A phagocytic route for uptake of double-stranded RNA in RNAi.

RNA interference (RNAi) has a range of physiological functions including as a defence mechanism against viruses. To protect uninfected cells in a multicellular organism, not only a cell-autonomous RNAi response is required but also a systemic one. However, the route of RNA spread in systemic RNAi remains unclear. Here we show that phagocytosis can be a route for double-stranded RNA uptake. Double-stranded RNA expressed in Escherichia coli induces robust RNAi in Drosophila S2 cells, with effectiveness comparable to that of naked dsRNA. We could separate this phagocytic uptake route from that for RNAi induced by naked dsRNA. Therefore, phagocytic uptake of dsRNA offers a potential route for systemic spread of RNAi

Whisker spot patterns: a noninvasive method of individual identification of Australian sea lions (Neophoca cinerea)

Reliable methods for identification of individual animals are advantageous for ecological studies of population demographics and movement patterns. Photographic identification, based on distinguishable patterns, unique shapes, or scars, is an effective technique already used for many species. We tested whether photographs of whisker spot patterns could be used to discriminate among individual Australian sea lion (Neophoca cinerea). Based on images of 53 sea lions, we simulated 5,000 patterns before calculating the probability of duplication in a study population. A total of 99% (± 1.5 SD) of patterns were considered reliable for a population of 50, 98% (± 1.7 SD) for 100, 92% (± 4.7 SD) for 500, and 88% (± 5.7 SD) for 1,000. We tested a semiautomatic approach by matching 16 known individuals at 3 different angles (70°, 90°, and 110°), 2 distances (1 and 2 m), and 6 separate times over a 1-year period. A point-pattern matching algorithm for pairwise comparisons produced 90% correct matches of photographs taken on the same day at 90°. Images of individuals at 1 and 2 m resulted in 89% correct matches, those photographed at different angles and different times (at 90°) resulted in 48% and 73% correct matches, respectively. Our results show that the Chamfer distance transform can effectively be used for individual identification, but only if there is very little variation in photograph angle. This point-pattern recognition application may also work for other otariid species

Eps15 and Dap160 control synaptic vesicle membrane retrieval and synapse development

Epidermal growth factor receptor pathway substrate clone 15 (Eps15) is a protein implicated in endocytosis, endosomal protein sorting, and cytoskeletal organization. Its role is, however, still unclear, because of reasons including limitations of dominant-negative experiments and apparent redundancy with other endocytic proteins. We generated Drosophila eps15-null mutants and show that Eps15 is required for proper synaptic bouton development and normal levels of synaptic vesicle (SV) endocytosis. Consistent with a role in SV endocytosis, Eps15 moves from the center of synaptic boutons to the periphery in response to synaptic activity. The endocytic protein, Dap160/intersectin, is a major binding partner of Eps15, and eps15 mutants phenotypically resemble dap160 mutants. Analyses of eps15 dap160 double mutants suggest that Eps15 functions in concert with Dap160 during SV endocytosis. Based on these data, we hypothesize that Eps15 and Dap160 promote the efficiency of endocytosis from the plasma membrane by maintaining high concentrations of multiple endocytic proteins, including dynamin, at synapses

A calcium channel or angiotensin converting enzyme inhibitor/angiotensin receptor blocker regime to reduced blood pressure variability in acute ischaemic stroke (CAARBS): A feasibility trial

Background: Trials of lowering blood pressure in patients with acute ischaemic stroke not undergoing thrombolysis have not demonstrated improved outcomes with intervention. Rather than absolute levels, it may be that blood pressure variability is important. However, there are no prospective randomised trials investigating the benefit of reducing blood pressure variability in this patient group. Aims: The primary aim of this trial was to determine the feasibility of recruitment to a randomised trial investigating the effect of different antihypertensive medications on blood pressure variability. Methods: CAARBS was a multi-centre, open-label, randomised parallel group controlled feasibility trial. Adults with a first mild-moderate ischaemic stroke or transient ischaemic attack, requiring antihypertensive therapy for secondary prevention, were randomised to a calcium channel blocker or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. Blood pressure and variability were measured at baseline, three weeks, and three months. Compliance with measurements and treatment was monitored. Results: Fourteen patients were recruited to the trial (0.6% of those screened), nine of whom completed follow-up. The majority of patients screened (98.1%) were ineligible. Compliance with the intervention was good, as were measurement completion rates (88.9% or higher in all cases except ambulatory measurements). No major adverse events were recorded. Conclusions: Recruitment to the trial was difficult due to patient ineligibility, suggesting that the current protocol is unlikely to be successful if scaled for a definitive trial. However, the intervention was safe, and compliance was good, suggesting a future trial with modified eligibility criteria could be successful. Trial registration: ISRCTN10853487

Golf participation after rotator cuff repair: functional outcomes, rate of return and factors associated with return to play

Background Golf is a popular sport involving overhead activity and engagement of the rotator cuff (RC). This study aimed to determine to what level golfers were able to return to golf following RC repair, the barriers to them returning to golf and factors associated with their failure to return to golf. Methods Patients preoperatively identifying as golfers undergoing RC repair at the study centre from 2012 to 2020 were retrospectively followed up with to assess their golf-playing status, performance and frequency of play and functional and quality of life (QoL) outcomes. Results Forty-seven golfers (40 men [85.1%] and 7 women [14.9%]) with a mean age of 56.8 years met the inclusion criteria, and 80.1% were followed up with at a mean of 27.1 months postoperatively. Twenty-nine patients (76.3%) had returned to golf with a mean handicap change of +1.0 (P=0.291). Golf frequency decreased from a mean of 1.8 rounds per week preinjury to 1.5 rounds per week postoperatively (P=0.052). The EuroQol 5-dimension 5-level (EQ-5D-5L) index and visual analog scale (EQ-VAS) score were significantly greater in those returning to golf (P=0.024 and P=0.002), although functional outcome measures were not significantly different. The primary barriers to return were ipsilateral shoulder dysfunction (78%) and loss of the habit of play (22%). Conclusions Golfers were likely (76%) to return to golf following RC repair, including mostly to their premorbid performance level with little residual symptomatology. Return to golf was associated with a greater QoL. Persistent subjective shoulder dysfunction (78%) was the most common barrier to returning to golf. Level of evidence Level IV

Supplying the wildlife trade as a livelihood strategy in a biodiversity hotspot

Much of the global wildlife trade is sourced from biodiversity-rich developing countries. These often have high levels of poverty and habitat loss, particularly in rural areas where many depend on natural resources. However, wildlife collection may incentivize local people to conserve habitats that support their livelihoods. Here we examined the contribution of the commercial collection of live animals to rural livelihoods in Madagascar, one of the world’s most important biodiversity hotspots. Using questionnaires, we investigated the prevalence, profitability relative to other livelihood activities, and local importance of the trade, and its capacity to provide incentives for conservation. Thirteen percent of households were engaged in live animal collection in the study area (~5% trapped reptiles and amphibians and the remainder trapped invertebrates). This formed part of a diverse livelihood strategy, and was more profitable than other activities (in terms of returns per unit of effort), with median earnings of ~US$100 per season (~25% of Gross National Income per year). However, trapping was part-time, usually undertaken by poorer members of the community, and often perceived as opportunistic, risky, and financially unreliable. Further, trappers and nontrappers held similar perceptions regarding conservation, suggesting wildlife trade currently does not incentivize enhanced stewardship of traded species and their habitats. Our study brings together a range of methodologies to present the most comprehensive insights into livelihoods and conservation in poor rural communities involved in the commercial collection of live animals to supply international trade. This improved understanding of the wider socioeconomic dimensions of wildlife trade can inform policy and management interventions for both the threats and opportunities associated with global trade in biodiversity both in Madagascar and more generally

Conservative management versus open reduction and internal fixation for mid-shaft clavicle fractures in adults - The Clavicle Trial: Study protocol for a multicentre randomized controlled trial

Background: Clavicle fractures account for around 4% of all fractures and up to 44% of fractures of the shoulder girdle. Fractures of the middle third (or mid-shaft) account for approximately 80% of all clavicle fractures. Management of this group of fractures is often challenging and the outcome can be unsatisfactory. In particular it is not clear whether surgery produces better outcomes than non-surgical management. Currently there is much variation in the use of surgery and a lack of good quality evidence to inform our decision.Methods/Design: We aim to undertake a multicentre randomised controlled trial evaluating the effectiveness and safety of conservative management versus open reduction and internal fixation for displaced mid-shaft clavicle fractures in adults. Surgical treatment will be performed using the Acumed clavicle fixation system. Conservative management will consist of immobilisation in a sling at the side in internal rotation for 6 weeks or until clinical or radiological union. We aim to recruit 300 patients. These patients will be followed-up for at least 9 months. The primary endpoint will be the rate of non-union at 3 months following treatment. Secondary endpoints will be limb function measured using the Constant-Murley Score and the Disabilities of the Arm, Shoulder and Hand (DASH) Score at 3 and 9 months post-operatively.Discussion: This article presents the protocol for a multicentre randomised controlled trial. It gives extensive details of, and the basis for, the chosen methods, and describes the key measures taken to avoid bias and to ensure validity.Trial Registration: United Kingdom Clinical Research Network ID: 8665. The date of registration of the trial is 07/09/2006. The date the first patient was recruited is 18/12/2007. © 2011 Longo et al; licensee BioMed Central Ltd

REFERQUAL: A pilot study of a new service quality assessment instrument in the GP Exercise Referral scheme setting

Background The development of an instrument accurately assessing service quality in the GP Exercise Referral Scheme (ERS) industry could potentially inform scheme organisers of the factors that affect adherence rates leading to the implementation of strategic interventions aimed at reducing client drop-out. Methods A modified version of the SERVQUAL instrument was designed for use in the ERS setting and subsequently piloted amongst 27 ERS clients. Results Test re-test correlations were calculated via Pearson's 'r' or Spearman's 'rho', depending on whether the variables were Normally Distributed, to show a significant (mean r = 0.957, SD = 0.02, p < 0.05; mean rho = 0.934, SD = 0.03, p < 0.05) relationship between all items within the questionnaire. In addition, satisfactory internal consistency was demonstrated via Cronbach's 'α'. Furthermore, clients responded favourably towards the usability, wording and applicability of the instrument's items. Conclusion REFERQUAL is considered to represent promise as a suitable tool for future evaluation of service quality within the ERS community. Future research should further assess the validity and reliability of this instrument through the use of a confirmatory factor analysis to scrutinise the proposed dimensional structure

Wildlife supply chains in Madagascar from local collection to global export

International trade in wildlife is a complex multi-billion dollar industry. To supply it, many animals are extracted from the wild, sourced from biodiversity-rich, developing countries. Whilst the trade has far-reaching implications for wildlife protection, there is limited information regarding the socio-economic implications in supply countries. Consequently, a better understanding of the costs and benefits of wildlife supply chains, for both livelihoods and conservation, is required to enhance wildlife trade management and inform its regulation. Using Madagascar as a case study, we used value chain analysis to explore the operation of legal wildlife trade on a national scale; we estimate the number of actors involved, the scale, value and profit distribution along the chain, and explore management options. We find that the supply of wildlife provided economic benefits to a number of actors, from local collectors, to intermediaries, exporters and national authorities. CITES-listed reptiles and amphibians comprised a substantial proportion of the quantity and value of live animal exports with a total minimum export value of 230,795USD per year. Sales prices of reptiles and amphibians increased over 100-fold between local collectors and exporters, with exporters capturing ~92% of final export price (or 57% when their costs are deducted). However, exporters shouldered the largest costs and financial risks. Local collectors obtained ~1.4% of the final sales price, and opportunities for poverty alleviation and incentives for sustainable management from the trade appear to be limited. Promoting collective management of species harvests at the local level may enhance conservation and livelihood benefits. However, this approach requires consideration of property rights and land-tenure systems. The complex and informal nature of some wildlife supply chains make the design and implementation of policy instruments aimed at enhancing conservation and livelihoods challenging. Nevertheless, value chain analysis provides a mechanism by which management actions can be more precisely targeted