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Modeling uncertainty in a database for physical gene mapping data.

We are building a database for the storage, retrieval, and graphical display of physical gene mapping data. To allow this information to be analyzed robustly, such a database must confront the inherent uncertainty of the data as a central design issue. The paper describes the overall database design, the types of gene mapping data which the system will contain, the types of uncertainty in the data, and certain of the design issues involved in allowing the database to handle uncertainty in a comprehensive fashion. Only if a full appreciation of uncertainty is built into the system from its inception will a physical gene mapping database be truly robust and successful.

Chromosome Mapping↗

Neurotoxicology dose/response assessment for several cholinesterase inhibitors: use of uncertainty factors.

Dose/response assessment for non-carcinogenic endpoints typically uses the Acceptable Daily Intake (ADI) or Reference Dose (RfD) approach, in which a dose believed to cause no toxic effect is divided by a number of safety or uncertainty factors (e.g., to control for variability and cross-species extrapolation), in order to estimate a dose presumed to have no adverse effects in humans. With the establishment of neurotoxicology testing guidelines, routine use of uncertainty factors to undertake neurotoxicity dose/response assessment procedures is likely. This approach to dose/response assessment has not yet been widely applied to neurotoxicity data. The purpose of this study was to assess the use of uncertainty factors and the assumptions underlying the use of the uncertainty factor method in assessing risk for several known human neurotoxicants. Because of the availability of a large neurotoxicity data base which included human exposure data, parathion, diisopropylfluorophosphate, physostigmine and acrylamide were chosen for this analysis. Literature searches were conducted for both human and animal data. The resulting data were assigned to one of five end point categories: Neurochemistry/neuropathology, physiology/consummatory behavior, sensory/motor, electrophysiology, and learning/memory behavior. No-observed-adverse-effect levels (NOAELs) and/or lowest-observed-adverse-effect levels (LOAELs) were determined when possible for each end point and for several species. Reference doses (RfDs) were calculated and compared across species. A number of issues and critical assumptions were identified.

Animals↗

Student and faculty assumptions about the nature of uncertainty in medicine and medical education.

Clinical reasoning involves an element of uncertainty. Teaching clinical reasoning involves understanding how students view uncertainty as well as how medical problems are solved. This study uses Perry's model of intellectual development to explore changes in how medical students, residents, and instructors think about the nature of knowledge. A total of 31 medical students, residents, and instructors completed the Widick and Knefelkamp Measure of Intellectual Development revised to focus specifically on uncertainty in medicine. Consistent with Perry's theory, scores reflected increasing degrees of acceptance of the role of uncertainty in medicine with increasing experience. Based on these results, it is concluded that to improve the effectiveness of teaching problem solving in medicine, faculty must challenge the assumptions held by medical students about the certainty of medical knowledge while teaching the process of clinical diagnosis.

Attitude↗

The measurement of uncertainty in illness.

The purpose of this investigation was to explore the role of uncertainty as a significant variable influencing patients' experiences in illness, treatment, and hospitalization. A theory was proposed on uncertainty in illness. Based upon this conceptualization, a 30-item scale tapping the uncertainty in symptomatology, diagnosis, treatment, relationship with care-givers, and planning for the future was developed. The Mishel Uncertainty in Illness Scale (MUIS) was factor analyzed and two factors were extracted from the data. Replication of the factor analysis provided support for the robustness of each factor. The reliability coefficient for each factor of the MUIS was highly adequate for both the initial and replication analyses. Three validation studies were conducted. Initial support for construct validity of the scale was demonstrated by the finding that the MUIS discriminates between treatment groups according to expected differences. Support for theoretical predictions was evidenced by the significant correlation between the MUIS and stress as measured by the Hospital Stress Events Scale. Convergent validity was supported by the finding that the MUIS correlates significantly with lack of comprehension.

Anxiety↗

Uncertainties in bone mineral density T scores.

In the diagnosis and management of osteopenia and osteoporosis, dual photon absorptiometric measurements of lumbar spine and proximal femur bone mineral density are interpreted by calculating a T score, which is the number of standard deviations by which a result deviates from the mean bone density in young adults of the same sex. Threshold values are then used to categorize patients as having osteopenia or osteoporosis. The uncertainty associated with a single bone mineral density measurement, as well as the uncertainties in the assumed values for the bone mineral density in young adults and the population standard deviation, combine to create an uncertainty in the calculated T score. It is estimated that 95% of bone density measurements have a T score uncertainty of less than 0.4. This means that a single measurement of bone mineral density should not be used in isolation to assign a given patient to a specific diagnostic category. Rather, a bone mineral density measurement should be regarded as only one of the variables that determine the risk of fracture in a given patient.

Absorptiometry, Photon↗

Uncertainty--a chemist's view.

Complete characterization of the performance of analytical methods requires an evaluation of the halo of uncertainty bracketing the reported result. Achieving a satisfactory estimate of this uncertainty is more important than how this estimate is produced. Enumeration of all conceivable error components--the so-called error budget approach--is one way to estimate the uncertainty, but it is not the only way. In fact, when applied to analytical chemistry this approach is likely to (1) overlook important variables and double count others, (2) avoid considering unknown and unknowable interactions and interferences, and (3) adjust for missing variables with an uncontrollable "Type B" component. The problem is one of experimental design. Alternative and more efficient ways of estimating uncertainty in analytical chemistry include the Youden ruggedness procedure, accompanied by a bonus of optimization, and the all-encompassing interlaboratory method-performance trial.

Chemistry Techniques, Analytical↗

Somatic awareness, uncertainty, and delay in care-seeking in acute heart failure.

Symptom monitoring is difficult for heart failure (HF) patients. Difficulties physically sensing and determining symptom meaning may lead to uncertainty and delay treatment. Somatic awareness may provide insight into symptom monitoring ability. A model combining physical and cognitive aspects of the symptom experience was developed to examine factors affecting care-seeking among HF patients. Adults hospitalized with acute HF were interviewed and completed questionnaires measuring somatic awareness and uncertainty. HF symptom duration prior to admission measured delay. HF specific somatic awareness and symptom pattern predicted delay. Uncertainty correlated with somatic awareness, but did not predict delay. Few responded to early HF symptoms delaying until acutely ill. Development of interventions to improve symptom monitoring is needed.

Acute Disease↗

On the translation of uncertainty from toxicokinetic to toxicodynamic models--the TCDD example.

When estimating human health risks from exposure to TCDD using toxicokinetic and toxicodynamic models, it is important to understand how model choice and assumptions necessary for modeling add to the uncertainty of risk estimates. Several toxicokinetic models have been proposed for the risk assessment of dioxins, in particular the elimination kinetics in humans has been a matter of constant debate. For a long time, a simple linear elimination kinetics has been common choice. Thus, it was used for the statistical analysis of the largest occupationally exposed cohort, the German Boehringer cohort. We challenge this assumption by considering, amongst others, a nonlinear modified Michaelis-Menten-type elimination kinetics, the so-called Carrier kinetics. Using the area under the lipid TCDD concentration time curve as dose metrics, we model the time to cancer-related death using the Cox proportional hazards model as toxicodynamic model. This risk assessment set-up was simulated in order to quantify uncertainty of both the dose (TCDD body burden) and the risk estimates, depending on the use of the kinetic model, variations of carcinogenic effect of TCDD and variations of latency period (lag time). If past exposure is estimated assuming a linear elimination kinetics although a Carrier kinetics actually holds, then high exposures in reality will be underestimated through statistical analysis and low exposures will be overestimated, respectively. This bias will carry over on the estimated individual concentration-time curves and the therefrom derived TCDD dose metric values. Using biased dose values when estimating a dose-response relationship will finally lead to biased risk estimates. The extent of bias and the decrease of precision are quantified in selected scenarios through this simulation approach. Our findings are in concordance with recent results in the field of dioxin risk assessment. They also reinforce the general demand for the scheduled uncertainty assessments in risk analyses.

Adult↗

From innumeracy to insight: the uncertainty of help versus harm in treatment of asymptomatic aortic aneurysms.

There is insufficient evidence that the surgical treatment of asymptomatic infrarenal aneurysms > 5.5 cm. is beneficial to patients. This is the result of serious complications of aneurysm surgery and the dearth of information from randomized trials. Based on evidence from the literature we defined scenarios and translated data into natural frequency trees to improve understanding of the uncertainty of help versus harm due to treatment of aneurysms. Our analysis shows that the majority of patients can expect little on longevity from surgery while they are at risk of dying from surgery or suffering from serious morbidity. We conclude that, as long as uncertainty persist, patients should be treated in hospitals that can show very low surgical mortality and major morbidity rates. To further resolve the problem of uncertainty randomized trials for larger aneurysms should be performed. Important issues to discuss are the lower and upper limits of the diameter of the aneurysms and the age and risk profiles of the patients to be included in such trials.

Aortic Aneurysm↗

Treatment of uncertainty and developing conceptual models for environmental risk assessments and radioactive waste disposal safety cases.

The common approach to performing quantitative risk assessments in the contaminated land industry in the UK lacks a formal methodology for the treatment of the full range of uncertainties and for documenting decisions regarding the development of conceptual models and the selection of computer codes. The approach presented here represents an alternative, more detailed, and systematic approach for developing conceptual models and addressing uncertainties when undertaking contaminated land risk assessments. It is intended that the advantages of this approach are recognised by practitioners in the contaminated land industry and adopted, where appropriate, to help improve the quality of contaminated land risk assessments. The identification of features, events, and processes (FEPs) has been applied to safety assessments of deep geological and near-surface disposal of radioactive wastes. One of the primary benefits of using this approach is in the development of conceptual models. The approach identifies the FEPs that need to be addressed during the development of conceptual models and in the selection of suitable computer codes that can be used to represent the conceptual models. This approach has been applied by BNFL at the low-level radioactive waste disposal site at Drigg in Cumbria and is currently being adopted for a contaminated land study at the Sellafield site, also in Cumbria. This paper presents the advantages of using FEPs in the development of conceptual models and the treatment of uncertainties. The paper also discusses the application of this approach to contaminated land studies and provides an example to demonstrate the application of the approach. BNFL's approach at the Drigg site involves the identification of components (features) and phenomena (events and processes) that govern interactions and dependencies between the components by arranging them in a matrix format.

Environmental Exposure↗

The influence of metal source uncertainty on cost-effective allocation of mine water pollution abatement in catchments.

In mine water pollution abatement, it is commonly assumed that known mine waste sites are the major pollution sources, thus neglecting the possibility of significant contribution from other old and diffuse sources within a catchment. We investigate the influence of different types of pollution source uncertainty on cost-effective allocation of abatement measures for mine water pollution. A catchment-scale cost-minimization model is developed and applied to the catchment of the river Dalälven, Sweden, in order to exemplify important effects of such source uncertainty. Results indicate that, if the pollution distribution between point and diffuse sources is partly unknown, downstream abatement measures, such as constructed wetlands, at given compliance boundaries are often cost-effective. If downstream abatement measures are not practically feasible, the pollution source distribution between point and diffuse mine water sources is critical for cost-effective solutions to abatement measure allocation in catchments. In contrast, cost-effective solutions are relatively insensitive to uncertainty in total pollutant discharge from mine water sources.

Cadmium↗

Decision making under uncertainty in case of soil remediation.

Decisions on soil remediation are one of the most difficult management issues of municipal and state agencies. The assessment of contamination is uncertain, the costs of remediation are high, and the impacts on the environment are multiple. This paper presents a general, transparent, and consistent method for decision making among the remediation alternatives. Soil washing, phytoremediation, and no remediation are exemplarily considered. Multi-criteria utility functions including (a) the cost of remediation (b) the impact on human health and agricultural productivity, and (c) the economic gain after remediation are constructed using probability density functions representing contamination for all site coordinates. Herewith, the probability of different types of (i) correct decisions such as a hit or a true rejection and (ii) erroneous decisions such as a false alarm or miss are examined. The decision theoretic model is applied to a case study on heavy metal contaminated soil. This case study reveals the non-linear structure of multi-criteria-decision making. The case study shows that the geostatistical uncertainties of the log-normal distributed soil contamination must be taken into account: When uncertainties are not considered and the utilities are assessed according to the estimated value for a spatial unit, only few (N=26) spatial units result where the utility score of the alternative soil washing are higher than the utility score to the no remediation alternative. However, when taking into account geostatistical uncertainties of the log-normal soil distribution this number is about ten times greater (N=237). Furthermore, the use of 'maximizing expected utility' as decision rule is critical in that it may lead to a high probability of misses.

Cadmium↗

A neural representation of categorization uncertainty in the human brain.

The ability to classify visual objects into discrete categories ("friend" versus "foe"; "edible" versus "poisonous") is essential for survival and is a fundamental cognitive function. The cortical substrates that mediate this function, however, have not been identified in humans. To identify brain regions involved in stimulus categorization, we developed a task in which subjects classified stimuli according to a variable categorical boundary. Psychophysical functions were used to define a decision variable, categorization uncertainty, which was systematically manipulated. Using event-related functional MRI, we discovered that activity in a fronto-striatal-thalamic network, consisting of the medial frontal gyrus, anterior insula, ventral striatum, and dorsomedial thalamus, was modulated by categorization uncertainty. We found this network to be distinct from the frontoparietal attention network, consisting of the frontal and parietal eye fields, where activity was not correlated with categorization uncertainty.

Adolescent↗

Limits of uncertainty in measured values of embolus-to-blood ratios in dual-frequency TCD recordings due to nonidentical sample volume shapes.

Transcranial Doppler (TCD) ultrasound (US) is widely used to detect cerebral embolisation. A drawback of the technique is that it is difficult to distinguish between small gaseous emboli and large solid emboli. One potential solution is to make measurements from blood and emboli at two different frequencies, because the frequency-dependence of ultrasonic backscatter will be different for the two types of emboli. Unfortunately, it is not possible to produce two identical sample volumes at two different frequencies, and this will introduce an uncertainty into any such measurements. Experimental measurements have been made of US fields distorted by temporal bone at 2.0 MHz and 2.5 MHz, and a mathematical model has been developed to examine the uncertainty introduced by the different field shapes at these frequencies. The results suggest that the uncertainties are sufficiently large (on the order of 2 to 4 dB) that a significant percentage of emboli are likely to be misclassified by the dual-frequency method.

Blood↗

Intolerance of uncertainty in obsessive-compulsive disorder.

Pathological doubt, a prominent feature of obsessive-compulsive disorder (OCD), may be related to difficulty tolerating ambiguous or uncertain situations. This is thought to be particularly true of those patients with checking compulsions. Intolerance of uncertainty (IU) has been studied extensively within the domains of worry and generalized anxiety; however, it has received relatively little empirical attention in OCD patients. We administered the Intolerance of Uncertainty Scale [Personality and Individual Differences 17 (1994) 791] to 55 clinic patients with OCD, 43 of whom had checking compulsions, and 14 nonanxious controls. OC checkers showed greater IU than did OC noncheckers and NACs. The latter two groups did not differ from each other. Furthermore, both repeating and checking rituals were associated with IU. Pathological doubt may be understood not only in terms of knowledge-based constructs, but also patients' emotional reaction to feelings of uncertainty. We discuss the implications for increasing tolerance via cognitive-behavioral therapy.

Adult↗

The comparative psychology of uncertainty monitoring and metacognition.

Researchers have begun to explore animals' capacities for uncertainty monitoring and metacognition. This exploration could extend the study of animal self-awareness and establish the relationship of self-awareness to other-awareness. It could sharpen descriptions of metacognition in the human literature and suggest the earliest roots of metacognition in human development. We summarize research on uncertainty monitoring by humans, monkeys, and a dolphin within perceptual and metamemory tasks. We extend phylogenetically the search for metacognitive capacities by considering studies that have tested less cognitively sophisticated species. By using the same uncertainty-monitoring paradigms across species, it should be possible to map the phylogenetic distribution of metacognition and illuminate the emergence of mind. We provide a unifying formal description of animals performances and examine the optimality of their decisional strategies. Finally, we interpret animals' and humans' nearly identical performances psychologically. Low-level, stimulus-based accounts cannot explain the phenomena. The results suggest granting animals a higher-level decision-making process that involves criterion setting using controlled cognitive processes. This conclusion raises the difficult question of animal consciousness. The results show that animals have functional features of or parallels to human conscious cognition. Remaining questions are whether animals also have the phenomenal features that are the feeling/knowing states of human conscious cognition, and whether the present paradigms can be extended to demonstrate that they do. Thus, the comparative study of metacognition potentially grounds the systematic study of animal consciousness.

Animals↗

Who's better not best: appropriate probabilistic uncertainty analysis.

The use of probabilistic analysis as a means for analyzing uncertainty within economic analysis has grown in popularity in recent years as it has been recognized as the most complete method for propagating uncertainty with respect to input parameters in terms of uncertainty about outcomes of interest. The World Health Organization (WHO) in a series of recent reports and publications have recognized the role of probabilistic analysis in what they term generalized cost-effectiveness analysis. However, there are fundamental problems with the analysis and the interpretation of such analysis as proposed by WHO. This study highlights three specific points for concern and offers constructive criticism by recommending more appropriate approaches.

Canada↗

Toward Class Imbalance and Uncertainty in Powder XRD Analysis: A Dual-Channel Fusion Network for Space Group Classification.

Accurate identification of space groups from powder X-ray diffraction (pXRD) is essential for understanding crystal structures and accelerating materials discovery. However, this task remains highly challenging due to inherent peak overlap, experimental noise, and the complexity of the 230-class classification problem. To address the critical issues of class imbalance and data scarcity, we first design a general physics-informed data augmentation pipeline. We then propose a dual-channel fusion uncertainty-aware network (DFUN) for automated space group classification. The DFUN architecture integrates two complementary feature representations: convolutional features extracted directly from raw diffraction profiles and domain-specific peak descriptors. These distinct representations are adaptively fused through a gating mechanism. Furthermore, to mitigate the inherent long-tailed distribution of crystallographic data, we employ a hybrid loss function that combines Focal Loss with Label Smoothing. Finally, we incorporate Monte Carlo Dropout to provide predictive uncertainty estimation, thereby enabling not only accurate classification but also a crucial assessment of the model's reliability. Evaluated on large-scale simulated data and two public data sets (opXRD and RRUFF), DFUN outperforms the evaluated baseline methods across the reported metrics. The framework also provides uncertainty-aware predictions, establishing DFUN as a robust and interpretable solution for high-throughput automated crystallographic analysis from powder diffraction.

Uncertainty↗