Design and Analysis of Multiple Events Case–Control Studies

Summary In case–control research where there are multiple case groups, standard analyses fail to make use of all available information. Multiple events case–control (MECC) studies provide a new approach to sampling from a cohort and are useful when it is desired to study multiple types of events in the cohort. In this design, subjects in the cohort who develop any event of interest are sampled, as well as a fraction of the remaining subjects. We show that a simple case–control analysis of data arising from MECC studies is biased and develop three general estimating‐equation‐based approaches to analyzing data from these studies. We conduct simulation studies to compare the efficiency of the various MECC analyses with each other and with the corresponding conventional analyses. It is shown that the gain in efficiency by using the new design is substantial in many situations. We demonstrate the application of our approach to a nested case–control study of the effect of oral sodium phosphate use on chronic kidney injury with multiple case definitions.     

Testing in Normal Mixture Models with Some Information on the Parameters

The aim of this paper is to study the distribution of the likelihood ratio for testing whether or not one is sampling from a mixture of two distributions or from a single distribution. We study the case where some information is available on the variation range of the parameters of populations. First we study the simplest case in which the difference between the mean of the two populations is known. We show certain distortions between theoretical and simulation results. Secondly, we show how this distortion spreads to the situation where this difference belongs to an interval. Finally, we give an example concerning the detection of major genes in animal population.     

Interaction between Fiscal and Monetary Policy in a Dynamic Nonlinear Model

The objective of this study is to verify the dynamics between fiscal policy, measured by public debt, and monetary policy, measured by a reaction function of a central bank. Changes in monetary policies due to deviations from their targets always generate fiscal impacts. We examine two policy reaction functions: the first related to inflation targets and the second related to economic growth targets. We find that the condition for stable equilibrium is more restrictive in the first case than in the second. We then apply our simulation model to Brazil and United Kingdom and find that the equilibrium is unstable in the Brazilian case but stable in the UK case.     

A general method for dealing with misclassification in regression: the misclassification SIMEX

We have developed a new general approach for handling misclassification in discrete covariates or responses in regression models. The simulation and extrapolation (SIMEX) method, which was originally designed for handling additive covariate measurement error, is applied to the case of misclassification. The statistical model for characterizing misclassification is given by the transition matrix Pi from the true to the observed variable. We exploit the relationship between the size of misclassification and bias in estimating the parameters of interest. Assuming that Pi is known or can be estimated from validation data, we simulate data with higher misclassification and extrapolate back to the case of no misclassification. We show that our method is quite general and applicable to models with misclassified response and/or misclassified discrete regressors. In the case of a binary response with misclassification, we compare our method to the approach of Neuhaus, and to the matrix method of Morrissey and Spiegelman in the case of a misclassified binary regressor. We apply our method to a study on caries with a misclassified longitudinal response.     

Deceptive intracardiac electrograms during an ICD interrogation. A clinical challenge

We present a case of a patient with significant structural heart disease from previous cardiac surgeries who presented for an electrophysiology study and radiofrequency ablation. The case highlights the significance of intra-atrial conduction delays in such patients and potential pitfalls it can present while interpreting intra-cardiac electrograms especially during implantable cardioverter defibrillator (ICD) interrogations.     

Study of the rotational diffusion properties of peptides in solution

In this paper we examine the theory and method for obtaining rotational diffusion coefficients for peptides in dilute solution from ¹³C-nmr spin-lattice relaxation data. We show that even for the case of nearly equal observed relaxation times of chemically and magnetically nonequivalent alpha-carbons marked rotational anisotropy will be the usual case. We describe two interactive, minicomputer programs which are of general use in this type of work. The implications of this study on spectral density-based conformational determinations of peptides is discussed.     

Longitudinal Studies of Binary Response Data Following Case–Control and Stratified Case–Control Sampling: Design and Analysis

Summary We discuss design and analysis of longitudinal studies after case–control sampling, wherein interest is in the relationship between a longitudinal binary response that is related to the sampling (case–control) variable, and a set of covariates. We propose a semiparametric modeling framework based on a marginal longitudinal binary response model and an ancillary model for subjects' case–control status. In this approach, the analyst must posit the population prevalence of being a case, which is then used to compute an offset term in the ancillary model. Parameter estimates from this model are used to compute offsets for the longitudinal response model. Examining the impact of population prevalence and ancillary model misspecification, we show that time‐invariant covariate parameter estimates, other than the intercept, are reasonably robust, but intercept and time‐varying covariate parameter estimates can be sensitive to such misspecification. We study design and analysis issues impacting study efficiency, namely: choice of sampling variable and the strength of its relationship to the response, sample stratification, choice of working covariance weighting, and degree of flexibility of the ancillary model. The research is motivated by a longitudinal study following case–control sampling of the time course of attention deficit hyperactivity disorder (ADHD) symptoms.     

Insights into the impact and use of research results in a residential long-term care facility: a case study

ABSTRACT: BACKGROUND: Engaging end users of research in the process of disseminating findings may increase the relevance of findings and their impact for users. We report findings from a case study that explored how involvement with the Translating Research in Elder Care (TREC) study influenced management and staff at one of 36 TREC facilities. We conducted the study at 'Restwood' (pseudonym) nursing home because the Director of Care engaged actively in the study and TREC data showed that this site differed on some areas from other nursing homes in the province. The aims of the case study were two-fold: to gain a better understanding of how frontline staff engage with the research process, and to gain a better understanding of how to share more detailed research results with management. METHODS: We developed an Expanded Feedback Report for use during this study. In it, we presented survey results that compared Restwood to the best performing site on all variables and participating sites in the province. Data were collected regarding the Expanded Feedback Report through interviews with management. Data from staff were collected through interviews and observation. We used content analysis to derive themes to describe key aspects related to the study aims. RESULTS: We observed the importance of understanding organizational routines and the impact of key events in the facility's environment. We gleaned additional information that validated findings from prior feedback mechanisms within TREC. Another predominant theme was the sense that the opportunity to engage in a research process was reaffirming for staff (particularly healthcare aides)--what they did and said mattered, and TREC provided a means of having one's voice heard. We gained valuable insight from the Director of Care about how to structure and format more detailed findings to assist with interpretation and use of results. CONCLUSIONS: Four themes emerged regarding staff engagement with the research process: sharing feedback reports from the TREC study; the meaning of TREC to staff; understanding organizational context; and using the study feedback for improvement at Restwood. This study has lessons for researchers on how to share research results with study participants, including management.     

Evaluation of the Diagnostic Utility of the Traditional and Revised WHO Dengue Case Definitions

Dengue, a mosquito-borne viral illness, is a major public health problem worldwide, and its incidence continues to increase. In 2009, the World Health Organization published guidelines that included a revision of the dengue case definition. Compared to the traditional definition, the revised case definition relies more on signs than on symptoms, making it more applicable to young children. We evaluated the diagnostic utility of both case definitions in two studies of pediatric dengue in Managua, Nicaragua. In a community-based cohort study, we included data from 3,407 suspected dengue cases, of which 476 were laboratory-confirmed. In the second study, we collected information from 1,160 participants recruited at the national pediatric reference hospital (723 laboratory-confirmed). In the cohort study, the traditional definition had 89.3% sensitivity and 43.1% specificity, while the revised definition yielded similar sensitivity (86.6%) and higher specificity (55.2%, p<0.001). In the hospital study, the traditional case definition yielded 96.7% sensitivity and 22.0% specificity, whereas the revised case definition had higher sensitivity (99.3%, p<0.001) but lower specificity (8.5%, p<0.001). We then evaluated the performance of two diagnostic models based on the signs/symptoms included in each definition by analyzing the effect of increasing numbers of signs/symptoms on the sensitivity and specificity of case capture. Receiver operating characteristic analysis showed a slightly better performance for the revised model in both studies. Interestingly, despite containing less symptoms that cannot be readily expressed by children aged less than 4 years, the revised definition did not perform better in this age group. Overall, our results indicate that both case definitions have similar capacity to diagnose dengue. Owing to their high sensitivity and low specificity, they should be primarily used for screening purposes. However, in a primary care setting, neither of the case definitions performed well as a screening test in younger children.     

Evaluating the use of friend or family controls in epidemiologic case-control studies

BackgroundTraditional methodologies for identifying and recruiting controls in epidemiologic case-control studies, such as random digit dialing or neighborhood walk, suffer from declining response rates. Here, we revisit the feasibility and comparability of using alternative sources of controls, specifically friend and family controls.MethodsWe recruited from a recently completed case-control study of non-Hodgkin lymphoma (NHL) among women in Los Angeles County where controls from the parent study were ascertained by neighborhood walk. We calculated participation rates and compared questionnaire responses between the friend/family controls and the original matched controls from the parent study.ResultsOf the 182 NHL case patients contacted, 111 (61%) agreed to participate in our feasibility study. 70 (63%) provided contact information for potential friend and/or family member controls. We were able to successfully contact and recruit a friend/family member for 92% of the case patients. This represented 46 friend controls and 54 family controls. Family controls significantly differed from original matched controls by sex and household income. Other characteristics were similar between friend controls and the original study’s neighborhood controls.ConclusionThe apparent comparability of neighborhood controls to friend and family controls among respondents in this study suggests that these alternative methods of control identification can serve as a complementary source of eligible controls in epidemiologic case-control studies.     

Using PCR-based detection and genotyping to trace Streptococcus salivarius meningitis outbreak strain to oral flora of radiology physician assistant

We recently investigated three cases of bacterial meningitis that were reported from a midwestern radiology clinic where facemasks were not worn during spinal injection of contrast agent during myelography procedures. Using pulsed field gel electrophoresis we linked a case strain of S. salivarius to an oral specimen of a radiology physician assistant (RPA). We also used a real-time PCR assay to detect S. salivarius DNA within a culture-negative cerebrospinal fluid (CSF) specimen. Here we extend this investigation through using a nested PCR/sequencing strategy to link the culture-negative CSF specimen to the case strain. We also provide validation of the real-time PCR assay used, demonstrating that it is not solely specific for Streptococcus salivarius, but is also highly sensitive for detection of the closely related oral species Streptococcus vestibularis. Through using multilocus sequence typing and 16S rDNA sequencing we further strengthen the link between the CSF case isolate and the RPA carriage isolate. We also demonstrate that the newly characterized strains from this study are distinct from previously characterized S. salivarius strains associated with carriage and meningitis.     

Does the Production of an Airbag Injure more People than the Airbag Saves in Traffic?

Social life cycle assessment (S‐LCA) has been discussed for some years in the LCA community. We raise two points of criticism against current S‐LCA approaches. First, the development of S‐LCA methodology has not, to date, been based on experience with actual case studies. Second, for social impacts to be meaningfully assessed in a life cycle perspective, social indicators need to be unambiguously interpreted in all social contexts along the life cycle. We here discuss an empirically based approach to S‐LCA, illustrated by a case study of an automobile airbag system. The aim of the case study is to compare the injuries and lives lost during the product life cycle of the airbag system (excluding waste handling impacts) with the injuries prevented and lives saved during its use. The indicator used for assessing social impacts in this study is disability‐adjusted life years (DALY). The results from this study indicate that the purpose of an airbag system, which is to save lives and prevent injuries, is justified also in a life cycle perspective.     

Had COVID-19 spread in the community before the first confirmed case in Nagasaki,Japan?

This retrospective study evaluated stored nasopharyngeal swab samples from Japanese patients with influenza-like illness during the 2019/2020 season. We aimed to determine whether COVID-19 had spread in the community before the first confirmed case. The period of influenza season during 2019/2020 in Nagasaki was shorter than in previous influenza seasons. When the first COVID-19 case was reported in Nagasaki prefecture, the number of influenza cases were very low. No positive results for SARS-CoV-2 were detected in 182 samples that were obtained from adult outpatients. Our results revealed no large-scale spread of COVID-19 in the community before the first confirmed case.     

Arguments for biodiversity conservation: factors influencing their observed effectiveness in European case studies

Making a strong case for biodiversity protection is central to meeting the biodiversity targets in international agreements such as the CBD and achieving the UN Sustainable Development Goals. Effective arguments are needed to convince diverse actors that protection is worthwhile, and can play a crucial role in closing the implementation gap between biodiversity policy targets and outcomes. Drawing on a database of arguments from 11 European case studies, along with additional interview and case study material from all 13 case studies of the BESAFE project, we analysed relationships between potential and observed effectiveness of arguments. Our results show that strong logic, robustness, and timing of arguments are necessary but not sufficient conditions for arguments to be effective. We find that use of multiple and diverse arguments can enhance effectiveness by broadening the appeal to wider audiences, especially when arguments are repeated and refined through constructive dialogue. We discuss the role of framing, bundling and tailoring arguments to audiences in increasing effectiveness. Our results provide further support for the current shift towards recognition of value pluralism in biodiversity science and decision-making. We hope our results will help to demonstrate more convincingly the value of biodiversity to stakeholders in decision processes and thus build better cases for its conservation.     

Mathematical analysis of the optimal habitat configurations for species persistence

We study a reaction-diffusion model in a binary environment made of habitat and non-habitat regions. Environmental heterogeneity is expressed through the species intrinsic growth rate coefficient. It was known that, for a fixed habitat abundance, species survival depends on habitat arrangements. Our goal is to describe the spatial configurations of habitat that maximise the chances of survival. Through numerical computations, we find that they are of two main types - ball-shaped or stripe-shaped. We formally prove that these optimal shapes depend on the habitat abundance and on the amplitude of the growth rate coefficient. We deduce from these observations that the optimal shape of the habitat realises a compromise between reducing the detrimental habitat edge effects and taking advantage of the domain boundary effects. In the case of an infinite-periodic environment, we prove that the optimal habitat shapes can be deduced from those in the case of a bounded domain.     

Identification of exacerbations in obstructive lung disease through biomarkers

Inflammation has been identified as an important factor for disease exacerbation in obstructive lung disease. In this study, we used neutrophil and eosinophil counts as biomarkers for exacerbation in obstructive lung disease. We conducted a case–control study within a cohort of patients frequenting an outpatient clinic of Respiratory Medicine using data from the Utrecht Patient Oriented Database (UPOD). Cases were patients with a hospital admission for obstructive lung disease in 2005. For each case, one control patient was sampled from the same study base. We identified 143 cases (118 patients with chronic obstructive pulmonary disease and 25 asthma patients) and 143 controls. Admission was associated with both neutrophilia (adjusted odds ratio (OR) 4.3; 95% confidence interval (CI) 2.2–8.5), and eosinophilia (adjusted OR 2.6; 95% CI 1.1–6.2). The association with eosinophilia was only seen in asthma patients. In conclusion, neutrophil and eosinophil counts seem to be useful biomarkers for identifying exacerbations in pharmacoepidemiological studies on obstructive lung disease.     

Consequential Life Cycle Assessment With Market‐Driven Design

This article describes the development of a consequential life cycle assessment (cLCA) with endogenous market‐driven design (MDD). Incorporation of MDD within cLCA (cLCA‐MDD) is beneficial because design decisions, influenced by market forces, are a major source of environmental emissions and resource consumption in many life cycle systems. cLCA‐MDD captures the environmental impact of these design responses resulting from industrial and policy decisions. We begin by developing the concept of cLCA‐MDD, then present a case study that demonstrates how design responses can be endogenously captured in a cLCA analysis. The case study is in two parts: First, we incorporate endogenous design responses into a cLCA of a mid‐size vehicle and, second, we conduct a policy analysis using a cLCA‐MDD approach. The case study illustrates that cLCA‐MDD can capture multiple “ripple effects” resulting from an industrial decision (e.g., downsizing a vehicle's engine) or a policy decision (e.g., raising gasoline taxes) and that these effects significantly influence results. A key challenge of the approach is appropriately managing and communicating uncertainties associated with the choice of economic parameters or models. We discuss sources of uncertainty in cLCA‐MDD and demonstrate a presentation scheme to facilitate communication of result sensitivity to uncertainties from input parameters, models, and model structure.     

Somatic stability in chorionic villi samples and other Huntington fetal tissues

We have studied different tissues from two affected fetuses with Huntington's disease (HD). In the first case the analysis was performed at 11 weeks of pregnancy; CAG repeats from seven different tissues were compared with the results obtained in the chorionic villi sample (CVS). We found 42 CAG repeats in all samples. In the second case the study was done at 12 weeks; eight tissues (including brain) were studied and compared with the CVS; in all of them, 44 CAG repeats were obtained. Our results show a somatic stability in the different analyzed tissues and suggest that mitotic instability can be a secondary consequence of neuronal degeneration and gliosis. Likewise, our data show great viability in the prenatal diagnosis (PD) of Huntington's disease using samples from any tissue.     

High efficiency protocol of DNA extraction from Micromys minutus mandibles from owl pellets: a tool for molecular research of cryptic mammal species

Owl pellets have high potential as a source of DNA. However, this noninvasive method of collecting DNA is rarely used, and its methodological aspects are poorly understood. We investigated the methodology for DNA extraction and amplification from owl pellets containing the smallest European rodent—the Harvest mouse Micromys minutus—as an example. We used mandibles identified in owl pellets for mitochondrial and nuclear DNA amplification. For DNA extraction, we tested two commercial protocols and utilized a protocol being a combination of two commercial kits which ensured high efficiency of DNA extraction. Additionally, we recorded that the amount of DNA was five times higher in extracts from teeth as compared to DNA extracts from jawbones derived from the same mandible. The quantity of DNA was significantly positively correlated with biological sample weight; however, the age of the pellet remains had an impact on the level of inhibition. We recorded inhibition in 40 % of mtDNA extracts derived from pellets older than 150 months, whereas in DNA extracts from pellets younger than 80 months, we did not observe a negative impact of inhibition on PCR efficiency. The amplification success rate was 89.9 % for the mitochondrial fragment and 39.4 % in the case of the nuclear fragment. We observed partial degradation of DNA evidenced by the fact that the longest fragments that we were able to amplify in the case of mtDNA were 450 and 200 bp for nuDNA. The study shows that pellets can be considered as a source of DNA and have high potential for molecular research in the case of threatened species and species that are difficult to study using standard field techniques.     

The Use of Case Studies in Establishing Feasibility for Wetland Restoration

Establishing restoration feasibility is a multifaceted process that requires consideration of the ecological, social, and economic conditions of a given site. Examining completed restoration projects that report successes and failures may enhance this complex decision‐making process. We describe five completed wetland restoration projects and identify commonalities among them to inform the process of establishing feasibility for proposed restoration projects. Most of the case studies identified the need to gather preexisting and historical information, develop scenarios through hydrologic modeling, study the restoration materials, use best professional judgement for unanswered questions, establish multigroup collaboration, gain public support from stakeholders, and monitor postrestoration. We applied these lessons to a study that evaluated the feasibility of restoring Dyke Marsh Preserve, a tidal freshwater marsh in Virginia that the National Park Service is mandated to preserve. We found that the use of case studies substantially increased confidence in the decision‐making process by focusing discussions on the most important ecological, social, and economic aspects of a potential restoration.