Innovative Financing in Early Recovery: The Liberia Health Sector Pool Fund - Working Paper 288

In post-conflict Liberia, the National Health Plan set out a process for transitioning from emergency to sustainability under government leadership. The Liberia Health Sector Pool Fund, which consists of DfID, Irish Aid, UNICEF, and UNHCR, was established to fund this plan and mitigate this transition by increasing institutional capacity, reducing the transaction costs associated with managing multiple donor projects, and fostering the leadership of the Liberian Health Ministry by allocating funds to national priorities. In this paper, we discuss the design of the health pool fund mechanism, assess its functioning, compare the pooled fund to other aid mechanisms used in Liberia, and look into the enabling conditions, opportunities, and challenges of the pool fundLiberia, national health plan, aid effectivenes

Towards preparative in vitro enzymatic synthesis of new polyketide metabolites

textModular polyketide synthases (PKSs) are the largest enzymes known to man and are responsible for synthesizing some of the most important human medicines. Their ability to construct stereochemically-rich carbon chains containing diverse substituents has inspired the biosynthetic community to engineer these factories for the in vitro synthesis of a small library of polyketide compounds. New complex polyketides are discovered every year, yet the lack of compound prohibits characterization and testing of these new compounds for medicinal properties. Smaller polyketide compounds generated in vitro could be organically manipulated to generate larger, more complex polyketide natural products and natural product analogs. Chemoenzymatic approaches like this would be extremely beneficial to the scientific community; however, there are still obstacles that must be overcome before the use of PKS for the preparative synthesis of an in vitro generated polyketide library would prove fruitful: purchasing substrates such as methylmalonyl-CoA is cost-prohibitive, PKSs are often difficult to express and purify, and the products generated are typically nonchromophoric. The use of a malonyl-CoA ligase from Streptomyces coelicolor (MatB) was investigated for the enzymatic synthesis of polyketide extender units such as methylmalonyl-CoA (Chapter 2). MatB synthesized a total of 5 CoA-linked extender units in vitro: malonyl-, methylmalonyl-, ethylmalonyl-, hydroxymalonyl- and methoxymalonyl-CoA. Two ternary complex structures of MatB with bound product and leaving group were also solved to sub-2Å resolution. MatB generated extender units were employed in the module-catalyzed synthesis of a triketide pyrone. The selectivity of a PKS module to incorporate a variety of side chains into triketide pyrones was also investigated (Chapter 3). A total of 10 triketide pyrone compounds were synthesized, 5 produced via modular "stuttering" and one possessing a terminal alkyne chemical handle. Lastly, nonchromphoric polyketide products were made visible upon copper(I)-catalyzed azide alkyne cycloaddition (CuAAC) with fluorescent sulforhodamine B azide revealing insights into in vitro reactivites of a PKS module (Chapter 4). The work described in this dissertation has helped advance the scientific community towards procuring an in vitro synthesized polyketide library for future synthetic applications.Biochemistr

in defense of Grass Grows: a play about mental illness

My mission as a mentally ill theatre artist is to challenge the commonly-perpetuated fictions that restrict public perception of mentally ill persons [MIPs]. A meta-analysis of plays from the Greek, Medieval, Victorian, Melodramatic, Naturalist, and Post- Naturalist eras reflected just how little progress has been made at exposing and eliminating popular myths about mental illness. While the theatrical canon offers evidence for the inadequacy of current representations of MIPs, the psychological literature offers steps forward for the artists telling these stories. Efforts to improve artist sensitivity to the complex realities of mental illness fail to educate with fact alone (Dale, Richards, Bradburn, Tadros, & Salama, 2014); positive change in public representations of mental illness only occurs in response to local, personally meaningful testimonies from MIPs themselves (Corrgian, 2012; Ciszek & Gallicano, 2013). It is no longer enough to credit pathology as real; we must give credit to the expertise of she within whom it manifests. Grass Grows is my response to the call for a new Theatre of Sanity that promotes pragmatic but hopeful stories about encountering the world through the lens of mental illness

Solar powered membrane distillation for seawater desalination

This thesis presents an investigation into the performance of a Membrane Distillation (MD) system used for seawater desalination. The research is focused on the effects of intermittent use of the MD module when powered with a solar energy collector. The aim is to assess the feasibility of directly powering an MD unit with a fluctuating input from a solar collector. An investigation into the effect of temperature on the microstructure of the membrane was carried out. In a series of experiments, samples of PTFE membrane were imaged while heated from 17 C to temperatures between 60 C and 80 C. It was found that the membrane pore size increased with increases in temperature. When heated to 80 C the pore diameter increased by 44%. Intermittent use of the system would cause the temperature of the MD module to fluctuate, therefore altering the membrane microstructure. An investigation was carried out to determine the in fluence of intermittent MD operation on the flux and conductivity of the distillate. The system was tested after overnight shutdown periods and was also tested with short term `on/off' periods of between 5 and 20 minutes, simulating the intermittent output from a concentrated solar collector. It was found that as the module was heated, the distillate flux produced increased, while the distillate conductivity decreased. Conversely, when the module cooled, the flux decreased and the quality of the distillate worsened. This was the result of the dependancy of membrane pore size on temperature

Dissecting cis and trans Determinants of Nucleosome Positioning: A Dissertation

Eukaryotic DNA is packaged in chromatin, whose repeating subunit, the nucleosome, consists of an octamer of histone proteins wrapped by about 147bp of DNA. This packaging affects the accessibility of DNA and hence any process that occurs on DNA, such as replication, repair, and transcription. An early observation from genome-wide nucleosome mapping in yeast was that genes had a surprisingly characteristic structure, which has motivated studies to understand what determines this architecture. Both sequence and trans acting factors are known to influence chromatin packaging, but the relative contributions of cis and trans determinants of nucleosome positioning is debated. Here we present data using genetic approaches to examine the contributions of cis and trans acting factors on nucleosome positioning in budding yeast. We developed the use of yeast artificial chromosomes to exploit quantitative differences in the chromatin structures of different yeast species. This allows us to place approximately 150kb of sequence from any species into the S.cerevisiae cellular environment and compare the nucleosome positions on this same sequence in different environments to discover what features are variant and hence regulated by trans acting factors. This method allowed us to conclusively show that the great preponderance of nucleosomes are positioned by trans acting factors. We observe the maintenance of nucleosome depletion over some promoter sequences, but partial fill-in of NDRs in some of the YAC v promoters indicates that even this feature is regulated to varying extents by trans acting factors. We are able to extend our use of evolutionary divergence in order to search for specific trans regulators whose effects vary between the species. We find that a subset of transcription factors can compete with histones to help generate some NDRs, with clear effects documented in a cbf1 deletion mutant. In addition, we find that Chd1p acts as a potential “molecular ruler” involved in defining the nucleosome repeat length differences between S.cerevisiae and K.lactis. The mechanism of this measurement is unclear as the alteration in activity is partially attributable to the N-terminal portion of the protein, for which there is no structural data. Our observations of a specialized chromatin structure at de novo transcriptional units along with results from nucleosome mapping in the absence of active transcription indicate that transcription plays a role in engineering genic nucleosome architecture. This work strongly supports the role of trans acting factors in setting up a dynamic, regulated chromatin structure that allows for robustness and fine-tuning of gene expression

Disparities in Referral initiation and Completion at an Urban FQHC Look-alike (FQHC-LA) Clinic

Introduction. The purpose of this study was to determine referral initiation and completion disparities across primary care encounters at the Hope Family Care Center (HFCC) in Kansas City, MO, by payor type (primary insurance): private insurance, Medicaid, Medicare, and self-pay. Methods. Data were collected and analyzed for all encounters (N = 4235) over a 15-month period including payor type, referral initiation and completion, and demographics. Referral initiation and completion were calculated by payor type and differences analyzed using Chi-square tests and t-tests. Logistic regression examined payor type association with referral initiation and completion, accounting for demographic variables. Results. Our analysis showed a meaningful difference in rate of referral to specialists by payor type. The Medicaid encounter referral initiation rate was higher than rates for all other payor types (7.4% vs. 5.0%), and self-pay encounters' referral initiation rate was lower than rates for all other payor types (3.8% vs. 6.4%).of initiating a referral compared to private insurance encounters. There was no difference in referral completion by payor type or demographic category. Conclusions. Equal referral completion rates across payor types suggested HFCC may have had well-established referral resources for patients. Higher referral initiation rates for Medicaid and lower for self-pay may suggest that insurance coverage offered financial confidence when seeking specialist care. Higher odds of Medicaid encounters initiating a referral could imply greater health needs among Medicaid patients.       &nbsp

Minimizing Bias in Biomass Allometry: Model Selection and Log‐Transformation of Data

Nonlinear regression is increasingly used to develop allometric equations for forest biomass estimation (i.e., as opposed to the traditional approach of log‐transformation followed by linear regression). Most statistical software packages, however, assume additive errors by default, violating a key assumption of allometric theory and possibly producing spurious models. Here, we show that such models may bias stand‐level biomass estimates by up to 100 percent in young forests, and we present an alternative nonlinear fitting approach that conforms with allometric theory

Chromatin \u27programming\u27 by sequence - is there more to the nucleosome code than %GC

The role of genomic sequence in directing the packaging of eukaryotic genomes into chromatin has been the subject of considerable recent debate. A new paper from Tillo and Hughes shows that the intrinsic thermodynamic preference of a given sequence in the yeast genome for the histone octamer can largely be captured with a simple model, and in fact is mostly explained by %GC. Thus, the rules for predicting nucleosome occupancy from genomic sequence are much less complicated than has been claimed