Enzymatic assay for urine lactose in the assessment of recent intravenous abuse of buprenorphine

Urine samples were analyzed for lactose to investigate if elevated lactose concentrations indicate recent (<48 hours) intravenous abuse of substances containing lactose as an excipient. Elevated lactose levels were found in samples given by patients who had recently injected substances intravenously, verified by fresh injection marks. Urine lactose assay can support clinical and toxicological findings when assessing substance abuse.Peer reviewe

Interaction between ATM and UAS operators in U-space operations and potential automation benefits

Uncrewed Aircraft Systems (UAS), commonly referred to as drones, are increasingly identified and applied in civil use cases, amongst them delivery of medical support systems, medicine, or hospital samples in urban areas. The rapid usage of drones in such context is enabled through advanced air mobility (AAM) and, in particular in Europe, the envisaged U-space ecosystem. When operating in U-space, airspace users are supported by numerous services, such as Flight Authorization or Conformance Monitoring. The level of automation and the number of available services is foreseen to increase in the coming years and decades, leveraging the U-space ecosystem from service level U1 with basic mandatory services only up to service level U4 with high automation. However, the U-space airspace may be in the vicinity of controlled airspace supervised by air traffic management (ATM) with conventional manned traffic managed and separated by air traffic control. In uncontrolled airspace, currently only non-binding Flight Information Services (FIS) are offered to crewed aircraft by Air Navigation Service Providers (ANSP). Especially in controlled and also in uncontrolled airspace , the (automated) interaction between U-space airspace users and ATM may be required and can improve safety of both crewed and uncrewed airspace users. Such cases include contingencies or emergencies on either part of the airspace, or requests to use the respective other airspace for urgent flight operations. To that aim, the U-space ecosystem is foreseen to be enriched with procedural and collaborative interfaces between U-space and ATM on the one hand, and the dynamic airspace reconfiguration service on the other hand. Still, the interaction could start from direct communication using voice channels and would need to evolve to automated, service-driven requests and responses, in order to ensure effectiveness and scalability. This paper aims to shed light on the various scenarios and use cases in the scope of UAS operations in which the efficient interaction between U-space airspace users and traditional ATM users is most likely necessary. Ongoing and completed research projects as well as reference material issued by e.g. aviation authorities, such as the European Union Aviation Safety Agency (EASA) or the Think Tank of the European Parliament, will be taken into account. The different applications of UAS in U-space are collected and investigated on the possibility or the requirement to interact with ATM. Focus will be given on specific scenarios necessitating close coordination and efficient interaction between U-space users and ATM services. Further, the roles and responsibilities of the actors in these scenarios, i.e. UAS operators, U-space service providers, and air traffic control, will be investigated. In addition, the level of automation and the interaction means is assessed against the current legislative requirements, and potential gaps are identified. The research is complemented with scenarios stemming from the SAFIR-Ready project, tasked by the European research program SESAR to develop advanced (U3) and full (U4) U-space services. The project is investigating requirements for medical transport tasks for drones in urban areas in order to ensure their operational readiness for short-term (emergency) flights. In a final step, the benefits that can be expected from increased automation, i.e. higher service levels of U-space that cover specific societal needs, are discussed. The findings of this paper can be a valuable input to both UAS operators and U-space service providers aiming to conduct AAM operations in effective collaboration with ATM

Measurement error as an explanation for the alcohol harm paradox : analysis of eight cohort studies

Background: Despite reporting lower levels of alcohol consumption, people with lower socio-economic status (SES) experience greater alcohol-related harm. Whether differential biases in the measurement of alcohol use could explain this apparent paradox is unknown. Using alcohol biomarkers to account for measurement error, we examined whether differential exposure to alcohol could explain the socio-economic differences in alcohol mortality. Methods: Participants from eight representative health surveys (n = 52 164, mean age 47.7 years) were linked to mortality data and followed up until December 2016. The primary outcome was alcohol-attributable mortality. We used income and education as proxies for SES. Exposures include self-reported alcohol use and four alcohol biomarkers [serum gamma-glutamyl transferase (available in all surveys), carbohydrate-deficient transferrin, alanine aminotransferase and aspartate aminotransferase (available in subsamples)]. We used shared frailty Cox proportional hazards to account for survey heterogeneity. Results: During a mean follow-up of 20.3 years, totalling 1056 844 person-years, there were 828 alcohol-attributable deaths. Lower SES was associated with higher alcohol mortality despite reporting lower alcohol use. Alcohol biomarkers were associated with alcohol mortality and improved the predictive ability when used in conjunction with self-reported alcohol use. Alcohol biomarkers explained a very small fraction of the socio-economic differences in alcohol mortality, since hazard ratios either slightly attenuated (percent attenuation range 1.0-12.1%) or increased. Conclusions: Using alcohol biomarkers in addition to self-reported alcohol use did not explain the socio-economic differences in alcohol mortality. Differential bias in the measurement of alcohol use is not a likely explanation for the alcohol-harm paradox.Peer reviewe

Modulation of multidrug-resistant clone success in <i>Escherichia coli</i> populations:a longitudinal, multi-country, genomic and antibiotic usage cohort study

BACKGROUND: The effect of antibiotic usage on the success of multidrug-resistant (MDR) clones in a population remains unclear. With this genomics-based molecular epidemiology study, we aimed to investigate the contribution of antibiotic use to Escherichia coli clone success, relative to intra-strain competition for colonisation and infection.METHODS: We sequenced all the available E coli bloodstream infection isolates provided by the British Society for Antimicrobial Chemotherapy (BSAC) from 2012 to 2017 (n=718) and combined these with published data from the UK (2001-11; n=1090) and Norway (2002-17; n=3254). Defined daily dose (DDD) data from the European Centre for Disease Prevention and Control (retrieved on Sept 21, 2021) for major antibiotic classes (β-lactam, tetracycline, macrolide, sulfonamide, quinolone, and non-penicillin β-lactam) were used together with sequence typing, resistance profiling, regression analysis, and non-neutral Wright-Fisher simulation-based modelling to enable systematic comparison of resistance levels, clone success, and antibiotic usage between the UK and Norway.FINDINGS: Sequence type (ST)73, ST131, ST95, and ST69 accounted for 892 (49·3%) of 1808 isolates in the BSAC collection. In the UK, the proportion of ST69 increased between 2001-10 and 2011-17 (p=0·0004), whereas the proportions of ST73 and ST95 did not vary between periods. ST131 expanded quickly after its emergence in 2003 and its prevalence remained consistent throughout the study period (apart from a brief decrease in 2009-10). The extended-spectrum β-lactamase (ESBL)-carrying, globally disseminated MDR clone ST131-C2 showed overall greater success in the UK (154 [56·8%] of 271 isolates in 2003-17) compared with Norway (51 [18·3%] of 278 isolates in 2002-17; p&lt;0·0001). DDD data indicated higher total use of antimicrobials in the UK, driven mainly by the class of non-penicillin β-lactams, which were used between 2·7-times and 5·1-times more in the UK per annum (ratio mean 3·7 [SD 0·8]). This difference was associated with the higher success of the MDR clone ST131-C2 (pseudo-R2 69·1%). A non-neutral Wright-Fisher model replicated the observed expansion of non-MDR and MDR sequence types under higher DDD regimes. INTERPRETATION: Our study indicates that resistance profiles of contemporaneously successful clones can vary substantially, warranting caution in the interpretation of correlations between aggregate measures of resistance and antibiotic usage. Our study further suggests that in countries with low-to-moderate use of antibiotics, such as the UK and Norway, the extent of non-penicillin β-lactam use modulates rather than determines the success of widely disseminated MDR ESBL-carrying E coli clones. Detailed understanding of underlying causal drivers of success is important for improved control of resistant pathogens.FUNDING: Trond Mohn Foundation, Marie Skłodowska-Curie Actions, European Research Council, Royal Society, and Wellcome Trust.</p