Observed Variability of the Solar Mg II h Spectral Line

The Mg II h&k doublet are two of the primary spectral lines observed by the Sun-pointing Interface Region Imaging Spectrograph (IRIS). These lines are tracers of the magnetic and thermal environment that spans from the photosphere to the upper chromosphere. We use a double gaussian model to fit the Mg II h profile for a full-Sun mosaic dataset taken 24-Aug-2014. We use the ensemble of high-quality profile fits to conduct a statistical study on the variability of the line profile as it relates the magnetic structure, dynamics, and center-to-limb viewing angle. The average internetwork profile contains a deeply reversed core and is weakly asymmetric at h2. In the internetwork, we find a strong correlation between h3 wavelength and profile asymmetry as well h1 width and h2 width. The average reversal depth of the h3 core is inversely related to the magnetic field. Plage and sunspots exhibit many profiles which do not contain a reversal. These profiles also occur infrequently in the internetwork. We see indications of magnetically aligned structures in plage and network in statistics associated with the line core, but these structures are not clear or extended in the internetwork. The center-to-limb variations are compared with predictions of semi-empirical model atmospheres. We measure a pronounced limb darkening in the line core which is not predicted by the model. The aim of this work is to provide a comprehensive measurement baseline and preliminary analysis on the observed structure and formation of the Mg II profiles observed by IRIS.Comment: Accepted for publicatio

Effects of culling white-tailed deer on tree regeneration and Microstegium vimineum, an invasive grass

Reduction of forest regeneration due to overbrowsing by white-tailed deer is a growing concern for land managers. Abundant deer can impede forest regeneration through direct predation on tree seedlings. Additionally high deer density can facilitate the establishment of a dense understory of browse tolerant plant species that shades seedlings and persists even in the absence of deer. In response to these challenges, land managers have sought to reduce deer herds to restore tree regeneration, but few studies have evaluated the effectiveness of this management. Our study took place in Catoctin Mountain Park, a US National Park Service unit with a history of high deer density. The park has been heavily invaded by Microstegium vimineum, an invasive grass that can completely cover the forest floor. Using permanent plots established prior to the start of deer management, we were able to assess the joint effects of deer culling and M. vimineum on tree seedling density. We found that tree seedling density increased in response to deer reductions. M. vimineum cover initially increased, but then decreased. Seedling densities were higher in plots with more M. vimineum cover, indicating that it did not form a recalcitrant understory that would suppress regeneration. However, eight years after deer management began, few tree seedlings were \u3e 30 cm tall, implying that it will be many years before they grow into the sapling stage. Our results indicate that deer culling can be an effective tool in restoring tree regeneration despite the presence of M. vimineum, but that success will require a long-term commitment

GRTS and Graphs: Monitoring Natural Resources in Urban Landscapes

Environmental monitoring programs are an important tool for providing land managers with a scientific basis for management decisions. However, many ecological processes operate on spatial scales that transcend management boundaries (Schonewald-Cox 1988). For example, adjacent lands may influence protected-area resources via edge effects, source-sink dynamics, or invasion processes (Jones et al. 2009). Hydrologic alterations outside management units also may have profound effects on the integrity of resources being managed (Pringle 2000). The impacts of climate change are presenting challenges to resource management at local-to-global scales (Karl et al. 2009). This potential disparity between ecological and political boundaries presents an interesting dilemma for natural resource monitoring and is readily apparent in urban and agricultural environments, which tend to be dominated by external stressors (Collins et al. 2000). Despite their limited control over external land use, natural resource managers are concerned with processes such as development in the surrounding landscape, as these may lead to habitat loss and degradation that directly impair their resources. As a consequence, the management of the natural resources in and around parks and other areas requires a broad and dynamic understanding of the spatio-temporal patterns of environmental change. If monitoring is to be successful in providing data that inform management, information about regional and landscape context should play a critical role in designing monitoring strategies

Justifying the constitutional regulation of political parties : a framework for analysis

What are the main reasons behind the regulation of political parties by contemporary constitutional practices? This article presents a framework for analysis which identifies types of justifications and actors involved in the process of regulation and their further influence on the outcomes of constitutionalization. The empirical focus is on the revelatory case of Luxembourg, which amended the constitution for the sole reason of giving parties constitutional status. The analysis suggests that the constitutional regulation of political parties depends on their current interests and power status. Additionally, the paper draws attention to the involvement of external actors and nevertheless to the changing nature of contemporary constitutionalism

A Methodological approach to supporting organisational learning

Many organizations need to respond quickly to change and their workers need to regularly develop new knowledge and skills. The prevailing approach to meeting these demands is on-the-job training, but this is known to be highly ineffective, cause stress and devalue workplace autonomy. Conversely, organizational learning is a process through which workers learn gradually in the work context through experience, reflection on work practice and collaboration with colleagues. Our approach aims to support and enhance organizational learning around enriched work representations. Work representations are tools and documents used to support collaborative working and learning. These are enriched through associations with formal knowledge models and informal discourse. The work representations, informal discourse and associated knowledge models together form on organizational memory from which knowledge can be retrieved later. Our methodological approach to supporting organizational learning is drawn from three industrial case studies concerned with machine maintenance, team planning and hotline support. The methodology encompasses development and design activities, a description of the roles and duties required to sustain the long-term use of the tools, and applicability criteria outlining the kind of organizations that can benefit from this approach

Lymphocytic infiltration in stage II microsatellite stable colorectal tumors: A retrospective prognosis biomarker analysis

Background: Identifying stage II patients with colorectal cancer (CRC) at higher risk of progression is a clinical priority in order to optimize the advantages of adjuvant chemotherapy while avoiding unnecessary toxicity. Recently, the intensity and the quality of the host immune response in the tumor microenvironment have been reported to have an important role in tumorigenesis and an inverse association with tumor progression. This association is well established in microsatellite instable CRC. In this work, we aim to assess the usefulness of measures of T-cell infiltration as prognostic biomarkers in 640 stage II, CRC tumors, 582 of them confirmed microsatellite stable. Methods and findings: We measured both the quantity and clonality index of T cells by means of T-cell receptor (TCR) immunosequencing in a discovery dataset (95 patients with colon cancer diagnosed at stage II and microsatellite stable, median age 67, 30% women) and replicated the results in 3 additional series of stage II patients from 2 countries. Series 1 and 2 were recruited in Barcelona, Spain and included 112 fresh frozen (FF, median age 69, 44% women) and 163 formalin-fixed paraffin-embedded (FFPE, median age 67, 39% women) samples, respectively. Series 3 included 270 FFPE samples from patients recruited in Haifa, Northern Israel, as part of a large case-control study of CRC (median age 73, 46% women). Median follow-up time was 81.1 months. Cox regression models were fitted to evaluate the prognostic value of T-cell abundance and Simpson clonality of TCR variants adjusting by sex, age, tumor location, and stage (IIA and IIB). In the discovery dataset, higher TCR abundance was associated with better prognosis (hazard ratio [HR] for ≥Q1 = 0.25, 95% CI 0.10-0.63, P = 0.003). A functional analysis of gene expression on these tumors revealed enrichment in pathways related to immune response. Higher values of clonality index (lower diversity) were not associated with worse disease-free survival, though the HR for ≥Q3 was 2.32 (95% CI 0.90-5.97, P = 0.08). These results were replicated in an independent FF dataset (TCR abundance: HR = 0.30, 95% CI 0.12-0.72, P = 0.007; clonality: HR = 3.32, 95% CI 1.38-7.94, P = 0.007). Also, the association with prognosis was tested in 2 independent FFPE datasets. The same association was observed with TCR abundance (HR = 0.41, 95% CI 0.18-0.93, P = 0.03 and HR = 0.56, 95% CI 0.31-1, P = 0.042, respectively, for each FFPE dataset). However, the clonality index was associated with prognosis only in the FFPE dataset from Israel (HR = 2.45, 95% CI 1.39-4.32, P = 0.002). Finally, a combined analysis combining all microsatellite stable (MSS) samples demonstrated a clear prognosis value both for TCR abundance (HR = 0.39, 95% CI 0.26-0.57, P = 1.3e-06) and the clonality index (HR = 2.13, 95% CI 1.44-3.15, P = 0.0002). These associations were also observed when variables were considered continuous in the models (HR per log2 of TCR abundance = 0.85, 95% CI 0.78-0.93, P = 0.0002; HR per log2 or clonality index = 1.16, 95% CI 1.03-1.31, P = 0.016). Limitations: This is a retrospective study, and samples had been preserved with different methods. Validation series lack complete information about microsatellite instability (MSI) status and pathology assessment. The Molecular Epidemiology of Colorectal Cancer (MECC) study had information about overall survival instead of progression-free survival. Conclusion: Results from this study demonstrate that tumor lymphocytes, assessed by TCR repertoire quantification based on a sequencing method, are an independent prognostic factor in microsatellite stable stage II CRC

Fiber deprivation and microbiome-borne curli shift gut bacterial populations and accelerate disease in a mouse model of Parkinson's disease.

peer reviewedParkinson's disease (PD) is a neurological disorder characterized by motor dysfunction, dopaminergic neuron loss, and alpha-synuclein (αSyn) inclusions. Many PD risk factors are known, but those affecting disease progression are not. Lifestyle and microbial dysbiosis are candidates in this context. Diet-driven gut dysbiosis and reduced barrier function may increase exposure of enteric neurons to toxins. Here, we study whether fiber deprivation and exposure to bacterial curli, a protein cross-seeding with αSyn, individually or together, exacerbate disease in the enteric and central nervous systems of a transgenic PD mouse model. We analyze the gut microbiome, motor behavior, and gastrointestinal and brain pathologies. We find that diet and bacterial curli alter the microbiome and exacerbate motor performance, as well as intestinal and brain pathologies, but to different extents. Our results shed important insights on how diet and microbiome-borne insults modulate PD progression via the gut-brain axis and have implications for lifestyle management of PD.Deciphering the impact of exposures from the gut microbiome-derived molecular complex in human health and diseas

Mendelian randomization of circulating polyunsaturated fatty acids and colorectal cancer risk

Background: Results from epidemiologic studies examining polyunsaturated fatty acids (PUFA) and colorectal cancer risk are inconsistent. Mendelian randomization may strengthen causal inference from observational studies. Given their shared metabolic pathway, examining the combined effects of aspirin/NSAID use with PUFAs could help elucidate an association between PUFAs and colorectal cancer risk. Methods: Information was leveraged from genome-wide association studies (GWAS) regarding PUFA-associated SNPs to create weighted genetic scores (wGS) representing genetically predicted circulating blood PUFAs for 11,016 non-Hispanic white colorectal cancer cases and 13,732 controls in the Genetics and Epidemiology of Colorectal Cancer Consortium (GECCO). Associations per SD increase in the wGS were estimated using unconditional logistic regression. Interactions between PUFA wGSs and aspirin/NSAID use on colorectal cancer risk were also examined. Results: Modest colorectal cancer risk reductions were observed per SD increase in circulating linoleic acid [ORLA = 0.96; 95% confidence interval (CI) = 0.93-0.98; P = 5.2 × 10-4] and α-linolenic acid (ORALA = 0.95; 95% CI = 0.92-0.97; P = 5.4 × 10-5), whereas modest increased risks were observed for arachidonic (ORAA = 1.06; 95% CI = 1.03-1.08; P = 3.3 × 10-5), eicosapentaenoic (OREPA = 1.04; 95% CI = 1.01-1.07; P = 2.5 × 10-3), and docosapentaenoic acids (ORDPA = 1.03; 95% CI = 1.01-1.06; P = 1.2 × 10-2). Each of these effects was stronger among aspirin/NSAID nonusers in the stratified analyses. Conclusions: Our study suggests that higher circulating shorter-chain PUFAs (i.e., LA and ALA) were associated with reduced colorectal cancer risk, whereas longer-chain PUFAs (i.e., AA, EPA, and DPA) were associated with an increased colorectal cancer risk. Impact: The interaction of PUFAs with aspirin/NSAID use indicates a shared colorectal cancer inflammatory pathway. Future research should continue to improve PUFA genetic instruments to elucidate the independent effects of PUFAs on colorectal cancer

Combining Asian and European genome-wide association studies of colorectal cancer improves risk prediction across racial and ethnic populations

Polygenic risk scores (PRS) have great potential to guide precision colorectal cancer (CRC) prevention by identifying those at higher risk to undertake targeted screening. However, current PRS using European ancestry data have sub-optimal performance in non-European ancestry populations, limiting their utility among these populations. Towards addressing this deficiency, we expand PRS development for CRC by incorporating Asian ancestry data (21,731 cases; 47,444 controls) into European ancestry training datasets (78,473 cases; 107,143 controls). The AUC estimates (95% CI) of PRS are 0.63(0.62-0.64), 0.59(0.57-0.61), 0.62(0.60-0.63), and 0.65(0.63-0.66) in independent datasets including 1681-3651 cases and 8696-115,105 controls of Asian, Black/African American, Latinx/Hispanic, and non-Hispanic White, respectively. They are significantly better than the European-centric PRS in all four major US racial and ethnic groups (p-values < 0.05). Further inclusion of non-European ancestry populations, especially Black/African American and Latinx/Hispanic, is needed to improve the risk prediction and enhance equity in applying PRS in clinical practice

Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries

In the version of this article initially published, the author affiliations incorrectly listed “Candiolo Cancer Institute FPO-IRCCS, Candiolo (TO), Italy” as “Candiolo Cancer Institute, Candiolo, Italy.” The change has been made to the HTML and PDF versions of the article