Genetic determinants of co-accessible chromatin regions in activated T cells across humans.

Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression

Prospectus, October 27, 1999

https://spark.parkland.edu/prospectus_1999/1027/thumbnail.jp

Differential Gene Expression in Primary Breast Tumors Associated with Lymph Node Metastasis

Lymph node status remains one of the most useful prognostic indicators in breast cancer; however, current methods to assess nodal status disrupt the lymphatic system and may lead to secondary complications. Identification of molecular signatures discriminating lymph node-positive from lymph node-negative primary tumors would allow for stratification of patients requiring surgical assesment of lymph nodes. Primary breast tumors from women with negative (n = 41) and positive (n = 35) lymph node status matched for possible confounding factors were subjected to laser microdissection and gene expression data generated. Although ANOVA analysis (P < .001, fold-change >1.5) revealed 13 differentially expressed genes, hierarchical clustering classified 90% of node-negative but only 66% of node-positive tumors correctly. The inability to derive molecular profiles of metastasis in primary tumors may reflect tumor heterogeneity, paucity of cells within the primary tumor with metastatic potential, influence of the microenvironment, or inherited host susceptibility to metastasis

Renewable energy in fisheries and aquaculture: Case studies from the United States

Fisheries and aquaculture are highly reliant on fossil fuels and must transition to renewable energy to reduce carbon emissions and meet global planetary heath goals. Here, we assessed total and renewable energy use in farmed catfish and wild-caught salmon, two of the largest seafood sectors in the United States (U.S.). Interviews were used to explore participants’ views of key barriers and opportunities to replace fossil fuel use. Modeled scenarios were used to assess changes in grid source energy and electricity costs for the farmed catfish sector using the U.S. EIA National Energy Modeling System. We found that renewable energy makes up 5% of direct energy use in catfish aquaculture in Mississippi and Alabama. Catfish industry interviewees indicate that cheap electricity costs and diurnal energy use are barriers to onsite implementation of renewables. Projected renewable energy use for the catfish sector could be as high as 41% of total direct energy use in 2050 under modeled scenarios, which would result in 86% lower CO2 emissions but 34% higher electricity costs. For wild-capture pink salmon from Prince William Sound, Alaska (AK) and sockeye salmon from Bristol Bay, AK, renewable energy makes up 2% and 0% of direct energy use, respectively. Wild-caught salmon industry interviewees identified the short duration of the fishing season as a barrier for onsite renewable energy, though there is a desire for more regional renewable energy technologies to lower electricity costs and increase reliability. Proposed renewable energy projects at utilities in fish processing towns in AK would only make modest improvements in the share of direct energy from renewables due to fuel use by fishing vessels. This is the first study to characterize current and potential renewable energy use among parts of the fisheries and aquaculture sectors in the U.S. We found that energy needs for fisheries and aquaculture are influenced by their often-remote location, production methods, and seasonal energy demands, which require context-specific solutions. There is the need for federal and state policies and incentives to shift energy sources used in these sectors to meet national and international climate change goals while supporting food security.publishedVersio

The state of the Martian climate

60°N was +2.0°C, relative to the 1981–2010 average value (Fig. 5.1). This marks a new high for the record. The average annual surface air temperature (SAT) anomaly for 2016 for land stations north of starting in 1900, and is a significant increase over the previous highest value of +1.2°C, which was observed in 2007, 2011, and 2015. Average global annual temperatures also showed record values in 2015 and 2016. Currently, the Arctic is warming at more than twice the rate of lower latitudes

Adjuvant capecitabine plus bevacizumab versus capecitabine alone in patients with colorectal cancer (QUASAR 2): an open-label, randomised phase 3 trial

Background Antiangiogenic agents have established efficacy in the treatment of metastatic colorectal cancer. We investigated whether bevacizumab could improve disease-free survival in the adjuvant setting after resection of the primary tumour. Methods For the open-label, randomised, controlled QUASAR 2 trial, which was done at 170 hospitals in seven countries, we recruited patients aged 18 years or older with WHO performance status scores of 0 or 1 who had undergone potentially curative surgery for histologically proven stage III or high-risk stage II colorectal cancer. Patients were randomly assigned (1:1) to receive eight 3-week cycles of oral capecitabine alone (1250 mg/m2 twice daily for 14 days followed by a break for 7 days) or the same regimen of oral capecitabine plus 16 cycles of 7·5 mg/kg bevacizumab by intravenous infusion over 90 min on day 1 of each cycle. Randomisation was done by a computer-generated schedule with use of minimisation with a random element stratified by age, disease stage, tumour site, and country. The study was open label and no-one was masked to treatment assignment. The primary endpoint was 3-year disease-free survival, assessed in the intention-to-treat population. Toxic effects were assessed in patients who received at least one dose of randomised treatment. This trial is registered with the ISRCTN registry, number ISRCTN45133151. Findings Between April 25, 2005, and Oct 12, 2010, 1952 eligible patients were enrolled, of whom 1941 had assessable data (968 in the capecitabine alone group and 973 in the capecitabine and bevacizumab group). Median follow-up was 4·92 years (IQR 4·00–5·16). Disease-free survival at 3 years did not differ between the groups (75·4%, 95% CI 72·5–78·0 in the capecitabine and bevacizumab group vs 78·4%, 75·7–80·9 in the capecitabine alone group; hazard ratio 1·06, 95% CI 0·89–1·25, p=0·54). The most common grade 3–4 adverse events were hand–foot syndrome (201 [21%] of 963 in the capecitabine alone group vs 257 [27%] of 959 in the capecitabine and bevacizumab group) and diarrhoea (102 [11%] vs 104 [11%]), and, with the addition of bevacizumab, expected increases were recorded in all-grade hypertension (320 [33%] vs 75 [8%]), proteinuria (197 [21%] vs 49 [5%]), and wound healing problems (30 [3%] vs 17 [2%]). 571 serious adverse events were reported (221 with capecitabine alone and 350 with capecitabine and bevacizumab). Most of these were gastrointestinal (n=245) or cardiovascular (n=169). 23 deaths within 6 months of randomisation were classified as being related to treatment, eight in the capecitabine alone group and 15 in the capecitabine and bevacizumab group. Interpretation The addition of bevacizumab to capecitabine in the adjuvant setting for colorectal cancer yielded no benefit in the treatment of an unselected population and should not be used

Impact of water filling on terminal ileum intubation with a distal-tip mucosal exposure device

Background and Aims Endocuff improves detection at colonoscopy but seems to impede terminal ileal (TI) intubation. We assessed the impact of Endocuff Vision (EV) on TI intubation using adult or pediatric colonoscopes and evaluated whether filling the cecum with gas versus water affected the impact of EV on TI intubation. Methods Using a prospectively recorded quality control database, we explored the impact of EV on TI intubation in ≤1 minute. We used adult and pediatric colonoscopes and tested the effect of filling the cecum with gas versus water. If the initial attempt failed, then the alternative (water vs gas) was tried as a rescue method. Results TI intubation in ≤1 minute occurred in 91% of colonoscopies without EV versus 65% with EV, but the use of the pediatric colonoscope with EV had a higher success rate for TI intubation in ≤1 minute compared with the adult colonoscope with EV (73% vs 57%, P = .043). TI intubation in ≤1 minute was more successful with EV when the cecum was filled with water rather than gas (74% vs 56%, P = .019), but the benefit of water filling was limited to the adult colonoscope with EV. When EV was in place, water filling was more successful as a rescue method of TI intubation (58% vs 21%, P = .011). Conclusions EV adversely affects TI intubation, particularly for adult colonoscopes. Water filling of the cecum mitigates the impact of EV on TI intubation with adult colonoscopes

CAMAU Project: Research Report (April 2018)

‘Learning about Progression’ is a suite of research-based resources designed to provide evidence to support the building of learning progression frameworks in Wales. ‘Learning about Progression’ seeks to deepen our understanding of current thinking about progression and to explore different purposes that progression frameworks can serve to improve children and young people’s learning. These resources include consideration of how this evidence relates to current developments in Wales and derives a series of principles to serve as touchstones to make sure that, as practices begin to develop, they stay true to the original aspirations of A Curriculum for Wales – A Curriculum for Life. It also derives, from the review of evidence, a number of fundamental questions for all those involved in the development of progression frameworks to engage

CAMAU Project: Research Report (April 2018)

‘Learning about Progression’ is a suite of research-based resources designed to provide evidence to support the building of learning progression frameworks in Wales. ‘Learning about Progression’ seeks to deepen our understanding of current thinking about progression and to explore different purposes that progression frameworks can serve to improve children and young people’s learning. These resources include consideration of how this evidence relates to current developments in Wales and derives a series of principles to serve as touchstones to make sure that, as practices begin to develop, they stay true to the original aspirations of A Curriculum for Wales – A Curriculum for Life. It also derives, from the review of evidence, a number of fundamental questions for all those involved in the development of progression frameworks to engage