Identifying potential drug targets in the kinomes of two monogenean species.

Protein kinases are enzymes involved in essential biological processes such as signal transduction, transcription, metabolism, and the cell cycle. Human kinases are targets for several drugs approved by the US Food and Drug Administration. Therefore, the identification and classification of kinases in other organisms, including pathogenic parasites, is an interesting subject of study. Monogeneans are platyhelminths, mainly ectoparasites, capable of causing health problems in farmed fish. Although some genomes and transcriptomes are available for monogenean species, their full repertoire of kinases is unknown. The aim of this study was to identify and classify the putative kinases in the transcriptomes of two monogeneans, Rhabdosynochus viridisi and Scutogyrus longicornis, and then to predict potential monogenean drug targets (MDTs) and selective inhibitor drugs using computational approaches. Monogenean kinases having orthologs in the lethal phenotype of C. elegans but not in fish or humans were considered MDTs. A total of 160 and 193 kinases were identified in R. viridisi and S. longicornis, respectively. Of these, 22 kinases, belonging mainly to the major groups CAMK, AGC, and TK, were classified as MDTs, five of which were evaluated further. Molecular docking analysis indicated that dihydroergotamine, ergotamine, and lomitapide have the highest affinity for the kinases BRSK and MEKK1. These well-known drugs could be evaluated in future studies for potential repurposing as anti-monogenean agents. The present study contributes valuable data for the development of new antiparasitic candidates for finfish aquaculture.

A quantitative evaluation of aerosol generation during cardiopulmonary resuscitation.

It is unclear if cardiopulmonary resuscitation is an aerosol-generating procedure and whether this poses a risk of airborne disease transmission to healthcare workers and bystanders. Use of airborne transmission precautions during cardiopulmonary resuscitation may confer rescuer protection but risks patient harm due to delays in commencing treatment. To quantify the risk of respiratory aerosol generation during cardiopulmonary resuscitation in humans, we conducted an aerosol monitoring study during out-of-hospital cardiac arrests. Exhaled aerosol was recorded using an optical particle sizer spectrometer connected to the breathing system. Aerosol produced during resuscitation was compared with that produced by control participants under general anaesthesia ventilated with an equivalent respiratory pattern to cardiopulmonary resuscitation. A porcine cardiac arrest model was used to determine the independent contributions of ventilatory breaths, chest compressions and external cardiac defibrillation to aerosol generation. Time-series analysis of participants with cardiac arrest (n = 18) demonstrated a repeating waveform of respiratory aerosol that mapped to specific components of resuscitation. Very high peak aerosol concentrations were generated during ventilation of participants with cardiac arrest with median (IQR [range]) 17,926 (5546-59,209 [1523-242,648]) particles.l-1 , which were 24-fold greater than in control participants under general anaesthesia (744 (309-2106 [23-9099]) particles.l-1 , p < 0.001, n = 16). A substantial rise in aerosol also occurred with cardiac defibrillation and chest compressions. In a complimentary porcine model of cardiac arrest, aerosol recordings showed a strikingly similar profile to the human data. Time-averaged aerosol concentrations during ventilation were approximately 270-fold higher than before cardiac arrest (19,410 (2307-41,017 [104-136,025]) vs. 72 (41-136 [23-268]) particles.l-1 , p = 0.008). The porcine model also confirmed that both defibrillation and chest compressions generate high concentrations of aerosol independent of, but synergistic with, ventilation. In conclusion, multiple components of cardiopulmonary resuscitation generate high concentrations of respiratory aerosol. We recommend that airborne transmission precautions are warranted in the setting of high-risk pathogens, until the airway is secured with an airway device and breathing system with a filter.

A quantitative evaluation of aerosol generation during awake tracheal intubation.

Aerosol-generating procedures are medical interventions considered high risk for transmission of airborne pathogens. Tracheal intubation of anaesthetised patients is not high risk for aerosol generation; however, patients often perform respiratory manoeuvres during awake tracheal intubation which may generate aerosol. To assess the risk, we undertook aerosol monitoring during a series of awake tracheal intubations and nasendoscopies in healthy participants. Sampling was undertaken within an ultraclean operating theatre. Procedures were performed and received by 12 anaesthetic trainees. The upper airway was topically anaesthetised with lidocaine and participants were not sedated. An optical particle sizer continuously sampled aerosol. Passage of the bronchoscope through the vocal cords generated similar peak median (IQR [range]) aerosol concentrations to coughing, 1020 (645-1245 [120-48,948]) vs. 1460 (390-2506 [40-12,280]) particles.l-1 respectively, p = 0.266. Coughs evoked when lidocaine was sprayed on the vocal cords generated 91,700 (41,907-166,774 [390-557,817]) particles.l-1 which was significantly greater than volitional coughs (p < 0.001). For 38 nasendoscopies in 12 participants, the aerosol concentrations were relatively low, 180 (120-525 [0-9552]) particles.l-1 , however, five nasendoscopies generated peak aerosol concentrations greater than a volitional cough. Awake tracheal intubation and nasendoscopy can generate high concentrations of respiratory aerosol. Specific risks are associated with lidocaine spray of the larynx, instrumentation of the vocal cords, procedural coughing and deep breaths. Given the proximity of practitioners to patient-generated aerosol, airborne infection control precautions are appropriate when undertaking awake upper airway endoscopy (including awake tracheal intubation, nasendoscopy and bronchoscopy) if respirable pathogens cannot be confidently excluded.

A high-density 3-dimensional culture model of human glioblastoma for rapid screening of therapeutic resistance.

Glioblastoma is among the most lethal cancers, with no known cure. A multitude of therapeutics are being developed or in clinical trials, but currently there are no ways to predict which patient may benefit the most from which drug. Assays that allow prediction of the tumor's response to anti-cancer drugs may improve clinical decision-making. Here, we present a high-density 3D primary cell culture model for short-term testing from resected glioblastoma tissue that is set up on the day of surgery, established within 7 days and viable for at least 3 weeks. High-density 3D cultures contain tumor and host cells, including microglia, and retain key histopathological characteristics of their parent tumors, including proliferative activity, expression of the marker GFAP, and presence of giant cells. This provides a proof-of-concept that 3D primary cultures may be useful to model tumor heterogeneity. Importantly, we show that high-density 3D cultures can be used to test chemotherapy response within a 2-3-week timeframe and are predictive of patient response to Temozolomide therapy. Thus, primary high-density 3D cultures could be a useful tool for brain cancer research and prediction of therapeutic resistance.

Clinical features and overall survival of osteosarcoma of the mandible.

Osteosarcoma is the most common bone sarcoma and is typically found in the distal femur, proximal tibia, and proximal humerus. While several factors are known to influence survival, less is known regarding the influence of primary tumor location. This study describes the clinical features and prognosis of mandibular osteosarcoma. The SEER database was utilized to identify cases of mandibular osteosarcoma diagnosed between 2004 and 2015. Sex, age, grade, histological subtype, tumor size, tumor extension, presence of metastasis at diagnosis, and therapeutic intervention were determined. Osteosarcomas originating from other sites were assessed for comparison. There were 164 cases of mandibular osteosarcoma identified, representing 5.5% of all surveyed osteosarcomas. The 2-, 5-, and 10-year overall survival rates were 79.9%, 65.6% and 58.5%, respectively. Survival was worse for patients with older age, larger tumor size, metastatic disease, and absence of surgical resection. Compared to other sites, mandibular osteosarcomas were significantly smaller tumors and were far less likely to metastasize. Mandibular osteosarcoma manifested at an older age than the more common extremity osteosarcomas and presented with smaller tumors. Rates of metastasis of jaw osteosarcoma were much lower than osteosarcoma found in the extremities, while mortality rates were comparable.

On-microscope staging of live cells reveals changes in the dynamics of transcriptional bursting during differentiation.

Determining the mechanisms by which genes are switched on and off during development is a key aim of current biomedical research. Gene transcription has been widely observed to occur in a discontinuous fashion, with short bursts of activity interspersed with periods of inactivity. It is currently not known if or how this dynamic behaviour changes as mammalian cells differentiate. To investigate this, using an on-microscope analysis, we monitored mouse α-globin transcription in live cells throughout erythropoiesis. We find that changes in the overall levels of α-globin transcription are most closely associated with changes in the fraction of time a gene spends in the active transcriptional state. We identify differences in the patterns of transcriptional bursting throughout differentiation, with maximal transcriptional activity occurring in the mid-phase of differentiation. Early in differentiation, we observe increased fluctuation in transcriptional activity whereas at the peak of gene expression, in early erythroblasts, transcription is relatively stable. Later during differentiation as α-globin expression declines, we again observe more variability in transcription within individual cells. We propose that the observed changes in transcriptional behaviour may reflect changes in the stability of active transcriptional compartments as gene expression is regulated during differentiation.

Anaesthetists' current practice and perceptions of aerosol-generating procedures: a mixed-methods study.

The evidence base surrounding the transmission risk of 'aerosol-generating procedures' has evolved primarily through quantification of aerosol concentrations during clinical practice. Consequently, infection prevention and control guidelines are undergoing continual reassessment. This mixed-methods study aimed to explore the perceptions of practicing anaesthetists regarding aerosol-generating procedures. An online survey was distributed to the Membership Engagement Group of the Royal College of Anaesthetists during November 2021. The survey included five clinical scenarios to identify the personal approach of respondents to precautions, their hospital's policies and the associated impact on healthcare provision. A purposive sample was selected for interviews to explore the reasoning behind their perceptions and behaviours in greater depth. A total of 333 survey responses were analysed quantitatively. Transcripts from 18 interviews were coded and analysed thematically. The sample was broadly representative of the UK anaesthetic workforce. Most respondents and their hospitals were aware of, supported and adhered to UK guidance. However, there were examples of substantial divergence from these guidelines at both individual and hospital level. For example, 40 (12%) requested respiratory protective equipment and 63 (20%) worked in hospitals that required it to be worn whilst performing tracheal intubation in SARS-CoV-2 negative patients. Additionally, 173 (52%) wore respiratory protective equipment whilst inserting supraglottic airway devices. Regarding the use of respiratory protective equipment and fallow times in the operating theatre: 305 (92%) perceived reduced efficiency; 376 (83%) perceived a negative impact on teamworking; 201 (64%) were worried about environmental impact; and 255 (77%) reported significant problems with communication. However, 269 (63%) felt the negative impacts of respiratory protection equipment were appropriately balanced against the risks of SARS-CoV-2 transmission. Attitudes were polarised about the prospect of moving away from using respiratory protective equipment. Participants' perceived risk from COVID-19 correlated with concern regarding stepdown (Spearman's test, R = 0.36, p < 0.001). Attitudes towards aerosol-generating procedures and the need for respiratory protective equipment are evolving and this information can be used to inform strategies to facilitate successful adoption of revised guidelines.

Quantitative evaluation of aerosol generation from upper airway suctioning assessed during tracheal intubation and extubation sequences in anaesthetized patients.

BACKGROUND: Open respiratory suctioning is defined as an aerosol generating procedure (AGP). Laryngopharyngeal suctioning, used to clear secretions during anaesthesia, is widely managed as an AGP. However, it is uncertain whether upper airway suctioning should be designated as an AGP due to the lack of both aerosol and epidemiological evidence. AIM: To assess the relative risk of aerosol generation by upper airway suctioning during tracheal intubation and extubation in anaesthetized patients. METHODS: This prospective environmental monitoring study was undertaken in an ultraclean operating theatre setting to assay aerosol concentrations during intubation and extubation sequences, including upper airway suctioning, for patients undergoing surgery (N=19). An optical particle sizer (particle size 0.3-10 µm) sampled aerosol 20 cm above the patient's mouth. Baseline recordings (background, tidal breathing and volitional coughs) were followed by intravenous induction of anaesthesia with neuromuscular blockade. Four periods of laryngopharyngeal suctioning were performed with a Yankauer sucker: pre-laryngoscopy, post-intubation, pre-extubation and post-extubation. FINDINGS: Aerosol was reliably detected {median 65 [interquartile range (IQR) 39-259] particles/L} above background [median 4.8 (IQR 1-7) particles/L, P<0.0001] when sampling in close proximity to the patient's mouth during tidal breathing. Upper airway suctioning was associated with a much lower average aerosol concentration than breathing [median 6.0 (IQR 0-12) particles/L, P=0.0007], and was indistinguishable from background (P>0.99). Peak aerosol concentrations recorded during suctioning [median 45 (IQR 30-75) particles/L] were much lower than during volitional coughs [median 1520 (IQR 600-4363) particles/L, P<0.0001] and tidal breathing [median 540 (IQR 300-1826) particles/L, P<0.0001]. CONCLUSION: Upper airway suctioning during airway management was not associated with a higher aerosol concentration compared with background, and was associated with a much lower aerosol concentration compared with breathing and coughing. Upper airway suctioning should not be designated as a high-risk AGP.

Quantitative evaluation of aerosol generation during manual facemask ventilation.

Manual facemask ventilation, a core component of elective and emergency airway management, is classified as an aerosol-generating procedure. This designation is based on one epidemiological study suggesting an association between facemask ventilation and transmission during the SARS-CoV-1 outbreak in 2003. There is no direct evidence to indicate whether facemask ventilation is a high-risk procedure for aerosol generation. We conducted aerosol monitoring during routine facemask ventilation and facemask ventilation with an intentionally generated leak in anaesthetised patients. Recordings were made in ultraclean operating theatres and compared against the aerosol generated by tidal breathing and cough manoeuvres. Respiratory aerosol from tidal breathing in 11 patients was reliably detected above the very low background particle concentrations with median [IQR (range)] particle counts of 191 (77-486 [4-1313]) and 2 (1-5 [0-13]) particles.l-1 , respectively, p = 0.002. The median (IQR [range]) aerosol concentration detected during facemask ventilation without a leak (3 (0-9 [0-43]) particles.l-1 ) and with an intentional leak (11 (7-26 [1-62]) particles.l-1 ) was 64-fold (p = 0.001) and 17-fold (p = 0.002) lower than that of tidal breathing, respectively. Median (IQR [range]) peak particle concentration during facemask ventilation both without a leak (60 (0-60 [0-120]) particles.l-1 ) and with a leak (120 (60-180 [60-480]) particles.l-1 ) were 20-fold (p = 0.002) and 10-fold (0.001) lower than a cough (1260 (800-3242 [100-3682]) particles.l-1 ), respectively. This study demonstrates that facemask ventilation, even when performed with an intentional leak, does not generate high levels of bioaerosol. On the basis of this evidence, we argue facemask ventilation should not be considered an aerosol-generating procedure.

The impact of a mobile COVID-19 polymerase chain reaction laboratory at a large tertiary hospital during the first wave of the pandemic: A retrospective analysis.

BACKGROUND: The onset of the COVID-19 pandemic in South Africa (SA) created numerous supply challenges. Demand for diagnostic testing overwhelmed the capacity to deliver. We describe the utility and outcomes of a mobile laboratory staffed by non-laboratory healthcare workers and established to perform polymerase chain reaction (PCR) testing for the rapid diagnosis of COVID-19 at a large hospital in SA. OBJECTIVES: To describe the performance of the mobile PCR COVID-19 laboratory. The secondary objective was to determine the prevalence of COVID-19 infections in the non-COVID intensive care unit (ICU). METHODS: This was a retrospective descriptive study of data from the newly established mobile COVID-19 PCR laboratory database and the non-COVID ICU database during the first peak of the COVID-19 pandemic (20 May - 8 August 2020) at a tertiary hospital in SA. RESULTS: The mobile laboratory received 1 113 emergency COVID-19 PCR test requests for patients with non-COVID clinical presentations. The median (interquartile range) turnaround time was 152 (123 - 184) minutes (n=36). Primary outcome (20 May - 19 June, n=315): The sensitivity and specificity were 95% and 97%, respectively, and the positive and negative predictive values 82.4% and 99.2%, respectively. Secondary outcomes (9 June - 8 August): The prevalence of COVID-19 infections among patients admitted to the multidisciplinary adult and paediatric non-COVID ICU was 2.4% (n=4/168). The mean (standard deviation) COVID-19 positive rate for the mobile laboratory during this period was 18.1% (6%). The prevalence of COVID-19 infections among medical staff in the non-COVID ICU was 3.1% (n=1/32). CONCLUSIONS: The establishment of a mobile PCR laboratory staffed by non-laboratory healthcare workers during the COVID-19 pandemic provided a rapid, accurate and clinically effective solution for emergency hospital admissions with non-COVID-19 presentations.

Microbial Diversity and Function in Shallow Subsurface Sediment and Oceanic Lithosphere of the Atlantis Massif.

The marine lithospheric subsurface is one of the largest biospheres on Earth; however, little is known about the identity and ecological function of microorganisms found in low abundance in this habitat, though these organisms impact global-scale biogeochemical cycling. Here, we describe the diversity and metabolic potential of sediment and endolithic (within rock) microbial communities found in ultrasmall amounts (101 to 104 cells cm-3) in the subsurface of the Atlantis Massif, an oceanic core complex on the Mid-Atlantic Ridge that was sampled on International Ocean Discovery Program (IODP) Expedition 357. This study used fluorescence-activated cell sorting (FACS) to enable the first amplicon, metagenomic, and single-cell genomic study of the shallow (<20 m below seafloor) subsurface of an actively serpentinizing marine system. The shallow subsurface biosphere of the Atlantis Massif was found to be distinct from communities observed in the nearby Lost City alkaline hydrothermal fluids and chimneys, yet similar to other low-temperature, aerobic subsurface settings. Genes associated with autotrophy were rare, although heterotrophy and aerobic carbon monoxide and formate cycling metabolisms were identified. Overall, this study reveals that the shallow subsurface of an oceanic core complex hosts a biosphere that is not fueled by active serpentinization reactions and by-products. IMPORTANCE The subsurface rock beneath the ocean is one of the largest biospheres on Earth, and microorganisms within influence global-scale nutrient cycles. This biosphere is difficult to study, in part due to the low concentrations of microorganisms that inhabit the vast volume of the marine lithosphere. In spite of the global significance of this biosphere, little is currently known about the microbial ecology of such rock-associated microorganisms. This study describes the identity and genomic potential of microorganisms in the subsurface rock and sediment at the Atlantis Massif, an underwater mountain near the Mid-Atlantic Ridge. To enable our analyses, fluorescence-activated cell sorting (FACS) was used as a means to concentrate cells from low biomass environmental samples for genomic analyses. We found distinct rock-associated microorganisms and found that the capacity for microorganisms to utilize organic carbon was the most prevalent form of carbon cycling. We additionally identified a potential role for carbon monoxide metabolism in the subsurface.

A quantitative evaluation of aerosol generation during supraglottic airway insertion and removal.

Many guidelines consider supraglottic airway use to be an aerosol-generating procedure. This status requires increased levels of personal protective equipment, fallow time between cases and results in reduced operating theatre efficiency. Aerosol generation has never been quantitated during supraglottic airway use. To address this evidence gap, we conducted real-time aerosol monitoring (0.3-10-µm diameter) in ultraclean operating theatres during supraglottic airway insertion and removal. This showed very low background particle concentrations (median (IQR [range]) 1.6 (0-3.1 [0-4.0]) particles.l-1 ) against which the patient's tidal breathing produced a higher concentration of aerosol (4.0 (1.3-11.0 [0-44]) particles.l-1 , p = 0.048). The average aerosol concentration detected during supraglottic airway insertion (1.3 (1.0-4.2 [0-6.2]) particles.l-1 , n = 11), and removal (2.1 (0-17.5 [0-26.2]) particles.l-1 , n = 12) was no different to tidal breathing (p = 0.31 and p = 0.84, respectively). Comparison of supraglottic airway insertion and removal with a volitional cough (104 (66-169 [33-326]), n = 27), demonstrated that supraglottic airway insertion/removal sequences produced <4% of the aerosol compared with a single cough (p < 0.001). A transient aerosol increase was recorded during one complicated supraglottic airway insertion (which initially failed to provide a patent airway). Detailed analysis of this event showed an atypical particle size distribution and we subsequently identified multiple sources of non-respiratory aerosols that may be produced during airway management and can be considered as artefacts. These findings demonstrate supraglottic airway insertion/removal generates no more bio-aerosol than breathing and far less than a cough. This should inform the design of infection prevention strategies for anaesthetists and operating theatre staff caring for patients managed with supraglottic airways.

Novel use of social media to assess and improve coastal flood forecasts and hazard alerts.

Coastal communities and infrastructure need protection from flooding and wave overtopping events. Assessment of hazard prediction methods, used in sea defence design, defence performance inspections and forecasting services, requires observations at the land-sea interface but these are rarely collected. Here we show how a database of hindcast overtopping events, and the conditions that cause them, can be built using qualitative overtopping information obtained from social media. We develop a database for a case study site at Crosby in the Northwest of England, use it to test the standard methods applied in operational flood forecasting services and new defence design, and suggest improvements to these methods. This novel approach will become increasingly important to deliver long-term, cost-effective coastal management solutions as sea-levels rise and coastal populations grow. At sites with limited, or no, monitoring or forecasting services, this approach, especially if combined with citizen science initiatives, could underpin the development of simplified early warning systems.

Middle ratings rise regardless of grammatical construction: Testing syntactic variability in a repeated exposure paradigm.

People perceive sentences more favourably after hearing or reading them many times. A prominent approach in linguistic theory argues that these types of exposure effects (satiation effects) show direct evidence of a generative approach to linguistic knowledge: only some sentences improve under repeated exposure, and which sentences do improve can be predicted by a model of linguistic competence that yields natural syntactic classes. However, replications of the original findings have been inconsistent, and it remains unclear whether satiation effects can be reliably induced in an experimental setting at all. Here we report four findings regarding satiation effects in wh-questions across German and English. First, the effects pertain to zone of well-formedness rather than syntactic class: all intermediate ratings, including calibrated fillers, increase at the beginning of the experimental session regardless of syntactic construction. Second, though there is satiation, ratings asymptote below maximum acceptability. Third, these effects are consistent across judgments of superiority effects in English and German. Fourth, wh-questions appear to show similar profiles in English and German, despite these languages being traditionally considered to differ strongly in whether they show effects on movement: violations of the superiority condition can be modulated to a similar degree in both languages by manipulating subject-object initiality and animacy congruency of the wh-phrase. We improve on classic satiation methods by distinguishing between two crucial tests, namely whether exposure selectively targets certain grammatical constructions or whether there is a general repeated exposure effect. We conclude that exposure effects can be reliably induced in rating experiments but exposure does not appear to selectively target certain grammatical constructions. Instead, they appear to be a phenomenon of intermediate gradient judgments.

Systematic review of the use of translated patient-reported outcome measures in cancer trials.

BACKGROUND: Patient-reported outcomes (PROs) are used in clinical trials to assess the effectiveness and tolerability of interventions. Inclusion of participants from different ethnic backgrounds is essential for generalisability of cancer trial results. PRO data collection should include appropriately translated patient-reported outcome measures (PROMs) to minimise missing data and sample attrition. METHODS: Protocols and/or publications from cancer clinical trials using a PRO endpoint and registered on the National Institute for Health Research Portfolio were systematically reviewed for information on recruitment, inclusion of ethnicity data, and use of appropriately translated PROMs. Semi-structured interviews were conducted with key stakeholders to explore barriers and facilitators for optimal PRO trial design, diverse recruitment and reporting, and use of appropriately translated PROMs. RESULTS: Eighty-four trials met the inclusion criteria, only 14 (17%) (n = 4754) reported ethnic group data, and ethnic group recruitment was low, 611 (13%). Although 8 (57%) studies were multi-centred and multi-national, none reported using translated PROMs, although available for 7 (88%) of the studies. Interviews with 44 international stakeholders identified a number of perceived barriers to ethnically diverse recruitment including diverse participant engagement, relevance of ethnicity to research question, prominence of PROs, and need to minimise investigator burden. Stakeholders had differing opinions on the use of translated PROMs, the impact of trial designs, and recruitment strategies on diverse recruitment. Facilitators of inclusive research were described and examples of good practice identified. CONCLUSIONS: Greater transparency is required when PROs are used as primary or secondary outcomes in clinical trials. Protocols and publications should demonstrate that recruitment was accessible to diverse populations and facilitated by trial design, recruitment strategies, and appropriate PROM usage. The use of translated PROMs should be made explicit when used in cancer clinical trials.

Report on G4-Med, a Geant4 benchmarking system for medical physics applications developed by the Geant4 Medical Simulation Benchmarking Group.

BACKGROUND: Geant4 is a Monte Carlo code extensively used in medical physics for a wide range of applications, such as dosimetry, micro- and nanodosimetry, imaging, radiation protection, and nuclear medicine. Geant4 is continuously evolving, so it is crucial to have a system that benchmarks this Monte Carlo code for medical physics against reference data and to perform regression testing. AIMS: To respond to these needs, we developed G4-Med, a benchmarking and regression testing system of Geant4 for medical physics. MATERIALS AND METHODS: G4-Med currently includes 18 tests. They range from the benchmarking of fundamental physics quantities to the testing of Monte Carlo simulation setups typical of medical physics applications. Both electromagnetic and hadronic physics processes and models within the prebuilt Geant4 physics lists are tested. The tests included in G4-Med are executed on the CERN computing infrastructure via the use of the geant-val web application, developed at CERN for Geant4 testing. The physical observables can be compared to reference data for benchmarking and to results of previous Geant4 versions for regression testing purposes. RESULTS: This paper describes the tests included in G4-Med and shows the results derived from the benchmarking of Geant4 10.5 against reference data. DISCUSSION: Our results indicate that the Geant4 electromagnetic physics constructor G4EmStandardPhysics_option4 gives a good agreement with the reference data for all the tests. The QGSP_BIC_HP physics list provided an overall adequate description of the physics involved in hadron therapy, including proton and carbon ion therapy. New tests should be included in the next stage of the project to extend the benchmarking to other physical quantities and application scenarios of interest for medical physics. CONCLUSION: The results presented and discussed in this paper will aid users in tailoring physics lists to their particular application.

Trial of remote continuous versus intermittent NEWS monitoring after major surgery (TRaCINg): a feasibility randomised controlled trial.

BACKGROUND: Despite medical advances, major surgery remains high risk with up to 44% of patients experiencing postoperative complications. Early recognition of postoperative complications is crucial in reducing morbidity and preventing long-term disability. The current standard of care is intermittent manual vital signs monitoring, but new wearable remote monitors offer the benefits of continuous vital signs monitoring without limiting the patient's mobility. The aim of this study was to evaluate the feasibility, acceptability and clinical outcomes of continuous remote monitoring after major surgery. METHODS: The study was a randomised, controlled, unblinded, parallel group, feasibility trial. Adult patients undergoing elective major surgery were randomly assigned to receive continuous remote monitoring and normal National Early Warning Score (NEWS) monitoring (intervention group) or normal NEWS monitoring alone (control group). Continuous remote monitoring was achieved using the SensiumVitals® wireless patch which is worn on the patient's chest and monitors heart rate, respiratory rate and temperature continuously, and alerts the nurse when there is deviation from pre-set physiological norms. Feasibility was assessed by evaluating recruitment rate, adherence to protocol and randomisation and the amount of missing data. Clinical outcomes included time to antibiotics in cases of sepsis, length of hospital stay, number of critical care admissions and rate of hospital readmission within 30 days of discharge. RESULTS: One hundred and thirty-six patients were randomised between October 2018 and April 2019: 67 to the control group and 69 to the intervention group. Recruitment was completed prior to the 12 month target with a high rate of eligibility and consent. Missing data was limited only to questionnaire responses; no participants were lost to follow-up and only one participant was withdrawn due to loss of capacity. The number of patients classed as 'drop-out' due to design (8.1%) were less than anticipated, and there were no participants who crossed over into the alternative trial allocation group. Seventeen participants in the intervention group (28%) did not adhere to the monitoring protocol. No formal comparisons between arms was undertaken; however, participants had fewer unplanned critical care admissions (1 versus 5) and had a shorter average length of hospital stay (11.6 days (95% confidence interval 9.5-13.7 days) versus 16.2 days (95% confidence interval 11.3-21.2 days)) in the continuous vital signs monitoring group. The time taken to receive antibiotics in cases of sepsis was similar in both arms. A cost-utility analysis indicated that the remote monitoring system was cost-saving when compared to standard NEWS monitoring alone. CONCLUSIONS: It is feasible to perform a large-scale randomised controlled trial of continuous remote monitoring after major surgery. Progression to a definitive multicentre randomised controlled trial would be appropriate, taking consideration of factors, such as patient adherence, that might mask the potential benefit of additional monitoring. TRIAL REGISTRATION: ISRCTN registry with study ID ISRCTN16601772 . Registered 30 August 2017.