Assessing cost-effectiveness of drug interventions for schizophrenia

Objective: To assess from a health sector perspective the incremental cost-effectiveness of eight drug treatment scenarios for established schizophrenia. Method: Using a standardized methodology, costs and outcomes are modelled over the lifetime of prevalent cases of schizophrenia in Australia in 2000. A two-stage approach to assessment of health benefit is used. The first stage involves a quantitative analysis based on disability-adjusted life years (DALYs) averted, using best available evidence. The robustness of results is tested using probabilistic uncertainty analysis. The second stage involves application of 'second filter' criteria (equity, strength of evidence, feasibility and acceptability) to allow broader concepts of benefit to be considered. Results: Replacing oral typicals with risperidone or olanzapine has an incremental cost-effectiveness ratio (ICER) of A$48 000 and A$92 000/DALY respectively. Switching from low-dose typicals to risperidone has an ICER of A$80 000. Giving risperidone to people experiencing side-effects on typicals is more cost-effective at A$20 000. Giving clozapine to people taking typicals, with the worst course of the disorder and either little or clear deterioration, is cost-effective at A$42 000 or A$23 000/DALY respectively. The least cost-effective intervention is to replace risperidone with olanzapine at A$160 000/DALY. Conclusions: Based on an A$50 000/DALY threshold, low-dose typical neuroleptics are indicated as the treatment of choice for established schizophrenia, with risperidone being reserved for those experiencing moderate to severe side-effects on typicals. The more expensive olanzapine should only be prescribed when risperidone is not clinically indicated. The high cost of risperidone and olanzapine relative to modest health gains underlie this conclusion. Earlier introduction of clozapine however, would be cost-effective. This work is limited by weaknesses in trials (lack of long-term efficacy data, quality of life and consumer satisfaction evidence) and the translation of effect size into a DALY change. Some stakeholders, including SANE Australia, argue the modest health gains reported in the literature do not adequately reflect perceptions by patients, clinicians and carers, of improved quality of life with these atypicals.

Time-resolved photoluminescence spectroscopy of ligand-capped PbS nanocrystals

PbS nanocrystals are synthesized using colloidal techniques and have their surfaces capped with oleic acid. The absorption band edge of the PbS nanocrystals is tuned between 900 and 580 nm. The PbS nanocrystals exhibit tuneable photoluminescence with large non-resonant Stokes shifts of up to 500 mcV. The magnitude of the Stokes shift is found to be dependent upon the size of PbS nanocrystals. Time-resolved photoluminescence spectroscopy of the PbS nanocrystals reveals that the photouminescence has an extraordinarily long lifetime of 1 mus. This long fluorescence lifetime is attributed to the effect of dielectric screening similar to that observed in other IV-VI semiconductor nanocrystals.

The role of habitat disturbance and recovery in metapopulation persistence

Classical metapopulation theory assumes a static landscape. However, empirical evidence indicates many metapopulations are driven by habitat succession and disturbance. We develop a stochastic metapopulation model, incorporating habitat disturbance and recovery, coupled with patch colonization and extinction, to investigate the effect of habitat dynamics on persistence. We discover that habitat dynamics play a fundamental role in metapopulation dynamics. The mean number of suitable habitat patches is not adequate for characterizing the dynamics of the metapopulation. For a fixed mean number of suitable patches, we discover that the details of how disturbance affects patches and how patches recover influences metapopulation dynamics in a fundamental way. Moreover, metapopulation persistence is dependent not only oil the average lifetime of a patch, but also on the variance in patch lifetime and the synchrony in patch dynamics that results from disturbance. Finally, there is an interaction between the habitat and metapopulation dynamics, for instance declining metapopulations react differently to habitat dynamics than expanding metapopulations. We close, emphasizing the importance of using performance measures appropriate to stochastic systems when evaluating their behavior, such as the probability distribution of the state of the. metapopulation, conditional on it being extant (i.e., the quasistationary distribution).

The 2dF-SDSS LRG and QSO survey: the star formation histories of luminous red galaxies

We present a detailed investigation into the recent star formation histories of 5697 luminous red galaxies (LRGs) based on the H delta (4101 angstrom), and [O II] (3727 angstrom) lines and the D4000 index. LRGs are luminous (L > 3L*) galaxies which have been selected to have photometric properties consistent with an old, passively evolving stellar population. For this study, we utilize LRGs from the recently completed 2dF-SDSS LRG and QSO Survey (2SLAQ). Equivalent widths of the H delta and [O II] lines are measured and used to define three spectral types, those with only strong H delta absorption (k+a), those with strong [O II] in emission (em) and those with both (em+a). All other LRGs are considered to have passive star formation histories. The vast majority of LRGs are found to be passive (similar to 80 per cent); however, significant numbers of k+a (2.7 per cent), em+a (1.2 per cent) and em LRGs (8.6 per cent) are identified. An investigation into the redshift dependence of the fractions is also performed. A sample of SDSS MAIN galaxies with colours and luminosities consistent with the 2SLAQ LRGs is selected to provide a low-redshift comparison. While the em and em+a fractions are consistent with the low-redshift SDSS sample, the fraction of k+a LRGs is found to increase significantly with redshift. This result is interpreted as an indication of an increasing amount of recent star formation activity in LRGs with redshift. By considering the expected lifetime of the k+a phase, the number of LRGs which will undergo a k+a phase can be estimated. A crude comparison of this estimate with the predictions from semi-analytic models of galaxy formation shows that the predicted level of k+a and em+a activities is not sufficient to reconcile the predicted mass growth for massive early types in a hierarchical merging scenario.

A study of field emission from semiconductors

In an attempt to clarify the behaviour of semi-conductor field emitters the properties of a narrow band gap material were investigated. A retarding potential analyser was built and tested using a tungsten emitter. The energy distribution of electrons emitted from single crystals of lead telluride (band gap 0.3 eV) and gallium phosphide (band gap 2.26 eV) were measured. The halfwidths of the distributions are discussed with respect to the relevant parameters for the materials. Methods of tip preparation had to be developed. The halfwidth of the energy distribution of electrons field emitted from carbon fibres was measured to be 0.21 ± 0.01 eV. A mechanism explaining the long lifetime of the emitters in poor vacuua is proposed.

Carrier lifetime and exciton saturation in a strain-balanced InGaAs/InAsP multiple-quantum-well

The bleaching of the n = 1 heavy-hole and light-hole exciton absorption has been studied at room temperature and zero bias in a strain-balanced InGaAs/InAsP multiple quantum well. Pump-probe spectroscopy was used to measure the decay of the light-hole absorption saturation, giving a hole lifetime of only 280 ps. As only 16 meV separates the light- and heavy-hole bands, the short escape time can be explained by thermalization between these bands followed by thermionic emission over the heavy-hole barrier. The saturation density was estimated to be 1 × 1016 cm-3; this is much lower than expected for tensile-strained wells where both heavy and light holes have large in-plane masses. © 1998 American Institute of Physics.

Fabrication of high quality optical coherence tomography (OCT) calibration artefacts using femtosecond inscription

Optical coherence tomography (OCT) is a non-invasive three-dimensional imaging system that is capable of producing high resolution in-vivo images. OCT is approved for use in clinical trials in Japan, USA and Europe. For OCT to be used effectively in a clinical diagnosis, a method of standardisation is required to assess the performance across different systems. This standardisation can be implemented using highly accurate and reproducible artefacts for calibration at both installation and throughout the lifetime of a system. Femtosecond lasers can write highly reproducible and highly localised micro-structured calibration artefacts within a transparent media. We report on the fabrication of high quality OCT calibration artefacts in fused silica using a femtosecond laser. The calibration artefacts were written in fused silica due to its high purity and ability to withstand high energy femtosecond pulses. An Amplitude Systemes s-Pulse Yb:YAG femtosecond laser with an operating wavelength of 1026 nm was used to inscribe three dimensional patterns within the highly optically transmissive substrate. Four unique artefacts have been designed to measure a wide variety of parameters, including the points spread function (PSF), modulation transfer function (MTF), sensitivity, distortion and resolution - key parameters which define the performance of the OCT. The calibration artefacts have been characterised using an optical microscope and tested on a swept source OCT. The results demonstrate that the femtosecond laser inscribed artefacts have the potential of quantitatively and qualitatively validating the performance of any OCT system.

Synthesis of novel and stable g-C3N4/N-doped SrTiO3 hybrid nanocomposites with improved photocurrent and photocatalytic activity under visible light irradiation

Hybrid nanocomposites based on N-doped SrTiO3 nanoparticles wrapped in g-C3N4 nanosheets were successfully prepared by a facile and reproducible polymeric citrate and thermal exfoliation method. The results clearly indicated that the N-doped SrTiO3 nanoparticles are successfully wrapped in layers of the g-C3N4 nanosheets. The g-C3N4/N-doped SrTiO3 nanocomposites showed absorption edges at longer wavelengths compared with the pure g-C3N4 as well as N-doped SrTiO3. The hybrid nanocomposites exhibit an improved photocurrent response and photocatalytic activity under visible light irradiation. Interestingly, the hybrid nanocomposite possesses high photostability and reusability. Based on experimental results, the possible mechanism for prolonged lifetime of the photoinduced charge carrier was also discussed. The high performance of the g-C3N4/N-doped SrTiO3 photocatalysts is due to the synergic effect at the interface of g-C3N4 and N-doped SrTiO3 hetero/nanojunction including the high separation efficiency of the charge carrier, band energy matching and the suppressed recombination rate. Therefore, the hybrid photocatalyst could be of potential interest for water splitting and environmental remediation under natural sunlight.

A comparison of in situ constant and falling head permeameter tests to assess the distribution of clogging within horizontal subsurface flow constructed wetlands

Clogging is the main operational problem associated with horizontal subsurface flow constructed wetlands (HSSF CWs). The measurement of saturated hydraulic conductivity has proven to be a suitable technique to assess clogging within HSSF CWs. The vertical and horizontal distribution of hydraulic conductivity was assessed in two full-scale HSSF CWs by using two different in situ permeameter methods (falling head (FH) and constant head (CH) methods). Horizontal hydraulic conductivity profiles showed that both methods are correlated by a power function (FH= CH 0.7821, r 2=0.76) within the recorded range of hydraulic conductivities (0-70 m/day). However, the FH method provided lower values of hydraulic conductivity than the CH method (one to three times lower). Despite discrepancies between the magnitudes of reported readings, the relative distribution of clogging obtained via both methods was similar. Therefore, both methods are useful when exploring the general distribution of clogging and, specially, the assessment of clogged areas originated from preferential flow paths within full-scale HSSF CWs. Discrepancy between methods (either in magnitude and pattern) aroused from the vertical hydraulic conductivity profiles under highly clogged conditions. It is believed this can be attributed to procedural differences between the methods, such as the method of permeameter insertion (twisting versus hammering). Results from both methods suggest that clogging develops along the shortest distance between water input and output. Results also evidence that the design and maintenance of inlet distributors and outlet collectors appear to have a great influence on the pattern of clogging, and hence the asset lifetime of HSSF CWs. © Springer Science+Business Media B.V. 2011.

Synthesis and characterisation of interfacial layers in organic solar cells

The quest for renewable energy sources has led to growing attention in the research of organic photovoltaics (OPVs), as a promising alternative to fossil fuels, since these devices have low manufacturing costs and attractive end-user qualities, such as ease of installation and maintenance. Wide application of OPVs is majorly limited by the devices lifetime. With the development of new encapsulation materials, some degradation factors, such as water and oxygen ingress, can almost be excluded, whereas the thermal degradation of the devices remains a major issue. Two aspects have to be addressed to solve the problem of thermal instability: bulk effects in the photoactive layer and interfacial effects at the photoactive layer/charge-transporting layers. In this work, the interface between photoactive layer and electron-transporting zinc oxide (ZnO) in devices with inverted architecture was engineered by introducing polymeric interlayers, based on zinc-binding ligands, such as 3,4-dihydroxybenzene and 8-hydroxyquinoline. Also, a cross-linkable layer of poly(3,4-dimethoxystyrene) and its fullerene derivative were studied. At first, controlled reversible addition-fragmentation chain transfer (RAFT) polymerisation was employed to achieve well-defined polymers in a range of molar masses, all bearing a chain-end functionality for further modifications. Resulting polymers have been fully characterised, including their thermal and optical properties, and introduced as interlayers to study their effect on the initial device performance and thermal stability. Poly(3,4-dihydroxystyrene) and its fullerene derivative were found unsuitable for application in devices as they increased the work function of ZnO and created a barrier for electron extraction. On the other hand, their parental polymer, poly(3,4-dimethoxystyrene), and its fullerene derivative, upon cross-linking, resulted in enhanced efficiency and stability of devices, if compared to control. Polymers based on 8-hydroxyquinoline ligand had a negative effect on the initial stability of the devices, but increased the lifetime of the cells under accelerated thermal stress. Comprehensive studies of the key mechanisms, determining efficiency, such as charge generation and extraction, were performed by using time-resolved electrical and spectroscopic techniques, in order to understand in detail the effect of the interlayers on the device performance. Obtained results allow deeper insight into mechanisms of degradation that limit the lifetime of devices and prompt the design of better materials for the interface stabilisation.

Who you are and what you do:the role of entrepreneurial human capital in the demand and supply of external finance of high-tech start-ups

The existence of adequate financial capital at start-up as well as during the lifetime of a firm is considered to be vital not only for its survival but also for its effective trading and growth, as it can act as a buffer against unforeseen difficulties (Cooper, Gimeno-Gascon, & Woo, 1994; Chandler & Hanks, 1998; Venkataraman & Van de Ven, 1998; Cassar, 2004). Inadequate or inappropriate capital structure is often the most common reason for a large proportion of small business failures (Chaganti, DeCarolis, & Deeds, 1995).

Covalent protein adduction by drugs of abuse

Recreational abuse of the drugs cocaine, methamphetamine, and morphine continues to be prevalent in the United States of America and around the world. While numerous methods of detection exist for each drug, they are generally limited by the lifetime of the parent drug and its metabolites in the body. However, the covalent modification of endogenous proteins by these drugs of abuse may act as biomarkers of exposure and allow for extension of detection windows for these drugs beyond the lifetime of parent molecules or metabolites in the free fraction. Additionally, existence of covalently bound molecules arising from drug ingestion can offer insight into downstream toxicities associated with each of these drugs. This research investigated the metabolism of cocaine, methamphetamine, and morphine in common in vitro assay systems, specifically focusing on the generation of reactive intermediates and metabolites that have the potential to form covalent protein adducts. Results demonstrated the formation of covalent adduction products between biological cysteine thiols and reactive moieties on cocaine and morphine metabolites. Rigorous mass spectrometric analysis in conjunction with in vitro metabolic activation, pharmacogenetic reaction phenotyping, and computational modeling were utilized to characterize structures and mechanisms of formation for each resultant thiol adduction product. For cocaine, data collected demonstrated the formation of adduction products from a reactive arene epoxide intermediate, designating a novel metabolic pathway for cocaine. In the case of morphine, data expanded on known adduct-forming pathways using sensitive and selective analysis techniques, following the known reactive metabolite, morphinone, and a proposed novel metabolite, morphine quinone methide. Data collected in this study describe novel metabolic events for multiple important drugs of abuse, culminating in detection methods and mechanistic descriptors useful to both medical and forensic investigators when examining the toxicology associated with cocaine, methamphetamine, and morphine.

Geochemical and isotopic composition of Bransfield Basin Lavas collected during SONNE cruise SO155

Bransfield Basin is an actively extending marginal basin separating the inactive South Shetland arc from the northern Antarctic Peninsula. Rift-related volcanism is widespread throughout the central Bransfield Basin, but the wider eastern Bransfield Basin was previously unsampled. Lavas recovered from the eastern subbasin form three distinct groups: (1) Bransfield Group has moderate large-ion lithophile element (LILE) enrichment relative to normal mid-ocean ridge basalt (NMORB), (2) Gibbs Group has strong LILE enrichment and is restricted to a relic seamount interpreted as part of the South Shetland arc, and (3) fresh alkali basalt was recovered from the NE part of the basin near Spanish Rise. The subduction-related component in Bransfield and Gibbs Group lavas is a LILE-rich fluid with radiogenic Sr, Nd, and Pb isotope compositions derived predominantly from subducting sediment. These lavas can be modeled as melts from Pacific MORB source mantle contaminated by up to 5% of the subduction-related component. They further reveal that Pacific mantle, rather than South Atlantic mantle, has underlain Bransfield Basin since 3 Ma. Magma productivity decreases abruptly east of Bridgeman Rise, and lavas with the least subduction component outcrop at that end. Both the eastward decrease in subduction component and occurrence of young alkali basalts require that subduction-modified mantle generated during the lifetime of the South Shetland arc has been progressively removed from NE to SW. This is inconsistent with previous models suggesting continued slow subduction at the South Shetland Trench but instead favors models in which the South Scotia Ridge fault has propagated westward since 3 Ma generating transtension across the basin.

Nutrients of pore water in sediments of the central equatorial Pacific

Shipboard whole-core squeezing was used to measure pore water concentration vs depth profiles of [NO3]-, O2 and SiO2 at 12 stations in the equatorial Pacific along a transect from 15°S to 11°N at 135°W. The [NO3]- and SiO2 profiles were combined with fine-scale resistivity and porosity measurements to calculate benthic fluxes. After using O2 profiles, coupled with the [NO3]- profiles, to constrain the C:N of the degrading organic matter, the [NO3]- fluxes were converted to benthic organic carbon degradation rates. The range in benthic organic carbon degradation rates is 7-30 ?mol cm**-2 y**-1, with maximum values at the equator and minimum values at the southern end of the transect. The zonal trend of benthic degradation rates, with its equatorial maximum and with elevated values skewed to the north of the equator, is similar to the pattern of primary production observed in the region. Benthic organic carbon degradation is 1-2% of primary production. The range of benthic biogenic silica dissolution rates is 6.9-20 µmol cm**-2 y**-1, representing 2.5-5% of silicon fixation in the surface ocean of the region. Its zonal pattern is distinctly different from that of organic carbon degradation: the range in the ratio of silica dissolution to carbon degradation along the transect is 0.44-1.7 mol Si mol C**-1, with maximum values occurring between 12°S and 2°S, and with fairly constant values of 0.5-0.7 north of the equator. A box model calculation of the average lifetime of the organic carbon in the upper 1 cm of the sediments, where 80 +/- 11% of benthic organic carbon degradation occurs, indicates that it is short: from 3.1 years at high flux stations to 11 years at low flux stations. The reactive component of the organic matter must have a shorter lifetime than this average value. In contrast, the average lifetime of biogenic silica in the upper centimeter of these sediments is 55 +/- 28 years, and shows no systematic variations with benthic flux.

Optical Control of Magnetic Feshbach Resonances by Closed-Channel Electromagnetically Induced Transparency

Optical control of interactions in ultracold gases opens new fields of research by creating ``designer" interactions with high spatial and temporal resolution. However, previous optical methods using single optical fields generally suffer from atom loss due to spontaneous scattering. This thesis reports new optical methods, employing two optical fields to control interactions in ultracold gases, while suppressing spontaneous scattering by quantum interference. In this dissertation, I will discuss the experimental demonstration of two optical field methods to control narrow and broad magnetic Feshbach resonances in an ultracold gas of $^6$Li atoms. The narrow Feshbach resonance is shifted by $30$ times its width and atom loss suppressed by destructive quantum interference. Near the broad Feshbach resonance, the spontaneous lifetime of the atoms is increased from $0.5$ ms for single field methods to $400$ ms using our two optical field method. Furthermore, I report on a new theoretical model, the continuum-dressed state model, that calculates the optically induced scattering phase shift for both the broad and narrow Feshbach resonances by treating them in a unified manner. The continuum-dressed state model fits the experimental data both in shape and magnitude using only one free parameter. Using the continuum-dressed state model, I illustrate the advantages of our two optical field method over single-field optical methods.