Multifractal characterization of nystagmus eye movements.

In this work, we investigate the multifractal properties of eye movement dynamics of children with infantile nystagmus, particularly the fluctuations of its velocity. The eye movements of three children and one adult with infantile nystagmus were evaluated in a simple task in comparison with 28 children with no ocular pathologies. Four indices emerge from the analysis: the classical Hurst exponent, the singularity strength corresponding to the maximum of the singularity spectrum, the asymmetry of the singularity spectrum, and the multifractal strength, each of which characterizes a particular aspect of eye movement dynamics. Our findings indicate that, when compared to children with no ocular pathologies, patients with infantile nystagmus present lower values of all indices. Except for the multifractal strength, the difference in the remaining indices is statistically significant. To test whether the characterization of patients with infantile nystagmus in terms of multifractality indices allows them to be distinguished from children without ocular pathologies, we performed an unsupervised clustering analysis and classified the subjects using supervised clustering techniques. The results indicate that these indices do, indeed, distinctively characterize the eye movements of patients with infantile nystagmus.

Modelling the eye movements of dyslexic children during reading as a continuous time random walk.

The study of eye movements during reading is considered a valuable tool for understanding the underlying cognitive processes and for its ability to detect alterations that could be associated with neurocognitive deficiencies or visual conditions. During reading, the gaze moves from one position to the next on the text performing a saccade-fixation sequence. This dynamics resembles processes usually described as continuous time random walk, where the jumps are the saccadic movements and waiting times are the duration of fixations. The time between jumps (intersaccadic time) consists of stochastic waiting time and flight time, which is a function of the jump length (the amplitude of the saccade). This motivates the present proposal of a model of eye movements during reading in the framework of the intermittent random walk but considering the time between jumps as a combined stochastic-deterministic process. The parameters used in this model were obtained from records of eye movements of children with dyslexia and typically developed for children performing a reading task. The jump lengths arise from the characteristics of the selected text. The time required for the flights was obtained based on a previously proposed model. Synthetic signals were generated and compared with actual eye movement signals in a complexity-entropy plane.

Graphite-oxide hybrid multi-degree of freedom resonator metamaterial for broadband sound absorption.

Low frequency broadband sound absorption for thin structures is still a great challenge. A new concept of a stackable hybrid resonator metamaterial is proposed which exhibits super broadband low-frequency sound absorption. The proposed metamaterial is based on micrometric scale thickness Graphene Oxide (GO) embedded in a stacked structure or used as external skin in a designed honeycomb (HC) structure. The stackable nature of the proposed structure allows the GO-HC cores to be embedded within micro-perforated panels (MPP) providing enhanced stiffness/strength to the structure and high absorption characteristics. We demonstrate how the exploitation of the GO elastic and mass properties result in multiple hybrid structural-acoustic resonances. These resonances are tailored to occur in a frequency range of interest by the theoretical calculation of the sound absorption coefficient. The theoretical model combines the mutual interaction between the structural dynamic of the GO foil and acoustic higher modes of the HC core cell as well as stacked MPP-HC/GO-HC cores. The result is a multi-degree of freedom hybrid resonator which provides subwavelength scale broadband sound absorption in low frequency range between 300 and 2500 Hz.

Nonlinear elastic multi-path reciprocal method for damage localisation in composite materials.

Nonlinear ultrasonic techniques rely on the measurement of nonlinear elastic effects caused by the interaction of ultrasonic waves with the material damage, and have shown high sensitivity to detect micro-cracks and defects in the early stages. This paper presents a nonlinear ultrasonic technique, here named nonlinear elastic multi-path reciprocal method, for the identification and localisation of micro-damage in composite laminates. In the proposed methodology, a sparse array of surface bonded ultrasonic transducers is used to measure the second harmonic elastic response associated with the material flaw. A reciprocal relationship of nonlinear elastic parameters evaluated from multiple transmitter-receiver pairs is then applied to locate the micro-damage. Experimental results on a damaged composite panel revealed that an accurate damage localisation was obtained using the normalised second order nonlinear parameter with a high signal-to-noise-ratio (∼11.2dB), whilst the use of bicoherence coefficient provided high localisation accuracy with a lower signal-to-noise-ratio (∼1.8dB). The maximum error between the calculated and the real damage location was nearly 13mm. Unlike traditional linear ultrasonic techniques, the proposed nonlinear elastic multi-path reciprocal method allows detecting material damage on composite materials without a priori knowledge of the ultrasonic wave velocity nor a baseline with the undamaged component.

Nonlinear elastic wave tomography for the imaging of corrosion damage.

This paper presents a nonlinear elastic wave tomography method, based on ultrasonic guided waves, for the image of nonlinear signatures in the dynamic response of a damaged isotropic structure. The proposed technique relies on a combination of high order statistics and a radial basis function approach. The bicoherence of ultrasonic waveforms originated by a harmonic excitation was used to characterise the second order nonlinear signature contained in the measured signals due to the presence of surface corrosion. Then, a radial basis function interpolation was employed to achieve an effective visualisation of the damage over the panel using only a limited number of receiver sensors. The robustness of the proposed nonlinear imaging method was experimentally demonstrated on a damaged 2024 aluminium panel, and the nonlinear source location was detected with a high level of accuracy, even with few receiving elements. Compared to five standard ultrasonic imaging methods, this nonlinear tomography technique does not require any baseline with the undamaged structure for the evaluation of the corrosion damage, nor a priori knowledge of the mechanical properties of the specimen.

In vitro and in vivo antimutagenic effects of DIG, a herbal preparation of Berberis vulgaris, Taraxacum officinale and Arctium lappa, against mitomycin C.

DIG, a liquid herbal preparation made from a mixture of diluted mother tinctures of Berberis vulgaris, Taraxacum officinale and Arctium lappa, was assessed for its antimutagenic properties against mitomycin C. The micronucleus assay on Chinese hamster ovary (CHO)-K1 cells was used to evaluate the in vitro anticlastogenic activity of DIG compared to those of separately diluted mother tinctures. The micronucleus assay was performed on mouse erythrocytes and the comet assay was performed on mouse liver, kidney, lung, brain and testicles to assess the protective effects of DIG (0.2 and 2 % at libitum) against an intraperitoneal injection of mitomycin C (1 mg Kg(-1)) in mice. DIG exerted a powerful anticlastogenic activity, under both pretreatment and simultaneous treatment conditions as assessed by the micronucleus assay in CHO-K1 cells. Its protective activity was greater than that observed for each mother tincture. DIG reduced micronuclei levels in mouse erythrocytes and suppressed >80 % of DNA strand breaks in the liver, kidney, lung, brain and testicles of mice exposed to mitomycin C.

Genotoxicity of mixtures of glyphosate and atrazine and their environmental transformation products before and after photoactivation.

The photo-inducible cytogenetic toxicity of glyphosate, atrazine, aminomethyl phosphoric acid (AMPA), desethyl-atrazine (DEA), and their various mixtures was assessed by the in vitro micronucleus assay on CHO-K1 cells. Results demonstrated that the cytogenetic potentials of pesticides greatly depended on their physico-chemical environment. The mixture made with the four pesticides exhibited the most potent cytogenetic toxicity, which was 20-fold higher than those of the most active compound AMPA, and 100-fold increased after light-irradiation. Intracellular ROS assessment suggested the involvement of oxidative stress in the genotoxic impact of pesticides and pesticide mixtures. This study established that enhanced cytogenetic activities could be observed in pesticide mixtures containing glyphosate, atrazine, and their degradation products AMPA and DEA. It highlighted the importance of cocktail effects in environmental matrices, and pointed out the limits of usual testing strategies based on individual molecules, to efficiently estimate environmental risks.

Genotoxic and clastogenic activity of saponins extracted from Nauclea bark as assessed by the micronucleus and the comet assays in Chinese Hamster Ovary cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Bark extracts of Nauclea latifolia, Nauclea diderrichii, Nauclea pobeguinii and Nauclea vandergutchii are used in traditional medicine in West and South Africa for the treatment of fevers, diarrhea and malaria. AIM OF THE STUDY: To estimate the possible long-term toxicity and genotoxicity of plant extracts (dichloromethane, methanol, water/methanol, water) and saponins. MATERIALS AND METHODS: The clastogenicity of plant extracts and saponins was assessed by the micronucleus assay performed on Chinese Hamster Ovary cells. The DNA-damaging activity of saponin mixture was assessed by the comet assay on Chinese Hamster ovary cells. RESULTS: Hydromethanolic extracts from Nauclea latifolia, Nauclea diderrichii and Nauclea pobeguinii exhibited a significant clastogenic/aneugenic activity without S9 mix. The hydromethanolic extract from Nauclea diderrichii was the most clastogenic/aneugenic fraction with a Minimal Active Concentration (MAC) of 23.1 µgm L(-1). It was submitted to a separation step leading to six main saponins identified as quinovic acid glycosides (saponins A, D, E, G, J, K). None of the isolated saponins exerted a significant clastogenic/aneugenic activity by the micronucleus assay, however a mixture made with equal quantities of each of the six saponins exhibited a direct genotoxic/clastogenic activity as assessed by both the micronucleus assay and the comet assay on Chinese Hamster Ovary cells. CONCLUSION: Saponins present in the hydromethanolic extracts of Nauclea induced synergistic in vitro DNA-damage and chromosome mutations in mammalian cells. This genotoxic activity was probably due to the capacity of Nauclea saponins to reduce cell defense against oxidative stress through the inhibition of glutathione-S-transferase activity.

Bioenergetics and DNA alteration of normal human fibroblasts by hexavalent chromium.

The effects of hexavalent chromium on mitochondria of normal human fibroblasts were investigated through the measurement of oxygen consumption, and its genotoxic effect through the analysis of chromium DNA adducts and oxidative DNA lesions. ROS production was also quantified. Chromium diminished oxygen consumption by cells in a concentration-dependent manner (IC(50)=66±8µM). This effect can be attributed to an alteration in mitochondrial functions, leading to defective glucose catabolism. The Comet assay, performed with and without the lesion-specific enzyme formamidopyrimidine-DNA glycosylase (Fpg), highlighted the extent of oxidative DNA base damage. DNA base damage was induced with low concentrations (0.5-3µM) of Cr(VI), whereas bioenergetic disturbance was only observed at higher concentrations (20-500µM).

Different genotoxic profiles between depleted and enriched uranium.

Uranium is an alpha-particle-emitting heavy metal. Its genotoxicity results from both its chemical and its radiological properties that vary with its isotopic composition (12% enriched uranium in (235)U (EU) has a specific activity 20 times higher than 0.3% depleted uranium in (235)U (DU)). The influence of the isotopic composition of uranium on its genotoxic profile (clastogenic/aneugenic) has never been described. The present study evaluated genotoxic profile of uranium with the cytokinesis-block micronucleus centromere assay. C3H10T1/2 mouse embryo fibroblasts were contaminated with either DU or EU at different concentrations (5 microM, 50 microM and 500 microM). Cells received low doses ranging from 0.3 microGy to 760.5 microGy. The frequency of binucleated cells with one micronucleus increased with increasing concentrations of both DU and EU in the same way. EU induced more centromere-negative micronuclei and nucleoplasmic bridges than DU. A correlation between these two clastogenic markers and ionizing radiation doses was observed. Finally, this study showed that the genotoxic profile of uranium depends on its isotopic composition. DU and EU are low and high clastogens, respectively. However, DU aneugenic effects remain high. Thus, there is a need to study the potential role of aneugenic effects of DU in carcinogenic risk assessment linked to uranium internal exposure.

Evolution of DNA strand-breaks in cultured spermatocytes: the Comet Assay reveals differences in normal and gamma-irradiated germ cells.

In reproductive toxicity assessment, in vitro systems can be used to determine mechanisms of action of toxicants. However, they generally investigate the immediate effects of toxicants, on isolated germ cells or spermatozoa. We report here the usefulness of in vitro cultures of rat spermatocytes and Sertoli cells, in conjunction with the Comet Assay to analyze the evolution of DNA strand-breaks and thus to determine DNA damage in germ cells. We compared cultures of normal and gamma-irradiated germ cells. In non-irradiated spermatocytes, the Comet Assay revealed the presence of DNA strand-breaks, which numbers decreased with the duration of the culture, suggesting the involvement of DNA repair mechanisms related to the meiotic recombination. In irradiated cells, the evolution of DNA strand-breaks was strongly modified. Thus our model is able to detect genotoxic lesions and/or DNA repair impairment in cultured spermatocytes. We propose this model as an in vitro tool for the study of genotoxic injuries on spermatocytes.

Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: A dose escalating phase I/II study.

Patients with inoperable pancreatic cancer have a dismal prognosis with a mean life expectancy of 3-6 months. New treatment modalities are thus urgently needed. Telomerase is expressed in 85-90% of pancreas cancer, and immunogenic telomerase peptides have been characterised. A phase I/II study was conducted to investigate the safety, tolerability, and immunogenecity of telomerase peptide vaccination. Survival of the patients was also recorded. Forty-eight patients with non-resectable pancreatic cancer received intradermal injections of the telomerase peptide GV1001 at three dose levels, in combination with granulocyte-macrophage colony-stimulating factor. The treatment period was 10 weeks. Monthly booster vaccinations were offered as follow-up treatment. Immune responses were measured as delayed-type hypersensitivity skin reaction and in vitro T-cell proliferation. GV1001 was well tolerated. Immune responses were observed in 24 of 38 evaluable patients, with the highest ratio (75%) in the intermediate dose group. Twenty-seven evaluable patients completed the study. Median survival for the intermediate dose-group was 8.6 months, significantly longer for the low- (P = 0.006) and high-dose groups (P = 0.05). One-year survival for the evaluable patients in the intermediate dose group was 25%. The results demonstrate that GV1001 is immunogenic and safe to use. The survival data indicate that induction of an immune response is correlated with prolonged survival, and the vaccine may offer a new treatment option for pancreatic cancer patients, encouraging further clinical studies.

Ten cases of feline mesothelioma: an immunohistochemical and ultrastructural study.

In the cat only 10 cases of mesothelioma, mainly of the peritoneum, have been previously reported. This paper describes a further 10 cases, eight pleural and two peritoneal, in males and females aged 1-17 years. Histologically, five tumours were epithelial, three fibrosarcomatous and two biphasic. Immunohistochemical markers used in human pathology for the identification of mesotheliomas include vimentin, cytokeratin (CK) AE1/AE3, HBME-1, CK 5/6, calretinin, thrombomodulin, carcinoembryonic antigen (CEA), CD15, E-cadherin and desmin. All 10 feline mesotheliomas were positive for vimentin and CK AE1/AE3, six were positive for HBME-1, two for CK5/6, three for CEA and four for E-cadherin. All were negative for desmin and calretinin. Antibodies to thrombomodulin and CD15 failed to cross-react with feline tissues. Electron microscopy, performed in four cases, revealed microvillar structures, desmosomes and intracytoplasmic lumina, confirming its value as a diagnostic tool. The study showed that mesothelial marker antibodies commonly used in human patients can be used for the diagnosis of feline mesothelioma, preferably as a panel of antibodies rather than only one.

A combined analysis of XRCC1, XRCC3, GSTM1 and GSTT1 polymorphisms and centromere content of micronuclei in welders.

The aims of the present study were to assess clastogenic and aneugenic properties of welding fumes using fluorescent in situ hybridization (FISH) with a human pancentromeric DNA probe. The involvement of genetic polymorphisms in DNA repair genes (p.Arg399Gln of XRCC1 and p.Thr241Met of XRCC3) and in detoxification genes (GSTM1 and GSTT1) on the centromere content of micronuclei (MN) was also evaluated. This study included 27 male welders working without any collective protection device and a control group (n = 30). The welders showed significantly higher levels of chromosome/genome damage compared to the controls. The frequencies of MN and centromere-positive MN (C+MN) per 1,000 binucleated cells were significantly higher in the exposed group than in the control group (7.1 per thousand +/- 3.7 versus 4.9 per thousand +/- 1.8; P = 0.012 and 3.5 per thousand +/- 1.8 versus 2.4 per thousand +/- 1.2; P = 0.018, respectively, Mann-Whitney U-test). The centromere-negative MN (C-MN) frequency was higher in the exposed subjects than in the controls (3.6 per thousand +/- 3.4 versus 2.5 per thousand +/- 1.4), but the Mann-Whitney U-test did not yield a significant result. In the total population, the GSTM1 and GSTT1 polymorphisms significantly affected the frequencies of C-MN and C+MN defined by FISH. GSTM1 positive subjects showed an increased C-MN frequency and GSTT1 null subjects showed an elevated C+MN frequency. When GSTM1 and GSTT1 genotypes were included in multiple regression analysis, the effect of the occupational exposure could better be demonstrated; both C+MN and C-MN were significantly increased in the welders. Our results suggest that the combined analysis of genetic polymorphisms and centromeres in MN may improve the sensitivity of the micronucleus assay in detecting genotoxic effects.

Risk assessment of welders using analysis of eight metals by ICP-MS in blood and urine and DNA damage evaluation by the comet and micronucleus assays; influence of XRCC1 and XRCC3 polymorphisms.

The aims of the present study were to assess the occupational risk of welders using analysis of metals in biological fluids, DNA damage evaluation by complementary genotoxic endpoints and the incidence of polymorphisms in DNA repair genes. A biomonitoring study was conducted that included biometrology (blood and urinary concentrations of aluminium, cadmium, chromium, cobalt, lead, manganese, nickel, zinc by ICP-MS), comet and cytokinesis-block micronucleus assays in peripheral lymphocytes and genetic polymorphisms of XRCC1 (p.Arg399Gln) and XRCC3 (p.Thr241Met). This study included 60 male welders divided into two groups: group 1 working without any collective protection device and group 2 equipped with smoke extraction systems. A control group (n = 30) was also included in the study. Higher chromium, lead and nickel blood and urinary concentrations were detected in the two groups of welders compared to controls. Statistically differences between welders of group 1 and group 2 were found for blood concentration of cobalt and urinary concentrations of aluminium, chromium, lead and nickel. The alkaline comet assay revealed that welders had a significant increase of OTMchi2 distribution at the end of a work week compared to the beginning; a significant induction of DNA strand breaks at the end of the week was observed in 20 welders out of 30. The cytokinesis-block micronucleus assay showed that welders of group 1 had a higher frequency of chromosomal damage than controls. The XRCC1 variant allele coding Gln amino acid at position 399 was found to be associated with a higher number of DNA breaks as revealed by the comet assay. Increased metal concentrations in biological fluids, DNA breaks and chromosomal damage in lymphocytes emphasized the need to develop safety programmes for welders.

[Characteristics and evolution of consultants, their risk factors and their behavior at the free anonymous HIV screening center of Colmar (France)]. / Caractéristiques et évolution des consultants, des facteurs de risque et des comportements dans un Centre d'Information et de Dépistage Anonyme et Gratuit du VIH.

INTRODUCTION: Data collected in free anonymous HIV screening centers (Centre d'Information et de Dépistage Anonyme et Gratuit du VIH, CIdAG) are numerous but poorly exploited. The characteristics of the consultants, their risk factors and their behavior were rarely analyzed previously. MATERIAL AND METHODS: Data of 3995 patients attending the CIdAG of Colmar between January 93 and February 99 were prospectively analyzed. Two 18-month periods at the beginning and end of the study were compared. RESULTS: The activity of the center was stable. Nine HIV infections were detected (2 p. 1000 consulting). The male/female ratio was 1.2 and the mean age was 26 years. The proportion of very young patients (<20 years) was 30 p. 100 and increased significantly between the two periods. Six per cent of the consultants were male homo/bisexuals and 2 p. 100 used intravenous drugs. A regular use of condoms when having occasional sexual relations was reported by 40 p. 100 of consultants before 20 years of age, but this proportion decreased regularly as the age increased. It was minimal among intravenous drug users (19 p. 100), and greater among male homo/bisexuals (46 p. 100) than among male heterosexuals (37 p. 100) and women (33 p. 100). This proportion increased significantly during the study period in heterosexual men and women but not in male homo/bisexuals. The number of sexual partners did not vary but the knowledge of the partners'status for HIV infection and drug addiction progressed significantly. Some subjects who attended the centre several times were identified anonymously. They differed from the other consultants by an older age (mean: 31), a higher proportion of male homo/bisexuals (14 p. 100) and a less regular use of condom (26 p. 100). COMMENTS: In some French anonymous HIV screening centers, information and prevention currently appears to prevail over detecting new HIV infections. Modifying at-risk behaviour is difficult. Current messages for prevention must be improved.

Urine mutagenicity and lymphocyte DNA damage in fruit growers occupationally exposed to the fungicide captan.

AIMS: To determine haematological parameters, urine mutagenicity (on three Salmonella typhimurium strains), and DNA damage (using the comet assay) in mononuclear leucocytes of farmers before and after a one-day spraying period of pear and apple trees with the fungicide captan in usual conditions. METHODS: Fruit growers were exposed to captan during the 1998 (n = 12) and/or the 2000 spraying seasons (n = 17). Biological samples were collected on the morning of the day of spraying (S1), the evening after spraying (S2), and the morning of the day after (S3). The UK Predictive Operator Exposure Model (UK-POEM) was used to quantify pesticide exposure intensity. RESULTS: No effect was observed on haematological parameters for these two spraying seasons. Proportions of mutagenic urine samples did not significantly differ between S1 and S2/S3 sampling points. In contrast with strains TA97a and YG1041 mainly sensitive to frameshift mutations, a positive trend was observed between the difference (S3-S1) of mutagenic power on strain TA102 detecting base-pair mutations and the exposure predicted value given by UK-POEM, mainly due to parameters related to protective clothing. No significant variations in DNA damage levels were observed between S1 and S3, nor were correlations observed with parameters of pesticide exposure. CONCLUSIONS: A one-day spraying period with captan and other pesticides does not significantly induce DNA damages in mononuclear leucocytes. In contrast, an inefficient protective clothing could correlate with an increase in urine mutagenicity as assessed by the TA102 tester strain.

Implication of nitro group reduction in the mutagenic and chromosome damaging activities of 22 new 5-nitroisoquinolines by the Salmonella mutagenicity test and the cytokinesis-blocked micronucleus assay.

The mutagenic (MUT) and chromosome-damaging (CHR) activities of 22 potential antimalarial drugs (5-nitroisoquinoline derivatives) were evaluated by the Salmonella test and the cytokinesis-blocked micronucleus assay (CBMN). The Salmonella mutagenicity test was performed with and without metabolic activation (S9 mix) in S. typhimurium strains TA100 and YG1042 (an overproducing nitroreductase and O-acetyltransferase TA100 strain). The CBMN was carried out on human lymphocytes without metabolic activation. Four concentrations were tested: 1, 10, 100 and 1000 ng/ml. MUT was expressed as minimal mutagenic concentrations (MMC, microM) and CHR was expressed as minimal chromosome-damaging concentrations (MCDC, nM) to compare both activities. All the 5-nitroisoquinoline compounds were mutagenic in TA100. MMC ranged from 0.1 to 52.9 microM in TA100. A statistically significant decrease in MMC was observed in YG1042 (8 x 10(-3) to 3.5 microM), implicating reduction of the nitro group. Modulation of MUT by S9 mix was not significant in TA100 and YG1042. CHR was detected in 13 products for at least one concentration. Among the chromosome-damaging compounds, the MCDC ranged from 2.9 x 10(-3) to 3.6 nM. No relationship was found between MUT and CHR, suggesting two distinct pathways of DNA damage.

Acentromeric micronuclei are increased in peripheral blood lymphocytes of untreated cancer patients.

Increased micronucleated cell rates, dicentric chromosomes, and other chromosomal damages have been reported in lymphocytes of cancer patients prior to the initiation of chemotherapy, and/or radiotherapy. The cause of these chromosomal damages in these lymphocytes remains unclear. In the present work, we investigated whether these micronuclei mainly reflect structural or numerical chromosomal aberrations by applying the cytokinesis-blocked micronucleus (CBMN) assay in combination with fluorescent in situ hybridization (FISH) of a DNA centromeric probe on blood samples of 10 untreated cancer patients (UCPs), and 10 healthy subjects (HSs). Micronucleated binucleated lymphocyte rate was significantly increased in patients (mean+/-S.D.: 19.0 per thousand +/-14.1 versus 9.2 per thousand +/-4.6 in controls). Trinucleated cytokinesis-blocked cells were not significantly higher in patients than in controls. Acentromeric, centromeric, and multicentromeric micronucleus levels were two-fold higher in patients than in controls, but the difference was significant only with acentromeric micronuclei. The percentage of micronuclei containing one or more centromeres averaged 69.2, and 71.5% in patients, and controls, respectively. The percentage of micronuclei containing several centromeres was 44.7% in patients, and 54.6% in controls. Among centromere-positive micronuclei, the percentage of micronuclei containing several centromeres averaged 59.7% in patients, and 75.4% in controls. These results indicate that genetic instability in peripheral blood lymphocytes of UCPs occurs because of enhanced chromosome breakage. However, a substantial proportion of this genetic instability occurs because of defects in chromosome segregation.