Cell lineage analysis of acute leukemia relapse uncovers the role of replication-rate heterogeneity and microsatellite instability

Human cancers display substantial intratumoral genetic heterogeneity, which facilitates tumor survival under changing microenvironmental conditions. Tumor substructure and its effect on disease progression and relapse are incompletely understood. In the present study, a high-throughput method that uses neutral somatic mutations accumulated in individual cells to reconstruct cell lineage trees was applied to hundreds of cells of human acute leukemia harvested from multiple patients at diagnosis and at relapse. The reconstructed cell lineage trees of patients with acute myeloid leukemia showed that leukemia cells at relapse were shallow (divide rarely) compared with cells at diagnosis and were closely related to their stem cell subpopulation, implying that in these instances relapse might have originated from rarely dividing stem cells. In contrast, among patients with acute lymphoid leukemia, no differences in cell depth were observed between diagnosis and relapse. In one case of chronic myeloid leukemia, at blast crisis, most of the cells at relapse were mismatch-repair deficient. In almost all leukemia cases, > 1 lineage was observed at relapse, indicating that diverse mechanisms can promote relapse in the same patient. In conclusion, diverse relapse mechanisms can be observed by systematic reconstruction of cell lineage trees of patients with leukemia.     

Bullying perpetration and victimization associations to suicide behavior: a longitudinal study

Previous studies have reported a longitudinal association between cybervictimization and suicidal thoughts and behavior. However, the relationship between cyber-perpetration and prospective suicide risk remains unclear. The sample was composed of 2150 at-risk adolescents (mean age 15.42), enrolled in Vocational Education and Training high schools in Israel. Cyberbullying, traditional bullying, depression, hostility, serious suicidal ideations, and suicide attempts were assessed through self-report questionnaires at the beginning of the school year and one year later. All types of victimization and preparation were cross-sectionally associated with suicide ideation and attempts. Longitudinal associations were found between cyber-perpetration and suicidal ideation/attempts. Cyber-perpetrators were found to be over twice more likely to report serious suicidal ideation (OR = 2.04) or attempt suicide (OR = 2.64) in the subsequent year compared to noninvolved adolescents. These associations were significant even after adjusting for baseline depression, hostility, and traditional bullying. Traditional bullying perpetration was prospectively associated with suicide attempts. Traditional victimization was cross-sectionally associated with suicide ideation and attempts but not prospectively. Cybervictimization was prospectively associated with suicide ideation but not to suicide attempts. The findings demonstrate the prospective risk of involvement in bullying in regard to suicide ideation and behavior. Cyberbullying was found to be a somewhat differentiated phenomena from traditional bullying.

     

Categorical and anti-categorical approaches to US racial/ethnic groupings: revisiting the National 2009 H1N1 Flu Survey (NHFS)

Intersectionality theory calls for the understanding of race/ethnicity, sex/gender and class as interlinked. Intersectional analysis can contribute to public health both through furthering understanding of power dynamics causing health disparities, and by pointing to heterogeneities within, and overlap between, social groups. The latter places the usefulness of social categories in public health under scrutiny. Drawing on McCall we relate the first approach to categorical and the second to anti-categorical intersectionality. Here, we juxtapose the categorical approach with traditional between-group risk calculations (e.g. odds ratios) and the anti-categorical approach with the statistical concept of discriminatory accuracy (DA), which is routinely used to evaluate disease markers in epidemiology. To demonstrate the salience of this distinction, we use the example of racial/ethnic identification and its value for predicting influenza vaccine uptake compared to other conceivable ways of organizing attention to social differentiation. We analyzed data on 56,434 adults who responded to the NHFS. We performed logistic regressions to estimate odds ratios and computed the area under the receiver operating characteristic curve (AU-ROC) to measure DA. Above age, the most informative variables were education and household poverty status, with race/ethnicity providing minor additional information. Our results show that the practical value of standard racial/ethnic categories for making inferences about vaccination status is questionable, because of the high degree of outcome variability within, and overlap between, categories. We argue that, reminiscent of potential tension between categorical and anti-categorical perspectives, between-group risk should be placed and understood in relationship to measures of DA, to avoid the lure of misguided individual-level interventions.     

Initial exposed phosphatidylserine levels correlate with cellular response to cytotoxic drugs

Phosphatidylserine's (PS) membranal distribution is associated with an expanding variety of biological processes. We studied the relevance of preliminarily exposed membranal PS levels to cellular effects of cytotoxic agents. PBL of normal controls (n = 18) and patients with doxorubicin-treated breast carcinoma (n = 27) or 5'-fluorouracil-treated colorectal cancer (n = 32) were assayed before and after drug infusion. Membranal expression levels of PS, adhesion molecules (CD18, CD11a-c, CD63) and Fas-R of leukocyte subtypes were assessed by flow cytometer. Statistical analysis was implemented. Our results demonstrate external expression of PS on all leukocyte subpopulations despite non-apoptotic light scatter characteristics. Several distinct features were observed of which the more prominent were: leukocyte subtypes each display characteristic PS levels; cancer patients' PBL display higher preliminary PS levels than normal controls in all cell groups; and existence of negative correlations between initial membranal PS levels and drug-induced changes in its expression. Our findings underscore the complex involvement of PS in PBL apoptosis and possibly drug resistance.     

Mortality among Hispanics in metropolitan Chicago: an examination based on vital statistics data

This paper analyzes the mortality of Mexican Americans and Puerto Ricans residing in the Chicago metropolitan area. In a comparison of these two groups with nonHispanic whites in the same area, it was found that Hispanic mortality is unusually low for the two leading causes of death in the mainstream U.S. population. Explanations discussed include underdiagnosis, underreporting of illness, the "healthy migrant" thesis and possible return migration of elderly ill.