Applied Epidemiology of Vaccine Preventable Diseases and Outbreaks in New South Wales

The National Centre for Immunisation Research and Surveillance (NCIRS) is located within the Kids Research Institute (KRI) at Westmead Children’s Hospital. It is somewhat hidden away from the children’s hospital, and no easier to navigate internally once you find the building on your first day. During my two years there, I was part of the Coverage, Evaluation and Surveillance (CES) Program Stream, which met monthly to discuss achievements and deliverables of the group. As an active member, I was encouraged to keep the group up to date on my progress throughout my MAE journey. The Western Sydney Public Health Unit (WSPHU) is located at Cumberland Hospital adjacent to Westmead Children’s Hospital. I spent two weeks at the PHU, observing and assisting wherever possible. I helped with a measles outbreak, including contract tracing, interviewing people, maintaining clinical line lists, informing high-risk people of a measles-clinic and assisting medical staff during the running of the measles-clinic. During this emergency response, all high-risk people (including pregnant mothers and newborn babies) were contacted and provided with appropriate prophylaxis to prevent illness. During my time there, I was also very fortunate to lead a Salmonella outbreak investigation (Chapter 3). The Communicable Diseases Branch (CDB) is located in the Ministry of Health building in North Sydney. I spent almost four months there conducting the epidemiological investigation (Chapter 4). During my time at the CDB, I attended staff meetings, afternoon debriefs, surveillance meetings and an in-house emergency response workshop. I was also very fortunate to be funded to attend the OzFoodNet whole genome workshop in Melbourne. I also assisted with two Legionella outbreaks, where I helped to maintain line-lists and the Sit-Rep, and attended the afternoon meetings, where I was asked to take, transcribe and distribute minutes of meeting from time to time. I truly enjoyed my experience at the CDB, NSW Health. 1.2 Summary of my public health experience 1.2.1 Analysis of a public health dataset (Chapter 2) In November 2005, hepatitis A vaccine was funded under the Australian National Immunisation Program for Indigenous children aged 12-24 months in the targeted jurisdictions of Queensland, South Australia, Western Australia and the Northern Territory. I reviewed the epidemiology of hepatitis A from 2000-2014 using data from the Australian National Notifiable Diseases Surveillance System, the National Hospital Morbidity Database, and Australian Bureau of Statistics causes-of-death data. Overall, the national hepatitis A immunisation program has had a significant impact in the targeted population with relatively modest vaccine coverage, with evidence of substantial herd protection effects. 1.2.2 Outbreak Investigation (Chapter 3) During May 2015, an increase in Salmonella Agona cases was reported from western Sydney, Australia. I present the public health actions used to investigate and control this increase. A descriptive case-series investigation was conducted. Six outbreak cases were identified; all had consumed cooked tuna sushi rolls purchased within a western Sydney shopping complex. Onset of illness for outbreak cases occurred between 7 April and 24 May 2015. Salmonella was isolated from food samples collected from the implicated premise and a prohibition order issued. No further cases were identified following this action. In addition, this outbreak investigation also demonstrated genomics-enhanced public health action, where whole genome sequencing significantly enhanced the resolution of the epidemiological investigation. 1.2.3 Epidemiological investigation (Chapter 4) Among adults, pneumococcal pneumonia causes significant mortality and morbidity. While the funding of polysaccharide pneumococcal vaccines have reduced the incidence of invasive pneumococcal disease (IPD) in older people, uncertainty remains regarding their effectiveness against reducing the hospitalisation rate due to community acquired pneumonia. In this study I use linked-data to document that approximately one in seven hospital admissions coded for pneumococcal pneumonia in older people of NSW were due to invasive pneumococcal disease. The remaining six hospital admissions were presumptive non-invasive pneumococcal pneumonia cases. I also documented significant declines in the rate and severity of hospitalisations over time due to presumptive non-invasive pneumococcal pneumonia. The pneumococcal polysaccharide vaccine that was used for adults has not been consistently shown to be effective against non-invasive pneumococcal pneumonia hospitalisations, while the conjugate vaccine used in the children program has provided substantial indirect protection against IPD to adults. The results presented here could impact on cost-effectiveness of pneumococcal vaccine programs in Australia. 1.2.4 Evaluation of a surveillance system (Chapter 5) The AusVaxSafety enhanced active surveillance system was established in 2014 and has two main functions. Firstly, to gather near real-time data of AEFI following seasonal influenza vaccination of children aged between six months and five; secondly, to collate, interpret and disseminate these results in near real-time to stakeholders and the public. AusVaxSafety was evaluated to assess the usefulness of the information collected; identify strengths and limitations; and provide feedback to stakeholders regarding recommendations to the system. During the 2015 influenza season, the AusVaxSafety successfully demonstrated, in real-time, that influenza vaccines registered for used in children aged six months to five years were safe, well tolerated, and that the AEFIs experienced were within expected ranges

Use of Equivalent Relative Utility (ERU) to Evaluate Artificial Intelligence-Enabled Rule-Out Devices

We investigated the use of equivalent relative utility (ERU) to evaluate the effectiveness of artificial intelligence (AI)-enabled rule-out devices that use AI to identify and autonomously remove non-cancer patient images from radiologist review in screening mammography.We reviewed two performance metrics that can be used to compare the diagnostic performance between the radiologist-with-rule-out-device and radiologist-without-device workflows: positive/negative predictive values (PPV/NPV) and equivalent relative utility (ERU). To demonstrate the use of the two evaluation metrics, we applied both methods to a recent US-based study that reported an improved performance of the radiologist-with-device workflow compared to the one without the device by retrospectively applying their AI algorithm to a large mammography dataset. We further applied the ERU method to a European study utilizing their reported recall rates and cancer detection rates at different thresholds of their AI algorithm to compare the potential utility among different thresholds. For the study using US data, neither the PPV/NPV nor the ERU method can conclude a significant improvement in diagnostic performance for any of the algorithm thresholds reported. For the study using European data, ERU values at lower AI thresholds are found to be higher than that at a higher threshold because more false-negative cases would be ruled-out at higher threshold, reducing the overall diagnostic performance. Both PPV/NPV and ERU methods can be used to compare the diagnostic performance between the radiologist-with-device workflow and that without. One limitation of the ERU method is the need to measure the baseline, standard-of-care relative utility (RU) value for mammography screening in the US. Once the baseline value is known, the ERU method can be applied to large US datasets without knowing the true prevalence of the dataset

Transcriptional and Proteomic Analysis of a Ferric Uptake Regulator (Fur) Mutant of Shewanella oneidensis: Possible Involvement of Fur in Energy Metabolism, Transcriptional Regulation, and Oxidative Stress

The iron-directed, coordinate regulation of genes depends on the fur (ferric uptake regulator) gene product, which acts as an iron-responsive, transcriptional repressor protein. To investigate the biological function of a fur homolog in the dissimilatory metal-reducing bacterium Shewanella oneidensis MR-1, a fur knockout strain (FUR1) was generated by suicide plasmid integration into this gene and characterized using phenotype assays, DNA microarrays containing 691 arrayed genes, and two-dimensional polyacrylamide gel electrophoresis. Physiological studies indicated that FUR1 was similar to the wild-type strain when they were compared for anaerobic growth and reduction of various electron acceptors. Transcription profiling, however, revealed that genes with predicted functions in electron transport, energy metabolism, transcriptional regulation, and oxidative stress protection were either repressed (ccoNQ, etrA, cytochrome b and c maturation-encoding genes, qor, yiaY, sodB, rpoH, phoB, and chvI) or induced (yggW, pdhC, prpC, aceE, fdhD, and ppc) in the fur mutant. Disruption of fur also resulted in derepression of genes (hxuC, alcC, fhuA, hemR, irgA, and ompW) putatively involved in iron uptake. This agreed with the finding that the fur mutant produced threefold-higher levels of siderophore than the wild-type strain under conditions of sufficient iron. Analysis of a subset of the FUR1 proteome (i.e., primarily soluble cytoplasmic and periplasmic proteins) indicated that 11 major protein species reproducibly showed significant (P < 0.05) differences in abundance relative to the wild type. Protein identification using mass spectrometry indicated that the expression of two of these proteins (SodB and AlcC) correlated with the microarray data. These results suggest a possible regulatory role of S. oneidensis MR-1 Fur in energy metabolism that extends the traditional model of Fur as a negative regulator of iron acquisition systems

Ocean processes at the Antarctic continental slope

The Antarctic continental shelves and slopes occupy relatively small areas, but, nevertheless, are important for global climate, biogeochemical cycling and ecosystem functioning. Processes of water mass transformation through sea ice formation/melting and ocean-atmosphere interaction are key to the formation of deep and bottom waters as well as determining the heat flux beneath ice shelves. Climate models, however, struggle to capture these physical processes and are unable to reproduce water mass properties of the region. Dynamics at the continental slope are key for correctly modelling climate, yet their small spatial scale presents challenges both for ocean modelling and for observational studies. Cross-slope exchange processes are also vital for the flux of nutrients such as iron from the continental shelf into the mixed layer of the Southern Ocean. An © 2014 The Authors

Oral language expectations for African American children in grades 1 through 5

http://deepblue.lib.umich.edu/bitstream/2027.42/83317/1/Oral_language_expectations_for_African_American_children_in_grades_1_through_5.pd

The Role of Galactic Winds on Molecular Gas Emission from Galaxy Mergers

We assess the impact of starburst and AGN feedback-driven winds on the CO emission from galaxy mergers, and, in particular, search for signatures of these winds in the simulated CO morphologies and emission line profiles. We do so by combining a 3D non-LTE molecular line radiative transfer code with smoothed particle hydrodynamics (SPH) simulations of galaxy mergers that include prescriptions for star formation, black hole growth, a multiphase interstellar medium (ISM), and the winds associated with star formation and black hole growth. Our main results are: (1) Galactic winds can drive outflows of masses ~10^8-10^9 Msun which may be imaged via CO emission line mapping. (2) AGN feedback-driven winds are able to drive imageable CO outflows for longer periods of time than starburst-driven winds owing to the greater amount of energy imparted to the ISM by AGN feedback compared to star formation. (3) Galactic winds can control the spatial extent of the CO emission in post-merger galaxies, and may serve as a physical motivation for the sub-kiloparsec scale CO emission radii observed in local advanced mergers. (4) Secondary emission peaks at velocities greater than the circular velocity are seen in the CO emission lines in all models. In models with winds, these high velocity peaks are seen to preferentially correspond to outflowing gas entrained in winds, which is not the case in the model without winds. The high velocity peaks seen in models without winds are typically confined to velocity offsets (from the systemic) < 1.7 times the circular velocity, whereas the models with AGN feedback-driven winds can drive high velocity peaks to ~2.5 times the circular velocity.Comment: Accepted by ApJ; Minor revisions; Resolution tests include

Phonological features of child African American English

http://deepblue.lib.umich.edu/bitstream/2027.42/83323/1/Phonological_features_of_child_African_American_English.pd

Low Friction Flows of Liquids at Nanopatterned Interfaces

With the recent important development of microfluidic systems, miniaturization of flow devices has become a real challenge. Microchannels, however, are characterized by a large surface to volume ratio, so that surface properties strongly affect flow resistance in submicrometric devices. We present here results showing that the concerted effect of wetting . properties and surface roughness may considerably reduce friction of the fluid past the boundaries. The slippage of the fluid at the channel boundaries is shown to be drastically increased by using surfaces that are patterned at the nanometer scale. This effect occurs in the regime where the surface pattern is partially dewetted, in the spirit of the 'superhydrophobic' effects that have been recently discovered at the macroscopic scales. Our results show for the first time that, in contrast to the common belief, surface friction may be reduced by surface roughness. They also open the possibility of a controlled realization of the 'nanobubbles' that have long been suspected to play a role in interfacial slippag

Relationships Between Neuromuscular Function and Functional Balance Performance in Firefighters

The purpose of the present study was to examine the relationships between neuromuscular function and functional balance performance in firefighters. Fifty career firefighters (35.1±7.5yr) performed isometric leg extension and flexion muscle actions to examine peak torque (PT), and absolute (aTQ) and normalized (nTQ; %PT) rapid torque variables at 50, 100, 150, and 200ms. A performance index (PI) was determined from the functional balance assessment completion time. Partial correlations were used to examine the relationship between the PI and the maximal and rapid TQ variables for each muscle and the composite value, while controlling for demographic data related to the PI. Multiple regression analyses examined the relative contributions of the maximal and rapid aTQ variables, and demographic data on the PI. After controlling for age and %BF, the majority of the later aTQ and nTQ variables (100– 200ms) and PT were associated with the PI (r=−0.501–−0.315). Age, %BF, and aTQ100 explained 42– 50% of the variance in the PI. Lower rapid strength, increased age, and poorer body composition were related to worse performance during the functional balance assessment. Strategies to improve rapid strength and %BF, especially in aging firefighters may impact dynamic balance abilities in firefighters

Theory of x-ray absorption by laser-aligned symmetric-top molecules

We devise a theory of x-ray absorption by symmetric-top molecules which are aligned by an intense optical laser. Initially, the density matrix of the system is composed of the electronic ground state of the molecules and a thermal ensemble of rigid-rotor eigenstates. We formulate equations of motion of the two-color (laser plus x rays) rotational-electronic problem. The interaction with the laser is assumed to be nonresonant; it is described by an electric dipole polarizability tensor. X-ray absorption is approximated as a one-photon process. It is shown that the equations can be separated such that the interaction with the laser can be treated independently of the x rays. The laser-only density matrix is propagated numerically. After each time step, the x-ray absorption is calculated. We apply our theory to study adiabatic alignment of bromine molecules (Br2). The required dynamic polarizabilities are determined using the ab initio linear response methods coupled-cluster singles (CCS), second-order approximate coupled-cluster singles and doubles (CC2), and coupled-cluster singles and doubles (CCSD). For the description of x-ray absorption on the sigma_g 1s --> sigma_u 4p resonance, a parameter-free two-level model is used for the electronic structure of the molecules. Our theory opens up novel perspectives for the quantum control of x-ray radiation.Comment: 14 pages, 4 figures, 1 table, RevTeX4, revise