128 research outputs found

    Does Travel Time to a Radiation Facility Impact Patient Decision-making Regarding Treatment for Prostrate Cancer? A Study of the New Hampshire State Cancer Registry

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    Purpose: We sought to determine whether further distance from a radiation center is associated with lower utilization of external beam radiation therapy (XRT). Methods: We retrospectively identified patients with a new diagnosis of localized prostate cancer (CaP) within the New Hampshire State Cancer Registry from 2004 to 2011. Patients were categorized by age, D’Amico risk category, year of treatment, marital status, season of diagnosis, urban/rural residence, and driving time to the nearest radiation facility. Treatment decisions were stratified into those requiring multiple trips (XRT) or a single trip (surgery or brachytherapy). Multivariable regression analysis was performed. Results: A total of 4,731 patients underwent treatment for newly diagnosed CaP during the study period, including 1,575 multitrip (XRT) and 3,156 singletrip treatments. Of these, 87.6% lived within a 30-minute drive to a radiation facility. In multivariable analysis, time to the nearest radiation facility was not associated with treatment decisions (P = .26). However, higher risk category, older age, married status, and winter diagnosis were associated with XRT (P \u3c .05). More recent year of diagnosis and urban residence were associated with single-trip therapy (primarily surgery) (P \u3c .05). There was a significant interaction between travel time and season of diagnosis (P = .03), as well as a marginally significant interaction with urban/rural status (P = .07). Conclusion: Overall, further travel time to a radiation facility was not associated with lower utilization of XRT. These data are encouraging regarding access to care for CaP in New Hampshire

    A series of crystallographically characterized linear and branched σ-alkane complexes of rhodium : from propane to 3-methylpentane

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    We thank the EPSRC (EP/M024210, and the UK National Crystallography Service), the Leverhulme Trust (RPG-2015-447), and SGC Chemicals for funding, T. M. Boyd (York) for experimental assistance and useful discussions, and Dr. M. Chadwick (Imperial College) for the initial synthesis of [1-isoprene][BAr ] . This work used the ARCHER UK National Supercomputing Service ( http://www.archer.ac.uk ) and the Cirrus UK National Tier-2 HPC Service at the EPCC ( http://www.cirrus.ac.uk ) funded by the University of Edinburgh and the EPSRC (EP/P020267/1).Using solid-state molecular organometallic (SMOM) techniques, in particular solid/gas single-crystal to single-crystal reactivity, a series of σ-alkane complexes of the general formula [Rh(Cy2PCH2CH2PCy2)(ηn:ηm-alkane)][BArF4] have been prepared (alkane = propane, 2-methylbutane, hexane, 3-methylpentane; ArF = 3,5-(CF3)2C6H3). These new complexes have been characterized using single crystal X-ray diffraction, solid-state NMR spectroscopy and DFT computational techniques and present a variety of Rh(I)···H-C binding motifs at the metal coordination site: 1,2-η2:η2 (2-methylbutane), 1,3-η2:η2 (propane), 2,4-η2:η2 (hexane), and 1,4-η1:η2 (3-methylpentane). For the linear alkanes propane and hexane, some additional Rh(I)···H-C interactions with the geminal C-H bonds are also evident. The stability of these complexes with respect to alkane loss in the solid state varies with the identity of the alkane: from propane that decomposes rapidly at 295 K to 2-methylbutane that is stable and instead undergoes an acceptorless dehydrogenation to form a bound alkene complex. In each case the alkane sits in a binding pocket defined by the {Rh(Cy2PCH2CH2PCy2)}+ fragment and the surrounding array of [BArF4]- anions. For the propane complex, a small alkane binding energy, driven in part by a lack of stabilizing short contacts with the surrounding anions, correlates with the fleeting stability of this species. 2-Methylbutane forms more short contacts within the binding pocket, and as a result the complex is considerably more stable. However, the complex of the larger 3-methylpentane ligand shows lower stability. Empirically, there therefore appears to be an optimal fit between the size and shape of the alkane and overall stability. Such observations are related to guest/host interactions in solution supramolecular chemistry and the holistic role of 1°, 2°, and 3° environments in metalloenzymes.Peer reviewe

    Pancreatic cancer survival trends in the US from 2001 to 2014: a CONCORD-3 study

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    Background Survival from pancreatic cancer is low worldwide. In the US, the 5-year relative survival has been slightly higher for women, whites and younger patients than for their counterparts, and differences in age and stage at diagnosis may contribute to this pattern. We aimed to examine trends in survival by race, stage, age and sex for adults (15-99 years) diagnosed with pancreatic cancer in the US. Methods This population-based study included 399,427 adults registered with pancreatic cancer in 41 US state cancer registries during 2001-2014, with follow-up to December 31, 2014. We estimated age-specific and age-standardized net survival at 1 and 5 years. Results Overall, 12.3% of patients were blacks, and 84.2% were whites. About 9.5% of patients were diagnosed with localized disease, but 50.5% were diagnosed at an advanced stage; slightly more among blacks, mainly among men. No substantial changes were seen over time (2001-2003, 2004-2008, 2009-2014). In general, 1-year net survival was higher in whites than in blacks (26.1% vs. 22.1% during 2001-2003, 35.1% vs. 31.4% during 2009-2014). This difference was particularly evident among patients with localized disease (49.6% in whites vs. 44.6% in blacks during 2001-2003, 60.1% vs. 55.3% during 2009-2014). The survival gap between blacks and whites with localized disease was persistent at 5 years after diagnosis, and it widened over time (from 24.0% vs. 21.3% during 2001-2003 to 39.7% vs. 31.0% during 2009-2014). The survival gap was wider among men than among women. Conclusions gaps in 1-and 5-year survival between blacks and whites were persistent throughout 2001-2014, especially for patients diagnosed with a localized tumor, for which surgery is currently the only treatment modality with the potential for cure

    Promoting Evidence-based Veterinary Medicine through the online resource ‘EBVM Learning’: User feedback

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    ‘EBVM Learning’ is a freely available resource created in 2015 by an international team with the support of RCVS Knowledge. The resource comprises a series of online modules teaching the fundamental concepts of evidence-based veterinary medicine (EBVM) (Ask, Acquire, Appraise, Apply & Assess) supported by case studies, exercises, worked examples and quizzes. The aim of the current study (undertaken in 2019) was to review ‘EBVM Learning’ to ensure its ongoing relevance and usefulness to the range of learners engaged in EBVM. Feedback was gathered from stakeholder groups using website statistics and feedback forms, a survey and semi-structured interviews to provide a combination of quantitative and qualitative data.Website statistics revealed an international audience and a steady increase in visitors exceeding 1,000 per month in August 2020. Feedback via the online form (n=35) and survey (n=71) indicated that the resource was well structured, with an appropriate level and amount of content, useful examples and quizzes and the majority of respondents would use it again. Semi-structured interviews of educators (n=5) and veterinarians (n=8) identified three themes: features of the ‘EBVM Learning’ resource (strengths, suggestions for improvement), embedding the resource in education (undergraduate, postgraduate) and promoting EBVM (challenges, motivation for engagement). At a project team workshop the results were used to plan updates to the existing content and to identify new ways to promote learning and engagement. An updated version of ‘EBVM Learning’ was developed.‘EBVM Learning’ is helping to produce the next generation of evidence-based practitioners and enabling to engage in the concepts of EBVM as part of their clinical practice

    Counting the bodies: Estimating the numbers and spatial variation of Australian reptiles, birds and mammals killed by two invasive mesopredators

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    Aim Introduced predators negatively impact biodiversity globally, with insular fauna often most severely affected. Here, we assess spatial variation in the number of terrestrial vertebrates (excluding amphibians) killed by two mammalian mesopredators introduced to Australia, the red fox (Vulpes vulpes) and feral cat (Felis catus). We aim to identify prey groups that suffer especially high rates of predation, and regions where losses to foxes and/or cats are most substantial. Location Australia. Methods We draw information on the spatial variation in tallies of reptiles, birds and mammals killed by cats in Australia from published studies. We derive tallies for fox predation by (i) modelling continental-scale spatial variation in fox density, (ii) modelling spatial variation in the frequency of occurrence of prey groups in fox diet, (iii) analysing the number of prey individuals within dietary samples and (iv) discounting animals taken as carrion. We derive point estimates of the numbers of individuals killed annually by foxes and by cats and map spatial variation in these tallies. Results Foxes kill more reptiles, birds and mammals (peaking at 1071 km−2 year−1) than cats (55 km−2 year−1) across most of the unmodified temperate and forested areas of mainland Australia, reflecting the generally higher density of foxes than cats in these environments. However, across most of the continent – mainly the arid central and tropical northern regions (and on most Australian islands) – cats kill more animals than foxes. We estimate that foxes and cats together kill 697 million reptiles annually in Australia, 510 million birds and 1435 million mammals. Main conclusions This continental-scale analysis demonstrates that predation by two introduced species takes a substantial and ongoing toll on Australian reptiles, birds and mammals. Continuing population declines and potential extinctions of some of these species threatens to further compound Australia's poor contemporary conservation record

    Covalent Modification of Lipids and Proteins in Rat Hepatocytes, and In Vitro, by Thioacetamide Metabolites

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    This document is the Accepted Manuscript version of a Published Work that appeared in final form in Chemical Research in Toxicology, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/tx3001658Thioacetamide (TA) is a well-known hepatotoxin in rats. Acute doses cause centrilobular necrosis and hyperbilirubinemia while chronic administration leads to biliary hyperplasia and cholangiocarcinoma. Its acute toxicity requires its oxidation to a stable S-oxide (TASO) that is oxidized further to a highly reactive S,S-dioxide (TASO2). To explore possible parallels between the metabolism, covalent binding and toxicity of TA and thiobenzamide (TB) we exposed freshly isolated rat hepatocytes to [14C]-TASO or [13C2D3]-TASO. TLC analysis of the cellular lipids showed a single major spot of radioactivity that mass spectral analysis showed to consist of N-acetimidoyl PE lipids having the same side chain composition as the PE fraction from untreated cells; no carbons or hydrogens from TASO were incorporated into the fatty acyl chains. Many cellular proteins contained N-acetyl- or N-acetimidoyl lysine residues in a 3:1 ratio (details to be reported separately). We also oxidized TASO with hydrogen peroxide in the presence of dipalmitoyl phosphatidylenthanolamine (DPPE) or lysozyme. Lysozyme was covalently modified at five of its six lysine side chains; only acetamide-type adducts were formed. DPPE in liposomes also gave only amide-type adducts, even when the reaction was carried out in tetrahydrofuran with only 10% water added. The exclusive formation of N-acetimidoyl PE in hepatocytes means that the concentration or activity of water must be extremely low in the region where TASO2 is formed, whereas at least some of the TASO2 can hydrolyze to acetylsulfinic acid before it reacts with cellular proteins. The requirement for two sequential oxidations to produce a reactive metabolite is unusual, but it is even more unusual that a reactive metabolite would react with water to form a new compound that retains a high degree of chemical reactivity toward biological nucleophiles. The possible contribution of lipid modification to the hepatotoxicity of TA/TASO remains to be determined

    Nutrient and microbial water quality of the upper Ganga river, India: identification of pollution sources

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    The Ganga River is facing mounting environmental pressures due to rapidly increasing human population, urbanisation, industrialisation and agricultural intensification, resulting in worsening water quality, ecological status and impacts on human health. A combined inorganic chemical, algal and bacterial survey (using flow cytometry and 16S rRNA gene sequencing) along the upper and middle Ganga (from the Himalayan foothills to Kanpur) was conducted under pre-monsoon conditions. The upper Ganga had total phosphorus (TP) and total dissolved nitrogen concentrations of less than 100 μg l−1 and 1.0 mg l−1, but water quality declined at Kannauj (TP = 420 μg l−1) due to major nutrient pollution inputs from human-impacted tributaries (principally the Ramganga and Kali Rivers). The phosphorus and nitrogen loads in these two tributaries and the Yamuna were dominated by soluble reactive phosphorus and ammonium, with high bacterial loads and large numbers of taxa indicative of pathogen and faecal organisms, strongly suggesting sewage pollution sources. The high nutrient concentrations, low flows, warm water and high solar radiation resulted in major algal blooms in the Kali and Ramganga, which greatly impacted the Ganga. Microbial communities were dominated by members of the Phylum Proteobacteria, Bacteriodetes and Cyanobacteria, with communities showing a clear upstream to downstream transition in community composition. To improve the water quality of the middle Ganga, and decrease ecological and human health risks, future mitigation must reduce urban wastewater inputs in the urbanised tributaries of the Ramganga, Kali and Yamuna Rivers

    A Series of Crystallographically Characterized Linear and Branched s- Alkane Complexes of Rhodium: From Propane to 3-Methylpentane

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    Using solid-state molecular organometallic (SMOM) techniques, in particular solid/gas single-crystal to single-crystal reactivity, a series of σ-alkane complexes of the general formula [Rh(Cy2PCH2CH2PCy2)(ηn:ηm-alkane)][BArF4] have been prepared (alkane = propane, 2-methylbutane, hexane, 3-methylpentane; ArF = 3,5-(CF3)2C6H3). These new complexes have been characterized using single crystal X-ray diffraction, solid-state NMR spectroscopy and DFT computational techniques and present a variety of Rh(I)···H–C binding motifs at the metal coordination site: 1,2-η2:η2 (2-methylbutane), 1,3-η2:η2 (propane), 2,4-η2:η2 (hexane), and 1,4-η1:η2 (3-methylpentane). For the linear alkanes propane and hexane, some additional Rh(I)···H–C interactions with the geminal C–H bonds are also evident. The stability of these complexes with respect to alkane loss in the solid state varies with the identity of the alkane: from propane that decomposes rapidly at 295 K to 2-methylbutane that is stable and instead undergoes an acceptorless dehydrogenation to form a bound alkene complex. In each case the alkane sits in a binding pocket defined by the {Rh(Cy2PCH2CH2PCy2)}+ fragment and the surrounding array of [BArF4]− anions. For the propane complex, a small alkane binding energy, driven in part by a lack of stabilizing short contacts with the surrounding anions, correlates with the fleeting stability of this species. 2-Methylbutane forms more short contacts within the binding pocket, and as a result the complex is considerably more stable. However, the complex of the larger 3-methylpentane ligand shows lower stability. Empirically, there therefore appears to be an optimal fit between the size and shape of the alkane and overall stability. Such observations are related to guest/host interactions in solution supramolecular chemistry and the holistic role of 1°, 2°, and 3° environments in metalloenzymes
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