RENEB Inter-Laboratory Comparison 2021: The Dicentric Chromosome Assay.

After large-scale radiation accidents where many individuals are suspected to be exposed to ionizing radiation, biological and physical retrospective dosimetry assays are important tools to aid clinical decision making by categorizing individuals into unexposed/minimally, moderately or highly exposed groups. Quality-controlled inter-laboratory comparisons of simulated accident scenarios are regularly performed in the frame of the European legal association RENEB (Running the European Network of Biological and Physical retrospective Dosimetry) to optimize international networking and emergency readiness in case of large-scale radiation events. In total 33 laboratories from 22 countries around the world participated in the current RENEB inter-laboratory comparison 2021 for the dicentric chromosome assay. Blood was irradiated in vitro with X rays (240 kVp, 13 mA, ∼75 keV, 1 Gy/min) to simulate an acute, homogeneous whole-body exposure. Three blood samples (no. 1: 0 Gy, no. 2: 1.2 Gy, no. 3: 3.5 Gy) were sent to each participant and the task was to culture samples, to prepare slides and to assess radiation doses based on the observed dicentric yields from 50 manually or 150 semi-automatically scored metaphases (triage mode scoring). Approximately two-thirds of the participants applied calibration curves from irradiations with γ rays and about 1/3 from irradiations with X rays with varying energies. The categorization of the samples in clinically relevant groups corresponding to individuals that were unexposed/minimally (0-1 Gy), moderately (1-2 Gy) or highly exposed (>2 Gy) was successfully performed by all participants for sample no. 1 and no. 3 and by ≥74% for sample no. 2. However, while most participants estimated a dose of exactly 0 Gy for the sham-irradiated sample, the precise dose estimates of the samples irradiated with doses >0 Gy were systematically higher than the corresponding reference doses and showed a median deviation of 0.5 Gy (sample no. 2) and 0.95 Gy (sample no. 3) for manual scoring. By converting doses estimated based on γ-ray calibration curves to X-ray doses of a comparable mean photon energy as used in this exercise, the median deviation decreased to 0.27 Gy (sample no. 2) and 0.6 Gy (sample no. 3). The main aim of biological dosimetry in the case of a large-scale event is the categorization of individuals into clinically relevant groups, to aid clinical decision making. This task was successfully performed by all participants for the 0 Gy and 3.5 Gy samples and by 74% (manual scoring) and 80% (semiautomatic scoring) for the 1.2 Gy sample. Due to the accuracy of the dicentric chromosome assay and the high number of participating laboratories, a systematic shift of the dose estimates could be revealed. Differences in radiation quality (X ray vs. γ ray) between the test samples and the applied dose effect curves can partly explain the systematic shift. There might be several additional reasons for the observed bias (e.g., donor effects, transport, experimental conditions or the irradiation setup) and the analysis of these reasons provides great opportunities for future research. The participation of laboratories from countries around the world gave the opportunity to compare the results on an international level.

Position estimation using neural networks in semi-monolithic PET detectors.

Objective. The goal of this work is to experimentally compare the 3D spatial and energy resolution of a semi-monolithic detector suitable for total-body positron emission tomography (TB-PET) scanners using different surface crystal treatments and silicon photomultiplier (SiPM) models.Approach. An array of 1 × 8 lutetium yttrium oxyorthosilicate (LYSO) slabs of 25.8 × 3.1 × 20 mm3separated with Enhanced Specular Reflector (ESR) was coupled to an array of 8 × 8 SiPMs. Three different treatments for the crystal were evaluated: ESR + RR + B,with lateral faces black (B) painted and a retroreflector (RR) layer added to the top face; ESR +RR, with lateral faces covered with ESR and a RR layer on the top face and; All ESR, with lateral and top sides with ESR. Additionally, two SiPM array models from Hamamatsu Photonics belonging to the series S13361-3050AE-08 (S13) and S14161-3050AS-08 (S14) have been compared. Coincidence data was experimentally acquired using a22Na point source, a pinhole collimator, a reference detector and moving the detector under study in 1 mm steps in thex- andDOI- directions. The spatial performance was evaluated by implementing a neural network (NN) technique for the impact position estimation in thex- (monolithic) andDOIdirections.Results. Energy resolution values of 16 ± 1%, 11 ± 1%, 16 ± 1%, 15 ± 1%, and 13 ± 1% were obtained for theS13-ESR + B + RR,S13-AllESR,S14-ESR + B + RR,S14-ESR + RR,andS14-AllESR, respectively. Regarding positioning accuracy, mean average error of 1.1 ± 0.5, 1.3 ± 0.5 and 1.3 ± 0.5 were estimated for thex- direction and 1.7 ± 0.8, 2.0 ± 0.9 and 2.2 ± 1.0 for theDOI- direction, for the ESR + B + RR, ESR + RR and All ESR cases, respectively, regardless of the SiPM model.Significance. Overall, the obtained results show that the proposed semi-monolithic detectors are good candidates for building TB-PET scanners.

Unsupervised detection and classification of heartbeats using the dissimilarity matrix in PCG signals.

BACKGROUND AND OBJECTIVE: Auscultation is the first technique applied to the early diagnose of any cardiovascular disease (CVD) in rural areas and poor-resources countries because of its low cost and non-invasiveness. However, it highly depends on the physician's expertise to recognize specific heart sounds heard through the stethoscope. The analysis of phonocardiogram (PCG) signals attempts to segment each cardiac cycle into the four cardiac states (S1, systole, S2 and diastole) in order to develop automatic systems applied to an efficient and reliable detection and classification of heartbeats. In this work, we propose an unsupervised approach, based on time-frequency characteristics shown by cardiac sounds, to detect and classify heartbeats S1 and S2. METHODS: The proposed system consists of a two-stage cascade. The first stage performs a rough heartbeat detection while the second stage refines the previous one, improving the temporal localization and also classifying the heartbeats into types S1 and S2. The first contribution is a novel approach that combines the dissimilarity matrix with the frame-level spectral divergence to locate heartbeats using the repetitiveness shown by the heart sounds and the temporal relationships between the intervals defined by the events S1/S2 and non-S1/S2 (systole and diastole). The second contribution is a verification-correction-classification process based on a sliding window that allows the preservation of the temporal structure of the cardiac cycle in order to be applied in the heart sound classification. The proposed method has been assessed using the open access databases PASCAL, CirCor DigiScope Phonocardiogram and an additional sound mixing procedure considering both Additive White Gaussian Noise (AWGN) and different kinds of clinical ambient noises from a commercial database. RESULTS: The proposed method outperforms the detection and classification performance of other recent state-of-the-art methods. Although our proposal achieves the best average accuracy for PCG signals without cardiac abnormalities, 99.4% in heartbeat detection and 97.2% in heartbeat classification, its worst average accuracy is always above 92% for PCG signals with cardiac abnormalities, signifying an improvement in heartbeat detection/classification above 10% compared to the other state-of-the-art methods evaluated. CONCLUSIONS: The proposed method provides the best detection/classification performance in realistic scenarios where the presence of cardiac anomalies as well as different types of clinical environmental noises are active in the PCG signal. Of note, the promising modelling of the temporal structures of the heart provided by the dissimilarity matrix together with the frame-level spectral divergence, as well as the removal of a significant number of spurious heart events and recovery of missing heart events, both corrected by the proposed verification-correction-classification algorithm, suggest that our proposal is a successful tool to be applied in heart segmentation.

Effect of lycopene supplementation to bovine oocytes exposed to heat shock during in vitro maturation.

We investigated the effect of the antioxidant lycopene supplemented into the in vitro maturation medium (TCM-199 with 20 ng/mL epidermal growth factor and 50 mg/mL gentamycin) in a heat shock (HS) model to mimic in vivo heat stress conditions. Bovine cumulus-oocyte complexes were supplemented with 0.2 µM lycopene (or not supplemented; control) under HS (40.5 °C) and non-HS (NHS; 38.5 °C) during maturation. After 22 h of maturation, we evaluated the nuclear status of the oocytes, the level of reactive oxygen species (ROS) production, and the respective blastocyst development and quality (via differential staining). Data were fitted in logistic and linear regression models, and the replicates were set as a random effect. The nuclear maturation was higher in NHS (84.0 ± 3.2%; least square mean ± standard error) than HS control (60.4 ± 4.3%; P < 0.001). Remarkably, the nuclear maturation in HS lycopene (71.7 ± 4.1%) was similar to NHS control (P = 0.7). Under HS conditions lycopene reduced ROS production (27.4 ± 4.8; relative fluorescence units (RFU)) in comparison to HS control (33.8 ± 1.8 RFU; P = 0.009). However, the ROS production in NHS lycopene (18.9 ± 2.0 RFU) was similar to NHS control (18.7 ± 1.8 RFU; P = 0.9). The cleavage rate in HS lycopene (76.1 ± 3.3%) was not lower than NHS lycopene (83.3 ± 2.5%; P > 0.1). On the day 8 of embryo development, the blastocyst rate was higher for NHS lycopene (55.2 ± 4.7%) versus NHS control (44.5 ± 4.7%; P = 0.04), but under HS the day 8 blastocyst rate was similar between control (29.9 ± 4.2%) and lycopene (32.3 ± 4.2%; P = 0.9). Lycopene supplementation increased the cell number of the embryos (total cell, trophectoderm, and inner cell mass numbers) under NHS conditions (P > 0.03). The apoptotic cell ratio was lower in lycopene (NHS and HS) versus control (NHS and HS) (P > 0.04). Lycopene has the ability to scavenge oocyte ROS and improved the cleavage rate of embryos under HS conditions. However, this could not be translated to a higher blastocyst development, which remained lower under HS. Results of our study indicate that antioxidant supplementation like lycopene during the maturation of bovine cumulus-oocyte complexes may be routinely used to improve blastocyst rate and quality under standard maturation conditions.

Ensemble of neural networks for 3D position estimation in monolithic PET detectors.

We propose an ensemble of multilayer feedforward neural networks to estimate the 3D position of photoelectric interactions in monolithic detectors. The ensemble is trained with data generated from optical Monte Carlo simulations only. The originality of our approach is to exploit simulations to obtain reference data, in combination with a variability reduction that the network ensembles offer, thus, removing the need of extensive per-detector calibration measurements. This procedure delivers an ensemble valid for any detector of the same design. We show the capability of the ensemble to solve the 3D positioning problem through testing four different detector designs with Monte Carlo data, measurements from physical detectors and reconstructed images from the MindView scanner. Network ensembles allow the detector to achieve a 2-2.4 mm FWHM, depending on its design, and the associated reconstructed images present improved SNR, CNR and SSIM when compared to those based on the MindView built-in positioning algorithm.

[Evaluation of postoperative myocardial injury by heart-type fatty acid-binding protein in off-pump coronary artery bypass grafting surgery]. / Valoración del daño miocárdico mediante la medición de la heart-fatty acid-binding protein en cirugía de revascularización coronaria sin circulación extracorpórea. Estudio preliminar.

BACKGROUND AND GOAL OF STUDY: Postoperative myocardial infarction is a serious and frequent complication of cardiac surgery. Nonetheless, diagnosis in this context it is occasionally challenging. We sought to evaluate the kinetics and diagnostic accuracy of the new biomarker « heart-type fatty acid-binding protein ¼ (h-FABP) in the early detection of myocardial injury in patients undergoing off-pump coronary artery bypass grafting, compared with classical biomarkers. MATERIALS AND METHODS: A prospective study was conducted on 17 consecutive patients who underwent off-pump coronary artery bypass grafting during a 2 month period. Blood samples were drawn for measurement of myocardial ischemic injury biomarkers (h-FABP, troponin, creatine kinase [CK] and CK-MB), at baseline (T1), immediate post-coronary artery bypass grafting (T2), on ICU admission (T3), and after 4 (T4), 8 (T5), 24 (T6) and 48 h (T7). Perioperative ischemic complications, defined according to electrocardiographic, echocardiographic and hemodynamic criteria, were recorded. RESULTS: Earlier biomarkers peak plasma values occurred at T4 with troponin (2.9 ± 5.2 ng/mL), and at T5 with h-FABP (37.9 ± 55.5 ng/mL). Maximum values of CK and CK-MB occurred later, both in T6 (741 ± 779 and 37 ± 51 U/L, respectively). The optimized cut-off obtained for h-FABP was 19 ng/mL, providing a sensitivity and specificity of 77 and 75%, respectively, for diagnosis of perioperative ischemic injury, with an area under the ROC curve for h-FABP of 0.83 (95% CI 0.6-1.0) vs. 0.63 (95% CI 0.33-0.83) for troponin. This cut-off value for h-FABP is reached on average at T2 (mean value of h-FABP at T2: 18.9 ± 21.5 ng/mL). CONCLUSION: This is the first study evaluating the kinetics of h-FABP biomarker in perioperative off-pump coronary artery bypass grafting, and the cut-off value established could help to extend earlier detection of myocardial ischemia in this context.

Realising the European network of biodosimetry: RENEB-status quo.

Creating a sustainable network in biological and retrospective dosimetry that involves a large number of experienced laboratories throughout the European Union (EU) will significantly improve the accident and emergency response capabilities in case of a large-scale radiological emergency. A well-organised cooperative action involving EU laboratories will offer the best chance for fast and trustworthy dose assessments that are urgently needed in an emergency situation. To this end, the EC supports the establishment of a European network in biological dosimetry (RENEB). The RENEB project started in January 2012 involving cooperation of 23 organisations from 16 European countries. The purpose of RENEB is to increase the biodosimetry capacities in case of large-scale radiological emergency scenarios. The progress of the project since its inception is presented, comprising the consolidation process of the network with its operational platform, intercomparison exercises, training activities, proceedings in quality assurance and horizon scanning for new methods and partners. Additionally, the benefit of the network for the radiation research community as a whole is addressed.

Curcumin and trans-resveratrol exert cell cycle-dependent radioprotective or radiosensitizing effects as elucidated by the PCC and G2-assay.

Curcumin and trans-resveratrol are well-known antioxidant polyphenols with radiomodulatory properties, radioprotecting non-cancerous cells while radiosensitizing tumor cells. This dual action may be the result of their radical scavenging properties and their effects on cell-cycle checkpoints that are activated in response to radiation-induced chromosomal damage. It could be also caused by their effect on regulatory pathways with impact on detoxification enzymes, the up-regulation of endogenous protective systems, and cell-cycle-dependent processes of DNA damage. This work aims to elucidate the mechanisms underlying the dual action of these polyphenols and investigates under which conditions they exhibit radioprotecting or radiosensitizing properties. The peripheral blood lymphocyte test system was used, applying concentrations ranging from 1.4 to 140µM curcumin and 2.2 to 220µM trans-resveratrol. The experimental design focuses first on their radioprotective effects in non-cycling lymphocytes, as uniquely visualized using cell fusion-mediated premature chromosome condensation, excluding, thus, cell-cycle interference to repair processes and activation of checkpoints. Second, the radiosensitizing potential of these chemicals on the induction of chromatid breaks in cultured lymphocytes following G2-phase irradiation was evaluated by a standardized G2-chromosomal radiosensitivity predictive assay. This assay uses caffeine for G2-checkpoint abrogation and it was applied to obtain an internal control for radiosensitivity testing, which simulates conditions similar to those of the highly radiosensitive lymphocytes of AT patients. The results demonstrate for the first time the cell-cycle-dependent action of these polyphenols. When non-cycling cells are irradiated, the radioprotective properties of curcumin and trans-resveratrol are more prominent. However, when cycling cells are irradiated during G2-phase, the radiosensitizing features of these compounds are more pronounced. This observation offers a new biological basis for the mechanisms underlying the action of these polyphenols in cancer radiotherapy.

Realising the European Network of Biodosimetry (RENEB).

In Europe, a network for biological dosimetry has been created to strengthen the emergency preparedness and response capabilities in case of a large-scale nuclear accident or radiological emergency. Through the RENEB (Realising the European Network of Biodosimetry) project, 23 experienced laboratories from 16 European countries will establish a sustainable network for rapid, comprehensive and standardised biodosimetry provision that would be urgently required in an emergency situation on European ground. The foundation of the network is formed by five main pillars: (1) the ad hoc operational basis, (2) a basis of future developments, (3) an effective quality-management system, (4) arrangements to guarantee long-term sustainability and (5) awareness of the existence of RENEB. RENEB will thus provide a mechanism for quick, efficient and reliable support within the European radiation emergency management. The scientific basis of RENEB will concurrently contribute to increased safety in the field of radiation protection.

Assessment in vitro of cytogenetic and genotoxic effects of propolis on human lymphocytes.

We evaluated the genetic damage by ethanolic extract of propolis (EEP) induced to human lymphocytes which were exposed to increasing concentrations (0-2000µgml(-1)). The results indicated that EEP reduced significantly the mitotic index (MI) and proliferation index (PI) when high concentrations of EEP were used. Sister chromatid exchange (SCE) rates indicated that EEP could have genotoxic effects at high concentrations. Exposure of the cells to the amount of ethanol used as solvent did not alter either the MI and cell proliferation kinetics (CPK), or the rate of SCE. The results showed: (a) statistical increase in the percentage the cells with CAs and in the frequency of SCE at the highest concentrations, (b) a decrease in MI and in the CPK values was observed, (c) no effect was noticed in negative controls. In conclusion, it can be assumed that high concentrations of EEP have a cyto and genotoxic effect, in vitro, for human peripheral lymphocytes.

Prevalence of Trypanosoma cruzi infection in pregnant Latin American women and congenital transmission rate in a non-endemic area: the experience of the Valencian Health Programme (Spain).

This study describes the results of the health programme implemented in the Valencian Community (Spain) to achieve an early diagnosis of Chagas disease in pregnant Latin American women and their newborns. During 2009 and 2010, 1975 women living in the health districts of three university hospitals were enrolled via midwives or at the time of delivery. Diagnosis of disease was performed using two serological tests with different antigens. Congenital infection was diagnosed by parasitological, molecular or serological methods from blood samples obtained at birth or in subsequent controls. The overall seroprevalence of Chagas infection in pregnant women from 16 different endemic countries was 11·4%. Infection was higher in those from countries in the Gran Chaco Region (Bolivia, 34·1%; Paraguay, 7·4%; Argentina, 5·3%). Eight newborn infants from Bolivian mothers had congenital Chagas which represents a vertical transmission rate of 3·7%. In conclusion, this work supports the benefits of offering an early diagnosis to pregnant women and newborns during routine prenatal healthcare.

Concentration-Dependent Protection by Ethanol Extract of Propolis against γ-Ray-Induced Chromosome Damage in Human Blood Lymphocytes.

Radioprotection with natural products may be relevant to the mitigation of ionizing radiation-induced damage in mammalian systems; in this sense, propolis extracts have shown effects such as antioxidant, antitumoral, anti-inflammatory, and immunostimulant. We report for the first time a cytogenetic study to evaluate the radioprotective effect, in vitro, of propolis against radiation-induced chromosomal damage. Lymphocytes were cultured with increasing concentrations of ethanol extract of propolis (EEP), including 20, 40, 120, 250, 500, 750, 1000, and 2000 µg mL(-1) and then exposed to 2 Gy γ-rays. A significant and concentration-dependent decrease is observed in the frequency of chromosome aberrations in samples treated with EEP. The protection against the formation of dicentrics was concentration-dependent, with a maximum protection at 120 µg mL(-1) of EEP. The observed frequency of dicentrics is described as negative exponential function, indicating that the maximum protectible fraction of dicentrics is approximately 44%. Free radical scavenging and antioxidant activities are the mechanisms that these substances use to protect cells from ionizing radiation.

Biological and physical methods for risk estimation in interventional radiology: a detrimental effect approach.

Interventional radiologists and staff members are frequently exposed to the effects of direct and scattered radiation, which undergo in deterministic effects (radiodermitis, aged skin, cataracts, telangiectasia in nasal region, vasocellular epitelioms, hands depilation) and/or stochastic ones (cancer incidence). A methodology has been proposed for estimating the radiation risk or detriment from a group of six exposed interventional radiologists of the Hospital Universitario La Fe (Valencia, Spain), which had developed general exposition symptoms attributable to deterministic effects of ionizing radiation. Equivalent doses have been periodically registered using termoluminiscence dosimeters (TLD's) and wrist dosimeters, H(p)(10) and H(p)(0.07), respectively, and estimated through the observation of translocations in lymphocytes of peripheral blood (biological methods), by extrapolating the yield of translocations to their respective dose-effect curves. The software RADRISK has been applied for estimating radiation risks in these occupational radiation exposures. The minimum and maximum average excess ratio for skin cancer has been, using wrist physical doses, of [1.03 × 10(-3), 5.06 × 10(-2)], concluding that there is not an increased risk of skin cancer incidence. The minimum and maximum average excess ratio for leukemia has been, using TLD physical doses, of [7.84 × 10(-2), 3.36 × 10(-1)], and using biological doses, of [1.40 × 10(-1), 1.51], which is considerably higher than incidence rates, showing an excess radio-induced risk of leukemia in the group under study. Finally, the maximum radiological detriment in the group, evaluated as the total number of radio-induced cancers using physical dosimetry, has been of 2.18 per 1000 person-year (skin and leukemia), and using biological dosimetry of 9.20 per 1000 PY (leukemia). As a conclusion, this study has provided an assessment of the non-deterministic effects (rate of radio-induced cancer incidence) attributable to the group under study due to their professional activity.

Radiation effects analysis in a group of interventional radiologists using biological and physical dosimetry methods.

Interventional radiologists and staff members are frequently exposed to protracted and fractionated low doses of ionizing radiation, which extend during all their professional activities. These exposures can derive, due to the effects of direct and scattered radiation, in deterministic effects (radiodermitis, aged skin, cataracts, telangiectasia in nasal region, vasocellular epitelioms, hands depilation) and/or stochastic ones (cancer incidence). A methodology has been proposed for estimating the radiation risk or detriment from a group of six exposed interventional radiologists of the Hospital Universitario La Fe (Valencia, Spain), which had developed general exposition symptoms attributable to deterministic effects of ionizing radiation. Equivalent doses have been periodically registered using TLD's and wrist dosimeters, H(p)(10) and H(p)(0.07), respectively, and estimated through the observation of translocations in lymphocytes of peripheral blood (biological methods), by extrapolating the yield of translocations to their respective dose-effect curves. The software RADRISK has been applied for estimating radiation risks in these occupational radiation exposures. This software is based on transport models from epidemiological studies of population exposed to external sources of ionizing radiation, such as Hiroshima and Nagasaki atomic bomb survivors [UNSCEAR, Sources and effects of ionizing radiation: 2006 report to the general assembly, with scientific annexes. New York: United Nations; 2006]. The minimum and maximum average excess ratio for skin cancer has been, using wrist physical doses, of [1.03x10(-3), 5.06x10(-2)], concluding that there is not an increased risk of skin cancer incidence. The minimum and maximum average excess ratio for leukemia has been, using TLD physical doses, of [7.84x10(-2), 3.36x10(-1)], and using biological doses, of [1.40x10(-1), 1.51], which is considerably higher than incidence rates, showing an excess radio-induced risk of leukemia in the group under study. Finally, the maximum radiological detriment in the group, evaluated as the total number of radio-induced cancers using physical dosimetry, has been of 2.18/1000 person-year (skin and leukemia), and using biological dosimetry of 9.20/1000 PY (leukemia). As a conclusion, this study has provided an assessment of the non-deterministic effects (rate of radio-induced cancer incidence) attributable to the group under study due to their professional activity.

Unexplained overexposures on physical dosimetry reported by biological dosimetry.

The Medical Service of the Radiation Protection Service from the University Hospital La Fe (Valencia, Spain), carries out medical examinations of the workers occupationally exposed to ionising radiation. The Biological Dosimetry Laboratory is developing its activity since 2001. Up to now, the activities have been focused in performing biological dosimetry studies of Interventionists workers from La Fe Hospital. Recently, the Laboratory has been authorized by the Health Authority in the Valencian Community. Unexplained overexposures of workers and patients are also studied. Workers suspected of being overexposed to ionising radiation were referred for investigation by cytogenetic analysis. Two of these were from Hospitals of the Valencian Community and one belonged to an uranium mine from Portugal. Hospital workers had a physical dose by thermoluminiscence dosimeters (TLD) that exceeded the established limit. The worker of the uranium mine received a dose from a lost source of Cesium 137 with an activity of 170 mCi. All three cases showed normal values after the hematological analysis. Finally, the aim of this study consist to determine whether the dose showed by the dosimeter is reliable or not. In the case of workers that wore dosimeter, it is concluded that the doses measured by dosimeter are not corresponding to real doses. Hospital worker with a physical dose of 2.6 Sv and 0.269 Sv had an estimated absorbed dose by biological dosimetry of 0.076 Gy (0-0.165 Gy) and 0 Gy (0-0.089 Gy), respectively. In case of the mine worker an estimated absorbed dose of 0.073 Gy (0-0.159 Gy) was obtained by biological dosimetry. In all cases we used the odds ratio to present the results due to a very low frequency of observed aberrations [1].