Search

In this paper we develop a general mixture model that incorporates a non-constant water fraction. A novel energy for the system is devised that allows for different water levels to be considered in the host and viable cell regions. For the first time the energy provides a way to flux the water out of the necrotic core and produce stable tumor spheroids with liquid centers. The model is also capable of producing invasive tumors with a detailed morphology. Parameter studies are performed to characterize the model. The parameters that can influence the size of the stable tumor and the growth rate are identified and the parameter regimes that can destabilize the tumor are explored. We demonstrate that this model is able to capture a wide range of tumor behavior. In particular, water fraction parameters for the host and viable cell regions allows us to consider the effects of different water fraction levels in the host and viable cell regions. Finally, the non-constant water fraction model is extended to describe hierarchical structures that incorporate cancer stem cells. This model is capable of producing a detailed invasive morphology that has hierarchical and heterogeneous cell distributions and develops necrotic cores. The model is also capable of forming stable tumors with heterogeneous cell distributions. A parameter study on the positive and negative feedback rates for the stem cell differentiation rate shows how the morphology of the tumor is dependent on the sensitivity to these parameters and possible avenues for therapy are seen.

Chronic breathlessness (dyspnoea) can be defined as an unpleasant awareness of breathing at a level of exercise which would not cause symptoms in a healthy person of the same age (or which did not previously cause symptoms), persisting for more than 1 month. Breathlessness may be accompanied by other symptoms such as chest tightness, cough, or wheeze, which together with the patient’s comorbidities and risk factors for specific diseases help shape the differential diagnosis.

Asthma is a disorder of airway smooth muscle and airway inflammation, manifested by variable airflow limitation. This definition continues to be refined in light of developments in the understanding of asthma’s pathophysiology, immunology, and treatment.

The Aappaluttoq, Siggartartulik, and Kigutilik gem corundum deposits are hosted by the Fiskenæsset Anorthosite Complex in SW Greenland. These deposits are some of the largest ruby and sapphire deposits in the world yet have received little scientific attention. During regional granulite metamorphism (2817 Ma; U-Pb EMPA monazite), leucogabbroic rocks alter towards more Na-enriched compositions causing Ca-feldspar to recrystallize. This liberates the Al required for metamorphic opaque corundum formation in an orthogneissic host. Subsequent retrogression through the amphibolite facies (2747-2555 Ma, U-Pb EMPA monazite) and local scale hydrous metasomatism (2660 Ma, U-Pb EMPA monazite) causes recrystallization of the mineral assemblage and the formation of three distinct gem corundum bearing lithologies: 1) phlogopitite, 2) altered leucogabbro, 3) altered ultramafic rock containing sapphirine and gedrite-anthophyllite. Intrusion of local granitoids (2747-2714 Ma, U-Pb TIMS zircon) provided a hydrous fluid which infiltrated and metasomatised the regional assemblage and was channeled along preexisting lithological boundaries (leucogabbro-ultramafic, leucogabbro-melanogabbro). The primary host for gem corundum is the 2-8 meter wide phlogopitite unit formed at 700 to 815°C and 5 to 8 kbar. This unit contains up to 20% corundum, of which at least 5% is gem quality. The phlogopite represents the quenched granitic-metasomatic fluid; EMPA and LA-ICP-MS analysis confirm a fluid composition depleted in S, Cu, Ca, Pr, Nd, Sm, Te, Cs, Ba, Se and transition metals, and enriched in Rb, Sr, Cr, and the HREEs. This is consistent with a granitic source rich in Si-K-Mg-Rb-Ba-Cs-Nb-Ta-Ga-H₂O±Cr±U±CO₂. The other two corundum-bearing units show similar variations except are typically more depleted in Cu, Te, S, Rb, and Sr. Corundum δ18O analyses define a tight range between 1.49‰ and 5.3‰, with a mean of 3.2 ± 0.9‰. This suggests the interaction or mixing of meteoric water with the metasomatic fluid at some point during gem recrystallization. Worldwide ultramafic-amphibolitic gem corundum deposits show similar low δ18O, mineralogy, mineral chemistry, and local geology. This study proposes the use of amphibolite-type as an all-encompassing gem deposit model to explain several enigmatic deposits elsewhere in the world.

Diabetes mellitus (DM) is an important coronary artery disease (CAD) risk factor, however the concept of ‘DM as a CAD equivalent’ remains controversial. We aimed to explore the prognostic impact of DM and CAD in patients undergoing SPECT MPI. 20,309 patients (Age: 53±27, 57% male) with 4.5

A 54-year-old heavy smoker was admitted with a 2-week history of pleuritic chest pain, cough, shortness of breath and weight loss. He had not improved despite a course of antibiotics from his general practitioner. He was commenced on intravenous antibiotics for presumed pneumonia based on his chest X-ray, which seemed to show left middle zone opacification (figure 1), and after 2 days, he was discharged with a further oral antibiotic course. Figure 1 Posteroanterior chest X-ray …

Introduction: Current guidelines require a chest x-ray 1 hour post transcutaneous imaging-guided lung biopsy, in order to rule-out pneumothorax. This delays patient discharge, leads to longer waiting times and more radiation. Thoracic ultrasound (TUSS) is proven to be a safe and fast tool that has very high specificity in ruling-out pneumothorax, when performed by trained chest physicians. Objective: To assess the efficacy and safety of a TUSS-only protocol to rule-out post biopsy pneumothorax. Methods: 48 patients had US-guided biopsy (USGB) for peripheral lung/mediastinal lesions. Mean age 66.8 (SD± 12.0), mean FEV1 (Lts) was 1.61 (SD± 0.55), mean tumour size was 38.3mm (SD± 27.0) and mean distance from skin was 14.2mm (SD± 9.0). Tumours were located in lower lobes in 45.8% and in upper lobes in 54.2%. A bilateral 6-point TUSS (2D and M-mode) was performed before the biopsy as a baseline. Another 6-point TUSS was performed 10 minutes and 30 minutes post USGB, establishing presence of “sliding” and “seashore” signs. All patients were discharged home 30 minutes post biopsy and followed up with a phonecall later the same day. Results: Both “sliding” and “seashore” signs were present post USGB in 46/48 patients (95.8%). In 2 patients there was no clear “sliding” but there was “seashore” sign post biopsy. None of the patients reported shortness of breath or haemoptysis. One patient reported new pleuritic pain, had a repeat TUSS and chest x-ray and confirmed to have a small subcutaneous haematoma. Conclusions: TUSS performed by trained chest physicians can safely rule-out pneumothorax post USGB.

Introduction: Transthoracic ultrasound is an important tool in assessing pleural effusions and placement of chest drains. It also demonstrates pleural-based masses and lung tumours abutting the pleura, lesions usually suitable for US-guided biopsy (USGB). This procedure is not being widely performed by chest physicians. Objective: To assess safety and efficacy of USGB performed by chest physicians in outpatient setting. Methods: The procedures were carried out in outpatient setting between August 2015-January 2016. Apart from informed written consent, checking clotting and omitting antiplatelet/anticoagulants, no special preparations were undertaken. Under real-time US, lesions involving/abutting the pleura which were >15mm were sampled 1-3 times with a full-core biopsy needle (Biopince® 18G). Repeat US was done 10 minutes and 30 minutes post-biopsy, ruling-out pneumothorax. Patients were discharged home 30 minutes post-biopsy. Results: 48 patients had USGB for lung/mediastinal tumours. Biopsies were histologically deemed adequate in 97.9%, with overall yield 97.9% and yield for malignancy 91.6% (44/48), all in accordance with The Royal College of Radiologists. In 1 patient with a negative biopsy, malignancy was diagnosed at surgery. Complications were minimal with one case of minor haemoptysis (2%) and one case of small subcutaneous hematoma (2%). We had no pneumothoraces and no deaths (0%). After the introduction of the service the waiting list for tissue diagnosis has disappeared. Conclusion: USGB can be performed by trained chest physicians with excellent yield and very low complication rate in outpatients. When used appropriately, it reduces the waiting list for tissue diagnosis.

We propose a new nonparametric estimator for the volatility structure of the zero-coupon yield curve inside the Heath-Jarrow-Morton framework. The estimator incorporates cross-sectional restrictions along the maturity dimension, and also allows for measurement errors, which can arise from estimation of the yield curve from noisy data. The estimates are implemented with daily CRSP bond data.

There have been substantial changes in banking industries throughout the world in the last two decades. While many of the effects of these changes in the US have been documented, the increasingly global nature of regulation in recent years makes understanding the effects of these changes in other countries imperative. This paper examines Australian bank returns during the period 1981–1993, employing a switching-regression methodology. We find that several structural changes have occurred, coinciding with (i) the release of deregulatory initiatives by the Australian government in the early 1980s, (ii) the flotation of the Australian dollar and the licensing of foreign banks, and (iii) the implementation of the Basle accord risk-based capital measures. Moreover, we report important differences in the relations between bank returns and both interest rates and exchange rates relative to those reported in US studies.

Epidemiological data on primary biliary cirrhosis (PBC) in the Southern Hemisphere is scarce. Our aim was to perform a population-based epidemiological study of PBC in Canterbury, New Zealand. Multiple case-finding methods were employed. All public and private, adult and pediatric outpatient clinics, hospital discharge summaries, and laboratory and pathology reports were searched to identify all cases in the region. Cases were included if at least two of the following criteria were fulfilled: (1) positive anti-mitochondrial antibodies, (2) elevated alkaline phosphatase for greater than 6 months, and (3) compatible liver histology. A total of 71 cases of PBC were included. The incidence in 2008 was 0.8 (95% confidence interval (CI) 0.1–1.6) per 100,000. The point prevalence on December 31, 2008 was 9.9 (95% CI 7.1–12.7) per 100,000. Male to female ratio was 1:11. At presentation, 45% were asymptomatic. Age at diagnosis peaked at the seventh decade with mean age at diagnosis of 61 (95% CI 58–64). This is the first population-based epidemiological study of PBC conducted in New Zealand and only the second in the Southern Hemisphere. The incidence and prevalence are lower than the Northern Hemisphere, even though the majority of our population has shared genetic background with some of these countries. Our study has provided further support to the hypothesis that there may be a protective effect or lack of a risk factor for PBC in New Zealand.

The copines are a family of C2- and von Willebrand factor A-domain-containing proteins that have been proposed to respond to increases in intracellular calcium by translocating to the plasma membrane. The copines have been reported to interact with a range of cell signalling and cytoskeletal proteins, which may therefore be targeted to the membrane following increases in cellular calcium. However, neither the function of the copines, nor their actual movement to the plasma membrane, has been fully established in mammalian cells. Here, we show that copines-1, -2, -3, -6 and -7 respond differently to a methacholine-evoked intracellular increase in calcium in human embryonic kidney cell line-293 cells, and that their membrane association requires different levels of intracellular calcium. We demonstrate that two of these copines associate with different intracellular vesicles following calcium entry into cells, and identify a novel conserved amino acid sequence that is required for their membrane translocation in living cells. Our data show that the von Willebrand factor A-domain of the copines modulates their calcium sensitivity and intracellular targeting. Together, these findings suggest a different set of roles for the members of this protein family in mediating calcium-dependent processes in mammalian cells.