Mantle Potential Temperatures of 4.5 to 47 MA Hawaiian Volcanoes Using Olivine Thermometry: Implications for Melt Flux Variations

M.S. University of Hawaii at Manoa 2016.Includes bibliographical references.Hawaiian Ridge volcanoes vary in volume by a factor of 50 due to variations in the melt flux of the Hawai‘i mantle plume. One potential cause for these variations is the plume’s temperature. The objective of this study is to evaluate the relationship between melt flux variations and mantle potential temperature (Tp) of the plume during the formation of the Northwest Hawaiian Ridge (NWHR) that extends 2800 km northwest of the main Hawaiian Islands. Using olivine thermometry of 25 lavas from 10 Hawaiian volcanoes ranging from 1 x 103 km3 to 54 x 103 km3 in volume and 4.5 to 47 Ma in age, mantle potential temperatures are calculated. High-precision electron microprobe analysis of olivine compositions revealed that most of these volcanoes shared similar olivine forsterite (Fo) compositions (~80-88% Fo) with the exception of high forsterite olivines in Gardner lavas (91.85 % Fo, the highest measured in Hawaiian lavas). The highest forsteritic olivines from each sample were used to estimate parental magma compositions. A Monte Carlo simulation method was used to calculate the olivine-liquid equilibration temperature (Tol-liq) of these magmas, the Tp, and uncertainties in temperature associated with equilibrium assumptions made for parental magma composition estimates. The minimum Tol-liq and Tp are for Daikakuji lavas from the second smallest examined volcano at northern end of NWHR (1335 ± 26; 1374 ± 48 oC). The maximum Tp is at Gardner, the largest volcano located in the central part of the NWHR (1614 ± 26; 1703 ± 56 oC). These results yield a Tp increase of 329 oC for the ≥ 12.4 Ma section of the NWHR. Southeast of Gardner, Tp decreases at Mokumanamana to 1521 ± 50 oC. The Tp of the NWHR volcanoes between Mokumanamana and West Nīhoa show no systematic change similar to variations in the melt flux. The maximum Tp from the southeastern portion of the NWHR was from Nīhoa (1632 ± 54 oC) and the minimum Tp from West Nīhoa (1517 ± 56 oC). A second increase in Tp was observed from new Tp estimates for Kaua‘i (1567 ± 42 oC) to the current estimate range for volcanoes of the Island of Hawai‘i (1632 oC ≥ Tp ≥ 1690 oC). These variations in Tp along the Hawaiian Ridge follow an equivalent trend that is observed in the melt flux. The maximum Tp from each volcano have significant Spearman’s rank correlations with the distance from Mauna Loa, the melt flux, and volumes of these volcanoes. These correlations suggest that there is a strong coupling between the melt flux and the temperature of the Hawaiian mantle plume. Tp estimates from the Galápagos and Iceland hotspots show an opposite cooling trend over time. The Louisville hotspot track shows a dramatic decrease in the melt flux since 20 Ma. The Tp estimates from this study show that the Hawaiian hotspot is unique. The plume’s thermal history shows two instances of increasing Tp with increasing melt flux

New Insights from Seafloor Mapping of a Hawaiian Marine Monument

On 15 June 2006, when U.S. President George W. Bush signed the proclamation creating the Papahānaumokuākea Marine National Monument (PMNM), he probably wasn’t thinking about underwater morphology. To fully understand the coral reefs and marine ecosystems that the monument was created to protect, however, scientists need to have a detailed picture of the seafloor features, home to corals and other species, as well as the geologic history of the area. Thanks to a recent, multi-institution expedition, such a seafloor features that will not only inform conservation efforts but also enable geologists and geophysicists to revise their understanding of Hawaii’s complex geologic past. Specifically, data should help scientists answer fundamental questions about the area’s regional geology. For instance, which seamounts were truly formed because of Hawaiian hotspot volcanism, and which seamounts were not

Sequencing of Androgen-Deprivation Therapy of Short Duration With Radiotherapy for Nonmetastatic Prostate Cancer (SANDSTORM): A Pooled Analysis of 12 Randomized Trials

PURPOSE: The sequencing of androgen-deprivation therapy (ADT) with radiotherapy (RT) may affect outcomes for prostate cancer in an RT-field size-dependent manner. Herein, we investigate the impact of ADT sequencing for men receiving ADT with prostate-only RT (PORT) or whole-pelvis RT (WPRT). MATERIALS AND METHODS: Individual patient data from 12 randomized trials that included patients receiving neoadjuvant/concurrent or concurrent/adjuvant short-term ADT (4-6 months) with RT for localized disease were obtained from the Meta-Analysis of Randomized trials in Cancer of the Prostate consortium. Inverse probability of treatment weighting (IPTW) was performed with propensity scores derived from age, initial prostate-specific antigen, Gleason score, T stage, RT dose, and mid-trial enrollment year. Metastasis-free survival (primary end point) and overall survival (OS) were assessed by IPTW-adjusted Cox regression models, analyzed independently for men receiving PORT versus WPRT. IPTW-adjusted Fine and Gray competing risk models were built to evaluate distant metastasis (DM) and prostate cancer-specific mortality. RESULTS: Overall, 7,409 patients were included (6,325 neoadjuvant/concurrent and 1,084 concurrent/adjuvant) with a median follow-up of 10.2 years (interquartile range, 7.2-14.9 years). A significant interaction between ADT sequencing and RT field size was observed for all end points (P interaction < .02 for all) except OS. With PORT (n = 4,355), compared with neoadjuvant/concurrent ADT, concurrent/adjuvant ADT was associated with improved metastasis-free survival (10-year benefit 8.0%, hazard ratio [HR], 0.65; 95% CI, 0.54 to 0.79; P < .0001), DM (subdistribution HR, 0.52; 95% CI, 0.33 to 0.82; P = .0046), prostate cancer-specific mortality (subdistribution HR, 0.30; 95% CI, 0.16 to 0.54; P < .0001), and OS (HR, 0.69; 95% CI, 0.57 to 0.83; P = .0001). However, in patients receiving WPRT (n = 3,049), no significant difference in any end point was observed in regard to ADT sequencing except for worse DM (HR, 1.57; 95% CI, 1.20 to 2.05; P = .0009) with concurrent/adjuvant ADT. CONCLUSION: ADT sequencing exhibits a significant impact on clinical outcomes with a significant interaction with field size. Concurrent/adjuvant ADT should be the standard of care where short-term ADT is indicated in combination with PORT

Methionine biosynthesis and transport are functionally redundant for the growth and virulence of Salmonella Typhimurium

Methionine (Met) is an amino acid essential for many important cellular and biosynthetic functions, including the initiation of protein synthesis and S-adenosylmethionine-mediated methylation of proteins, RNA, and DNA. The de novo biosynthetic pathway of Met is well conserved across prokaryotes but absent from vertebrates, making it a plausible antimicrobial target. Using a systematic approach, we examined the essentiality of de novo methionine biosynthesis in Salmonella enterica serovar Typhimurium, a bacterial pathogen causing significant gastrointestinal and systemic diseases in humans and agricultural animals. Our data demonstrate that Met biosynthesis is essential for S. Typhimurium to grow in synthetic medium and within cultured epithelial cells where Met is depleted in the environment. During systemic infection of mice, the virulence of S. Typhimurium was not affected when either de novo Met biosynthesis or high-affinity Met transport was disrupted alone, but combined disruption in both led to severe in vivo growth attenuation, demonstrating a functional redundancy between de novo biosynthesis and acquisition as a mechanism of sourcing Met to support growth and virulence for S. Typhimurium during infection. In addition, our LC-MS analysis revealed global changes in the metabolome of S. Typhimurium mutants lacking Met biosynthesis and also uncovered unexpected interactions between Met and peptidoglycan biosynthesis. Together, this study highlights the complexity of the interactions between a single amino acid, Met, and other bacterial processes leading to virulence in the host and indicates that disrupting the de novo biosynthetic pathway alone is likely to be ineffective as an antimicrobial therapy against S. Typhimurium

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK.

BACKGROUND: A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. METHODS: This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. FINDINGS: Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0-75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4-97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8-80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3-4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. INTERPRETATION: ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials. FUNDING: UK Research and Innovation, National Institutes for Health Research (NIHR), Coalition for Epidemic Preparedness Innovations, Bill & Melinda Gates Foundation, Lemann Foundation, Rede D'Or, Brava and Telles Foundation, NIHR Oxford Biomedical Research Centre, Thames Valley and South Midland's NIHR Clinical Research Network, and AstraZeneca

Safety and efficacy of the ChAdOx1 nCoV-19 vaccine (AZD1222) against SARS-CoV-2: an interim analysis of four randomised controlled trials in Brazil, South Africa, and the UK

Background A safe and efficacious vaccine against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), if deployed with high coverage, could contribute to the control of the COVID-19 pandemic. We evaluated the safety and efficacy of the ChAdOx1 nCoV-19 vaccine in a pooled interim analysis of four trials. Methods This analysis includes data from four ongoing blinded, randomised, controlled trials done across the UK, Brazil, and South Africa. Participants aged 18 years and older were randomly assigned (1:1) to ChAdOx1 nCoV-19 vaccine or control (meningococcal group A, C, W, and Y conjugate vaccine or saline). Participants in the ChAdOx1 nCoV-19 group received two doses containing 5 × 1010 viral particles (standard dose; SD/SD cohort); a subset in the UK trial received a half dose as their first dose (low dose) and a standard dose as their second dose (LD/SD cohort). The primary efficacy analysis included symptomatic COVID-19 in seronegative participants with a nucleic acid amplification test-positive swab more than 14 days after a second dose of vaccine. Participants were analysed according to treatment received, with data cutoff on Nov 4, 2020. Vaccine efficacy was calculated as 1 - relative risk derived from a robust Poisson regression model adjusted for age. Studies are registered at ISRCTN89951424 and ClinicalTrials.gov, NCT04324606, NCT04400838, and NCT04444674. Findings Between April 23 and Nov 4, 2020, 23 848 participants were enrolled and 11 636 participants (7548 in the UK, 4088 in Brazil) were included in the interim primary efficacy analysis. In participants who received two standard doses, vaccine efficacy was 62·1% (95% CI 41·0–75·7; 27 [0·6%] of 4440 in the ChAdOx1 nCoV-19 group vs71 [1·6%] of 4455 in the control group) and in participants who received a low dose followed by a standard dose, efficacy was 90·0% (67·4–97·0; three [0·2%] of 1367 vs 30 [2·2%] of 1374; pinteraction=0·010). Overall vaccine efficacy across both groups was 70·4% (95·8% CI 54·8–80·6; 30 [0·5%] of 5807 vs 101 [1·7%] of 5829). From 21 days after the first dose, there were ten cases hospitalised for COVID-19, all in the control arm; two were classified as severe COVID-19, including one death. There were 74 341 person-months of safety follow-up (median 3·4 months, IQR 1·3–4·8): 175 severe adverse events occurred in 168 participants, 84 events in the ChAdOx1 nCoV-19 group and 91 in the control group. Three events were classified as possibly related to a vaccine: one in the ChAdOx1 nCoV-19 group, one in the control group, and one in a participant who remains masked to group allocation. Interpretation ChAdOx1 nCoV-19 has an acceptable safety profile and has been found to be efficacious against symptomatic COVID-19 in this interim analysis of ongoing clinical trials

Exploring the barriers to using assistive technology for individuals with chronic conditions: a meta-synthesis review

Purpose: Assistive technology can provide a key tool to enabling independence, greater inclusion and participation in society for individuals with chronic conditions. This potential is currently not always realized due to barriers to accessing and using assistive technology. This review aims to identify the common barriers to acquiring and using assistive technology for users with chronic conditions through a systematic meta-synthesis. This differs from other systematic reviews by applying a transdiagnostic approach to identify if barriers are common across chronic conditions. Materials and methods: A systematic literature search of five scientific databases (PubMed, SCOPUS, PsycINFO, CINAHL and Medline) was conducted to identify relevant qualitative studies. The search was conducted in November 2019. For the identified articles, thematic content analysis was conducted and the methodological quality was evaluated using the Critical Appraisal Skills Programme (CASP) checklist for qualitative research. Results: Forty papers met the inclusion criteria and were included in the analysis. Fifty-one descriptive themes grouped into six overarching analytical themes were identified from the studies. The analytical themes identified were: the design and function of the assistive technology, service provision, information and awareness, psychological barriers, support network and societal barriers. Conclusions: The barriers are interconnected and common across different health conditions. More involvement in personalized care for developing strategies, adaptation of home technologies and provision of assistive technology could overcome the service provision and design barriers to assistive technology. Accessible information and providing greater awareness will be important to overcoming information, psychological and societal barriers to assistive technology. Implications for rehabilitation: Individuals with chronic conditions face complex barriers to acquiring and using assistive technology as a result of the devices themselves, their individual context, the healthcare context where assistive technology is provided and wider societal barriers. The provision of assistive technology needs to change away from the traditional medical model of the “expert” clinician and instead focus on more user involvement to deliver personalised care that utilises the users lived knowledge and experiences. Assistive technology provision should be considered alongside how to adapt everyday mainstream technology to meet user needs; the provision of devices should encourage creative problem solving rather then relying on pre-defined prescription lists of assistive technology

The hydraulic characteristics of Roman lead water pipes: An experimental investigation

An experimental investigation was conducted on two lengths of Roman lead water pipe excavated near Corbridge, Northumberland, England. The pipes date from approximately AD 80. One length of pipe contained a sleeve joint. The pipes were linked to a pump system using 3 D-printed connectors, and the hydraulic head loss along the pipe was measured. The pipe without a joint was used to determine a value for the wall roughness height, fitting the results to the Darcy-Weisbach equation. The wall roughness height obtained was assumed to apply to the pipe with the joint, and the additional head loss observed was then assumed to be due to the joint, allowing determination of a local loss coefficient. The pipes have a sinter encrustation, indicating that they had typically flowed partially full. Using this as an indication of water depth and deriving topographical information from the excavation report, the likely flow the pipes carried during their operational life was estimated. It was concluded that the pipe wall roughness coefficient ks was 0.9 mm, the joint local loss coefficient was 1.159, and that during operation the pipe probably carried around 17 litres/minute