Toxicity profile of the immunomodulatory thalidomide analogue, lenalidomide : Phase I clinical trial of three dosing schedules in patients with solid malignancies

Thalidomide is an anti-angiogenic agent currently used to treat patients with malignant cachexia or multiple myeloma. Lenalidomide (CC-5013) is an immunomodulatory thalidomide analogue licensed in the United States of America (USA) for the treatment of a subtype of myelodysplastic syndrome. This two-centre, open-label phase I study evaluated dose-limiting toxicities in 55 patients with malignant solid tumours refractory to standard chemotherapies. Lenalidomide capsules were consumed once daily for 12 weeks according to one of the following three schedules: (I) 25 mg daily for the first 7 d, the daily dose increased by 25 mg each week up to a maximum daily dose of 150 mg; (II) 25 mg daily for 21 d followed by a 7-d rest period, the 4-week cycle repeated for 3 cycles; (III) 10 mg daily continuously. Twenty-six patients completed the study period. Two patients experienced a grade 3 hypersensitivity rash. Four patients in cohort I and 4 patients in cohort II suffered grade 3 or 4 neutropaenia. In 2 patients with predisposing medical factors, grade 3 cardiac dysrhythmia was recorded. Grade 1 neurotoxicity was detected in 6 patients. One complete and two partial radiological responses were measured by computed tomography scanning; 8 patients had stable disease after 12 weeks of treatment. Fifteen patients remained on treatment as named patients; 1 with metastatic melanoma remains in clinical remission 3.5 years from trial entry. This study indicates the tolerability and potential clinical efficacy of lenalidomide in patients with advanced solid tumours who have previously received multi-modality treatment. Depending on the extent of myelosuppressive pre-treatment, dose schedules (II) or (III) are advocated for large-scale trials of long-term administration. © 2006 Elsevier Ltd. All rights reserved.

Pitfalls in the use of kappa when interpreting agreement between multiple raters in reliability studies

OBJECTIVE To compare different reliability coefficients (exact agreement, and variations of the kappa (generalised, Cohen's and Prevalence Adjusted and Biased Adjusted (PABAK))) for four physiotherapists conducting visual assessments of scapulae. DESIGN Inter-therapist reliability study. SETTING Research laboratory. PARTICIPANTS 30 individuals with no history of neck or shoulder pain were recruited with no obvious significant postural abnormalities. MAIN OUTCOME MEASURES Ratings of scapular posture were recorded in multiple biomechanical planes under four test conditions (at rest, and while under three isometric conditions) by four physiotherapists. RESULTS The magnitude of discrepancy between the two therapist pairs was 0.04 to 0.76 for Cohen's kappa, and 0.00 to 0.86 for PABAK. In comparison, the generalised kappa provided a score between the two paired kappa coefficients. The difference between mean generalised kappa coefficients and mean Cohen's kappa (0.02) and between mean generalised kappa and PABAK (0.02) were negligible, but the magnitude of difference between the generalised kappa and paired kappa within each plane and condition was substantial; 0.02 to 0.57 for Cohen's kappa and 0.02 to 0.63 for PABAK, respectively. CONCLUSIONS Calculating coefficients for therapist pairs alone may result in inconsistent findings. In contrast, the generalised kappa provided a coefficient close to the mean of the paired kappa coefficients. These findings support an assertion that generalised kappa may lead to a better representation of reliability between three or more raters and that reliability studies only calculating agreement between two raters should be interpreted with caution. However, generalised kappa may mask more extreme cases of agreement (or disagreement) that paired comparisons may reveal.

Tissue viability imaging of skin microcirculation following exposure to whole body cryotherapy (-110°C) and cold water immersion (8°C)

Cryotherapy is currently used in various clinical, rehabilitative, and sporting settings. However, very little is known regarding the impact of cooling on the microcirculatory response. Objectives: The present study sought to examine the influence of two commonly employed modalities of cryotherapy, whole body cryotherapy (WBC; -110°C) and cold water immersion(CWI; 8±1°C), on skin microcirculation in the mid- thigh region. Methods: The skin area examined was a 3 × 3 cm located between the most anterior aspect of the inguinal fold and the patella. Following 10 minutes of rest, 5 healthy, active males were exposed to either WBC for 3 minutes or CWI for 5 minutes in a randomised order. Volunteers lay supine for five minutes after treatment, in order to monitor the variation of red blood cell (RBC) concentration in the region of interest for a duration of 40 minutes. Microcirculation response was assessed using a non-invasive, portable instrument known as a Tissue Viability imaging system. After a minimum of seven days, the protocol was repeated. Subjective assessment of the volunteer’s thermal comfort and thermal sensation was also recorded. Results: RBC was altered following exposure to both WBC and CWI but appeared to stabilise approximately 35 minutes after treatments. Both WBC and CWI affected thermal sensation (p < 0.05); however no betweengroup differences in thermal comfort or sensation were recorded (p > 0.05). Conclusions: As both WBC and CWI altered RBC, further study is necessary to examine the mechanism for this alteration during whole body cooling.

Pupil shape as viewed along the horizontal visual field

Purpose: Changes in pupil size and shape are relevant for peripheral imagery by affecting aberrations and how much light enters and/or exits the eye. The purpose of this study is to model the pattern of pupil shape across the complete horizontal visual field and to show how the pattern is influenced by refractive error. Methods: Right eyes of thirty participants were dilated with 1% cyclopentolate and images were captured using a modified COAS-HD aberrometer alignment camera along the horizontal visual field to ±90°. A two lens relay system enabled fixation at targets mounted on the wall 3m from the eye. Participants placed their heads on a rotatable chin rest and eye rotations were kept to less than 30°. Best-fit elliptical dimensions of pupils were determined. Ratios of minimum to maximum axis diameters were plotted against visual field angle. Results: Participants’ data were well fitted by cosine functions, with maxima at (–)1° to (–)9° in the temporal visual field and widths 9% to 15% greater than predicted by the cosine of the field angle . Mean functions were 0.99cos[( + 5.3)/1.121], R2 0.99 for the whole group and 0.99cos[( + 6.2)/1.126], R2 0.99 for the 13 emmetropes. The function peak became less temporal, and the width became smaller, with increase in myopia. Conclusion: Off-axis pupil shape changes are well described by a cosine function which is both decentered by a few degrees and flatter by about 12% than the cosine of the viewing angle, with minor influences of refraction.

Literature review : use of respite by carers of people with dementia

Respite care is a cornerstone service for the home management of people with dementia. It is used by carers to mitigate the stress related to the demands of caring by allowing time for them to rest and do things for themselves, thus maintaining the caring relationship at home and perhaps forestalling long-term placement in a residential aged care facility. Despite numerous anecdotal reports in support of respite care, its uptake by carers of people with dementia remains relatively low. The aim of this paper was to examine the factors that constitute the use of respite by carers of people with dementia by reviewing quantitative and qualitative research predominantly from the years 1990 to 2012. Seventysix international studies of different types of respite care were included for this review and their methods were critically appraised. The key topics identified were in relation to information access, the barriers to carers realising need for and seeking respite, satisfaction with respite services including the outcomes for carers and people with dementia, the characteristics of an effective respite service and the role of health workers in providing appropriate respite care. Finally, limitations with considering the literature as a whole were highlighted and recommendations made for future research.

Chinese fashion designers in Shanghai : identifying a fresh perspective about their role in the world order of fashion

Shanghai possesses an apt legacy, once referred to as “Paris of the East”. Municipal aspirations for Shanghai to assume a position among the great fashion cities of the world have been integrated in the recent re-shaping of this modern city into a role model for Chinese creative enterprise yet China is still known primarily as centre of clothing production. Increasingly however, “Made in China” is being replaced by “Created in China” drawing attention to two distinct consumer markets for Chinese designers. Fashion designers who have entered the global fashion system for education or by showing their collections have generally adopted a design aesthetic that aligns with Western markets, allowing little competitive advantage. In contrast, Chinese designers who rest their attention on the domestic Chinese market find a disparate, highly competitive marketplace. The pillars of authenticity that for foreign fashion brands extend far into their cultural and creative histories, often for many decades in the case of Louis Vuitton, Hermes and Christian Dior do not yet exist in China in this era of rapid globalisation. Here, the cultural bedrock allows these same pillars to extend only thirty years or so into the past reaching the moments when Deng Xiaoping granted China’s creative entrepreneurs passage. To this end, interviews with fashion designers in Shanghai have been undertaken during the last twelve months for a PhD dissertation. Production of culture theory has been used to identify working methods, practices of production and the social and cultural milieu necessary for designers to achieve viability.

A Literature Review of Wellness, Wellbeing and Quality of Life Issues as they impact upon the Australian Mining Sector

Australia’s mining boom Global demand for minerals and energy products has fuelled Australia’s recent resources boom and has led to the rapid expansion of mining projects not only in remote locations but increasingly in settled traditionally agricultural rural areas. A fundamental shift has also occurred in the provisioning of skilled and semi-skilled workers. The huge acceleration in industry demand for labour has been accompanied by the entrenchment of workforce arrangements largely dependent on fly-in, fly-out (FIFO) and drive–in, drive–out (DIDO) non-resident workers (NRWs). While NRWs are working away from their homes, they are usually accommodated in work camps or ‘villages’ for the duration of their work cycle which are normally comprised of many consecutive days of 12-hour day- and night-shifts. The health effects of this form of employment and the accompanying lifestyle is increasingly becoming contentious. Impacts on personal wellness, wellbeing and quality of life essentially remain under-researched and thus misunderstood. Sodexo in Australia Sodexo began operations in Australia in 1982, and has since become a leader in providing Quality of Life (QOL) services to businesses across the country. The 6,000 Australian employees are part of a global Sodexo team of 413,000 people. Sodexo in Australia designs, delivers and manages on-site their QOL services at 320 diverse site locations, including remote sites. Sodexo operates in a range of sectors, including the mining industry. Service plans are tailored to suit the individual needs of organisations. Sodexo Remote Sites has previously conducted unpublished research among mining workers in Australia. The results highlighted needs and expectations of Australian mining workers. Main insights about workers’ requirements were directed towards: • contacts with closest; • warm rest time around proper and varied meals; • additional services to help them better enjoy their life onsite and/or make the most of it; • organise their transportation; • promote community living; and • finding balance between professional and personal life. The brief for this current research is aimed at building upon this knowledge. Research brief Expectations for quality of life and wellness and wellbeing services are increasing dramatically. It's getting costlier and more difficult to retain valuable employees. This is particularly the case in the Australian mining sector. Given the level of interest in ensuring healthy workplaces in Australia, Sodexo has commissioned QUT to conduct a literature review. The objectives as specified by Sodexo are: Objective 1: To define the concepts of wellness and wellbeing and quality of life in Australia Objective 2: To examine how wellness and wellbeing are developed within organisations in Australia and how they impact on employee and organizational performance. More specifically, to review the literature that could be sourced about: • challenges of the mining environment; • the mining lifestyle – implications for health, wellness and daily life; • personal health and wellness of Australian mining workers; • factors affecting health in mines and perceived support for health and wellness; and • the impact of employer investment in health on perceptions and behaviour of employees. Objective 3: To determine what impact employee wellness and well-being has on the performance of mining workers. More specifically, to review the literature that could be sourced about: • impact of obesity, alcohol, tobacco use on companies; and • links between employee engagement and satisfaction and company productivity. Accordingly this review has attempted to ascertain what factors an organisation should focus on in order to reduce absenteeism and turnover and increase commitment, satisfaction, safety and productivity, with specific reference to the mining industry in Australia. The structure of the report aligns with the stated objectives in that each of the first three parts address an objective. Part IV summarises prominent issues that have arisen and offers some concluding observations and comments.

Learning routines used by firms during construction of infrastructure projects using the alliance procurement method

Collaborative contracting has emerged over the past 15 years as an innovative project delivery framework that is particularly suited to infrastructure projects. Australia leads the world in the development of project and program alliance approaches to collaborative delivery. These approaches are considered to promise superior project results. However, very little is known about the learning routines that are most widely used in support of collaborative projects in general and alliance projects in particular. The literature on absorptive capacity and dynamic capabilities indicates that such learning enhances project performance. The learning routines employed at corporate level during the operation of collaborative infrastructure projects in Australia were examined through a large survey conducted in 2013. This paper presents a descriptive summary of the preliminary findings. The survey captured the experiences of 320 practitioners of collaborative construction projects, including public and private sector clients, contractors, consultants and suppliers (three per cent of projects were located in New Zealand, but for brevity’s sake the sample is referred to as Australian). The majority of projects identified used alliances (78.6%); whilst 9% used Early Contractor Involvement (ECI) contracts and 2.7% used Early Tender Involvement contracts, which are ‘slimmer’ types of collaborative contract. The remaining 9.7% of respondents used traditional contracts that employed some collaborative elements. The majority of projects were delivered for public sector clients (86.3%), and/or clients experienced with asset procurement (89.6%). All of the projects delivered infrastructure assets; one third in the road sector, one third in the water sector, one fifth in the rail sector, and the rest spread across energy, building and mining. Learning routines were explored within three interconnected phases: knowledge exploration, transformation and exploitation. The results show that explorative and exploitative learning routines were applied to a similar extent. Transformative routines were applied to a relatively low extent. It was also found that the most highly applied routine is ‘regularly applying new knowledge to collaborative projects’; and the least popular routine was ‘staff incentives to encourage information sharing about collaborative projects’. Future research planned by the authors will examine the impact of these routines on project performance.

Alcohol ingestion impairs maximal post-exercise rates of myofibrillar protein synthesis following a single bout of concurrent training

Introduction The culture in many team sports involves consumption of large amounts of alcohol after training/competition. The effect of such a practice on recovery processes underlying protein turnover in human skeletal muscle are unknown. We determined the effect of alcohol intake on rates of myofibrillar protein synthesis (MPS) following strenuous exercise with carbohydrate (CHO) or protein ingestion. Methods In a randomized cross-over design, 8 physically active males completed three experimental trials comprising resistance exercise (8×5 reps leg extension, 80% 1 repetition maximum) followed by continuous (30 min, 63% peak power output (PPO)) and high intensity interval (10×30 s, 110% PPO) cycling. Immediately, and 4 h post-exercise, subjects consumed either 500 mL of whey protein (25 g; PRO), alcohol (1.5 g·kg body mass−1, 12±2 standard drinks) co-ingested with protein (ALC-PRO), or an energy-matched quantity of carbohydrate also with alcohol (25 g maltodextrin; ALC-CHO). Subjects also consumed a CHO meal (1.5 g CHO·kg body mass−1) 2 h post-exercise. Muscle biopsies were taken at rest, 2 and 8 h post-exercise. Results Blood alcohol concentration was elevated above baseline with ALC-CHO and ALC-PRO throughout recovery (P<0.05). Phosphorylation of mTORSer2448 2 h after exercise was higher with PRO compared to ALC-PRO and ALC-CHO (P<0.05), while p70S6K phosphorylation was higher 2 h post-exercise with ALC-PRO and PRO compared to ALC-CHO (P<0.05). Rates of MPS increased above rest for all conditions (~29–109%, P<0.05). However, compared to PRO, there was a hierarchical reduction in MPS with ALC-PRO (24%, P<0.05) and with ALC-CHO (37%, P<0.05). Conclusion We provide novel data demonstrating that alcohol consumption reduces rates of MPS following a bout of concurrent exercise, even when co-ingested with protein. We conclude that alcohol ingestion suppresses the anabolic response in skeletal muscle and may therefore impair recovery and adaptation to training and/or subsequent performance.

Effect of exercise training on skeletal muscle cytokine expression in the elderly

Aging is associated with increased circulating pro-inflammatory and lower anti-inflammatory cytokines. Exercise training, in addition to improving muscle function, reduces these circulating pro-inflammatory cytokines. Yet, few studies have evaluated changes in the expression of cytokines within skeletal muscle after exercise training. The aim of the current study was to examine the expression of cytokines both at rest and following a bout of isokinetic exercise performed before and after 12 weeks of resistance exercise training in young (n = 8, 20.3 ± 0.8 yr) and elderly men (n = 8, 66.9 ± 1.6 yr). Protein expression of various cytokines was determined in muscle homogenates. The expression of MCP-1, IL-8 and IL-6 (which are traditionally classified as ‘pro-inflammatory’) increased substantially after acute exercise. By contrast, the expression of the anti-inflammatory cytokines IL-4, IL-10 and IL-13 increased only slightly (or not at all) after acute exercise. These responses were not significantly different between young and elderly men, either before or after 12 weeks of exercise training. However, compared with the young men, the expression of pro-inflammatory cytokines 2 h post exercise tended to be greater in the elderly men prior to training. Training attenuated this difference. These data suggest that the inflammatory response to unaccustomed exercise increases with age. Furthermore, regular exercise training may help to normalize this inflammatory response, which could have important implications for muscle regeneration and adaptation in the elderly.

The pre-socialization of future journalists

While the role of university journalism education in the professionalization of journalists has been extensively debated, systematic and comparative studies of journalism students are still scarce. This paper reports the findings from a comparative study of journalism students in seven countries: Australia, Brazil, Chile, Mexico, Spain, Switzerland, and the United States. The data show a number of similarities, but also important differences between pre-professional cultures in journalism around the world. The findings are in line with recent conceptualizations of media systems, although some variations and particularities are observed at the country level. While students in all countries reject a loyal approach and favor a citizen-oriented role, they also do so to different extents. Brazilian and Chilean students believe in the citizen-oriented and watchdog roles, whereas their counterparts in Australia, Switzerland, and the United States favor the consumer-oriented approach to a greater extent. Mexican and Spanish students, on the other hand, while supporting the citizen-oriented role, reject the loyal role comparatively less than the rest of the countries.

National curriculum reform and equipping pre-service teachers to teach about Australia in the Asian Century

Currently a range of national policy settings are reshaping schooling and teacher education in Australia. This paper presents some of the findings from a small qualitative pilot study conducted with a group of final year pre-service teachers studying a secondary social science curriculum method unit in an Australian university. One of the study’s research objectives aimed at identifying how students reflected on their capacity to navigate curriculum change and, more specifically, on teaching about Australia and Asia in the forthcoming implementation of the first national history curriculum. The unit was designed and taught by the researcher on the assumption that beginning social science teachers need to be empowered to deal with the curriculum change they’ll encounter throughout their careers. The pilot study’s methodology was informed by a constructivist approach to grounded theory and its scope was limited to one semester with volunteer students. Of the pre-service teacher reflections on their preparedness to teach, this paper reports on the content, pedagogy and learning they experienced in one segment of the unit with specific reference to the new history curriculum’s ‘Australia in a world history’ approach and the development of Asia literacy. The findings indicate that whilst pre-service teachers valued the opportunity to engage with learning experiences which enhanced their intercultural understanding and extended their pedagogical and content knowledge on campus, the nature of the final practicum in schools was also influential in shaping their preparedness to enter the profession.

Statutory right of user - its impact in practice?

Scenario 1 A buys a two storey commercial building built along the only street frontage to the property. Vehicles cannot reach the rear of the property as the building extends across the entire width of the land. A bought the building with full knowledge that vehicular access to the rest of the property had been compromised by a desire to obtain maximum street frontage for the building which was occupied by a commercial tenant. On street parking is scarce in the surrounding area. A (to the knowledge of the adjoining owner B) constructs a carpark at the rear of the building. The employees of A’s tenant have been using the carpark obtaining access via a driveway on B’s land. To formalise this arrangement, A seeks a right of way for vehicles to travel down B’s driveway to access the carpark...

Police officer in-vehicle discomfort : appointments carriage method and vehicle seat features

Musculoskeletal pain is commonly reported by police officers. A potential cause of officer discomfort is a mismatch between vehicle seats and the method used for carrying appointments. Twenty-five police officers rated their discomfort while seated in: (1) a standard police vehicle seat, and (2) a vehicle seat custom-designed for police use. Discomfort was recorded in both seats while wearing police appointments on: (1) a traditional appointments belt, and (2) a load-bearing vest / belt combination (LBV). Sitting in the standard vehicle seat and carrying appointments on a traditional appointments belt were both associated with significantly elevated discomfort. Four vehicle seat features were most implicated as contributing to discomfort: back rest bolster prominence; lumbar region support; seat cushion width; and seat cushion bolster depth. Authorising the carriage of appointments using a LBV is a lower cost solution with potential to reduce officer discomfort. Furthermore, the introduction of custom-designed vehicle seats should be considered.

Pore size distribution and accessible pore size distribution in bituminous coals

The porosity and pore size distribution of coals determine many of their properties, from gas release to their behavior on carbonization, and yet most methods of determining pore size distribution can only examine a restricted size range. Even then, only accessible pores can be investigated with these methods. Small-angle neutron scattering (SANS) and ultra small-angle neutron scattering (USANS) are increasingly used to characterize the size distribution of all of the pores non-destructively. Here we have used USANS/SANS to examine 24 well-characterized bituminous and subbituminous coals: three from the eastern US, two from Poland, one from New Zealand and the rest from the Sydney and Bowen Basins in Eastern Australia, and determined the relationships of the scattering intensity corresponding to different pore sizes with other coal properties. The range of pore radii examinable with these techniques is 2.5nm to 7μm. We confirm that there is a wide range of pore sizes in coal. The pore size distribution was found to be strongly affected by both rank and type (expressed as either hydrogen or vitrinite content) in the size range 250nm to 7μm and 5 to 10nm, but weakly in intermediate regions. The results suggest that different mechanisms control coal porosity on different scales. Contrast-matching USANS and SANS were also used to determine the size distribution of the fraction of the pores in these coals that are inaccessible to deuterated methane, CD4, at ambient temperature. In some coals most of the small (~10nm) pores were found to be inaccessible to CD4 on the time scale of the measurement (~30min–16h). This inaccessibility suggests that in these coals a considerable fraction of inherent methane may be trapped for extended periods of time, thus reducing the effectiveness of methane release from (or sorption by) these coals. Although the number of small pores was less in higher rank coals, the fraction of total pores that was inaccessible was not rank dependent. In the Australian coals, at the 10nm to 50nm size scales the pores in inertinites appeared to be completely accessible to CD4, whereas the pores in the vitrinite were about 75% inaccessible. Unlike the results for total porosity that showed no regional effects on relationships between porosity and coal properties, clear regional differences in the relationships between fraction of closed porosity and coal properties were found. The 10 to 50nm-sized pores of inertinites of the US and Polish coals examined appeared less accessible to methane than those of the inertinites of Australian coals. This difference in pore accessibility in inertinites may explain why empirical relationships between fluidity and coking properties developed using Carboniferous coals do not apply to Australian coals.