HOMA insulin sensitivity index and the risk of all-cause mortality and cardiovascular disease events in the general population : the Australian diabetes, obesity and lifestyle study (AusDiab) study

Aims/hypothesis We assessed whether the relationships between insulin sensitivity and all-cause mortality as well as fatal or non-fatal cardiovascular disease (CVD) events are independent of elevated blood glucose, high blood pressure, dyslipidaemia and body composition in individuals without diagnosed diabetes.
Methods Between 1999 and 2000, baseline fasting insulin, glucose and lipids, 2 h plasma glucose, HbA1c, anthropometrics, blood pressure, medication use, smoking and history of CVD were collected from 8,533 adults aged >35 years from the population-based Australian Diabetes, Obesity and Lifestyle study. Insulin sensitivity was estimated by HOMA of insulin sensitivity (HOMA-%S). Deaths and fatal or non-fatal CVD events were ascertained through linkage to the National Death Index and medical records adjudication.
Results After a median of 5.0 years there were 277 deaths and 225 CVD events. HOMA-%S was not associated with all-cause mortality. Compared with the most insulin-sensitive quintile, the combined fatal or non-fatal CVD HR (95% CI) for quintiles of decreasing HOMA-%S were 1.1 (0.6–1.9), 1.4 (0.9–2.3), 1.6 (1.0–2.5) and 2.0 (1.3–3.1), adjusting for age and sex. Smoking, CVD history, hypertension, lipid-lowering medication, total cholesterol and waist-to-hip ratio moderately attenuated this relationship. However, the association was rendered non-significant by adding HDL. Fasting plasma glucose, but not HOMA-%S significantly improved the prediction of CVD, beyond that seen with other risk factors.
Conclusions/interpretation In this cohort, HOMA-%S showed no association with all-cause mortality and only a modest association with CVD events, largely explained by its association with HDL. Fasting plasma glucose was a better predictor of CVD than HOMA-%S.

Vigilantism, the press and signal crimes 2006 - 2007

The clear presence of vengeance as an underlying motive behind calls for self-help in the immediate aftermath of some violent homicides indicates that community protection is largely irrelevant where vigilantism is associated with these 'signal crimes'. This paper documents the characteristics of five major cases between 2006 and 2007 where the threat ofcommunity-generated vigilante activity received media coverage, the nature of that coverage, the role of police in cautioning the public to reassert their legitimacy and monopoly over the correct procedures for conducting criminal
investigations and the implications of these issues in light of the moral 'outrage' associated with the status of the victim in each case. In an era of increased community concern about crime, it appears vigilantism is an important rhetorical indicator of the level of collective insecurity prompted by fatal assaults, especially in regional areas characterised by underlying racial
tensions and cases involving vulnerable child victims. However, when viewed alongside the virtual victimhood promoted by stylised press reporting, it appears 'vigilantism' is a pertinent signifier of public anxiety over the timing, location and antecedents of some serious violent crimes, rather than a descriptor of any substantive community-generated measures aimed at promoting greater levels of public safety.

Thromboyytic therapy for acute ischaemic stroke : successful implementation in an Australian tertiary hospital

Background: The use of tissue-type plasminogen activator (t-PA) in ischaemic stroke outside of experienced stroke centres remains controversial. The aim of this study was to present the initial experience with t-PA in patients with ischaemic stroke at an institution with no prior experience in i.v. stroke thrombolysis and to compare results to published reports.

Methods: Prospective audit of 888 patients with consecutive stroke and transient ischaemic attack admitted to a 426-bed tertiary referral hospital from March 2003 to October 2005. Main outcome measures were treatment rate, exclusion criteria, protocol violations, intracerebral haemorrhage, disability (modified Rankin scale) and mortality at 3 months.

Results: Over the study period, 72 patients received t-PA (11% of ischaemic strokes). The main reason for exclusion was presentation beyond 3 h of onset (44%); if all eligible patients had arrived within 3 h, treatment rate was estimated at 32.5%. Protocol violations occurred in 15 (21%) patients. There were seven (10%) asymptomatic intracerebral haemorrhage and one (1%) non-fatal symptomatic intracerebral haemorrhage. At 3 months, 37% had achieved excellent recovery (modified Rankin scale 0–1) and seven (10%) had died. The delivery and outcomes associated with the use of t-PA were comparable to the results of the National Institute of Neurological Disorders and Stroke trial and meta-analysis of open-labelled studies.

Conclusion: With appropriate infrastructure and protocols, previously inexperienced tertiary referral centres can replicate the experience and outcome measures reported by clinical trials of t-PA in patients with stroke.

East Timor in 2008 : year of reconstruction

The article discusses reconstruction of East Timor in 2008 after the near-fatal shooting of President Jose Ramos-Horta and the death of his rival Major Alfredo Reinado. It notes near state collapse following the desertion of soldiers in 2006 and returning displaced persons to their homes in the aftermath.

The Sawankhalok ceramic industry

A techno-historical study of a commercial initiative by 13th century Thai village potters to produce domestic stoneware ceramics. However their enterprise's success attracted the exploitative interest of regional trade entrepreneurs whose specialisation of the industry created a fatal lack of efficiency and flexibility.

The role of ATP7A in copper homeostasis

Menkes disease is a fatal genetic copper deficiency. The Menkes protein (ATP7A) was found to remove copper from tissues in mice that expressed the human ATP7A. Promising results were obtained with the use of a new copper complex for treatment of Menkes disease using a mouse model.

A question of self-preservation : immunopathology in influenza virus infection

Influenza A viruses that circulate normally in the human population cause a debilitating, though generally transient, illness that is sometimes fatal, particularly in the elderly. Severe complications arising from pandemic influenza or the highly pathogenic avian H5N1 viruses are often associated with rapid, massive inflammatory cell infiltration, acute respiratory distress, reactive hemophagocytosis and multiple organ involvement. Histological and pathological indicators strongly suggest a key role for an excessive host response in mediating at least some of this pathology. Here, we review the current literature on how various effector arms of the immune system can act deleteriously to initiate or exacerbate pathological damage in this viral pneumonia. Generally, the same immunological factors mediating tissue damage during the anti-influenza immune response are also critical for efficient elimination of virus, thereby posing a significant challenge in the design of harmless yet effective therapeutic strategies for tackling influenza virus.

Neurological complication of systemic cancer

Neurological complications of systemic cancer—those arising outside the nervous system—can be distressing, disabling, and sometimes fatal. Diagnosis is often difficult because different neurological disorders may present with similar signs and symptoms. Furthermore, comorbid neurological illnesses, common in elderly patients with cancer, can complicate diagnosis. Early diagnosis and aggressive treatment can improve neurological symptoms and can substantially enhance a patient's quality of life. We approach the problem of neurological complications of systemic cancer as would a neurologist: first by identifying the anatomical area or areas that are affected (ie, brain, spinal cord, peripheral nerve), then by evaluating the diagnostic approach, considering the symptoms and signs and including appropriate laboratory tests, and finally, by recommending treatment. We focus on disorders that are difficult to diagnose, need neurological consultation, and for which effective treatments exist.

The burden of disease and injury in Australia

This report provides an overview of results from the Australian Burden of Disease and Injury Study undertaken by the AIHW during 1998 and 1999. The Study uses the methods developed for the Global Burden of Disease Study, adapted to the Australian context and drawing extensively on Australian sources of population health data. It provides a comprehensive assessment of the amount of ill health and disability, the ‘burden of disease’ in Australia in 1996.

Mortality, disability, impairment, illness and injury arising from 176 diseases, injuries and risk factors are measured using a common metric, the Disability-Adjusted Life Year or DALY. One DALY is a lost year of ‘healthy’ life and is calculated as a combination of years of life lost due to premature mortality (YLL) and equivalent ‘healthy’ years of life lost due to disability (YLD). This report provides estimates of the contribution of fatal and non-fatal health outcomes to the total burden of disease and injury measured in DALYs in Australia in 1996.

The Australian burden of disease study : measuring the loss of health from diseases, injuries and risk factors

This is an overview of the first burden of disease and injury studies carried out in Australia. Methods developed for the World Bank and World Health Organization Global Burden of Disease Study were adapted and applied to Australian population health data. Depression was found to be the top- ranking cause of non-fatal disease burden in Australia, causing 8% of the total years lost due to disability in 1996. Mental disorders overall were responsible for nearly 30% of the non-fatal disease burden. The leading causes of total disease burden (disability-adjusted life years [DALYs]) were ischaemic heart disease and stroke, together causing nearly 18% of the total disease burden. Depression was the fourth leading cause of disease burden, accounting for 3.7% of the total burden. Of the 10 major risk factors to which the disease burden can be attributed, tobacco smoking causes an estimated 10% of the total disease burden in Australia, followed by physical inactivity (7%).

Therapeutic equivalence and the generic competition paradox

Following the passage of the Waxman-Hatch Act (1984), FDA approval for a generic drug requires the establishment of bio-equivalence between the generic drug and an FDA approved branded drug. However, a large body of evidence in the medical community suggests that bio-equivalence does not guarantee therapeutic equivalence; in some instances the lack of therapeutic equivalence can lead to fatal consequences for patients switching to generic products. In this paper, we construct a simple model to analyze the implications of therapeutic non-equivalence between branded and generic drugs. We show, theoretically and empirically, that this distinction can provide a plausible explanation of the generic competition paradox.

In vitro studying corrosion behaviour of biocorrodible Mg alloys

The idea of bioabsorbable/biocorrodible stents has gained increasing attention in the last decade. Permanent coronary stents, traditionally made from 316L grade stainless steel, are routinely used for the treatment of blocked arteries. However, these stents can cause complications such as restenosis, thrombosis and the need for the patient to undergo prolonged antiplatelet therapy. Biodegradable metal stents provide an opportunity for the stent to remain in place for a period to ensure restoration of function and then degrade through a carefully controlled bio-corrosion process. Among the number of potentially suitable materials, Magnesium alloys have shown great promise as a stent material due to their non-toxicity [1] and the corrosion rates attainable in biological environments. However, a carefully controlled corrosion process is essential in order to avoid hyper hydrogen generation and the fatal consequences that follow. In addition uniform corrosion is a basic requirement to maintain the mechanical integrity and load bearing characteristics. Work being undertaken in our laboratories focuses on controlling the corrosion behaviour of magnesium in a simulated biological environment in the presence of protein. In the investigation reported here the Mg alloy has been examined using Scanning Electrochemical Microscope (SECM) to visualize the corrosion process and identify the corrosion pattern. Complementary bulk electrochemical techniques (EIS and potentiodynamic polarization) have been used to acquire kinetic and mechanistic information. Early results obtained by SECM have revealed the tendency towards pitting corrosion in the early stages which subsequently develops in to filiform corrosion.

In a city like Delhi: urban spirituality, sustainability and women

This paper is intended to be provocative as a way of exposing any fatal flaws in its logic. It advocates a pragmatic foundational role for spirituality upon which sustainable development can be built. It goes on to assert the importance of articulating spiritual dimensions of urban communities as integral to the spiritual and general sustainability of cities.

Death or survival from invasive pneumococcal disease in Scotland: associations with serogroups and multilocus sequence types

We describe associations between death from invasive pneumococcal disease (IPD) and particular serogroups and sequence types (STs) determined by multilocus sequence typing (MLST) using data from Scotland. All IPD episodes where blood or cerebrospinal fluid (CSF) culture isolates were referred to the Scottish Haemophilus, Legionella, Meningococcal and Pneumococcal Reference Laboratory (SHLMPRL) from January 1992 to February 2007 were matched to death certification records by the General Register Office for Scotland. This represented 5959 patients. The median number of IPD cases in Scotland each year was 292. Deaths, from any cause, within 30 days of pneumococcal culture from blood or CSF were considered to have IPD as a contributing factor. Eight hundred and thirty-three patients died within 30 days of culture of Streptococcus pneumoniae from blood or CSF [13.95 %; 95 % confidence interval (13.10, 14.80)]. The highest death rates were in patients over the age of 75. Serotyping data exist for all years but MLST data were only available from 2001 onward. The risk ratio of dying from infection due to particular serogroups or STs compared to dying from IPD due to all other serogroups or STs was calculated. Fisher’s exact test with Bonferroni adjustment for multiple testing was used. Age adjustment was accomplished using the Cochran–Mantel–Haenszel test and 95 % confidence intervals were reported. Serogroups 3, 11 and 16 have increased probability of causing fatal IPD in Scotland while serogroup 1 IPD has a reduced probability of causing death. None of the 20 most common STs were significantly associated with death within 30 days of pneumococcal culture, after age adjustment. We conclude that there is a stronger association between a fatal outcome and pneumococcal capsular serogroup than there is between a fatal outcome and ST.

New insights into the role of MHC diversity in devil facial tumour disease

Devil facial tumour disease (DFTD) is a fatal contagious cancer that has decimated Tasmanian devil populations. The tumour has spread without invoking immune responses, possibly due to low levels of Major Histocompatibility Complex (MHC) diversity in Tasmanian devils. Animals from a region in north-western Tasmania have lower infection rates than those in the east of the state. This area is a genetic transition zone between sub-populations, with individuals from north-western Tasmania displaying greater diversity than eastern devils at MHC genes, primarily through MHC class I gene copy number variation. Here we test the hypothesis that animals that remain healthy and tumour free show predictable differences at MHC loci compared to animals that develop the disease.