What goes in, must come out:combining scat-based molecular diet analysis and quantification of ingested microplastics in a marine top predator

Context: Microplastics (plastic particles &lt;5 mm in size) are highly available for ingestion by a wide range of organisms, either through direct consumption or indirectly, via trophic transfer, from prey to predator. The latter is a poorly understood, but potentially major, route of microplastic ingestion for marine top predators.Approach: We developed a novel and effective methodology pipeline to investigate dietary exposure of wild top predators (grey seals; Halichoerus grypus) to microplastics, by combining scat-based molecular techniques with a microplastic isolation method. We employed DNA metabarcoding, a rapid method of biodiversity assessment, to garner detailed information on prey composition from scats, and investigated the potential relationship between diet and microplastic burden.Results: Outcomes of the method development process and results of both diet composition from metabarcoding analysis and detection of microplastics are presented. Importantly, the pipeline performed well and initial results suggest the frequency of microplastics detected in seal scats may be related to the type of prey consumed. Conclusions: Our non-invasive, data rich approach maximises time and resource-efficiency, while minimising costs and sample volumes required for analysis. This pipeline could be used to underpin a much-needed increase in understanding of the relationship between diet composition and rates of microplastic ingestion in high trophic-level species.<br/

Adaptive Control Based on Retrospective Cost Optimization

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/83558/1/AIAA-46741-507.pd

The beneficial effects of TAVI in mitral insufficiency.

Background Although everolimus potentially improves long-term heart transplantation (HTx) outcomes, its early postoperative safety profile had raised concerns and needs optimization. Methods This 6-month, open-label, multicenter randomized trial was designed to compare the cumulative incidence of a primary composite safety endpoint comprising wound healing delays, pericardial effusion, pleural effusion needing drainage, and renal insufficiency events (estimated glomerular filtration rate ≤30/mL/min per 1.73 m2) in de novo HTx recipients receiving immediate everolimus (EVR-I) (≤144 hours post-HTx) or delayed everolimus (EVR-D) (4-6 weeks post-HTx with mycophenolate mofetil as a bridge) with reduced-dose cyclosporine A. Cumulative incidence of biopsy-proven rejection ≥ 2R, rejection with hemodynamic compromise, graft loss, or death was the secondary composite efficacy endpoint. Results Overall, 181 patients were randomized to the EVR-I (n = 89) or EVR-D (n = 92) arms. Incidence of primary safety endpoint was higher for EVR-I than EVR-D arm (44.9% vs 32.6%; P = 0.191), mainly driven by a higher rate of pericardial effusion (33.7% vs 19.6%; P = 0.04); wound healing delays, acute renal insufficiency events, and pleural effusion occurred at similar frequencies in the study arms. Efficacy failure was not significantly different in EVR-I arm versus EVR-D arm (37.1% vs 28.3%; P = 0.191). Three patients in the EVR-I arm and 1 in the EVR-D arm died. Incidence of clinically significant adverse events leading to discontinuation was higher in EVR-I arm versus EVR-D arm (P = 0.02). Conclusions Compared with immediate initiation, delayed everolimus initiation appeared to provide a clinically relevant early safety benefit in de novo HTx recipients, without compromising efficacy. © 2017 The Author(s). Published by Wolters Kluwer Health, Inc

Intervention planning for Antibiotic Review Kit (ARK): a digital and behavioural intervention to safely review and reduce antibiotic prescriptions in acute and general medicine

Background Hospital antimicrobial stewardship strategies, such as ‘Start Smart, Then Focus’ in the UK, balance the need for prompt, effective antibiotic treatment with the need to limit antibiotic overuse using ‘review and revise’. However, only a minority of review decisions are to stop antibiotics. Research suggests that this is due to both behavioural and organizational factors. Objectives To develop and optimize the Antibiotic Review Kit (ARK) intervention. ARK is a complex digital, organizational and behavioural intervention that supports implementation of ‘review and revise’ to help healthcare professionals safely stop unnecessary antibiotics. Methods A theory-, evidence- and person-based approach was used to develop and optimize ARK and its implementation. This was done through iterative stakeholder consultation and in-depth qualitative research with doctors, nurses and pharmacists in UK hospitals. Barriers to and facilitators of the intervention and its implementation, and ways to address them, were identified and then used to inform the intervention’s development. Results A key barrier to stopping antibiotics was reportedly a lack of information about the original prescriber’s rationale for and their degree of certainty about the need for antibiotics. An integral component of ARK was the development and optimization of a Decision Aid and its implementation to increase transparency around initial prescribing decisions. Conclusions The key output of this research is a digital and behavioural intervention targeting important barriers to stopping antibiotics at review (see http://bsac-vle.com/ark-the-antibiotic-review-kit/ and http://antibioticreviewkit.org.uk/). ARK will be evaluated in a feasibility study and, if successful, a stepped-wedge cluster-randomized controlled trial at acute hospitals across the NHS

Patient engagement with antibiotic messaging in secondary care: a qualitative feasibility study of the ‘review & revise’ experience

Background: We aimed to investigate and optimise the acceptability and usefulness of a patient leaflet about antibiotic prescribing decisions made during hospitalisation, and to explore individual patient experiences and preferences regarding the process of antibiotic prescription ‘review & revise’ which is a key strategy to minimise antibiotic overuse in hospitals. Methods: In this qualitative study, run within the feasibility study of a large, cluster-randomised stepped wedge trial of 36 hospital organisations, a series of semi-structured, think-aloud telephone interviews were conducted and data were analysed using thematic analysis. Fifteen adult patients who had experienced a recent acute medical hospital admission during which they had been prescribed antimicrobials and offered a patient leaflet about antibiotic prescribing were recruited to the study. Results: Participants reacted positively to the leaflet, reporting that it was both an accessible and important source of information which struck the appropriate balance between informing and reassuring. Participants all valued open communication with clinicians, and were keen to be involved in antibiotic prescribing decisions, with individuals reporting positive experiences regarding antibiotic prescription changes or stopping. Many participants had prior experience or knowledge of antibiotics and resistance, and generally welcomed efforts to reduce antibiotic usage. Overall, there was a feeling that healthcare professionals (HCPs) are trusted experts providing the most appropriate treatment for individual patient conditions. Conclusions: This study offers novel insights into how patients within secondary care are likely to respond to messages advocating a reduction in the use of antibiotics through the ‘review & revise’ approach. Due to the level of trust that patients place in their care provider, encouraging HCPs within secondary care to engage patients with greater communication and information provision could provide great advantages in the drive to reduce antibiotic use. It may also be beneficial for HCPs to view patient experiences as cumulative events that have the potential to impact future behaviour around antibiotic use. Finally, pre-testing messages about antibiotic prescribing and resistance is vital to dispelling any misconceptions either around effectiveness of treatment for patients, or perceptions of how messages may be received

p85 regulatory subunit of PI3K mediates cAMP–PKA and estrogens biological effects on growth and survival

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Developing a behavioural intervention package to identify and amend incorrect penicillin allergy records in UK general practice and subsequently change antibiotic use

Objectives: To develop a behavioural intervention package to support clinicians and patients to amend incorrect penicillin allergy records in general practice. The intervention aimed to: (1) support clinicians to refer patients for penicillin allergy testing (PAT), (2) support patients to attend for PAT and (3) support clinicians and patients to prescribe or consume penicillin, when indicated, following a negative PAT result. Methods: Theory-based, evidence-based and person-based approaches were used in the intervention development. We used evidence from a rapid review, two qualitative studies, and expert consultations with the clinical research team to identify the intervention ‘guiding principles’ and develop an intervention plan. Barriers and facilitators to the target behaviours were mapped to behaviour change theory in order to describe the proposed mechanisms of change. In the final stage, think-aloud interviews were conducted to optimise intervention materials. Results: The collated evidence showed that the key barriers to referral of patients by clinicians were limited experience of referral and limited knowledge of referral criteria and PAT. Barriers for patients attending PAT were lack of knowledge of the benefits of testing and lack of motivation to get tested. The key barriers to the prescription and consumption of first-line penicillin following a negative test result were patient and clinician beliefs about the accuracy of PAT and whether taking penicillin was safe. Intervention materials were designed and developed to address these barriers. Conclusions: We present a novel behavioural intervention package designed to address the multiple barriers to uptake of PAT in general practice by clinicians and patients. The intervention development details how behaviour change techniques have been incorporated to hypothesise how the intervention is likely to work to help amend incorrect penicillin allergy records. The intervention will go on to be tested in a feasibility trial and randomised controlled trial in England

Analisi della variabilità genetica della razza Gentile di Puglia mediante microsatelliti

La razza Gentile di Puglia conta circa 2813 soggetti allevati in 29 aziende distribuite sui territori di Puglia, Abruzzo, Calabria e Molise (dati Asso.Na.Pa del 2006); da decenni si sta verificando una costante e preoccupante contrazione numerica degli esemplari appartenenti alla razza. La pecora Gentile presenta una produzione di latte modesta in termini quantitativi, sebbene l’elevato contenuto in grasso e proteine lo rendano particolarmente idoneo alla lavorazione casearia. In tale contesto la caratterizzazione genetica della razza Gentile di Puglia, attraverso lo studio della variabilità genetica con approccio di tipo molecolare, potrebbe rappresentare un valido strumento per la sal- vaguardia della razza e per la valorizzazione delle sue produzioni

DNA Damage, Homology-Directed Repair, and DNA Methylation

To explore the link between DNA damage and gene silencing, we induced a DNA double-strand break in the genome of Hela or mouse embryonic stem (ES) cells using I-SceI restriction endonuclease. The I-SceI site lies within one copy of two inactivated tandem repeated green fluorescent protein (GFP) genes (DR-GFP). A total of 2%–4% of the cells generated a functional GFP by homology-directed repair (HR) and gene conversion. However, ~50% of these recombinants expressed GFP poorly. Silencing was rapid and associated with HR and DNA methylation of the recombinant gene, since it was prevented in Hela cells by 5-aza-2′-deoxycytidine. ES cells deficient in DNA methyl transferase 1 yielded as many recombinants as wild-type cells, but most of these recombinants expressed GFP robustly. Half of the HR DNA molecules were de novo methylated, principally downstream to the double-strand break, and half were undermethylated relative to the uncut DNA. Methylation of the repaired gene was independent of the methylation status of the converting template. The methylation pattern of recombinant molecules derived from pools of cells carrying DR-GFP at different loci, or from an individual clone carrying DR-GFP at a single locus, was comparable. ClustalW analysis of the sequenced GFP molecules in Hela and ES cells distinguished recombinant and nonrecombinant DNA solely on the basis of their methylation profile and indicated that HR superimposed novel methylation profiles on top of the old patterns. Chromatin immunoprecipitation and RNA analysis revealed that DNA methyl transferase 1 was bound specifically to HR GFP DNA and that methylation of the repaired segment contributed to the silencing of GFP expression. Taken together, our data support a mechanistic link between HR and DNA methylation and suggest that DNA methylation in eukaryotes marks homologous recombined segments