Morphological and physiological traits as indicators of drought tolerance in tallgrass prairie plants

Master of ScienceDepartment of BiologyJesse B. NippertThe Konza Prairie in northern Kansas, USA contains over 550 vascular plant species; of which, few have been closely studied. These species are adapted to environmental stress as imposed by variable temperature, precipitation, fire, and grazing. Understanding which plant traits relate to drought responses will allow us to both predict drought tolerance and potential future shifts in plant community composition from changes in local climate. Morphological and physiological measurements were taken on 121 species of herbaceous tallgrass prairie plants grown from seed in a growth chamber. Gas exchange measurements including maximum photosynthetic rate, stomatal conductance to water vapor, and intercellular CO[subscript]2 concentration were measured. All plants were exposed to a drought treatment and were monitored daily until stomatal conductance was zero. At this point, critical leaf water potential (Ψ[subscript]crit), an indicator of physiological drought tolerance was assessed. Other measurements include root length, diameter, volume, and mass, leaf area, leaf tissue density, root tissue density, and root to shoot ratio. Traits were compared using pair-wise bivariate analysis and principal component analysis (PCA). A dichotomy was found between dry-adapted plants with thin, dense leaves and roots, high leaf angle, and highly negative Ψ[subscript]crit and hydrophiles which have the opposite profile. A second axis offers more separation based on high photosynthetic rate, high conductance rate, and leaf angle, but fails to provide a distinction between C[subscript]3 and C[subscript]4 species. When tested independently, grasses and forbs both showed drought tolerance strategies similar to the primary analysis. Matching up these axes with long term abundance data suggests that species with drought tolerance traits have increased abundance on Konza, especially in upland habitats. However, traits that relate to drought tolerance mirror relationships with nutrient stress, confounding separation of low water versus low nutrient strategies. My results not only illustrate the utility of morphological and physiological plant traits in classifying drought responses across a range of species, but as functional traits in predicting both drought tolerance in individual species and relative abundance across environmental gradients of water availability

Protecting patient privacy when sharing patient-level data from clinical trials

Abstract Background Greater transparency and, in particular, sharing of patient-level data for further scientific research is an increasingly important topic for the pharmaceutical industry and other organisations who sponsor and conduct clinical trials as well as generally in the interests of patients participating in studies. A concern remains, however, over how to appropriately prepare and share clinical trial data with third party researchers, whilst maintaining patient confidentiality. Clinical trial datasets contain very detailed information on each participant. Risk to patient privacy can be mitigated by data reduction techniques. However, retention of data utility is important in order to allow meaningful scientific research. In addition, for clinical trial data, an excessive application of such techniques may pose a public health risk if misleading results are produced. After considering existing guidance, this article makes recommendations with the aim of promoting an approach that balances data utility and privacy risk and is applicable across clinical trial data holders. Discussion Our key recommendations are as follows: 1. Data anonymisation/de-identification: Data holders are responsible for generating de-identified datasets which are intended to offer increased protection for patient privacy through masking or generalisation of direct and some indirect identifiers. 2. Controlled access to data, including use of a data sharing agreement: A legally binding data sharing agreement should be in place, including agreements not to download or further share data and not to attempt to seek to identify patients. Appropriate levels of security should be used for transferring data or providing access; one solution is use of a secure ‘locked box’ system which provides additional safeguards. Summary This article provides recommendations on best practices to de-identify/anonymise clinical trial data for sharing with third-party researchers, as well as controlled access to data and data sharing agreements. The recommendations are applicable to all clinical trial data holders. Further work will be needed to identify and evaluate competing possibilities as regulations, attitudes to risk and technologies evolve

Sustainability education beyond the classroom: how the “exploding university” nurtures collective intelligence across local and global communities

This chapter explores how the authors expanded their teaching and learning beyond the classroom at Manchester Metropolitan University in the UK. It puts forward the theoretical concept of the “exploding university” as a way to help develop a critical yet hopeful understanding of collective problems at local and global scales. This helps them explore three interrelated initiatives that brought teachers, students, and communities together, namely a sustainability festival, research project on animal rehoming, and community tree-planting drive. The chapter illuminates how exploding the work beyond the classroom enabled everyone involved to take action on the challenges that matter to them, while also developing a “collective intelligence” about their underlying causes. The exploding university thus emerges as a theoretical and practical model, which we can use to inspire students to actively critique, reimagine, and reconstruct the world around them. The authors conclude by encouraging and supporting others who might wish to embark on similar journeys themselves

Working Time Society consensus statements: Evidence-based effects of shift work on physical and mental health

Ferguson, SA ORCiD: 0000-0002-9682-7971; Sargent, C ORCiD: 0000-0001-5340-4701Potential effects of shift work on health are probably related to the misalignment between the light-dark cycle and the human activity-rest cycle. Light exposure at night mediates these effects, including social misalignment and leads to an inversion of activity and rest, which, in turn, is linked to changes in behaviours. This article reviews the epidemiological evidence on the association between shift work and health, and possible mechanisms underlying this association. First, evidence from findings of the meta-analyses and systematic reviews published in the last 10 years is presented. In addition, it reports the larger single-occupation studies and recent large population-based studies of the general workforce. Koch's postulates were used to evaluate the evidence related to the development of disease as a result of exposure to shift work. Finally, we discussed limitations of the multiple pathways that link shift work with specific disorders and the methodological challenges facing shift work research. We concluded that the clearest indications of shift work being the cause of a disease are given when there is a substantial body of evidence from high quality field studies showing an association and there is good evidence from laboratory studies supporting a causal explanation of the link

Assessing copy number aberrations and copy neutral loss of heterozygosity across the genome as best practice: An evidence based review of clinical utility from the cancer genomics consortium (CGC) working group for myelodysplastic syndrome, myelodysplastic/myeloproliferative and myeloproliferative neoplasms

Multiple studies have demonstrated the utility of chromosomal microarray (CMA) testing to identify clinically significant copy number alterations (CNAs) and copy-neutral loss-of-heterozygosity (CN-LOH) in myeloid malignancies. However, guidelines for integrating CMA as a standard practice for diagnostic evaluation, assessment of prognosis and predicting treatment response are still lacking. CMA has not been recommended for clinical work-up of myeloid malignancies by the WHO 2016 or the NCCN 2017 guidelines but is a suggested test by the European LeukaemiaNet 2013 for the diagnosis of primary myelodysplastic syndrome (MDS). The Cancer Genomics Consortium (CGC) Working Group for Myeloid Neoplasms systematically reviewed peer-reviewed literature to determine the power of CMA in (1) improving diagnostic yield, (2) refining risk stratification, and (3) providing additional genomic information to guide therapy. In this manuscript, we summarize the evidence base for the clinical utility of array testing in the workup of MDS, myelodysplastic/myeloproliferative neoplasms (MDS/MPN) and myeloproliferative neoplasms (MPN). This review provides a list of recurrent CNAs and CN-LOH noted in this disease spectrum and describes the clinical significance of the aberrations and how they complement gene mutation findings by sequencing. Furthermore, for new or suspected diagnosis of MDS or MPN, we present suggestions for integrating genomic testing methods (CMA and mutation testing by next generation sequencing) into the current standard-of-care clinical laboratory testing (karyotype, FISH, morphology, and flow)

International Sexual Health And REproductive health (I-SHARE) survey during COVID-19: study protocol for online national surveys and global comparative analyses.

BACKGROUND: COVID-19 may have a profound impact on sexual health, reproductive health and social life across the world. Shelter in place regulations that have extended across the globe may influence condomless sex, exacerbate intimate partner violence and reduce access to essential reproductive health services. Population representative research is challenging during shelter in place, leaving major gaps in our understanding of sexual and reproductive health during COVID-19. This International Sexual Health And ReproductivE health (I-SHARE) study protocol manuscript describes a common plan for online national surveys and global comparative analyses. METHODS: The purpose of this cross-sectional study is to better understand sexual and reproductive health in selected countries during the COVID-19 pandemic and facilitate multinational comparisons. Participants will be recruited through an online survey link disseminated through local, regional and national networks. In each country, a lead organisation will be responsible for organising ethical review, translation and survey administration. The consortium network provides support for national studies, coordination and multinational comparison. We will use multilevel modelling to determine the relationship between COVID-19 and condomless sex, intimate partner violence, access to reproductive health services, HIV testing and other key items. This study protocol defines primary outcomes, prespecified subanalyses and analysis plans. CONCLUSION: The I-SHARE study examines sexual and reproductive health at the national and global level during the COVID-19 pandemic. We will use multilevel modelling to investigate country-level variables associated with outcomes of interest. This will provide a foundation for subsequent online multicountry comparison using more robust sampling methodologies

Breast-Cancer-Specific Mortality in Patients Treated Based on the 21-Gene Assay: A SEER Population-Based Study

The 21-gene Recurrence Score assay is validated to predict recurrence risk and chemotherapy benefit in hormone-receptor-positive (HR+) invasive breast cancer. To determine prospective breast-cancer-specific mortality (BCSM) outcomes by baseline Recurrence Score results and clinical covariates, the National Cancer Institute collaborated with Genomic Health and 14 population-based registries in the the Surveillance, Epidemiology, and End Results (SEER) Program to electronically supplement cancer surveillance data with Recurrence Score results. The prespecified primary analysis cohort was 40–84 years of age, and had node-negative, HR+, HER2-negative, nonmetastatic disease diagnosed between January 2004 and December 2011 in the entire SEER population, and Recurrence Score results (N = 38,568). Unadjusted 5-year BCSM were 0.4% (n = 21,023; 95% confidence interval (CI), 0.3–0.6%), 1.4% (n = 14,494; 95% CI, 1.1–1.7%), and 4.4% (n = 3,051; 95% CI, 3.4–5.6%) for Recurrence Score \u3c 18, 18–30, and ≥ 31 groups, respectively (P \u3c 0.001). In multivariable analysis adjusted for age, tumor size, grade, and race, the Recurrence Score result predicted BCSM (P \u3c 0.001). Among patients with node-positive disease (micrometastases and up to three positive nodes; N = 4,691), 5-year BCSM (unadjusted) was 1.0% (n = 2,694; 95% CI, 0.5–2.0%), 2.3% (n = 1,669; 95% CI, 1.3–4.1%), and 14.3% (n = 328; 95% CI, 8.4–23.8%) for Recurrence Score \u3c 18, 18–30, ≥ 31 groups, respectively (P \u3c 0.001). Five-year BCSM by Recurrence Score group are reported for important patient subgroups, including age, race, tumor size, grade, and socioeconomic status. This SEER study represents the largest report of prospective BCSM outcomes based on Recurrence Score results for patients with HR+, HER2-negative, node-negative, or node-positive breast cancer, including subgroups often under-represented in clinical trials

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

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

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