Opportunistic use of a wool-like artificial material as lining of Tit (Paridae) nests

The lining material is a key element of bird nests primarily serving as insulation for the adult, eggs and/or chicks but collection of such material will have an energetic cost. This study investigated the nest building effort of four species of tit (Paridae) in an English wood by determining the use of colored, wool-like artificial nest lining material over the period 2000-2010. The distances that birds carried the material from source to nest was recorded for each nest as an indirect measure of the energetic cost of collection of nest material by individual birds. Birds did not always use nest material from the nearest source to their nest and some birds collected material from 2, 3 or 4 well-separated sources. There was no detectable color preference in choice of material and few birds would travel more than 200 m to gather the material. Use of the material appeared to depend on the species. Within defined areas around material dispensers not all individual Great Tits (Parus major) used the artificial material and, for all species examined, the proportion of birds using the material declined with increasing distance between source and nest. Use of artificial material suggested that selection of nest materials was probably opportunistic but also reflected the preference of these species for a wool-like nest-lining

Variation in suspected cancer referral pathways in primary care:comparative analysis across the International Benchmarking Cancer Partnership

BACKGROUND: International variations in cancer outcomes persist and may be influenced by differences in the accessibility and organisation of cancer patient pathways. More evidence is needed to understand to what extent variations in the structure of primary care referral pathways for cancer investigation contribute to differences in the timeliness of diagnoses and cancer outcomes in different countries. AIM: To explore the variation in primary care referral pathways for the management of suspected cancer across different countries. DESIGN AND SETTING: Descriptive comparative analysis using mixed methods across the International Cancer Benchmarking Partnership (ICBP) countries. METHOD: Schematics of primary care referral pathways were developed across 10 ICBP jurisdictions. The schematics were initially developed using the Aarhus statement (a resource providing greater insight and precision into early cancer diagnosis research) and were further supplemented with expert insights through consulting leading experts in primary care and cancer, existing ICBP data, a focused review of existing evidence on the management of suspected cancer, published primary care cancer guidelines, and evaluations of referral tools and initiatives in primary care. RESULTS: Referral pathway schematics for 10 ICBP jurisdictions were presented alongside a descriptive comparison of the organisation of primary care management of suspected cancer. Several key areas of variation across countries were identified: inflexibility of referral pathways, lack of a managed route for non-specific symptoms, primary care practitioner decision-making autonomy, direct access to investigations, and use of emergency routes. CONCLUSION: Analysing the differences in referral processes can prompt further research to better understand the impact of variation on the timeliness of diagnoses and cancer outcomes. Studying these schematics in local contexts may help to identify opportunities to improve care and facilitate discussions on what may constitute best referral practice

Protocol for a feasibility study incorporating a randomised pilot trial with an embedded process evaluation and feasibility economic analysis of ThinkCancer!: a primary care intervention to expedite cancer diagnosis in Wales

Abstract Background Compared to the rest of Europe, the UK has relatively poor cancer outcomes, with late diagnosis and a slow referral process being major contributors. General practitioners (GPs) are often faced with patients presenting with a multitude of non-specific symptoms that could be cancer. Safety netting can be used to manage diagnostic uncertainty by ensuring patients with vague symptoms are appropriately monitored, which is now even more crucial due to the ongoing COVID-19 pandemic and its major impact on cancer referrals. The ThinkCancer! workshop is an educational behaviour change intervention aimed at the whole general practice team, designed to improve primary care approaches to ensure timely diagnosis of cancer. The workshop will consist of teaching and awareness sessions, the appointment of a Safety Netting Champion and the development of a bespoke Safety Netting Plan and has been adapted so it can be delivered remotely. This study aims to assess the feasibility of the ThinkCancer! intervention for a future definitive randomised controlled trial. Methods The ThinkCancer! study is a randomised, multisite feasibility trial, with an embedded process evaluation and feasibility economic analysis. Twenty-three to 30 general practices will be recruited across Wales, randomised in a ratio of 2:1 of intervention versus control who will follow usual care. The workshop will be delivered by a GP educator and will be adapted iteratively throughout the trial period. Baseline practice characteristics will be collected via questionnaire. We will also collect primary care intervals (PCI), 2-week wait (2WW) referral rates, conversion rates and detection rates at baseline and 6 months post-randomisation. Participant feedback, researcher reflections and economic costings will be collected following each workshop. A process evaluation will assess implementation using an adapted Normalisation Measure Development (NoMAD) questionnaire and qualitative interviews. An economic feasibility analysis will inform a future economic evaluation. Discussion This study will allow us to test and further develop a novel evidenced-based complex intervention aimed at general practice teams to expedite the diagnosis of cancer in primary care. The results from this study will inform the future design of a full-scale definitive phase III trial. Trial registration ClinicalTrials.gov NCT04823559. </jats:sec

Charged and Hydrophobic Surfaces on the A Chain of Shiga-Like Toxin 1 Recognize the C-Terminal Domain of Ribosomal Stalk Proteins

Shiga-like toxins are ribosome-inactivating proteins (RIP) produced by pathogenic E. coli strains that are responsible for hemorrhagic colitis and hemolytic uremic syndrome. The catalytic A1 chain of Shiga-like toxin 1 (SLT-1), a representative RIP, first docks onto a conserved peptide SD[D/E]DMGFGLFD located at the C-terminus of all three eukaryotic ribosomal stalk proteins and halts protein synthesis through the depurination of an adenine base in the sarcin-ricin loop of 28S rRNA. Here, we report that the A1 chain of SLT-1 rapidly binds to and dissociates from the C-terminal peptide with a monomeric dissociation constant of 13 µM. An alanine scan performed on the conserved peptide revealed that the SLT-1 A1 chain interacts with the anionic tripeptide DDD and the hydrophobic tetrapeptide motif FGLF within its sequence. Based on these 2 peptide motifs, SLT-1 A1 variants were generated that displayed decreased affinities for the stalk protein C-terminus and also correlated with reduced ribosome-inactivating activities in relation to the wild-type A1 chain. The toxin-peptide interaction and subsequent toxicity were shown to be mediated by cationic and hydrophobic docking surfaces on the SLT-1 catalytic domain. These docking surfaces are located on the opposite face of the catalytic cleft and suggest that the docking of the A1 chain to SDDDMGFGLFD may reorient its catalytic domain to face its RNA substrate. More importantly, both the delineated A1 chain ribosomal docking surfaces and the ribosomal peptide itself represent a target and a scaffold, respectively, for the design of generic inhibitors to block the action of RIPs

Use of anthropogenic material affects bird nest arthropod community structure: influence of urbanisation, and consequences for ectoparasites and fledging success

Nests are a critically important factor in determining the breeding success of many species of birds. Nevertheless, we have surprisingly little understanding of how local environment helps shape materials used in construction, how this differs among related species using similar nest sites, or if materials used directly or indirectly influence the numbers of offspring successfully reared. We also have little understanding of any potential links between nest construction and the assemblage of invertebrates which inhabit the nest and in particular, with ectoparasites. We addressed these questions by monitoring the success rates of nest-box using Blue Tits Cyanistes caeruleus and Great Tits Parus major, from rural, urban greenspace and urban garden settings. We collected used nests, identified arthropods present, and measured the proportions of highly processed anthropogenic materials used in their construction. Some 25% of Great Tit nest materials were of an anthropogenic source and this was consistent across habitats, while Blue Tits used little (1-2%) except in gardens (~16%), suggesting that Great Tits preferentially sought out these materials. In fledged nests, increasing use of anthropogenic material was associated with lower general arthropod diversity and ectoparasite predator abundance (Blue Tits only) but higher levels of Siphonapterans (fleas). Higher arthropod diversity was associated with lower flea numbers, suggesting that increased diversity played a role in limiting flea numbers. No direct link was found between breeding success and either anthropogenic material usage, or arthropod diversity and abundance. However, breeding success declined with increasing urbanisation in both species and increased with nest weight in Blue Tits. The interplay between urbanisation and bird ecology is complex; our work shows that subtle anthropogenic influences may have indirect and unexpected consequences for urban birds

The GacA global regulator is required for the appropriate expression of Erwinia chrysanthemi 3937 pathogenicity genes during plant infection

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