***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Sister  chromatid exchange ( SCE ) analysis  in peripheral blood lymphocytes is a well established technique that aims to evaluate human exposure to toxic agents . The individual mean value of SCE per cell had been the only recommended index to measure the extent of this cytogenetic damage until the early 1980 's , when the concept of high frequency cells ( HFC ) was introduced to increase the sensitivity of the assay . All statistical analyses proposed thus far to h and le these data are based on measures which refer to the individual mean values and not to the single cell . Although this approach allows the use of simple statistical methods , part of the information provided by the distribution of SCE per single cell within the individual is lost . Using the appropriate methods developed for the analysis of correlated data , it is possible to exploit all the available information . In particular , the use of r and om-effects models seems to be very promising for the analysis of clustered binary data such as HFC . Logistic normal r and om-effects models , which allow modelling of the correlation among cells within individuals , have been applied to data from a large study population to highlight the advantages of using this methodology in human biomonitoring studies . The inclusion of r and om-effects terms in a regression model could explain a significant amount of variability , and accordingly change point and /or interval estimates of the corresponding coefficients . Examples of coefficients that change across different regression models and their interpretation are discussed in detail . One model that seems particularly appropriate is the r and om intercepts and r and om slopes model An approach to sample size planning for multiple regression is presented that emphasizes accuracy in parameter estimation ( AIPE ) . The AIPE approach yields precise estimates of population parameters by providing necessary sample sizes in order for the likely widths of confidence intervals to be sufficiently narrow . One AIPE method yields a sample size such that the expected width of the confidence interval around the st and ardized population regression coefficient is equal to the width specified . An enhanced formulation ensures , with some stipulated probability , that the width of the confidence interval will be no larger than the width specified . Issues involving st and ardized regression coefficients and r and om predictors are discussed , as are the philosophical differences between AIPE and the power analytic approaches to sample size planning Micronucleus ( MN ) expression in peripheral blood lymphocytes is well established as a st and ard method for monitoring chromosome damage in human population s. The first results of an analysis of pooled data from laboratories using the  cytokinesis-block micronucleus ( CBMN ) assay  and participating in the HUMN ( HUman MicroNucleus project ) international collaborative study are presented . The effects of laboratory protocol , scoring criteria , and host factors on baseline micronucleated binucleate cell ( MNC ) frequency are evaluated , and a reference range of " normal " values against which future studies may be compared is provided . Primary data from historical records were su bmi tted by 25 laboratories distributed in 16 countries . This result ed in a data base of nearly 7000 subjects . Potentially significant differences were present in the methods used by participating laboratories , such as in the type of culture medium , the concentration of cytochalasin-B , the percentage of fetal calf serum , and in the culture method . Differences in criteria for scoring micronuclei were also evident . The overall median MNC frequency in nonexposed ( i.e. , normal ) subjects was 6.5 per thous and and the interquartile range was between 3 and 12 per thous and . An increase in MNC frequency with age was evident in all but two laboratories . The effect of gender , although not so evident in all data bases , was also present , with females having a 19 % higher level of MNC frequency ( 95 % confidence interval : 14 - 24 % ) . Statistical analyses were performed using r and om-effects models for correlated data . Our best model , which included exposure to genotoxic factors , host factors , methods , and scoring criteria , explained 75 % of the total variance , with the largest contribution attributable to laboratory methods This longitudinal , prospect i ve study sought to establish whether pediatric Crohn 's disease ( CD ) and ulcerative colitis ( UC ) are associated with increased levels of cytogenetic damage and whether folate supplementation in combination with other treatments mitigates cytogenetic damage in children with inflammatory bowel disease ( IBD ) . After a 1-mo treatment and folate supplementation , all clinical tests in CD ( n = 24 ) and UC ( n = 17 ) patients improved . Patients with CD were comparable in the cytogenetic response with controls ( n = 28 ) assessed by micronucleus ( MN ) assay , but both groups differed from the UC group . While the MN frequency in epithelial cells slightly decreased from first to second observations in CD patients ( p = 0.05 ) and controls ( p = 0.11 ) , an increase was observed in UC patients ( p = 0.001 ) . Similar changes were observed in blood lymphocytes result ing in significantly higher levels of the MNs and chromosome bridges in UC patients . These preliminary findings of a difference in chromosome damage between pediatric UC patients compared with CD patients and healthy controls warrant confirmation and expansion to determine ( 1 ) the role of cytogenetic damage in the pathogenesis of these diseases , ( 2 ) relative contribution of treatment and folate supplementation , and ( 3 ) potential links to the eventual development of cancer in some patients The frequency of  micronuclei ( MN )  in peripheral blood lymphocytes ( PBL ) is extensively used as a biomarker of chromosomal damage and genome stability in human population s. Much theoretical evidence has been accumulated supporting the causal role of MN induction in cancer development , although prospect i ve cohort studies are needed to vali date MN as a cancer risk biomarker . A total of 6718 subjects from of 10 countries , screened in 20 laboratories for MN frequency between 1980 and 2002 in ad hoc studies or routine cytogenetic surveillance , were selected from the data base of the HUman MicroNucleus ( HUMN ) international collaborative project and followed up for cancer incidence or mortality . To st and ardize for the inter-laboratory variability subjects were classified according to the percentiles of  MN  distribution within each laboratory as low , medium or high frequency . A significant increase of all cancers incidence was found for subjects in the groups with medium ( RR=1.84 ; 95 % CI : 1.28 - 2.66 ) and high MN frequency ( RR=1.53 ; 1.04 - 2.25 ) . The same groups also showed a decreased cancer-free survival , i.e. P=0.001 and P=0.025 , respectively . This association was present in all national cohorts and for all major cancer sites , especially urogenital ( RR=2.80 ; 1.17 - 6.73 ) and gastro-intestinal cancers ( RR=1.74 ; 1.01 - 4.71 ) . The results from the present study provide preliminary evidence that MN frequency in PBL is a predictive biomarker of cancer risk within a population of healthy subjects . The current wide-spread use of the MN assay provides a valuable opportunity to apply this assay in the planning and validation of cancer surveillance and prevention programs Chromium ( Cr ) and nickel ( Ni ) are widely used industrial chemicals . Welders in India are inclined to possible occupational Cr and Ni exposure . The carcinogenic potential of metals is a major issue in defining human health risk from exposure . Hence , in the present investigation , 102 welders and an equal number of control subjects were monitored for DNA damage in blood leucocytes utilizing the Comet assay .  The two groups had similar mean ages and smoking prevalences . A few subjects were r and omly selected for estimation of Cr and Ni content in whole blood by inductively coupled plasma mass spectrometry . The Comet  assay was carried out to quantify basal DNA damage . The mean comet tail length was used to measure DNA damage . Welders had higher Cr and Ni content when compared with controls ( Cr , 151.65 versus 17.86 micro g/l ; Ni 132.39 versus 16.91 micro g/l ; P < 0.001 ) . The results indicated that the welders had a larger mean comet tail length than that of the controls ( mean + /- SD , 23.05 + /- 3.86 versus 8.94 + /- 3.16 ; P < 0.001 ) . In addition , the micronucleus test on buccal epithelial cells was carried out in a few r and omly selected subjects . Welders showed a significant increase in micronucleated cells compared with controls ( 1.30 versus 0.32 ; P < 0.001 ) . Analysis of variance revealed that occupational exposure ( P < 0.05 ) had a significant effect on DNA mean tail length , whereas smoking and age had no significant effect on DNA damage . The current study suggested that chronic occupational exposure to Cr and Ni during welding could lead to increased levels of DNA damage This study evaluated cytogenetic damage by measuring the frequency of micronucleated cells ( MNC ) in peripheral blood and buccal mucosa of head- and -neck cancer patients undergoing radiotherapy .  MNC frequencies were assessed in 31 patients before , during , and after radiotherapy , and in 17 healthy controls matched for gender , age , and smoking habits . Results showed no statistically significant difference between patients and controls prior to radiotherapy in cytokinesis-blocked lymphocytes or buccal mucosa cells . During treatment , increased MNC frequencies were observed in both cell types . Micronucleated lymphocyte levels remained high in sample s collected 30 to 140 days after the end of treatment , while MNC frequency in buccal mucosa decreased to values statistically similar to baseline values . There is controversy over the effects of age , smoking habit , tumor stage , and /or metastasis on MNC frequency . However , increased frequency of micronucleated buccal mucosa cells was seen in patients under 60 years old and in those with tumors > 4 cm . In conclusion , the data show that radiotherapy has a potent clastogenic effect in circulating lymphocytes and buccal mucosa cells of head- and -neck cancer patients , and that the baseline MNC frequency in these two tissues is not a sensitive marker for head- and neck neoplasm OBJECTIVE To assess the effect of cyclophosphamide ( CYC ) and the influence of CYP2D6 polymorphism on micronuclei expression in patients with systemic lupus erythematosus ( SLE ) . METHODS  Micronuclei ( MN ) assays were performed in oral mucosa sweeps of 49 patients with SLE , receiving and not receiving CYC therapy , and 43 healthy controls . In patients receiving CYC the MN assay was repeated 14 days after CYC administration . SLE patients underwent determination of the CYP2D6 allele expressed in peripheral blood by polymerase chain reaction amplification . These results were compared with CYP2D6 distribution in a healthy population from the same geographic area . The results were analyzed by Mann-Whitney U and chi-square tests . RESULTS Twenty-four patients with SLE received CYC boluses . The mean age of SLE patients was 32 + /- 10 years ; mean disease duration was 7 + /- 6 years .  Basal expression of MN was similar in the groups investigated and increased significantly in those exposed to CYC ( CYC group 44 % , no CYC group 5 % , healthy controls 9 % ; p = 0.001 ) . We found no association between the CYP2D6 allele expressed and MN induction . Poor metabolizers were overrepresented in SLE subjects as compared with 139 healthy controls ( p < 0.05 ) . CONCLUSION Genotoxicity , as assessed by the MN assay , is increased in patients with SLE after CYC boluses . The CYP2D6 allele expressed in SLE patients does not have a role in CYC induced chromosomal injury Biomonitoring studies on cytogenetic outcomes  in humans should be considered as epidemiological studies , rather than r and omized trials . Under this light the emphasis given to the achievement of a significant p-value should be reduced , since this measure suffers from major limitations . The use of a point estimate ( and its corresponding confidence interval ) to measure the association between exposure and effect offers several advantages , including the adjustment for confounding , and the evaluation of possible interaction between factors . In most instances the use of multivariate statistical methods allows an efficient analysis of these studies , even in presence of a small sample size and several covariates . In this paper we re-analyzed four biomonitoring studies by using multivariate methods to estimate relative risks through statistical modeling . The use of multiple regression techniques allowed the computation of point estimates of association and their confidence intervals for each covariate evaluated by the studies considered ; the estimate of the effect of confounding variables such as smoking habits , age and gender ; and the presence of interaction between covariates . Measures of association estimated through univariate and multivariate statistical approaches are compared . The advantages of the latter technique are discussed 
    Output:
    
Poisson or Negative Binomial are the preferred statistical models when more than 2000 cells are scored .