Weber Water Fair: A Partnership for Water Conservation Awareness for Fourth Grade Youth

Weber Water Fair engages 4th grade youth through hands-on learning to explore water conservation and quality issues. Development and evaluation of a water education experience that meets the needs of state education standards is described. The Water Fair experience is easily adapted to meet the need for hands-on learning about water for public schools in a variety of geographic areas

TB176: Agrelation: A Computerized Decision-making Tool for Coloraod Potato Beetle Population Management and Environmental Quality Concerns

Many facets of Maine potato production have been simulated with computer models and expert systems. Given the ongoing improvement of computer technology and validation of past efforts, scientists can now combine several agricultural submodels into one holistic and user-friendly computer application. This bulletin reports on the development of one such application—Agrelation—aimed at modeling a portion of Maine potato production and management.https://digitalcommons.library.umaine.edu/aes_techbulletin/1032/thumbnail.jp

Synergistic effects of targeted PI3K signaling inhibition and chemotherapy in liposarcoma.

While liposarcoma is the second most common soft tissue malignant tumor, the molecular pathogenesis in this malignancy is poorly understood. Our goal was therefore to expand the understanding of molecular mechanisms that drive liposarcoma and identify therapeutically-susceptible genetic alterations. We studied a cohort of high-grade liposarcomas and benign lipomas across multiple disease sites, as well as two liposarcoma cell lines, using multiplexed mutational analysis. Nucleic acids extracted from diagnostic patient tissue were simultaneously interrogated for 150 common mutations across 15 essential cancer genes using a clinically-validated platform for cancer genotyping. Western blot analysis was implemented to detect activation of downstream pathways. Liposarcoma cell lines were used to determine the effects of PI3K targeted drug treatment with or without chemotherapy. We identified mutations in the PIK3CA gene in 4 of 18 human liposarcoma patients (22%). No PIK3CA mutations were identified in benign lipomas. Western blot analysis confirmed downstream activation of AKT in both PIK3CA mutant and non-mutant liposarcoma samples. PI-103, a dual PI3K/mTOR inhibitor, effectively inhibited the activation of the PI3K/AKT in liposarcoma cell lines and induced apoptosis. Importantly, combination with PI-103 treatment strongly synergized the growth-inhibitory effects of the chemotherapy drugs doxorubicin and cisplatin in liposarcoma cells. Taken together, these findings suggest that activation of the PI3K/AKT pathway is an important cancer mechanism in liposarcoma. Targeting the PI3K/AKT/pathway with small molecule inhibitors in combination with chemotherapy could be exploited as a novel strategy in the treatment of liposarcoma

Effects of haemodynamically atrio-ventricular optimized His-pacing on heart failure symptoms and exercise capacity: The His Optimized Pacing Evaluated for Heart Failure (HOPE-HF) randomised, double-blind, cross-over trial

Aims: Excessive prolongation of PR interval impairs coupling of AV contraction, which reduces left ventricular pre-load and stroke volume, and worsens symptoms. His-bundle pacing allows AV-delay shortening while maintaining normal ventricular activation. HOPE-HF evaluated whether AV-optimized His pacing is preferable to no-pacing, in double-blind cross-over fashion, in patients with heart failure, left ventricular ejection fraction (LVEF) ≤40%, PR interval ≥200ms and either QRS ≤140ms or right BBB. Methods and results: Patients had atrial and His-bundle leads implanted (and an ICD lead if clinically indicated) and were randomized, to 6-months of pacing and 6-months of no-pacing utilizing a cross-over design. The primary outcome was peak oxygen uptake during symptom-limited exercise. Quality of life, LVEF and patients' holistic symptomatic preference between arms were secondary outcomes. 167 patients were randomized: 90% men, 69±10 years, QRS duration 124±26ms, PR interval 249±59ms, LVEF 33±9%. Neither peak VO2 (+0.25 ml/min/kg, 95% CI -0.23 to +0.73, p=0.3) nor LVEF (+0.5%, 95% CI -0.7 to 1.6, p=0.4) changed with pacing but Minnesota Living with Heart Failure quality of life improved significantly (-3.7, 95% CI -7.1 to -0.3, p=0.03). 76% of patients preferred His-bundle pacing-on and 24% pacing-off (p Conclusion: His-bundle pacing did not increase peak oxygen uptake but, under double-blind conditions, significantly improved quality of life and was symptomatically preferred by the clear majority of patients. Ventricular pacing delivered via the His bundle did not adversely impact ventricular function during the 6 months

Doppler assessment of aortic stenosis: a 25-operator study demonstrating why reading the peak velocity is superior to velocity time integral

Aims Measurements with superior reproducibility are useful clinically and research purposes. Previous reproducibility studies of Doppler assessment of aortic stenosis (AS) have compared only a pair of observers and have not explored the mechanism by which disagreement between operators occurs. Using custom-designed software which stored operators’ traces, we investigated the reproducibility of peak and velocity time integral (VTI) measurements across a much larger group of operators and explored the mechanisms by which disagreement arose. Methods and results Twenty-five observers reviewed continuous wave (CW) aortic valve (AV) and pulsed wave (PW) left ventricular outflow tract (LVOT) Doppler traces from 20 sequential cases of AS in random order. Each operator unknowingly measured each peak velocity and VTI twice. VTI tracings were stored for comparison. Measuring the peak is much more reproducible than VTI for both PW (coefficient of variation 10.1 vs. 18.0%; P < 0.001) and CW traces (coefficient of variation 4.0 vs. 10.2%; P < 0.001). VTI is inferior because the steep early and late parts of the envelope are difficult to trace reproducibly. Dimensionless index improves reproducibility because operators tended to consistently over-read or under-read on LVOT and AV traces from the same patient (coefficient of variation 9.3 vs. 17.1%; P < 0.001). Conclusion It is far more reproducible to measure the peak of a Doppler trace than the VTI, a strategy that reduces measurement variance by approximately six-fold. Peak measurements are superior to VTI because tracing the steep slopes in the early and late part of the VTI envelope is difficult to achieve reproducibly

Left ventricular scar and the acute hemodynamic effects of multivein and multipolar pacing in cardiac resynchronization

Background We sought to determine whether presence, amount and distribution of scar impacts the degree of acute hemodynamic response (AHR) with multisite pacing. Multi-vein pacing (MVP) or multipolar pacing (MPP) with a multi-electrode left ventricular (LV) lead may offer benefits over conventional biventricular pacing in patients with myocardial scar. Methods In this multi-center study left bundle branch block patients underwent an hemodynamic pacing study measuring LV dP/dtmax. Patients had cardiac magnetic resonance scar imaging to assess the effect of scar presence, amount and distribution on AHR. Results 24 patients (QRS 171 ± 20 ms) completed the study (83% male). An ischemic etiology was present in 58% and the mean scar volume was 6.0 ± 7.0%. Overall discounting scar, MPP and MVP showed no significant AHR increase compared to an optimized “best BiV” (BestBiV) site. In a minority of patients (6/24) receiver-operator characteristic analysis of scar volume (cut off 8.48%) predicted a small AHR improvement with MPP (sensitivity 83%, specificity 94%) but not MVP. Patients with scar volume > 8.48% had a MPP-BestBiV of 3 ± 6.3% vs. −6.4 ± 7.7% for those below the cutoff. There was a significant correlation between the difference in AHR and scar volume for MPP-BestBiV (R = 0.49, p = 0.02) but not MVP-BestBiV(R = 0.111, p = 0.62). The multielectrode lead positioned in scar predicted MPP AHR improvement (p = 0.04). Conclusions Multisite pacing with MPP and MVP shows no AHR benefit in all-comers compared to optimized BestBiV pacing. There was a minority of patients with significant scar volume in relation to the LV site that exhibited a small AHR improvement with MPP

Plutonium Migration during the Leaching of Cemented Radioactive Waste Sludges

One of the most challenging components of the UK nuclear legacy is Magnox sludge, arising from the corrosion of Mg alloy-clad irradiated metallic U fuel that has been stored in high pH ponds. The sludges mainly comprise Mg hydroxide and carbonate phases, contaminated with fission products and actinides, including Pu. Cementation and deep geological disposal is one option for the long-term management of this material, but there is a need to understand how Pu may be leached from the waste, if it is exposed to groundwater. Here, we show that cemented Mg(OH)2 powder prepared with Pu(IV)aq is altered on contact with water to produce a visibly altered ‘leached zone’, which penetrates several hundred microns into the sample. In turn, this zone shows slow leaching of Pu, with long-term leaching rates between 1.8–4.4 × 10−5% of total Pu per day. Synchrotron micro-focus X-ray fluorescence mapping identified decreased Pu concentration within the ‘leached zone’. A comparison of micro-focus X-ray absorption spectroscopy (µ-XAS) spectra collected across both leached and unleached samples showed little variation, and indicated that Pu was present in a similar oxidation state and coordination environment. Fitting of the XANES spectra between single oxidation state standards and EXAFS modeling showed that Pu was present as a mixture of Pu(IV) and Pu(V). The change in Pu oxidation from the stock solution suggests that partial Pu oxidation occurred during sample ageing. Similarity in the XAS spectra from all samples, with different local chemistries, indicated that the Pu oxidation state was not perturbed by macro-scale variations in cement chemistry, surface oxidation, sample aging, or the leaching treatment. These experiments have demonstrated the potential for leaching of Pu from cementitious waste forms, and its underlying significance requires further investigation

Plutonium Migration during the Leaching of Cemented Radioactive Waste Sludges

One of the most challenging components of the UK nuclear legacy is Magnox sludge, arising from the corrosion of Mg alloy-clad irradiated metallic U fuel that has been stored in high pH ponds. The sludges mainly comprise Mg hydroxide and carbonate phases, contaminated with fission products and actinides, including Pu. Cementation and deep geological disposal is one option for the long-term management of this material, but there is a need to understand how Pu may be leached from the waste, if it is exposed to groundwater. Here, we show that cemented Mg(OH)2 powder prepared with Pu(IV)aq is altered on contact with water to produce a visibly altered ‘leached zone’, which penetrates several hundred microns into the sample. In turn, this zone shows slow leaching of Pu, with long-term leaching rates between 1.8–4.4 × 10−5% of total Pu per day. Synchrotron micro-focus X-ray fluorescence mapping identified decreased Pu concentration within the ‘leached zone’. A comparison of micro-focus X-ray absorption spectroscopy (µ-XAS) spectra collected across both leached and unleached samples showed little variation, and indicated that Pu was present in a similar oxidation state and coordination environment. Fitting of the XANES spectra between single oxidation state standards and EXAFS modeling showed that Pu was present as a mixture of Pu(IV) and Pu(V). The change in Pu oxidation from the stock solution suggests that partial Pu oxidation occurred during sample ageing. Similarity in the XAS spectra from all samples, with different local chemistries, indicated that the Pu oxidation state was not perturbed by macro-scale variations in cement chemistry, surface oxidation, sample aging, or the leaching treatment. These experiments have demonstrated the potential for leaching of Pu from cementitious waste forms, and its underlying significance requires further investigation

A DOCK8-WIP-WASp complex links T cell receptors to the actin cytoskeleton

Wiskott-Aldrich syndrome (WAS) is associated with mutations in the WAS protein (WASp), which plays a critical role in the initiation of T cell receptor–driven (TCR-driven) actin polymerization. The clinical phenotype of WAS includes susceptibility to infection, allergy, autoimmunity, and malignancy and overlaps with the symptoms of dedicator of cytokinesis 8 (DOCK8) deficiency, suggesting that the 2 syndromes share common pathogenic mechanisms. Here, we demonstrated that the WASp-interacting protein (WIP) bridges DOCK8 to WASp and actin in T cells. We determined that the guanine nucleotide exchange factor activity of DOCK8 is essential for the integrity of the subcortical actin cytoskeleton as well as for TCR-driven WASp activation, F-actin assembly, immune synapse formation, actin foci formation, mechanotransduction, T cell transendothelial migration, and homing to lymph nodes, all of which also depend on WASp. These results indicate that DOCK8 and WASp are in the same signaling pathway that links TCRs to the actin cytoskeleton in TCR-driven actin assembly. Further, they provide an explanation for similarities in the clinical phenotypes of WAS and DOCK8 deficiency.United States. Public Health Service (RO1AI114588)United States. Public Health Service (K08AI114968