Time to Discipline? Estimating the Risks and Impact of Public-School Discipline

In the three essays in this thesis, I explore the effect of school discipline policies on the suspension of public-school students, in an urban setting. In the first essay, using aggregate data, I investigate the effect of zero-tolerance disciplinary polices on secondary-school students. Capitalizing on a natural experiment, I used a “differences-in-differences” analytic approach to explore any benefit of a hypothesized deterrent effect and to estimate the impact of the abrupt expansion of zero-tolerance policies in one large urban school district. I found that Black students were suspended from school more often following the policy change, while suspensions of White students remained unchanged. In addition, expulsions from school, following the policy change, more than doubled for Black students, compared to only a small increase for White students. In the second essay, and the same urban setting, I employed continuous-time survival analysis in a student-level event-history dataset to estimate the risk of middle-school students’ first suspension of the school year. I found that this risk differed by three factors: (a) when the suspension occurred, (b) student grade-level, and (c) student race. At the beginning of the school year, this risk of first suspension for eighth-grade students was double the risk for sixth-grade students, although this difference diminished over time. Additionally, the risk for Black students was more than ten times the risk for White students. In the third essay, I extended my work further, using repeated-spells survival analysis to describe the timing of suspensions over the duration of the students’ entire middle-school careers. I found that—once a student had been suspended from middle school for the first time—the median time until a second suspension was less than one school year, and the median time until a third suspension was about one semester. These risks also differed substantially by gender, race, and poverty level. The risk of a first suspension for boys was substantially higher than for girls. This risk was also higher for poor students than for non-poor students. However, the risks of both a first suspension and subsequent suspensions were substantially higher for Black students, compared to White students, even after controlling for differences in poverty among the groups. Taken together, these analyses underscore disparities in school disciplinary practices, based on important student demographic characteristics, while providing an updated and more methodologically sound way of describing these effects

Molecular dissection of the mechanism by which EWS/FLI expression compromises actin cytoskeletal integrity and cell adhesion in Ewing sarcoma.

Ewing sarcoma is the second-most-common bone cancer in children. Driven by an oncogenic chromosomal translocation that results in the expression of an aberrant transcription factor, EWS/FLI, the disease is typically aggressive and micrometastatic upon presentation. Silencing of EWS/FLI in patient-derived tumor cells results in the altered expression of hundreds to thousands of genes and is accompanied by dramatic morphological changes in cytoarchitecture and adhesion. Genes encoding focal adhesion, extracellular matrix, and actin regulatory proteins are dominant targets of EWS/FLI-mediated transcriptional repression. Reexpression of genes encoding just two of these proteins, zyxin and α5 integrin, is sufficient to restore cell adhesion and actin cytoskeletal integrity comparable to what is observed when the EWS/FLI oncogene expression is compromised. Using an orthotopic xenograft model, we show that EWS/FLI-induced repression of α5 integrin and zyxin expression promotes tumor progression by supporting anchorage-independent cell growth. This selective advantage is paired with a tradeoff in which metastatic lung colonization is compromised

Plasmodium yoelii-Infected A. stephensi Inefficiently Transmit Malaria Compared to Intravenous Route

It was recently reported that when mosquitoes infected with P. berghei sporozoites feed on mice, they deposit approximately 100–300 sporozoites in the dermis. When we inoculate P. yoelii (Py) sporozoites intravenously (IV) into BALB/c mice, the 50% infectious dose (ID50) is often less than 3 sporozoites, indicating that essentially all Py sporozoites in salivary glands are infectious. Thus, it should only take the bite of one infected mosquito to infect 100% of mice. In human subjects, it takes the bite of at least 5 P. falciparum-infected mosquitoes to achieve 100% blood stage infection. Exposure to 1–2 infected mosquitoes only leads to blood stage infection in approximately 50% of subjects. If mosquitoes carrying Py sporozoites inoculate 100–300 sporozoites per bite, and 1 to 2 mosquito bites achieve 50% blood stage infection rates, then this would suggest that the majority of sporozoites inoculated by mosquitoes into the dermis are not responsible for a productive infection, or that a significant number of sporozoite-infected mosquitoes do not inoculate any sporozoites. The objective of this study was to determine if this is the case. We therefore studied the infectivity to mice of the bites of 1, 2, 4, or 5–8 Py-infected mosquitoes. The bite of one Py sporozoite-infected mosquito caused blood stage infection in 41.4% (12/29) of mice, two bites infected 66.7% (22/33), four bites infected 75% (18/24), and five to eight bites infected 100% (21/21). These findings demonstrate that inoculation of sporozoites by mosquito bite is much less efficient than IV inoculation of Py sporozoites by needle and syringe. Such data may have implications for determining the best route and dose of administration to humans of our attenuated P. falciparum sporozoite vaccine, the scientific basis of which is immunity by bites from irradiated infected mosquitoes, and suggest that the challenge is to develop a method of administration that approximates IV inoculation, not one that mimics mosquito bite

Robust, reproducible, industrialized, standard membrane feeding assay for assessing the transmission blocking activity of vaccines and drugs against Plasmodium falciparum.

BackgroundA vaccine that interrupts malaria transmission (VIMT) would be a valuable tool for malaria control and elimination. One VIMT approach is to identify sexual erythrocytic and mosquito stage antigens of the malaria parasite that induce immune responses targeted at disrupting parasite development in the mosquito. The standard Plasmodium falciparum membrane-feeding assay (SMFA) is used to assess transmission-blocking activity (TBA) of antibodies against candidate immunogens and of drugs targeting the mosquito stages. To develop its P. falciparum sporozoite (SPZ) products, Sanaria has industrialized the production of P. falciparum-infected Anopheles stephensi mosquitoes, incorporating quantitative analyses of oocyst and P. falciparum SPZ infections as part of the manufacturing process.MethodsThese capabilities were exploited to develop a robust, reliable, consistent SMFA that was used to assess 188 serum samples from animals immunized with the candidate vaccine immunogen, Pfs25, targeting P. falciparum mosquito stages. Seventy-four independent SMFAs were performed. Infection intensity (number of oocysts/mosquito) and infection prevalence (percentage of mosquitoes infected with oocysts) were compared between mosquitoes fed cultured gametocytes plus normal human O(+) serum (negative control), anti-Pfs25 polyclonal antisera (MRA39 or MRA38, at a final dilution in the blood meal of 1:54 as positive control), and test sera from animals immunized with Pfs25 (at a final dilution in the blood meal of 1:9).ResultsSMFA negative controls consistently yielded high infection intensity (mean = 46.1 oocysts/midgut, range of positives 3.7-135.6) and infection prevalence (mean = 94.2%, range 71.4-100.0) and in positive controls, infection intensity was reduced by 81.6% (anti-Pfs25 MRA39) and 97.0% (anti-Pfs25 MRA38), and infection prevalence was reduced by 12.9 and 63.5%, respectively. A range of TBAs was detected among the 188 test samples assayed in duplicate. Consistent administration of infectious gametocytes to mosquitoes within and between assays was achieved, and the TBA of anti-Pfs25 control antibodies was highly reproducible.ConclusionsThese results demonstrate a robust capacity to perform the SMFA in a medium-to-high throughput format, suitable for assessing large numbers of experimental samples of candidate antibodies or drugs

A One-Dimensional Volcanic Plume Model for Predicting Ash Aggregation

During explosive volcanic eruptions, volcanic ash is ejected into the atmosphere, impacting aircraft safety and downwind communities. These volcanic clouds tend to be dominated by fine ash (μm in diameter), permitting transport over hundreds to thousands of kilometers. However, field observations show that much of this fine ash aggregates into clusters or pellets with faster settling velocities than individual particles. Models of ash transport and deposition require an understanding of aggregation processes, which depend on factors like moisture content and local particle collision rates. In this study, we develop a Plume Model for Aggregate Prediction, a one-dimensional (1D) volcanic plume model that predicts the plume rise height, concentration of water phases, and size distribution of resulting ash aggregates from a set of eruption source parameters. The plume model uses a control volume approach to solve mass, momentum, and energy equations along the direction of the plume axis. The aggregation equation is solved using a fixed pivot technique and incorporates a sticking efficiency model developed from analog laboratory experiments of particle aggregation within a novel turbulence tower. When applied to the 2009 eruption of Redoubt Volcano, Alaska, the 1D model predicts that the majority of the plume is over-saturated with water, leading to a high rate of aggregation. Although the mean grain size of the computed Redoubt aggregates is larger than the measured deposits, with a peak at 1 mm rather than 500 μm, the present results provide a quantitative estimate for the magnitude of aggregation in an eruption

Short Report: Therapeutic Efficacy of Chloroquine Combined with Primaquine Against \u3ci\u3ePlasmodium falciparum\u3c/i\u3e in Northeastern Papua, Indonesia

Chloroquine combined with primaquine was evaluated for therapy of uncomplicated malaria caused by Plasmodium falciparum in nonimmune Javanese migrants to northeastern Papua, Indonesia. Subjects were randomized to treatment with standard chloroquine therapy (25 mg/kg in 3 doses over the course of 48 hours) with 30 mg primaquine administered daily for 28 days (n = 25) or a placebo of primaquine (n = 28). The 14-day cumulative incidence of therapeutic failure was 56% with primaquine and 79% with placebo (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.1–1.3; P = 0.08). Primaquine administered daily created a marginally significant improvement in therapeutic efficacy at day 14, but not at day 7 (20% versus 36%; OR, 0.2; 95% CI, 0.1–1.8; P = 0.2) or day 28 (82% versus 93%; OR, 0.31; 95% CI, 0.04–2.1; P = 0.23). This report corroborates studies suggesting that therapeutic doses of primaquine exert no discernible effect on parasitemia by P. falciparum

Short Report: Therapeutic Efficacy of Chloroquine Combined with Primaquine Against \u3ci\u3ePlasmodium falciparum\u3c/i\u3e in Northeastern Papua, Indonesia

Chloroquine combined with primaquine was evaluated for therapy of uncomplicated malaria caused by Plasmodium falciparum in nonimmune Javanese migrants to northeastern Papua, Indonesia. Subjects were randomized to treatment with standard chloroquine therapy (25 mg/kg in 3 doses over the course of 48 hours) with 30 mg primaquine administered daily for 28 days (n = 25) or a placebo of primaquine (n = 28). The 14-day cumulative incidence of therapeutic failure was 56% with primaquine and 79% with placebo (odds ratio [OR], 0.35; 95% confidence interval [CI], 0.1–1.3; P = 0.08). Primaquine administered daily created a marginally significant improvement in therapeutic efficacy at day 14, but not at day 7 (20% versus 36%; OR, 0.2; 95% CI, 0.1–1.8; P = 0.2) or day 28 (82% versus 93%; OR, 0.31; 95% CI, 0.04–2.1; P = 0.23). This report corroborates studies suggesting that therapeutic doses of primaquine exert no discernible effect on parasitemia by P. falciparum

Treatment of Chloroquine-Resistant \u3ci\u3ePlasmodium vivax\u3c/i\u3e with Chloroquine and Primaquine or Halofantrine

Optimal therapy gor infection by chloroquine-resistant Plasmodium vivax has not been established. From 1992 to 1994 during three separate studies, 147 Javanese residents of Irian Jaya infected by P. vivax were treated with either chloroquine (2 5 mg of base/kg during 3 days or 10mg of base/kg in one dose) plus primaquine (1 0 mg/kg during 28 days or 2.5 mg/kg during 3 days)( n = 78), chloroquine plus placebo( n = 50), or halofantrine (24 mg base/kg in 12 h; n = 19). There was no difference in tolerance to or side effects of any of the regimens. Within 14 days of starting therapy, therapeutic failure among these patients was 44% for chloroquine, 5% for chloroquine plus primaquine (P \u3c .001), and 0 for halofantrine (P \u3c .001). After 28 days, therapeutic failure was 78%, 15%, and 6% respectively. Thus, chloroquine plus primaquine in combination and halofantrine alone are effective therapies for chloroquine-resistant P. vivax