Platinum-based chemotherapy in metastatic breast cancer : the Leicester (UK) experience

Aims: After failure of anthracycline- and taxane-based chemotherapy in metastatic breast cancer, treatment options until recently were limited. Until the introduction of capecitabine and vinorelbine, no standard regimen was available. We conducted a retrospective study to determine the efficacy and toxicity of platinum-based chemotherapy in metastatic breast cancer. Materials and methods: Forty-two women with metastatic breast cancer previously treated with anthracyclines (93%) and/or taxanes (36%) received mitomycin-vinblastine-cisplatin (MVP) (n = 23), or cisplatin-etoposide (PE) (n = 19), as first-, second- and third-line treatment at a tertiary referral centre between 1997 and 2002. Chemotherapy was given every 3 weeks as follows: mitomycin-C (8 mg/m 2) (cycles 1, 2, 4, 6), vinblastine (6 mg/m 2), and cisplatin (50 mg/m 2) all on day 1; and cisplatin (75 mg/m 2) and etoposide (100 mg/m 2) on day 1 and (100 mg/m 2) orally twice a day on days 2-3. Results: The response rate for 40 evaluable patients (MVP: n = 23; PE: n = 17) was 18% (95% confidence interval [CI]: 9-32%). The response rate to MVP was 13% (95% CI: 5-32%, one complete and two partial responses) and to PE 24% (10-47%, four partial responses). Disease stabilised in 43% (26-63%) and 47% (26-69%) of women treated with MVP and PE, respectively. After a median follow-up of 18 months, 37 women (MVP: n = 19; PE: n = 18) died from their disease. Median (range) progression-free survival and overall survival were 6 months (0.4-18.7) and 9.9 months (1.3-40.8), respectively. Median progression-free survival for the MVP and PE groups was 5.5 and 6.2 months (Log-rank, P = 0.82), and median overall survival was 10.2 and 9.4 months (Log-rank, P = 0.46), respectively. The main toxicity was myelosuppression. Grades 3-4 neutropenia was more common in women treated with PE than in women treated with MVP (74% vs 30%; P = 0.012), but the incidence of neutropenic sepsis, relative to the number of chemotherapy cycles, was low (7% overall). The toxicity-related hospitalisation rate was 1.2 admissions per six cycles of chemotherapy. No treatment-related deaths occurred. MVP and PE chemotherapy have modest activity and are safe in women with metastatic breast cancer. © 2005 The Royal College of Radiologists. Published by Elsevier Ltd. All rights reserved.

Prospective observational study of dementia and delirium in the acute hospital setting

Background: Dementia and delirium appear to be common among older patients admitted to acute hospitals, although there are few Australian data regarding these important conditions. Aim: The aim of this study was to determine the prevalence and incidence of dementia and delirium among older patients admitted to acute hospitals in Queensland and to profile these patients. Method: Prospective observational cohort study (n = 493) of patients aged 70 years and older admitted to general medical, general surgical and orthopaedic wards of four acute hospitals in Queensland between 2008 and 2010. Trained research nurses completed comprehensive geriatric assessments and obtained detailed information about each patient’s physical, cognitive and psychosocial functioning using the interRAI Acute Care and other standardised instruments. Nurses also visited patients daily to identify incident delirium. Two physicians independently reviewed patients’ medical records and assessments to establish the diagnosis of dementia and/or delirium. Results: Overall, 29.4% of patients (n = 145) were considered to have cognitive impairment, including 102 (20.7% of the total) who were considered to have dementia. This rate increased to 47.4% in the oldest patients (aged 90 years). The overall prevalence of delirium at admission was 9.7% (23.5% in patients with dementia), and the rate of incident delirium was 7.6% (14.7% in patients with dementia). Conclusion: The prevalence of dementia and delirium among older patients admitted to acute hospitals is high and is likely to increase with population aging. It is suggested that hospital design, staffing and processes should be attuned better to meet these patients’ needs.

Prospective observational study of dementia in older patients admitted to acute hospitals

Aim Few Australian studies have examined the impact of dementia on hospital outcomes. The aim of this study was to determine the relative contribution of dementia to adverse outcomes in older hospital patients. Method Prospective observational cohort study (n = 493) of patients aged ≥70 years admitted to four acute hospitals in Queensland. Trained research nurses completed comprehensive geriatric assessments using standardised instruments and collected data regarding adverse outcomes. The diagnosis of dementia was established by independent physician review of patients' medical records and assessments. Results Patients with dementia (n = 102, 20.7%) were significantly older (P = 0.01), had poorer functional ability (P < 0.01), and were more likely to have delirium at admission (P < 0.01) than patients without dementia. Dementia (odds ratio = 4.8, P < 0.001) increased the risk of developing delirium during the hospital stay. Conclusion Older patients with dementia are more impaired and vulnerable than patients without dementia and are at greater risk of adverse outcomes when hospitalised.

Nonrigid face alignment for unknown subject in video

Non-rigid face alignment is a very important task in a large range of applications but the existing tracking based non-rigid face alignment methods are either inaccurate or requiring person-specific model. This dissertation has developed simultaneous alignment algorithms that overcome these constraints and provide alignment with high accuracy, efficiency, robustness to varying image condition, and requirement of only generic model.

Consequences of introducing mandatory reporting legislation for child sexual abuse

To improve detection of child sexual abuse, many jurisdictions have enacted mandatory reporting laws requiring selected persons to report known and suspected cases. In Ireland, the Child First approach previously incorporated only a policy-based approach to reporting. Due to a perceived lack of efficacy, the Children First Bill was drafted in 2012 to shift this policy guidance to a legislative approach. What effects will the new legislative reporting duties have on numbers of reports, and outcomes of reports, of suspected child sexual abuse? This paper will shed light on these important questions by presenting results of analyses of the introduction of legislative reporting obligations in two Australian States. Three questions will be explored: 1. Does introducing reporting legislation result in enhanced detection of child sexual abuse? 2. Do different reporter groups have different patterns of reporting? 3. What do the patterns of report numbers and outcomes indicate for child protection systems and communities?

Non-invasive clinical measurement of the viscoelastic properties of tendon using acoustic wave transmission

Background. In isotropic materials, the speed of acoustic wave propagation is governed by the bulk modulus and density. For tendon, which is a structural composite of fluid and collagen, however, there is some anisotropy requiring an adjustment for Poisson's ratio. This paper explores these relationships using data collected, in vivo, on human Achilles tendon and then compares estimates of elastic modulus and hysteresis against published values from in vitro mechanical tests. Methods. Measurements using conventional B-model ultrasound imaging, inverse dynamics and acoustic transmission techniques were used to determine dimensions, loading conditions and longitudinal speed of sound in the Achilles tendon during a series of isometric plantar flexion exercises against body weight. Upper and lower bounds for speed of sound versus tensile stress in the tendon were then modelled and estimates of the elastic modulus and hysteresis of the Achilles tendon derived. Results. Axial speed of sound varied between 1850 and 2090 ms-1 with a non-linear, asymptotic dependency on the level of tensile stress (5-35 MPa) in the tendon. Estimates derived for the elastic modulus of the Achilles tendon ranged between 1-2 GPa. Hysteresis derived from models of the stress-strain relationship, ranged from 3-11%. Discussion. Estimates of elastic modulus agree closely with those previously reported from direct measurements obtained via mechanical tensile tests on major weight bearing tendons in vitro [1,2]. Hysteresis derived from models of the stress-strain relationship is consistent with direct measures from various mamalian tendon (7-10%) but is lower than previous estimates in human tendon (17-26%) [3]. This non-invasive method would appear suitable for monitoring changes in tendon properties during dynamic sporting activities.

Recovery of transverse strain in high–stress tendons following exercise

Background. This study evaluated the time course of recovery of transverse strain in the Achilles and patellar tendons following a bout of resistance exercise. Methods. Seventeen healthy adults underwent sonographic examination of the right patellar (n = 9) or Achilles (n = 8) tendons immediately prior to and following 90 repetitions of weight–bearing exercise. Quadriceps and gastrocnemius exercise were performed against an effective resistance of 175% and 250% body weight, respectively. Sagittal tendon thickness was determined 20 mm from the tendon enthesis and transverse strain was repeatedly monitored over a 24 hour recovery period. Results. Resistance exercise resulted in an immediate decrease in Achilles (t7 = 10.6, P<.01) and patellar (t8 = 8.9, P<.01) tendon thickness, resulting in an average transverse strain of 0.14 ± 0.04 and 0.18 ± 0.05. While the average strain was not significantly different between tendons, older age was associated with a reduced transverse strain response (r=0.63, P<.01). Recovery of transverse strain, in contrast, was prolonged compared with the duration of loading and exponential in nature. The mean primary recovery time was not significantly different between Achilles (6.5 ± 3.2 hours) and patellar (7.1 ± 3.2 hours) tendons and body weight accounted for 62% and 64% of the variation in recovery time, respectively. Discussion. Despite structural and biochemical differences between the Achilles and patellar tendons [1], the mechanisms underlying transverse creep–recovery in vivo appear similar and are highly time dependent. Primary recovery required about 7 hours in healthy tendons, with full recovery requiring up to 24 hours. These in vivo recovery times are similar to those reported for axial creep recovery of the vertebral disc in vitro [2], and may be used clinically to guide physical activity to rest ratios in healthy adults. Optimal ratios for high–stress tendons in clinical populations, however, remain unknown and require further attention in light of the knowledge gained in this study.

Percutaneous coronary intervention with drug-eluting stents or coronary artery bypass surgery in subjects with type 2 diabetes : evaluation of: Farkouth ME, Domanski M, Sleeper LA, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med 2012;367(25):2375-84, and Contini GA, Nicolini F, Fortuna D, et al. Five-year outcomes of surgical or percutaneous myocardial revascularization in diabetic patients. Int J Cardiol 2012. [Epub ahead of print]

There is debate as to whether percutaneous coronary intervention (PCI) with drug-eluting stents or coronary artery bypass surgery (CABG) is the best procedure for subjects with type 2 diabetes and coronary artery disease requiring revascularization. There is some evidence that following these procedures there is less further revascularization with CABG than PCI in subjects with diabetes. Two recent studies; the FREEDOM (Future Revascularization Evaluation in patients with Diabetes mellitus: Optimal Management of Multivessel Disease) trial, and a trial using a real world diabetic population from a Registry, have shown that the benefits of CABG over PCI in subjects with type 2 diabetes extends to lower rates of death and myocardial infarct, in addition to lower rates of revascularization. However, the rates of stroke may be higher with CABG than PCI with drug-eluting stents in this population. Thus, if CABG is going to be preferred to PCI in subjects with type 2 diabetes and multivessel coronary disease, consideration should be given to how to reduce the rates of stroke with CABG.

The roles of plant dsRNA-binding proteins in RNAi-like pathways

Dicers are associated with double-stranded RNA-binding proteins (dsRBPs) in animals. In the plant, Arabidopsis, there are four dicer-like (DCL) proteins and five potential dsRBPs. These DCLs act redundantly and hierarchically. However, we show there is little or no redundancy or hierarchy amongst the DRBs in their DCL interactions. DCL1 operates exclusively with DRB1 to produce micro (mi)RNAs, DCL4 operates exclusively with DRB4 to produce trans-acting (ta) siRNAs and 21nt siRNAs from viral RNA. DCL2 and DCL3 produce viral siRNAs without requiring assistance from any dsRBP. DRB2, DRB3 and DRB5 appear unnecessary for mi-, tasi-, viral si-, or heterochromatinising siRNA production but act redundantly in a developmental pathway. © 2008 Federation of European Biochemical Societies.

Dying feet in ICU : why might extracorporeal membrane oxygenation machines cause necrotic feet?

Background Extracorporeal membrane oxygenation (ECMO) is used for severe lung and/or heart failure in intensive care units (ICU). The Prince Charles Hospital (TPCH) has one of the largest ECMO units in Australia. Its use rapidly increased during the H1N1 (“swine flu”) pandemic and an increase in pedal complications resulted. The relationship between ECMO and pedal complications has been described, particularly in children, though no strong data exists. This paper presents a case series of foot complications in patients having received ECMO treatment. Methods We present nine cases of severe foot complications resulting from patients receiving ECMO treatment at TPCH in 2009–2012. Results Case ages ranged from 16 - 58 years and three were male. Six cases had an unremarkable medical history prior to H1N1 or H1N2 infection, one had Cardiomyopathy, one had received a lung transplant, and one had multi-organ failure post-sepsis. Common medications prescribed included vasopressors, antibiotics, and sedatives. All cases showed signs of markedly impaired peripheral perfusion whilst on ECMO and seven developed increasing areas of foot necrosis. Outcomes include two bilateral below knee amputations, two multiple digital amputations, one Reflex Sympathetic Dystrophy Syndrome, three pressure injuries, and three deaths. Conclusion Necrosis of the feet appears to occur more readily in younger people requiring ECMO treatment than others in ICU. The authors are conducting further studies to investigate associations between particular infections, medical history, medications, or machine techniques and severe foot complications. Some of these early results will also be presented at this conference.

Queensland diabetic foot hospitalisations (2005-10) : in what state is our foot hospital problem?

Background Diabetes foot complications are a leading cause of overall avoidable hospital admissions. Since 2006, the Queensland Diabetes Clinical Network has implemented programs aimed at reducing diabetes-related hospitalisation. The aim of this retrospective observational study was to determine the incidence of diabetes foot-related hospital admissions in Queensland from 2005 to 2010. Methods Data on all primary diabetes foot-related admissions in Queensland from 2005-2010 was obtained using diabetes foot-related ICD-10-AM (hospital discharge) codes. Queensland diabetes foot-related admission incidences were calculated using general population data from the Australian Bureau of Statistics. Furthermore, diabetes foot-related sub-group admissions were analysed. Chi-squared tests were used to assess changes in admissions over time. Results Overall, 24,917 diabetes foot-related admissions occurred, resulting in the use of 260,085 bed days or 1.4% of all available Queensland hospital bed days (18,352,152). The primary reasons for these admissions were foot ulcers (49.8%), cellulitis (20.7%), peripheral vascular disease (17.8%) and osteomyelitis (3.8%). The diabetes foot-related admission incidence among the general population (per 100,000) reduced by 22% (103.0 in 2005, to 80.7 in 2010, p < 0.001); bed days decreased by 18% (1,099 to 904, p < 0.001). Conclusion Diabetes foot complications appear to be the primary reason for 1.4 out of every 100 hospital beds used in Queensland. There has been a significant reduction in the incidence of diabetes foot-related admissions in Queensland between 2005 and 2010. This decrease has coincided with a corresponding decrease in amputations and the implementation of several diabetes foot clinical programs throughout Queensland.

Use and usefulnss of PDSs in the financial planning context

Following considerable criticism of the complexity and lack of readability of product disclosure statements (PDSs), regulatory changes were introduced requiring shorter PDSs for certain investment products. This paper reports the findings of an online survey of financial planners regarding use of managed investment scheme (MIS) PDSs with clients, the perceived usefulness of PDSs as an information source, and their views on shorter PDSs. Our findings highlight major concerns about the usefulness of the PDS and disclosure reforms.

Odometry-driven inference to link multiple exemplars of a location

A major challenge for robot localization and mapping systems is maintaining reliable operation in a changing environment. Vision-based systems in particular are susceptible to changes in illumination and weather, and the same location at another time of day may appear radically different to a system using a feature-based visual localization system. One approach for mapping changing environments is to create and maintain maps that contain multiple representations of each physical location in a topological framework or manifold. However, this requires the system to be able to correctly link two or more appearance representations to the same spatial location, even though the representations may appear quite dissimilar. This paper proposes a method of linking visual representations from the same location without requiring a visual match, thereby allowing vision-based localization systems to create multiple appearance representations of physical locations. The most likely position on the robot path is determined using particle filter methods based on dead reckoning data and recent visual loop closures. In order to avoid erroneous loop closures, the odometry-based inferences are only accepted when the inferred path's end point is confirmed as correct by the visual matching system. Algorithm performance is demonstrated using an indoor robot dataset and a large outdoor camera dataset.

A novel energy efficient controllable stiffness joint

Achieving energy efficient legged locomotion is an important goal for the future of robot mobility. This paper presents a novel joint for legged locomotion that is energy efficient for two reasons. The first reason is the configuration of the elastic elements and actuator which we show analytically has lower energy losses than the typical arrangement. The second is that the joint stiffness, and hence stance duration, is controllable without requiring any energy from the actuator. Further, the joint stiffness can be changed significantly during the flight phase, from zero to highly rigid. Results obtained from a prototype hopper, demonstrate that the joint allows continuous and peak hopping via torque control. The results also demonstrate that the hopping frequency can be varied between 2.2Hz and 4.6Hz with associated stance duration of between 0.35 and 0.15 seconds.

Training-free probability models for whole-image based place recognition

Whole-image descriptors such as GIST have been used successfully for persistent place recognition when combined with temporal filtering or sequential filtering techniques. However, whole-image descriptor localization systems often apply a heuristic rather than a probabilistic approach to place recognition, requiring substantial environmental-specific tuning prior to deployment. In this paper we present a novel online solution that uses statistical approaches to calculate place recognition likelihoods for whole-image descriptors, without requiring either environmental tuning or pre-training. Using a real world benchmark dataset, we show that this method creates distributions appropriate to a specific environment in an online manner. Our method performs comparably to FAB-MAP in raw place recognition performance, and integrates into a state of the art probabilistic mapping system to provide superior performance to whole-image methods that are not based on true probability distributions. The method provides a principled means for combining the powerful change-invariant properties of whole-image descriptors with probabilistic back-end mapping systems without the need for prior training or system tuning.