Procedural confidence in hospital based practitioners: implications for the training and practice of doctors at all grades

<p>Abstract</p> <p>Background</p> <p>Medical doctors routinely undertake a number of practical procedures and these should be performed competently. The UK Postgraduate Medical Education and Training Board (PMETB) curriculum lists the procedures trainees should be competent in. We aimed to describe medical practitioner's confidence in their procedural skills, and to define which practical procedures are important in current medical practice.</p> <p>Methods</p> <p>A cross sectional observational study was performed measuring procedural confidence in 181 hospital practitioners at all grades from 2 centres in East Anglia, England.</p> <p>Results</p> <p>Both trainees and consultants provide significant service provision. SpR level doctors perform the widest range and the highest median number of procedures per year. Most consultants perform few if any procedures, however some perform a narrow range at high volume. Cumulative confidence for the procedures tested peaks in the SpR grade. Five key procedures (central line insertion, lumbar puncture, pleural aspiration, ascitic aspiration, and intercostal drain insertion) are the most commonly performed, are seen as important generic skills, and correspond to the total number of procedures for which confidence can be maintained. Key determinants of confidence are gender, number of procedures performed in the previous year and total number of procedures performed.</p> <p>Conclusion</p> <p>The highest volume of service requirement is for six procedures. The procedural confidence is dependent upon gender, number of procedures performed in the previous year and total number of procedures performed. This has implications for those designing the training curriculum and with regards the move to shorten the duration of training.</p

CRISPR-delivery particles targeting nuclear receptor-interacting protein 1 (Nrip1) in adipose cells to enhance energy expenditure

RNA-guided, engineered nucleases derived from the prokaryotic adaptive immune system CRISPR-Cas represent a powerful platform for gene deletion and editing. When used as a therapeutic approach, direct delivery of Cas9 protein and single-guide RNA (sgRNA) could circumvent the safety issues associated with plasmid delivery and therefore represents an attractive tool for precision genome engineering. Gene deletion or editing in adipose tissue to enhance its energy expenditure, fatty acid oxidation, and secretion of bioactive factors through a browning process presents a potential therapeutic strategy to alleviate metabolic disease. Here, we developed CRISPR-delivery particles, denoted CriPs, composed of nano-size complexes of Cas9 protein and sgRNA that are coated with an amphipathic peptide called Endo-Porter that mediates entry into cells. Efficient CRISPR-Cas9-mediated gene deletion of ectopically expressed GFP by CriPs was achieved in multiple cell types, including a macrophage cell line, primary macrophages, and primary pre-adipocytes. Significant GFP loss was also observed in peritoneal exudate cells with minimum systemic toxicity in GFP-expressing mice following intraperitoneal injection of CriPs containing Gfp-targeting sgRNA. Furthermore, disruption of a nuclear co-repressor of catabolism, the Nrip1 gene, in white adipocytes by CriPs enhanced adipocyte browning with a marked increase of uncoupling protein 1 (UCP1) expression. Of note, the CriP-mediated Nrip1 deletion did not produce detectable off-target effects. We conclude that CriPs offer an effective Cas9 and sgRNA delivery system for ablating targeted gene products in cultured cells and in vivo, providing a potential therapeutic strategy for metabolic disease

Multi-year chemical composition of the fine-aerosol fraction in Athens, Greece, with emphasis on the contribution of residential heating in wintertime

In an attempt to take effective action towards mitigating pollution episodes in Athens, precise knowledge of PM2.5 composition and its sources is a prerequisite. Thus, a 2-year chemical composition dataset from aerosol samples collected in an urban background site in central Athens from December 2013 to March 2016 has been obtained and a positive matrix factorization (PMF) was applied in order to identify and apportion fine aerosols to their sources. A total of 850 aerosol samples were collected on a 12 to 24&thinsp;h basis and analyzed for major ions, trace elements, and organic and elemental carbon, allowing us to further assess the impact of residential heating as a source of air pollution over Athens.The ionic and carbonaceous components were found to constitute the major fraction of the PM2.5 aerosol mass. The annual contribution of the ion mass (IM), particulate organic mass (POM), dust, elemental carbon (EC), and sea salt (SS) was calculated at 31&thinsp;%, 38&thinsp;%, 18&thinsp;%, 8&thinsp;%, and 3&thinsp;%, respectively, and exhibited considerable seasonal variation. In winter, the share of IM was estimated down to 23&thinsp;%, with POM&thinsp;+ EC being the dominant component accounting for 52&thinsp;% of the PM2.5 mass, while in summer, IM (42&thinsp;%) and carbonaceous aerosols (41&thinsp;%) contributed almost equally.Results from samples collected on a 12&thinsp;h basis (day and night) during the three intensive winter campaigns indicated the impact of heating on the levels of a series of compounds. Indeed, PM2.5, EC, POM, NO3−, C2O42−, non sea salt (nss) K+ and selected trace metals including Cd and Pb were increased by up to a factor of 4 in the night compared to the day, highlighting the importance of heating on air quality in Athens. Furthermore, in order to better characterize wintertime aerosol sources and quantify the impact of biomass burning on PM2.5 levels, source apportionment was performed. The data can be interpreted on the basis of six sources, namely biomass burning (31&thinsp;%), vehicular emissions (19&thinsp;%), heavy oil combustion (7&thinsp;%), regional secondary (21&thinsp;%), marine aerosols (9&thinsp;%), and dust particles (8&thinsp;%). Regarding night-to-day patterns their contributions shifted from 19&thinsp;%, 19&thinsp;%, 8&thinsp;%, 31&thinsp;%, 12&thinsp;%, and 10&thinsp;% of the PM2.5 mass during day to 39&thinsp;%, 19&thinsp;%, 6&thinsp;%, 14&thinsp;%, 7&thinsp;%, and 7&thinsp;% during the night, underlining the significance of biomass burning as the main contributor to fine particle levels during nighttime in winter.</p

CRISPR-enhanced human adipocyte \u27browning\u27 as cell therapy for metabolic disease [preprint]

Obesity and type 2 diabetes (T2D) are associated with poor tissue responses to insulin [1,2], disturbances in glucose and lipid fluxes [3-5] and comorbidities including steatohepatitis [6] and cardiovascular disease [7,8]. Despite extensive efforts at prevention and treatment [9,10], diabetes afflicts over 400 million people worldwide [11]. Whole body metabolism is regulated by adipose tissue depots [12-14], which include both lipid-storing white adipocytes and less abundant \u27brown\u27 and \u27brite/beige\u27 adipocytes that express thermogenic uncoupling protein UCP1 and secrete factors favorable to metabolic health [15-18]. Application of clustered regularly interspaced short palindromic repeats (CRISPR) gene editing [19,20] to enhance \u27browning\u27 of white adipose tissue is an attractive therapeutic approach to T2D. However, the problems of cell-selective delivery, immunogenicity of CRISPR reagents and long term stability of the modified adipocytes are formidable. To overcome these issues, we developed methods that deliver complexes of SpyCas9 protein and sgRNA ex vivo to disrupt the thermogenesis suppressor gene NRIP1 [21,22] with near 100% efficiency in human or mouse adipocytes. NRIP1 gene disruption at discrete loci strongly ablated NRIP1 protein and upregulated expression of UCP1 and beneficial secreted factors, while residual Cas9 protein and sgRNA were rapidly degraded. Implantation of the CRISPR-enhanced human or mouse brown-like adipocytes into high fat diet fed mice decreased adiposity and liver triglycerides while enhancing glucose tolerance compared to mice implanted with unmodified adipocytes. These findings advance a therapeutic strategy to improve metabolic homeostasis through CRISPR-based genetic modification of human adipocytes without exposure of the recipient to immunogenic Cas9 or delivery vectors

Sources and processes that control the submicron organic aerosol composition in an urban Mediterranean environment (Athens): a high temporal-resolution chemical composition measurement study

Submicron aerosol chemical composition was studied during a year-long period (26 July 2016–31 July 2017) and two wintertime intensive campaigns (18 December 2013–21 February 2014 and 23 December 2015–17 February 2016), at a central site in Athens, Greece, using an Aerosol Chemical Speciation Monitor (ACSM). Concurrent measurements included a particle-into-liquid sampler (PILS-IC), a scanning mobility particle sizer (SMPS), an AE-33 Aethalometer, and ion chromatography analysis on 24 or 12&thinsp;h filter samples. The aim of the study was to characterize the seasonal variability of the main submicron aerosol constituents and decipher the sources of organic aerosol (OA). Organics were found to contribute almost half of the submicron mass, with 30&thinsp;min resolution concentrations during wintertime reaching up to 200&thinsp;µg&thinsp;m−3. During winter (all three campaigns combined), primary sources contributed about 33&thinsp;% of the organic fraction, and comprised biomass burning (10&thinsp;%), fossil fuel combustion (13&thinsp;%), and cooking (10&thinsp;%), while the remaining 67&thinsp;% was attributed to secondary aerosol. The semi-volatile component of the oxidized organic aerosol (SV-OOA; 22&thinsp;%) was found to be clearly linked to combustion sources, in particular biomass burning; part of the very oxidized, low-volatility component (LV-OOA; 44&thinsp;%) could also be attributed to the oxidation of emissions from these primary combustion sources. These results, based on the combined contribution of biomass burning organic aerosol (BBOA) and SV-OOA, indicate the importance of increased biomass burning in the urban environment of Athens as a result of the economic recession. During summer, when concentrations of fine aerosols are considerably lower, more than 80&thinsp;% of the organic fraction is attributed to secondary aerosol (SV-OOA 31&thinsp;% and LV-OOA 53&thinsp;%). In contrast to winter, SV-OOA appears to result from a well-mixed type of aerosol that is linked to fast photochemical processes and the oxidation of primary traffic and biogenic emissions. Finally, LV-OOA presents a more regional character in summer, owing to the oxidation of OA over the period of a few days.</p

Global patient outcomes after elective surgery: prospective cohort study in 27 low-, middle- and high-income countries.

BACKGROUND: As global initiatives increase patient access to surgical treatments, there remains a need to understand the adverse effects of surgery and define appropriate levels of perioperative care. METHODS: We designed a prospective international 7-day cohort study of outcomes following elective adult inpatient surgery in 27 countries. The primary outcome was in-hospital complications. Secondary outcomes were death following a complication (failure to rescue) and death in hospital. Process measures were admission to critical care immediately after surgery or to treat a complication and duration of hospital stay. A single definition of critical care was used for all countries. RESULTS: A total of 474 hospitals in 19 high-, 7 middle- and 1 low-income country were included in the primary analysis. Data included 44 814 patients with a median hospital stay of 4 (range 2-7) days. A total of 7508 patients (16.8%) developed one or more postoperative complication and 207 died (0.5%). The overall mortality among patients who developed complications was 2.8%. Mortality following complications ranged from 2.4% for pulmonary embolism to 43.9% for cardiac arrest. A total of 4360 (9.7%) patients were admitted to a critical care unit as routine immediately after surgery, of whom 2198 (50.4%) developed a complication, with 105 (2.4%) deaths. A total of 1233 patients (16.4%) were admitted to a critical care unit to treat complications, with 119 (9.7%) deaths. Despite lower baseline risk, outcomes were similar in low- and middle-income compared with high-income countries. CONCLUSIONS: Poor patient outcomes are common after inpatient surgery. Global initiatives to increase access to surgical treatments should also address the need for safe perioperative care. STUDY REGISTRATION: ISRCTN5181700

A direct method to quantify methanol-soluble organic carbon for brown carbon absorption studies

The current research provides a newly developed method to quantify methanol-soluble organic carbon (MeS_OC) in aerosol samples. This analytical procedure allows an accurate separation of MeS-OC component, which is critical for the calculation of mass absorption efficiency (MAE) of ambient Brown Carbon (BrC) and consequently its climate relevant potential. The method includes extraction, filtering and condensation stages, leading to the preparation of a highly concentrated product in which MeS-OC can be precisely quantified by a Sunset Carbon Analyzer in a single analysis step. This method can be applied on aerosol collected using either high or low volume samplers, since a relatively small filter area is required for the determination. Furthermore, it eliminates any misestimation of the MeS-OC mass that may appear in other reported techniques that don't seem to include the precise separation of methanol-soluble fraction in their quantification process. • The mass quantification of methanol-soluble organic carbon is essential, contributing up to 50% to the absorptivity of organic aerosol (BrC) at shorter wavelengths. • The method provides a direct measurement of methanol-soluble aerosol components, resolving any potential uncertainties of previously applied methods. • The adoption of this direct quantification approach leads to a rationalization of past MAE estimates for BrC with implications for radiative transfer models

Can the "Euro-leaf" logo affect consumers' willingness-to-buy and willingness-to-pay for organic food and attract consumers' preferences? An empirical study in Greece

The "Euro-leaf" organic certification logo was adopted and made compulsory by the European Union (EU) a few years ago; the level of consumers' recognition of this logo has been explored. This paper provides important insights into the effectiveness of the logo in the Greek market. The "Euro-leaf" logo was compared with the two previous EU organic logos; i.e., the voluntary "Organic Farming" and the withdrawn "Bio". In total, 472 face-to-face interviews were conducted using actual presentations of five officially certified food products. The aim of this research was to investigate the consumers' willingness-to-buy (WTB), willingness-to-pay (WTP), and their preference towards each of the three logos used for the certification of organic products. Our analysis concludes that for the time being the new logo has failed to develop into a powerful instrument for affecting consumers' WTB and WTP. Furthermore, it was found to have been the least influential factor that determined their preferences. Design changes and improvements might be necessary in order to better communicate the organic food message.</p

High-content phenotypic screen to identify small molecule enhancers of Parkin-dependent ubiquitination and mitophagy

Mitochondrial dysfunction and aberrant mitochondrial homeostasis are key aspects of Parkinson's disease (PD) pathophysiology. Mutations in PINK1 and Parkin proteins lead to autosomal recessive PD, suggesting that defective mitochondrial clearance via mitophagy is key in PD etiology. Accelerating the identification and/or removal of dysfunctional mitochondria could therefore provide a disease-modifying approach to treatment. To that end, we performed a high-content phenotypic screen (HCS) of ∼125,000 small molecules to identify compounds that positively modulate mitochondrial accumulation of the PINK1-Parkin-dependent mitophagy initiation marker p-Ser65-Ub in Parkin haploinsufficiency (Parkin +/R275W) human fibroblasts. Following confirmatory counter-screening and orthogonal assays, we selected compounds of interest that enhance mitophagy-related biochemical and functional endpoints in patient-derived fibroblasts. Identification of inhibitors of the ubiquitin-specific peptidase and negative regulator of mitophagy USP30 within our hits further validated our approach. The compounds identified in this work provide a novel starting point for further investigation and optimization

Is In-Vivo laparoscopic simulation learning a step forward in the Undergraduate Surgical Education?

Background Essentials Skills in the Management of Surgical Cases – ESMSC is an International Combined Applied Surgical Science and Wet Lab course addressed at the Undergraduate level. Laparoscopic Skills is a fundamental element of Surgical Education and various Simulation-Based Learning (SBL) models have been endorsed. This study aims to explore if there is any significant difference in delegates&apos; performance depending on whether they completed In Vivo module prior to the equivalent in the laparoscopic simulator. Materials and methods 37 Medical Students from various EU countries were divided in 2 groups, and both completed the “Fundamentals in Laparoscopic Surgery” module in the Dry-lab Laparoscopic Simulator as well as the same module “In Vivo” on a swine model. Group A (18 students, 48.6%) completed the “Fundamentals in Laparoscopic Surgery - FLS” module prior to the “In Vivo”, whereas group B completed the “In Vivo” module first. Direct Observation of Procedural Skills (DOPS) were used to assess delegates&apos; performance. Results The mean DOPS scores for the “FLS” and “In Vivo” models were 2.27 ± 0.902 and 2.03 ± 0.833, respectively, and the delegates&apos; performance was not statistically significantly different between them (p = 0.128). There was no statistically significant difference in the scores among different gender, year of study, school and handedness groups. The alteration in the sequence between Dry-lab “FLS” and “In Vivo” modules did not affect the performance in neither the “FLS” nor the “In Vivo” models. Conclusions The inexpensive, but low-fidelity “FLS” model could serve an equal alternative Simulation-Based Learning model for the early undergraduate training. Our study demonstrated that high fidelity In Vivo simulation for laparoscopic skills does not affect significantly the improvement in the delegates&apos; performance at the undergraduate level. Further studies should be conducted to identify at which stage of training should high fidelity simulation be introduced. © 2017 The Author