Processing of polycaprolactone and polycaprolactone-based copolymers into 3D scaffolds and their cellular responses

Synthetic polymers have attracted much attention in tissue engineering due to their ability to modulate biomechanical properties. This study investigated the feasibility of processing poly(varepsilon-caprolactone) (PCL) homopolymer, PCL-poly(ethylene glycol) (PEG) diblock, and PCL-PEG-PCL triblock copolymers into three-dimensional porous scaffolds. Properties of the various polymers were investigated by dynamic thermal analysis. The scaffolds were manufactured using the desktop robot-based rapid prototyping technique. Gross morphology and internal three-dimensional structure of scaffolds were identified by scanning electron microscopy and micro-computed tomography, which showed excellent fusion at the filament junctions, high uniformity, and complete interconnectivity of pore networks. The influences of process parameters on scaffolds' morphological and mechanical characteristics were studied. Data confirmed that the process parameters directly influenced the pore size, porosity, and, consequently, the mechanical properties of the scaffolds. The in vitro cell culture study was performed to investigate the influence of polymer nature and scaffold architecture on the adhesion of the cells onto the scaffolds using rabbit smooth muscle cells. Light, scanning electron, and confocal laser microscopy showed cell adhesion, proliferation, and extracellular matrix formation on the surface as well as inside the structure of both scaffold groups. The completely interconnected and highly regular honeycomb-like pore morphology supported bridging of the pores via cell-to-cell contact as well as production of extracellular matrix at later time points. The results indicated that the incorporation of hydrophilic PEG into hydrophobic PCL enhanced the overall hydrophilicity and cell culture performance of PCL-PEG copolymer. However, the scaffold architecture did not significantly influence the cell culture performance in this study.

Human cortical processing of colour and pattern

Investigated human visual processing of simple two-colour patterns using a delayed match to sample paradigm with positron emission tomography (PET). This study is unique in that the authors specifically designed the visual stimuli to be the same for both pattern and colour recognition with all patterns being abstract shapes not easily verbally coded composed of two-colour combinations. The authors did this to explore those brain regions required for both colour and pattern processing and to separate those areas of activation required for one or the other. 10 right-handed male volunteers aged 18–35 yrs were recruited. The authors found that both tasks activated similar occipital regions, the major difference being more extensive activation in pattern recognition. A right-sided network that involved the inferior parietal lobule, the head of the caudate nucleus, and the pulvinar nucleus of the thalamus was common to both paradigms. Pattern recognition also activated the left temporal pole and right lateral orbital gyrus, whereas colour recognition activated the left fusiform gyrus and several right frontal regions.

New insights into appetite, inflammation and the use of fish oil in hemodialysis patients

Protein-energy wasting (PEW) is commonly seen in patients with chronic kidney disease (CKD). The condition is characterised by chronic, systemic low-grade inflammation which affects nutritional status by a variety of mechanisms including reducing appetite and food intake and increasing muscle catabolism. PEW is linked with co-morbidities such as cardiovascular disease, and is associated with lower quality of life, increased hospitalisations and a 6-fold increase in risk of death1. Significant gender differences have been found in the severity and effects of several markers of PEW. There have been limited studies testing the ability of anti-inflammatory agents or nutritional interventions to reduce the effects of PEW in dialysis patients. This thesis makes a significant contribution to the understanding of PEW in dialysis patients. It advances understanding of measurement techniques for two of the key components, appetite and inflammation, and explores the effect of fish oil, an anti-inflammatory agent, on markers of PEW in dialysis patients. The first part of the thesis consists of two methodological studies conducted using baseline data. The first study aims to validate retrospective ratings of hunger, desire to eat and fullness on visual analog scales (VAS) (paper and pen and electronic) as a new method of measuring appetite in dialysis patients. The second methodological study aims to assess the ability of a variety of methods available in routine practice to detect the presence of inflammation. The second part of the thesis aims to explore the effect of 12 weeks supplementation with 2g per day of Eicosapentaenoic Acid (EPA), a longchain fatty acid found in fish oil, on markers of PEW. A combination of biomarkers and psychomarkers of appetite and inflammation are the main outcomes being explored, with nutritional status, dietary intake and quality of life included as secondary outcomes. A lead in phase of 3 months prior to baseline was used so that each person acts as their own historical control. The study also examines whether there are gender differences in response to the treatment. Being an exploratory study, an important part of the work is to test the feasibility of the intervention, thus the level of adherence and factors associated with adherence are also presented. The studies were conducted at the hemodialysis unit of the Wesley Hospital. Participants met the following criteria: adult, stage 5 CKD on hemodialysis for at least 3 months, not expected to receive a transplant or switch to another dialysis modality during the study, absence of intellectual impairment or mental illness impairing ability to follow instructions or complete the intervention. A range of intermediate, clinical and patient-centred outcome measures were collected at baseline and 12 weeks. Inflammation was measured using five biomarkers: c-reactive protein (CRP), interleukin-6 (IL6), intercellular adhesion molecule (sICAM-1), vascular cell adhesion molecule (sVCAM-1) and white cell count (WCC). Subjective appetite was measured using the first question from the Appetite and Dietary Assessment (ADAT) tool and VAS for measurements of hunger, desire to eat and fullness. A novel feature of the study was the assessment of the appetite peptides leptin, ghrelin and peptide YY as biomarkers of appetite. Nutritional status/inflammation was assessed using the Malnutrition-Inflammation Score (MIS) and the Patient-Generated Subjective Global Assessment (PG-SGA). Dietary intake was measured using 3-day records. Quality of life was measured using the Kidney Disease Quality of Life Short Form version 1.3 (KDQOL-SF™ v1.3 © RAND University), which combines the Short-Form 36 (SF36) with a kidney-disease specific module2. A smaller range of these variables was available for analysis during the control phase (CRP, ADAT, dietary intake and nutritional status). Statistical analysis was carried out using SPSS version 14 (SPSS Inc, Chicago IL, USA). Analysis of the first part of the thesis involved descriptive and bivariate statistics, as well as Bland-Altman plots to assess agreement between methods, and sensitivity analysis/ROC curves to test the ability of methods to predict the presence of inflammation. The unadjusted (paired ttests) and adjusted (linear mixed model) change over time is presented for the main outcome variables of inflammation and appetite. Results are shown for the whole group followed by analyses according to gender and adherence to treatment. Due to the exploratory nature of the study, trends and clinical significance were considered as important as statistical significance. Twenty-eight patients (mean age 61±17y, 50% male, dialysis vintage 19.5 (4- 101) months) underwent baseline assessment. Seven out of 28 patients (25%) reported sub-optimal appetite (self-reported as fair, poor or very poor) despite all being well nourished (100% SGA A). Using the VAS, ratings of hunger, but not desire to eat or fullness, were significantly (p<0.05) associated with a range of relevant clinical variables including age (r=-0.376), comorbidities (r=-0.380) nutritional status (PG-SGA score, r=-0.451), inflammatory markers (CRP r=-0.383; sICAM-1 r=-0.387) and seven domains of quality of life. Patients expressed a preference for the paper and pen method of administering VAS. None of the tools (appetite, MIS, PG-SGA, albumin or iron) showed an acceptable ability to detect patients who are inflamed. It is recommended that CRP should be tested more frequently as a matter of course rather than seeking alternative methods of measuring inflammation. 27 patients completed the 12 week intervention. 20 patients were considered adherent based on changes in % plasma EPA, which rose from 1.3 (0.94)% to 5.2 (1.1)%, p<0.001, in this group. The major barriers to adherence were forgetting to take the tablets as well as their size. At 12 weeks, inflammatory markers remained steady apart from the white cell count which decreased (7.6(2.5) vs 7.0(2.2) x109/L, p=0.058) and sVCAM-1 which increased (1685(654) vs 2249(925) ng/mL, p=0.001). Subjective appetite using VAS increased (51mm to 57mm, +12%) and there was a trend towards reduction in peptide YY (660(31) vs 600(30) pg/mL, p=0.078). There were some gender differences apparent, with the following adjusted change between baseline and week 12: CRP (males -3% vs females +17%, p=0.19), IL6 (males +17% vs females +48%, p=0.77), sICAM-1 (males -5% vs females +11%, p=0.07), sVCAM-1 (males +54% vs females +19%, p=0.08) and hunger ratings (males 20% vs females -5%, p=0.18). On balance, males experienced a maintainence or reduction in three inflammatory markers and an improvement in hunger ratings, and therefore appeared to have responded better to the intervention. Compared to those who didn’t adhere, adherent patients maintained weight (mean(SE) change: +0.5(1.6) vs - 0.8(1.2) kg, p=0.052) and fat-free mass (-0.1 (1.6) vs -1.8 (1.8) kg, p=0.045). There was no difference in change between the intervention and control phase for CRP, appetite, nutritional status or dietary intake. The thesis makes a significant contribution to the evidence base for understanding of PEW in dialysis patients. It has advanced knowledge of methods of assessing inflammation and appetite. Retrospective ratings of hunger on a VAS appear to be a valid method of assessing appetite although samples which include patients with very poor appetite are required to confirm this. Supplementation with fish oil appeared to improve subjective appetite and dampen the inflammatory response. The effectiveness of the intervention is influenced by gender and adherence. Males appear to be more responsive to the primary outcome variables than females, and the quality of response is improved with better adherence. These results provide evidence to support future interventions aimed at reducing the effects of PEW in dialysis patients.

Fouling of tubular ceramic membranes during processing of cane sugar juice

This paper examines the fouling characteristics of four tubular ceramic membranes with pore sizes 300 kDa, 0.1 μm and 0.45 μm installed in a pilot plant at a sugar factory for processing clarified cane sugar juices. All the membranes, except the one with a pore size of 0.45 μm, generally gave reproducible results through the trials, were easy to clean and could handle operation at high volumetric concentration factors. Analysis of fouled and cleaned ceramic membranes revealed that polysaccharides, lipids and to a lesser extent, polyphenols, as well as other colloidal particles cause fouling of the membranes. Electrostatic and hydrophobic forces cause strong aggregation of the polymeric components with one another and with colloidal particles. To combat irreversible fouling of the membranes, treatment options that result in the removal of particles having a size range of 0.2–0.5 μm and in addition remove polymeric impurities, need to be identified. Chemical and microscopic evaluations of the juices and the structural characterisation of individual particles and aggregates identified options to mitigate the fouling of membranes. These include conditioning the feed prior to membrane filtration to break up the network structure formed between the polymers and particles in the feed and the use of surfactants to prevent the aggregation of polymers and particles.

Gender differences in the effect of fish oil on appetite, inflammation and nutritional status in haemodialysis patients

Background: Haemodialysis patients show signs of chronic inflammation and reduced appetite, which is associated with a worse clinical status and an increased mortality risk. Fish oil has anti-inflammatory properties and may be useful as a therapeutic treatment. There is limited evidence to indicate the feasibility and efficacy of this intervention in dialysis patients. The present study aimed to compare the effect of 12 weeks of supplementation with fish oil on markers of appetite and inflammation in male and female haemodialysis patients. Methods: The study was conducted in 28 haemodialysis patients. All patients were prescribed 3 g of fish oil per day for 12 weeks. Changes in appetite, plasma fatty acid profiles and inflammatory markers were measured at baseline and at 12 weeks. Results: The mean (SD) increase in percent plasma eicosapentaenoic acid was statistically significant [1.1 (0.8) to 4.1 (2.2), P < 0.001], which was a strong indicator of good adherence. There were trends towards reductions in peptide YY (−9%; P = 0.078) and an increase in subjective sensations of hunger (+12%; P = 0.406), which reflects an increase in motivation to eat. Males (n = 13) experienced a more marked increase in hunger compared to females (+23% versus −6%), which was associated with maintenance in C-reactive protein and interleukin-6, and a reduction in soluble intercellular adhesion molecule-1. Conclusions: The results obtained demonstrate meaningful trends towards improvements in subjective appetite and certain inflammatory markers (although no change in dietary intake) and this effect was more pronounced in males. However, the levels of some inflammatory markers increased in females and this requires further study. The high level of adherence achieved indicates that an intervention requiring patients to consume four fish oil capsules per day is achievable. This was a short-term study and the effects need to be confirmed in a randomised controlled trial.

Digital processing of diffusion-tensor images of avascular tissues

Diffusion is the process that leads to the mixing of substances as a result of spontaneous and random thermal motion of individual atoms and molecules. It was first detected by the English botanist Robert Brown in 1827, and the phenomenon became known as ‘Brownian motion’. More specifically, the motion observed by Brown was translational diffusion – thermal motion resulting in random variations of the position of a molecule. This type of motion was given a correct theoretical interpretation in 1905 by Albert Einstein, who derived the relationship between temperature, the viscosity of the medium, the size of the diffusing molecule, and its diffusion coefficient. It is translational diffusion that is indirectly observed in MR diffusion-tensor imaging (DTI). The relationship obtained by Einstein provides the physical basis for using translational diffusion to probe the microscopic environment surrounding the molecule.

Individual differences in drivers’ cognitive processing of road safety messages

Using Gray and McNaughton’s (2000) revised Reinforcement Sensitivity Theory (r-RST), we examined the influence of personality on processing of words presented in gain-framed and loss-framed anti-speeding messages and how the processing biases associated with personality influenced message acceptance. The r-RST predicts that the nervous system regulates personality and that behaviour is dependent upon the activation of the Behavioural Activation System (BAS), activated by reward cues and the Fight-Flight-Freeze System (FFFS), activated by punishment cues. According to r-RST, individuals differ in the sensitivities of their BAS and FFFS (i.e., weak to strong), which in turn leads to stable patterns of behaviour in the presence of rewards and punishments, respectively. It was hypothesised that individual differences in personality (i.e., strength of the BAS and the FFFS) would influence the degree of both message processing (as measured by reaction time to previously viewed message words) and message acceptance (measured three ways by perceived message effectiveness, behavioural intentions, and attitudes). Specifically, it was anticipated that, individuals with a stronger BAS would process the words presented in the gain-frame messages faster than those with a weaker BAS and individuals with a stronger FFFS would process the words presented in the loss-frame messages faster than those with a weaker FFFS. Further, it was expected that greater processing (faster reaction times) would be associated with greater acceptance for that message. Driver licence holding students (N = 108) were recruited to view one of four anti-speeding messages (i.e., social gain-frame, social loss-frame, physical gain-frame, and physical loss-frame). A computerised lexical decision task assessed participants’ subsequent reaction times to message words, as an indicator of the extent of processing of the previously viewed message. Self-report measures assessed personality and the three message acceptance measures. As predicted, the degree of initial processing of the content of the social gain-framed message mediated the relationship between the reward sensitive trait and message effectiveness. Initial processing of the physical loss-framed message partially mediated the relationship between the punishment sensitive trait and both message effectiveness and behavioural intention ratings. These results show that reward sensitivity and punishment sensitivity traits influence cognitive processing of gain-framed and loss-framed message content, respectively, and subsequently, message effectiveness and behavioural intention ratings. Specifically, a range of road safety messages (i.e., gain-frame and loss-frame messages) could be designed which align with the processing biases associated with personality and which would target those individuals who are sensitive to rewards and those who are sensitive to punishments.

The national railway of Sarah Island : Richard Flanagan's Gould's Book of Fish

In the latter half of the nineteenth century the railway became an emblem of technological advancement, stood for the improvement and progression of European life, and became a recognizable symbol for the achievements of governments and citizens. The implementation and use of the railway became closely linked with notions of national identity and character. The railway became an identifiable artefact in official history but at the same time it became a part of everyday life. Richard Flanagan’s Gould’s Book of Fish retells the life-story of a fictionalized convict sent to Sarah Island and who paints fish, eventually he metamorphoses into one. It could be thought that a novel set in convict times would have little to do with notions of national identity, technological advancement, and railway travel. However, Richard Flanagan, in this very complex, almost surreal, novel, has used the construction of a fictional national railway as one of the ways to explore Australia's complex relationship with history and space. The novel tells of the plans of a history-loving Commandant and his desire to build a national railway on Sarah Island. This paper explores how Sarah Island becomes a metonym for Australia as a whole and Flanagan's novel takes on a metaphysical dimension as he reveals the struggles that emerge when official history collides with non-official versions. The fabulations of the novel contribute to an historical reconstruction of the spatial/architectural history of the Tasmanian colonial project.

Developmentally and transgene regulated nuclear processing of primary transcripts of chalcone synthase A in petunia

The introduction of chalcone synthase A transgenes into petunia plants can result in degradation of chalcone synthase A RNAs and loss of chalcone synthase, a process called cosuppression or post-transcriptional gene silencing. Here we show that the RNA degradation is associated with changes in premRNA processing, i.e. loss of tissue specificity in transcript cleavage patterns, accumulation of unspliced molecules, and use of template-specific secondary poly(A) sites. These changes can also be observed at a lower level in leaves but not flowers of nontransgenic petunias. Based on this, a model is presented of how transgenes may disturb the carefully evolved, developmentally controlled post-transcriptional regulation of chalcone synthase gene expression by influencing the survival rate of the endogenous and their own mRNA.

ZnO layers for opto-electronic applications from solution-based and low-temperature processing of an organometallic precursor

As printed and flexible plastic electronic gadgets become increasingly viable today, there is a need to develop materials that suit the fabrication processes involved. Two desirable requirements are solution-processable active materials or precursors and low-temperature processability. In this article, we describe a straightforward method of depositing ZnO films by simple spin coating of an organometallic diethylzinc precursor solution and annealing the resulting film at low temperatures (≤200 °C) without involving any synthetic steps. By controlling the humidity in which annealing is conducted, we are able to adjust the intrinsic doping level and carrier concentration in diethylzinc-derived ZnO. Doped or conducting transport layers are greatly preferable to undoped layers as they enable low-resistance contacts and minimize the potential drops. This ability to controllably realize doped ZnO is a key feature of the fabrication process that we describe in this article. We employ field-effect measurements as a diagnostic tool to measure doping levels and mobilities in ZnO and demonstrate that doped ZnO with high charge carrier concentration is ideal for solar cell applications. Respectable power conversion efficiencies (up to 4.5%) are achieved in inverted solar cells that incorporate diethylzinc-derived ZnO films as the electron transport layer and organic blends as the active material. Extensions of this approach to grow ternary and quaternary films with organometallic precursor chemicals will enable solution based growth of a number of semiconductor films as well as a method to dope them.