In Situ Sensors for the Chemical Industry- Final Report

The project focused on analytical techniques that can be applied in situ. The innovative component of this project is the focus on achieving a significant breakthrough in two of the three primary Process Analytical (PA) fields. PA measurements can roughly be broken down into: Single component measurements, Multiple component measurements and Multiple component isomer analysis. This project targeted single component measurements and multiple component measurements with two basic technologies, and to move these measurements to the process, achieving many of the process control needs. During the project the following achievements were made: Development of a low cost Tunable Diode Laser (TDL) Analyzer system for measurement of 1) Oxygen in process and combustion applications, 2) part per million (ppm) H2O impurities in aggressive service, 3) ppm CO in large scale combustion systems. This product is now commercially available Development of a process pathlength enhanced (high sensitivity) Laser Based Analyzer for measurement of product impurities. This product is now commercially available. Development of signal processing methods to eliminate measurement errors in complex and changing backgrounds (critical to chemical industry measurements). This development is incorporated into 2 commercially available products. Development of signal processing methods to allow multi-component measurements in complex chemical streams. This development is incorporated into 2 commercially available products. Development of process interface designs to allow in-situ application of TDL technology in aggressive (corrosive, high temperature, high pressure) commonly found in chemical processes. This development is incorporated in the commercially available ASI TDL analyzer. Field proving of 3 laser-based analyzer systems in process control and combustion applications at Dow Chemical. Laser based analyzers have been available for >5yrs, however significant product price/performance issues have minimized their applicability in the chemical industry. In order to take advantage of the promise of this technology a number of technology advances were required, within price limits for market acceptance. This project significantly advanced the state of TDL technology for application in chemical industry applications. With these advances a commercially available product now exists that has already achieved market success and is installed in critical applications. The ability to make fast, sensitive and accurate measurements inside the chemical processes is now delivering improved process control, energy efficiency and emissions control within the U.S. Chemical Industry. Despite the success we enjoyed for the laser-based sensors, there were significant technical barriers for the solid-state sensors. With exception of a generic close-coupled extractive housing and electronics interface, there were significant issues with all of the solid-state sensor devices we sought to develop and test. Ultimately, these issues were roadblocks that prevented further development and testing. The fundamental limitations of available sensor materials that we identified, formulated and tested were overwhelming. This situation forced our team to cancel these portions of the project and focus our resources on laser-based sensor techniques. The barriers of material compatibility, sensitivity, speed of response, chemical interferences, etc. are surmountable in the field of solid-state sensors. Inability to address any single one of these attributes will prevent wide-implementation into this market. This situation is plainly evident by the lack of such devices in the online analyzer market (for petrochemicals)

Toll-like receptor 3 activation impairs excitability and synaptic activity via TRIF signalling in immature rat and human neurons

Toll like receptor 3 (TLR3) belongs to a family of pattern recognition receptors that recognise molecules found on pathogens referred to as pathogen associated molecular patterns (PAMPs). Its involvement in innate immunity is well known but despite its presence in the central nervous system (CNS), our knowledge of its function is limited. Here, we have investigated whether TLR3 activation modulates synaptic activity in primary hippocampal cultures and induced pluripotent stem cell (iPSC)-derived neurons. Synaptically driven spontaneous action potential (AP) firing was significantly reduced by the TLR3 specific activator, poly I:C, in a concentration-dependent manner following both short (5 min) and long exposures (1h) in rat hippocampal cultures. Notably, the consequence of TLR3 activation on neuronal function was reproduced in iPSC-derived cortical neurons, with poly I:C (25µg/ml, 1h) significantly inhibiting sAP firing. We examined the mechanisms underlying these effects, with poly I:C significantly reducing peak sodium current, an effect dependent on the MyD88-independent TRIF dependent pathway. Furthermore, poly I:C (25µg/ml, 1h) resulted in a significant reduction in miniature excitatory postsynaptic potential (mEPSC) frequency and amplitude and significantly reduced surface AMPAR expression. These novel findings reveal that TLR3 activation inhibits neuronal excitability and synaptic activity through multiple mechanisms, with this being observed in both rat and human iPSC-derived neurons. These data might provide further insight into how TLR3 activation may contribute to neurodevelopmental disorders following maternal infection and in patients with increased susceptibility to herpes simplex encephalitis

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Late Bronze Age objects

The Sculptor’s Cave is one of the most enigmatic prehistoric sites in Britain. Excavated in the 1920s and 1970s, new analysis of the archive has revealed a complex history of funerary and ritual activity from the Late Bronze Age to the Roman Iron Age. Using innovative methods and new techniques, this volume re-examines the results of earlier excavations and places the site in its wider British and European context

Advanced Combustion Diagnostics and Control for Furnaces, Fired Heaters and Boilers

The objective of this project was to develop and apply enabling tools and methods towards advanced combustion diagnostics and control of fired-equipment in large-scale petrochemical manufacturing. There are a number of technology gaps and opportunities for combustion optimization, including technologies involving advanced in-situ measurements, modeling, and thermal imaging. These technologies intersect most of manufacturing and energy systems within the chemical industry. This project leveraged the success of a previous DOE funded project led by Dow, where we co-developed an in-situ tunable diode laser (TDL) analyzer platform (with Analytical Specialties Inc, now owned by Yokogawa Electric Corp.). The TDL platform has been tested and proven in a number of combustion processes within Dow and outside of Dow. The primary focus of this project was on combustion diagnostics and control applied towards furnaces, fired heaters and boilers. Special emphasis was placed on the development and application of in-situ measurements for O2, CO and methane since these combustion gases are key variables in optimizing and controlling combustion processes safely. Current best practice in the industry relies on measurements that suffer from serious performance gaps such as limited sampling volume (point measurements), poor precision and accuracy, and poor reliability. Phase I of the project addressed these gaps by adding improved measurement capabilities such as CO and methane (ppm analysis at combustion zone temperatures) as well as improved optics to maintain alignment over path lengths up to 30 meters. Proof-of-concept was demonstrated on a modern olefins furnace located at Dow Chemical's facility in Freeport TX where the improved measurements were compared side-by-side to accepted best practice techniques (zirconium oxide and catalytic bead or thick film sensors). After developing and installing the improved combustion measurements (O2, CO, and methane), we also demonstrated the ability to improve control of an olefins furnace (via CO-trim) that resulted in significant energy savings and lower emissions such as NOx and other greenhouse gases. The cost to retrofit measurements on an existing olefins furnace was found to be very attractive, with an estimated payback achieved in 4 months or less

Advanced Combustion Diagnostics and Control for Furnaces, Fired Heaters and Boilers

The objective of this project was to develop and apply enabling tools and methods towards advanced combustion diagnostics and control of fired-equipment in large-scale petrochemical manufacturing. There are a number of technology gaps and opportunities for combustion optimization, including technologies involving advanced in-situ measurements, modeling, and thermal imaging. These technologies intersect most of manufacturing and energy systems within the chemical industry. This project leveraged the success of a previous DOE funded project led by Dow, where we co-developed an in-situ tunable diode laser (TDL) analyzer platform (with Analytical Specialties Inc, now owned by Yokogawa Electric Corp.). The TDL platform has been tested and proven in a number of combustion processes within Dow and outside of Dow. The primary focus of this project was on combustion diagnostics and control applied towards furnaces, fired heaters and boilers. Special emphasis was placed on the development and application of in-situ measurements for O2, CO and methane since these combustion gases are key variables in optimizing and controlling combustion processes safely. Current best practice in the industry relies on measurements that suffer from serious performance gaps such as limited sampling volume (point measurements), poor precision and accuracy, and poor reliability. Phase I of the project addressed these gaps by adding improved measurement capabilities such as CO and methane (ppm analysis at combustion zone temperatures) as well as improved optics to maintain alignment over path lengths up to 30 meters. Proof-of-concept was demonstrated on a modern olefins furnace located at Dow Chemical's facility in Freeport TX where the improved measurements were compared side-by-side to accepted best practice techniques (zirconium oxide and catalytic bead or thick film sensors). After developing and installing the improved combustion measurements (O2, CO, and methane), we also demonstrated the ability to improve control of an olefins furnace (via CO-trim) that resulted in significant energy savings and lower emissions such as NOx and other greenhouse gases. The cost to retrofit measurements on an existing olefins furnace was found to be very attractive, with an estimated payback achieved in 4 months or less

Two Facets of Stress and Indirect Effects on Child Diet Through Emotion-Driven Eating

Objective Stress has been associated with high-calorie, low-nutrient food intake (HCLN) and emotion-driven eating (EDE). However, effects on healthy food intake remain unknown. This study examined two facets of stress (self-efficacy, perceived helplessness) and food consumption, mediated by EDE. Methods Cross-sectional data from fourth-graders (n = 978; 52% female, 28% Hispanic) in an obesity intervention used self-report to assess self-efficacy, helplessness, EDE, fruit/vegetable (FV) intake, and high-calorie/low-nutrient (HCLN) food. Results Higher stress self-efficacy was associated with higher FV intake, β = .354, p \u3c 0.001, and stress perceived helplessness had an indirect effect on HCLN intake through emotion-driven eating, indirect effect = .094, p \u3c 0.001; χ2(347) = 659.930, p \u3c 0.001, CFI = 0.940, TLI = 0.930, RMSEA = 0.030, p = 1.00, adjusting for gender, ethnicity, BMI z-score, and program group. Conclusions and implications Stress self-efficacy may be more important for healthy food intake and perceived helplessness may indicate emotion-driven eating and unhealthy snack food intake. Obesity prevention programs may consider teaching stress management techniques to avoid emotion-driven eating

Radioprotective agents to prevent cellular damage due to ionizing radiation

Abstract Medical imaging has become a central component of patient care to ensure early and accurate diagnosis. Unfortunately, many imaging modalities use ionizing radiation to generate images. Ionizing radiation even in low doses can cause direct DNA damage and generate reactive oxygen species and free radicals, leading to DNA, protein, and lipid membrane damage. This cell damage can lead to apoptosis, necrosis, teratogenesis, or carcinogenesis. As many as 2% of cancers (and an associated 15,000 deaths annually) can be linked to computed tomography exposure alone. Radioprotective agents have been investigated using various models including cells, animals, and recently humans. The data suggest that radioprotective agents working through a variety of mechanisms have the potential to decrease free radical damage produced by ionizing radiation. Radioprotective agents may be useful as an adjunct to medical imaging to reduced patient morbidity and mortality due to ionizing radiation exposure. Some radioprotective agents can be found in high quantities in antioxidant rich foods, suggesting that a specific diet recommendation could be beneficial in radioprotection