Effect of x‐y coupling on the beam breakup instability

In solenoidal beam transport systems, motions in the x and y directions are coupled by the v×B force. A two‐dimensional coupled mode description of the beam breakup (BBU) instability is presented; its dispersion relation is derived and compared with the one‐dimensional BBU dispersion relation. In the two‐dimensional description, instability growth is doubled and two additional wave modes are found in the regime of strong focusing. In the weak focusing regime, the two‐dimensional description gives the same dispersion relation as the one‐dimensional model.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69723/2/APPLAB-58-7-699-1.pd

Vitamin D Status and TB Treatment Outcomes in Adult Patients in Tanzania: A Cohort Study.

Vitamin D is an immunomodulator and can alter response to tuberculosis (TB) treatment, though randomised trials have been inconclusive to date. We present one of the first comprehensive analysis of the associations between vitamin D status and TB treatment, T-cell counts and nutritional outcomes by HIV status. Cohort study. Outpatient clinics in Tanzania. 25-hydroxyvitamin D levels were assessed in a cohort of 677 patients with TB (344 HIV infected) initiating anti-TB treatment at enrolment in a multivitamin supplementation (excluding vitamin D) trial (Clinicaltrials.gov identifier: NCT00197704). Information on treatment outcomes such as failure and relapse, HIV disease progression, T-cell counts and anthropometry was collected routinely, with a median follow-up of 52 and 30 months for HIV-uninfected and HIV-infected patients, respectively. Cox and binomial regression, and generalised estimating equations were used to assess the association of vitamin D status with these outcomes. Mean 25-hydroxyvitamin D concentrations at enrolment were 69.8 (±21.5) nmol/L (27.9 (±8.6) ng/mL). Vitamin D insufficiency (<75 nmol/L) was associated with a 66% higher risk of relapse (95% CI 4% to 164%; 133% higher risk in HIV-uninfected patients). Each unit higher 25-hydroxyvitamin D levels at baseline were associated with a decrease of 3 (p=0.004) CD8 and 3 (p=0.01) CD3 T-cells/µL during follow-up in patients with HIV infection. Vitamin D insufficiency was also associated with a greater decrease of body mass index (BMI; -0.21 kg/m(2); 95% CI -0.39 to -0.02), during the first 8 months of follow-up. No association was observed for vitamin D status with mortality or HIV disease progression. Adequate vitamin D status is associated with a lower risk of relapse and with improved nutritional indicators such as BMI in patients with TB, with or without HIV infection. Further research is needed to determine the optimal dose of vitamin D and effectiveness of daily vitamin D supplementation among patients with TB

The survival-incorporated median versus the median in the survivors or in the always-survivors: What are we measuring? And why?

Many clinical studies evaluate the benefit of treatment based on both survival and other ordinal/continuous clinical outcomes, such as neurocognitive scores or quality-of-life scores. In these studies, there are situations when the clinical outcomes are truncated by death, where subjects die before their clinical outcome is measured. Treating outcomes as "missing" or "censored" due to death can be misleading for treatment effect evaluation. We show that if we use the median in the survivors or in the always-survivors to summarize clinical outcomes, we may conclude a trade-off exists between the probability of survival and good clinical outcomes, even in settings where both the probability of survival and the probability of any good clinical outcome are better for one treatment. Therefore, we advocate not always treating death as a mechanism through which clinical outcomes are missing, but rather as part of the outcome measure. To account for the survival status, we describe the survival-incorporated median as an alternative summary measure for outcomes in the presence of death. The survival-incorporated median is the threshold such that 50\% of the population is alive with an outcome above that threshold. We use conceptual examples to show that the survival-incorporated median provides a simple and useful summary measure to inform clinical practice

Sensitivity Analysis for the Assessment of Causal Vaccine Effects on Viral Load in HIV Vaccine Trials

Vaccines with limited ability to prevent HIV infection may positively impact the HIV/AIDS pandemic by preventing secondary transmission and disease in vaccine recipients who become infected. To evaluate the impact of vaccination on secondary transmission and disease, efficacy trials assess vaccine effects on HIV viral load and other surrogate endpoints measured after infection. A standard test that compares the distribution of viral load between the infected subgroups of vaccine and placebo recipients does not assess a causal effect of vaccine, because the comparison groups are selected after randomization. To address this problem, we formulate clinically relevant causal estimands using the principal stratification framework developed by Frangakis and Rubin (2002), and propose a class of logistic selection bias models whose members identify the estimands. Given a selection model in the class, procedures are developed for testing and estimation of the causal effect of vaccination on viral load in the principal stratum of subjects who would be infected regardless of randomization assignment. We show how the procedures can be used for a sensitivity analysis that quantifies how the causal effect of vaccination varies with the presumed magnitude of selection bias

A Trial of the Effect of Micronutrient Supplementation on Treatment Outcome, T Cell Counts, Morbidity, and Mortality in Adults with Pulmonary Tuberculosis.

Tuberculosis (TB) often coincides with nutritional deficiencies. The effects of micronutrient supplementation on TB treatment outcomes, clinical complications, and mortality are uncertain. We conducted a randomized, double-blind, placebo-controlled trial of micronutrients (vitamins A, B complex, C, and E, as well as selenium) in Dar es Salaam, Tanzania. We enrolled 471 human immunodeficiency virus (HIV)-infected and 416 HIV-negative adults with pulmonary TB at the time of initiating chemotherapy and monitored them for a median of 43 months. Micronutrients decreased the risk ofTB recurrence by 45% overall (95% confidence interval [CI], 7% to 67%; P = .02) and by 63% in HIV-infected patients (95% CI, 8% to 85%; P = .02). There were no significant effects on mortality overall; however, we noted a marginally significant 64% reduction of deaths in HIV-negative subjects (95% CI, -14% to 88%; P = .08). Supplementation increased CD3+ and CD4+ cell counts and decreased the incidence of extrapulmonary TB and genital ulcers in HIV-negative patients. Micronutrients reduced the incidence of peripheral neuropathy by 57% (95% CI, 41% to 69%; P < .001), irrespective of HIV status. There were no significant effects on weight gain, body composition, anemia, or HIV load. Micronutrient supplementation could improve the outcome in patients undergoing TB chemotherapy in Tanzania

Continuing or adding IL-2 in patients treated with antiretroviral therapy (ACTG Protocol A5051, a rollover trial of ACTG Protocol A328)

<p>Abstract</p> <p>Background</p> <p>Effective antiretroviral therapy reduces HIV-1 RNA levels, improves CD4 T-cell counts, and lowers the risk of opportunistic infections and malignancies. Interleukin-2 (IL-2) has been shown to increase CD4 T-cell numbers mainly by expanding CD4 cells and by prolonging their half-lives. HIV-infected patients previously enrolled into A328 had been randomized to antiretroviral therapy (ART) alone or ART followed by IL-2. In A5051, 53 patients from A328 who had previously received IL-2 were allowed to continue IL-2 for an additional 80 weeks; 27 patients who had received ART alone received IL-2 for 80 weeks.</p> <p>Results</p> <p>The patients previously receiving IL-2 continued to have elevated CD4 levels with extended use of IL-2. The prior ART-alone recipients had increases in CD4 levels to comparable levels as the prior IL-2 recipients (median 804 versus 847 cells/mm³at week 72; 60% versus 9% had >50% increase in A5051 to week 72, p < 0.001). Those who had previously received IL-2 required fewer IL-2 cycles to maintain their CD4 T-cell counts compared to those newly initiating IL-2. The treatments were well tolerated with no significant differences in toxicity or discontinuations between those newly versus previously receiving IL-2. There were few clinical events observed.</p> <p>Conclusions</p> <p>Although sustained CD4 T-cell count increases were seen with IL-2 administration as in other studies, the absence of clinical benefit in two recent randomized trials has demonstrated no apparent role for IL-2 as a therapy in HIV disease.</p> <p>Trial Registration</p> <p>A5051 ClinicalTrials.gov Identifier: NCT00000923.</p

Microwave growth from the beam breakup instability in long‐pulse electron beam experiments

The beam breakup (BBU) instability has been investigated in high‐current, long‐pulse electron beams propagating through microwave cavities. Experiments are performed using a relativistic electron‐beam generator with diode parameters: 0.7–0.8 MV, 1–15 kA, and 0.5–1.5 μs. The magnitude of the solenoidal magnetic field places these experiments in an intermediate regime between strong focusing and weak focusing. The electron‐beam transport system consists of ten identical pillbox cavities each containing a small microwave loop antenna designed to detect the TM110 beam breakup mode. The TM110 microwave mode is primed in the first cavity by a magnetron tuned to the resonance frequency of 2.5 GHz. The BBU instability growth is measured through the amplification of the 2.5 GHz microwaves between the second and tenth cavities. Strong growth (25–38 dB) of the TM110 microwave signal is observed when the initial cavity is primed exactly on resonance, with a rapid decrease of the growth rate off‐resonance. The magnitude of microwave growth is consistent with the predictions of BBU theory.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/69350/2/APPLAB-61-6-642-1.pd

The beam breakup instability in quadrupole and solenoidal electron‐beam transport systems

Dispersion relations are derived to determine the growth rate, dominant wavelength, and group velocity of disturbances caused by the beam breakup instability. Considerations include weak and strong focusing, x‐y coupling in solenoidal transport, the spacing of accelerator cavities, and periodically pulsed beams. Beam breakup growth is minimum when the cavity spacing equals an integral number of half‐betatron wavelengths for quadrupole focusing, and an integral number of betatron wavelengths for solenoidal focusing. Minimum growth is also found for periodic pulses separated by an integral number of half‐periods of the TM110 cavity mode. Expressions for beam breakup growth at the minima are obtained.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/71286/2/JAPIAU-71-7-3091-1.pd