A risk management strategy for public-private partnerships : San Francisco's Yerba Buena Gardens

Thesis (M.S.)--Massachusetts Institute of Technology, Dept. of Architecture, 1991.Includes bibliographical references (leaves 140-151).by Peter B. Benson and Lisa C. Flaster.M.S

The Champlain Thrust and Related Features Near Middlebury,Vermont

Guidebook for field trips in Vermont: 64th annual meeting October 13, 14, 15, 1972 Burlington, Vermont: Trip B-

Net Shape Spin Formed Cryogenic Aluminum Lithium Cryogenic Tank Domes for Lower Cost Higher Performance Launch Vehicles

With the goal of lower cost (simplified manufacturing and lower part count) and higher performance (higher strength to weight alloys) the NASA Technical Maturation Program in 2006 funded a proposal to investigate spin forming of space launch vehicle cryogenic tank domes. The project funding continued under the NASA Exploration Technology Development Program through completion in FY12. The first phase of the project involved spin forming of eight, 1 meter diameter "path finder" domes. Half of these were processed using a concave spin form process (MT Aerospace, Augsburg Germany) and the other half using a convex process (Spincraft, Boston MA). The convex process has been used to produce the Ares Common Bulkhead and the concave process has been used to produce dome caps for the Space Shuttle light weight external tank and domes for the NASDA H2. Aluminum Lithium material was chosen because of its higher strength to weight ratio than the Aluminum 2219 baseline. Aluminum lithium, in order to obtain the desired temper (T8), requires a cold stretch after the solution heat treatment and quench. This requirement favors the concave spin form process which was selected for scale up. This paper describes the results of processing four, 5.5 meter diameter (upper stage scale) net shaped spin formed Aluminum Lithium domes. In order to allow scalability beyond the limits of foundry and rolling mills (about 12 foot width) the circular blank contained one friction stir weld (heavy lifter scales require a flat blank containing two welds). Mechanical properties data (tensile, fracture toughness, stress corrosion, and simulated service testing) for the parent metal and weld will also be discussed

Real-world evidence was feasible for estimating effectiveness of chemotherapy in breast cancer; a cohort study

Objective: Evidence-based guidelines recommend adjuvant chemotherapy in early stage breast cancer whenever treatment benefit is considered sufficient to outweigh the associated risks. However, many groups of patients were either excluded from or underrepresented in the clinical trials that form the evidence base for this recommendation. This study aims to determine whether using administrative healthcare data – Real World Data (RWD) - and econometric methods for causal analysis to provide ‘Real World Evidence’ (RWE) are feasible methods for addressing this gap.Methods: Cases of primary breast cancer in women from 2001 to 2015 were extracted from the Scottish cancer registry (SMR06) and linked to other routine health records (inpatient and outpatient visits). Four methods were used to estimate the effect of adjuvant chemotherapy on disease-specific and overall mortality: (1) regression with adjustment for covariates (2) propensity score matching (3) instrumental variables analysis and (4) regression discontinuity design. Hazard ratios for breast cancer mortality and all-cause mortality were compared to those from a meta-analysis of randomised trials.Results: 39,805 cases included in the analyses. Regression adjustment, propensity score matching and instrumental variables were feasible while regression discontinuity was not. Effectiveness estimates were similar between RWE and randomised trials for breast cancer mortality but not for all-cause mortality.Conclusions: RWE methods are a feasible means to generate estimates of effectiveness of adjuvant chemotherapy in early stage breast cancer. However, such estimates must be interpreted in the context of the available randomised evidence and the potential biases of the observational methods.<br/

Antigenic specificity of antibody-dependent cell-mediated cytotoxicity directed against human immunodeficiency virus in antibody-positive sera

Antibody-dependent cell-mediated cytotoxicity (ADCC) specific for human immunodeficiency virus (HIV) has been described for HIV-infected individuals. To determine the antigenic specificity of this immune response and to define its relationship to the disease state, an ADCC assay was developed using Epstein-Barr virus-transformed lymphoblastoid cell line targets infected with vaccinia virus vectors expressing HIV proteins. The vaccinia virus vectors induced appropriate HIV proteins (envelope glycoproteins gp160, gp120, and gp41 or gag proteins p55, p40, p24, and p17) in infected lymphoblastoid cell lines as demonstrated by radioimmunoprecipitation and syncytia formation with c8166 cells. Killer cell-mediated, HIV-specific ADCC was found in sera from HIV-seropositive but not HIV-seronegative hemophiliacs. This HIV-specific response was directed against envelope glycoprotein but was completely absent against target cells expressing the HIV gag proteins. The ADCC directed against gp160 was present at serum dilutions up to 1/316,000. There was no correlation between serum ADCC titer and the stage of HIV-related illness as determined by T-helper-cell numbers. These experiments clearly implicated gp160 as the target antigen of HIV-specific ADCC activity following natural infection. Vaccines which stimulate antibodies directed against gp160, which are capable of mediating ADCC against infected cells, could be important for protection against infection by cell-associated virus

Strategies for Understanding and Reducing the Plasmodium vivax and Plasmodium ovale Hypnozoite Reservoir in Papua New Guinean Children: A Randomised Placebo-Controlled Trial and Mathematical Model

The undetectable hypnozoite reservoir for relapsing Plasmodium vivax and P. ovale malarias presents a major challenge for malaria control and elimination in endemic countries. This study aims to directly determine the contribution of relapses to the burden of P. vivax and P. ovale infection, illness, and transmission in Papua New Guinean children.; From 17 August 2009 to 20 May 2010, 524 children aged 5-10 y from East Sepik Province in Papua New Guinea (PNG) participated in a randomised double-blind placebo-controlled trial of blood- plus liver-stage drugs (chloroquine [CQ], 3 d; artemether-lumefantrine [AL], 3 d; and primaquine [PQ], 20 d, 10 mg/kg total dose) (261 children) or blood-stage drugs only (CQ, 3 d; AL, 3 d; and placebo [PL], 20 d) (263 children). Participants, study staff, and investigators were blinded to the treatment allocation. Twenty children were excluded during the treatment phase (PQ arm: 14, PL arm: 6), and 504 were followed actively for 9 mo. During the follow-up time, 18 children (PQ arm: 7, PL arm: 11) were lost to follow-up. Main primary and secondary outcome measures were time to first P. vivax infection (by qPCR), time to first clinical episode, force of infection, gametocyte positivity, and time to first P. ovale infection (by PCR). A basic stochastic transmission model was developed to estimate the potential effect of mass drug administration (MDA) for the prevention of recurrent P. vivax infections. Targeting hypnozoites through PQ treatment reduced the risk of having at least one qPCR-detectable P. vivax or P. ovale infection during 8 mo of follow-up (P. vivax: PQ arm 0.63/y versus PL arm 2.62/y, HR = 0.18 [95% CI 0.14, 0.25], p &lt; 0.001; P. ovale: 0.06 versus 0.14, HR = 0.31 [95% CI 0.13, 0.77], p = 0.011) and the risk of having at least one clinical P. vivax episode (HR = 0.25 [95% CI 0.11, 0.61], p = 0.002). PQ also reduced the molecular force of P. vivax blood-stage infection in the first 3 mo of follow-up (PQ arm 1.90/y versus PL arm 7.75/y, incidence rate ratio [IRR] = 0.21 [95% CI 0.15, 0.28], p &lt; 0.001). Children who received PQ were less likely to carry P. vivax gametocytes (IRR = 0.27 [95% CI 0.19, 0.38], p &lt; 0.001). PQ had a comparable effect irrespective of the presence of P. vivax blood-stage infection at the time of treatment (p = 0.14). Modelling revealed that mass screening and treatment with highly sensitive quantitative real-time PCR, or MDA with blood-stage treatment alone, would have only a transient effect on P. vivax transmission levels, while MDA that includes liver-stage treatment is predicted to be a highly effective strategy for P. vivax elimination. The inclusion of a directly observed 20-d treatment regime maximises the efficiency of hypnozoite clearance but limits the generalisability of results to real-world MDA programmes.; These results suggest that relapses cause approximately four of every five P. vivax infections and at least three of every five P. ovale infections in PNG children and are important in sustaining transmission. MDA campaigns combining blood- and liver-stage treatment are predicted to be a highly efficacious intervention for reducing P. vivax and P. ovale transmission.; ClinicalTrials.gov NCT02143934