The new conception of the theatre as interpreted by Appia, Craig and Reinhardt

Thesis (M.A.)--Boston Universit

Expressionism in the drama

Thesis (M.A.)--Boston Universit

Novel Inducers of the Envelope Stress Response BaeSR in Salmonella Typhimurium: BaeR Is Critically Required for Tungstate Waste Disposal

The RpoE and CpxR regulated envelope stress responses are extremely important for SalmonellaTyphimurium to cause infection in a range of hosts. Until now the role for BaeSR in both the Salmonella Typhimurium response to stress and its contribution to infection have not been fully elucidated. Here we demonstrate stationary phase growth, iron and sodium tungstate as novel inducers of the BaeRregulon, with BaeR critically required for Salmonella resistance to sodium tungstate. We show that functional overlap between the resistance nodulation-cell division (RND) multidrug transporters, MdtA, AcrD and AcrB exists for the waste disposal of tungstate from the cell. We also point to a role for enterobactinsiderophores in the protection of enteric organisms from tungstate, akin to the scenario in nitrogen fixing bacteria. Surprisingly, BaeR is the first envelope stress response pathway investigated in S. Typhimurium that is not required for murine typhoid in either ityS or ityR mouse backgrounds. BaeR is therefore either required for survival in larger mammals such as pigs or calves, an avian host such as chickens, or survival out with the host altogether where Salmonella and related enterics must survive in soil and water

Further characterisation of the envelope stress responses of Salmonella Typhimurium

Salmonella serovars are enteric pathogens of economic and clinical importance. The ability of Salmonella spp. to sense and adapt to exogenous stresses contributes towards infection severity and prevalence. The envelope stress responses promote survival within and between hosts by maintaining envelope homeostasis and promoting the rapid response to environmental insults. In this study, we present the first comprehensive analysis of the Cpx regulated transcriptome in S. Typhimurium, identifying 116 genes as novel members of the S. Typhimurium Cpx regulon. Transcriptomic analyses, EMSAs and mutant screens further establish CpxAR as a major contributor to S. Typhimurium virulence through regulation of SPI-1, and as a regulator of post-transcriptional modification through the positive and negative regulation of small regulatory RNAs (invR, omrA and omrB). Our data confirm Cpx contribution to copper tolerance, a positive regulator of the heat shock sigma factor rpoH and adds polyamine homeostasis and regulation of host cell apoptosis to the growing list of Cpx regulated processes. Furthermore, we present the first transcriptomic investigation into the ZraSR two-component signal transduction system and characterisation of its accessory protein, ZraP. We suggest ZraR mediated positive regulation of the virulence factors MntH and GroEL, GroSL, DnaK and ClpB (the heat shock chaperones). In addition, we show critical requirement of ZraSR for maximal carbon-starvation induced cross-resistance to heat and polymyxin B. The ZraR regulon described here includes functional groups required to promote survival within the Salmonella containing vacuole and genes contributing towards anaerobic metabolism. This work provides the foundations for investigating the contribution of ZraSR to Salmonella hostpathogen interactions and the potential this newly characterised ESR has as a target for investigating Salmonella survival within host cells. Together these investigations highlight the potential ESRs could hold as critical contributors to Salmonella pathogenicity and as therapeutic targets for the treatment of Salmonella infections

Neonatal mortality within 24 hours of birth in six low- and lower-middle-income countries

OBJECTIVE: To assess the rates, timing and causes of neonatal deaths and the burden of stillbirths in rural Uttar Pradesh, India. We discuss the implications of our findings for neonatal interventions. METHODS: We used verbal autopsy interviews to investigate 1048 neonatal deaths and stillbirths. FINDINGS: There were 430 stillbirths reported, comprising 41% of all deaths in the sample. Of the 618 live births, 32% deaths were on the day of birth, 50% occurred during the first 3 days of life and 71% were during the first week. The primary causes of death on the first day of life (i.e. day 0) were birth asphyxia or injury (31%) and preterm birth (26%). During days 1–6, the most frequent causes of death were preterm birth (30%) and sepsis or pneumonia (25%). Half of all deaths caused by sepsis or pneumonia occurred during the first week of life. The proportion of deaths attributed to sepsis or pneumonia increased to 45% and 36% during days 7–13 and 14–27, respectively. CONCLUSION: Stillbirths and deaths on the day of birth represent a large proportion of perinatal and neonatal deaths, highlighting an urgent need to improve coverage with skilled birth attendants and to ensure access to emergency obstetric care. Health interventions to improve essential neonatal care and care-seeking behavior are also needed, particularly for preterm neonates in the early postnatal period

A novel block non-symmetric preconditioner for mixed-hybrid finite-element-based flow simulations

In this work we propose a novel block preconditioner, labelled Explicit Decoupling Factor Approximation (EDFA), to accelerate the convergence of Krylov subspace solvers used to address the sequence of non-symmetric systems of linear equations originating from flow simulations in porous media. The flow model is discretized blending the Mixed Hybrid Finite Element (MHFE) method for Darcy's equation with the Finite Volume (FV) scheme for the mass conservation. The EDFA preconditioner is characterized by two features: the exploitation of the system matrix decoupling factors to recast the Schur complement and their inexact fully-parallel computation by means of restriction operators. We introduce two adaptive techniques aimed at building the restriction operators according to the properties of the system at hand. The proposed block preconditioner has been tested through an extensive experimentation on both synthetic and real-case applications, pointing out its robustness and computational efficiency

Core components for effective infection prevention and control programmes: new WHO evidence-based recommendations

Abstract Health care-associated infections (HAI) are a major public health problem with a significant impact on morbidity, mortality and quality of life. They represent also an important economic burden to health systems worldwide. However, a large proportion of HAI are preventable through effective infection prevention and control (IPC) measures. Improvements in IPC at the national and facility level are critical for the successful containment of antimicrobial resistance and the prevention of HAI, including outbreaks of highly transmissible diseases through high quality care within the context of universal health coverage. Given the limited availability of IPC evidence-based guidance and standards, the World Health Organization (WHO) decided to prioritize the development of global recommendations on the core components of effective IPC programmes both at the national and acute health care facility level, based on systematic literature reviews and expert consensus. The aim of the guideline development process was to identify the evidence and evaluate its quality, consider patient values and preferences, resource implications, and the feasibility and acceptability of the recommendations. As a result, 11 recommendations and three good practice statements are presented here, including a summary of the supporting evidence, and form the substance of a new WHO IPC guideline

Ideal and reality: do countries adopt and follow recommended procedures in comprehensive multiyear planning guidelines for national immunization programmes?

BACKGROUND: Meticulous steps and procedures are proposed in planning guidelines for the development of comprehensive multiyear plans for national immunization programmes. However, we know very little about whether the real-life experience of those who adopt these guidelines involves following these procedures as expected. Are these steps and procedures followed in practice? We examined the adoption and usage of the guidelines in planning national immunization programmes and assessed whether the recommendations in these guidelines are applied as consistently as intended. METHODS: We gathered information from the national comprehensive multiyear plans developed by 77 low-income countries. For each of the 11 components, we examined how each country applied the four recommended steps of situation analysis, problem prioritization, selection of interventions, and selection of indicators. We then conducted an analysis to determine the patterns of alignment of the comprehensive multiyear plans with those four recommended planning steps. RESULTS: Within the first 3 years following publication of the guidelines, 66 (86%) countries used the tool to develop their comprehensive multiyear plans. The funding conditions attached to the use of these guidelines appeared to influence their rapid adoption and usage. Overall, only 33 (43%) countries fully applied all four recommended planning steps of the guidelines. CONCLUSIONS: Adoption and usage of the guidelines for the development of comprehensive multiyear plans for national immunization programmes were rapid. However, our findings show substantial variation between the proposed planning ideals set out in the guidelines and actual use in practice. A better understanding of factors that influence how recommendations in public health guidelines are applied in practice could contribute to improvements in guidelines design. It could also help adjust strategies used to introduce them into public health programmes, with the ultimate goal of a greater health impact