The national army and armed groups in the eastern Congo: untangling the Gordian knot of Insecurity

The final report of the Usalama Project presents the conclusions of 18-month field research on the national army and armed groups in the eastern DRC in three parts: an analysis of armed mobilization, focusing on the region of North and South Kivu; an examination of the FARDC; and a critical review of past and current efforts in the field of demobilization and army reform. Written by Jason Stearns, Judith Verweijen and Maria Eriksson Baaz, the report finds that in the DRC’s current political order, the mobilization of armed groups and hence violence is an effective strategy to obtain power and control resources. Troubled army policies only contribute to armed mobilization. By repeatedly integrating armed groups into the FARDC, the government has not only provided incentives for further insurrection, it has effectively sanctioned impunity. Untangling this Gordian knot will require a comprehensive political and military strategy, aligning local, national, and international initia­tive

How (and Why) NCLB Failed to Close the Achievement Gap:Evidence from North Carolina, 1998-2004

Recent state and national policy changes for public education are premised upon the idea that high-stakes tests can improve student outcomes and close achievement gaps. Opponents maintain that such policies fail on both counts. Using a unique longitudinal dataset from North Carolina, we find that high-stakes tests have failed to close achievement gaps associated with social class and race, and that the persistence of these gaps is related, at least in part, to academic tracking. Such findings add to the questions being raised about such policies as No Child Left Behind

Exposição à segregação racial na escola e na sala de aula nas escolas de ensino médio e as conquistas dos estudantes de faculdade de Charlotte-Mecklenburg

In this study we investigate Charlotte Mecklenburg Schools (CMS) high school graduates’ academic performance in the first year of college and test whether their exposure to racial segregation in high school at both the school and classroom levels affected their college freshman grade point averages. Utilizing administrative data from the Roots of STEM Success Project, we track the CMS class of 2004 from middle school through its first year of education in the University of North Carolina (UNC) system. Our findings show that segregation among schools and among classes within schools compromises college achievement for students of color while offering no significant benefits to white students’ college achievement.En este estudio investigamos el rendimiento académico de los graduados de escuelas secundarias de Charlotte Mecklenburg Schools (CMS) en su primer año de universidad y probamos si la exposición a segregación racial durante la escuela secundaria al nivel colegio y clase afecta su promedio de rendimiento académico en la universidad.  Utilizando datos administrativos del Roots of STEM Success Project, seguimos a la clase de estudiantes del CMS del 2004 desde la escuela media hasta su primer año de universidad en el sistema universitario de Carolina del Norte (UNC).  Nuestros resultados muestran que la segregación entre colegios y entre clase dentro de un colegio deteriora el rendimiento académico en la universidad de los estudiantes de color, mientras al mismo tiempo no ofrece beneficios significativos al rendimiento académico de los estudiantes blancos en la universidad.Nesse estudo nós investigamos os formandos do ensino secundário das escolas do condado de Mecklenburg em Charlotte (CMS) e o desempenho acadêmico no primeiro ano de faculdade, e testamos para ver se a exposição à segregação racial na escola de ensino secundário, tanto na escola como na sala de aula afetou as notas desses alunos no primeiro ano de faculdade.  Utilizando dados administrativos obtidos através do Roots of STEM Success Project, nós acompanhamos a classe de 2004 de CMS desde o ensino médio até o primeiro ano de faculdade na Universidade da Carolina do Norte (UNC). Nossos resultados mostram que a segregação entre escolas e entre salas de aula dentro da escola comprometem as conquistas na faculdade para estudantes negros mas não oferecem benefícios significativos em relação à conquistas na faculdade para estudantes brancos

Socioeconomic status and modification of atherosclerotic cardiovascular disease risk prediction: Epidemiological analysis using data from the Atherosclerosis Risk In Communities study

OBJECTIVE: Examine whether the relationship between the pooled cohort equations (PCE) predicted 10-year risk for atherosclerotic cardiovascular disease (ASCVD) and absolute risk for ASCVD is modified by socioeconomic status (SES). DESIGN: Population-based longitudinal cohort study-Atherosclerosis Risk in Communities (ARIC)-investigating the development of cardiovascular disease across demographic subgroups. SETTING: Four communities in the USA-Forsyth County, North Carolina, Jackson, Mississippi, suburbs of Minneapolis, Minnesota and Washington County, Maryland. PARTICIPANTS: We identified 9782 ARIC men and women aged 54-73 without ASCVD at study visit 4 (1996-1998). PRIMARY OUTCOME MEASURES: Risk ratio (RR) differences in 10-year incident hospitalisations or death for ASCVD by SES and PCE predicted 10-year ASCVD risk categories to assess for risk modification. SES measures included educational attainment and census-tract neighbourhood deprivation using the Area Deprivation Index. PCE risk categories were 0%-5%, \u3e5%-10%, \u3e10%-15% and \u3e15%. SES as a prognostic factor to estimate ASCVD absolute risk categories was further investigated as an interaction term with the PCE. RESULTS: ASCVD RRs for participants without a high school education (referent college educated) increased at higher PCE estimated risk categories and was consistently \u3e1. Results indicate education is both a risk modifier and delineates populations at higher ASCVD risk independent of PCE. Neighbourhood deprivation did modify association but was less consistent in direction of effect. However, for participants residing in the most deprived neighbourhoods (referent least deprived neighbourhoods) with a PCE estimated risk \u3e10%-15%, risk was significantly elevated (RR 1.65, 95% CI 1.05 to 2.59). Education and neighbourhood deprivation inclusion as an interaction term on the PCE risk score was statistically significant (likelihood ratio p≤0.0001). CONCLUSIONS: SES modifies the association between PCE estimated risk and absolute risk of ASCVD. SES added into ASCVD risk prediction models as an interaction term may improve our ability to predict absolute ASCVD risk among socially disadvantaged populations

Effects of exemestane and letrozole therapy on plasma concentrations of estrogens in a randomized trial of postmenopausal women with breast cancer

PURPOSE: Inter-individual differences in estrogen concentrations during treatment with aromatase inhibitors (AIs) may contribute to therapeutic response and toxicity. The aim of this study was to determine plasma concentrations of estradiol (E2), estrone (E1), and estrone sulfate (E1S) in a large cohort of AI-treated breast cancer patients. METHODS: In a randomized, multicenter trial of postmenopausal women with early-stage breast cancer starting treatment with letrozole (n = 241) or exemestane (n = 228), plasma estrogen concentrations at baseline and after 3 months were quantitated using a sensitive mass spectrometry-based assay. Concentrations and suppression below the lower limit of quantification (LLOQ) were compared between estrogens and between drugs. RESULTS: The ranges of baseline estrogen concentrations were <LLOQ-361 pg/mL for E2, <LLOQ-190 pg/mL for E1, and 8.3-4060 pg/mL for E1S. For E2, the frequency of suppression below the LLOQ was not statistically significantly different between AIs (exemestane: 89.0%, letrozole: 86.9%, p = 0.51). However, patients on letrozole were more likely to achieve suppression below the LLOQ of both E1 (exemestane: 80.1%, letrozole: 90.1%, p = 0.005) and E1S (exemestane: 17.4%, letrozole: 54.9%, p = 4.34e-15). After 3 months of AI therapy, the ranges of estrogen concentrations were <LLOQ-63.8 pg/mL, <LLOQ-36.7 pg/mL, and <LLOQ-1090 pg/mL for E2, E1, and E1S, respectively. During treatment, 16 patients had an increased concentration compared to the baseline concentration of at least one estrogen. CONCLUSIONS: Letrozole had greater suppression of plasma E1 and E1S than exemestane, though the response was highly variable among patients. Additional research is required to examine the clinical relevance of differential estrogen suppression

Association of Variants in Candidate Genes with Lipid Profiles in Women with Early Breast Cancer on Adjuvant Aromatase Inhibitor Therapy

Purpose: Aromatase inhibitors can exert unfavorable effects on lipid profiles; however, previous studies have reported inconsistent results. We describe the association of single-nucleotide polymorphisms (SNP) in candidate genes with lipid profiles in women treated with adjuvant aromatase inhibitors. Experimental design: We conducted a prospective observational study to test the associations between SNPs in candidate genes in estrogen signaling and aromatase inhibitor metabolism pathways with fasting lipid profiles during the first 3 months of aromatase inhibitor therapy in postmenopausal women with early breast cancer randomized to adjuvant letrozole or exemestane. We performed genetic association analysis and multivariable linear regressions using dominant, recessive, and additive models. Results: A total of 303 women had complete genetic and lipid data and were evaluable for analysis. In letrozole-treated patients, SNPs in CYP19A1, including rs4646, rs10046, rs700518, rs749292, rs2289106, rs3759811, and rs4775936 were significantly associated with decreases in triglycerides by 20.2 mg/dL and 39.3 mg/dL (P < 0.00053), respectively, and with variable changes in high-density lipoprotein (HDL-C) from decreases by 4.2 mg/dL to increases by 9.8 mg/dL (P < 0.00053). Conclusions: Variants in CYP19A1 are associated with decreases in triglycerides and variable changes in HDL-C in postmenopausal women on adjuvant aromatase inhibitors. Future studies are needed to validate these findings, and to identify breast cancer survivors who are at higher risk for cardiovascular disease with aromatase inhibitor therapy

Human and mouse essentiality screens as a resource for disease gene discovery

The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures of how essential a gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice by the International Mouse Phenotyping Consortium and essentiality screens carried out on human cell lines. We propose a cross-species gene classification across the Full Spectrum of Intolerance to Loss-of-function (FUSIL) and demonstrate that genes in five mutually exclusive FUSIL categories have differing biological properties. Most notably, Mendelian disease genes, particularly those associated with developmental disorders, are highly overrepresented among genes non-essential for cell survival but required for organism development. After screening developmental disorder cases from three independent disease sequencing consortia, we identify potentially pathogenic variants in genes not previously associated with rare diseases. We therefore propose FUSIL as an efficient approach for disease gene discovery. Discovery of causal variants for monogenic disorders has been facilitated by whole exome and genome sequencing, but does not provide a diagnosis for all patients. Here, the authors propose a Full Spectrum of Intolerance to Loss-of-Function (FUSIL) categorization that integrates gene essentiality information to aid disease gene discovery