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Computing the rate of evolution in spatially structured populations is difficult. A key quantity is the fixation time of a single mutant with relative reproduction rate r which invades a population of residents. We say that the fixation time is "fast" if it is at most a polynomial function in terms of the population size N. Here we study fixation times of advantageous mutants (r > 1) and neutral mutants (r = 1) on directed graphs, which are those graphs that have at least some one-way connections. We obtain three main results. First, we prove that for any directed graph the fixation time is fast, provided that r is sufficiently large. Second, we construct an efficient algorithm that gives an upper bound for the fixation time for any graph and any r ≥ 1. Third, we identify a broad class of directed graphs with fast fixation times for any r ≥ 1. This class includes previously studied amplifiers of selection, such as Superstars and Metafunnels. We also show that on some graphs the fixation time is not a monotonically declining function of r; in particular, neutral fixation can occur faster than fixation for small selective advantages. Author summary: Populations of reproducing individuals evolve by accumulating mutations. When a single individual acquires a mutation, it takes some time until the mutation spreads across the population. Depending on the structure of the population, this so-called fixation time could be relatively short or exceedingly long. The structure of biological populations can be represented by graphs. The vertices of the graph denote individuals and the edges indicate possible reproductive events. Directed graphs are defined as those graphs that have some one-way edges. It is known that very long fixation times can arise for certain directed graphs. In this work, we consider a standard process of evolutionary dynamics. We show that for many directed graphs the fixation time is short. We show that fixation time is always short in the ecological scenario describing the spread of an invasive species in an ecosystem. We also show that while advantageous mutations generally fixate faster than neutral mutations, there are interesting exceptions. Finally, we provide concrete bounds for fixation time on any population structure. Those bounds serve as guarantees for simulation-based and computational explorations of the space of all directed graphs. [ABSTRACT FROM AUTHOR]

This study aimed to describe how video laryngoscopy is used outside the operating room within the hospital setting. Specifically, we aimed to summarise the evidence for the use of video laryngoscopy outside the operating room, and detail how it appears in current clinical practice guidelines. A literature search was conducted across two databases (MEDLINE and Embase), and all articles underwent screening for relevance to our aims and pre-determined exclusion criteria. Our results include 14 clinical practice guidelines, 12 interventional studies, 38 observational studies. Our results show that video laryngoscopy is likely to improve glottic view and decrease the incidence of oesophageal intubations; however, it remains unclear as to how this contributes to first-pass success, overall intubation success and clinical outcomes such as mortality outside the operating room. Furthermore, our results indicate that the appearance of video laryngoscopy in clinical practice guidelines has increased in recent years, and particularly through the COVID-19 pandemic. Current COVID-19 airway management guidelines unanimously introduce video laryngoscopy as a first-line (rather than rescue) device. [ABSTRACT FROM AUTHOR]

Background: This paper aimed to describe the airway practices of intensive care units (ICUs) in Australia and New Zealand specific to patients presenting with COVID-19 and to inform whether consistent clinical practice was achieved. Specific clinical airway guidelines were endorsed in March 2020 by the Australian and New Zealand Intensive Care Society (ANZICS) and College of Intensive Care Medicine (CICM). Methods and findings: Prospective, structured questionnaire for all ICU directors in Australia and New Zealand was completed by 69 ICU directors after email invitation from ANZICS. The online questionnaire was accessible for three weeks during September 2020 and analysed by cloud-based software. Basic ICU demographics (private or public, metropolitan or rural) and location, purchasing, airway management practices, guideline uptake, checklist and cognitive aid use and staff training relevant to airway management during the COVID-19 pandemic were the main outcome measures. The 69 ICU directors reported significant simulation-based inter-professional airway training of staff (97%), and use of video laryngoscopy (94%), intubation checklists (94%), cognitive aids (83%) and PPE "spotters" (89%) during the airway management of patients with COVID-19. Tracheal intubation was almost always performed by a Specialist (97% of ICUs), who was more likely to be an intensivist than an anaesthetist (61% vs 36%). There was a more frequent adoption of specific airway guidelines for the management of COVID-19 patients in public ICUs (94% vs 71%) and reliance on specialist intensivists to perform intubations in private ICUs (92% vs 53%). Conclusion: There was a high uptake of a standardised approach to airway management in COVID-19 patients in ICUs in Australia and New Zealand, likely due to endorsement of national guidelines. [ABSTRACT FROM AUTHOR]

Background/objectives: Advances in cancer management have resulted in improved survival rates, particularly in children and young adults. However, treatment may adversely affect reproductive outcomes among female cancer survivors. The objective of this study was to investigate their risk of adverse perinatal outcomes compared to the general population. Design/methods: We performed a population-based analysis, including all female cancer survivors diagnosed before the age of 40 years between 1981 and 2012. Pregnancy and perinatal complications were identified through linkage of the Scottish Cancer Registry with hospital discharge records based on the Community Health Index (CHI) database. We compared 1,629 female cancer survivors with a first ever singleton pregnancy after diagnosis, with controls matched on age, deprivation quintile, and year of cancer diagnosis selected from the general population (n = 8,899). Relative risks and 95%-confidence intervals of perinatal risks were calculated using log-binomial regression. Results: Survivors were more likely to give birth before 37 weeks of gestation (relative risk (RR]) 1.32, 95%-CI 1.10–1.59), but did not show an increased risk of low birth weight (<2.5kg: RR 1.15, 95%-CI 0.94–1.39), and were less likely to give birth to offspring small for gestational age (RR 0.81, 95%-CI 0.68–0.98). Operative delivery and postpartum haemorrhage were more common but approached rates in controls with more recent diagnosis. The risk of congenital abnormalities was not increased (RR 1.01, 95%-CI 0.85–1.20). Conclusion: Cancer survivors have an increased risk of premature delivery and postpartum haemorrhage, but their offspring are not at increased risk for low birth weight or congenital abnormalities. In recent decades there has been a normalisation of delivery method in cancer survivors, nevertheless careful management remains appropriate particularly for those diagnosed in childhood. [ABSTRACT FROM AUTHOR]

Background: Lung and upper aero-digestive tract (UADT) cancer risk are associated with low socioeconomic circumstances and routinely measured using area socioeconomic indices. We investigated effect of country of birth, marital status, one area deprivation measure and individual socioeconomic variables (economic activity, education, occupational social class, car ownership, household tenure) on risk associated with lung, UADT and all cancer combined (excluding non melanoma skin cancer). Methods: We linked Scottish Longitudinal Study and Scottish Cancer Registry to follow 203,658 cohort members aged 15+ years from 1991–2006. Relative risks (RR) were calculated using Poisson regression models by sex offset for person-years of follow-up. Results: 21,832 first primary tumours (including 3,505 lung, 1,206 UADT) were diagnosed. Regardless of cancer, economically inactivity (versus activity) was associated with increased risk (male: RR 1.14, 95% CI 1.10–1.18; female: RR 1.06, 95% CI 1.02–1.11). For lung cancer, area deprivation remained significant after full adjustment suggesting the area deprivation cannot be fully explained by individual variables. No or non degree qualification (versus degree) was associated with increased lung risk; likewise for UADT risk (females only). Occupational social class associations were most pronounced and elevated for UADT risk. No car access (versus ownership) was associated with increased risk (excluding all cancer risk, males). Renting (versus home ownership) was associated with increased lung cancer risk, UADT cancer risk (males only) and all cancer risk (females only). Regardless of cancer group, elevated risk was associated with no education and living in deprived areas. Conclusions: Different and independent socioeconomic variables are inversely associated with different cancer risks in both sexes; no one socioeconomic variable captures all aspects of socioeconomic circumstances or life course. Association of multiple socioeconomic variables is likely to reflect the complexity and multifaceted nature of deprivation as well as the various roles of these dimensions over the life course. [ABSTRACT FROM AUTHOR]

Background: Adjuvant chemotherapy in early stage breast cancer has been shown to reduce mortality in a large meta-analysis of over 100 randomised trials. However, these trials largely excluded patients aged 70 years and over or with higher levels of comorbidity. There is therefore uncertainty about whether the effectiveness of adjuvant chemotherapy generalises to these groups, hindering patient and clinician decision-making. This study utilises administrative healthcare data-real world data (RWD)-and econometric methods for causal analysis to estimate treatment effectiveness in these trial-underrepresented groups.Methods and Findings: Women with early breast cancer aged 70 years and over and those under 70 years with a high level of comorbidity were identified and their records extracted from Scottish Cancer Registry (2001-2015) data linked to other routine health records. A high level of comorbidity was defined as scoring 1 or more on the Charlson comorbidity index, being in the top decile of inpatient stays, and/or having 5 or more visits to specific outpatient clinics, all within the 5 years preceding breast cancer diagnosis. Propensity score matching (PSM) and instrumental variable (IV) analysis, previously identified as feasible and valid in this setting, were used in conjunction with Cox regression to estimate hazard ratios for death from breast cancer and death from all causes. The analysis adjusts for age, clinical prognostic factors, and socioeconomic deprivation; the IV method may also adjust for unmeasured confounding factors. Cohorts of 9,653 and 7,965 were identified for women aged 70 years and over and those with high comorbidity, respectively. In the ≥70/high comorbidity cohorts, median follow-up was 5.17/6.53 years and there were 1,935/740 deaths from breast cancer. For women aged 70 years and over, the PSM-estimated HR was 0.73 (95% CI 0.64-0.95), while for women with high comorbidity it was 0.67 (95% CI 0.51-0.86). This translates to a mean predicted benefit in terms of overall survival at 10 years of approximately3% (percentage points) and 4%, respectively. A limitation of this analysis is that use of observational data means uncertainty remains both from sampling uncertainty and from potential bias from residual confounding.Conclusions: The results of this study, as RWD, should be interpreted with caution and in the context of existing and emerging randomised data. The relative effectiveness of adjuvant chemotherapy in reducing mortality in patients with early stage breast cancer appears to be generalisable to the selected trial-underrepresented groups. [ABSTRACT FROM AUTHOR]