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The personalised oncology paradigm remains challenging to deliver despite technological advances in genomics-based identification of actionable variants combined with the increasing focus of drug development on these specific targets. To ensure we continue to build concerted momentum to improve outcomes across all cancer types, financial, technological and operational barriers need to be addressed. For example, complete integration and certification of the ‘molecular tumour board’ into ‘standard of care’ ensures a unified clinical decision pathway that both counteracts fragmentation and is the cornerstone of evidence-based delivery inside and outside of a research setting. Generally, integrated delivery has been restricted to specific (common) cancer types either within major cancer centres or small regional networks. Here, we focus on solutions in real-world integration of genomics, pathology, surgery, oncological treatments, data from clinical source systems and analysis of whole-body imaging as digital data that can facilitate cost-effectiveness analysis, clinical trial recruitment, and outcome assessment. This urgent imperative for cancer also extends across the early diagnosis and adjuvant treatment interventions, individualised cancer vaccines, immune cell therapies, personalised synthetic lethal therapeutics and cancer screening and prevention. Oncology care systems worldwide require proactive step-changes in solutions that include inter-operative digital working that can solve patient centred challenges to ensure inclusive, quality, sustainable, fair and cost-effective adoption and efficient delivery. Here we highlight workforce, technical, clinical, regulatory and economic challenges that prevent the implementation of precision oncology at scale, and offer a systematic roadmap of integrated solutions for standard of care based on minimal essential digital tools. These include unified decision support tools, quality control, data flows within an ethical and legal data framework, training and certification, monitoring and feedback. Bridging the technical, operational, regulatory and economic gaps demands the joint actions from public and industry stakeholders across national and global boundaries.
A 77-year-old, 120 kg female presents for a craniotomy and resection of her posterior fossa tumor. The surgeon prefers her to be placed in the sitting position for the operation. She has a medical history significant for diabetes (DM), hypertension (HTN), congestive heart failure (CHF), and gastroesophageal reflux disease (GERD). She is a nonsmoker with unknown exercise tolerance due to her decreased mobility secondary to osteoarthritis (OA) of her knees. What pre-operative labs and studies would you like? What monitors will you use? Should the procedure be done in the sitting position? Is venous air embolism (VAE) a concern? Will you use N2O? How would you identify a VAE? Can you prevent a VAE? How would you treat a VAE?
A 5-year-old boy presents with a 1-week history of headaches, visual changes, and ataxia. A large infratentorial mass is discovered on MRI. He is scheduled for craniotomy and resection of the tumor. What are your specific concerns: pre-operative, intra-operative, and post-operative? How will you induce anesthesia? What are your concerns about the patient’s intra-operative positioning? What will you do to mitigate the risks? Do you plan to extubate the patient at the end of the case?
Background: The Neuromuscular Disease Network for Canada (NMD4C) aims to improve the care of Canadians with neuromuscular diseases. It has identified a need to support clinicians in implementing clinical guidelines with the use of checklists for initial evaluation and clinical follow-ups. The objective of the study was to develop a pragmatic management checklist to support clinical guidelines for diagnosis and follow-up of myotonic dystrophy type 1 (DM1). Methods: A practice-based DM1 checklist will be reviewed by a panel of 35 experts using an online survey. The survey has been drafted using the Appraisal of Guidelines Research and Evaluation tool for assessing Recommendation Excellence (AGREE-REX). The experts will rate: (1) the quality of each checklist recommendation, and (2) the applicability of each recommendation based on their clinical setting. Scores will be compiled and discussed among experts to achieve consensus. Results: The compiled checklist items were organized into three sections: (1) initial evaluation, (2) follow-up visit and (3) general treatment recommendations. Feedback from experts across Canada, results on feasibility, and a finalized checklist will be presented. Conclusions: The development of a feasible treatment checklist is a useful KT tool that DM1 experts across Canada could apply in their own clinical settings.
The advancement of technology on the modern commercial flight deck has allowed flight crew members to utilise multiple sources of information to maintain the safety of their flight. Having multiple sources of flight deck information, capable of displaying the same type of information, can lead to a situation in which a pilot encounters conflicting information. Understanding how a pilot makes a decision when faced with an information conflict on the flight deck is important to ensure appropriate design of flight-deck information systems and effective pilot training. This effort utilised data collected from 25 airline pilots who experienced information conflicts on a simulated B-737 flight deck, in conjunction with a theoretical review of how information conflicts impact decision making, to develop a theoretical model of pilot decision-making in the presence of an information conflict. This manuscript describes the model, along with the theory-driven and data-driven approaches utilised to develop the model.
Our paper examines whether the impact of abusive supervision on on-the-job embeddedness (JEM) is stronger than on job satisfaction (JSAT), affective organizational commitment (AOC), and turnover intentions. We also examine whether the mediation impact of on-the-JEM in the linkage between abusive supervision and turnover intentions is stronger than the mediation impacts of JSAT and AOC. Data gathered from restaurant service workers in three waves in Ghana were used to test the abovementioned linkages via structural equation modeling. The findings illustrate that all hypotheses are supported. Specifically, the influence of abusive supervision on on-the-JEM is stronger than on traditional attitudinal variables. Additional findings demonstrate that the mediation effect of on-the-JEM in the relationship between abusive supervision and proclivity to quit is stronger than the mediation effects of JSAT and AOC. Implications for theory and managers are offered in our paper.
Pulmonary arteriovenous malformation is a rare disease leading to cyanosis, where there is a direct relation between the pulmonary artery and pulmonary vein without a capillary structure. Arteriovenous fistulae may be single or multiple. Clinical signs emerge depending on the size of the fistulae and amount of shunt. Due to the advancements in transcatheter devices and increased experience render enable the fistula embolisation procedure as an alternative to surgical treatment. Extracorporeal membrane oxygenation is used to support the patient haemodynamically and respirationally in cases of treatment-resistant, severe and revocable cardiac or pulmonary sufficiency. This paper presents an infant patient with pulmonary arteriovenous malformation, who had haemodynamic instability due to severe hypoxia and received successful transcatheter fistula embolisation via extracorporeal membrane oxygenation under emergency conditions.
Intensity-modulated radiation therapy (IMRT) treatment delivery requires pre-treatment patient-specific quality assurance (QA) for the dosimetry verification due to its complex multileaf-collimator movement. The prostate target close position between the bladder and rectum requires a tight margin during planning, and mistreatment would have a huge impact on the patient. A commercially available QA tool consists of a homogeneous medium and does not represent an exact photon interaction on the tumour and also on the nearby healthy organ.
Objective:
A heterogeneous male pelvis phantom was developed and investigated the efficiency of the treatment planning system (TPS) calculation on the off-axis region.
Methods:
Polymethyl methacrylate was used for the phantom housing, and the material closed to the bladder, rectum and prostate density was chosen to construct the organ models. The phantom was scanned and validated by the computed tomography number and density. An IMRT treatment was planned in the Monaco TPS, and a thermoluminescent dosimeter (TLD-100) was used to validate the point dosimetry. In addition, an EGSnrc Monte Carlo simulation was carried out to validate the phantom dosimetry.
Results & Discussion:
The dose measurement between TLD-100, TPS, and EGSnrc was compared and validated in the pelvis phantom. In the prostate region, the dose difference was within ± 5%, and the maximum dose difference outside-the-irradiated field was up to 20·07 % and 47·31 % in TPS and TLD-100, respectively. Meanwhile, the measured dose was lower than the calculated dose, and it was apparent for the dose outside-the-irradiated field.
Conclusion:
The developed heterogeneity male pelvis phantom was validated and verified to be an important QA device for validating radiation dosimetry in the pelvis region. The dose outside-the-irradiated field was underestimated by both TPS and TLD, respectively.
Drops subjected to electric fields can deform into singular shapes exhibiting apparent sharp tips. At high field strengths, a perfectly conducting drop surrounded by a perfectly insulating exterior fluid deforms into a prolate-shaped drop with conical ends and can exist in hydrostatic equilibrium. On the conical ends, capillary stress, which is due to the out-of-plane curvature and is singular, balances electric normal stress which is also singular. If the two phases are not perfect conductors/insulators but are both leaky dielectrics and the drop is much more conducting and viscous than the exterior, electric tangential stress disrupts the hydrostatic force balance and leads to jet emission from the cone's apex. If, however, the physical situation is inverted so that a weakly conducting, slightly viscous drop is immersed in a highly conducting, more viscous exterior, the drop deforms into an oblate lens-like profile before eventually becoming unstable. In experiments, the equator of a lenticular drop superficially resembles a wedge prior to instability. Such a drop disintegrates by equatorial streaming by ejecting a thin liquid sheet from its equator. We show theoretically by performing a local analysis that a lenticular drop's equatorial profile can be a wedge only if an approximate form of the surface charge transport equation – continuity of normal current condition – is used. Moreover, we demonstrate via numerical simulation that such wedge-shaped drops do not become unstable and therefore cannot emit equatorial sheets. We then show by transient simulations how equatorial streaming can occur when charge transport along the interface is analysed without approximation.
There is a paucity of evidence about the prevalence and risk factors for symptomatic infection among children. This study aimed to describe the prevalence of symptomatic coronavirus disease 2019 (COVID-19) and its risk factors in children and adolescents aged 0–18 years in Qatar. We conducted a cross-sectional study of all children aged 0–18 years diagnosed with COVID-19 using polymerase chain reaction in Qatar during the period 1st March to 31st July 2020. A generalised linear model with a binomial family and identity link was used to assess the association between selected factors and the prevalence of symptomatic infection. A total of 11 445 children with a median age of 8 years (interquartile range (IQR) 3–13 years) were included in this study. The prevalence of symptomatic COVID-19 was 36.6% (95% confidence interval (CI) 35.7–37.5), and it was similar between children aged <5 years (37.8%), 5–9 years (34.3%) and 10 + years (37.3%). The most frequently reported symptoms among the symptomatic group were fever (73.5%), cough (34.8%), headache (23.2%) and sore throat (23.2%). Fever (82.8%) was more common in symptomatic children aged <5 years, while cough (38.7%) was more prevalent in those aged 10 years or older, compared to other age groups. Variables associated with an increased risk of symptomatic infection were; contact with confirmed cases (RD 0.21; 95% CI 0.20–0.23; P = 0.001), having visited a health care facility (RD 0.54; 95% CI 0.45–0.62; P = 0.001), and children aged under 5 years (RD 0.05; 95% CI 0.02–0.07; P = 0.001) or aged 10 years or older (RD 0.04; 95% CI 0.02–0.06; P = 0.001). A third of the children with COVID-19 were symptomatic with a higher proportion of fever in very young children and a higher proportion of cough in those between 10 and 18 years of age.
Surfactants at fluid interfaces not only lower and cause gradients in surface tension but can induce additional surface rheological effects in response to dilatational and shear deformations. Surface tension and surface viscosities are both functions of surfactant concentration. Measurement of surface tension and determination of its effects on interfacial flows are now well established. Measurement of surface viscosities, however, is notoriously difficult. Consequently, quantitative characterization of their effects in interfacial flows has proven challenging. One reason behind this difficulty is that, with most existing methods of measurement, it is often impossible to isolate the effects of surface viscous stresses from those due to Marangoni stresses. Here, a combined asymptotic and numerical analysis is presented of the pinch-off of a surfactant-covered Newtonian liquid jet. Similarity solutions obtained from slender-jet theory and numerical solutions are presented for jets with and without surface rheological effects. Near pinch-off, it is demonstrated that Marangoni stresses become negligible compared to other forces. The rate of jet thinning is shown to be significantly lowered by surface viscous effects. From analysis of the dynamics near the pinch-off singularity, a simple analytical formula is derived for inferring surface viscosities. Three-dimensional, axisymmetric simulations confirm the validity of the asymptotic analyses but also demonstrate that a thinning jet traverses a number of intermediate regimes before eventually entering the final asymptotic regime.
When a poorly conducting drop that is surrounded by a more conducting exterior fluid is subjected to an electric field, the drop can deform into an oblate shape at low field strengths. Such drops become unstable at high field strengths and display two types of dynamics, dimpling and equatorial streaming, the physics of which is currently not understood. If the drop is more viscous, dimples form and grow at the poles of the drop and eventually the discocyte-shaped drop breaks up to form a torus. If the exterior fluid is more viscous, the drop deforms into a lens and sheds rings from the equator that subsequently break into a number of smaller droplets. A theoretical explanation as to why dimple- and lens-shaped drops occur, and the mechanisms for the onset of these instabilities, are provided by determining steady-state solutions by simulation and inferring their stability from bifurcation analysis. For large drop viscosities, electric shear stress is shown to play a dominant role and to result in dimpling. For small drop viscosities, equatorial normal stresses (electric, hydrodynamic and capillary) become unbounded and lead to the lens shape.
As two spherical gas bubbles of radii $\tilde {R}$ are brought together inside a liquid of density $\tilde {\rho }$, viscosity $\tilde {\mu }$ and surface tension $\tilde {\sigma }$, the liquid sheet separating them drains, thins and ultimately ruptures. The instant and location at which the bubbles make contact, and whereby a circular hole of vanishingly small radius is formed in the thin sheet, represent the occurrence of a finite-time singularity. The large curvature near the edge of the sheet where the hole has just formed, and where the two bubbles are now connected via a microscopic gas bridge, drives liquid to flow radially outward, causing the sheet to retract and the radius of the hole $\tilde {R}_{min}$ to increase with time. Recent work in this area has uncovered self-similarity and universal scaling regimes when two bubbles coalesce in a Newtonian fluid. Motivated by applications in which the exterior is a deformation-rate-thinning, power-law fluid, recent studies on bubble coalescence in Newtonian fluids are extended to coalescence in power-law fluids. In such fluids, viscosity decreases with deformation rate $\dot {\tilde {\gamma }}$ raised to the $n - 1$ power where $0 < n \le 1$ ($n = 1$ for a Newtonian fluid). Attention is focused here on power-law fluids that are slightly viscous at zero deformation rate, i.e. when the Ohnesorge number $Oh = \tilde {\mu }_{0}/(\tilde {\rho } \tilde {R} \tilde {\sigma })^{1/2}$ is small ($Oh \ll 1$) and where $\tilde {\mu }_0$ is the zero-deformation-rate viscosity. A combination of thin-film theory and three-dimensional, axisymmetric computations is used to probe the dynamics in the aftermath of the singularity. Heretofore unexplored regimes are uncovered, and criteria are developed for transitions between different regimes. The existence of a truly inviscid regime, predicted long ago by Keller (Phys. Fluids, vol. 26, 1983, pp. 3451–3453) and which comes into play as a purely geometrical limit of the free-surface shape, is also reported. New insights are presented on the much studied Newtonian limit beyond the initial regime reported by Munro et al. (J. Fluid Mech., vol. 773, 2015, R3). The paper concludes with a phase diagram in $(n, \tilde {R}_{min}/\tilde {R})$-space, where the index $n$ characterizes the fluid and $\tilde {R}_{min}/\tilde {R}$ the extent of coalescence, that highlights the various regimes and transitions between them.
Highly stretched liquid drops, or filaments, surrounded by a gas are routinely encountered in nature and industry. Such filaments can exhibit complex and unexpected dynamics as they contract under the action of surface tension. Instead of simply retracting to a sphere of the same volume, low-viscosity filaments exceeding a critical aspect ratio undergo localized pinch-off at their two ends resulting in a sequence of daughter droplets – a phenomenon called endpinching – which is an archetype breakup mode that is distinct from the classical Rayleigh–Plateau instability seen in jet breakup. It has been shown that endpinching can be precluded in filaments of intermediate viscosity, with the so-called escape from endpinching being understood heretofore only qualitatively as being caused by a viscous mechanism. Here, we show that a similar escape can also occur in nearly inviscid filaments when surfactants are present at the free surface of a recoiling filament. The fluid dynamics of the escape phenomenon is probed by numerical simulations. The computational results are used to show that the escape is driven by the action of Marangoni stress. Despite the apparently distinct physical origins of escape in moderately viscous surfactant-free filaments and that in nearly inviscid but surfactant-covered filaments, it is demonstrated that the genesis of all escape events can be attributed to a single cause – the generation of vorticity at curved interfaces. By analysing vorticity dynamics and the balance of vorticity in recoiling filaments, the manner in which surface tension gradients and concomitant Marangoni stresses can lead to escape from endpinching is clarified.
We invited 108 psychiatrists of Sudanese origin, working in and outside Sudan, to take part in a study looking at the most appropriate method for scaling up mental health services in Sudan. Of those psychiatrists who were approached, 81 (75%) responded. Among the respondents, 30 (37%) resided and worked in Sudan, and 51 (63%) worked outside Sudan (mostly in the UK and Arab Gulf States). Most respondents preferred the lay counsellor model (43, 53.2%) to address the current shortage of human resources for scaling up mental health services.
Obsessive Compulsive Personality Disorder (OCPD) is a common, highly co-morbid disorder. Subjected to comparatively little research, OCPD shares aspects of phenomenology and neuropsychology with obsessive-compulsive spectrum disorders and neurodevelopmental disorders such as autism spectrum disorder (ASD). A greater understanding of this interrelationship would provide new insights into its diagnostic classification and generate new research and treatment heuristics.
Aims
To investigate the distribution of OCPD traits within a cohort of OCD patients. To evaluate the clinical overlap between traits of OCPD, OCD and ASD, as well as level of insight and treatment resistance.
Method
We interviewed 73 consenting patients from a treatment seeking OCD Specialist Service. We evaluated the severity of OCPD traits (Compulsive Personality Assessment Scale; CPAS), OCD symptoms (Yale–Brown Obsessive Compulsive Scale; Y-BOCS), ASD traits (Adult Autism Spectrum Quotient; AQ) and insight (Brown Assessment of Beliefs Scale; BABS).
Results
Out of 67 patients, 24 (36%) met DSM-IV criteria for OCPD, defined using the CPAS. Using Pearson's test, CPAS scores significantly (P < 0.01) correlated with total AQ and selected AQ domains but not with BABS. Borderline significant correlation was observed with Y-BOCS (P = 0.07). OCPD was not over-represented in a highly resistant OCD subgroup.
Conclusion
Disabling OCPD traits are common in the OCD clinic. They strongly associate with ASD traits, less strongly with OCD severity and do not appear related to poor insight or highly treatment-resistant OCD. The impact of OCPD on OCD treatment outcomes requires further research.
Disclosure of interest
This work did not receive funding from external sources. Over the past few years, Dr. Fineberg has received financial support in various forms from the following: Shire, Otsuka, Lundbeck, Glaxo-SmithKline, Servier, Cephalon, Astra Zeneca, Jazz pharmaceuticals, Bristol Myers Squibb, Novartis, Medical Research Council (UK), National Institute for Health Research (UK), Wellcome Foundation, European College of Neuropsychopharmacology, UK College of Mental Health Pharmacists, British Association for Psychopharmacology, International College of Obsessive-Compulsive Spectrum Disorders, International Society for Behavioural Addiction, World Health Organization, Royal College of Psychiatrists.
Short-term peripheral venous catheter–related bloodstream infection (PVCR-BSI) rates have not been systematically studied in resource-limited countries, and data on their incidence by number of device days are not available.
Methods:
Prospective, surveillance study on PVCR-BSI conducted from September 1, 2013, to May 31, 2019, in 727 intensive care units (ICUs), by members of the International Nosocomial Infection Control Consortium (INICC), from 268 hospitals in 141 cities of 42 countries of Africa, the Americas, Eastern Mediterranean, Europe, South East Asia, and Western Pacific regions. For this research, we applied definition and criteria of the CDC NHSN, methodology of the INICC, and software named INICC Surveillance Online System.
Results:
We followed 149,609 ICU patients for 731,135 bed days and 743,508 short-term peripheral venous catheter (PVC) days. We identified 1,789 PVCR-BSIs for an overall rate of 2.41 per 1,000 PVC days. Mortality in patients with PVC but without PVCR-BSI was 6.67%, and mortality was 18% in patients with PVC and PVCR-BSI. The length of stay of patients with PVC but without PVCR-BSI was 4.83 days, and the length of stay was 9.85 days in patients with PVC and PVCR-BSI. Among these infections, the microorganism profile showed 58% gram-negative bacteria: Escherichia coli (16%), Klebsiella spp (11%), Pseudomonas aeruginosa (6%), Enterobacter spp (4%), and others (20%) including Serratia marcescens. Staphylococcus aureus were the predominant gram-positive bacteria (12%).
Conclusions:
PVCR-BSI rates in INICC ICUs were much higher than rates published from industrialized countries. Infection prevention programs must be implemented to reduce the incidence of PVCR-BSIs in resource-limited countries.