DEVELOPING REPRODUCIBLE ANTIBACTERIAL SURFACES USING THERMAL IMPRINT TECHNOLOGY

Staphylococcus aureus is a naturally occurring bacterium carried in human respiratory systems and on skin. Dangerous Staphylococcus infections in hospitals are of specific concern due to the high traffic and open wounds that exist in such facilities. One way these facilities can prevent on-site contraction of Staphylococcus infections is through rigorous disinfection of surfaces exposed to human contact. While disinfection with cleaning solutions can be effective, this method provides only a temporary solution. In contrast to temporary disinfection of surfaces, another approach may be to prevent the spread of Staphylococcus infections by engineering surfaces that are inherently antibacterial. Physicochemical properties of bacteria and the surfaces on which they live can influence bacterial adhesion to a surface. Recently, studies have been conducted which examine the effect of nanoscale features on biological specimens. Researchers have found that particular patterns naturally dissuade bacteria from attaching to and contaminating surfaces. To build on this research, further work to create a reliable, cost-efficient, and reproducible antibacterial surface is needed. In this project, potentially antibacterial surfaces will be developed using thermal imprinting. A non-pathogenic form of Staphylococcus aureus will be used as a model Staphylococcus organism to test and quantify bacterial health on such surfaces. Although medical facilities present an obvious market for such surfaces, these patterning techniques can be used on other surfaces such as door knobs and toilet seats. Because of the inexpensive fabrication methods and materials, this research could lead to antibacterial surfaces being made readily available to populations no matter their socioeconomic backgrounds

Whispers of Conversation between Thomas Merton and Sallie McFague on God, Self, and the World: Considering Engaged Spirituality Today

This dissertation focuses upon the question, how are we called to live? , relying on the thought and dialogue of Thomas Merton, a 20th Century Catholic monk, and Sallie McFague, a 21st Century Protestant theologian. This question is approached by examining Merton and McFague\u27s understandings of God, self, and the world as these aspects relate to the question and issue of Christian living. In exploring these areas this project brings together aspects of Christian spirituality, theology, and ethics to grasp the intimate relationship between faith and action, which is the essence of authentic Christian discipleship. Ultimately, the merging of faith and action seen in Merton and McFague\u27s lives and work suggest that they both possess and advocate for engaged spirituality, or spiritually rooted social action, as the central expression of Christian faith called for today. Their examples, brought together, convey truth and inspire all of us to live more authentically and to more fully contribute to the making of a better world

Automated subcortical brain segmentation using multispectral MRI for improved AD diagnosis and disease tracking

This thesis is a detailed investigation into subcortical changes in Alzheimer's disease (AD). Hippocampal volumes, shapes and diffusion metrics were investigated in different disease stages and presentations, and the ability of these metrics for disease group classification investigated. A new method for automated thalamic segmentation using multimodal imaging was developed and applied to two different datasets. Hippocampal volumes were found to be disproportionately affected by the apolipoprotein (APOE) e4 allele. Hippocampal volumes were also found to be reduced in subjects with the posterior cortical atrophy variant of AD. These changes were localized in the hippocampal tail region and hippocampal shape metrics were found to be superior to hippocampal volumes in differentiating these subjects from controls. The manual thalamic segmentation protocol developed was found to have good reliability, and a template library of thalamic segmentations was generated for use in automated pipelines. The manual segmentation protocol used both T1-weighted and diffusion magnetic resonance imaging (MRI) scans for improved segmentation accuracy. The template library was used for automatic segmentation of the thalamus and leave-one-out cross-validation revealed good segmentation reliability, better than that reported by the most widely used automated thalamic segmentation techniques. The thalami from subjects from the Alzheimer's disease neuroimaging initiative (ADNI)-GO/2 datasets, which includes control subjects, subjects with subjective memory complaints, with early mild cognitive impairment (EMCI), late mild cognitive impairment (LMCI) and AD, were segmented using the automated thalamic pipeline. Subjects with AD and mild cognitive impairment (MCI) were found to have lower thalamic volumes, as well as lower hippocampal volumes suggesting early thalamic involvement. Differences in diffusion metrics were found and some diffusion metrics were associated with subsequently higher atrophy rates. The inclusion of hippocampal and thalamic diffusion metrics, in addition to volumes were found to improve disease group classification. In summary, the work in this thesis extends existing knowledge about how the hippocampi and thalami are affected in Alzheimer's disease

New estimates of the number of children living with substance misusing parents: results from UK national household surveys

<p>Abstract</p> <p>Background</p> <p>The existing estimates of there being 250,000 - 350,000 children of problem drug users in the UK (ACMD, 2003) and 780,000 - 1.3 million children of adults with an alcohol problem (AHRSE, 2004) are extrapolations of treatment data alone or estimates from other countries, hence updated, local and broader estimates are needed.</p> <p>Methods</p> <p>The current work identifies profiles where the risk of harm to children could be increased by patterns of parental substance use and generates new estimates following secondary analysis of five UK national household surveys.</p> <p>Results</p> <p>The Health Survey for England (HSfE) and General Household Survey (GHS) (both 2004) generated consistent estimates - around 30% of children under-16 years (3.3 - 3.5 million) in the UK lived with at least one binge drinking parent, 8% with at least two binge drinkers and 4% with a lone (binge drinking) parent. The National Psychiatric Morbidity Survey (NPMS) indicated that in 2000, 22% (2.6 million) lived with a hazardous drinker and 6% (705,000) with a dependent drinker. The British Crime Survey (2004) and NPMS (2000) indicated that 8% (up to 978,000) of children lived with an adult who had used illicit drugs within that year, 2% (up to 256,000) with a class A drug user and 7% (up to 873,000) with a class C drug user. Around 335,000 children lived with a drug dependent user, 72,000 with an injecting drug user, 72,000 with a drug user in treatment and 108,000 with an adult who had overdosed. Elevated or cumulative risk of harm may have existed for the 3.6% (around 430,000) children in the UK who lived with a problem drinker who also used drugs and 4% (half a million) where problem drinking co-existed with mental health problems. Stronger indicators of harm emerged from the Scottish Crime Survey (2000), according to which 1% of children (around 12,000 children) had witnessed force being used against an adult in the household by their partner whilst drinking alcohol and 0.6% (almost 6000 children) whilst using drugs.</p> <p>Conclusion</p> <p>Whilst harm from parental substance use is not inevitable, the number of children living with substance misusing parents exceeds earlier estimates. Widespread patterns of binge drinking and recreational drug use may expose children to sub-optimal care and substance-using role models. Implications for policy, practice and research are discussed.</p

Cerebral atrophy in mild cognitive impairment and Alzheimer disease: rates and acceleration.

OBJECTIVE: To quantify the regional and global cerebral atrophy rates and assess acceleration rates in healthy controls, subjects with mild cognitive impairment (MCI), and subjects with mild Alzheimer disease (AD). METHODS: Using 0-, 6-, 12-, 18-, 24-, and 36-month MRI scans of controls and subjects with MCI and AD from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database, we calculated volume change of whole brain, hippocampus, and ventricles between all pairs of scans using the boundary shift integral. RESULTS: We found no evidence of acceleration in whole-brain atrophy rates in any group. There was evidence that hippocampal atrophy rates in MCI subjects accelerate by 0.22%/year2 on average (p = 0.037). There was evidence of acceleration in rates of ventricular enlargement in subjects with MCI (p = 0.001) and AD (p < 0.001), with rates estimated to increase by 0.27 mL/year2 (95% confidence interval 0.12, 0.43) and 0.88 mL/year2 (95% confidence interval 0.47, 1.29), respectively. A post hoc analysis suggested that the acceleration of hippocampal loss in MCI subjects was mainly driven by the MCI subjects that were observed to progress to clinical AD within 3 years of baseline, with this group showing hippocampal atrophy rate acceleration of 0.50%/year2 (p = 0.003). CONCLUSIONS: The small acceleration rates suggest a long period of transition to the pathologic losses seen in clinical AD. The acceleration in hippocampal atrophy rates in MCI subjects in the ADNI seems to be driven by those MCI subjects who concurrently progressed to a clinical diagnosis of AD

Whole genome sequencing of Mycobacterium tuberculosis reveals slow growth and low mutation rates during latent infections in humans

Very little is known about the growth and mutation rates of Mycobacterium tuberculosis during latent infection in humans. However, studies in rhesus macaques have suggested that latent infections have mutation rates that are higher than that observed during active tuberculosis disease. Elevated mutation rates are presumed risk factors for the development of drug resistance. Therefore, the investigation of mutation rates during human latency is of high importance. We performed whole genome mutation analysis of M. tuberculosis isolates from a multi-decade tuberculosis outbreak of the New Zealand Rangipo strain. We used epidemiological and phylogenetic analysis to identify four cases of tuberculosis acquired from the same index case. Two of the tuberculosis cases occurred within two years of exposure and were classified as recently transmitted tuberculosis. Two other cases occurred more than 20 years after exposure and were classified as reactivation of latent M. tuberculosis infections. Mutation rates were compared between the two recently transmitted pairs versus the two latent pairs. Mean mutation rates assuming 20 hour generation times were 5.5X10⁻¹⁰ mutations/bp/generation for recently transmitted tuberculosis and 7.3X10⁻¹¹ mutations/bp/generation for latent tuberculosis. Generation time versus mutation rate curves were also significantly higher for recently transmitted tuberculosis across all replication rates (p = 0.006). Assuming identical replication and mutation rates among all isolates in the final two years before disease reactivation, the u20hr mutation rate attributable to the remaining latent period was 1.6×10⁻¹¹ mutations/bp/generation, or approximately 30 fold less than that calculated during the two years immediately before disease. Mutations attributable to oxidative stress as might be caused by bacterial exposure to the host immune system were not increased in latent infections. In conclusion, we did not find any evidence to suggest elevated mutation rates during tuberculosis latency in humans, unlike the situation in rhesus macaques

Pilus distribution among lineages of group b <i>streptococcus</i>: an evolutionary and clinical perspective

&lt;b&gt;Background&lt;/b&gt;&lt;p&gt;&lt;/p&gt; Group B Streptococcus (GBS) is an opportunistic pathogen in both humans and bovines. Epidemiological and phylogenetic analyses have found strains belonging to certain phylogenetic lineages to be more frequently associated with invasive newborn disease, asymptomatic maternal colonization, and subclinical bovine mastitis. Pilus structures in GBS facilitate colonization and invasion of host tissues and play a role in biofilm formation, though few large-scale studies have estimated the frequency and diversity of the three pilus islands (PIs) across diverse genotypes. Here, we examined the distribution of pilus islands (PI) 1, 2a and 2b among 295 GBS strains representing 73 multilocus sequence types (STs) belonging to eight clonal complexes. PCR-based RFLP was also used to evaluate variation in the genes encoding pilus backbone proteins of PI-2a and PI-2b.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Results&lt;/b&gt;&lt;p&gt;&lt;/p&gt; All 295 strains harbored one of the PI-2 variants and most human-derived strains contained PI-1. Bovine-derived strains lacked PI-1 and possessed a unique PI-2b backbone protein allele. Neonatal strains more frequently had PI-1 and a PI-2 variant than maternal colonizing strains, and most CC-17 strains had PI-1 and PI-2b with a distinct backbone protein allele. Furthermore, we present evidence for the frequent gain and loss of genes encoding certain pilus types.&lt;p&gt;&lt;/p&gt; &lt;b&gt;Conclusions&lt;/b&gt;&lt;p&gt;&lt;/p&gt; These data suggest that pilus combinations impact host specificity and disease presentation and that diversification often involves the loss or acquisition of PIs. Such findings have implications for the development of GBS vaccines that target the three pilus islands

Gas-Modified Electrospinning with a Portable Device

Project Objective The objective of this work was to construct a miniaturized, portable electrospinning (ES) device for deposition on surfaces regardless of charge. We hope this device can be used by doctors in rural areas to deliver drug delivery bandages. Mathematical modeling was used to improve predictability of the completed portable ES device

Deposition of Drug-delivering Bandages via a Combined Electrostatic and Air-Driven Electrospinning Device

Electrospinning (ES) is an affordable manufacturing process to produce nanoscale, polymer fibers. During ES, a high voltage differential is required to draw out polymer fibers from a polymer solution at a charged spinneret. Fibers produced are then deposited onto an oppositely charged electrode. ES typically requires large, immovable equipment and conductive surfaces for deposition of fibers. Portability and on-demand ES of fiber mats onto non-conductive surfaces would enable use in re- mote locations with limited access to medicine