Despite advances in cancer genomics and the increased use of genomic medicine, metastatic cancer is still mostly an incurable and fatal disease. With diminishing returns from traditional drug discovery strategies, and high clinical failure rates, more emphasis is being placed on alternative drug discovery platforms, such as ex vivo approaches. Ex vivo approaches aim to embed biological relevance and inter-patient variability at an earlier stage of drug discovery, and to offer more precise treatment stratification for patients. However, these techniques also have a high potential to offer personalised therapies to patients, complementing and enhancing genomic medicine. Although an array of approaches are available to researchers, only a minority of techniques have made it through to direct patient treatment within robust clinical trials. Within this review, we discuss the current challenges to ex vivo approaches within clinical practice and summarise the contemporary literature which has directed patient treatment. Finally, we map out how ex vivo approaches could transition from a small-scale, predominantly research based technology to a robust and validated predictive tool. In future, these pre-clinical approaches may be integrated into clinical cancer pathways to assist in the personalisation of therapy choices and to hopefully improve patient experiences and outcomes.

The Disability Support Pension (DSP) is the major Australian government financial benefit program for people of working age with medical conditions and disabilities that restrict work capacity. Between 2012 and 2018 a series of policy reforms sought to restrict the growth in DSP payments and encourage more people with some work capacity to seek employment. We characterise changes in three markers of access to disability financial support over the reform period (1) DSP recipient rates (2) DSP grant (approval) rates and (3) the rate of unemployment benefit receipt in people with impaired work capacity. Results demonstrate a significant reduction in DSP receipt and grant rates, and significant increase in the rate of unemployment benefit receipt in working-age Australians with work disabling medical conditions and disability. These changes were not distributed uniformly. People whose primary medical condition was a musculoskeletal or circulatory system disorder demonstrated greater declines in DSP receipt and grant rates, while there was a more rapid increase in unemployment benefit receipt among people with primary mental health conditions. Some trend changes occur in periods during which new disability assessment and pension eligibility policies were introduced, though our ability to attribute changes to specific policy changes is limited.

We derive an effective macroscale description for the growth of tissue on a porous scaffold. A multiphase model is employed to describe the tissue dynamics; linearisation to facilitate a multiple-scale homogenisation provides an effective macroscale description, which incorporates dependence on the microscale structure and dynamics. In particular, the resulting description admits both interstitial growth and active cell motion. This model comprises Darcy flow, and differential equations for the volume fraction of cells within the scaffold and the concentration of nutrient, required for growth. These are coupled with Stokes-type cell problems on the microscale, incorporating dependence on active cell motion and pore scale structure. The cell problems provide the permeability tensors with which the macroscale flow is parameterised. A subset of solutions is illustrated by numerical simulations.

High definition video from a towed camera system was used to describe the deep-sea benthic habitats within an elongate depression located at the western margin of Rockall Bank in the Hatton–Rockall Basin. At depths greater than 1190 m, an extensive area (10 km long by 1.5 km wide) of what appeared to be reduced sediments, bacterial mats and flocculent matter indicated possible cold-seep habitat. Plumes of sediment-rich fluid were observed alongside raised elongate features that gave topographic relief to the otherwise flat seafloor. In the deepest section of the depression (1215 m) dense flocculent matter was observed suspended in the water column, in places obscuring the seabed. Away from the bacterial mats, the habitat changed rapidly to sediments dominated by tube-dwelling polychaete worms and then to deep-sea sedimentary habitats more typical for the water depth (sponges and burrowing megafauna in areas of gentle slopes, and coral gardens on steeper slopes).

In this article, we consider the spatial homogenisation of a multi-phase model for avascular tumour growth and response to chemotherapeutic treatment. The key contribution of this work is the derivation of a system of homogenised partial differential equations describing macroscopic tumour growth, coupled to transport of drug and nutrient, that explicitly incorporates details of the structure and dynamics of the tumour at the microscale. In order to derive these equations, we employ an asymptotic homogenisation of a microscopic description under the assumption of strong interphase drag, periodic microstructure, and strong separation of scales. The resulting macroscale model comprises a Darcy flow coupled to a system of reaction–advection partial differential equations. The coupled growth, response, and transport dynamics on the tissue scale are investigated via numerical experiments for simple academic test cases of microstructural information and tissue geometry, in which we observe drug- and nutrient-regulated growth and response consistent with the anticipated dynamics of the macroscale system.

A procedure for sampling defoliating forest insect larvae by beating them from foliage, used by the Forest Insect and Disease Survey of the Canadian Forestry Service to record population trends and predict future damage and control need in British Columbia, was tested over 150,000 acres on Vancouver Island. The parameters used were average numbers of larvae per collection and percentage positive collections. Results on the test species Acleris gloverana (Wlshm.) and Melanolophia imitata (Wlk.), on host Tsuga heterophylla (Raf.) Sarg., indicated that for low (normal) population levels the present system of choosing three-tree samples along roadsides was satisfactory but that weather conditions markedly affected sample results.

This report, which was sponsored by the Life Board of the Faculty and Institute of Actuaries, was originally published in November 1997.

Because it is referred to several times in the paper ‘Reserving, Pricing and Hedging for Policies with Guaranteed Annuity Options’, and in the discussions of the paper, and because it is not easily accessible elsewhere, it is printed here as a background paper for reference.

Trypanosoma cruzi is a protozoan parasite that infects vertebrates, causing in humans a pathological condition known as Chagas’ disease. The infection of host cells by T. cruzi involves a vast collection of molecules, including a family of 85 kDa GPI-anchored glycoproteins belonging to the gp85/trans-sialidase superfamily, which contains a conserved cell-binding sequence (VTVXNVFLYNR) known as FLY, for short. Herein, it is shown that BALB/c mice administered with a single dose (1 μg/animal, intraperitoneally) of FLY-synthetic peptide are more susceptible to infection by T. cruzi, with increased systemic parasitaemia (2-fold) and mortality. Higher tissue parasitism was observed in bladder (7·6-fold), heart (3-fold) and small intestine (3·6-fold). Moreover, an intense inflammatory response and increment of CD4+ T cells (1·7-fold) were detected in the heart of FLY-primed and infected animals, with a 5-fold relative increase of CD4+CD25+FoxP3+ T (Treg) cells. Mice treated with anti-CD25 antibodies prior to infection, showed a decrease in parasitaemia in the FLY model employed. In conclusion, the results suggest that FLY facilitates in vivo infection by T. cruzi and concurs with other factors to improve parasite survival to such an extent that might influence the progression of pathology in Chagas’ disease.

Weekly blood samples were collected from 42 Friesian cows between 5 weeks before and 10 weeks after calving, and analysed for serum cholesterol, albumin, total protein, glutamate-dehydrogenase, sorbitol-dehydrogenase and ornithine-carbamyl-transferase and blood glucose.

Cholesterol concentrations increased 2½-fold during the first 8 weeks of lactation. There was also a transient decrease in glucose concentration at calving, but there was no relationship between conception rate and the concentrations of these two constituents.

Albumin concentrations decreased at calving in some but not all cows and remained low for up to 2 weeks. Average concentrations of albumin determined by two analytical methods, a HABA dye-binding and a single radial diffusion assay method, were significantly lower (P < 0·05) between 0 and 2 weeks post-partum in eight cows which required four or more services than in 32 cows which conceived after fewer services. Similarly, the average decrease in concentration over calving was greater in those cows which conceived only after four or more services (P < 0·01).

Globulin concentrations (total protein minus albumin) decreased during the 5 weeks before, and increased in the 3 weeks following calving. The net change over calving was significantly related to conception rate, and the albumin/globulin ratio was reduced (P < 0·001) in the eight cows requiring four or more services.

Activities of all three enzymes doubled after calving, but there was no correlation between these increases and the decreases in albumin concentration, suggesting that, if liver insufficiency is a factor, it is probably due to malfunction rather than tissue damage.

A blood sample was taken at each hourly interval between 07.00 and 16.00 h on five consecutive days from each of two groups of five lactating and two groups of five nonlactating cows. The sampling was organized so that each cow was sampled twice daily and once at each time of day. Samples were analysed for blood glucose and haemoglobin, serum urea, inorganic phosphate, Ca, Mg, Na, K, total protein, albumin, Fe and Cu and plasma β-hydroxybutyrate. The sources of variation in the concentration of each constituent were determined.

Definite patterns of changes in concentrations with time of day were observed for β-hydroxybutyrate, urea, Ca, Na, Mg and Cu. In lactating cows there was a 2½-fold increase in the concentration of β-hydroxybutyrate from the lowest at 07.00 to the highest at 11.00 h. Variation in the concentrations of the other constituents with time of day was a relatively small proportion of the total variance.

It was concluded that diurnal variation in blood composition was unlikely to be a major source of error in interpretation for the usual constituents of a metabolic profile test. However, if β-hydroxybutyrate were to be included great care would be required in selecting a time for sampling.

Purpose: To evaluate the role of retrograde urethrography in treatment planning for salvage external beam radiotherapy in patients with increasing prostate-specific antigen levels after radical prostatectomy.

Methods and Materials: From July 1988 to December 2002, 173 consecutive patients received external beam radiotherapy for increasing prostate-specific antigen levels after radical prostatectomy. All 173 simulation films were reviewed, and retrograde urethrography was performed in 148 patients (86%). The distance between the line connecting the lower poles of the ischial tuberosities and site of abrupt narrowing of contrast material was measured in all 148 patients. This distance was compared with that measured in 148 consecutive patients with intact prostates who had retrograde urethrography while undergoing treatment planning for definitive radiotherapy.

Results: The mean (median) distance from the line connecting the lower poles of the ischial tuberosities to the abrupt narrowing seen in the urethrogram in patients with increasing prostate-specific antigen levels was 1.54cm (1.50cm) compared with 1.73cm (1.80cm) in those with intact prostates (p = 0.0145).

Conclusion: Retrograde urethrography is important in treatment planning for salvage radiotherapy of the prostate bed after radical prostatectomy to adequately treat the apex of the prostate bed.

Measurements of heat transfer from circular wires placed normal to a horizontal airstream have been made in the Reynolds number range 0·01 to 140. The Nusselt number can be related to the Reynolds number and temperature loading by an expression of the form$N \left(\frac {T_m}{T_\infty} \right)^{-0\cdot 17} = A + BR^n,$

where the values of n, A and B (see table 3) depend on whether the Reynolds number is above or below the value for which a vortex street exists in the wake of the wire. This value of the Reynolds number (R [eDot] 44) is independent of the intensity and scale of the stream turbulence. The theoretical heat transfer relation based on the Oseen approximation is approached asymptotically as R → 0, provided free convection is negligible.

Free convection effects diminish rapidly with increasing Reynolds number so that the orientation of the wire with respect to the vertical has a negligible influence on heat transfer except at very low velocities. For horizontal wires at very low Reynolds numbers, free convection is significant, when, roughly speaking, the Reynolds number is less than the cube root of the Grashof number.

In this work, the growth and characterization of GaAsSbN epilayers nearly lattice matched to GaAs, grown in an elemental solid source molecular beam epitaxy (MBE) system with a RF plasma nitrogen source, are discussed. The Sb and N compositions of the nearly lattice matched layers are 2.6% and 6.8%, respectively, as determined by high resolution x-ray diffraction (HRXRD) and secondary ion mass spectroscopy (SIMS) analysis. The layers are found to be fully strained as evidenced by the presence of Pendellosung fringes on the x-ray diffraction spectra.

Effects of in-situ and ex-situ annealing on the low temperature photoluminescence (PL) characteristics are discussed. The 10 K PL peak energy of 1 eV with a FWHM of 18 meV has been achieved on ex-situ annealed samples in N ambient. The temperature dependence of PL peak energy exhibits “S-shaped” behavior in the low temperature regime, indicative of the presence of localized excitons. Raman spectroscopy analysis has been carried out to determine the local structural changes on annealing.

In this paper we report the growth of GaAsSbN/GaAs single quantum well (SQW) heterostructures by molecular beam epitaxy (MBE) and their properties. A systematic study has been carried out to determine the effect of growth conditions, such as the source shutter opening sequence and substrate temperature, on the structural and optical properties of the layers. The substrate temperatures in the range of 450-470 °C were found to be optimal. Simultaneous opening of the source shutters (SS) resulted in N incorporation almost independent of substrate temperature and Sb incorporation higher at lower substrate temperatures.

The effects of ex-situ annealing in nitrogen ambient and in-situ annealing under As overpressure on the optical properties of the layers have also been investigated. A significant increase in photoluminescence (PL) intensity with reduced full width at half maxima (FWHM) in conjunction with a blue shift in the emission energy was observed on annealing the samples. In in-situ annealed samples, the PL line shapes were more symmetric and the temperature dependence of the PL peak energy indicated significant decrease in the exciton localization energy as exhibited by a less pronounced “S-shaped curve”. The “inverted S-shaped curve” observed in the temperature dependence of PL FWHM is also discussed. 1.61 μm emission with FWHM of 25 meV at 20K has been obtained in in-situ annealed GaAsSbN/GaAs SQW grown at 470 °C by SS.

In this investigation we have evaluated whether blockade of endothelin receptors influenced the renal haemodynamic and excretory responses to a period of ischaemia and reperfusion in the anaesthetised rat. The renal artery was occluded for 30 min and renal haemodynamic and excretory function followed for 90 min of reperfusion while either saline, the non-selective endothelin 1 receptor (ETA/ETB) antagonist SB209670 or the selective ETA receptor antagonist UK-350,926 was infused. In the post-ischaemic period, renal cortical and medullary perfusions were reduced by 40-50 %. When SB209670 was administered (30 µg kg-1 min-1 I.V.) for 30 min before, during and for 90 min after renal artery occlusion, cortical and medullary perfusions returned to baseline levels, responses different from those obtained during saline infusion (both P < 0.05). In the presence of UK-350,926 (30 µg kg-1 min-1 I.V.), perfusion in the medulla returned to baseline on clamp removal whereas that in the cortex remained depressed (P < 0.05). Renal ischaemia for 30 min decreased glomerular filtration rate during reperfusion and increased urine flow and sodium excretion 5- to 15-fold. UK-350,926 (30 µg kg-1 min-1 I.V.) reduced (P < 0.05) fluid excretion prior to ischaemia but during reperfusion, glomerular filtration rate returned to basal levels and there were progressive increases in fluid excretion which were smaller compared to the saline-treated group (all P < 0.05). The ischaemic challenge may cause release of endothelin, which acts on ETB receptors in the cortex and ETA receptors in the medulla to decrease perfusion. The blunted natriuresis and diuresis during blockade of ETA receptors may result from either a vascular or tubular action of endothelin. Experimental Physiology (2003) 88.4, 483-490.