Pharmaceutical benefits in Australia and Sweden: welfare policy and the cost of prescription drugs

Pharmaceutical benefits provide a stable framework within which consumers, prescribers, suppliers, pharmacists and other actors undertake transactions. The state in effect delivers a good that enhances individual autonomy. A major reason for the legitimacy enjoyed by pharmaceutical benefits in both Australia and Sweden is that these programs have strong attributes of universalism (rather than targeting). Sweden's predominantly public health system allows greater scope for pharmaceutical policy innovation. Australia's Pharmaceutical Benefits Scheme (PBS), while historically resilient and effective, is now wedged precariously between traditional considerations of equity and public health on the one hand, and constant pressure for increased marketisation on the other.

The effect of insulin and exercise on c-Cbl protein abundance and phosphorylation in insulin-resistant skeletal muscle in lean and obese Zucker rats.

Aims/hypothesis: Recruitment of the protein c-Cbl to the insulin receptor (IR) and its tyrosine phosphorylation via a pathway that is independent from phosphatidylinositol 3prime-kinase is necessary for insulin-stimulated GLUT4 translocation in 3T3-L1 adipocytes. The activation of this pathway by insulin or exercise has yet to be reported in skeletal muscle. Methods: Lean and obese Zucker rats were randomly assigned to one of three treatment groups: (i) control, (ii) insulin-stimulated or (iii) acute, exhaustive exercise. Hind limb skeletal muscle was removed and the phosphorylation state of IR, Akt and c-Cbl measured.  Results:   Insulin receptor phosphorylation was increased 12-fold after insulin stimulation (p<0.0001) in lean rats and threefold in obese rats. Acute exercise had no effect on IR tyrosine phosphorylation. Similar results were found for serine phosphorylation of Akt. Exercise did not alter c-Cbl tyrosine phosphorylation in skeletal muscle of lean or obese rats. However, in contrast to previous studies in adipocytes, c-Cbl tyrosine phosphorylation was reduced after insulin treatment (p<0.001). Conclusions/interpretation: We also found that c-Cbl associating protein expression is relatively low in skeletal muscle of Zucker rats compared to 3T3-L1 adipocytes and this could account for the reduced c-Cbl tyrosine phosphorylation after insulin treatment. Interestingly, basal levels of c-Cbl tyrosine phosphorylation were higher in skeletal muscle from insulin-resistant Zucker rats (p<0.05), but the physiological relevance is not clear. We conclude that the regulation of c-Cbl phosphorylation in skeletal muscle differs from that previously reported in adipocytes.

Grain size effect on the warm deformation behaviour of a Ti-IF steel

The effect of grain size on the warm deformation behaviour of a titanium stabilized interstitial free (IF) steel was investigated using hot torsion. The initial work hardening regime is followed by the development of a broad stress peak after which work softening occurs. The hypothetical saturation stress (Estrin–Mecking model) and the stress at final strain were relatively insensitive to grain size. However, the strain to the peak stress was strongly dependent on the grain size at low values of the Zener–Hollomon parameter. A simple phenomenological approach, using a combined Estrin–Mecking model and an Avrami type equation, was used to model the flow curves. The hypothetical saturation stress, the stress at final strain and the strain to peak stress were modelled using three different hyperbolic sine laws. A comparison with independent data from the literature shows that the apparent activation energy of deformation determined in this work (Q=372 kJ/mol) can be used to rationalize the steady-state stress in compression data found in the literature.

Effect of transformation volume contraction on the toughness of superelastic shape memory alloys

Shape memory alloys (SMAs) exhibit two very important properties: shape memory phenomenon and superelastic deformation due to intrinsic thermoelastic martensitic transformation. To fully exploit the potential of SMAs in developing functional structures or smart structures in mechanical and biomechanical engineering, it is important to understand and quantify the failure mechanisms of SMAs. This paper presents a theoretical study of the effect of phase-transformation-induced volume contraction on the fracture properties of superelastic SMAs. A simple model is employed to account for the forward and reverse phase transformation with pure volume change, which is then applied to numerically study the transformation field near the tip of a tensile crack. The results reveal that during steady-state crack propagation, the transformation zone extends ahead of the crack tip due to forward transformation while partial reverse transformation occurs in the wake. Furthermore, as a result of the volume contraction associated with the austenite-to-martensite transformation, the induced stress-intensity factor is positive. This is in stark contrast with the negative stress-intensity factor achieved in zirconia ceramics, which undergoes volume expansion during phase transformation. The reverse transformation has been found to have a negligible effect on the induced stress-intensity factor. An important implication of the present results is that the phase transformation with volume contraction in SMAs tends to reduce their fracture resistance and increase the brittleness.

Australia's residential building faults : a view from the state of Victoria

Presented is an examination of residential building faults in the Australian Slate of Victoria. The aim is to determine the interconnections between identified main house faults., with a view to establishing their cause· effect relationships. A total of 42753 residential houses in Victoria were examined for nine key faults fully documented in Archicentre's database. These faults are: rising damp. framing fault, illegal building, stump fault, timber rot, cracking, electrical fault, roof fault and water supply issue. Second to framing fault, roof fault was found to be closely associated with other house faults examined. Hence, this paper concludes that a properly framed and roofed house could limit most of these faults. As illegal building was observed to have only a little overall association with other house faults, this study has implications for the Australia Productivity Commission's on-going efforts to deregulate various aspects of the building and construction industry professions.

Housing price diffusion pattern of Australia's state capital cities

The ripple effect of house prices within metropolitan areas has recently been recognised by researchers. However, it is very difficult to formulate and measure this effect using conventional house price theories particularly in consideration of the spatial locations of cities. Based on econometrics principles of the cointegration test and the error correction model, this research develops an innovative approach to quantitatively examine the diffusion patterns of house prices in mega-cities of a country. Taking Australia's eight capital cities as an example, the proposed approach is validated in terms of an empirical study. The results show that a 1-1-2-4 diffusion pattern exists within these cities. Sydney is on the top tier with Melbourne in the second; Perth and Adelaide are in the third level and the other four cities lie on the bottom. This research may be applied to predict the regional housing market behavior in a country.

Rates of student-reported antisocial behavior, school suspensions, and arrests in Victoria, Australia and Washington State, United States

Background: Few methodologically rigorous international comparisons of student-reported antisocial behavior have been conducted. This paper examines whether there are differences in the frequency of both antisocial behavior and societal responses to antisocial behavior in Victoria, Australia and Washington State, United States. These 2 states were chosen due to their similarities on sociodemographic characteristics and their differences in policy frameworks around problem behavior including antisocial behavior and substance use.

Methods: State representative samples of students (N = 5769) in school grades 5, 7, and 9 in Victoria and Washington State completed a modified version of the Communities That Care self-report survey of behavior and societal responses to behavior. Chi-square analyses compared frequencies of antisocial behavior, school suspensions, and police arrests in the 2 states. Multivariate logistic regression analyses were conducted for each outcome measure to examine the effect of state, controlling for sample design, clustering of students within schools, age, socioeconomic status, and urbanicity.

Results: Few state differences in student-reported antisocial behavior were found, although frequencies varied across behavior type and grade level. Differences in societal responses were observed across grade levels with grade 5 Washington students reporting higher rates of school suspension. Older Washington students reported more arrests.

Conclusions: Rates of student antisocial behavior appear similar in these 2 states in Australia and the United States. However, youth in the United States relative to Australia may experience greater societal consequences for problem behavior. Further research is required to examine the impact of these consequences on subsequent behavior.

Effect of glycerol-induced hyperhydration on thermoregulation and metabolism during exercise in the heat

This study examined the effect of glycerol ingestion on fluid homeostasis, thermoregulation, and metabolism during rest and exercise. Six endurance-trained men ingested either 1 g glycerol in 20 ml H₂O.kg^-1 body weight (bw) (GLY) or 20 ml H₂O.kg^-1bw (CON) in a randomized double-blind fashion, 120 min prior to undertaking 90 min of steady state cycle exercise (SS) at 98 % of lactate threshold in dry heat (35 degrees C, 30 % RH), with ingestion of CHO-electrolyte beverage (6 % CHO) at 15-min intervals. A 15-min cycle, where performance was quantified in kJ, followed (PC). Pre-exercise urine volume was lower in GLY than CON (1119 ± 97 vs. 1503 ± 146 ml· 120 min^-1; p < .05). Heart rate was lower (p < .05) throughout SS in GLY, while forearm blood flow was higher (17.1 ± 1.5 vs. 13.7 ± 3.0 ml.100 g tissue·min^-1; p < .05) and rectal  temperature lower (38.7 ± 0.1 vs. 39.1 ± 0.1 ° C; p < .05) in GLY late in SS. Despite these changes, skin and muscle temperatures and circulating catecholamines were not different between trials. Accordingly, no differences were observed in muscle glycogenolysis, lactate accumulation, adenine nucleotide, and phosphocreatine degradation or inosine 5'-monophosphate accumulation when comparing GLY with CON. Of note, the work performed during PC was 5 % greater in GLY (252 ± 10 vs. 240 ± 9 kJ; p < .05). These results demonstrate that glycerol, when ingested with a bolus of water 2 hours prior to exercise, results in fluid retention, which is capable of reducing cardiovascular strain and enhancing thermoregulation. Furthermore, this practice increases exercise performance in the heat by mechanisms other than alterations in muscle metabolism.

Carbohydrate ingestion reduces skeletal muscle acetylcarnitine availability but has no effect on substrate phosphorylation at the onset of exercise in man

This study investigated the effect of reduced acetylcarnitine availability on oxidative metabolism during the transition from rest to steady-state exercise. Eight male subjects completed two randomised exercise trials at 68 % of the peak rate of O2 uptake (V̇O2,peak). On one occasion subjects ingested 1 g (kg body mass)−1 glucose 75 min prior to exercise (CHO), whereas the other trial acted as a control (CON). Muscle samples were obtained pre- and 75 min post-ingestion, and following 1 and 10 min of exercise. Plasma glucose and insulin were elevated (P < 0.05), and plasma free fatty acids (FFA) were lower at the onset of exercise in CHO. Acetylcarnitine (CON, 4.8 ± 1.8; CHO, 1.5 ± 0.9 mmol (kg dry mass (d.m.))−1, P < 0.05) and acetyl CoA (CON, 13.2 ± 2.3; CHO, 6.3 ± 0.6 μmol (kg d.m.)−1, P < 0.05) were lower at rest, whereas pyruvate dehydrogenase activation (PDHa) was greater in CHO compared with CON (CON, 0.78 ± 0.07; CHO, 1.44 ± 0.19 mmol min−1 (kg wet mass (w.m.))−1). Respiratory exchange ratio (RER) was significantly elevated during exercise in CHO. The acetyl groups increased at similar rates at the onset of exercise (1 min) and there was no difference in substrate phosphorylation as determined from lactate accumulation and phosphocreatine degradation between trials. Subsequently, oxidative metabolism during the transition from rest to steady-state exercise was not affected by prior carbohydrate ingestion. Although exercise resulted in the rapid activation of PDH in both trials, PDHa was greater at 1 min in CHO (CON, 2.36 ± 0.22; CHO, 2.91 ± 0.18 mmol min−1 (kg w.m.)−1). No differences in muscle metabolite levels and PDHa were observed after 10 min of moderate exercise between trials. In summary, at rest, carbohydrate ingestion induced multiple metabolic changes which included decreased acetylcarnitine availability and small increases in PDHa. The prior changes in PDHa and acetylcarnitine availability had no effect on substrate phosphorylation and oxidative metabolism at the onset of exercise. These data suggest that acetylcarnitine availability is unlikely to be the site of metabolic inertia during the transition from rest to steady-state moderate intensity exercise.

Effect of accurate exercise on uncoupling protein3 is a fat metabolism-mediated effect

Human and rodent uncoupling protein (UCP)3 mRNA is upregulated after acute exercise. Moreover, exercise increases plasma levels of free fatty acid (FFA), which are also known to upregulate UCP3. We investigated whether the upregulation of UCP3 after exercise is an effect of exercise per se or an effect of FFA levels or substrate oxidation. Seven healthy untrained men [age: 22.7 ± 0.6 yr; body mass index: 23.8 ± 1.0 kg/m²; maximal O₂ uptake (VO_{2 max}): 3,852 ± 211 ml/min] exercised at 50% VO_{2 max} for 2 h and then rested for 4 h. Muscle biopsies and blood samples were taken before and immediately after 2 h of exercise and 1 and 4 h in the postexercise period. To modulate plasma FFA levels and fat/glucose oxidation, the experiment was performed two times, one time with glucose ingestion and one time while fasting. UCP3 mRNA and UCP3 protein were determined by RT-competitive PCR and Western blot. In the fasted state, plasma FFA levels significantly increased (P < 0.0001) during exercise (293 ± 25 vs. 1,050 ± 127 μmol/l), whereas they were unchanged after glucose ingestion (335 ± 54 vs. 392 ± 74 µmol/l). Also, fat oxidation was higher after fasting (P < 0.05), whereas glucose oxidation was higher after glucose ingestion (P < 0.05). In the fasted state, UCP3L mRNA expression was increased significantly (P < 0.05) 4 h after exercise (4.6 ± 1.2 vs. 9.6 ± 3.3 amol/µg RNA). This increase in UCP3L mRNA expression was prevented by glucose ingestion. Acute exercise had no effect on UCP3 protein levels. In conclusion, we found that acute exercise had no direct effect on UCP3 mRNA expression. Abolishing the commonly observed increase in plasma FFA levels and/or fatty acid oxidation during and after exercise prevents the upregulation of UCP3 after acute exercise. Therefore, the previously observed increase in UCP3 expression appears to be an effect of prolonged elevation of plasma FFA levels and/or increased fatty acid oxidation.

Peroxisome proliferator-activated receptor-γ coactivator-1 and insulin resistance: acute effect of fatty acids

Aims/hypothesis Peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1 (PPARGC1), a coactivator regulating the transcription of genes involved in oxidative metabolism, is downregulated in patients with type 2 diabetes and in their first-degree relatives. Whether this downregulation is a cause or effect of early aberrations in the development of insulin resistance, such as disturbances in fat metabolism, is unknown. We examined whether lipid-induced insulin resistance was associated with downregulation of expression of skeletal muscle genes involved in oxidative metabolism and mitochondrial biogenesis in humans.
Materials and methods Nine healthy lean male subjects underwent a 6-h hyperinsulinaemic–euglycaemic clamp with simultaneous infusion of either a lipid emulsion or glycerol as a control. Blood was sampled at regular time points and muscle biopsies were taken before and after every test. Intramuscular triacylglycerol (IMTG) content was determined by Oil Red O staining and gene expression was measured by quantitative PCR.
Results Lipid infusion resulted in a ∼2.7-fold increase in plasma NEFA levels and a 31±6% decrease in insulin sensitivity (p=0.001). The infusion of lipids resulted in a ∼1.6-fold increase in IMTG (p=0.02), whereas during the clamp with glycerol infusion IMTG tended to decrease to ∼53% of preinfusion levels (p=0.065). Lipid infusion decreased PPARGC1A, PPARGC1B and PPARA expression to ∼61, 77 and ∼52% of basal values respectively, whereas expression of uncoupling protein 3 was upregulated 1.8-fold (all p<0.05).
Conclusions/interpretation Acute elevation of plasma NEFA levels, leading to muscular fat accumulation and insulin resistance, downregulates PPARGC1A, PPARGC1B and PPARA expression, suggesting that the decrease in PPARGC1 expression observed in the (pre)diabetic state may be the result, rather than the cause of lipid-induced insulin resistance.

The effect of school suspensions and arrests on subsequent adolescent antisocial behavior in Australia and the United States

Purpose: To examine the effect of school suspensions and arrests (i.e., being taken into police custody) on subsequent adolescent antisocial behavior such as violence and crime, after controlling for established risk and protective factors in Victoria, Australia and Washington State, United States (U.S.). Methods: This article reports on analyses of two points of data collected 1 year apart within a cross-national longitudinal study of the development of antisocial behavior, substance use, and related behaviors in approximately 4000 students aged 12 to 16 years in Victoria, Australia and Washington State, U.S. Students completed a modified version of the Communities That Care self-report survey of behavior, as well as risk and protective factors across five domains (individual, family, peer, school, and community). Multivariate logistic regression analyses investigate the effect of school suspensions and arrests on subsequent antisocial behavior, holding constant individual, family, peer, school, and community level influences such as being female, student belief in the moral order, emotional control, and attachment to mother. Results: At the first assessment, school suspensions and arrests were more commonly reported in Washington, and school suspensions significantly increased the likelihood of antisocial behavior 12 months later, after holding constant established risk and protective factors (adjusted odds ratio [OR] 1.5, 95% confidence interval [CI] 1.1–2.1, _p < .05). Predictors of antisocial behavior spanned risk and protective factors across five individual and ecological areas of risk. Risk factors in this study were pre-existing antisocial behavior (OR 3.6, CI 2.7–4.7, _p < .001), association with antisocial peers (OR 1.8, CI 1.4–2.4, _p < .001), academic failure (OR 1.3, CI 1.1–1.5, _p < .01), and perceived availability of drugs in the community (OR 1.3, CI 1.1–1.5, _p < .001). Protective factors included being female (OR 0.7, CI 0.5–0.9, _p < .01), student belief in the moral order (OR 0.8, CI 0.6–1.0, p < .05), student emotional control (OR 0.7, CI 0.6–0.8, _p < .001), and attachment to mother (OR 0.8, CI 0.7–1.0, _p < .05). Conclusions:  School suspensions may increase the likelihood of future antisocial behavior. Further research is required to both replicate this finding and establish the mechanisms by which school suspensions exert their effects.