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Can you trust results from modeling and simulation? This text provides a framework for assessing the reliability of and uncertainty included in the results used by decision makers and policy makers in industry and government. The emphasis is on models described by PDEs and their numerical solution. Procedures and results from all aspects of verification and validation are integrated with modern methods in uncertainty quantification and stochastic simulation. Methods for combining numerical approximation errors, uncertainty in model input parameters, and model form uncertainty are presented in order to estimate the uncertain response of a system in the presence of stochastic inputs and lack of knowledge uncertainty. This new edition has been extensively updated, including a fresh look at model accuracy assessment and the responsibilities of management for modeling and simulation activities. Extra homework problems and worked examples have been added to each chapter, suitable for course use or self-study.
In Michigan, United States of America, where Asian parasitoids were released to manage emerald ash borer, Agrilus planipennis Fairmaire (Coleoptera: Buprestidae), we monitored four native parasitoids that also attack the invasive beetle – Atanycolus cappaerti Marsh and Strazanac, A. simplex (Cresson), and Spathius laflammei Provancher (all Hymenoptera: Braconidae), and Phasgonophora sulcata Westwood (Hymenoptera: Chalcididae) – using yellow pan traps and tree dissections. Adult A. cappaerti, followed by A. simplex, had the broadest seasonal activity, S. laflammei was captured primarily in the first half of the growing season, and P. sulcata was restricted to mid-summer. Adult abundances of native species varied among years but, except for P. sulcata, were never significantly lower than the established Asian emerald ash borer larval parasitoids, Tetrastichus planipennisi Yang (Hymenoptera: Eulophidae) and Spathius galinae Belokobylskij and Strazanac (Hymenoptera: Braconidae). Densities of emerald ash borer larvae parasitised by A. cappaerti or P. sulcata did not differ significantly from those of the two Asian species. Although adult A. simplex and S. laflammei were frequently captured, we did not confirm parasitisation of any emerald ash borer larvae by these two species, suggesting that they rarely attack emerald ash borer. We did not find any negative correlations between adult or immature parasitoid abundance of any parasitoid species, suggesting that any interspecific competition that may be occurring is negligible.
Quantifying and assessing the computational accuracy of coarse-graining simulations of turbulence is challenging and imperative to achieve prediction – computations and results with a quantified and adequate degree of uncertainty that can be confidently used in projects without reference data. Verification, validation, and uncertainty quantification (VVUQ) provide the tools and metrics to accomplish such an objective. This chapter reviews these methods and illustrates their importance to coarse-graining models. Toward this end, we first describe the sources of computational errors and uncertainties in coarse-graining simulations of turbulence, followed by the concepts of VVUQ. Next, we utilize the modified equation analysis and the physical interpretation of a complex problem to demonstrate the role of VVUQ in evaluating and enhancing the fidelity and confidence in numerical simulations. This is crucial to achieving predictive rather than postdictive simulations.
In laboratory testing, a novel hydrogen peroxide gas plasma endoscope sterilizer consistently reduced vegetative organisms, but not bacterial spores, to undetectable levels in the presence of high organism load (≥6.5 log10) and organic material and salts. These findings highlight the importance of meticulous cleaning of endoscopes prior to sterilization.
In the Origins of Kant’s Aesthetics, Robert Clewis characterises Kant’s early views of aesthetic normativity in terms of a synthesis of a rationalist appeal to laws of sensibility and an empiricist appeal to rules of taste that are arrived at through consensus about great works of art. On the consensus approach, sharing the experience of beauty with others is itself a source of pleasure and normativity. For Clewis, the mature Kant no longer ties aesthetic normativity to sociality, but instead grounds it in the a priori principle of judgement. In these comments, I challenge Clewis’ narrative about Kant’s development and argue that the mature Kant continues to connect aesthetic normativity to the sociality of taste.
The Kable doctrine is, and has always been, a difficult legal principle to define. For over a decade, and despite much academic attention, it had little consequence for state power. Until recently, the High Court deftly avoided its application by employing a number of techniques. As the politics of law and order in the states have increased, state Parliaments have felt emboldened by these cases to test the outer limits of their legislative power. In such an environment, federal anti-terrorism measures, introduced as extraordinary responses necessary for the exceptional nature of terrorism, have crept into general state policing and expanded. It is in this arena that the Kable doctrine has emerged once again. The principle is now vital to understanding the very real limits of state power, particularly in the law and order arena. This article traces the Court's approach to the principle in three recent cases involving the states' anti-organised crime measures (International Finance Trust Co v New South Wales Crime Commission, South Australia v Totani, and Wainohu v New South Wales) before offering some conclusions about where the current jurisprudence leaves the states and their perpetual campaign to achieve law and order.
Hand, foot and mouth disease (HFMD) is a contagious communicable disease, with a high incidence in children aged under 10 years. It is a mainly self-limiting disease but can also cause serious neurological or cardiopulmonary complications in some cases, which can lead to death. Little is known about the burden of HMFD on primary care health care services in the UK. The aim of this work was to describe trends in general practitioner (GP) consultations for HFMD in England from January 2017 to December 2022 using a syndromic surveillance network of GPs. Daily GP consultations for HFMD in England were extracted from 1 January 2017 to 31 December 2022. Mean weekly consultation rates per 100,000 population and 95% confidence intervals (CI) were calculated. Consultation rates and rate ratios (RR) were calculated by age group and sex. During the study period, the mean weekly consultation rate for HFMD (per 100,000 registered GP patients) was 1.53 (range of 0.27 to 2.47). In England, children aged 1–4 years old accounted for the largest affected population followed by children <1 years old. We observed a seasonal pattern of HFMD incidence during the non-COVID years, with a seasonal peak of mean weekly rates between months of September and December. HFMD is typically diagnosed clinically rather than through laboratory sampling. Therefore, the ability to look at the daily HFMD consultation rates provides an excellent epidemiological overview on disease trends. The use of a novel GP-in-hours surveillance system allowed a unique epidemiological insight into the recent trends of general practitioner consultations for HFMD. We demonstrate a male predominance of cases, the impact of the non-pharmaceutical interventions during the COVID-19 pandemic, and a change in the week in which the peak number of cases happens post-pandemic.
Drawing on Roman Catholic and ecumenical expertise, this article takes an honest look at the experiences and hopes of those abused. Many in the churches assume that victims seek financial compensation or legal redress. However, research indicates that many victims primarily seek truth and justice as a means of closure and that their struggles with church leadership arise when truth and justice are repeatedly withheld. This makes forgiveness near-impossible and often results in the victim being re-traumatized by the systemic re-abuse they experience. Ultimately, there is no substitute for full and genuine meeting with victims, which requires the church to lay aside its power and authority and engage with humility and proper deference to the victims abused at the hands of the church. Without such openness, the victims cannot move on, and neither can the churches.
Narcolepsy is a chronic neurological disorder characterized by excessive daytime sleepiness (EDS), among other symptoms. Previous studies of narcolepsy have largely relied on quantitative methods, providing limited insight into the patient experience. This study used qualitative interviews to better understand this rare condition.
Methods
Patients with narcolepsy (types 1 [NT1] and 2 [NT2]) were recruited using convenience and snowball sampling. Trained qualitative researchers conducted hour-long, individual interviews. Interview transcripts were coded and thematically analyzed using inductive and deductive approaches.
Results
Twenty-two adults with narcolepsy (NT1=12; NT2=10) participated (average age: NT1=35; NT2=44). Most were female (NT1=83%; NT2=70%) and white (NT1=75%; NT2=60%). Average times since diagnosis were 7 years (NT1) and 11 years (NT2).
At disease onset, symptoms experienced included EDS (NT1=83%; NT2=80%)—sometimes involving sleep attacks (NT1=35%; NT2=50%)—fatigue (NT1=42%; NT2=30%), oversleeping (NT1=33%; NT2=20%), and cataplexy (NT1=42%). Participants sought a diagnosis from healthcare professionals including sleep specialists, neurologists, pulmonologists, psychiatrists, and primary care physicians. Many participants reported receiving a narcolepsy diagnosis >10 years after symptom onset (NT1=50%; NT2=60%). During that time, patients reported misdiagnoses, including depression, sleep apnea, and attention-deficit/hyperactivity disorder.
Common symptoms included EDS (NT1=100%; NT2=90%), cognitive impairment (NT1=92%; NT2=100%), and fatigue (NT1=75%; NT2=90%). All participants with NT1 reported cataplexy. Participants rated these symptoms as among the most bothersome.
Conclusions
Study results provide descriptions of narcolepsy symptoms and the often challenging journey toward seeking a diagnosis. By using patient-centered, qualitative methods, this study fills a gap by providing additional insights into the patient experience of narcolepsy.
The Antarctic Treaty System has put in place international agreements to provide comprehensive protection of the Antarctic environment. Despite this high degree of protection, human presence on the continent has resulted in environmental contamination, particularly at locations established prior to the development of the more stringent codes of conduct in recent decades. Rehabilitation of legacy contaminated sites is a priority for environmental management, and a framework for such efforts has been established. In this contribution, we re-evaluate the rehabilitation of the site of the former Vanda Station, a New Zealand outpost occupied from 1969 to 1991. We describe the design and implementation of the restoration, which included the removal of many tonnes of contaminated soils and groundwater, along with the post-action monitoring of the site. Our goal is to determine where challenges to the use of recent guidelines would have arisen. We found that while guidelines on clean-up of contaminated sites in Antarctica are valuable, challenges to implementation remain. These largely reflect a lack of understanding of the consequences of contamination on Antarctic ecosystems and the trajectory of natural rehabilitation. We present recommendations on how to address some of these challenges.
This study evaluated the impact of 2015/2016 prescribing guidance on antidepressant prescribing choices in children.
Methods
A retrospective e-cohort study of whole population routine electronic healthcare records was conducted. Poisson regression was undertaken to explore trends over time for depression, antidepressant prescribing, indications and secondary care contacts. Time trend analysis was conducted to assess the impact of guidance.
Results
A total of 643 322 primary care patients in Wales UK, aged 6–17 years from 2010–2019 contributed 3 215 584 person-years of follow-up. Adjusted incidence of depression more than doubled (IRR for 2019 = 2.8 [2.5–3.2]) with similar trends seen for antidepressants. Fluoxetine was the most frequently prescribed first-line antidepressant. Citalopram comprised less than 5% of first prescriptions in younger children but 22.9% (95% CI 22.0–23.8; 95% CI 2533) in 16–17-year-olds. Approximately half of new antidepressant prescribing was associated with depression. Segmented regression analysis showed that prescriptions of ‘all’ antidepressants, Fluoxetine and Sertraline were increasing before the guidance. This upward trend flattened for both ‘all’ antidepressants and Fluoxetine and steepened for Sertraline. Citalopram prescribing was decreasing significantly pre guidance being issued with no significant change afterward.
Conclusions
Targeted intervention is needed to address rising rates of depression in children. Practitioners are partially adhering to local and national guidance. The decision-making process behind prescribing choices is likely to be multi-factorial. Activities to support implementation of guidance should be adopted in relation to safety in prescribing of antidepressants in children including timely availability of talking therapies and specialist mental health services.
Innovation is needed for the growing number of patients with chronic obstructive pulmonary disease (COPD). Pulmonary rehabilitation (PR) is effective in improving exercise tolerance and quality of life, but these benefits do not appear to be sustained. This highlights the need for cost effective methods to maintain benefits on completion of therapy. The findings of a large trial from the UK are reported.
Methods
A two-center randomized controlled trial of patients discharged from PR compared the costs and benefits of PR maintenance with standard care. National Health Service (NHS) resource use, personal expenditure, and societal costs were recorded over one year, and bottom-up costing was undertaken for the PR maintenance program. Changes in health-related quality of life were recorded using the EQ-5D-5L, and differences were compared with the level identified as significant for COPD. A cost utility analysis was undertaken from an NHS perspective; uncertainties in cost and outcome data were incorporated into a sensitivity analysis. Cost-effectiveness ratios and cost-effectiveness acceptability curves (CEACs) were computed.
Results
The study included 116 patients who had finished PR within the last four weeks. The economic analysis showed that mean healthcare costs per patient for PR maintenance were approximately GBP139.72 (EUR165.57) lower than for usual care. The observed 0.118 advantage in mean quality-adjusted life-years (QALYs) (p<0.05) was above the threshold (0.051) for COPD significance. CEACs indicated there was a 97 percent chance of achieving GBP20,000 (EUR23,699.80) per QALY (NICE acceptance level ≤GBP30,000 (EUR35,549.70). Patient and societal costs increased this percentage. It was estimated that if patients with COPD completed a maintenance program following PR, the NHS could save up to GBP28.6 million (EUR33.89 million).
Conclusions
Our findings confirm that a structured PR maintenance program is highly cost effective in extending the benefits of short-term PR. The trial, undertaken during COVID, also signals the potential for emerging digital innovations to provide future transformative change in delivering self-management programs to sustain health and reduce NHS costs for people living with chronic conditions.
Inference is considered for the marginal distribution of X, when (X, Y) has a truncated bivariate normal distribution. The Y variable is truncated, but only the X values are observed. The relationship of this distribution to Azzalini's “skew-normal” distribution is obtained. Method of moments and maximum likelihood estimation are compared for the three-parameter Azzalini distribution. Samples that are uniformative about the skewness of this distribution may occur, even for large n. Profile likelihood methods are employed to describe the uncertainty involved in parameter estimation. A sample of 87 Otis test scores is shown to be well-described by this model.
Free-recall verbal learning is analyzed in terms of a probability model. The general theory assumes that the probability of recalling a word on any trial is completely determined by the number of times the word has been recalled on previous trials. Three particular cases of this general theory are examined. In these three cases, specific restrictions are placed upon the relation between probability of recall and number of previous recalls. The application of these special cases to typical experimental data is illustrated. An interpretation of the model in terms of set theory is suggested but is not essential to the argument.
A multivariate analysis based on transmitted information is presented. It is shown that sample transmitted information provides a simple method for measuring and testing association in multi-dimensional contingency tables. Relations with analysis of variance are pointed out, and statistical tests are described.
Analysis of variance and uncertainty analysis are analogous techniques for partitioning variability. In both analyses negative interaction terms due to negative covariance terms that appear when non-orthogonal predictor variables are allowed may occur. Uncertainties can be estimated directly from variances if the form of distribution is assumed. The decision as to which of the techniques to use depends partly on the properties of the criterion variable. Only uncertainty analysis may be used with a non-metric criterion. Since uncertainties are dimensionless (using no metric), however, uncertainty analysis has a generality which may make it useful even when variances can be computed.
A simple model for fluctuating interresponse times is developed and studied. It involves a mechanism that generates regularly spaced excitations, each of which can trigger off a response after a random delay. The excitations are not observable, but their periodicity is reflected in a regular patterning of responses. The probability distribution of the time between responses is derived and its properties are analyzed. Several limiting cases are also examined.
Formulas are derived by which, given the factor loadings and the internal reliability of a test of unit length, the following estimates can be made: (1) the common-factor loadings for a similar (homogeneous) test of length n; (2) the number of times (n) that a test needs to be lengthened homogeneously to achieve a factor loading of a desired magnitude; and (3) the correlation between two tests, either or both of which have been altered in length, as a function of (a) the new factor loadings in the altered tests or (b) the original loadings in the unit-length tests. The appropriate use of the derived formulas depends upon the fulfillment of four assumptions enumerated.