The role of chemical activation in the formation and loss of atmospheric carbonyl species

The Earth’s atmosphere is often compared to a low temperature combustion system in which solar energy drives radical oxidation of trace gases. The OH radical is the key daytime radical oxidant and reacts rapidly with the majority of the anthropogenic and biogenic volatile organic compounds (VOCs) released to the atmosphere. Over the past two decades, field campaigns in remote regions, characterised by high concentrations of hydrocarbons, such as isoprene, but relatively low concentrations of NOx (NO + NO2) have highlighted significant discrepancies between measured and modelled concentrations of OH; with modelled OH concentrations underestimating the measured daytime values by up to an order of magnitude. Consequently, a number of experimental and theoretical studies have sought novel OH generating reactions that are currently not implemented into atmospheric models. One such suggestion is that under low NOx conditions (sub 100 pptv), certain peroxy radical species, formed following the addition of O2 to radicals produced through OH initiated VOC oxidation, might undergo unimolecular dissociation reactions that regenerate OH. In this thesis, a number of OH initiated oxidation systems have been studied which produce radical intermediates that recycle OH in the presence of O2. These systems have been investigated experimentally by monitoring the OH directly using laser flash photolysis coupled with laser induced fluorescence (LFP – LIF). By monitoring the OH kinetics directly, it is possible to quantify the yield of OH recycled in the presence of O2 as a function of pressure, temperature, and O2 concentration from the ratio of rate coefficients measured in the presence and absence of O2; this OH cycling methodology was used extensively in the work presented here. The first experimental work presented in this thesis focused on the OH initiated oxidation of a series of alkynes (acetylene, propyne, and 2-butyne). These reactions proceed initially via OH addition across the alkyne triple bond, to generate an adduct that exists in two energetically distinct conformations. These adducts react rapidly with O2 to generate a bicarbonyl species and recycle OH, or an organic acid and acyl radical as first generation products; with product branching ratios dictated by the stereochemistry of the adduct at the point of reaction with O2. The nascent adduct forms following the OH + alkyne reaction with excess energy. It is widely accepted that at pressures relevant to the troposphere, any excess energy in reaction products is dissipated through inelastic collisions prior to the onset of secondary bimolecular chemistry. However, experimental and theoretical work presented here suggests that under atmospheric conditions, a significant fraction of the total product yield associated with the OH + alkyne/O2 systems, form before the internal quantum states of the adducts have fully relaxed. The product branching observed for the OH + alkyne/O2 system is said to be influenced by chemical activation, whereby the exothermicity of an initial reaction is utilised by the products to undergo secondary reactions not accessible to the thermalised products. Attention then turns to OH oxidation reactions that proceed via a hydrogen-atom abstraction channel. Abstraction reactions are often considered to deposit the majority of the available reaction exothermicity into the newly formed bond, particularly if the reaction involved has an early transition state. Experimental evidence presented here suggests that some atmospherically relevant carbonyl reactions, that are considered to proceed via direct hydrogen-atom abstraction, partition a significant fraction of the reaction exothermicity into the radical fragment. The OH + acetaldehyde, CH3CHO, reaction is considered an archetypal abstraction reaction. The acetyl, CH3CO, produced is known to react with O2 at low pressures to generate OH, with a unity yield at zero pressure. However, the pressure dependent OH yields observed for the OH + CH3CHO/O2 system suggest that ~15% of the CH3CO produced through the OH + CH3CHO reaction dissociates promptly to CH3 + CO. CH3CO fragmentation requires more than 50% of the total exothermicity of the OH + CH3CHO reaction to be channelled into the CH3CO. The second hydrogen-abstraction channel considered here is the OH + glyoxal, (HCO)2, reaction that results in production of the HC(O)CO radical. HC(O)CO chemistry is governed by a competition between unimolecular dissociation, and bimolecular association with O2. Recent calculations have suggested that the HC(O)CO + O2 reaction proceeds directly to OH + CO + CO2. This channel has been verified here through experiment, with OH yields associated with the OH + (HCO)2/O2 reaction quantified for the first time as a function of pressure (5 – 80 Torr), temperature (212 – 295 K), and O2 concentration. The OH yields increase with O2 concentration under all experimental conditions, as the bimolecular HC(O)CO + O2 reaction increasingly competes with unimolecular HC(O)CO decomposition, but converge on a limiting yield under high O2 conditions, suggesting that a fraction of the HC(O)CO produced following the OH + (HCO)2 reaction dissociates promptly to HCO + CO. In the final experimental section of this thesis a laser system was developed to detect HCO via LIF. Attempts were made to monitor both prompt and growth HCO signal following the Cl + (HCO)2 reaction, and quantify the rate of thermal HC(O)CO decomposition as a function of pressure at low temperatures (212 K). However, rapid HCO removal was observed at the low experimental temperatures required. Further experimental evidence suggested that HCO reacts rapidly with (HCO)2 and other aldehydes at 212 K. Quantitative studies focused on the reaction of HCO with formaldehyde, HCHO, and acetaldehyde, CH3CHO, with rate coefficients of (3.44 ± 0.15) and (1.24 ± 0.05) × 10-11 cm3 molecule-1 s-1 measured, respectively

Whole-genome analysis of Exserohilum rostratum from an outbreak of fungal meningitis and other infections

Exserohilum rostratum was the cause of most cases of fungal meningitis and other infections associated with the injection of contaminated methylprednisolone acetate produced by the New England Compounding Center (NECC). Until this outbreak, very few human cases of Exserohilum infection had been reported, and very little was known about this dematiaceous fungus, which usually infects plants. Here, we report using whole-genome sequencing (WGS) for the detection of single nucleotide polymorphisms (SNPs) and phylogenetic analysis to investigate the molecular origin of the outbreak using 22 isolates of E. rostratum retrieved from 19 case patients with meningitis or epidural/spinal abscesses, 6 isolates from contaminated NECC vials, and 7 isolates unrelated to the outbreak. Our analysis indicates that all 28 isolates associated with the outbreak had nearly identical genomes of 33.8 Mb. A total of 8 SNPs were detected among the outbreak genomes, with no more than 2 SNPs separating any 2 of the 28 genomes. The outbreak genomes were separated from the next most closely related control strain by ∼136,000 SNPs. We also observed significant genomic variability among strains unrelated to the outbreak, which may suggest the possibility of cryptic speciation in E. rostratum

Representations of sport in the revolutionary socialist press in Britain, 1988–2012

This paper considers how sport presents a dualism to those on the far left of the political spectrum. A long-standing, passionate debate has existed on the contradictory role played by sport, polarised between those who reject it as a bourgeois capitalist plague and those who argue for its reclamation and reformation. A case study is offered of a political party that has consistently used revolutionary Marxism as the basis for its activity and how this party, the largest in Britain, addresses sport in its publications. The study draws on empirical data to illustrate this debate by reporting findings from three socialist publications. When sport did feature it was often in relation to high profile sporting events with a critical tone adopted and typically focused on issues of commodification, exploitation and alienation of athletes and supporters. However, readers’ letters, printed in the same publications, revealed how this interpretation was not universally accepted, thus illustrating the contradictory nature of sport for those on the far left

Effects of Aging on the Biomechanics of Slips and Falls

Although much has been learned in recent decades about the deterioration of muscular strength, gait adaptations, and sensory degradation among older adults, little is known about how these intrinsic changes affect biomechanical parameters associated with slip-induced fall accidents. In general, the objective of this laboratory study was to investigate the process of initiation, detection, and recovery of inadvertent slips and falls. We examined the initiation of and recovery from foot slips among three age groups utilizing biomechanical parameters, muscle strength, and sensory measurements. Forty-two young, middle-age, and older participants walked around a walking track at a comfortable pace. Slippery floor surfaces were placed on the track over force platforms at random intervals without the participants’ awareness. Results indicated that younger participants slipped as often as the older participants, suggesting that the likelihood of slip initiation is similar across all age groups; however, older individuals’ recovery process was much slower and less effective. The ability to successfully recover from a slip (thus preventing a fall) is believed to be affected by lower extremity muscle strength and sensory degradation among older individuals. Results from this research can help pinpoint possible intervention strategies for improving dynamic equilibrium among older adults

Characterizing and Improving the Data Reduction Pipeline for the Keck OSIRIS Integral Field Spectrograph

OSIRIS is a near-infrared (1.0--2.4 $\mu$m) integral field spectrograph operating behind the adaptive optics system at Keck Observatory, and is one of the first lenslet-based integral field spectrographs. Since its commissioning in 2005, it has been a productive instrument, producing nearly half the laser guide star adaptive optics (LGS AO) papers on Keck. The complexity of its raw data format necessitated a custom data reduction pipeline (DRP) delivered with the instrument in order to iteratively assign flux in overlapping spectra to the proper spatial and spectral locations in a data cube. Other than bug fixes and updates required for hardware upgrades, the bulk of the DRP has not been updated since initial instrument commissioning. We report on the first major comprehensive characterization of the DRP using on-sky and calibration data. We also detail improvements to the DRP including characterization of the flux assignment algorithm; exploration of spatial rippling in the reduced data cubes; and improvements to several calibration files, including the rectification matrix, the bad pixel mask, and the wavelength solution. We present lessons learned from over a decade of OSIRIS data reduction that are relevant to the next generation of integral field spectrograph hardware and data reduction software design.Comment: 18 pages, 16 figures; accepted for publication in A

Diagnostic and cost utility of whole exome sequencing in peripheral neuropathy.

OBJECTIVE: To explore the diagnostic utility and cost effectiveness of whole exome sequencing (WES) in a cohort of individuals with peripheral neuropathy. METHODS: Singleton WES was performed in individuals recruited though one pediatric and one adult tertiary center between February 2014 and December 2015. Initial analysis was restricted to a virtual panel of 55 genes associated with peripheral neuropathies. Patients with uninformative results underwent expanded analysis of the WES data. Data on the cost of prior investigations and assessments performed for diagnostic purposes in each patient was collected. RESULTS: Fifty patients with a peripheral neuropathy were recruited (median age 18 years; range 2-68 years). The median time from initial presentation to study enrollment was 6 years 9 months (range 2 months-62 years), and the average cost of prior investigations and assessments for diagnostic purposes AU$4013 per patient. Eleven individuals received a diagnosis from the virtual panel. Eight individuals received a diagnosis following expanded analysis of the WES data, increasing the overall diagnostic yield to 38%. Two additional individuals were diagnosed with pathogenic copy number variants through SNP microarray. CONCLUSIONS: This study provides evidence that WES has a high diagnostic utility and is cost effective in patients with a peripheral neuropathy. Expanded analysis of WES data significantly improves the diagnostic yield in patients in whom a diagnosis is not found on the initial targeted analysis. This is primarily due to diagnosis of conditions caused by newly discovered genes and the resolution of complex and atypical phenotypes

Mutations in RAB39B Cause X-Linked Intellectual Disability and Early-Onset Parkinson Disease with alpha-Synuclein Pathology

Advances in understanding the etiology of Parkinson disease have been driven by the identification of causative mutations in families. Genetic analysis of an Australian family with three males displaying clinical features of early-onset parkinsonism and intellectual disability identified a approximately 45 kb deletion resulting in the complete loss of RAB39B. We subsequently identified a missense mutation (c.503C>A [p.Thr168Lys]) in RAB39B in an unrelated Wisconsin kindred affected by a similar clinical phenotype. In silico and in vitro studies demonstrated that the mutation destabilized the protein, consistent with loss of function. In vitro small-hairpin-RNA-mediated knockdown of Rab39b resulted in a reduction in the density of alpha-synuclein immunoreactive puncta in dendritic processes of cultured neurons. In addition, in multiple cell models, we demonstrated that knockdown of Rab39b was associated with reduced steady-state levels of alpha-synuclein. Post mortem studies demonstrated that loss of RAB39B resulted in pathologically confirmed Parkinson disease. There was extensive dopaminergic neuron loss in the substantia nigra and widespread classic Lewy body pathology. Additional pathological features included cortical Lewy bodies, brain iron accumulation, tau immunoreactivity, and axonal spheroids. Overall, we have shown that loss-of-function mutations in RAB39B cause intellectual disability and pathologically confirmed early-onset Parkinson disease. The loss of RAB39B results in dysregulation of alpha-synuclein homeostasis and a spectrum of neuropathological features that implicate RAB39B in the pathogenesis of Parkinson disease and potentially other neurodegenerative disorders

The impact of mental health recovery narratives on recipients experiencing mental health problems: Qualitative analysis and change model.

BACKGROUND: Mental health recovery narratives are stories of recovery from mental health problems. Narratives may impact in helpful and harmful ways on those who receive them. The objective of this paper is to develop a change model identifying the range of possible impacts and how they occur. METHOD: Semi-structured interviews were conducted with adults with experience of mental health problems and recovery (n = 77). Participants were asked to share a mental health recovery narrative and to describe the impact of other people's recovery narratives on their own recovery. A change model was generated through iterative thematic analysis of transcripts. RESULTS: Change is initiated when a recipient develops a connection to a narrator or to the events descripted in their narrative. Change is mediated by the recipient recognising experiences shared with the narrator, noticing the achievements or difficulties of the narrator, learning how recovery happens, or experiencing emotional release. Helpful outcomes of receiving recovery narratives are connectedness, validation, hope, empowerment, appreciation, reference shift and stigma reduction. Harmful outcomes are a sense of inadequacy, disconnection, pessimism and burden. Impact is positively moderated by the perceived authenticity of the narrative, and can be reduced if the recipient is experiencing a crisis. CONCLUSIONS: Interventions that incorporate the use of recovery narratives, such as peer support, anti-stigma campaigns and bibliotherapy, can use the change model to maximise benefit and minimise harms from narratives. Interventions should incorporate a diverse range of narratives available through different mediums to enable a range of recipients to connect with and benefit from this material. Service providers using recovery narratives should preserve authenticity so as to maximise impact, for example by avoiding excessive editing

Large Adaptive Optics Survey for Substellar Objects around Young, Nearby, Low-mass Stars with Robo-AO

We present results from the Large Adaptive optics Survey for Substellar Objects, where the goal is to directly image new substellar companions ( 11.8), while only 23₋₆⁺¹¹% of the remaining 22 stars with no detected companion have significant accelerations. The significance of the acceleration decreases with increasing companion separation. These young accelerating low-mass stars with companions will eventually yield dynamical masses with future orbit monitoring