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Analyzes migration streams between metropolitan and nonmetropolitan areas, 1975-93, in terms of sex, race, age, educational attainment, poverty level, and occupational status. Distinct shifts included nonmetro gains and retention of the young and better-educated during the 1970s, loss of those groups in the 1980s, and increased nonmetro population retention during the early 1990s. Contains 34 references. (SV)

Background: Progression rates from initial HIV-1 infection to advanced AIDS vary significantly among infected individuals. A distinct subgroup of HIV-1-infected individuals--termed viremic non-progressors (VNP) or controllers--do not seem to progress to AIDS, maintaining high CD4+ T cell counts despite high levels of viremia for many years. Several studies have evaluated multiple host factors, including immune activation, trying to elucidate the atypical HIV-1 disease progression in these patients; however, limited work has been done to characterize viral factors in viremic controllers. Methods: We analyzed HIV-1 isolates from three VNP individuals and compared the replicative fitness, near full-length HIV-1 genomes and intra-patient HIV-1 genetic diversity with viruses from three typical (TP) and one rapid (RP) progressor individuals. Results: Viremic non-progressors and typical patients were infected for >10 years (range 10-17 years), with a mean CD4+ T-cell count of 472 cells/mm³ (442-529) and 400 cells/mm³ (126-789), respectively. VNP individuals had a less marked decline in CD4+ cells (mean -0.56, range -0.4 to -0.7 CD4+/month) than TP patients (mean -10.3, -8.2 to -13.1 CD4+/month). Interestingly, VNP individuals carried viruses with impaired replicative itness, compared to HIV-1 isolates from the TP and RP patients (p < 0.05, 95% CI). Although analyses of the near full-length HIV-1 genomes showed no clear patterns of single-nucleotide polymorphisms (SNP) that could explain the decrease in replicative fitness, both the number of SNPs and HIV-1 population diversity correlated inversely with the replication capacity of the viruses (r = -0.956 and r = -0.878, p < 0.01, respectively). Conclusion: It is likely that complex multifactorial parameters govern HIV-1 disease progression in each individual, starting with the infecting virus (phenotype, load, and quasispecies diversity) and the intrinsic ability of the host to respond to the infection. Here we analyzed a subset of viremic controller patients and demonstrated that similar to the phenomenon observed in patients with a discordant response to antiretroviral therapy (i.e., high CD4+ cell counts with detectable plasma HIV-1 RNA load), reduced viral replicative fitness seems to be linked to slow disease progression in these antiretroviral-naïve individuals. [ABSTRACT FROM AUTHOR]

The twin processes of population concentration and deconcentration, working at the regional, metropolitan-nonmetropolitan and local levels, have defined the redistribution of the American people in the twentieth century. Over most of this period, there was a massive concentration of population into cities, with a multiplication of places as urbanization spread and larger centers captured ever greater numbers. Although growth generally was at the periphery of such places, with the widespread use of the automobile there was in addition a spread of population into formerly rural nearby areas. The recognition of this led to the adoption of the metropolitan area concept in 1950, and on this basis one may generalize that at least until 1970 the twentieth century settlement process could be described as concentration into metropolitan areas and deconcentration within these areas. The analysis of population redistribution by size of place within nonmetropolitan areas has shown that since the 1950s patterns of growth have supported a more deconcentrated settlement pattern.

Neurotoxicity is a common side effect of chemotherapy treatment, with unclear molecular mechanisms. Clinical studies suggest that the most frequent neurotoxic adverse events affect memory and learning, attention, concentration, processing speeds and executive function. Emerging preclinical research points toward direct cellular toxicity and induction of neuroinflammation as key drivers of neurotoxicity and subsequent cognitive impairment. Emerging data now show detectable levels of some chemotherapeutic agents within the CNS, indicating potential disruption of blood brain barrier integrity or transport mechanisms. Blood brain barrier disruption is a key aspect of many neurocognitive disorders, particularly those characterized by a proinflammatory state. Importantly, many proinflammatory mediators able to modulate the blood brain barrier are generated by tissues and organs that are targets for chemotherapy-associated toxicities. This review therefore aims to explore the hypothesis that peripherally derived inflammatory cytokines disrupt blood brain barrier permeability, thereby increasing direct access of chemotherapeutic agents into the CNS to facilitate neuroinflammation and central neurotoxicity. [ABSTRACT FROM AUTHOR]

Why do regimes delegate authority over a territory to nonstate militias, in effect voluntarily sacrificing their monopoly over the use of violence? This article argues that two factors increase the probability of states delegating control to a proxy militia, namely, military purges and armed conflict. Military purges disrupt intelligence-gathering structures and the organizational capacity of the military. To counteract this disruption, military leaders subcontract the task of control and repression to allied militias that have the local intelligence skills necessary to manage the civilian population. This argument is conditioned by whether the state faces an armed insurgency in a given region since intelligence, control, and repression are needed most where the state is being challenged. This hypothesis is tested on unique data for all subnational regions within Myanmar during the period 1962 to 2010 and finds that proxy militias are more likely to be raised in conflict areas after military purges. [ABSTRACT FROM AUTHOR]

Existing empirical research suggests that human resource officials, managers, and in-house counsel influence the meaning of antidiscrimination law by communicating an altered ideology of what civil rights laws mean that is colored with managerial values. This article explores how insurance companies play a critical and, as yet, unrecognized role in mediating the meaning of antidiscrimination law through Employment Practice Liability Insurance ( EPLI). My analysis draws from, links, and contributes to two literatures that examine organizational behavior in different ways: new institutional organizational sociology studies of how organizations respond to legal regulation and sociolegal insurance scholars' research on how institutions govern through risk. Through participant observation at EPLI conferences, interviews, and content analysis of insurance loss prevention manuals, my study bridges these two literatures and highlights how the insurance field uses a risk-based logic to construct the threat of employment law and influence the form of compliance from employers. Faced with uncertain legal risk concerning potential discrimination violations, insurance institutions elevate the risk and threat in the legal environment and offer EPLI and a series of risk-management services that build discretion into legal rules and mediate the nature of civil rights compliance. My data suggest that insurance risk-management services may sometimes be compatible with civil rights goals of improving equality, due process, and fair governance in workplace settings, but at other times may simply make discrimination claims against employers more defensible. [ABSTRACT FROM AUTHOR]

Background: Considerable progress has been made in our understanding of the biological basis for cancer therapy-induced mucosal barrier injury (mucositis). The last formal review of the subject by MASCC/ISOO was published in 2007; consequently, an update is timely. Methods: Panel members reviewed the biomedical literature on mucositis pathobiology published between January 2005 and December 2011. Results: Recent research has provided data on the contribution of tissue structure changes, inflammation and microbiome changes to the development of mucositis. Additional research has focused on targeted therapy-induced toxicity, toxicity clustering and the investigation of genetic polymorphisms in toxicity prediction. This review paper summarizes the recent evidence on these aspects of mucositis pathobiology. Conclusion: The ultimate goal of mucositis researchers is to identify the most appropriate targets for therapeutic interventions and to be able to predict toxicity risk and personalize interventions to genetically suitable patients. Continuing research efforts are needed to further our understanding of mucositis pathobiology and the pharmacogenomics of toxicity. [ABSTRACT FROM AUTHOR]

Summary Chemotherapy-induced mucositis is characterized by damage of mucous membranes throughout the alimentary tract (AT). Extracellular matrix (ECM) components play a vital role in maintaining mucosal barrier integrity by regulating cellular apoptosis, proliferation and differentiation of overlying epithelial cells. The aims of this study were to characterize the changes in epithelial cell kinetics and to investigate the expression of the ECM components in the gastrointestinal tract following irinotecan administration. Female dark agouti rats were treated with single 200 mg/kg dose irinotecan and killed at various time points (1, 6, 24, 48, 72, 96 and 144 h) after treatment. Ki67 immunostaining and TUNEL were used to assess proliferation and apoptosis, respectively, in the jejunum and colon. Masson trichrome staining and picro-sirius red staining were used to determine the level of collagen, and immunohistochemistry was used to further assess collagen IV, fibronectin and laminin 1 and 2 expression in these tissues. Irinotecan halved cellular proliferation in the jejunum and colon at 48 and 24 h, respectively, while apoptosis peaked at 6 h ( P < 0.05). There was a substantial increase in total collagen deposits around crypts from 24 h in both regions. However, collagen IV expression decreased significantly in the crypt region in a delayed fashion ( P < 0.05). Fibronectin expression decreased significantly in jejunum and colon from 6 to 24 h following treatment ( P < 0.05). Irinotecan induced a significant alteration in epithelial cell kinetics in both the jejunum and colon, and this correlated with changes in ECM component expression. Changes in ECM expression may have a direct impact on the loss of mucosal layer integrity evident in chemotherapy-induced mucositis. [ABSTRACT FROM AUTHOR]

Mucositis is a major oncological problem, caused by the cytotoxic effects of cancer chemotherapy and radiotherapy. Irinotecan is used to treat a variety of solid tumours, through the inhibition of DNA topoisomerase I and is linked with severe mucositis and diarrhoea. Mucus production appears to be increased, which may contribute to the development of diarrhoea. Dark agouti rats were treated with irinotecan, and tissues collected at several time points up to 72 h. Goblet cells and mucin secretion were investigated, as well as mucin expression (Muc2 and Muc4) and kruppel-like factor (Klf) 4 using immunohistochemistry in the gastrointestinal tract. Both goblet cells and cells positive for Muc expression were counted, and analysed statistically using the Mann–Whitney U test with Bonferroni correction. Goblet cells decreased significantly after irinotecan treatment. However, mucin secretion increased. Mucin expression changed significantly after treatment. Muc2 and Muc4 decreased significantly in the villi of the jejunum after treatment, Muc2 and Muc4 decreased significantly in the crypts. Muc2 decreased significantly in the colon. Irinotecan causes an increase in mucin secretion and a net decrease in mucin-producing goblet cells, and the expression of Muc2 and Muc4 in the gastrointestinal tract is altered following treatment. Increased mucin secretion is likely to be related to altered mucin expression, and may contribute to chemotherapy-induced diarrhoea. [ABSTRACT FROM AUTHOR]