Identifying and Measuring the Effect of Firm Clusters Among Certified Organic Processors and Handlers

This paper investigates the certified organic handler sector, a specialized component of the middle part of the farm-to-table marketing chain, and documents the impacts of firm agglomeration (or firm clusters) on firm-level performance or firm-level decisions. After accounting for endogeneity in firm clustering, our findings confirm that firm clusters have significant impacts, though the estimate of the impact depends on how a firm cluster is defined. For example, significant impacts on sales per employee range from an additional $0.17 million to$1.47 million, depending on whether a small or large number of firms is used as the minimum number to define a firm cluster.firm clusters, organic, treatment effects, Agribusiness, Agricultural and Food Policy, Community/Rural/Urban Development,

Spatio-Temporal Neural Changes After Task-Switching Training in Old Age

In the present study, we aimed at examining selective neural changes after taskswitching training in old age by not only considering the spatial location but also the timescale of brain activation changes (i.e., sustained/block-related or transient/trialrelated timescales). We assigned a sample of 50 older adults to a task-switching training or an active single-task control group. We administered two task paradigms, either sensitive to transient (i.e., a context-updating task) or sustained (i.e., a delayedrecognition working-memory task) dynamics of cognitive control. These dynamics were captured by utilizing an appropriate event-related or block-related functional magnetic resonance imaging design. We captured selective changes in task activation during the untrained tasks after task-switching training compared to an active control group. Results revealed changes at the neural level that were not evident from only behavioral data. Importantly, neural changes in the transient-sensitive context updating task were found on the same timescale but in a different region (i.e., in the left inferior parietal lobule) than in the task-switching training task (i.e., ventrolateral PFC, inferior frontal junction, superior parietal lobule), only pointing to temporal overlap, while neural changes in the sustained-sensitive delayed-recognition task overlapped in both timescale and region with the task-switching training task (i.e., in the basal ganglia), pointing to spatio-temporal overlap. These results suggest that neural changes after task-switching training seem to be critically supported by the temporal organization of neural processing.Deutsche Forschungsgemeinschaft (DFG

Temporal trends in pregnancy-associated stroke and its outcomes among women with hypertensive disorders of pregnancy

Funding PW is funded by a NIHR Transitional Research Fellowship. CCG is part-funded by West Midlands ARC. LCC is funded by a NIHR Professorship (RP-2014-05-019). This paper presents independent research funded by the NIHR. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care. The funders had no involvement in the conduct of this research.Peer reviewedPublisher PD

Daratumumab With Cetrelimab, an Anti-PD-1 Monoclonal Antibody, in Relapsed/Refractory Multiple Myeloma

Patients with relapsed or refractory multiple myeloma have an immunosuppressive state with upregulation of programmed death receptor-1 on immune effector cells. Treatment with daratumumab plus cetrelimab, which targets the programmed death receptor-1, was evaluated in 9 patients with relapsed or refractory multiple myeloma. No new safety concerns were identified for the combination. The potential clinical benefit of daratumumab plus cetrelimab remains uncertain. Background: Daratumumab is approved for relapsed or refractory multiple myeloma (RRMM) as monotherapy or in combination regimens. We evaluated daratumumab plus cetrelimab, a programmed death receptor-1 inhibitor, in RRMM. Patients and Methods: This open-label, multiphase study enrolled adults with RRMM with >= 3 prior lines of therapy. Part 1 was a safety run-in phase examining dose-limiting toxicities of daratumumab (16 mg/kg intravenously weekly for cycles 1-2, biweekly for cycles 3-6, and monthly thereafter) plus cetrelimab (240 mg intravenously biweekly, all cycles). In Parts 2 and 3, patients were to be randomized to daratumumab with or without cetrelimab (same schedule as Part 1). Endpoints included safety, overall response rate, pharmacokinetics, and biomarker analyses. Results: Nine patients received daratumumab plus cetrelimab in the safety run-in, and 1 received daratumumab in Part 2 before administrative study termination following a data monitoring committee's global recommendation to stop any trial including daratumumab combined with inhibitors of programmed death receptor-1 or its ligand (programmed death-ligand 1). The median follow-up times were 6.7 months (safety run-in) and 0.3 months (Part 2). No dose-limiting toxicities occurred. All 10 patients had >= 1 treatment-emergent adverse event; 7 patients had grade 3 to 4 treatment-emergent adverse events, and none led to treatment discontinuation or death. In the safety run-in, 7 (77.7%) patients had > 1 infusion-related reaction (most grade 1-2), and 1 had a grade 2 immune-mediated reaction. Among safety run-in patients, the overall response rate was 44.4%. Conclusions: No new safety concerns were identified for daratumumab plus cetrelimab in RRMM. The short study duration and small population limit complete analysis of this combination. (C) 2020 The Author(s). Published by Elsevier Inc

Genetic Background Can Result in a Marked or Minimal Effect of Gene Knockout (GPR55 and CB2 Receptor) in Experimental Autoimmune Encephalomyelitis Models of Multiple Sclerosis

PMCID: PMC379391

The Structure of Episodic Memory: Ganeri's ‘Mental Time Travel and Attention’

We offer a framework for assessing what the structure of episodic memory might be, if one accepts the Buddhist denial of persisting selves. This paper is a response to Jonardon Ganeri's paper "Mental time travel and attention", which explores Buddhaghosa's ideas about memory. (It will eventually be published with a reply by Ganeri)

Risk factors for breast cancer in postmenopausal Caucasian and Chinese-Canadian women

Abstract Introduction Striking differences exist between countries in the incidence of breast cancer. The causes of these differences are unknown, but because incidence rates change in migrants, they are thought to be due to lifestyle rather than genetic differences. The goal of this cross-sectional study was to examine breast cancer risk factors in populations with different risks for breast cancer. Methods We compared breast cancer risk factors among three groups of postmenopausal Canadian women at substantially different risk of developing breast cancer - Caucasians (N = 413), Chinese women born in the West or who migrated to the West before age 21 (N = 216), and recent Chinese migrants (N = 421). Information on risk factors and dietary acculturation were collected by telephone interviews using questionnaires, and anthropometric measurements were taken at a home visit. Results Compared to Caucasians, recent Chinese migrants weighed on average 14 kg less, were 6 cm shorter, had menarche a year later, were more often parous, less often had a family history of breast cancer or a benign breast biopsy, a higher Chinese dietary score, and a lower Western dietary score. For most of these variables, Western born Chinese and early Chinese migrants had values intermediate between those of Caucasians and recent Chinese migrants. We estimated five-year absolute risks for breast cancer using the Gail Model and found that risk estimates in Caucasians would be reduced by only 11% if they had the risk factor profile of recent Chinese migrants for the risk factors in the Gail Model. Conclusions Our results suggest that in addition to the risk factors in the Gail Model, there likely are other factors that also contribute to the large difference in breast cancer risk between Canada and China

Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas

Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts