Using a novel source-localized phase regressor technique for evaluation of the vascular contribution to semantic category area localization in BOLD fMRI.

Numerous studies have shown that gradient-echo blood oxygen level dependent (BOLD) fMRI is biased toward large draining veins. However, the impact of this large vein bias on the localization and characterization of semantic category areas has not been examined. Here we address this issue by comparing standard magnitude measures of BOLD activity in the Fusiform Face Area (FFA) and Parahippocampal Place Area (PPA) to those obtained using a novel method that suppresses the contribution of large draining veins: source-localized phase regressor (sPR). Unlike previous suppression methods that utilize the phase component of the BOLD signal, sPR yields robust and unbiased suppression of large draining veins even in voxels with no task-related phase changes. This is confirmed in ideal simulated data as well as in FFA/PPA localization data from four subjects. It was found that approximately 38% of right PPA, 14% of left PPA, 16% of right FFA, and 6% of left FFA voxels predominantly reflect signal from large draining veins. Surprisingly, with the contributions from large veins suppressed, semantic category representation in PPA actually tends to be lateralized to the left rather than the right hemisphere. Furthermore, semantic category areas larger in volume and higher in fSNR were found to have more contributions from large veins. These results suggest that previous studies using gradient-echo BOLD fMRI were biased toward semantic category areas that receive relatively greater contributions from large veins

Effect of continuous irradiation on proliferation of CHO-K1 and xrs-6 cells under low and high oxygen conditions

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Nuclear Science and Engineering, 2009.Cataloged from PDF version of thesis.Includes bibliographical references (p. 49-51).The goals of this research were to determine: 1) the effect of continuous irradiation on Chinese Hamster Ovary cells, CHO-K1 (wild type) and xrs-6 cells (mutant), and 2) the effect of continuous irradiation under low (5%) and high (20%) ambient oxygen conditions. Other authors have found continuous irradiation at low dose rates to have beneficial effects on cells. Oxygen is known to be harmful to DNA as it induces free radicals. The CHO-K1 cells were continuously irradiated for 7 weeks on Am 241 foils at a photon dose rate of 1.76 ± 0.02 cGy/hr. The xrs-6 cells were irradiated for one week on the same foils. Using the CyQUANT assay, the CHO-K1 cells showed no statistically significant difference in proliferation between the irradiated and control cells, even for total accumulated doses (> 20 Gy) that are lethal when delivered acutely. The same result was observed with the xrs-6 cells. However, when plated in flasks as opposed to well-plates, the cells showed lower rates of proliferation when irradiated, by a factor of 2 for CHO-K1 and by a factor of 50 to 100 for xrs-6. There was no significant difference in proliferation of both cells lines in the low and high oxygen conditions.by An T. Vu.S.B

Radiation therapy of pediatric brain tumors : comparison of long-term health effects and costs between proton therapy and IMRT

Thesis (S.M. in Technology and Policy)--Massachusetts Institute of Technology, Engineering Systems Division, Technology and Policy Program; and, (S.M.)--Massachusetts Institute of Technology, Dept. of Nuclear Science and Engineering, 2011.Cataloged from PDF version of thesis.Includes bibliographical references (p. 101-109).Radiation therapy is an important component of pediatric brain tumor treatment. However, radiation-induced damage can lead to adverse long-term health effects. Proton therapy has the ability to reduce the dose delivered to healthy tissue when compared to photon radiation therapy, but this dose benefit comes at a significantly higher initial cost, as proton therapy is 2 to 3 times more expensive to deliver than photon therapy. This thesis provides a framework for the evaluation of health and cost effectiveness of proton therapy compared to Intensity Modulated Radiation Therapy (IMRT). Proton therapy and IMRT treatment plans of patients treated for low-grade gliomas (LGGs) were analyzed to provide risk estimates of long-term health effects based on the dose distributions. A Markov simulation model was developed to estimate the health effects and costs of proton therapy and IMRT. The model tracked a pediatric cohort treated for LGGs at age 5. In the model, the patients were at risk of acquiring IQ loss, growth hormone deficiency (GHD), hypothyroidism, hearing loss, and secondary cancer. Patients faced risks of death due to tumor recurrence, secondary cancer, and normal death. In addition, a review of literature was performed to estimate the costs and additional health risks not determined from the patient treatment plans. The simulation results show that proton therapy can be cost effective in the treatment of LGGs based on the health risks estimated from the patients treatment plans. The cost associated with IQ loss and GHD were the main contributors to the total costs from long-term health effects. Proton therapy also results in a lower level of IQ loss and a lower risk of acquiring other long-term health effects. However, the relative difference in IQ point loss between the treatment modalities is small in the limited number of patients studied. There is a need to further investigate the advantages of proton therapy in reducing the dose delivered to the relevant parts of the brain to lower the risks of adverse health effects, especially for IQ loss.by An Thien Vu.S.M.S.M.in Technology and Polic

Universality in odd-even harmonic generation and application in terahertz waveform sampling

Odd-even harmonics emitted from a laser-target system imprint rich, subtle information characterizing the system's dynamical asymmetry, which is desirable to decipher. In this Letter, we discover a simple universal relation between the odd-even harmonics and the asymmetry of the THz-assisted laser-atomic system -- atoms in a fundamental mid-IR laser pulse combined with a THz laser. First, we demonstrate numerically and then analytically formulize the harmonic even-to-odd ratio as a function of the THz electric field, the source of the system's asymmetry. Notably, we suggest a scaling that makes the obtained rule universal, independent of the parameters of both the fundamental pulse and atomic target. This universality facilitates us to propose a general pump-probe scheme for THz waveform sampling from the even-to-odd ratio, measurable within a conventional compact setup

Trends in, projections of, and inequalities in reproductive, maternal, newborn and child health service coverage in Vietnam 2000-2030: A Bayesian analysis at national and sub-national levels

Background: To assess the reproductive, maternal, newborn and child health (RMNCH) service coverage in Vietnam with trends in 2000-2014, projections and probability of achieving targets in 2030 at national and sub-national levels; and to analyze the socioeconomic, regional and urban-rural inequalities in RMNCH service indicators. Methods: We used national population-based datasets of 44,624 households in Vietnam from 2000 to 2014. We applied Bayesian regression models to estimate the trends in and projections of RMNCH indicators and the probabilities of achieving the 2030 targets. Using the relative index, slope index, and concentration index of inequality, we examined the patterns and trends in RMNCH coverage inequality. Findings: We projected that 9 out of 17 health service indicators (53%) would likely achieve the 2030 targets at the national level, including at least one and four ANC visits, BCG immunization, access to improved water and adequate sanitation, institutional delivery, skilled birth attendance, care-seeking for pneumonia, and ARI treatment. We observed very low coverages and zero chance of achieving the 2030 targets at national and sub-national levels in early initiation and exclusive breastfeeding, family planning needs satisfied, and oral rehydration therapy. The most deprived households living in rural areas and the Northwest, Northeast, North Central, Central Highlands, and Mekong River Delta regions would not reach the 80% immunization coverage of DPT3, Polio3, Measles and full immunization. We found socioeconomic, regional, and urban-rural inequalities in all RMNCH indicators in 2014 and no change in inequalities over 15 years in the lowest-coverage indicators. Interpretation: Vietnam has made substantial progress toward UHC. By improving the government\u27s health system reform efforts, re-allocating resources focusing on people in the most impoverished rural regions, and restructuring and enhancing current health programs, Vietnam can achieve the UHC targets and other health-related SDGs

Regulation of SOX11 expression through CCND1 and STAT3 in mantle cell lymphoma

The neural transcription factor SOX11 is usually highly expressed in typical mantle cell lymphoma (MCL), but it is absent in the more indolent form of MCL. Despite being an important diagnostic marker for this hard-to-treat malignancy, the mechanisms of aberrant SOX11 expression are largely unknown. Herein, we describe 2 modes of SOX11 regulation by the cell-cycle regulator cyclin D1 (CCND1) and the signal transducer and activator of transcription 3 (STAT3). We found that ectopic expression of CCND1 in multiple human MCL cell lines resulted in increased SOX11 transcription, which correlated with increased acetylated histones H3K9 and H3K14 (H3K9/14Ac). Increased H3K9/14Ac and SOX11 expression was also observed after histone deacetylase 1 (HDAC1) or HDAC2 was depleted by RNA interference or inhibited by the HDAC inhibitor vorinostat. Mechanistically, we showed that CCND1 interacted with and sequestered HDAC1 and HDAC2 from the SOX11 locus, leading to SOX11 upregulation. Interestingly, our data revealed a potential inverse relationship between phosphorylated Y705 STAT3 and SOX11 expression in MCL cell lines, primary tumors, and patient-derived xenografts. Functionally, inactivation of STAT3 by inhibiting the upstream Janus kinase (JAK) 1 or JAK2 or by STAT3 knockdown was found to increase SOX11 expression, whereas interleukin-21 (IL-21)–induced STAT3 activation or overexpression of the constitutively active form of STAT3 decreased SOX11 expression. In addition, targeting SOX11 directly by RNA interference or indirectly by IL-21 treatment induced toxicity in SOX11^+ MCL cells. Collectively, we demonstrate the involvement of CCND1 and STAT3 in the regulation of SOX11 expression, providing new insights and therapeutic implications in MCL

Mapping for engagement: setting up a community based participatory research project to reach underserved communities at risk for Hepatitis C in Ho Chi Minh City, Vietnam

Background: Approximately 1. 07 million people in Vietnam are infected with hepatitis C virus (HCV). To address this epidemic, the South East Asian Research Collaborative in Hepatitis (SEARCH) launched a 600-patient cohort study and two clinical trials, both investigating shortened treatment strategies for chronic HCV infection with direct-acting antiviral drugs. We conducted ethnographic research with a subset of trial participants and found that the majority were aware of HCV infection and its implications and were motivated to seek treatment. However, people who inject drugs (PWID), and other groups at risk for HCV were under-represented, although injecting drug use is associated with high rates of HCV. Material and Methods: We designed a community-based participatory research (CBPR) study to engage in dialogues surrounding HCV and other community-prioritized health issues with underserved groups at risk for HCV in Ho Chi Minh City. The project consists of three phases: situation analysis, CBPR implementation, and dissemination. In this paper, we describe the results of the first phase (i.e., the situation analysis) in which we conducted desk research and organized stakeholder mapping meetings with representatives from local non-government and community-based organizations where we used participatory research methods to identify and analyze key stakeholders working with underserved populations. Results: Twenty six institutions or groups working with the key underserved populations were identified. Insights about the challenges and dynamics of underserved communities were also gathered. Two working groups made up of representatives from the NGO and CBO level were formed. Discussion: Using the information provided by local key stakeholders to shape the project has helped us to build solid relationships, give the groups a sense of ownership from the early stages, and made the project more context specific. These steps are not only important preliminary steps for participatory studies but also for other research that takes place within the communities

Fusion in diffusion MRI for improved fibre orientation estimation: an application to the 3T and 7T data of the Human Connectome Project

Determining the acquisition parameters in diffusion magnetic resonance imaging (dMRI) is governed by a series of trade-offs. Images of lower resolution have less spatial specificity but higher signal to noise ratio (SNR). At the same time higher angular contrast, important for resolving complex fibre patterns, also yields lower SNR. Considering these trade-offs, the Human Connectome Project (HCP) acquires high quality dMRI data for the same subjects at different field strengths (3T and 7T), which are publically released. Due to differences in the signal behavior and in the underlying scanner hardware, the HCP 3T and 7T data have complementary features in k- and q-space. The 3T dMRI has higher angular contrast and resolution, while the 7T dMRI has higher spatial resolution. Given the availability of these datasets, we explore the idea of fusing them together with the aim of combining their benefits. We extend a previously proposed data-fusion framework and apply it to integrate both datasets from the same subject into a single joint analysis. We use a generative model for performing parametric spherical deconvolution and estimate fibre orientations by simultaneously using data acquired under different protocols. We illustrate unique features from each dataset and how they are retained after fusion. We further show that this allows us to complement benefits and improve brain connectivity analysis compared to analyzing each of the datasets individually