Reversal of facial selectivity in a thia-Claisen rearrangement by incorporation of a vinylic bromine substituent

Thia-Claisen rearrangements have been carried out using N-benzylpyrrolidine-2-thione and chiral allylic bromides derived from D-mannitol. Introduction of a bromine atom onto the double bond of the allylic bromide reverses the sense of diastereoselectivity in the [3,3]-sigmatropic rearrangement. Density functional theory calculations lead us to rationalise the observed selectivity in terms of a Cíeplak effect

Assessing availability and greenhouse gas emissions of lignocellulosic biomass feedstock supply – case study for a catchment in England

© 2019 Society of Chemical Industry and John Wiley & Sons, Ltd.Feedstocks from lignocellulosic biomass (LCB) include crop residues and dedicated per¬ennial biomass crops. The latter are often considered superior in terms of climate change mitigation potential. Uncertainty remains over their availability as feedstocks for biomass provision and the net greenhouse gas emissions (GHG) during crop production. Our objective was to assess the optimal land allocation to wheat and Miscanthus in a specific case study located in England, to increase bio¬mass availability, improve the carbon balance (and reduce the consequent GHG emissions), and mini¬mally constrain grain production losses from wheat. Using soil and climate variables for a catchment in east England, biomass yields and direct nitrogen emissions were simulated with validated process-based models. A ‘Field to up-stream factory gate’ life-cycle assessment was conducted to estimate indirect management-related GHG emissions. Results show that feedstock supply from wheat straw can be supplemented beneficially with LCB from Miscanthus grown on selected low-quality soils. In our study, 8% of the less productive arable land area was dedicated to Miscanthus, increasing total LCB provision by about 150%, with a 52% reduction in GHG emission per ton LCB delivered and only a minor effect on wheat grain production (−3%). In conclusion, even without considering the likely carbon sequestration in impoverished soils, agriculture should embrace the opportunities to provide the bioeconomy with LCB from dedicated, perennial crops.Peer reviewe

A genomics-informed, SNP association study reveals FBLN1 and FABP4 as contributing to resistance to fleece rot in Australian Merino sheep

<p>Abstract</p> <p>Background</p> <p>Fleece rot (FR) and body-strike of Merino sheep by the sheep blowfly <it>Lucilia cuprina </it>are major problems for the Australian wool industry, causing significant losses as a result of increased management costs coupled with reduced wool productivity and quality. In addition to direct effects on fleece quality, fleece rot is a major predisposing factor to blowfly strike on the body of sheep. In order to investigate the genetic drivers of resistance to fleece rot, we constructed a combined ovine-bovine cDNA microarray of almost 12,000 probes including 6,125 skin expressed sequence tags and 5,760 anonymous clones obtained from skin subtracted libraries derived from fleece rot resistant and susceptible animals. This microarray platform was used to profile the gene expression changes between skin samples of six resistant and six susceptible animals taken immediately before, during and after FR induction. Mixed-model equations were employed to normalize the data and 155 genes were found to be differentially expressed (DE). Ten DE genes were selected for validation using real-time PCR on independent skin samples. The genomic regions of a further 5 DE genes were surveyed to identify single nucleotide polymorphisms (SNP) that were genotyped across three populations for their associations with fleece rot resistance.</p> <p>Results</p> <p>The majority of the DE genes originated from the fleece rot subtracted libraries and over-representing gene ontology terms included defense response to bacterium and epidermis development, indicating a role of these processes in modulating the sheep's response to fleece rot. We focused on genes that contribute to the physical barrier function of skin, including keratins, collagens, fibulin and lipid proteins, to identify SNPs that were associated to fleece rot scores.</p> <p>Conclusions</p> <p>We identified FBLN1 (fibulin) and FABP4 (fatty acid binding protein 4) as key factors in sheep's resistance to fleece rot. Validation of these markers in other populations could lead to vital tests for marker assisted selection that will ultimately increase the natural fleece rot resistance of Merino sheep.</p

IMPLEmenting a clinical practice guideline for acute low back pain evidence-based manageMENT in general practice (IMPLEMENT) : cluster randomised controlled trial study protocol

Background: Evidence generated from reliable research is not frequently implemented into clinical practice. Evidence-based clinical practice guidelines are a potential vehicle to achieve this. A recent systematic review of implementation strategies of guideline dissemination concluded that there was a lack of evidence regarding effective strategies to promote the uptake of guidelines. Recommendations from this review, and other studies, have suggested the use of interventions that are theoretically based because these may be more effective than those that are not. An evidencebased clinical practice guideline for the management of acute low back pain was recently developed in Australia. This provides an opportunity to develop and test a theory-based implementation intervention for a condition which is common, has a high burden, and for which there is an evidence-practice gap in the primary care setting. Aim: This study aims to test the effectiveness of a theory-based intervention for implementing a clinical practice guideline for acute low back pain in general practice in Victoria, Australia. Specifically, our primary objectives are to establish if the intervention is effective in reducing the percentage of patients who are referred for a plain x-ray, and improving mean level of disability for patients three months post-consultation. Methods/Design: This study protocol describes the details of a cluster randomised controlled trial. Ninety-two general practices (clusters), which include at least one consenting general practitioner, will be randomised to an intervention or control arm using restricted randomisation. Patients aged 18 years or older who visit a participating practitioner for acute non-specific low back pain of less than three months duration will be eligible for inclusion. An average of twenty-five patients per general practice will be recruited, providing a total of 2,300 patient participants. General practitioners in the control arm will receive access to the guideline using the existing dissemination strategy. Practitioners in the intervention arm will be invited to participate in facilitated face-to-face workshops that have been underpinned by behavioural theory. Investigators (not involved in the delivery of the intervention), patients, outcome assessors and the study statistician will be blinded to group allocation. Trial registration: Australian New Zealand Clinical Trials Registry ACTRN012606000098538 (date registered 14/03/2006).The trial is funded by the NHMRC by way of a Primary Health Care Project Grant (334060). JF has 50% of her time funded by the Chief Scientist Office3/2006). of the Scottish Government Health Directorate and 50% by the University of Aberdeen. PK is supported by a NHMRC Health Professional Fellowship (384366) and RB by a NHMRC Practitioner Fellowship (334010). JG holds a Canada Research Chair in Health Knowledge Transfer and Uptake. All other authors are funded by their own institutions

Relationships between CYP2D6 phenotype, breast cancer and hot flushes in women at high risk of breast cancer receiving prophylactic tamoxifen: results from the IBIS-I trial

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Estimated pre-morbid IQ effects on cognitive and functional outcomes in Alzheimer disease: a longitudinal study in a treated cohort

Abstract Background Cognitive reserve is thought to influence the degree of neuropathology needed for diagnosis of Alzheimer disease (AD). Cognitive reserve can be operationally defined as the hypothesized capacity of the mature adult brain to sustain the effects of disease or injury without manifesting clinical symptoms of AD, but sufficient to cause clinical dementia in an individual possessing less cognitive reserve. Its effect on the subsequent course of AD is less clear. Pre-morbid IQ is a useful measure of cognitive reserve. Methods We studied 659 consecutive patients with AD at a tertiary referral memory clinic. Patients were assessed on six cognitive tests at baseline. Activities of Daily Living (ADL) were measured on the Instrumental Activities of Daily Living (IADL) scale and Physical Self-Maintenance Scale (PSMS). The National Adult Reading Test (NART) was used to estimate pre-morbid IQ. Patients were followed up after starting a cholinesterase inhibitor over 78 weeks. Mixed general linear models estimated the effects of NART on cognition and ADL. Results Three hundred and fifty-five patients had NART scored with a mean estimated pre-morbid IQ of 104.7 (standard deviation 18.5). NART increased overall cognitive ability by 2.7% for every 10 IQ points (p Conclusion Our data support the hypothesis that cognitive reserve continues to have a limited influence on cognition after AD has been diagnosed and thus, indirectly, has an impact on ADL.</p

A novel nonhuman primate model for influenza transmission

Studies of influenza transmission are necessary to predict the pandemic potential of emerging influenza viruses. Currently, both ferrets and guinea pigs are used in such studies, but these species are distantly related to humans. Nonhuman primates (NHP) share a close phylogenetic relationship with humans and may provide an enhanced means to model the virological and immunological events in influenza virus transmission. Here, for the first time, it was demonstrated that a human influenza virus isolate can productively infect and be transmitted between common marmosets (Callithrix jacchus), a New World monkey species. We inoculated four marmosets with the 2009 pandemic virus A/California/07/2009 (H1N1pdm) and housed each together with a naïve cage mate. We collected bronchoalveolar lavage and nasal wash samples from all animals at regular intervals for three weeks post-inoculation to track virus replication and sequence evolution. The unadapted 2009 H1N1pdm virus replicated to high titers in all four index animals by 1 day post-infection. Infected animals seroconverted and presented human-like symptoms including sneezing, nasal discharge, labored breathing, and lung damage. Transmission occurred in one cohabitating pair. Deep sequencing detected relatively few genetic changes in H1N1pdm viruses replicating in any infected animal. Together our data suggest that human H1N1pdm viruses require little adaptation to replicate and cause disease in marmosets, and that these viruses can be transmitted between animals. Marmosets may therefore be a viable model for studying influenza virus transmission. © 2013 Moncla et al

Evidence-based care of older people with suspected cognitive impairment in general practice: protocol for the IRIS cluster randomised trial

Background: Dementia is a common and complex condition. Evidence-based guidelines for the management of people with dementia in general practice exist; however, detection, diagnosis and disclosure of dementia have been identified as potential evidence-practice gaps. Interventions to implement guidelines into practice have had varying success. The use of theory in designing implementation interventions has been limited, but is advocated because of its potential to yield more effective interventions and aid understanding of factors modifying the magnitude of intervention effects across trials. This protocol describes methods of a randomised trial that tests a theory-informed implementation intervention that, if effective, may provide benefits for patients with dementia and their carers. Aims: This trial aims to estimate the effectiveness of a theory-informed intervention to increase GPs’ (in Victoria, Australia) adherence to a clinical guideline for the detection, diagnosis, and management of dementia in general practice, compared with providing GPs with a printed copy of the guideline. Primary objectives include testing if the intervention is effective in increasing the percentage of patients with suspected cognitive impairment who receive care consistent with two key guideline recommendations: receipt of a i) formal cognitive assessment, and ii) depression assessment using a validated scale (primary outcomes for the trial). Methods: The design is a parallel cluster randomised trial, with clusters being general practices. We aim to recruit 60 practices per group. Practices will be randomised to the intervention and control groups using restricted randomisation. Patients meeting the inclusion criteria, and GPs’ detection and diagnosis behaviours directed toward these patients, will be identified and measured via an electronic search of the medical records nine months after the start of the intervention. Practitioners in the control group will receive a printed copy of the guideline. In addition to receipt of the printed guideline, practitioners in the intervention group will be invited to participate in an interactive, opinion leader-led, educational face-to-face workshop. The theory-informed intervention aims to address identified barriers to and enablers of implementation of recommendations. Researchers responsible for identifying the cohort of patients with suspected cognitive impairment, and their detection and diagnosis outcomes, will be blind to group allocation. Trial registration: Australian New Zealand Clinical Trials Registry: ACTRN12611001032943 (date registered 28 September, 2011)

Global Initiative for Asthma (GINA) strategy 2021 - executive summary and rationale for key changes.

The Global Initiative for Asthma (GINA) Strategy Report provides clinicians with an annually updated evidence-based strategy for asthma management and prevention, which can be adapted for local circumstances (e.g., medication availability). This article summarizes key recommendations from GINA 2021, and the evidence underpinning recent changes. GINA recommends that asthma in adults and adolescents should not be treated solely with short-acting beta2-agonist (SABA), because of the risks of SABA-only treatment and SABA overuse, and evidence for benefit of inhaled corticosteroids (ICS). Large trials show that as-needed combination ICS-formoterol reduces severe exacerbations by ≥60% in mild asthma compared with SABA alone, with similar exacerbation, symptom, lung function and inflammatory outcomes as daily ICS plus as-needed SABA. Key changes in GINA 2021 include division of the treatment figure for adults/adolescents into two tracks. Track 1 (preferred) has low-dose ICS-formoterol as the reliever at all steps: as-needed only in Steps 1-2 (mild asthma), and with daily maintenance ICS formoterol (maintenance-and-reliever therapy, MART) in Steps 3-5. Track 2 (alternative) has as-needed SABA across all steps, plus regular ICS (Step 2) or ICS-long-acting beta2-agonist (LABA) (Steps 3-5). For adults with moderate-to-severe asthma, GINA makes additional recommendations in Step 5 for add-on long-acting muscarinic antagonists and azithromycin, with add-on biologic therapies for severe asthma. For children 6-11 years, new treatment options are added at Steps 3-4. Across all age-groups and levels of severity, regular personalized assessment, treatment of modifiable risk factors, self-management education, skills training, appropriate medication adjustment and review remain essential to optimize asthma outcomes

Introducing a new breed of wine yeast: interspecific hybridisation between a commercial Saccharomyces cerevisiae wine yeast and Saccharomyces mikatae

Interspecific hybrids are commonplace in agriculture and horticulture; bread wheat and grapefruit are but two examples. The benefits derived from interspecific hybridisation include the potential of generating advantageous transgressive phenotypes. This paper describes the generation of a new breed of wine yeast by interspecific hybridisation between a commercial Saccharomyces cerevisiae wine yeast strain and Saccharomyces mikatae, a species hitherto not associated with industrial fermentation environs. While commercially available wine yeast strains provide consistent and reliable fermentations, wines produced using single inocula are thought to lack the sensory complexity and rounded palate structure obtained from spontaneous fermentations. In contrast, interspecific yeast hybrids have the potential to deliver increased complexity to wine sensory properties and alternative wine styles through the formation of novel, and wider ranging, yeast volatile fermentation metabolite profiles, whilst maintaining the robustness of the wine yeast parent. Screening of newly generated hybrids from a cross between a S. cerevisiae wine yeast and S. mikatae (closely-related but ecologically distant members of the Saccharomyces sensu stricto clade), has identified progeny with robust fermentation properties and winemaking potential. Chemical analysis showed that, relative to the S. cerevisiae wine yeast parent, hybrids produced wines with different concentrations of volatile metabolites that are known to contribute to wine flavour and aroma, including flavour compounds associated with non-Saccharomyces species. The new S. cerevisiae x S. mikatae hybrids have the potential to produce complex wines akin to products of spontaneous fermentation while giving winemakers the safeguard of an inoculated ferment.Jennifer R. Bellon, Frank Schmid, Dimitra L. Capone, Barbara L. Dunn, Paul J. Chamber