Design of a crushing and agglomeration process for manufacturing bagasse charcoal

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Mechanical Engineering, 2006.Includes bibliographical references (leaves 33-34).In Haiti, wood and wood charcoal are common fuels for cooking. This practice has contributed to deforestation, leading to erosion and fatal floods. The availability of charcoal made from a different source other than wood, such as agricultural waste, might provide Haitians with an alternative, more sustainable fuel, which in turn may reduce fuel prices. MIT students have developed various methods for producing charcoal out of simple inexpensive devices. In a current manufacturing process, carbonized bagasse is crushed to a powder, then mixed and agglomerated with yucca binder into balls. A novel method may reduce operator exposure and inhalation of charcoal fines by keeping primary manufacturing phases in the oil drum and reducing the operational steps of transferring the material from one location to another. The goal of this thesis was to understand, test, and optimize the parameters of this novel crushing and agglomeration process. The final prototype was found to effectively crushing charcoal and mix charcoal with binder to some extent, while being an inexpensive alternative to reduce overall charcoal exposure. However, the mixing and agglomeration was not sufficiently uniform and further designs should be considered to increase uniformity of mixing of binder and charcoal.by Victoria Y. Fan.S.B

Performance-based fi nancing at the Global Fund to Fight AIDS, Tuberculosis and Malaria: an analysis of grant ratings and funding, 2003–12

Background Performance-based fi nancing can be used by global health funding agencies to improve programme performance and thus value for money. The Global Fund to Fight AIDS, Tuberculosis and Malaria was one of the fi rst global-health funders to deploy a performance-based fi nancing system. However, its complex, multistep system for calculating and paying on grant ratings has several components that are subjective and discretionary. We aimed to test the association between grant ratings and disbursements, an indication of the extent to which incentives for performance are transmitted to grant recipients. Methods We obtained publicly available data for 508 Global Fund grants from 2003 to 2012 with performance ratings and corresponding disbursements, merged with other datasets that contained data for relevant country characteristics. We used regression analysis to identify predictors of grant disbursements in phase 2 (typically the latter 3 of 5 years of a grant), using two dependent variables: whether a grant had any phase-2 disbursements, and the phase-2 disbursement amount. In a separate analysis, we also investigated the predictors of grant performance ratings. Findings Grant performance rating in phase 1 was positively associated with having any disbursements in phase 2, but no association was seen between phase-1 ratings and phase-2 disbursement amounts. Further more, performance ratings are not replicable by external observers, both because subjective and discretionary decisions are made in the generation of performance measures and because the underlying data are not available. Interpretation The Global Fund’s present performance-based funding system does not adequately convey incentives for performance to recipients, and the organisation should redesign this system to explicitly link a portion of the funds to a simple performance measure in health coverage or outcomes, measured independently and robustly

Global Budget Payment: Proposing the CAP Framework

To control ever-increasing costs, global budget payment has gained attention but has unclear impacts on health care systems. We propose the CAP framework that helps navigate 3 domains of difficult design choices in global budget payment: Constraints in resources (capitation vs facility-based budgeting; hard vs soft budget constraints), Agent-principal in resource allocation (individual vs group providers in resource allocation; single vs multiple pipes), and Price adjustment. We illustrate the framework with empirical examples and draw implications for policy makers

Going beyond GDP with a parsimonious indicator : inequality-adjusted healthy lifetime income

Per capita GDP has limited use as a well-being indicator because it does not capture many dimensions that imply a good life, such as health and equality of opportunity. However, per capita GDP has the virtues of easy interpretation and can be calculated with manageable data requirements. Against this backdrop, a need exists for a measure of well-being that preserves the advantages of per capita GDP, but also includes health and equality. We propose a new parsimonious indicator to fill this gap and calculate it for 149 countries

BRICS' role in global health and the promotion of universal health coverage: the debate continues.

The acronym BRIC was coined by Jim O’Neill, a senior executive at Goldman Sachs, to denote four emerging national economies: Brazil, the Russian Federation, India and China. Although BRICS and other multinational groupings may be useful to policy-makers involved in the development of some foreign policies, it remains unclear if such groupings have a role in the study and development of global health policy. We examine the debate around this issue and focus on BRICS’ potential role in the promotion of universal health coverage – an “umbrella” goal for health in the post-2015 development framework. We do not argue that BRICS has no value as a grouping. The constituent nations do have some things in common: they are all large, populous, diverse countries with many different ethnic, social and – in some cases – religious divisions. They share these characteristics with some other countries, such as Indonesia, Nigeria, Indonesia and Pakistan, that have made less progress toward universal health coverage but may be able to learn from BRICS’ experiences. There is no doubt that, in the promotion of universal health coverage, there is a need for collaboration and shared learning. However, a grouping of countries that may make sense in the coordination of global macroeconomic policy cannot be assumed to be relevant in the development of any global health policy

Homologous and heterologous desensitization of guanylyl cyclase-B signaling in GH3 somatolactotropes

The guanylyl cyclases, GC-A and GC-B, are selective receptors for atrial and C-type natriuretic peptides (ANP and CNP, respectively). In the anterior pituitary, CNP and GC-B are major regulators of cGMP production in gonadotropes and yet mouse models of disrupted CNP and GC-B indicate a potential role in growth hormone secretion. In the current study, we investigate the molecular and pharmacological properties of the CNP/GC-B system in somatotrope lineage cells. Primary rat pituitary and GH3 somatolactotropes expressed functional GC-A and GC-B receptors that had similar EC50 properties in terms of cGMP production. Interestingly, GC-B signaling underwent rapid homologous desensitization in a protein phosphatase 2A (PP2A)-dependent manner. Chronic exposure to either CNP or ANP caused a significant down-regulation of both GC-A- and GC-B-dependent cGMP accumulation in a ligand-specific manner. However, this down-regulation was not accompanied by alterations in the sub-cellular localization of these receptors. Heterologous desensitization of GC-B signaling occurred in GH3 cells following exposure to either sphingosine-1-phosphate or thyrotrophin-releasing hormone (TRH). This heterologous desensitization was protein kinase C (PKC)-dependent, as pre-treatment with GF109203X prevented the effect of TRH on CNP/GC-B signaling. Collectively, these data indicate common and distinct properties of particulate guanylyl cyclase receptors in somatotropes and reveal that independent mechanisms of homologous and heterologous desensitization occur involving either PP2A or PKC. Guanylyl cyclase receptors thus represent potential novel therapeutic targets for treating growth-hormone-associated disorders

Pan-viral serology implicates enteroviruses in acute flaccid myelitis.

Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)1-6. Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)2. CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM

MicroRNA Regulation of Human Protease Genes Essential for Influenza Virus Replication

Influenza A virus causes seasonal epidemics and periodic pandemics threatening the health of millions of people each year. Vaccination is an effective strategy for reducing morbidity and mortality, and in the absence of drug resistance, the efficacy of chemoprophylaxis is comparable to that of vaccines. However, the rapid emergence of drug resistance has emphasized the need for new drug targets. Knowledge of the host cell components required for influenza replication has been an area targeted for disease intervention. In this study, the human protease genes required for influenza virus replication were determined and validated using RNA interference approaches. The genes validated as critical for influenza virus replication were ADAMTS7, CPE, DPP3, MST1, and PRSS12, and pathway analysis showed these genes were in global host cell pathways governing inflammation (NF-κB), cAMP/calcium signaling (CRE/CREB), and apoptosis. Analyses of host microRNAs predicted to govern expression of these genes showed that eight miRNAs regulated gene expression during virus replication. These findings identify unique host genes and microRNAs important for influenza replication providing potential new targets for disease intervention strategies

Decoding the regulatory network of early blood development from single-cell gene expression measurements.

Reconstruction of the molecular pathways controlling organ development has been hampered by a lack of methods to resolve embryonic progenitor cells. Here we describe a strategy to address this problem that combines gene expression profiling of large numbers of single cells with data analysis based on diffusion maps for dimensionality reduction and network synthesis from state transition graphs. Applying the approach to hematopoietic development in the mouse embryo, we map the progression of mesoderm toward blood using single-cell gene expression analysis of 3,934 cells with blood-forming potential captured at four time points between E7.0 and E8.5. Transitions between individual cellular states are then used as input to develop a single-cell network synthesis toolkit to generate a computationally executable transcriptional regulatory network model of blood development. Several model predictions concerning the roles of Sox and Hox factors are validated experimentally. Our results demonstrate that single-cell analysis of a developing organ coupled with computational approaches can reveal the transcriptional programs that underpin organogenesis.We thank J. Downing (St. Jude Children's Research Hospital, Memphis, TN, USA) for the Runx1-ires-GFP mouse. Research in the authors' laboratory is supported by the Medical Research Council, Biotechnology and Biological Sciences Research Council, Leukaemia and Lymphoma Research, the Leukemia and Lymphoma Society, Microsoft Research and core support grants by the Wellcome Trust to the Cambridge Institute for Medical Research and Wellcome Trust - MRC Cambridge Stem Cell Institute. V.M. is supported by a Medical Research Council Studentship and Centenary Award and S.W. by a Microsoft Research PhD Scholarship.This is the accepted manuscript for a paper published in Nature Biotechnology 33, 269–276 (2015) doi:10.1038/nbt.315