Information Exchange and global economic regulation - for whose benefit?

Offshore financial centres have both the sovereign right and the moral right to insist that information exchange be limited to matters of common criminality and governed by due legal process for the protection of both their own residents and citizens an

Urban water policy: in need of economics

The thesis of this article is that Australian urban water supply and pricing policies are not well grounded in rational economic thinking. It questions the policy consensus that water is necessarily so scarce in Australia as to require the sorts of penal charges, water restrictions and use regulations which are being imposed or being considered for imposition upon urban users. It also questions the policy consensus on vetoing new dams for urban water supply, a consensus from which Queensland is partly defecting

Microwave-assisted synthesis of a MK2 inhibitor by Suzuki-Miyaura coupling for study in Werner syndrome cells

Microwave-assisted Suzuki-Miyaura cross-coupling reactions have been employed towards the synthesis of three different MAPKAPK2 (MK2) inhibitors to study accelerated aging in Werner syndrome (WS) cells, including the cross-coupling of a 2-chloroquinoline with a 3-pyridinylboronic acid, the coupling of an aryl bromide with an indolylboronic acid and the reaction of a 3-amino-4-bromopyrazole with 4-carbamoylphenylboronic acid. In all of these processes, the Suzuki-Miyaura reaction was fast and relatively efficient using a palladium catalyst under microwave irradiation. The process was incorporated into a rapid 3-step microwave-assisted method for the synthesis of a MK2 inhibitor involving 3-aminopyrazole formation, pyrazole C-4 bromination using N-bromosuccinimide (NBS), and Suzuki-Miyaura cross-coupling of the pyrazolyl bromide with 4-carbamoylphenylboronic acid to give the target 4-arylpyrazole in 35% overall yield, suitable for study in WS cells

Microwave-assisted synthesis of a MK2 inhibitor by Suzuki-Miyaura coupling for study in Werner syndrome cells

Microwave-assisted Suzuki-Miyaura cross-coupling reactions have been employed towards the synthesis of three different MAPKAPK2 (MK2) inhibitors to study accelerated aging in Werner syndrome (WS) cells, including the cross-coupling of a 2-chloroquinoline with a 3-pyridinylboronic acid, the coupling of an aryl bromide with an indolylboronic acid and the reaction of a 3-amino-4-bromopyrazole with 4-carbamoylphenylboronic acid. In all of these processes, the Suzuki-Miyaura reaction was fast and relatively efficient using a palladium catalyst under microwave irradiation. The process was incorporated into a rapid 3-step microwave-assisted method for the synthesis of a MK2 inhibitor involving 3-aminopyrazole formation, pyrazole C-4 bromination using N-bromosuccinimide (NBS), and Suzuki-Miyaura cross-coupling of the pyrazolyl bromide with 4-carbamoylphenylboronic acid to give the target 4-arylpyrazole in 35% overall yield, suitable for study in WS cells

The effect of RO3201195 and a pyrazolyl ketone P38 MAPK inhibitor library on the proliferation of Werner syndrome cells

No description supplie

Correlates of knee bone marrow lesions in younger adults

Background: Subchondral bone marrow lesions (BMLs) play a key role in the pathogenesis of osteoarthritis (OA) and are associated with pain and structural progression in knee OA. However, little is known about clinical significance and determinants of BMLs of the knee joint in younger adults. We aimed to describe the prevalence and environmental (physical activity), structural (cartilage defects, meniscal lesions) and clinical (pain, stiffness, physical dysfunction) correlates of BMLs in younger adults and to determine whether cholesterol levels measured 5 years prior were associated with current BMLs in young adults. Methods: Subjects broadly representative of the Australian young adult population (n = 328, aged 31–41 years, female 48.7 %) underwent T1- and proton density-weighted fat-suppressed magnetic resonance imaging (MRI) in their dominant knee. BMLs, cartilage defects, meniscal lesions and cartilage volume were measured. Knee pain was assessed by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and physical activity was measured by the International Physical Activity Questionnaire (IPAQ). Cholesterol levels including high-density lipoprotein (HDL) were assessed 5 years prior to MRI. Results: The overall prevalence of BML was 17 % (grade 1: 10.7 %, grade 2: 4.3 %, grade 3: 1.8 %). BML was positively associated with increasing age and previous knee injury but not body mass index. Moderate physical activity (prevalence ratio (PR):0.93, 95 % CI: 0.87, 0.99) and HDL cholesterol (PR:0.36, 95 % CI: 0.15, 0.87) were negatively associated with BML, while vigorous activity (PR:1.02, 95 % CI: 1.01, 1.03) was positively associated with medial tibiofemoral BMLs. BMLs were associated with more severe total WOMAC knee pain (>5 vs ≤5, PR:1.05, 95 % CI: 1.02, 1.09) and WOMAC dysfunction (PR:1.75, 95 % CI: 1.07, 2.89), total knee cartilage defects (PR:2.65, 95 % CI: 1.47, 4.80) and total meniscal lesion score (PR:1.92, 95 % CI: 1.13, 3.28). Conclusions: BMLs in young adults are associated with knee symptoms and knee structural lesions. Moderate physical activity and HDL cholesterol are beneficially associated with BMLs; in contrast, vigorous physical activity is weakly but positively associated with medial tibiofemoral BMLs

In the aftermath of the National Children's Study: Is large birth cohort data still a priority?

The 2014 decisionto stop the US National Children’s Study (NCS) brings to the forefront questions about what has been lost and how studies such as this might still be important almost 20years after initiation in 2000. The rationale then was clear. Little progress had been made in the previous decades in understanding the causes of many major childhood disorders, and there was insufficient evidence available to confidently mount interventions to prevent many of them. A lack of evidence from cohort studies with prospective data had left a major evidence gap in childhood disease etiology, in stark contrast to efforts involving successful research on adult diseases where cohort studies were a central component

Impact of adiposity on cardiac structure in adult life: the Childhood Determinants of Adult Health (CDAH) study.

BACKGROUND: We have examined the association between adiposity and cardiac structure in adulthood, using a life course approach that takes account of the contribution of adiposity in both childhood and adulthood. METHODS: The Childhood Determinants of Adult Health study (CDAH) is a follow-up study of 8,498 children who participated in the 1985 Australian Schools Health and Fitness Survey (ASHFS). The CDAH follow-up study included 2,410 participants who attended a clinic examination. Of these, 181 underwent cardiac imaging and provided complete data. The measures were taken once when the children were aged 9 to 15 years, and once in adult life, aged 26 to 36 years. RESULTS: There was a positive association between adult left ventricular mass (LVM) and childhood body mass index (BMI) in males (regression coefficient (β) 0.41; 95% confidence interval (CI): 0.14 to 0.67; p = 0.003), and females (β = 0.53; 95% CI: 0.34 to 0.72; p < 0.001), and with change in BMI from childhood to adulthood (males: β = 0.27; 95% CI: 0.04 to 0.51; p < 0.001, females: β = 0.39; 95% CI: 0.20 to 0.58; p < 0.001), after adjustment for confounding factors (age, fitness, triglyceride levels and total cholesterol in adulthood). After further adjustment for known potential mediating factors (systolic BP and fasting plasma glucose in adulthood) the relationship of LVM with childhood BMI (males: β = 0.45; 95% CI: 0.19 to 0.71; p = 0.001, females: β = 0.49; 95% CI: 0.29 to 0.68; p < 0.001) and change in BMI (males: β = 0.26; 95% CI: 0.04 to 0.49; p = 0.02, females: β = 0.40; 95% CI: 0.20 to 0.59; p < 0.001) did not change markedly. CONCLUSIONS: Adiposity and increased adiposity from childhood to adulthood appear to have a detrimental effect on cardiac structure

Association of childhood obesity with female infertility in adulthood: a 25-year follow-up study

Objective To evaluate whether childhood obesity is associated with infertility in women's reproductive-aged life. Design Prospective longitudinal study. Setting Not applicable. Intervention(s) None. Patient(s) A total of 1,544 girls, aged 7–15 years in 1985, and who completed questionnaires at follow-up in 2004-2006 and/or 2009-2011. Main Outcome Measure(s) Infertility was defined as having difficulty conceiving (had tried for ≥12 months to become pregnant without succeeding) or having seen a doctor because of trouble becoming pregnant. Result(s) At ages from 7–11 years, girls at both the lower and upper end of the body mass index (BMI) z score had increased risk of infertility. Compared with normal weight girls, those with obesity at ages 7–11 years were more likely in adulthood to report infertility (adjusted relative risk [aRR] = 2.94, 95% confidence interval [CI] 1.48–5.84), difficulty conceiving (aRR = 3.89, 95% CI 1.95–7.77), or having seen a doctor because of trouble becoming pregnant (aRR = 3.65, 95% CI 1.90–7.02) after adjusting for childhood age, follow-up length, highest parental education, and marital status. Conclusion(s) Childhood obesity before 12 years of age appears to increase the risk of female infertility in later life

Predicting overweight and obesity in young adulthood from childhood body-mass index: comparison of cutoffs derived from longitudinal and cross-sectional data

Background Historically, cutoff points for childhood and adolescent overweight and obesity have been based on population-specific percentiles derived from cross-sectional data. To obtain cutoff points that might better predict overweight and obesity in young adulthood, we examined the association between childhood body-mass index (BMI) and young adulthood BMI status in a longitudinal cohort. Methods In this study, we used data from the International Childhood Cardiovascular Cohort (i3C) Consortium (which included seven childhood cohorts from the USA, Australia, and Finland) to establish childhood overweight and obesity cutoff points that best predict BMI status at the age of 18 years. We included 3779 children who were followed up from 1970 onwards, and had at least one childhood BMI measurement between ages 6 years and 17 years and a BMI measurement specifically at age 18 years. We used logistic regression to assess the association between BMI in childhood and young adulthood obesity. We used the area under the receiver operating characteristic curve (AUROC) to assess the ability of fitted models to discriminate between different BMI status groups in young adulthood. The cutoff points were then compared with those defined by the International Obesity Task Force (IOTF), which used cross-sectional data, and tested for sensitivity and specificity in a separate, independent, longitudinal sample (from the Special Turku Coronary Risk Factor Intervention Project [STRIP] study) with BMI measurements available from both childhood and adulthood. Findings The cutoff points derived from the longitudinal i3C Consortium data were lower than the IOTF cutoff points. Consequently, a larger proportion of participants in the STRIP study was classified as overweight or obese when using the i3C cutoff points than when using the IOTF cutoff points. Especially for obesity, i3C cutoff points were significantly better at identifying those who would become obese later in life. In the independent sample, the AUROC values for overweight ranged from 0·75 (95% CI 0·70–0·80) to 0·88 (0·84–0·93) for the i3C cutoff points, and the corresponding values for the IOTF cutoff points ranged from 0·69 (0·62–0·75) to 0·87 (0·82–0·92). For obesity, the AUROC values ranged from 0·84 (0·75–0·93) to 0·90 (0·82–0·98) for the i3C cutoff points and 0·57 (0·49–0·66) to 0·76 (0·65–0·88) for IOTF cutoff points. Interpretation The childhood BMI cutoff points obtained from the i3C Consortium longitudinal data can better predict risk of overweight and obesity in young adulthood than can standards that are currently used based on cross-sectional data. Such cutoff points should help to more accurately identify children at risk of adult overweight or obesity