, F., McGee, D., McManus, J. F., Mekik, F., Middleton, J. L., Missiaen, L., Not, C., Pichat, S., Robinson, L. F., Rowland, G. H., Roy-Barman, M., Alessandro, Torfstein, A., Winckler, G., & Zhou, Y. 230 Th normalization: new insights on an essential tool for quantifying sedimentary fluxes in the modern and quaternary ocean. Paleoceanography and Paleoclimatology, 35(2), (2020): e2019PA003820, doi:10.1029/2019PA003820.230Th normalization is a valuable paleoceanographic tool for reconstructing high‐resolution sediment fluxes during the late Pleistocene (last ~500,000 years). As its application has expanded to ever more diverse marine environments, the nuances of 230Th systematics, with regard to particle type, particle size, lateral advective/diffusive redistribution, and other processes, have emerged. We synthesized over 1000 sedimentary records of 230Th from across the global ocean at two time slices, the late Holocene (0–5,000 years ago, or 0–5 ka) and the Last Glacial Maximum (18.5–23.5 ka), and investigated the spatial structure of 230Th‐normalized mass fluxes. On a global scale, sedimentary mass fluxes were significantly higher during the Last Glacial Maximum (1.79–2.17 g/cm2kyr, 95% confidence) relative to the Holocene (1.48–1.68 g/cm2kyr, 95% confidence). We then examined the potential confounding influences of boundary scavenging, nepheloid layers, hydrothermal scavenging, size‐dependent sediment fractionation, and carbonate dissolution on the efficacy of 230Th as a constant flux proxy. Anomalous 230Th behavior is sometimes observed proximal to hydrothermal ridges and in continental margins where high particle fluxes and steep continental slopes can lead to the combined effects of boundary scavenging and nepheloid interference. Notwithstanding these limitations, we found that 230Th normalization is a robust tool for determining sediment mass accumulation rates in the majority of pelagic marine settings (>1,000 m water depth).We thank Zanna Chase and one anonymous reviewer for valuable feedback. K. M. C. was supported by a Postdoctoral Scholarship at WHOI. L. M. acknowledges funding from the Australian Research Council grant DP180100048. The contribution of C. T. H., J. F. M., and R. F. A. were supported in part by the U.S. National Science Foundation (US‐NSF). G. H. R. was supported by the Natural Environment Research Council (grant NE/L002434/1). S. L. J. acknowledges support from the Swiss National Science Foundation (grants PP002P2_144811 and PP00P2_172915). This study was supported by the Past Global Changes (PAGES) project, which in turn received support from the Swiss Academy of Sciences and the US‐NSF. This work grew out of a 2018 workshop in Aix‐Marseille, France, funded by PAGES, GEOTRACES, SCOR, US‐NSF, Aix‐Marseille Université, and John Cantle Scientific. All data are publicly available as supporting information to this document and on the National Center for Environmental Information (NCEI) at https://www.ncdc.noaa.gov/paleo/study/28791

Patterns of Sociodemographic and Clinicopathologic Characteristics of Stages II and III Colorectal Cancer Patients by Age: Examining Potential Mechanisms of Young-Onset Disease

Background and Aims. As a first step toward understanding the increasing incidence of colorectal cancer (CRC) in younger (age < 50) populations, we examined demographic, clinicopathologic, and socioeconomic characteristics and treatment receipt in a population-based sample of patients newly diagnosed with stages II and III CRC. Methods. Patients were sampled from the National Cancer Institute’s Patterns of Care studies in 1990/91, 1995, 2000, 2005, and 2010 (n=6,862). Tumor characteristics and treatment data were obtained through medical record review and physician verification. We compared sociodemographic and clinicopathologic characteristics and treatment patterns of younger (age < 50) and older (age 50–69, age ≥ 70) CRC patients. Results. Younger patients were more likely to be black (13%) and Hispanic (15%) than patients aged 50–69 years (11% and 10%, resp.) and ≥70 years (7% each). A larger proportion of young white (41%) and Hispanic (33%) patients had rectal tumors, whereas tumors in the right colon were the most common in young black patients (39%). The majority of younger patients received chemotherapy and radiation therapy, although receipt of microsatellite instability testing was suboptimal (27%). Conclusion. Characteristics of patients diagnosed with young-onset CRC differ considerably by race/ethnicity, with a higher proportion of black and Hispanic patients diagnosed at the age of < 50 years

Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia: Review of Clinical Manifestations as Foundations for Therapeutic Development

A comprehensive review of published literature was conducted to elucidate the genetics, neuropathology, imaging findings, prevalence, clinical course, diagnosis/clinical evaluation, potential biomarkers, and current and proposed treatments for adult-onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP), a rare, debilitating, and life-threatening neurodegenerative disorder for which disease-modifying therapies are not currently available. Details on potential efficacy endpoints for future interventional clinical trials in patients with ALSP and data related to the burden of the disease on patients and caregivers were also reviewed. The information in this position paper lays a foundation to establish an effective clinical rationale and address the clinical gaps for creation of a robust strategy to develop therapeutic agents for ALSP, as well as design future clinical trials, that have clinically meaningful and convergent endpoints

Identifying Specific Chemotherapeutic Agents in Medicare Data: A Validation Study

Large healthcare databases are increasingly used to examine the dissemination and benefits and harms of chemotherapy treatment in routine practice, particularly among patients excluded from trials (e.g., the elderly). Misclassification of chemotherapy could bias estimates of frequency and association, warranting an updated assessment

Evidence Synthesis International (ESI): Position Statement

This paper is the initial Position Statement of Evidence Synthesis International, a new partnership of organizations that produce, support and use evidence synthesis around the world. The paper (i) argues for the importance of synthesis as a research exercise to clarify what is known from research evidence to inform policy, practice and personal decision making; (ii) discusses core issues for research synthesis such as the role of research evidence in decision making, the role of perspectives, participation and democracy in research and synthesis as a core component of evidence ecosystems; (iii) argues for 9 core principles for ESI on the nature and role of research synthesis; and (iv) lists the 5 main goals of ESI as a coordinating partnership for promoting and enabling the production and use of research synthesis