Assessment of retinal structure and visual function in association with diabetic peripheral neuropathy

Diabetes is an increasingly prevalent disease worldwide. Providing early management of the complications can prevent morbidity and mortality in this population. Peripheral neuropathy, a significant complication of diabetes, is the major cause of foot ulceration and amputation in diabetes. Delay in attending to complication of the disease contributes to significant medical expenses for diabetic patients and the community. Early structural changes to the neural components of the retina have been demonstrated to occur prior to the clinically visible retinal vasculature complication of diabetic retinopathy. Additionally visual functionloss has been shown to exist before the ophthalmoscopic manifestations of vasculature damage. The purpose of this thesis was to evaluate the relationship between diabetic peripheral neuropathy and both retinal structure and visual function. The key question was whether diabetic peripheral neuropathy is the potential underlying factor responsible for retinal anatomical change and visual functional loss in people with diabetes. This study was conducted on a cohort with type 2 diabetes. Retinal nerve fibre layer thickness was assessed by means of Optical Coherence Tomography (OCT). Visual function was assessed using two different methods; Standard Automated Perimetry (SAP) and flicker perimetry were performed within the central 30 degrees of fixation. The level of diabetic peripheral neuropathy (DPN) was assessed using two techniques - Quantitative Sensory Testing and Neuropathy Disability Score (NDS). These techniques are known to be capable of detecting DPN at very early stages. NDS has also been shown as a gold standard for detecting 'risk of foot ulceration'. Findings reported in this thesis showed that RNFL thickness, particularly in the inferior quadrant, has a significant association with severity of DPN when the condition has been assessed using NDS. More specifically it was observed that inferior RNFL thickness has the ability to differentiate individuals who are at higher risk of foot ulceration from those who are at lower risk, indicating that RNFL thickness can predict late-staged DPN. Investigating the association between RNFL and QST did not show any meaningful interaction, which indicates that RNFL thickness for this cohort was not as predictive of neuropathy status as NDS. In both of these studies, control participants did not have different results from the type 2 cohort who did not DPN suggesting that RNFL thickness is not a marker for diagnosing DPN at early stages. The latter finding also indicated that diabetes per se, is unlikely to affect the RNFL thickness. Visual function as measured by SAP and flicker perimetry was found to be associated with severity of peripheral neuropathy as measured by NDS. These findings were also capable of differentiating individuals at higher risk of foot ulceration; however, visual function also proved not to be a maker for early diagnosis of DPN. It was found that neither SAP, nor flicker sensitivity have meaningful associations with DPN when neuropathy status was measured using QST. Importantly diabetic retinopathy did not explain any of the findings in these experiments. The work described here is valuable as no other research to date has investigated the association between diabetic peripheral neuropathy and either retinal structure or visual function.

The aetiology, impact and management of cancer-related fatigue in patients with advanced cancer

Cancer-related fatigue (CRF) is a distressing symptom frequently experienced by patients with advanced cancer. While there have been some advances in the understanding of the management of fatigue associated with cancer treatment, CRF associated with advanced cancer remains a phenomenon that is not well-managed. The aetiologic factors associated with CRF, the impacts of CRF and the current management of CRF are discussed in this review article in relation to patients with advanced cancer. The paper concludes that while further research is required in the area, there are several potentially effective strategies currently available that can reduce the severity of CRF in patients with advanced cancer.

Corneal markers of diabetic neuropathy

Diabetic neuropathy is a significant clinical problem that currently has no effective therapy, and in advanced cases, leads to foot ulceration and lower limb amputation. The accurate detection, characterization and quantification of this condition are important in order to define at-risk patients, anticipate deterioration, monitor progression, and assess new therapies This review evaluates novel corneal methods of assessing diabetic neuropathy. Two new non-invasive corneal markers have emerged, and in cross-sectional studies have demonstrated their ability to stratify the severity of this disease. Corneal confocal microscopy allows quantification of corneal nerve parameters and non-contact corneal esthesiometry, the functional correlate of corneal structure, assesses the sensitivity of the cornea. Both these techniques are quick to perform, produce little or no discomfort for the patient, and are suitable for clinical settings. Each has advantages and disadvantages over traditional techniques for assessing diabetic neuropathy. Application of these new corneal markers for longitudinal evaluation of diabetic neuropathy has the potential to reduce dependence on more invasive, costly, and time-consuming assessments, such as skin biopsy.

Continuum of police crime : an empirical study of court cases

The great majority of police officers are committed to honourable and competent public service and consistently demonstrate integrity and accountability in carrying out the often difficult, complex and sometimes dangerous, activities involved in policing by consent. However, in every police agency there exists an element of dishonesty, lack of professionalism and criminal behaviour. This article is based on archival research of criminal behaviour in the Norwegian police force. A total of 60 police employees were prosecuted in court because of misconduct and crime from 2005 to 2010. Court cases were coded as two potential predictors of court sentence in terms of imprisonment days, ie, type of deviance and level of deviance. Categories of police crime and levels were organised according to a conceptual framework developed for assessing and managing police deviance. Empirical findings support the hypothesis that as the seriousness of police crime increases in breadth and depth so also does the severity of the court sentence as measured by time in prison.

Condition monitoring and diagnosis of injector faults in a diesel engine using in-cylinder pressure and acoustic emission techniques

Failing injectors are one of the most common faults in diesel engines. The severity of these faults could have serious effects on diesel engine operations such as engine misfire, knocking, insufficient power output or even cause a complete engine breakdown. It is thus essential to prevent such faults from occurring by monitoring the condition of these injectors. In this paper, the authors present the results of an experimental investigation on identifying the signal characteristics of a simulated incipient injector fault in a diesel engine using both in-cylinder pressure and acoustic emission (AE) techniques. A time waveform event driven synchronous averaging technique was used to minimize or eliminate the effect of engine speed variation and amplitude fluctuation. It was found that AE is an effective method to detect the simulated injector fault in both time (crank angle) and frequency (order) domains. It was also shown that the time domain in-cylinder pressure signal is a poor indicator for condition monitoring and diagnosis of the simulated injector fault due to the small effect of the simulated fault on the engine combustion process. Nevertheless, good correlations between the simulated injector fault and the lower order components of the enveloped in-cylinder pressure spectrum were found at various engine loading conditions.

Teachers' recognition and referral of anxiety disorders in primary school children

This study investigated the ability of primary school teachers to recognise and refer children with anxiety symptoms. Two hundred and ninety-nine primary school teachers completed a questionnaire exploring their recognition and referral responses to five hypothetical vignettes that described boys and girls with varying severity of anxiety symptoms. Results revealed that teachers were generally able to recognise and make the decision to refer children with severe levels of anxiety. However, they had difficulty distinguishing between children with moderate anxiety symptoms and a severe anxiety disorder. Female teachers were more likely to refer children than were male teachers. The implications and future research are discussed.

The role of the multiple banded antigen of ureaplasma parvum in intra-amniotic infection : major virulence factor or decoy?

The multiple banded antigen (MBA) is a predicted virulence factor of Ureaplasma species. Antigenic variation of the MBA is a potential mechanism by which ureaplasmas avoid immune recognition and cause chronic infections of the upper genital tract of pregnant women. We tested whether the MBA is involved in the pathogenesis of intra-amniotic infection and chorioamnionitis by injecting virulent or avirulent-derived ureaplasma clones (expressing single MBA variants) into the amniotic fluid of pregnant sheep. At 55 days of gestation pregnant ewes (n = 20) received intra-amniotic injections of virulent-derived or avirulent-derived U. parvum serovar 6 strains (2×104 CFU), or 10B medium (n = 5). Amniotic fluid was collected every two weeks post-infection and fetal tissues were collected at the time of surgical delivery of the fetus (140 days of gestation). Whilst chronic colonisation was established in the amniotic fluid of animals infected with avirulent-derived and virulent-derived ureaplasmas, the severity of chorioamnionitis and fetal inflammation was not different between these groups (p>0.05). MBA size variants (32–170 kDa) were generated in vivo in amniotic fluid samples from both the avirulent and virulent groups, whereas in vitro antibody selection experiments led to the emergence of MBA-negative escape variants in both strains. Anti-ureaplasma IgG antibodies were detected in the maternal serum of animals from the avirulent (40%) and virulent (55%) groups, and these antibodies correlated with increased IL-1β, IL-6 and IL-8 expression in chorioamnion tissue (p<0.05). We demonstrate that ureaplasmas are capable of MBA phase variation in vitro; however, ureaplasmas undergo MBA size variation in vivo, to potentially prevent eradication by the immune response. Size variation of the MBA did not correlate with the severity of chorioamnionitis. Nonetheless, the correlation between a maternal humoral response and the expression of chorioamnion cytokines is a novel finding. This host response may be important in the pathogenesis of inflammation-mediated adverse pregnancy outcomes.

Structural damage detection using frequency response functions and neural networks

This paper illustrates the damage identification and condition assessment of a three story bookshelf structure using a new frequency response functions (FRFs) based damage index and Artificial Neural Networks (ANNs). A major obstacle of using measured frequency response function data is a large size input variables to ANNs. This problem is overcome by applying a data reduction technique called principal component analysis (PCA). In the proposed procedure, ANNs with their powerful pattern recognition and classification ability were used to extract damage information such as damage locations and severities from measured FRFs. Therefore, simple neural network models are developed, trained by Back Propagation (BP), to associate the FRFs with the damage or undamaged locations and severity of the damage of the structure. Finally, the effectiveness of the proposed method is illustrated and validated by using the real data provided by the Los Alamos National Laboratory, USA. The illustrated results show that the PCA based artificial Neural Network method is suitable and effective for damage identification and condition assessment of building structures. In addition, it is clearly demonstrated that the accuracy of proposed damage detection method can also be improved by increasing number of baseline datasets and number of principal components of the baseline dataset.

Magnetic resonance spectroscopy and neurocognitive dysfunction in obstructive sleep apnea before and after CPAP treatment

STUDY OBJECTIVES: To determine whether cerebral metabolite changes may underlie abnormalities of neurocognitive function and respiratory control in OSA. DESIGN: Observational, before and after CPAP treatment. SETTING: Two tertiary hospital research institutes. PARTICIPANTS: 30 untreated severe OSA patients, and 25 age-matched healthy controls, all males free of comorbidities, and all having had detailed structural brain analysis using voxel-based morphometry (VBM). MEASUREMENTS AND RESULTS: Single voxel bilateral hippocampal and brainstem, and multivoxel frontal metabolite concentrations were measured using magnetic resonance spectroscopy (MRS) in a high resolution (3T) scanner. Subjects also completed a battery of neurocognitive tests. Patients had repeat testing after 6 months of CPAP. There were significant differences at baseline in frontal N-acetylaspartate/choline (NAA/Cho) ratios (patients [mean (SD)] 4.56 [0.41], controls 4.92 [0.44], P = 0.001), and in hippocampal choline/creatine (Cho/Cr) ratios (0.38 [0.04] vs 0.41 [0.04], P = 0.006), (both ANCOVA, with age and premorbid IQ as covariates). No longitudinal changes were seen with treatment (n = 27, paired t tests), however the hippocampal differences were no longer significant at 6 months, and frontal NAA/Cr ratios were now also significantly different (patients 1.55 [0.13] vs control 1.65 [0.18] P = 0.01). No significant correlations were found between spectroscopy results and neurocognitive test results, but significant negative correlations were seen between arousal index and frontal NAA/Cho (r = -0.39, corrected P = 0.033) and between % total sleep time at SpO(2) < 90% and hippocampal Cho/Cr (r = -0.40, corrected P = 0.01). CONCLUSIONS: OSA patients have brain metabolite changes detected by MRS, suggestive of decreased frontal lobe neuronal viability and integrity, and decreased hippocampal membrane turnover. These regions have previously been shown to have no gross structural lesions using VBM. Little change was seen with treatment with CPAP for 6 months. No correlation of metabolite concentrations was seen with results on neurocognitive tests, but there were significant negative correlations with OSA severity as measured by severity of nocturnal hypoxemia. CITATION: O'Donoghue FJ; Wellard RM; Rochford PD; Dawson A; Barnes M; Ruehland WR; Jackson ML; Howard ME; Pierce RJ; Jackson GD. Magnetic resonance spectroscopy and neurocognitive dysfunction in obstructive sleep apnea before and after CPAP treatment.

Use of the iPhone for Cobb angle measurement in scoliosis

Purpose: The Cobb technique is the universally accepted method for measuring the severity of spinal deformities. Traditionally, Cobb angles have been measured using protractor and pencil on hardcopy radiographic films. The new generation of mobile phones make accurate angle measurement possible using an integrated accelerometer, providing a potentially useful clinical tool for assessing Cobb angles. The purpose of this study was to compare Cobb angle measurements performed using an Apple iPhone and traditional protractor in a series of twenty Adolescent Idiopathic Scoliosis patients. Methods: Seven observers measured major Cobb angles on twenty pre-operative postero-anterior radiographs of Adolescent Idiopathic Scoliosis patients with both a standard protractor and using an Apple iPhone. Five of the observers repeated the measurements at least a week after the original measurements. Results: The mean absolute difference between pairs of iPhone/protractor measurements was 2.1°, with a small (1°) bias toward lower Cobb angles with the iPhone. 95% confidence intervals for intra-observer variability were ±3.3° for the protractor and ±3.9° for the iPhone. 95% confidence intervals for inter-observer variability were ±8.3° for the iPhone and ±7.1° for the protractor. Both of these confidence intervals were within the range of previously published Cobb measurement studies. Conclusions: We conclude that the iPhone is an equivalent Cobb measurement tool to the manual protractor, and measurement times are about 15% less. The widespread availability of inclinometer-equipped mobile phones and the ability to store measurements in later versions of the angle measurement software may make these new technologies attractive for clinical measurement applications.

Thomas Young’s investigations in gradient-index optics

Purpose: James Clerk Maxwell is usually recognized as being the first, in 1854, to consider using inhomogeneous media in optical systems. However, some fifty years earlier Thomas Young, stimulated by his interest in the optics of the eye and accommodation, had already modeled some applications of gradient-index optics. These applications included using an axial gradient to provide spherical aberration-free optics and a spherical gradient to describe the optics of the atmosphere and the eye lens. We evaluated Young’s contributions. Method: We attempted to derive Young’s equations for axial and spherical refractive index gradients. Raytracing was used to confirm accuracy of formula. Results: We did not confirm Young’s equation for the axial gradient to provide aberration-free optics, but derived a slightly different equation. We confirmed the correctness of his equations for deviation of rays in a spherical gradient index and for the focal length of a lens with a nucleus of fixed index surrounded by a cortex of reducing index towards the edge. Young claimed that the equation for focal length applied to a lens with part of the constant index nucleus of the sphere removed, such that the loss of focal length was a quarter of the thickness removed, but this is not strictly correct. Conclusion: Young’s theoretical work in gradient-index optics received no acknowledgement from either his contemporaries or later authors. While his model of the eye lens is not an accurate physiological description of the human lens, with the index reducing least quickly at the edge, it represented a bold attempt to approximate the characteristics of the lens. Thomas Young’s work deserves wider recognition.

Where not to have a Heart Attack in Australia!: The Cardiac ARIA Index

Background/aims: Access to appropriate health care following an acute cardiac event is important for positive outcomes. The aim of the Cardiac ARIA index was to derive an objective, comparable, geographic measure reflecting access to cardiac services across Australia. Methods: Geographic Information Systems (GIS) were used to model a numeric-alpha index based on acute management from onset of symptoms to return to the community. Acute time frames have been calculated to include time for ambulance to arrive, assess and load patient, and travel to facility by road 40–80 kph. Results: The acute phase of the index was modelled into five categories: 1 [24/7 percutaneous cardiac intervention (PCI) ≤1 h]; 2 [24/7 PCI 1–3 h, and PCI less than an additional hour to nearest accident and emergency room (A&E)]: 3 [Nearest A&E ≤3 h (no 24/7 PCI within an extra hour)]: 4 [Nearest A&E 3–12 h (no 24/7 PCI within an extra hour)]: 5 [Nearest A&E 12–24 h (no 24/7 PCI within an extra hour)]. Discharge care was modelled into three categories based on time to a cardiac rehabilitation program, retail pharmacy, pathology services, hospital, GP or remote clinic: (A) all services ≤30 min; (B) >30 min and ≤60 min; (C) >60 min. Examples of the index indicate that the majority of population locations within capital cities were category 1A; Alice Springs and Byron Bay were 3A; and the Northern Territory town of Maningrida had minimal access to cardiac services with an index ranking of 5C. Conclusion: The Cardiac ARIA index provides an invaluable tool to inform appropriate strategies for the use of scarce cardiac resources.

Factors influencing speeding in school zones : the role of mindfulness

Background Excessive speed contributes to the incidence and severity of road crashes. The Theory of Planned Behaviour (TPB) has successfully explained variance in speeding intentions and behaviour. However, studies have shown that more than 40% of the variance in outcome measures of speeding remains unexplained, thus, suggesting additional constructs may help to enhance the TPB’s predictive power. Therefore, this study examined mindfulness; a promising construct which has not yet been tested as an additional TPB predictor. Aims The aims of this study were to explore drivers’ beliefs about speeding in school zones using the extended TPB as a framework and to examine the effect that mindfulness had on driver speeding behaviour in school zones. Methods Australian drivers (N = 17) participated in one of four focus group discussions. The overall sample was comprised of five males and twelve females who were aged between 17 to56 years. All participants were recruited via purposive sampling among 1st year psychology students at a large South East Queensland University. The group discussions took approximately one hour and were guided by a structured interview schedule which sought to elicit drivers’ beliefs, thoughts and opinions on speeding in school zones and the factors which motivate such behaviour. Results Overall, thematic analysis revealed some similar issues emerged across the groups. . In particular and perhaps somewhat unsurprisingly, given public concerns regarding the want to ensure the safety of school children, there was much agreement that speeding in school zones was dangerous and unacceptable. Somewhat paradoxically however, some participants also agreed that they had unintentionally or mindlessly sped in school zones. There were several factors that drivers believed influenced their speeding in school zones including their current mood (e.g., if in a bad mood, anxious, or excited they may be more likely to drive without awareness of, and being attentive to, their driving environment) and the extent to which they were familiar with the environment (i.e., more familiar contexts, more likely to drive mindlessly). Thus, although drivers expressed a belief that speeding in school zones was dangerous and acceptable, the extent to which a driver is mindful does influence whether or not a driver may actually engage in speeding in this context. Discussion and conclusions This study highlights the potential role of mindfulness in helping to explain speeding behaviour in school zones. Mindless drivers may speed unintentionally and while unintentional still be endangering the safety and lives of school children. The findings of this research suggest that unintentional speeding, especially in school zones, may be reduced by countermeasures which heighten the extent to which drivers are mindful of approaching and/or driving through a school zone, such as street markings and engineering measures (e.g.,flashing lights and speed bumps).

Ureaplasma parvum : understanding the complexities of intra-amniotic infection in an ovine model

The human Ureaplasma species are the most frequently isolated bacteria from the upper genital tract of pregnant women and can cause clinically asymptomatic, intra-uterine infections, which are difficult to treat with antimicrobials. Ureaplasma infection of the upper genital tract during pregnancy has been associated with numerous adverse outcomes including preterm birth, chorioamnionitis and neonatal respiratory diseases. The mechanisms by which ureaplasmas are able to chronically colonise the amniotic fluid and avoid eradication by (i) the host immune response and (ii) maternally-administered antimicrobials, remain virtually unexplored. To address this gap within the literature, this study investigated potential mechanisms by which ureaplasmas are able to cause chronic, intra-amniotic infections in an established ovine model. In this PhD program of research the effectiveness of standard, maternal erythromycin for the treatment of chronic, intra-amniotic ureaplasma infections was evaluated. At 55 days of gestation pregnant ewes received an intra-amniotic injection of either: a clinical Ureaplasma parvum serovar 3 isolate that was sensitive to macrolide antibiotics (n = 16); or 10B medium (n = 16). At 100 days of gestation, ewes were then randomised to receive either maternal erythromycin treatment (30 mg/kg/day for four days) or no treatment. Ureaplasmas were isolated from amniotic fluid, chorioamnion, umbilical cord and fetal lung specimens, which were collected at the time of preterm delivery of the fetus (125 days of gestation). Surprisingly, the numbers of ureaplasmas colonising the amniotic fluid and fetal tissues were not different between experimentally-infected animals that received erythromycin treatment or infected animals that did not receive treatment (p > 0.05), nor were there any differences in fetal inflammation and histological chorioamnionitis between these groups (p > 0.05). These data demonstrate the inability of maternal erythromycin to eradicate intra-uterine ureaplasma infections. Erythromycin was detected in the amniotic fluid of animals that received antimicrobial treatment (but not in those that did not receive treatment) by liquid chromatography-mass spectrometry; however, the concentrations were below therapeutic levels (<10 – 76 ng/mL). These findings indicate that the ineffectiveness of standard, maternal erythromycin treatment of intra-amniotic ureaplasma infections may be due to the poor placental transfer of this drug. Subsequently, the phenotypic and genotypic characteristics of ureaplasmas isolated from the amniotic fluid and chorioamnion of pregnant sheep after chronic, intra-amniotic infection and low-level exposure to erythromycin were investigated. At 55 days of gestation twelve pregnant ewes received an intra-amniotic injection of a clinical U. parvum serovar 3 isolate, which was sensitive to macrolide antibiotics. At 100 days of gestation, ewes received standard maternal erythromycin treatment (30 mg/kg/day for four days, n = 6) or saline (n = 6). Preterm fetuses were surgically delivered at 125 days of gestation and ureaplasmas were cultured from the amniotic fluid and the chorioamnion. The minimum inhibitory concentrations (MICs) of erythromycin, azithromycin and roxithromycin were determined for cultured ureaplasma isolates, and antimicrobial susceptibilities were different between ureaplasmas isolated from the amniotic fluid (MIC range = 0.08 – 1.0 mg/L) and chorioamnion (MIC range = 0.06 – 5.33 mg/L). However, the increased resistance to macrolide antibiotics observed in chorioamnion ureaplasma isolates occurred independently of exposure to erythromycin in vivo. Remarkably, domain V of the 23S ribosomal RNA gene (which is the target site of macrolide antimicrobials) of chorioamnion ureaplasmas demonstrated significant variability (125 polymorphisms out of 422 sequenced nucleotides, 29.6%) when compared to the amniotic fluid ureaplasma isolates and the inoculum strain. This sequence variability did not occur as a consequence of exposure to erythromycin, as the nucleotide substitutions were identical between chorioamnion ureaplasmas isolated from different animals, including those that did not receive erythromycin treatment. We propose that these mosaic-like 23S ribosomal RNA gene sequences may represent gene fragments transferred via horizontal gene transfer. The significant differences observed in (i) susceptibility to macrolide antimicrobials and (ii) 23S ribosomal RNA sequences of ureaplasmas isolated from the amniotic fluid and chorioamnion suggests that the anatomical site from which they were isolated may exert selective pressures that alter the socio-microbiological structure of the bacterial population, by selecting for genetic changes and altered antimicrobial susceptibility profiles. The final experiment for this PhD examined antigenic size variation of the multiple banded antigen (MBA, a surface-exposed lipoprotein and predicted ureaplasmal virulence factor) in chronic, intra-amniotic ureaplasma infections. Previously defined ‘virulent-derived’ and ‘avirulent-derived’ clonal U. parvum serovar 6 isolates (each expressing a single MBA protein) were injected into the amniotic fluid of pregnant ewes (n = 20) at 55 days of gestation, and amniotic fluid was collected by amniocentesis every two weeks until the time of near-term delivery of the fetus (at 140 days of gestation). Both the avirulent and virulent clonal ureaplasma strains generated MBA size variants (ranging in size from 32 – 170 kDa) within the amniotic fluid of pregnant ewes. The mean number of MBA size variants produced within the amniotic fluid was not different between the virulent (mean = 4.2 MBA variants) and avirulent (mean = 4.6 MBA variants) ureaplasma strains (p = 0.87). Intra-amniotic infection with the virulent strain was significantly associated with the presence of meconium-stained amniotic fluid (p = 0.01), which is an indicator of fetal distress in utero. However, the severity of histological chorioamnionitis was not different between the avirulent and virulent groups. We demonstrated that ureaplasmas were able to persist within the amniotic fluid of pregnant sheep for 85 days, despite the host mounting an innate and adaptive immune response. Pro-inflammatory cytokines (interleukin (IL)-1â, IL-6 and IL-8) were elevated within the chorioamnion tissue of pregnant sheep from both the avirulent and virulent treatment groups, and this was significantly associated with the production of anti-ureaplasma IgG antibodies within maternal sera (p < 0.05). These findings suggested that the inability of the host immune response to eradicate ureaplasmas from the amniotic cavity may be due to continual size variation of MBA surface-exposed epitopes. Taken together, these data confirm that ureaplasmas are able to cause long-term in utero infections in a sheep model, despite standard antimicrobial treatment and the development of a host immune response. The overall findings of this PhD project suggest that ureaplasmas are able to cause chronic, intra-amniotic infections due to (i) the limited placental transfer of erythromycin, which prevents the accumulation of therapeutic concentrations within the amniotic fluid; (ii) the ability of ureaplasmas to undergo rapid selection and genetic variation in vivo, resulting in ureaplasma isolates with variable MICs to macrolide antimicrobials colonising the amniotic fluid and chorioamnion; and (iii) antigenic size variation of the MBA, which may prevent eradication of ureaplasmas by the host immune response and account for differences in neonatal outcomes. The outcomes of this program of study have improved our understanding of the biology and pathogenesis of this highly adapted microorganism.

Incipient neurovulnerability and neuroprotection in early psychosis : a proton spectroscopy study of the anterior hippocampus at 3Tesla

Programmed cell death (PCD) and progenitor cell generation (of glial and in some brain areas also neuronal fate) in the CNS is an active process throughout life and is generally not associated with gliosis which means that PCD can be pathologically silent. The striking discovery that progenitor cell generation (of glial and in some brain areas neuronal fate) is widespread in the adult CNS (especially the hippocampus) suggest a much more dynamic scenario than previously thought and transcends the dichotomy between neurodevelopmental and neurodegenerative models of schizophrenia and related disorders. We suggest that the regulatory processes that control the regulation of PCD and the generation of progenitor cells may be disturbed in the early phase of psychotic disorders underpinning a disconnectivity syndrom at the onset of clinically overt disorders. An ongoing 1H-MRS study of the anterior hippocampus at 3 Tesla in mostly drug-naive first-episode psychosis patients suggests no change in NAA, but significant increases in myo-inositol and lactate. The data suggests that neuronal integrity in the anterior hippocampus is still intact at the early stage of illness or mainly only functionally impaired. However the increase in lactate and myo-inositol may reflect a potential disturbance of generation and PCD of progenitor cells (of glial and in selected brain areas also neuronal fate) at the onset of psychosis. If true the use of neuroprotective agents such as lithium or eicosapentaenoic acid (which inhibit PCD and support cell generation)in the early phase of psychotic disorders may be a potent treatment avenue to explore.