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A comparison of the responses to repeated experimental infections with Haemonchus contortus among Scottish Blackface lambs.

Twenty helminth-naive Scottish Blackface lambs were given three infections with 10,000 infective larvae of Haemonchus contortus at 8 week intervals. An additional six lambs served as uninfected controls and eight lambs were infectivity controls. The lambs were 7 months old at the start of the infection. Four of the 20 lambs developed severe haemonchosis and were put down during the experiment. The remaining 16 lambs plus uninfected controls were necropsied 8 weeks after the third infection. The mean faecal egg count peaked 6-8 weeks after the first infection, gave a second smaller peak 6-8 weeks after the second infection but produced no peak after the third infection. Mean red blood cell counts fell rapidly during the first infection, then rose gradually during the second and third infections. The mean values suggested that two infections were sufficient to produce effective immunity in the sheep population but they masked considerable individual variation. Eleven animals appeared relatively resistant following the first infection, while two animals were relatively susceptible to even the third infection. The repeatability of mean faecal egg counts or mean red blood cell counts for each animal during the replicate infections were very high, because the rankings of the individual sheep remained remarkably stable. Faecal egg counts were very strongly correlated with red blood cell counts. Multiple regression analysis showed that four factors--faecal egg counts, red blood cell counts, weight and sex--accounted for essentially all of the observed variation in worm burdens among the lambs. Therefore, under these controlled experimental conditions, additional markers appear unnecessary for the detection of resistance status.

Analysis of Variance↗

Trends in asthma-induced mortality in France from 1970-90.

OBJECTIVE: The object of this research was to study the evolution of asthma-induced mortality in France from 1970-90 in the whole population and by age group. DESIGN: Data from the French National Institute of Health and Medical Research (INSERM) and the population groups established by the French National Institute of Statistics and Economic Studies (INSEE) were used. The study was carried out on age-specific, crude and age-adjusted rates. RESULTS: In the general population, a drop in the age-adjusted rates can be observed from 1970-80 in men and only until 1975 in women, followed by an increase until 1986 and then another drop. The rates among women have become closer to those in men. Among those aged 5-34, a clear increase is apparent in the age-adjusted rates for both sexes, in particular in the groups aged 15-24 and 25-34. In the older age groups, this increase involves only men aged 55-64 and women from 65 years onward. CONCLUSION: It is highly unlikely that the variations observed can be explained by biases, and the increase seems therefore to be real, particularly in women and in those aged 5-34.

Adolescent↗

Genetic diversity and phylogeography of the Apennine yellow-bellied toad Bombina pachypus, with implications for conservation.

Genetic variation was investigated in 17 populations of the Italian endemic Apennine yellow-bellied toad using both mitochondrial (598 bp of the cytochrome b gene) and nuclear (21 allozyme loci) markers. Populations from central Calabria (southern Italy) showed the highest levels of intrapopulation genetic variation, whereas samples located north of this region were nearly lacking in variation. This appears to be a typical pattern of 'southern richness and northern purity', usually attributed to the prolonged population stability within southern refugia coupled with the loss of variation during postglacial northward expansion. However, the overall pattern of genetic variation observed has a strong geographical component, suggesting two Calabrian plains, Catanzaro and Crati-Sibari, as historical barriers to dispersal separating three population groups. These findings cannot be explained by the prolonged stability of southern populations alone, and suggest that the southern richness has been at least in part shaped by allopatric differentiation within the refugial range, followed by intermixing of previously differentiated lineages. From a conservation standpoint, Calabria is the major genetic diversity reservoir for this species, thus deserving particular conservation efforts. Furthermore, although the low intrapopulation genetic variation outside Calabria appears to be of clear historical origin, evidence of a current reduction of gene flow suggests that human disturbance has also played a part, particularly in the anthropogenic impacted Volturno river drainage basin.

Alleles↗

Stability of Mycobacterium tuberculosis IS6110 restriction fragment length polymorphism patterns and spoligotypes determined by analyzing serial isolates from patients with drug-resistant tuberculosis.

The stability of Mycobacterium tuberculosis IS6110 fingerprint patterns and spoligotypes has been assessed by analyzing serial isolates from patients with drug-resistant tuberculosis. Altogether, 165 M. tuberculosis isolates obtained from 56 patients have been analyzed. The time spans between the first and the last or a changed isolate from one patient ranged from 1 to 772 days. Among the 56 patients, 5 (9%) were infected with isolates with changes in their IS6110 fingerprint patterns. According to the total number of strains analyzed, 5% of the subsequent isolates showed variations in their IS6110 restriction fragment length polymorphism patterns compared to the pattern of the first isolates. Up to 10 isolates from one patient sampled at time intervals of up to 772 days with no changes in their IS6110 patterns have been analyzed. A statistically significant correlation could be found between changes in insertion sequence (IS) patterns and the increased time intervals over which the isolates were obtained, whereas changes in IS patterns are not correlated to changes in the drug resistance of the isolates. In contrast to the observed variations in IS6110 fingerprint patterns, no changes in the spoligotypes of the isolates analyzed could be found. In conclusion, our results confirm that the IS6110 fingerprint patterns of M. tuberculosis isolates have high degrees of stability. Compared to IS6110, the direct repeat (DR) region, which is the basis for spoligotyping, has a lower rate of change. Partial deletions, e.g., deletions induced by homologous recombination between the repetitive DR elements, could not be detected in this study.

Adult↗

Variations in surgical rates in Quebec: does access to teaching hospitals make a difference?

OBJECTIVE: To document the geographic variations in the rates of 10 common surgical procedures in Quebec and to examine the relation between surgical rates and level of access to teaching hospitals. DESIGN: Population-based rates standardized for age and sex were calculated from 1985-88 data from MED-ECHO (the provincial hospital discharge database) for each of the 32 community health districts (départements de santé communautaire [DSCs]) in Quebec. Variation across DSCs was analysed with the use of the ratio of the highest to the lowest rate, the coefficient of variation and the systematic component of variation. On the basis of an urbanization index designed by Statistics Canada, DSCs were classified as having a low, medium, high or very high level of access to teaching hospitals. PATIENTS: All Quebec residents except those whose DSC of residence could not be traced (accounting for no more than 1.7% of patients for any study procedure) and aboriginal people from northern Quebec. SURGICAL PROCEDURES STUDIED: Appendectomy, cesarean section, cholecystectomy, coronary artery bypass grafting (CABG), hysterectomy, inguinal hernia repair, prostatectomy, tonsillectomy with or without adenoidectomy, total hip replacement and varicose vein stripping. RESULTS: There was considerable systematic variation in the surgical rates for all 10 procedures. Cesarean section, the rates of which varied the least, still exhibited almost a twofold variation between the highest and lowest rates. The rates of tonsillectomy varied the most, by a factor of more than five. With a few exceptions there was relatively little relation between the rates of the procedures within the DSCs. The rates of appendectomy, cholecystectomy, hysterectomy and tonsillectomy tended to be lower in the DSCs containing teaching hospitals, whereas the reverse was true for CABG. For the other procedures the relation between the rates and the level of access to teaching hospitals was nonsignificant. CONCLUSIONS: The overall consistency of the observed variations with those of previous studies invites a closer look at the practice patterns and the scientific basis of the clinical decisions associated with procedures showing high variations in rates. The lack of a systematic relation between the surgical rates and the level of access to teaching hospitals challenges the belief that remote regions are underserved with respect to the procedures studied.

Female↗

First emulsion polymerization of styrene with sodium borohydride: evidence of the generation of radical intermediates by sodium borohydride in H2O.

Emulsion polymerization of styrene with sodium borohydride (NaBH4) in an aqueous sodium dodecyl sulfate (SDS) solution was successfully accomplished for the first time. Polystyrene with a high molecular weight (M(w) > 2 000 000) and a broad molecular weight distribution (MWD approximately 3.5) was obtained in a conversion of less than 30%. Several pieces of evidence that the polymerization proceeded through radical intermediates were observed. Variations in the concentration of NaBH4 showed a critical range in said concentration, i.e., a borderline that determined whether the main reaction was directed to either a polymerization or a competed reaction with variations in the NaBH4 level. Kinetic studies on the emulsion polymerization of styrene with NaBH4 performed at 50, 55, and 60 degrees C showed that the initiator had an approximately 50-min induction period. A plot of -ln(1 - X), where X is the fractional conversion, as a function of time resulted in a linear relationship, showing that the present initiator system followed first-order kinetics with respect to monomer concentration. The Arrhenius plot between ln k vs 1/T gave a good linear relation, and the overall activation energy was observed to be about 37.5 kcal/mol. The employment of CH3I with NaBH4 significantly increased conversion (>95%) and provided polystyrene with a well-controlled Mw and MWD (<2.3).

Journal Article↗

Chronobiology of alcohol: from chronokinetics to alcohol-related alterations of the circadian system.

The development of concepts in chronobiology is intimately linked to studies on alcohol, as a number of these are based on chronobiological variations observed in the metabolism of ethanol. This concerns circadian differences in its metabolism (chronokinetics) and effects (chronoefficacy and chronotoxicity) and also inherent circadian rhythmicity in the sensitivity of target organs to its effects (chronesthesy). Chronobiologic discoveries are also fertile grounds for understanding the biological and psychotropic effects of alcohol. Confusing effects, which are difficult to explain by conventional homeostatic theory, are easy to understand when considered in the context of the concepts of chronopharmacology, and thereby uncovering new pathways of investigation. Beyond the studies that have elucidated the rhythm-dependent variation in ethanol, chronobiology is opening new explanatory pathways concerning the attributes of the alcohol withdrawal syndrome and effects of alcohol on the development of the central nervous system, particularly the development of the internal clock, and on the alcohol-dependency syndrome. The concepts of chronopharmacology and chronotoxicology are of equal importance to the fields of occupational medicine and industry medicine.

Alcohol Drinking↗

Restriction map and alpha-amylase activity variation among Drosophila mutation accumulation lines.

The specific activities of alpha-amylase were measured for two sets of mutation accumulation lines, each set having originated from a different lethal-carrying second chromosome and SM1(Cy) chromosome and having been maintained by a balanced lethal system for about 300 generations. Significant variation was found to have accumulated among lines of both sets. Because of dysgenic crosses in the early generations of mutation accumulation, insertions or deletions of transposable elements in the Amy gene region were suspected of being the cause of this variation. In order to test this possibility, the structural changes in the 14 kb region of these chromosomes that includes the structural genes for alpha-amylase were investigated by restriction map analysis. We found that most part of the activity variation is due to replacements of a chromosomal region of SM1(Cy), including the structural genes for alpha-amylase, by the corresponding regions of the lethal chromosomes. One line also contained an insertion in this region but this line has an intermediate activity value. Thus, insertions of transposable elements into the Amy gene region were not found to be responsible for the new variation observed in alpha-amylase activity. If we remove those lines with structural changes from the analysis, the genetic variance of alpha-amylase specific activity among lines becomes non-significant in both sets of chromosomes.

Animals↗

Intra- and intercellular variations in the repair efficiency of O6-methylguanine, and their contribution to kinetic complexity.

Following administration to rats of various doses of N-nitrosodimethylamine (NDMA), O(6)-methylguanine (O(6)-meG) was lost from the DNA of four tissues (liver, white blood cells, lymph nodes, bone marrow) over two, sharply demarcated phases with substantially differing repair rates. Repair during each phase followed approximately first-order kinetics in O(6)-meG, even after a high dose of NDMA which caused substantial depletion of O(6)-alkylguanine-DNA alkyltransferase (AGT), a suicide repair protein. This is compatible with rate-determining adduct repair being brought about by a distinct, minor pool of AGT molecules which is rapidly replenished by de novo AGT synthesis. Similar biphasic repair kinetics were also observed in HepG2 cells treated in vitro with NDMA. In this case, the first phase of repair was inhibited by alpha-amanitin, an inhibitor of RNA polymerase II-mediated transcription. However, no dependence on transcriptional activity was found when O(6)-meG repair in specific gene sequences with different transcriptional status in rat liver was examined, suggesting that the effects of alpha-amanitin in HepG2 cells did not reflect inhibition of preferential repair of transcribed sequences. Repair was also examined in rat liver hepatocytes and non-parenchymal cells separately after administration of NDMA at non-AGT depleting doses. Within each cell-population, the repair followed single phase, first-order kinetics, with adduct loss from AGT-rich hepatocytes being significantly faster than from the relatively AGT-deficient non-parenchymal cells. In conclusion, differences in the AGT content of different cell subpopulations in the liver (and probably in other tissues), as well as additional cellular factors affecting repair efficiency, appear to determine the observed variation in the kinetics of repair of O(6)-meG. The additional cellular factors involved appear not to be related to the transcriptional state of the sequences being repaired, but may reflect different states of chromatin condensation.

Alkyl and Aryl Transferases↗

Refinement of the solution structure of the DNA dodecamer 5'd(CGCGPATTCGCG)2 containing a stable purine-thymine base pair: combined use of nuclear magnetic resonance and restrained molecular dynamics.

The solution structure of the self-complementary dodecamer 5'd(CGCGPATTCGCG)2, containing a purine-thymine base pair within the hexameric canonical recognition site GAATTC for the restriction endonuclease EcoRI, is investigated by nuclear magnetic resonance spectroscopy and restrained molecular dynamics. Nonexchangeable and exchangeable protons are assigned in a sequential manner. A set of 228 approximate interproton distance restraints are derived from two-dimensional nuclear Overhauser enhancement spectra recorded at short mixing times. These distances are used as the basis for refinement using restrained molecular dynamics in which the interproton distance restraints are incorporated into the total energy function of the system in the form of effective potentials. Eight calculations are carried out, four starting from classical A-DNA and four from classical B-DNA. In all cases convergence to very similar B-type structures is achieved with an average atomic root mean square (rms) difference between the eight converged structures of 0.7 +/- 0.2 A, compared to a value of 6.5 A for that between the two starting structures. It is shown that the introduction of the purine-thymine mismatch does not result in any significant distortion of the structure. The variations in the helical parameters display a clear sequence dependence. The variation in helix twist and propeller twist follows Calladine's rules and can be attributed to the relief of interstrand purine-purine clash at adjacent base pairs. Overall the structure is straight. Closer examination, however, reveals that the central 5 base pair steps describe a smooth bend directed toward the major groove with a radius of curvature of approximately 38 A, which is compensated by two smaller kinks in the direction of the minor groove at base pair steps 3 and 9. These features can be explained in terms of the observed variation in roll and slide.

Base Composition↗

Geographic variation in the incidence of treated end-stage renal disease.

To facilitate identification of geographic clusters of areas with high or low incidence of treated end-stage renal disease, the 1983 to 1988 incidence by county was studied among whites and nonwhites less than 60 yr of age in the United States. End-stage renal disease incidence counts for 1983 to 1988 were obtained from the United States Renal Data System data base and linked to the 1985 county population obtained from U.S. Census data. Maps were smoothed by the method adopted by the National Cancer Institute that smooths only according to variability of the local rates, ignoring geographic information on clustering of events. In addition to identifying specific counties with exceptionally high or low incidence, geographic patterns were observed with many similarities across whites and nonwhites: notably high rates of disease in areas of the Southwest, the Southeast and in counties with Native American reservations and low rates in the West and Northwest. On the basis of these findings, several hypotheses are presented to explain the observed variation in treated end-stage renal disease incidence rates.

Adult↗

Ribonucleic acid metabolism during planarian regeneration.

A method for the extraction of total RNA of the planarian Polycelis tenuis is described. This technique has been applied to the study of RNA synthesis in the course of regeneration. Synthesis of RNA begins 7 hrs after sectioning and proceeds in two phases. The first phase, from 7 to 21 hr is characterized by an increased rate of (3H) orotic acid incorporation into RNA up to the 18th after sectioning followed by a decrease between 18 and 21 hrs. The rate of precursor incorporation then had risen again in the second phase to the 30th hr and finally decreased slowly until completion of regeneration. Studies of the pool of nucleotide precursors, show that the observed variations of orotic acid incorporation into RNA reflect variations in RNA synthesis. Electrophoretic analysis of RNA labelled for 2 hrs at various times during regeneration shows that the product formed during the first phase of regeneration is mainly rRNA and low molecular weight RNA. The second phase of the regeneration process, from the 24th hr, is characterized by the appearance of both ribosomal and polydisperse RNAs. These heterogeneous RNA species are detected up to the 46th hr of regeneration, after which time rRNA again becomes predominent. The significance of the two phases of RNA metabolism of which this is the first observation during planarian regeneration is discussed in connection with other biochemical events which have been described during regeneration processes in planarians and other animals.

Animals↗

Genetic epidemiology of seropositivity for Trypanosoma cruzi infection in rural Goias, Brazil.

Chagas' disease is a zoonotic disease found throughout Latin America. Despite control programs in many of the affected countries, infection with Trypanosoma cruzi continues to be a major public health concern. In Brazil alone, approximately 53 million people live in endemic areas. Research with humans and with animal models indicates that there is variation in susceptibility to infection with T. cruzi. The reasons for this variation are not known although several studies have implicated genetic factors. An indirect immunofluorescence assay was used to assess seropositivity for T. cruzi infection in 716 adults from the municipality of Posse, Goias, Brazil. Detailed genealogic information was gathered at the time of sampling, which allowed assignment of 525 individuals to 146 pedigrees containing between two and 103 individuals; the remaining 191 unrelated individuals were retained as independents in the analysis. Using a maximum likelihood variance decomposition approach, we performed quantitative genetic analyses to determine if genetic factors could partially account for the observed pattern of seropositivity. The maximum likelihood estimate of the heritability of T. cruzi infection was 0.56 +/- 0.27 (mean +/- SE), indicating that genetic factors account for more than half of the observed variation in infection status. An additional 23% of the variation (c2 = 0.23 +/- 0.09) is attributable to the effects of shared environment, as assessed by common household. The results indicate that genetic factors play an important role in determining epidemiologic patterns of T. cruzi infection. Further characterization of these genetic factors may suggest new biologic areas to be targeted by prevention and intervention programs.

Adolescent↗

Preclinical validation of a monochrome real-time multiplex assay for translocations in childhood acute lymphoblastic leukemia.

PURPOSE: The purpose is to develop a real-time multiplex reverse transcription-PCR assay for detection and quantification of leukemia-specific chimeric transcripts that identify the genetic subgroups of acute lymphoblastic leukemias (ALLs) proposed by the WHO classification. EXPERIMENTAL DESIGN: Real-time multiplex assay for t(12;21), t(4;11), and t(1;19) with hypoxanthine phosphoribosyltransferase as internal standard used in tandem with a new real time quantitative-RT-PCR assay for the t(9;22). This new strategy was designed to yield an amplicon from each translocation with a distinct melting peak allowing dependable identification using only Sybr green I, without any need for expensive hybridization probes. RESULTS: We validated this method with 92 primary ALLs and identified 4 E2A-PBX1, 4 mBCR-ABL and 10 TEL-AML1. When compared with conventional RT-PCRs and Southern blot analyses, 100% concordance was obtained. During the course of these studies, we found marked variations in the levels of the TEL-AML1 transcripts in individual patients. We, therefore, extended the study to accurately and reproducibly determine TEL-AML1 mRNA levels in 47 additional patients with t(12;21). The results indicated that the level of expression of TEL-AML1 varied among individual patients, and it was independent of the WBC count. CONCLUSIONS: Our new real-time multiplex assay can be used for rapid, simple, and reliable classification of pediatric ALL. Its reproducible quantification results should also facilitate studies on minimal residual disease. The observed variation in TEL-AML1 transcript levels is of interest because it could reflect biological and/or clinical heterogeneity in the behavior of these leukemias.

Blotting, Southern↗

Age-dependent variations of antibody avidity.

Age-dependent variations of antibody avidity were studied in the C3HeB/FeJ mouse. Spleen cells from donors of different ages (10--720 days) were transferred and stimulated with TNP-HRBC in lethally irradiated syngenic recipients. The anti-TNP antibody response of the donor cells was estimated from the number of direct PFC per recipient spleen by the Jerne technique with TNP-SRBC. Avidity of the antibodies secreted by PFC was evaluated from the amount of added TNP-BSA that inhibited 50% of the anti-TNP PFC. Under these experimental conditions allowing the exclusion of any influence of the donor milieu during the immune response, age-dependent variations of the antibody response and avidity could be attributed to changes in the donor spleen cell population. Avidity was found to increase with the response and to vary parabolically with age. After appropriate correction of the number of PFC to make it independent from age, avidity values were fitted by a multiple curvilinear regression in which the independent variables playing a significant role were the corrected number of PFC in its linear term and the age in its linear and quadratic terms. From comparison of the standard coefficients of this regression, the observed variations of avidity could be attributed in part (82%) to the response and in part (18%) to the age. For any value of response, avidity increased 15-fold from day 10 to reach a maximum at day 110 and then declined 5-fold at the age of 720 days. Heterogeneity of avidity also changed parabolically with age as high avidity classes were present in adulthood and absent at 10 and 720 days.

Aging↗

The mean and variance of the number of segregating sites since the last hitchhiking event.

Tight linkage may cause a reduction of nucleotide diversity in a chromosomal region if an advantageous mutation appears in that region which is driven to fixation by directional selection. This process is usually called genetic hitchhiking. If selection is strong, the entire process takes place during a time period of length s/2 1n (2N) that is very short relative to 2N generations [s is the selection coefficient of the advantageous mutation and N the effective diploid population size]. On the time scale of 2N generations, which is characteristic for neutral evolution, we may therefore call this process a hitchhiking event. Using coalescent methods, we analyzed a model in which a hitchhiking event occurred in a chromosomal region of zero-recombination in the past at time x. Such a hitchhiking "catastrophe" wipes out completely genetic variation that existed in a population before that time. Standing variation observed at present must therefore be due to mutations that have arisen since time point x. Assuming that all newly arising mutations are neutral, we derived expressions for the expectation, variance and also for the higher moments of the number of nucleotide sites segregating in a sample of n genes as a function of x. The result for the first moment is then used to estimate the time back to the last hitchhiking event based on DNA polymorphism data from Drosophila. Assuming that directional selection is the sole determinant of the level of genetic variation in the gene regions surveyed, we obtained estimates of x that were typically in the order of 0.1N generations.

Analysis of Variance↗

One-mile run/walk and body mass index of an ethnically diverse sample of youth.

PURPOSE: The purpose of this study was to explore the relationship between cardiovascular fitness levels and body mass index (BMI) status among an ethnically diverse sample of youth. METHODS: The cross-sectional sample consisted of California fifth, seventh, and ninth graders (10-15 yr). Data presented included a total of 767,809 youth (M = 389,925, F = 377,884) from the following ethnic groups: African American 58,491; American Indian-Alaskan Natives 8,971; Asian 63,292; Filipino 22,598; Hispanic 330,758; Pacific Islanders 7,977; and white non-Hispanics 275,722. Performance on the 1-mile run/walk (seconds, MRW), height (cm), and weight (kg) measures were taken by physical education staff in public schools across California. Comparisons of MRW were analyzed with hierarchical multiple linear regression, controlling for height and weight for each age strata for males and females, separately. Youth were classified as overweight (> or = 95th percentile) or at risk for overweight (> or = 85th percentile, < 95th percentile) based on age-sex specific BMI growth charts. White non-Hispanics served as the comparison group for each analysis. RESULTS: Overall, significant (P < 0.01) differences were observed between white non-Hispanics and their ethnic peers for each age-sex strata for MRW. For males, MRW differences among ethnic groups minimized with increasing age, while differences in MRW increased for females with increasing age. Odds ratios calculated by logistic regression indicated that for both sexes, being Hispanic was associated with the greatest likelihood of being at risk or overweight, whereas being Asian and female was associated with a preventive effect. CONCLUSIONS: These data suggest 1) disparities in MRW exist among ethnic groups, after controlling for confounders; and 2) the variation observed in MRW is similar to those observed for physical activity.

Adolescent↗

Epidemiology, stage at diagnosis, and tumor biology of breast carcinoma in multiracial and multiethnic populations.

All women, regardless of their racial or ethnic origin or heritage, are at risk of developing breast cancer. Variations in breast carcinoma incidence rates among multicultural populations suggest that etiologic factors differ in their biologic expression and impact on disease outcome. Key among those factors that affect breast carcinoma development are the roles of genetics and the environment, the reproductive experience and the effects of endogenous and exogenous hormones in women, the change in immune status and host vulnerability, and the biologic determinants of breast carcinoma. Cultural dynamics, sociodemographic differences, and behavioral characteristics across population subgroups modulate how biologic disease is expressed among different races and ethnic groups. These interactions contribute to the observed variations in breast carcinoma incidence, mortality, and survival. Stage, a measure of disease status, is used to assess prognosis, plan treatment, and evaluate outcome. Numerous studies have reported a more advanced stage of breast carcinoma at diagnosis in racial/ethnic subgroups, especially among women from African American, Hispanic, American Indian, and native Hawaiian cultures. Factors associated with advanced stage at diagnosis in multicultural populations range from changes in the basic biological characteristics at the molecular and cellular level, to more complex behavioral attributes unique to a particular multicultural population, to societal issues-such as access to care and socioeconomic conditions-all of which impact on the health measure called "stage at diagnosis." Rapid advancements in knowledge of cancer biology and of genetic markers and tumor products are providing new mechanisms for identifying etiologic pathways that can be utilized for better screening, detection, treatment and monitoring of disease. Further studies are needed that evaluate the biologic and molecular alterations in tumor development, progression, and response to therapy. Public health attention needs to be directed toward the societal influences that impact breast carcinoma development, as well as augmenting recognition of the need for culturally appropriate, broad-based behavioral changes at the community level. In addition, continued efforts are needed to ensure the inclusion of multicultural population subgroups and minority investigators in all aspects of research-basic, clinical and applied.

Adult↗