Interpretation and reporting considerations of low-level DNA profiles following MinElute® purification of PowerPlex® 21 amplified products.

The generation of high-quality DNA profiles from trace amounts of DNA continues to be an issue in forensic casework. Several methods have been proposed over the years to increase recovery rates for low input DNA, including purification of PCR products, an increase in PCR cycle numbers and increasing injection time or voltage during electrophoresis. In this study, the characteristics of DNA profiles generated using QIAGEN MinElute® purification of Promega PowerPlex® 21 amplified products for low DNA input samples, ranging from 80 pg down to 4 pg, were evaluated. MinElute® purification was found to be a simple, effective and time efficient method, which can greatly improve the resolution of amplified PCR products, recovering 100% of donor concordant alleles from as little 16 pg of input template DNA and generating sufficient allelic information for interpretation from as low as 4 pg inputs. However, as is commonly observed with low template DNA samples, the results exhibited extensive disparity in the effects of stochastic variation in amplification, including increased heterozygote peak height imbalance, stutter ratios and instances of allelic drop-in and drop-out, both within and between replicates. As such, it is important that the extent and variability of these stochastic effects are appropriately incorporated in the development of robust profile interpretation guidelines for DNA profiles generated from purified PCR products.

Disease X epidemic control using a stochastic model and a deterministic approximation: Performance comparison with and without parameter uncertainties.

BACKGROUND: The spread of infectious diseases can be modeled using deterministic or stochastic models. A deterministic approximation of a stochastic model can be appropriate under some conditions, but is unable to capture the discrete nature of populations. We look into the choice of a model from the perspective of decision making. METHOD: We consider an emerging disease (Disease X) in a closed population modeled by a stochastic SIR model or its deterministic approximation. The objective of the decision maker is to minimize the cumulative number of symptomatic infected-days over the course of the epidemic by picking a vaccination policy. We consider four decision making scenarios: based on the stochastic model or the deterministic model, and with or without parameter uncertainty. We also consider different sample sizes for uncertain parameter draws and stochastic model runs. We estimate the average performance of decision making in each scenario and for each sample size. RESULTS: The model used for decision making has an influence on the picked policies. The best achievable performance is obtained with the stochastic model, knowing parameter values, and for a large sample size. For small sample sizes, the deterministic model can outperform the stochastic model due to stochastic effects. Resolving uncertainties may bring more benefit than switching to the stochastic model in our example. CONCLUSION: This article illustrates the interplay between the choice of a type of model, parameter uncertainties, and sample sizes. It points to issues to be considered when optimizing a stochastic model.

Cumulative Effective Dose During Fluoroscopically Guided Interventions (FGI): Analysis of More Than 5000 FGIs in a Single European Center.

BACKGROUND: The number of fluoroscopically guided interventions (FGI) has increased significantly over time. However, little attention has been paid to possible stochastic radiation effects. The aim of this retrospective study was to investigate the number of patients who received cumulative effective doses over 100 mSv during FGI procedures. MATERIAL AND METHODS: Five thousand five hundred and fifty four classified FGI procedures were included. Radiation dose data, retrieved from an in-house-dose-management system, was analysed. Effective doses and cumulative effective doses (CED) were calculated. Patients who received a CED > 100 mSv were identified. Radiology reports, patient age, imaging and clinical data of these patients were used to identify reasons for CED ≥ 100 mSv. RESULTS: One Hundred and thirty two (41.1% female) of 3981 patients received a CED > 100 mSy, with a mean CED of 173.5 ± 84.5 mSv. Mean age at first intervention was 66.1 ± 11.7 years. 81 (61.4%) of 132 were older than 64 years, one patient was < 30 years. 110 patients received ≥ 100 mSv within one year (83.4%), through FGIs: EVAR, pelvic/mesenteric interventions (stent or embolization), hepatic interventions (chemoembolization, TIPSS), embolization of cerebral aneurysms or arterio-venous-malformations. CONCLUSIONS: Substantial CED may occur in a small but not ignorable fraction of patients (~ 3%) undergoing FGIs. Approximately 2/3rd of patients may most likely not encounter radiation-related stochastic effects due to life-threatening diseases and age at first treatment > 65 years but 1/3rd may. Patients undergoing more than one FGI (77%) carry a higher risk of accumulating effective doses > 100 mSv. Remarkably, 23% received a mean CED 162.2 ± 72.3 mSv in a single procedure.

[Individual dosimetry as an element of health prevention for employees exposed to ionizing radiation]. / Dozymetria indywidualna jako element profilaktyki zdrowotnej pracowników narazonych na promieniowanie jonizujace.

The paper presents the current radiation protection standards, in line with the recommendations of the International Commission on Radiological Protection (ICRP), and their evolution over the years based on new knowledge about the biological effects of ionizing radiation and the changing attitude of people to the accepted risk. The work takes into account in particular the role of the dose limit principle and individual dose measurements in activities aimed at health prevention of individual people occupationally exposed to ionizing radiation. Med Pr Work Health Saf. 2023;74(6):527-39.

Coarse-Grained Modeling of EUV Patterning Process Reflecting Photochemical Reactions and Chain Conformations.

Enabling extreme ultraviolet lithography (EUVL) as a viable and efficient sub-10 nm patterning tool requires addressing the critical issue of reducing line edge roughness (LER). Stochastic effects from random and local variability in photon distribution and photochemical reactions have been considered the primary cause of LER. However, polymer chain conformation has recently attracted attention as an additional factor influencing LER, necessitating detailed computational studies with explicit chain representation and photon distribution to overcome the existing approach based on continuum models and random variables. We developed a coarse-grained molecular simulation model for an EUV patterning process to investigate the effect of chain conformation variation and stochastic effects via photon shot noise and acid diffusion on the roughness of the pattern. Our molecular simulation demonstrated that final LER is most sensitive to the variation in photon distributions, while material distributions and acid diffusion rate also impact LER; thus, the intrinsic limit of LER is expected even at extremely suppressed stochastic effects. Furthermore, we proposed and tested a novel approach to improve the roughness by controlling the initial polymer chain orientation.

Fixed/Preassigned-time stochastic synchronization of T-S fuzzy complex networks with partial or complete information communication.

This paper is devoted to analyzing Fixed/Preassigned-time synchronization of T-S fuzzy complex networks (TSFCNs) with stochastic effects. Unlike the existing results, partial information communication and complete information communication are all considered according to a Bernoulli distribution. Furthermore, different controllers with quantization are structured to realize our synchronization goal, and one of control parameters can switch based on the error information. Besides, we derive sufficient conditions to guarantee Fixed-time(FDT) and Preassigned-time(PAT) synchronization of TSFCNs, and analyze the difference of FDT and PAT synchronization. Finally, numerical examples and comparisons show that our results are valid.

ICRP PUBLICATION 152 Approved by the Commission in November 2021.

Radiation detriment is a concept developed by the International Commission on Radiological Protection to quantify the burden of stochastic effects from low-dose and/or low-dose-rate exposures to the human population. It is determined from the lifetime risks of cancer for a set of organs and tissues and the risk of heritable effects, taking into account the severity of the consequences. This publication provides a historical review of detriment calculation methodology since ICRP Publication 26, with details of the procedure developed in ICRP Publication 103, which clarifies data sources, risk models, computational methods, and rationale for the choice of parameter values. A selected sensitivity analysis was conducted to identify the parameters and calculation conditions that can be major sources of variation and uncertainty in the calculation of radiation detriment. It has demonstrated that sex, age at exposure, dose and dose-rate effectiveness factor, dose assumption in the calculation of lifetime risk, and lethality fraction have a substantial impact on radiation detriment values. Although the current scheme of radiation detriment calculation is well established, it needs to evolve to better reflect changes in population health statistics and progress in scientific understanding of radiation health effects. In this regard, some key parameters require updating, such as the reference population data and cancer severity. There is also room for improvement in cancer risk models based on the accumulation of recent epidemiological findings. Finally, the importance of improving the comprehensibility of the detriment concept and the transparency of its calculation process is emphasised.© 2022 ICRP. Published by SAGE.

Protección de embarazadas en radiología oral / Protection of pregnant women in oral radiology

Las radiografías dentales son necesarias para diagnosticar y hacer seguimiento de múltiples enfermedades orales. Sin embargo, debido a los conocidos efectos estocásticos de los rayos X dentales es imprescindible garantizar protección a los pacientes. Especial atención merecen las mujeres embarazadas por cuanto el feto es altamente vulnerable a la radiación, sobre todo enlas primeras semanas. Algunas recomendaciones de protección radiológica en esta población son: El uso de radiografías ha sido justificado; realizar el estudio 10 días después del inicio de la menstruación; informar del procedimiento a la embarazada a fin de evitar el miedo; optimizar el procedimiento (haz colimado, alto kVp, control manual de disparo, calibración regular etc.) y usar delantal plomado solo si las condiciones de optimización son insuficientes

Dental x-rays are necessary to diagnose and monitor multiple oral diseases. However, due to the well-known stochastic effects of dental X-rays, it is essential to guarantee patient protection. Pregnant women deserve special attention because the fetus is highly vulnerable to radiation, especially in the first weeks. Some recommendations for radiological protection in this population are the use of radiographs has been justified; conduct the study 10 days after the onset of menstruation; inform the pregnant woman about the procedure to avoid fear; optimize the procedure (collimated beam, high kVp, manual trip control, regular calibration etc.) and use a lead apron only if the optimization conditions are insufficient.

Radiation detriment calculation methodology: summary of ICRP Publication 152.

Radiation detriment is a concept to quantify the burden of stochastic effects from exposure of the human population to low-dose and/or low-dose-rate ionising radiation. As part of a thorough review of the system of radiological protection, the International Commission on Radiological Protection (ICRP) has compiled a report on radiation detriment calculation methodology as Publication 152. It provides a historical review of the detriment calculation with details of the procedure used in ICRP Publication 103. A selected sensitivity analysis was conducted to identify the parameters and calculation conditions that can be major sources of variation and uncertainty. It has demonstrated that sex, age at exposure, dose and dose-rate effectiveness factor, dose assumption in the lifetime risk calculation, and lethality fraction have a substantial impact on the calculated values of radiation detriment. Discussions are also made on the issues to be addressed and possible ways for improvement toward the revision of general recommendations. These include update of the reference population data and cancer severity parameters, revision of cancer risk models, and better handling of the variation with sex and age. Finally, emphasis is placed on transparency and traceability of the calculation, along with the need to improve the way of expressing and communicating the detriment.

Environmental and industrial developments in radiation cataractogenesis.

PURPOSE: This review discusses recent developments in our understanding of biological and physiological mechanisms underlying radiation cataractogenesis. The areas discussed include effects of low-dose exposures to the lens including potential relevance of non-targeted effects, the development of new personal-protective equipment (PPE) and standards in clinical and nuclear settings motivated by the updated ICRP recommendations to mitigate exposures to the lens of the eye. The review also looks at evidence from the field linking cataracts in birds and mammals to low dose exposures. CONCLUSIONS: The review suggests that there is evidence that cataractogenesis is not a tissue reaction (deterministic effect) but rather is a low dose effect which shows a saturable dose response relationship similar to that seen for non-targeted effects in general. The review concludes that new research is needed to determine the dose response relationship in environmental studies where field data are contradictory and lab studies confined to rodent models for human exposure studies.

Cytogenetic follow-up studies on humans with internal and external exposure to ionizing radiation.

Cells exposed to ionizing radiation have a wide spectrum of DNA lesions that include DNA single-strand breaks, DNA double-strand breaks (DSBs), oxidative base damage and DNA-protein crosslinks. Among them, DSB is the most critical lesion, which when mis-repaired leads to unstable and stable chromosome aberrations. Currently, chromosome aberration analysis is the preferred method for biological monitoring of radiation-exposed humans. Stable chromosome aberrations, such as inversions and balanced translocations, persist in the peripheral blood lymphocytes of radiation-exposed humans for several years and, therefore, are potentially useful tools to prognosticate the health risks of radiation exposure, particularly in the hematopoietic system. In this review, we summarize the cytogenetic follow-up studies performed by REAC/TS (Radiation Emergency Assistance Center/Training site, Oak Ridge, USA) on humans exposed to internal and external radiation. In the light of our observations as well as the data existing in the literature, this review attempts to highlight the importance of follow-up studies for predicting the extent of genomic instability and its impact on delayed health risks in radiation-exposed victims.

Physical Properties of Schwarzschild-deSitter Event Horizon Induced by Stochastic Quantum Gravity.

A new type of quantum correction to the structure of classical black holes is investigated. This concerns the physics of event horizons induced by the occurrence of stochastic quantum gravitational fields. The theoretical framework is provided by the theory of manifestly covariant quantum gravity and the related prediction of an exclusively quantum-produced stochastic cosmological constant. The specific example case of the Schwarzschild-deSitter geometry is looked at, analyzing the consequent stochastic modifications of the Einstein field equations. It is proved that, in such a setting, the black hole event horizon no longer identifies a classical (i.e., deterministic) two-dimensional surface. On the contrary, it acquires a quantum stochastic character, giving rise to a frame-dependent transition region of radial width δr between internal and external subdomains. It is found that: (a) the radial size of the stochastic region depends parametrically on the central mass M of the black hole, scaling as δr∼M3; (b) for supermassive black holes δr is typically orders of magnitude larger than the Planck length lP. Instead, for typical stellar-mass black holes, δr may drop well below lP. The outcome provides new insight into the quantum properties of black holes, with implications for the physics of quantum tunneling phenomena expected to arise across stochastic event horizons.

The use of dose quantities in radiological protection: ICRP publication 147 Ann ICRP 50(1) 2021.

The International Commission on Radiological Protection has recently published a report (ICRP Publication 147;Ann. ICRP50, 2021) on the use of dose quantities in radiological protection, under the same authorship as this Memorandum. Here, we present a brief summary of the main elements of the report. ICRP Publication 147 consolidates and clarifies the explanations provided in the 2007 ICRP Recommendations (Publication 103) but reaches conclusions that go beyond those presented in Publication 103. Further guidance is provided on the scientific basis for the control of radiation risks using dose quantities in occupational, public and medical applications. It is emphasised that best estimates of risk to individuals will use organ/tissue absorbed doses, appropriate relative biological effectiveness factors and dose-risk models for specific health effects. However, bearing in mind uncertainties including those associated with risk projection to low doses or low dose rates, it is concluded that in the context of radiological protection, effective dose may be considered as an approximate indicator of possible risk of stochastic health effects following low-level exposure to ionising radiation. In this respect, it should also be recognised that lifetime cancer risks vary with age at exposure, sex and population group. The ICRP report also concludes that equivalent dose is not needed as a protection quantity. Dose limits for the avoidance of tissue reactions for the skin, hands and feet, and lens of the eye will be more appropriately set in terms of absorbed dose rather than equivalent dose.

Quantum-Gravity Stochastic Effects on the de Sitter Event Horizon.

The stochastic character of the cosmological constant arising from the non-linear quantum-vacuum Bohm interaction in the framework of the manifestly-covariant theory of quantum gravity (CQG theory) is pointed out. This feature is shown to be consistent with the axiomatic formulation of quantum gravity based on the hydrodynamic representation of the same CQG theory developed recently. The conclusion follows by investigating the indeterminacy properties of the probability density function and its representation associated with the quantum gravity state, which corresponds to a hydrodynamic continuity equation that satisfies the unitarity principle. As a result, the corresponding form of stochastic quantum-modified Einstein field equations is obtained and shown to admit a stochastic cosmological de Sitter solution for the space-time metric tensor. The analytical calculation of the stochastic averages of relevant physical observables is obtained. These include in particular the radius of the de Sitter sphere fixing the location of the event horizon and the expression of the Hawking temperature associated with the related particle tunneling effect. Theoretical implications for cosmology and field theories are pointed out.

Consequences of multiple simultaneous opportunities to exploit others' efforts on free riding.

Individuals within a group do not all act in the same way: Typically, the investors (or producers) put efforts into producing resources while the free riders (or scroungers) benefit from these resources without contributing. In behavioral ecology, the prevalence of free riders can be predicted by a well-known game-theoretical model-the producer-scrounger (PS) model-where group members have the options to either search for resources (producers) or exploit the efforts of others (scroungers). The PS model has received some empirical support, but its predictions, surprisingly, are based on the strict assumption that only one resource can be exploited at a time. Yet, multiple simultaneous opportunities to exploit others' efforts should frequently occur in nature. Here, we combine analytic and simulation approaches to explore the effect of multiple simultaneous scrounging opportunities on tactic use. Our analyses demonstrate that scrounging rates should increase with the number of simultaneous opportunities. As such, the amount and spatial distribution (i.e., clumped vs. dispersed) of resources as well as the risk of predation are key predictors of scrounging behavior. Because scroungers contribute to reducing the speed of resource exploitation, the model proposed here has direct relevance to the exploitation and sustainability of renewable resources.

Stochastic yield catastrophes and robustness in self-assembly.

A guiding principle in self-assembly is that, for high production yield, nucleation of structures must be significantly slower than their growth. However, details of the mechanism that impedes nucleation are broadly considered irrelevant. Here, we analyze self-assembly into finite-sized target structures employing mathematical modeling. We investigate two key scenarios to delay nucleation: (i) by introducing a slow activation step for the assembling constituents and, (ii) by decreasing the dimerization rate. These scenarios have widely different characteristics. While the dimerization scenario exhibits robust behavior, the activation scenario is highly sensitive to demographic fluctuations. These demographic fluctuations ultimately disfavor growth compared to nucleation and can suppress yield completely. The occurrence of this stochastic yield catastrophe does not depend on model details but is generic as soon as number fluctuations between constituents are taken into account. On a broader perspective, our results reveal that stochasticity is an important limiting factor for self-assembly and that the specific implementation of the nucleation process plays a significant role in determining the yield.

The self-assembly of a large biological molecule from small building blocks is like finishing a puzzle of magnetic pieces by shaking the box. Even though each piece of the puzzle is attracted to its correct neighbours, the limited control makes it very hard to finish the puzzle in a short amount of time. The problem becomes even more difficult if several copies of the same puzzle are assembled in one box. If several puzzles start at the same time, the different parts might steal pieces from each other, making it impossible to successfully complete any of the puzzles. This is called a depletion trap. If the box is only shaken and there is no real control over individual pieces, these traps occur at random. Overcoming these random depletion traps is an important challenge when assembling nanostructures and other artificial molecules designed by humans without wasting many, potentially expensive, components. Previous studies have shown that when multiple copies of the same structure are assembled simultaneously, slowing the rate of initiation increases the yield of correctly-made structures. This prevents new structures from stealing pieces from existing structures before they are fully completed. Now, Gartner, Graf, Wilke et al. have used a mathematical model to show that changing the way initiation is delayed leads to different yields. This was especially true for small systems where fluctuations in the availability of the different pieces strongly enhanced the initiation of new structures. In these cases, the self-assembly process terminated undesirably with many incomplete structures. Nanostructures have various applications ranging from drug delivery to robotics. These findings suggest that in order to efficiently assemble biological molecules, the concentrations of the different building blocks need to be tightly controlled. A question for further research is to investigate strategies that reduce fluctuations in the availability of the building blocks to develop more efficient assembly protocols.

Examination of LT-DNA traces - literature overview and general recommendations of the Polish Speaking Working Group of the International Society for Forensic Genetics (ISFG-PL).

The available literature on traces characterised by a suboptimal amount of DNA, as well as expert research practice, show the complex nature of LT-DNA traces: from their detection and collection, through genetic analysis, up to the interpretation of final results. The aims of this paper are to systematise the current state of knowledge on handling LT-DNA traces and develop examination guidelines, as recommended by the Polish Speaking Working Group of the International Society for Forensic Genetics (ISFG-PL). The proposed guidelines should be followed by all Polish laboratories conducting forensic genetic analyses for the purpose of judicial proceedings.

Human individual radiation sensitivity and prospects for prediction.

In the past few decades, it has become increasingly evident that sensitivity to ionising radiation is variable. This is true for tissue reactions (deterministic effects) after high doses of radiation, for stochastic effects following moderate and possibly low doses, and conceivably also for non-cancer effects such as cardiovascular disease, the causal pathway(s) of which are not yet fully understood. A high sensitivity to deterministic effects is not necessarily correlated with a high sensitivity to stochastic effects. The concept of individual sensitivity to high and low doses of radiation has long been supported by data from patients with certain rare hereditary conditions. However, these syndromes only affect a small proportion of the general population. More relevant to the majority of the population is the notion that some part of the genetic contribution defining radiation sensitivity may follow a polygenic model, which predicts elevated risk resulting from the inheritance of many low-penetrance risk-modulating alleles. Can the different forms of individual radiation sensitivities be inferred from the reaction of cells exposed ex vivo to ionising radiation? Can they be inferred from analyses of individual genotypes? This paper reviews current evidence from studies of late adverse tissue reactions after radiotherapy in potentially sensitive groups, including data from functional assays, candidate gene approaches, and genome-wide association studies. It focuses on studies published in 2013 or later because a comprehensive review of earlier studies was published previously in a report by the UK Advisory Group on Ionising Radiation.

Stochastic Effects in Autoimmune Dynamics.

Among various possible causes of autoimmune disease, an important role is played by infections that can result in a breakdown of immune tolerance, primarily through the mechanism of "molecular mimicry". In this paper we propose and analyse a stochastic model of immune response to a viral infection and subsequent autoimmunity, with account for the populations of T cells with different activation thresholds, regulatory T cells, and cytokines. We show analytically and numerically how stochasticity can result in sustained oscillations around deterministically stable steady states, and we also investigate stochastic dynamics in the regime of bi-stability. These results provide a possible explanation for experimentally observed variations in the progression of autoimmune disease. Computations of the variance of stochastic fluctuations provide practically important insights into how the size of these fluctuations depends on various biological parameters, and this also gives a headway for comparison with experimental data on variation in the observed numbers of T cells and organ cells affected by infection.

Uncertainty Quantification of Microstructure-Governed Properties of Polysilicon MEMS.

In this paper, we investigate the stochastic effects of the microstructure of polysilicon films on the overall response of microelectromechanical systems (MEMS). A device for on-chip testing has been purposely designed so as to maximize, in compliance with the production process, its sensitivity to fluctuations of the microstructural properties; as a side effect, its sensitivity to geometrical imperfections linked to the etching process has also been enhanced. A reduced-order, coupled electromechanical model of the device is developed and an identification procedure, based on a genetic algorithm, is finally adopted to tune the parameters ruling microstructural and geometrical uncertainties. Besides an initial geometrical imperfection that can be considered specimen-dependent due to its scattering, the proposed procedure has allowed identifying an average value of the effective polysilicon Young's modulus amounting to 140 GPa, and of the over-etch depth with respect to the target geometry layout amounting to O = - 0.09 µ m. The procedure has been therefore shown to be able to assess how the studied stochastic effects are linked to the scattering of the measured input⁻output transfer function of the device under standard working conditions. With a continuous trend in miniaturization induced by the mass production of MEMS, this study can provide information on how to handle the foreseen growth of such scattering.