Nuapapuin A and sigmosceptrellins D and E: New norterpene cyclic peroxides from a southern Australian marine sponge, Sigmosceptrella sp.

A Sigmosceptrella sp. from the Great Australian Eight, Australia, has yielded the new norditerpene cyclic peroxide, nuapapuin A (2a), and the norsesterterpene cyclic peroxide sigmosceptrellin D (3a), characterized as the corresponding methyl esters 2b and 3b. The crude methylated sponge extract also yielded the new norsesterterpene cyclic peroxide sigmosceptrellin E methyl ester (4). Relative stereochemistry about C2, C3, and C6 was assigned by established empirical rules and absolute stereochemistry by the advanced Mosher procedure. A plausible biosynthetic pathway has been proposed that rationalizes key transformations in the biosynthesis of all known norterpene cyclic peroxides and related norterpene ketones, dienes and sigmosceptrins.

Hysterectomy fractions in New South Wales, 1971-2006

Hysterectomy fractions by age group for particular periods are of interest for: estimating proper population denominators for calculation of disease and procedure rates affecting the cervix and uterus; estimating the target population for Pap test programs, and response rates; and as a way of displaying the cumulative consequences of hysterectomies in a population. Hysterectomy fractions for populations can be determined by direct inquiry via a representative sample survey, or, as in this study, from prior hysterectomy rates of the cohorts of women which compose each age bracket. Hysterectomy data 1979-93 were obtained from the hospital In-patients Statistics Collection (ISC) which covers both public and private hospitals in NSW. Annual population denominators of women were obtained from Census data. Data were modelled by Poisson regression, using five.-year age group (15-greater than or equal to 85 years), annual period, and five-year birth cohort (APC model). Forward- and back-projection of the period effects were undertaken. The resultant NSW hysterectomy fractions by age and period are consistent with fractions obtained from modelled hysterectomy rates for Western Australia (1980-84), and fractions from national representative sample surveys (1989/90 and 1995) for younger women, but not for women aged greater than or equal to 70 years in 1995, which revealed higher hysterectomy fractions than modelled hysterectomy data would suggest. Hysterectomy fractions for NSW women by five-year age group for quinquennia centred on 1971 to 2006 are provided.

Some new examples for nonuniqueness of the evolution problem of harmonic maps

We find some new examples to show nonuniquence for the heat flow of harmonic maps where weak solutions satisfy the same monotonicity property.

New techniques in nutritional assessment: body composition methods

New techniques in air-displacement plethysmography seem to have overcome many of the previous problems of poor reproducibility and validity. These have made body-density measurements available to a larger range of individuals, including children, elderly and sick patients who often have difficulties in being submerged underwater in hydrodensitometry systems. The BOD POD air-displacement system (BOD POD body composition system; Life Measurement Instruments, Concord, CA, USA) is more precise than hydrodensitometry, is simple and rapid to operate (approximately 1 min measurements) and the results agree closely with those of hydrodensitometry (e.g. +/-3.4% for estimation of body fat). Body line scanners employing the principles of three-dimensional photography are potentially able to measure the surface area and volume of the body and its segments even more rapidly (approximately 10 s), but the validity of the measurements needs to be established. Advances in i.r. spectroscopy and mathematical modelling for calculating the area under the curve have improved precision for measuring enrichment of (H2O)-H-2 in studies of water dilution (CV 0.1-0.9% within the range of 400-1000 mu l/l) in saliva, plasma and urine. The technique is rapid and compares closely with mass spectrometry (bias 1 (SD 2) %). Advances in bedside bioelectrical-impedance techniques are making possible potential measurements of skinfold thicknesses and limb muscle mass electronically. Preliminary results suggest that the electronic method is more reproducible (intra-and inter-individual reproducibility for measuring skinfold thicknesses) and associated with less bias (+ 12%), than anthropometry (+ 40%). In addition to these selected examples, the 'mobility' or transfer of reference methods between centres has made the distinction between reference and bedside or field techniques less distinct than in the past.

Socio-economic, migrant and geographic differentials in coronary heart disease occurrence in New South Wales

Objective: This study examines the variation in coronary heart disease (CHD) mortality and acute myocardial infarction (AMI) by socio-economic status (SES), country of birth (COB) and geography (urban/rural) in the total population of New South Wales (Australia) in 1991-95. Method: CHD deaths and AMI are from complete enumerations of deaths and hospital admissions, respectively; and population denominators are from census information. Data are examined separately by sex, and comparisons of SES groups (based on municipalities), COB and region are analysed using Poisson regression, after adjustment for age. Results: The study identified higher risk for AMI admissions and CHD mortality in lower SES populations with significant linear trends, for both sexes, adjusted for age, region and COB. According to the population attributable fractions (PAF), 23-41% of the risk of CHD occurrence is due to SES lower than the highest quartile. The higher age-adjusted risk for CHD occurrence in rural and remote populations for both sexes, compared with urban communities, was lessened by adjustment for COB, and all but abolished when also adjusted for SES. COB analysis indicated significantly lower age-adjusted AMI admissions and CHD mortality compared with the Australian-born, Conclusions: Higher risks for CHD in rural populations compared with the capital city (Sydney) are due, in part, to lower SES, lesser migrant composition. Implications: Strategies for reducing CHD differentials should consider demographic factors and the fundamental need to reduce socio-economic inequalities, as well as targeting appropriate prevention measures.

Spider toxins: A new group of potassium channel modulators

Spider toxins that target potassium channels constitute a new class of pharmacological tools that can be used to probe the structure and function of these channels at the molecular level. The limited studies performed to date indicate that these peptide toxins may facilitate the analysis of K+ channels that have proved insensitive to peptide inhibitors isolated from other animal sources. Thus far, two classes of K+ channel-selective spider toxins have been isolated, sequenced, and pharmacologically characterised - the hanatoxins (HaTx) from Grammastola spatulata and heteropodatoxins (HpTx) from Heteropoda venatoria. The hanatoxins block Kv2.1 and Kv4.2 voltage-gated K+ channels. In Kv2.1 K+ channels this occurs as a consequence of a depolarising shift in the voltage dependence of activation and not by occlusion of the channel pore. These toxins show minimal sequence homology with other peptide inhibitors of K+ channels, but they do share some homology with other ion channel toxins from spiders, particularly with regard to the spacing between cysteine residues. We have recently isolated three K+ channel antagonists from the venom of the Australian funnel-web spider Hadronyche versuta; at least two of these toxins are likely to constitute a new class of spider toxins active on K+ channels as they are approximately twice as large as HaTx and HpTx.

Urban and rural suicide differentials in migrants and the Australian-born, New South Wales, Australia 1985-1994

We estimated risk of suicide in adults in New South Wales (NSW) by sex, country of birth and rural/urban residence, after adjusting for age; we also examined youth suicide (age 15-24 years). The study population was the entire population of NSW, Australia, aged greater than or equal to 15 years during the period 1985-1994. Poisson regression was used to examine the relationship between predictor variables and the risk of suicide, with the focus on migrant status and area of residence. A significantly higher risk of suicide was found in male migrants from Northern Europe and Eastern Europe/former USSR, compared to Australian-born males; a significantly lower suicide risk occurred in males from Southern Europe, the Middle East and Asia. In female migrants, those from UK/Eire, Northern Europe, Eastern Europe/former USSR and New Zealand exhibited a significantly higher risk of suicide compared to Australian-born females. A significantly lower risk of suicide occurred in females from the Middle East. Male migrants overall were at significantly lower risk of suicide than the Australian-born, while female migrants overall had a significantly higher risk of suicide than Australian-born females. Among migrant males overall, the rural-urban suicide risk differential was significantly higher for those living in non-metropolitan areas (RR = 1.9; 95% CI: 1.7-2.1). Suicide risk was significantly higher in non-metropolitan male immigrants from the UK/Eire (RR = 1.4; 95% CI: 1.1-1.7), Southern Europe (RR = 1.7; 95% CI: 1.2-2.4), Northern/Western Europe (1.5; 95% CI: 1.2-1.9), the Middle East (RR = 3.8; 95% CI: 1.9-7.8), New :Zealand (RR = 1.4; 95% CI: 1.0-1.8) and 'other' (RR = 2.6; 95% CI: 1.9-3.5), when compared to their urban counterparts. There was no statistically significant difference in suicide risk between rural and urban Australian-born males. For female suicide, significantly lower risk was found in female immigrants living in non-metropolitan areas who were from Northern/Western Europe (RR = 0.7; 95% CI: 0.4-0.96), as well as the Australian-born (RR = 0.7; 95% CI: 0.6-0.8), when compared to their urban counterparts. The non-metropolitan/metropolitan relative risk for suicide in female migrants overall was not significantly different from one. Among male youth there was a significantly higher suicide risk in non-metropolitan areas, with a relative risk estimate of 1.4 for Australian-born youth (95% CI: 1.2-1.5) and 1.7 for migrant youth (95% CI: 1.2-2.4), when compared with metropolitan counterparts. We conclude that suicide among migrant males living in non-metropolitan areas accounts for most of the excess of male suicide in rural NSW, and the significantly lower risk of suicide for non-metropolitan Australian-born women does not apply to migrant women. (C) 1999 Published by Elsevier Science Ltd. All rights reserved.

The plasma membrane calcium pump, its role and regulation: New complexities and possibilities

Significant progress has been achieved in elucidating the role of the plasma membrane Ca2+-ATPase in cellular Ca2+ homeostasis and physiology since the enzyme was first purified and physiology since the enzyme was first purified and cloned a number of years ago. The simple notion that the PM Ca2+-ATPase controls resting levels of [Ca2+](CYT) has been challenged by the complexity arising from the finding of four major isoforms and splice variants of the Ca2+ pump, and the finding that these are differentially localized in various organs and subcellular regions. Furthermore, the isoforms exhibit differential sensitivities to Ca2+, calmodulin, ATP, and kinase-mediated phosphorylation. The latter pathways of regulation can give rise to activation or inhibition of the Ca2+ pump activity, depending on the kinase and the particular Ca2+ pump isoform. Significant progress is being made in elucidating subtle and more profound roles of the PM Ca2+-ATPase in the control of cellular function. Further understanding of these roles awaits new studies in both transfected cells and intact organelles, a process that will be greatly aided by the development of new and selective Ca2+ pump inhibitors. (C) 1999 Elsevier Science Inc.

Changing patterns of coronary heart disease in the hunter region of New South Wales, Australia

A population-based observational study of men acid women aged 35-69 years in the Hunter Region of New South Wales, Australia, was conducted to assess the impact. of risk-factor modification and increased drug therapy on the trends in major coronary events and case fatality. From 1985 to 1993, there were 3006 coronary deaths and 6450 nonfatal major coronary events. Rates of death and nonfatal myocardial infarction declined, but there was an increase in hospital admissions for prolonged chess pain. Reductions in cigarette smoking, diastolic blood pressure, total cholesterol, and increased use of aspirin can fully explain the 3.3% (95% confidence interval [CI] 2.4, 4.2) average annual reduction in rates of major coronary events for men and the 4.1% (95% CI 2.7, 5.5) reduction for women. In contrast, increased use of aspirin, beta-blockers, fibrinolytic therapy, and angiotensin-converting enzyme inhibitors explain less than hall of the 8.9% (95% CI 5.9, 11.8) and 6.9% (95% CI 2.7, 10.9) average annual reduction in case fatality in hospital for men and women, respectively. These trends suggest a decline in severity of coronary heart disease consistent with reductions in risk-factor levels and improved acute medical treatment. J CLIN EPIDEMIOL 52;8:761-771, 1999. (C) 1999 Elsevier Science Inc.

Identification of a new ligand binding domain in the al subunit of the inhibitory glycine receptor

Four discontinuous extracellular sequence domains have been proposed to form the ligand binding sites of the ligand-gated ion channel receptor superfamily. In this study, we investigated the role of 12 contiguous residues of the inhibitory glycine receptor that define the proposed loop A ligand binding domain; Using the techniques of site-directed mutagenesis and patch-clamp electrophysiology, four of the 12 residues were shown to have impaired ligand binding. Three mutants, I93A, A101H, and N102A, resulted in significant (17-44-fold) increases in the agonist EC50 values as compared with the wild-type glycine receptor, whereas Hill coefficients, I-max values, and antagonist affinity remained largely unaffected. Consideration of receptor efficacy values indicates that these residues are involved in ligand binding rather than channel activation. A fourth mutant, W94A, failed to give rise to any glycine-activated currents, although cell-surface expression was observed, suggesting that this residue may also be involved in agonist binding. These data provide the most extensive characterization of the loop A ligand binding domain available to date and define two new residue locations, Ile(93) and Asn(102), as contributing to the four-loop model of ligand binding.

New integrable model of correlated electrons with off-diagonal long-range order from so(5) symmetry

We present a new integrable model for correlated electrons which is based on so(5) symmetry. By using an eta-pairing realization we construct eigenstates of the Hamiltonian with off-diagonal long-range order. It is also shown that these states lie in the ground state sector. We exactly solve the model on a one-dimensional lattice by the Bethe ansatz.