Implications for prediction and hazard assessment from the 2004 Parkfield earthquake.

Obtaining high-quality measurements close to a large earthquake is not easy: one has to be in the right place at the right time with the right instruments. Such a convergence happened, for the first time, when the 28 September 2004 Parkfield, California, earthquake occurred on the San Andreas fault in the middle of a dense network of instruments designed to record it. The resulting data reveal aspects of the earthquake process never before seen. Here we show what these data, when combined with data from earlier Parkfield earthquakes, tell us about earthquake physics and earthquake prediction. The 2004 Parkfield earthquake, with its lack of obvious precursors, demonstrates that reliable short-term earthquake prediction still is not achievable. To reduce the societal impact of earthquakes now, we should focus on developing the next generation of models that can provide better predictions of the strength and location of damaging ground shaking.

Thiazolidinediones inhibit TNFalpha induction of PAI-1 independent of PPARgamma activation.

Increased plasminogen activator inhibitor type 1 (PAI-1) levels are observed in endothelial cells stimulated by tumour necrosis factor alpha (TNFalpha). Thiazolidinediones (TZDs) may inhibit elevated endothelial cell PAI-1 accounting, in part, for the putative atheroprotective effects of TZDs. In an endothelial cell line, Rosiglitazone (RG) and Pioglitazone (PG) inhibited induction of PAI-1 by TNFalpha. The specific peroxisome proliferator-activated receptor gamma (PPARgamma) inhibitor, SR-202, failed to modulate this effect. RG also inhibited the effect of TNFalpha on a reporter gene construct harbouring the proximal PAI-1 promoter and PAI-1 mRNA in cells co-transfected with a dominant-negative PPARgamma construct. RG and PG attenuated TNFalpha-mediated induction of trans-acting factor(s) Nur77/Nurr1 and binding of nuclear proteins (NP) to the cis-acting element (NBRE). SR-202 failed to modulate these effects. The observations suggest TZDs inhibit TNFalpha-mediated PAI-1 induction independent of inducible PPARgamma activation and this may involve in the modulation of Nur77/Nurr1 expression and NP binding to the PAI-1 NBRE.

The prevention of type 2 diabetes--lifestyle change or pharmacotherapy? A challenge for the 21st century.

Diabetes mellitus is occurring in epidemic proportions in many countries. In Australia 7.4% of people over 25 years of age have diabetes (mostly type 2) and comparable or higher prevalences have been reported in the United States and a number of Asian countries. The enormous economic and social cost of this disease makes a compelling case for prevention. Epidemiological studies have shown clearly that type 2 diabetes results from an interaction between a genetic predisposition and lifestyle factors including obesity, sedentary behaviour and both calorie excess and various dietary constituents. The natural history of type 2 diabetes includes a preceding period of impaired glucose tolerance (IGT)/impaired fasting glucose (IFG) which provides an opportunity for targeted intervention within large communities. Lifestyle intervention studies have consistently shown that quite modest changes can reduce the progression from IGT to diabetes by 50-60%. It may, however, not be possible to translate these successful findings to larger cohorts or maintain the lifestyle changes longer term. This has lead to consideration of pharmacotherapy. While small studies with sulphonylureas are inconclusive, benefits have been found for metformin, acarbose and troglitazone. Big intervention studies with ramipril, rosiglitazone, valsartan and nateglinide are underway. Pharmacological intervention raises a whole range of ethical, economic and practical issues not the least of which is the problem of long term therapy of the 'otherwise well'.

Associations between outdoor air pollution and hospital admissions in Brisbane, Australia.

The authors investigated the effects of ambient air pollution on hospital admissions in Brisbane, Australia. The authors used the Air Pollution on Health: European Approach protocol to examine the effects of particles, ozone, sulfur dioxide, and nitrogen dioxide on daily hospital admissions for asthma and respiratory, cardiovascular, and digestive disorders (control diagnosis) that occurred during the period 1987-1994. Ozone was consistently associated with admissions for asthma and respiratory disease-with little evidence of a threshold. In two-pollutant models, the ozone effect was relatively unaffected by the control for high levels of other pollutants. Particulate pollution (measured by nephelometry) was associated positively with admissions for respiratory disease and admissions for asthma in summer, whereas a negative association was observed for cardiovascular admissions. Although sulfur dioxide was associated significantly with admissions for respiratory and cardiovascular disese, a significant association was also found for the control diagnosis of digestive disorders. No significant associations were found for nitrogen dioxide over the study period, although significantly positive seasonal interactions were found for asthma and respiratory disease in autumn, winter, and spring. It was concluded that current levels of ambient air pollution in Brisbane make a significant contribution to the variation in daily hospital admissions for asthma and respiratory disease.

Characterisation and source identification of PM10 aerosol samples collected with a high volume cascade impactor in Brisbane (Australia).

PM10 (particulate matter with aerodynamic diameter < 10 microm) samples of Brisbane air were collected and fractionated into six size fractions (< 0.5, 0.5-0.61, 0.61-1.3, 1.3-2.7, 2.7-4.9 and 4.9-10 microm) with a high volume cascade impactor. The chemical composition of the samples was analysed by techniques including Ion Beam Analysis. On average, 42% of the aerosol mass is in the > 2.7-microm size fraction, with the < 0.5-microm size fraction also contributes 41% of the aerosol mass. The composition of the < 1.3-microm aerosols is significantly different to that of the > 1.3-microm aerosols. The aerosol mass and concentrations of chemical components related to human activities show a bimodal size-distribution pattern, with most of the mass in the accumulation range (< 0.65 microm). The size geometric mean of aerosol mass is 0.96 microm in the samples collected from an industrial/residential site, and is 1.74 microm in the samples collected from a suburban site. The size geometric mean of concentrations of chemical components related to human activities ranges from 0.16 to 0.57 microm. The concentrations of crustal matter and sea salt show a unimodal size-distribution pattern, and with geometric means of 3.73 and 4.12 microm, respectively. Four source factors were resolved by multivariate analysis techniques for the size-fractionated aerosol samples, namely the soil, sea salt, organics and vehicular exhausts factors. The source fingerprints of the factors vary in the size ranges and have implications on the formation and dispersal processes of the particles. On average, the soil and sea salt factors contribute more than 80% of the aerosol mass in the > 2.7-microm fractions, while the organics and vehicular exhausts factors explain almost all the aerosol mass in the < 0.61-microm fractions.

Management of gestational diabetes with a conservative insulin protocol.

OBJECTIVE: To investigate whether 2-hour postprandial blood glucose levels up to 8.0 mmol/L affect maternal or neonatal outcomes in pregnancies complicated by gestational diabetes mellitus (GDM). DESIGN: Retrospective analysis of data collated by the Victorian Perinatal Data Collection Unit. PATIENTS: 394 GDM women and 394 control women matched for age and country of birth who gave birth at a university teaching hospital, 1991-1997. MAIN OUTCOME MEASURES: Maternal--hypertension/pre-eclampsia, obstetric intervention, gestation at delivery, length of hospital stay; neonatal--Apgar scores, time to establish respiration, birthweight, macrosomia, large or small for gestational age (LGA or SGA), fetopelvic disproportion, jaundice, hypoglycaemia. RESULTS: For most outcome measures there were no statistically significant differences between the GDM and control groups. However, in the GDM group, gestation was shorter, hospital stays longer and delivery interventions more common. CONCLUSION: Our study suggests that maternal and neonatal outcomes in GDM women are comparable with those of women without GDM when 2-hour postprandial glucose levels of up to 8mmol/L are maintained. This is 1.0 mmol/L higher than the current Australian Diabetes in Pregnancy Society recommendation.

SEISMOLOGY: Watching the Hayward Fault.

The Hayward fault, located on the east side of the San Francisco Bay, represents a natural laboratory for seismologists, because it does not sleep silently between major earthquakes. In his Perspective, Simpson discusses the study by Bürgmann et al., who have used powerful new techniques to study the fault. The results indicate that major earthquakes cannot originate in the northern part of the fault. However, surface-rupturing earthquakes have occurred in the area, suggesting that they originated to the north or south of the segment studied by Bürgmann et al. Fundamental questions remain regarding the mechanism by which plate tectonic stresses are transferred to the Hayward fault.

Associations between outdoor air pollution and daily mortality in Brisbane, Australia.

The results of several studies have indicated significant associations between daily mortality and air pollution, with little evidence of a threshold. In the current study, the authors examined daily mortality during the period 1987-1993 for the Brisbane region, which is the fastest-growing urban region in Australia (annual average concentration of particulate matter less than 10 microm in diameter = 27 microg/m3, maximum hourly sulfur dioxide level = 60 ppb, and maximum daily ozone hourly level = 118 ppb). The authors conducted a general estimating equation analysis, and they used autoregressive Poisson models for daily mortality to examine associations with air pollution variables. The authors used research methods developed in the Air Pollution on Health, European Approach (APHEA), project to control confounding effects of weather and temporal trends. The air pollutants examined included particulate pollution (measured by nephelometry [bsp data]), sulfur dioxide, ozone, and nitrogen dioxide. The results indicated that the associations between total daily mortality and particulate levels found in studies in the United States and other countries may be applicable in Brisbane, Australia. Ozone levels were also associated significantly with total daily mortality. There was little evidence of interaction between the ozone effects (mainly in summer) and particulates or with sulfur dioxide and nitrogen dioxide. The associations between pollutants (ozone, bsp) and daily mortality were significant only for individuals who were older than 65 y of age; positive associations were also found with cardiovascular disease categories, and the regression coefficients--when significant--were higher than those for total mortality. The results indicated a possible threshold for ozone levels, but a similar result for particulate levels was not apparent.

Seismicity remotely triggered by the magnitude 7.3 landers, california, earthquake.

The magnitude 7.3 Landers earthquake of 28 June 1992 triggered a remarkably sudden and widespread increase in earthquake activity across much of the western United States. The triggered earthquakes, which occurred at distances up to 1250 kilometers (17 source dimensions) from the Landers mainshock, were confined to areas of persistent seismicity and strike-slip to normal faulting. Many of the triggered areas also are sites of geothermal and recent volcanic activity. Static stress changes calculated for elastic models of the earthquake appear to be too small to have caused the triggering. The most promising explanations involve nonlinear interactions between large dynamic strains accompanying seismic waves from the mainshock and crustal fluids (perhaps including crustal magma).

Preferred meal patterns in non-insulin-dependent diabetes.

Current advice on the across-the-day distribution of energy and carbohydrate intakes in non-insulin-dependent diabetes (NIDD) is based on inadequate evidence. We have addressed this by a comparison of an even as opposed to a main evening meal pattern in 11 subjects with NIDD. Contributions of macronutrients to energy intake were fat 29%, protein 20% and carbohydrate 51% with each meal pattern. The peak glycaemic response in the morning was not as good as the response in the evening (P<0.01), where an even energy and carbohydrate spread was used; this contrasts with previous reports in healthy subjects where the morning response to glucose is better than that later in the day. This difference between peak morning and peak evening glycaemic response was not seen with a main evening meal. There was a lower overall glycaemic response with a main evening meal compared with an even meal pattern (P<0.01, by area comparison). The overall insulin response was not significantly different between the two meal patterns, although the sensitivity for insulin appeared better in the evening where there was an evening main meal.

Response of regional seismicity to the static stress change produced by the loma prieta earthquake.

The 1989 Loma Prieta, California, earthquake perturbed the static stress field over a large area of central California. The pattern of stress changes on major faults in the region predicted by models of the earthquake's dislocation agrees closely with changes in the regional seismicity rate after the earthquake. The agreement is best for models with low values of the coefficient of friction (0.1

Putative determinants of arterial wall compliance in NIDDM.

Aortoiliac arterial wall compliance was measured in apparently healthy subjects and in patients with non-insulin-dependent diabetes (NIDDM), on diet alone, who had no clinical evidence of peripheral arterial disease. Compliance was significantly lower in patients with diabetes. The two clinical groups were combined to provide as wide a range of blood glucose values as possible. After allowing for the influence of age, there were significant negative correlations between compliance and free fatty acid and insulin levels. These were almost completely accounted for by differences in blood glucose levels. Therefore, arterial compliance was best predicted on the basis of age and the area under the blood glucose curve.

Sucrose versus saccharin as an added sweetener in non-insulin-dependent diabetes: short- and medium-term metabolic effects.

Seventeen non-insulin-dependent diabetic patients were randomly allocated to their usual diet supplemented daily with either 28 g sucrose or 30 g starch (isoenergetic with sucrose) and saccharin (equivalent sweetness). After 6 weeks, the supplements were reversed. No significant treatment effects were observed on fasting concentrations of blood glucose, plasma insulin or serum triglycerides, or on urinary excretion of glucose, sodium or potassium. Following a standard breakfast with either sucrose or saccharin and starch, no differences between meal responses were observed. This study demonstrates no medium-term metabolic contraindications to including a moderate amount of sucrose in the diets of patients with non-insulin-dependent diabetes mellitus.

Temporal study of metabolic change when poorly controlled noninsulin-dependent diabetics change from low to high carbohydrate and fiber diet.

Thirteen poorly controlled noninsulin-dependent diabetic subjects ingested in succession over 5.5 wk their usual low-carbohydrate, low-fiber diet (LCF) for 3 d, a high-carbohydrate, high-fiber diet (HCF) for 3 wk, and the LCF diet again for 2 wk. All diets were designed to be individually isoenergetic. Fasting plasma glucose fell significantly during the HCF diet and then rose significantly during the last LCF diet. Dietary change rather than hospitalization had its full effect by 18 d. Urinary glucose excretion rose transiently on the HCF diet before also falling significantly. Similarly, pancreatic immunoreactive glucagon (IRG) fell significantly on the HCF diet and increased significantly on the LCF diet. No significant differences were observed in plasma insulin, serum free fatty acids, or monocyte insulin binding activity between the two diets. Reduction in circulating IRG may in part explain the lower fasting (or basal) plasma glucose observed on HCF diets.

Transthoracic needle aspiration biopsy. Review of 233 cases.

In 233 cases in which transthoracic needle aspiration was done at the Mayo Clinic from 1980 through 1983, the cytology slides, tissue fragments and patient histories were reviewed; the original and review diagnoses were compared and correlated with the subsequent clinical course. In most cases, the procedure was performed with an 18-gauge needle under fluoroscopic guidance, primarily in cases with suspected malignant masses that were considered to be not surgically resectable. In 70% of the cases, there was a history of malignancy, and 82% of the malignant lesions were of extrapulmonary origin. Correlation of the original diagnosis with the clinical course yielded 70% (164 cases) true positives, 6% (14 cases) true negatives, 16% (37 cases) false negatives, 0% false positives and 8% (18 cases) indeterminants. In none of the false-negative cases was the slide subsequently read as positive in a blind review. Of the true-positive cases, 12% had positive tissue fragments only, 37% had positive cytology smears only, and 51% had both positive smears and fragments. In 32% of the cases, there were radiologically demonstrable pneumothoraces, and in 12%, placement of a chest tube was required. Hemoptysis occurred in less than 5% of the cases. In summary, transthoracic needle biopsy provides an efficient way to accurately obtain diagnostic tissue, with acceptable minor complications.

Resistance to biological and chemical challenge in rodents treated with xerosin II, a natural product of Achromobacter xerosis.

The biological response-modifying activity of acid-precipitable material from Achromobacter xerosis was first described as suppression of viral pneumonia in mice. Later, this acid-precipitable material (xerosin) was found to have antiinflammatory activity and to induce tumor regression in chickens infected with Rous sarcoma virus. Here, we report further purification of xerosin resulting in a product (xerosin II) that retains high biological activity against viral and endotoxin-induced pneumonia in mice. In addition, we describe new activities of xerosin II in two rat tumor systems. Female CD rats received gastric intubations of 7,12-dimethylbenz(a)anthracene; 2 weeks later, half began 4 weeks of treatment with xerosin II, while others received saline only. Xerosin II treatment significantly delayed the appearance of the first palpable mammary tumors per rat. In female F344 rats implanted with the 13762 mammary tumor, 4 weeks of xerosin II treatment prolonged the survival of rats by an average of 5-11 days (12-24%) in two separate trials. Tumor growth and incidence of metastasis appeared unaffected by xerosin II treatment. Thus, this refined bacterial extract proved to be a potent biological response modifier in four different rodent systems.

Transcriptionally defective nucleocapsids of vesicular stomatitis virus from cells treated with indomethacin.

Indomethacin blocks the biosynthesis of vesicular stomatitis virus (VSV) at the level of primary transcription, RNA replication, and protein synthesis (P. K. Mukherjee and R. W. Simpson (1985), Virology 140, 188-191). Nucleocapsids of infecting virus particles recovered from indomethacin-treated cells were analyzed for in vitro transcriptase activity. Incorporation of [3H]UTP in mixtures containing nucleocapsids from HEp-2 cells pretreated with 10(-3) M indomethacin was inhibited approximately 80% compared to control reactions containing nucleocapsids from untreated infected cells. The level of inhibition of in vitro transcriptase activity of viral nucleocapsids from drug-treated cultures varied according to the cell line used for infection. After indomethacin removal, cells regained their ability to produce enzymatically competent viral-transcribing complexes unless they were subsequently exposed to metabolic inhibitors such as actinomycin D or alpha-amanitin. Enzymatically defective nucleocapsids from indomethacin-treated cells showed enhanced in vitro transcriptase activity in the presence of modulators of prostaglandins and cyclic nucleotides. Electrophoretic analysis of product from in vitro transcriptase reactions revealed that these defective nucleocapsids are unable to synthesize VSV messenger RNA or normal size leader RNA species but only smaller transcripts of undetermined identity.

Statistical modeling of restricted pollutant data sets to assess compliance with air quality criteria.

Three statistical models are used to predict the upper percentiles of the distribution of air pollutant concentrations from restricted data sets recorded over yearly time intervals. The first is an empirical quantile-quantile model. It requires firstly that a more complete date set be available from a base site within the same airshed, and secondly that the base and restricted data sets are drawn from the same distributional form. A two-sided Kolmogorov-Smirnov two-sample test is applied to test the validity of the latter assumption, a test not requiring the assumption of a particular distributional form. The second model represents the a priori selection of a distributional model for the air quality data. To demonstrate this approach the two-parameter lognormal, gamma and Weibull models and the one-parameter exponential model were separately applied to all the restricted data sets. A third model employs a model identification procedure on each data set. It selects the 'best fit' model.

Pathogenesis of cocaine-induced ischemic heart disease. Autopsy findings in a 21-year-old man.

A 21-year-old man with a five-year history of recreational intravenous cocaine abuse developed chest pain within one minute and cardiopulmonary arrest within one hour following an injection. He died and, on autopsy, was found to have severe coronary obstructive lesions, as a result of chronic intimal proliferation, and acute platelet thrombosis. Secondary chronic and acute myocardial ischemic lesions also were observed. Cocaine-induced coronary artery spasm may have occurred and produced focal endothelial injury and platelet aggregation; this pathogenetic mechanism may have accounted for both the chronic and the acute coronary obstructive lesions. In addition, lymphocytic myocarditis was present and may have been related to the long-term cocaine abuse.