Reactions of the epoxides of 1,3-butadiene and isoprene (2-methyl-1,3-butadiene) with oxygen, nitrogen and sulfur nucleophiles have been compared to enable a better molecular understanding of the ...relative human toxicities of these epoxides. Hydrolysis of rac.-ethenyloxirane in (18O)water gave 77% (2-18O)but-3-ene-1,2-diol and 23% (1-18O)but-3-ene-1,2-diol. The R:S ratio for but-3-ene-1,2-diol from hydrolysis of (S)-ethenyloxirane was 75:25. Hence, hydrolysis of ethenyloxirane occurs by competing SN2 attack at C-2 and C-3 in 3:1 ratio, with no SN1 component. Hydrolysis of rac.-2-ethenyl-2-methyloxirane gave 2-hydroxy-2-methylbut-3-en-1-ol (73%) and 27% of a 2:1 mixture of the E- and Z-isomers of 4-hydroxy-2-methylbut-2-en-1-ol. In (18O)water (2-18O)2-hydroxy-2-methylbut-3-en-1-ol was obtained. Formation of these products occurs via SN1 ionisation to resonance-stabilised allylic cations which are captured by water. Reaction of rac.-ethenyloxirane with l-valine methyl ester gave diastereoisomeric adducts from SN2 attack of the valine amino at both C-2 (substituted position) and C-3 of the oxirane. The corresponding reaction of rac.-2-methyl-2-ethenyloxirane gave diastereoisomeric adducts, (R, S)- and (S, S)–N-(2-hydroxy-2-methyl-3-buten-1-yl)-l-valine methyl ester, from SN2 attack of the valine amino solely at C-3. Reactions of rac.-2-ethenyl-2-methyloxirane with cysteine derivatives occurred at C-2 in neutral polar media (SN1 reaction) or at C-3 in basic media (SN2), whereas for ethenyloxirane products arose from attack at both C-2 and C-3. Reaction of meso-butadiene diepoxide (meso-2,2′-bioxirane) with l-valine methyl ester gave mainly 2:1 adducts, dimethyl 2,2'-(((2R,3S)-2,3-dihydroxybutane-1,4-diyl)bis(azanediyl))-(2S,2′S)-bis(3-methyl-butanoates), whereas 2-methyl-2,2′-bioxirane gave a mixture of 1:1 methyl 2-(3,4-dihydroxy-3-methylpyrrolidin-1-yl)-3-methylbutanoates and 2:1 adducts. Meso-2,2′-bioxirane reacted with N-acetylcysteine methyl ester in methanol to afford meso-thiolane-3,4-diol, by elimination of N-acetyldehydroalanine methyl ester from a precursor cyclic adduct. Similarly, 2-methyl-2,2′-bioxirane gave solely 3-methylthiolane-3,4-diols. Thus, the methyl group of isoprene has a subtle effect on the reactivity of its epoxides relative to those of butadiene and therefore, in the context of their toxicology, could abrogate crosslinking of nitrogen functions in biomolecules related to mutagenicity and carcinogenicity.
•Reactions of butadiene and isoprene epoxides with biologically related nucleophiles.•Fundamental difference in reactivity between the diene epoxides highlighted.•Isoprene methyl group has profound effect on adduction reactions of its epoxides.•Diene adductomics and human health implications.
In order for health care innovations to be effective and actionable, they must align with the needs and practice patterns of those delivering care at the bedside. While research has started to ...incorporate the patient voice, it has yet to fully invest in the expertise of frontline clinicians. Frontline clinicians carry a wealth of clinical knowledge and the lived experience of providing real-world medical care that the research community seeks to improve. We consider options for clinicians as research stakeholders along a continuum of engagement as outlined by the UCSF Clinical and Translational Science Institute from
minimal
to
supportive
to
participatory
. In order to make an effective value proposition to support reallocation of clinician time to research engagement, we advocate evaluating the impact of clinicians as stakeholders at both the process level (e.g., clinician satisfaction, study recruitment rates) and endpoint level (e.g., clinical outcomes). Investing in clinicians as research stakeholders can offer benefits for the individual, health system, and population by increasing the generalizability, adoption, and sustainability of effective interventions.
Erosion following fire has the potential to affect water quality, alter soil profiles and detrimentally affect human infrastructure. There is a clear need for environmental assessments to have regard ...for erosion concerns from prescribed burning. This study focussed on 10 prescribed burns conducted in the Southern Mount Lofty Ranges. Generalised additive modelling was used to determine the main significant environmental variables influencing the presence of sediment movement at 505 field-assessed sites. Sediment movement after the 10 prescribed burns was minor. Fire severity was a highly significant environmental determinant for the presence of sediment movement after prescribed burning. To predict erosion concerns, a suite of environmental variables is more reliable than focusing solely on slope steepness, as occurred before this study. These results indicate that erosion assessments need to consider a range of environmental variables to assess potential erosion and that land managers and scientists need to incorporate spatial sampling designs into erosion assessments.
Aim: To facilitate the uptake of evidence and to reduce the evidence practice gap for management of newborn pain through the development of a clinical practice guideline.
Method: An audit of ...practice and an appraisal of clinical practice guidelines were undertaken to establish current practices and guideline availability for the management of newborn pain in 23 hospitals in Australia. Guidelines were appraised using the Appraisal of Guidelines for Research and Evaluation instrument. A literature search was undertaken to acquire the evidence for best practice for management of newborn pain.
Results: Neonatal units in 17 hospitals had clinical practice guidelines. Each was peer reviewed and assessed according to the domains of the Appraisal of Guidelines for Research and Evaluation instrument. There was lack of consistency across the guidelines. As a result, a best practice guideline was developed based on current best evidence and the Royal Australian College of Physicians recommendations. To facilitate an ongoing compliance with the guideline, an audit tool was included together with algorithms for procedural pain and pain assessment.
Conclusion: The clinical practice guideline can be used by clinicians in varying settings such as the neonatal intensive care and special care unit. The document can be used to support existing practices or challenge clinicians to close the evidence practice gap for the management of newborn pain.
Capsule The population of Nightjars in the UK increased by over 36% between 1992 and 2004.
Aims To determine the population size and distribution of Nightjars in the UK and examine associations with ...forestry and heathland habitat features.
Methods A volunteer survey was supported by professional cover in remote parts of Wales, and areas of Dorset and lowland Scotland. Two visits to allocated 1-km squares were made between late May and mid-July. Each surveyor recorded the locations of calling males onto maps and the occurrence of habitat categories within 50 m of each Nightjar registration.
Results Observers surveyed 3264 1-km squares in 2004 and, on average, 78% of the target habitat (90% in southern England). The total number of males counted was 4131 (range 3850-4414), adjusted to 4606 (95% CL ± 913) to account for unsurveyed habitat. The adjusted total represented a 36% increase in 12 years. Nightjars were recorded in 275 10-km squares in 2004, a 2.6% increase since 1992. However, there was evidence of population decline and range contractions in northwest Britain, including north Wales, northwest England and in Scotland. In 2004, 57% of Nightjars were associated with forest plantations (similar to 1992) and 59% with heathland (slightly higher than in 1992).
Conclusion National objectives for Nightjar conservation (UK Biodiversity Action Plan: UKBAP) were reached in respect of population size and stability, but the target for a 5% range increase by 2003 was not met. The continued increase in the national population is probably attributable to habitat protection, management and restoration of heathlands, and the continued availability of clear-fell/young plantations in conifer forests. Management and/or protection/restoration/re-creation of these key habitats remains critical for the long-term objectives of UKBAP. The issue of providing foraging habitats, perhaps via agri-environment schemes, is also raised.
Common terns breed within the industrial complex at Shotton Steel Works, North Wales. Each journey between the breeding colony and the main feeding areas on the Dee estuary requires the terns to ...negotiate two spans of power lines. Here we investigated the risk of collision with power lines in relation to the time demands on adults, the age of birds and wind speed.
Systematic observations were made of terns journeying to and from the estuary during four phases of the breeding season (courtship, incubation, nestling and juvenile). Casualty surveys of the ground beneath the power lines were also completed, and in order to quantify the potential removal rate of bird casualties by predators, bird corpses were placed underneath the power lines and recounted after two, five and 14 days.
There was a greater than three-fold increase in the frequency of combined journeys made by terns from courtship to the nestling phase and this increase coincided with an increase in the proportion of adult terns which passed under or between the wires of the power lines. Terns also flew closer on average to the top earth wire during the nestling and fledging phases than during the courtship or incubation phases. Juvenile terns flew consistently closer to wires than adults with most juvenile crossings being < 1 m above the top wire. Only 7% of adults flew this close. Only two common tern casualties were found beneath wires (during the nestling phase) representing only 0·4% of the colony population. Since the removal rate of corpses by predators was very slow (around 6% in 14 days), the mortality rate of terns due to collisions with wires was also considered low.
Common terns are agile birds and suffered only low rates of direct mortality through collisions with power lines. However, the demands placed on parent birds during the breeding season caused a significant increase in their vulnerability to collision. This is a factor which has not previously been studied and has implications for a wider range of species.
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