The willingness of women to participate in a long-term trial of hormone replacement therapy : A qualitative study using focus groups.

The actual proportion of eligible people who participate in clinical trials is low. Consequently, a qualitative study of the willingness of women who are postmenopausal to participate in a long-term randomized control trial of hormone replacement therapy (HRT) designed to investigate the prevention of degenerative diseases was conducted. Focus group methodology was employed to explore the personal and social aspects of decision making about trial participation. Participants were randomly selected from the patient age-sex registers of four University of Adelaide general practices. Twenty-one women participated in four focus groups. The reasons for and against trial participation were examined using qualitative content analysis; ( n = 18) women were unwilling to participate in the trial. The lack of perceived individual benefit, minimal altruism, the risk of breast cancer and side effects, not wanting to take unnecessary medication, a ten-year commitment, and negative experiences of HRT use, were the main reasons given for not entering the trial. Of the few women ( n = 3) who clearly would enter the trial, free prescriptions and a positive history of using HRT were the main reasons for participation. The perceived disadvantages of clinical trials of HRT deter women from participating in a long-term clinical trial of HRT. An investment in education and information to eligible participants about both the risks and potential benefits of HRT may improve trial recruitment.

Cold-formed steel columns subject to local buckling at elevated temperatures

Fire safety design of building structures has received greater attention in recent times due to continuing losses of properties and lives in fires. However, the structural behaviour of thin-walled cold-formed steel columns under fire conditions is not well understood despite the increasing use of light gauge steels in building construction. Cold-formed steel columns are often subject to local buckling effects. Therefore a series of laboratory tests of lipped and unlipped channel columns made of varying steel thicknesses and grades was undertaken at uniform elevated temperatures up to 700°C under steady state conditions. Finite element models of the tested columns were also developed, and their elastic buckling and nonlinear analysis results were compared with test results at elevated temperatures. Effects of the degradation of mechanical properties of steel with temperature were included in the finite element analyses. The use of accurately measured yield stress, elasticity modulus and stress-strain curves at elevated temperatures provided a good comparison of the ultimate loads and load-deflection curves from tests and finite element analyses. The commonly used effective width design rules and the direct strength method at ambient temperature were then used to predict the ultimate loads at elevated temperatures by using the reduced mechanical properties. By comparing these predicted ultimate loads with those from tests and finite element analyses, the accuracy of using this design approach was evaluated.

Experimental study of load bearing cold-formed steel wall systems under fire conditions

Light Gauge Steel Framing (LSF) walls made of cold-formed and thin-walled steel lipped channel studs with plasterboard linings on both sides are commonly used in commercial, industrial and residential buildings. However, there is limited data about their structural and thermal performance under fire conditions while past research showed contradicting results about the benefits of using cavity insulation. A new composite wall panel was recently proposed to improve the fire resistance rating of LSF walls, where an insulation layer was used externally between the plasterboards on both sides of the wall frame instead of using it in the cavity. In this research 11 full scale tests were conducted on conventional load bearing steel stud walls with and without cavity insulation, and the new composite panel system to study their thermal and structural performance under standard fire conditions. These tests showed that the use of cavity insulation led to inferior fire performance of walls, and provided supporting research data. They demonstrated that the use of insulation externally in a composite panel enhanced the thermal and structural performance of LSF walls and increased their fire resistance rating. This paper presents the details of the LSF wall tests and the thermal and structural performance data and fire resistance rating of load-bearing wall assemblies lined with varying plasterboard-insulation configurations under two different load ratios. Fire test results including the time–temperature and deflection profiles are presented along with the failure times and modes.

Finite element modelling of load bearing cold-formed steel wall systems under fire conditions

Light Gauge Steel Framing (LSF) walls are made of cold-formed, thin-walled steel lipped channel studs with plasterboard linings on both sides. However, these thin-walled steel sections heat up quickly and lose their strength under fire conditions despite the protection provided by plasterboards. A new composite wall panel was recently proposed to improve the fire resistance rating of LSF walls, where an insulation layer was used externally between the plasterboards on both sides of the wall frame instead of using it in the cavity. A research study using both fire tests and numerical studies was undertaken to investigate the structural and thermal behaviour of load bearing LSF walls made of both conventional and the new composite panels under standard fire conditions and to determine their fire resistance rating. This paper presents the details of finite element models of LSF wall studs developed to simulate the structural performance of LSF wall panels under standard fire conditions. Finite element analyses were conducted under both steady and transient state conditions using the time-temperature profiles measured during the fire tests. The developed models were validated using the fire test results of 11 LSF wall panels with various plasterboard/insulation configurations and load ratios. They were able to predict the fire resistance rating within five minutes. The use of accurate numerical models allowed the inclusion of various complex structural and thermal effects such as local buckling, thermal bowing and neutral axis shift that occurred in thin-walled steel studs under non-uniform elevated temperature conditions. Finite element analyses also demonstrated the improvements offered by the new composite panel system over the conventional cavity insulated system.

Review of current fire design rules for cold-formed steel wall systems

Light gauge steel frame wall systems are commonly used in industrial and commercial buildings, and there is a need for simple fire design rules to predict their load capacities and fire resistance ratings. During fire events, the light gauge steel frame wall studs are subjected to non-uniform temperature distributions that cause thermal bowing, neutral axis shift and magnification effects and thus resulting in a combined axial compression and bending action on the studs. In this research, a series of full-scale fire tests was conducted first to evaluate the performance of light gauge steel frame wall systems with eight different wall configurations under standard fire conditions. Finite element models of light gauge steel frame walls were then developed, analysed under transient and steady-state conditions and validated using full-scale fire tests. Using the results from fire tests and finite element analyses, a detailed investigation was undertaken into the prediction of axial compression strength and failure times of light gauge steel frame wall studs in standard fires using the available fire design rules based on Australian, American and European standards. The results from both fire tests and finite element analyses were used to investigate the ability of these fire design rules to include the complex effects of non-uniform temperature distributions and their accuracy in predicting the axial compression strength of wall studs and the failure times. Suitable modifications were then proposed to the fire design rules. This article presents the details of this investigation on the fire design rules of light gauge steel frame walls and the results.

Development of improved fire design rules for cold-formed steel wall systems

Traditionally the fire resistance rating of LSF wall systems is based on approximate prescriptive methods developed using limited fire tests. Therefore a detailed research study into the performance of load bearing LSF wall systems under standard fire conditions was undertaken to develop improved fire design rules. It used the extensive fire performance results of eight different LSF wall systems from a series of full scale fire tests and numerical studies for this purpose. The use of previous fire design rules developed for LSF walls subjected to non-uniform elevated temperature distributions based on AISI design manual and Eurocode3 Parts 1.2 and 1.3 was investigated first. New simplified fire design rules based on AS/NZS 4600, North American Specification and Eurocode 3 Part 1.3 were then proposed in this study with suitable allowances for the interaction effects of compression and bending actions. The importance of considering thermal bowing, magnified thermal bowing and neutral axis shift in the fire design was also investigated. A spread sheet based design tool was developed based on the new design rules to predict the failure load ratio versus time and temperature curves for varying LSF wall configurations. The accuracy of the proposed design rules was verified using the test and FEA results for different wall configurations, steel grades, thicknesses and load ratios. This paper presents the details and results of this study including the improved fire design rules for predicting the load capacity of LSF wall studs and the failure times of LSF walls under standard fire conditions.

Improved design rules for cold-formed steel columns

Current design rules for determining the member strength of cold-formed steel columns are based on the effective length of the member and a single column capacity curve for both pin-ended and fixed-ended columns. This research has reviewed the use of AS/NZS 4600 design rules for their accuracy in determining the member compression capacities of slender cold-formed steel columns using detailed numerical studies. It has shown that AS/NZS 4600 design rules accurately predicted the capacities of pinned and fixed ended columns undergoing flexural buckling. However, for fixed ended columns undergoing flexural-torsional buckling, it was found that current AS/NZS 4600 design rules did not include the beneficial effect of warping fixity. Therefore AS/NZS 4600 design rules were found to be excessively conservative and hence uneconomical in predicting the failure loads obtained from tests and finite element analyses of fixed-ended lipped channel columns. Based on this finding, suitable recommendations have been made to modify the current AS/NZS 4600 design rules to more accurately reflect the results obtained from the numerical and experimental studies conducted in this research. This paper presents the details of this research on cold-formed steel columns and the results.

Improved design rules for fixed ended cold-formed steel columns subject to flexural-torsional buckling

This paper has presented the details of an investigation into the flexural and flexuraltorsional buckling behaviour of cold-formed structural steel columns with pinned and fixed ends. Current design rules for the member capacities of cold-formed steel columns are based on the same non-dimensional strength curve for both fixed and pinned-ended columns. This research has reviewed the accuracy of the current design rules in AS/NZS 4600 and the North American Specification in determining the member capacities of cold-formed steel columns using the results from detailed finite element analyses and an experimental study of lipped channel columns. It was found that the current Australian and American design rules accurately predicted the member capacities of pin ended lipped channel columns undergoing flexural and flexural torsional buckling. However, for fixed ended columns with warping fixity undergoing flexural-torsional buckling, it was found that the current design rules significantly underestimated the column capacities as they disregard the beneficial effect of warping fixity. This paper has therefore proposed improved design rules and verified their accuracy using finite element analysis and test results of cold-formed lipped channel columns made of three cross-sections and five different steel grades and thicknesses.

Thermal performance of load bearing cold-formed steel walls under fire conditions using numerical studies

Cold–formed Light gauge Steel Frame (LSF) wall systems are increasingly used in low-rise and multi-storey buildings and hence their fire safety has become important in the design of buildings. A composite LSF wall panel system was developed recently, where a thin insulation was sandwiched between two plasterboards to improve the fire performance of LSF walls. Many experimental and numerical studies have been undertaken to investigate the fire performance of non-load bearing LSF wall under standard conditions. However, only limited research has been undertaken to investigate the fire performance of load bearing LSF walls under standard and realistic design fire conditions. Therefore in this research, finite element thermal models of both the conventional load bearing LSF wall panels with cavity insulation and the innovative LSF composite wall panel were developed to simulate their thermal behaviour under standard and realistic design fire conditions. Suitable thermal properties were proposed for plasterboards and insulations based on laboratory tests and available literature. The developed models were then validated by comparing their results with available fire test results of load bearing LSF wall. This paper presents the details of the developed finite element models of load bearing LSF wall panels and the thermal analysis results. It shows that finite element models can be used to simulate the thermal behaviour of load bearing LSF walls with varying configurations of insulations and plasterboards. Failure times of load bearing LSF walls were also predicted based on the results from finite element thermal analyses. Finite element analysis results show that the use of cavity insulation was detrimental to the fire rating of LSF walls while the use of external insulation offered superior thermal protection to them. Effects of realistic design fire conditions are also presented in this paper.

Effects of whole body cryotherapy and cold water immersion on knee skin temperature

This study sought to a) compare and contrast the effect of 2 commonly used cryotherapy treatments, 4 min of − 110 °C whole body cryotherapy and 8 °C cold water immersion, on knee skin temperature and b) establish whether either protocol was capable of achieving a skin temperature ( < 13 °C) believed to be required for analgesic purposes. After ethics committee approval and written informed consent was obtained, 10 healthy males (26.5 ± 4.9 yr, 183.5 ± 6.0 cm, 90.7 ± 19.9 kg, 26.8 ± 5.0 kg/m 2 , 23.0 ± 9.3 % body fat; mean ± SD) participated in this randomised controlled crossover study. Skin temperature around the patellar region was assessed in both knees via non-contact, infrared thermal imaging and recorded pre-, immediately post-treatment and every 10 min thereafter for 60 min. Compared to baseline, average, minimum and maximum skin temperatures were significantly reduced (p < 0.001) immediately post-treatment and at 10, 20, 30, 40, 50 and 60 min after both cooling modalities. Average and minimum skin temperatures were lower (p < 0.05) immediately after whole body cryotherapy (19.0 ± 0.9 ° C) compared to cold water immersion (20.5 ± 0.6 ° C). However, from 10 to 60 min post, the average, minimum and maximum skin temperatures were lower (p < 0.05) following the cold water treatment. Finally, neither protocol achieved a skin temperature believed to be required to elicit an analgesic effect.

Serine protease inhibition and mitochondrial dysfunction associated with cisplatin resistance in human tumor cell lines: targets for therapy

Indicators of mitochondrial function were studied in two different cell culture models of cis-diamminedichloroplatinum-II (CDDP) resistance: the intrinsically resistant human ovarian cancer cell line CI-80-13S, and resistant clones (HeLa-S1a and HeLa-S1b) generated by stable expression of the serine protease inhibitor—plasminogen activator inhibitor type-2 (PAI-2), in the human cervical cancer cell line HeLa. In both models, CDDP resistance was associated with sensitivity to killing by adriamycin, etoposide, auranofin, bis[1,2-bis(diphenylphosphino)ethane]gold(I) chloride {[Au(DPPE)2]Cl}, CdCl2 and the mitochondrial inhibitors rhodamine-123 (Rhl23), dequalinium chloride (DeCH), tetraphenylphosphonium (TPP), and ethidium bromide (EtBr) and with lower constitutive levels of ATP. Unlike the HeLa clones, CI-80-13S cells were additionally sensitive to chloramphenicol, 1-methyl-4-phenylpyridinium ion (MPP+), rotenone, thenoyltrifluoroacetone (TTFA), and antimycin A, and showed poor reduction of 1-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT), suggesting a deficiency in NADH dehydrogenase and/or succinate dehydrogenase activities. Total platinum uptake and DNA-bound platinum were slightly lower in CI-80-13S than in sensitive cells. The HeLa-S1a and HeLa-S1b clones, on the other hand, showed poor reduction of triphenyltetrazolium chloride (TTC), indicative of low cytochrome c oxidase activity. Total platinum uptake by HeLa-S1a was similar to HeLa, but DNA-bound platinum was much lower than for the parent cell line. The mitochondria of CI-80-13S and HeLa-S1a showed altered morphology and were fewer in number than those of JAM and HeLa. In both models, CDDP resistance was associated with less platinum accumulation and with mitochondrial and membrane defects, brought about one case with expression of a protease inhibitor which is implicated in tumor progression. Such markers may identify tumors suitable for treatment with gold phosphine complexes or other mitochondrial inhibitors.

Interferon-free therapy for hepatitis C, how prepared is Australia for biosimilars?

The Hepatitis C virus (HCV) affects some 150 million people worldwide. However, unlike hepatitis A and B there is no vaccination for HCV and approximately 75% of people exposed to HCV develop chronic hepatitis. In Australia, around 226,700 people live with chronic HCV infection costing the government approximately $252 million per year. Historically, the standard approved/licenced treatment for HCV is pegylated interferon with ribavirin. There are major drawbacks with interferon-based therapy including side effects, long duration of therapy, limited access and affordability. Our previous survey of an at-risk population reported HCV treatment coverage of only 5%. Since April 2013, a new class of interferon-free treatments for chronic HCV is subsidised under the Pharmaceutical Benefits Scheme: boceprevir and telaprevir - estimated to cost the Australian Government in excess of $220 million over five years. Other biologic interferon-free therapeutic agents are scheduled to enter the Australian market. Use of small molecule generic pharmaceuticals has been advocated as a means of public cost savings. However, with the new biologic agents, generics (biosimilars) may not be feasible or straightforward, due to long patent life; marketing exclusivity; and regulatory complexity for these newer products.

Pharmacogenetics of migraine : genetic variants and their potential role in migraine therapy

Migraine is a paroxysmal neurological disorder affecting up to 6% of males and 18% of females in the general population, and has been demonstrated to have a strong, but complex, genetic component. Genetic investigation of migraine provides hope that new targets for medications and individual specific therapy will be developed. The identification of polymorphisms or genetic biomarkers for disease susceptibility and treatment should aid in providing a better understanding of migraine pathology and, consequently, more appropriate and efficient treatment for migraineurs. In this review, we will discuss results investigating genetic biomarkers for migraine and their potential role in future therapy planning.

A pharmacogenomic evaluation of migraine therapy

Migraine is a common idiopathic primary headache disorder with significant mental, physical and social health implications. Accompanying an intense unilateral pulsating head pain other characteristic migraine symptoms include nausea, emesis, phonophobia, photophobia and in approximately 20-30% of migraine cases, neurologic disturbances associated with the aura phase. Although selective serotonin (5-HT) receptor agonists (i.e., 5-HT(1B/1D)) are successful in alleviating migrainous symptoms in < or = 70% of known sufferers, for the remaining 30%, additional migraine abortive medications remain unsuccessful, not tested or yet to be identified. Genetic characterization of the migrainous disorder is making steady progress with an increasing number of genomic susceptibility loci now identified on chromosomes 1q, 4q, 5q, 6p, 11q, 14q, 15q, 17p, 18q, 19p and Xq. The 4q, 5q, 17p and 18q loci involve endophenotypic susceptibility regions for various migrainous symptoms. In an effort to develop individualized pharmacotherapeutics, the identification of these migraine endophenotypic loci may well be the catalyst needed to aid in this goal. In this review the authors discuss the present treatment of migraine, known genomic susceptibility regions and results from migraine (genetic) association studies. The authors also discuss pharmacogenomic considerations for more individualized migraine prophylactic treatments.

Medical nutrition therapy and simple interventions can improve intake in patients who eat poorly in hospital

The Australasian Nutrition Care Day Survey (ANCDS) reported two-in-five patients in Australian and New Zealand hospitals consume ≤50% of the offered food. The ANCDS found a significant association between poor food intake and increased in-hospital mortality after controlling for confounders (nutritional status, age, disease type and severity)1. Evidence for the effectiveness of medical nutrition therapy (MNT) in hospital patients eating poorly is lacking. An exploratory study was conducted in respiratory, neurology and orthopaedic wards of an Australian hospital. At baseline, 24-hour food intake (0%, 25%, 50%, 75%, 100% of offered meals) was evaluated for patients hospitalised for ≥2 days and not under dietetic review. Patients consuming ≤50% of offered meals due to nutrition-impact symptoms were referred to ward dietitians for MNT with food intake re-evaluated on day-7. 184 patients were observed over four weeks. Sixty-two patients (34%) consumed ≤50% of the offered meals. Simple interventions (feeding/menu assistance, diet texture modifications) improved intake to ≥75% in 30 patients who did not require further MNT. Of the 32 patients referred for MNT, baseline and day-7 data were available for 20 patients (68±17years, 65% females, BMI: 22±5kg/m2, median energy, protein intake: 2250kJ, 25g respectively). On day-7, 17 participants (85%) demonstrated significantly higher consumption (4300kJ, 53g; p<0.01). Three participants demonstrated no improvement due to ongoing nutrition-impact symptoms. “Percentage food intake” was a quick tool to identify patients in whom simple interventions could enhance intake. MNT was associated with improved dietary intake in hospital patients. Further research is needed to establish a causal relationship.