Auditor independence and fee dependence

This study investigates whether fee dependence within the audit firms' offices jeopardises auditor independence. Fee dependence is examined at both the national audit firm level as well as the local office level and in a setting where public disclosure of fees is mandatory. We focus our tests on audit fee dependence and at the same time we control for the effects of non-audit service fee dependence post the 1989 mergers. We operationalise the exercise of independent judgement in auditing by the propensity to issue qualified audit opinions. If fee dependence affects auditors' independent judgement, then auditors are less likely to qualify the accounts. The study's results show that the level of auditor fee dependence does not affect auditor propensity to issue unqualified audit opinions. The findings remain robust to a number of sensitivity tests including the analyses controlling for the effects of non-audit service fee dependence and other settings in which there is heightened pressure on auditors to confront the effects of fee dependence on exercising independent audit judgement. (C) 2002 Elsevier Science B.V. All rights reserved.

Fate of swallowed interleukin 8 and TNF alpha and effect on the wistar rat gut

To evaluate the passage of cytokines through the gastrointestinal tract, we investigated the digestion of interleukin-8 (IL-8) and tumour necrosis factor α (TNFα), in vitro and in vivo, and their propensity to induce intestinal inflammation. We serially immuno-assayed IL-8 and TNFα solutions co-incubated with each of three pancreatin preparations at pH 4.5 and pH 8. We gavaged IL-8, TNFα and marker into 15 Wistar rats, and measured their faecal cytokine concentrations by ELISA and histologically examined their guts. IL-8 immunoreactivity was extinguished by all pancreatin preparations after 1 h of incubation at 37 °C. TNFα concentration progressively fell from 1 to 4 h with all enzyme preparations. Buffer control samples maintained their cytokine concentrations throughout incubation. No IL-8 or TNFα was detected in any rat faecal pellets. There was no significant proinflammatory effect of the gavaged cytokines on rat intestine. IL-8 and TNFα in aqueous solution could well be fully digested in the CF gut when transit time is normal and exogenous enzymes are provided, although cytokines swallowed in viscous sputum may be protected from such digestion. Copyright © 2011 Elsevier B.V. All rights reserved

Melanoma in adolescents: A case-control study of risk factors in Queensland, Australia

The incidence of melanoma increases markedly in the second decade of life but almost nothing is known of the causes of melanoma in this age group. We report on the first population-based case-control study of risk factors for melanoma in adolescents (15-19 years). Data were collected through personal interviews with cases, controls and parents. A single examiner conducted full-body nevus counts and blood samples were collected from cases for analysis of the CDKN2A melanoma predisposition gene. A total of 201 (80%) of the 250 adolescents with melanoma diagnosed between 1987 and 1994 and registered with the Queensland Cancer Registry and 205 (79%) of 258 age-, gender- and location-matched controls who were contacted agreed to participate. The strongest risk factor associated with melanoma in adolescents in a multivariate model was the presence of more than 100 nevi 2 mm or more in diameter (odds ratio [OR] = 46.5, 95% confidence interval [Cl] = 11.4-190.8). Other risk factors were red hair (OR = 5.4, 95%Cl = 1.0-28.4); blue eyes (OR = 4.5, 95%Cl = 1.5- 13.6); inability to tan after prolonged sun exposure (OR = 4.7, 95%Cl = 0.9-24.6); heavy facial freckling (OR = 3.2, 95% Cl = 0.9-12.3); and family history of melanoma (OR = 4.0, 95%Cl = 0.8-18.9). Only 2 of 147 cases tested had germline variants or mutations in CDKN2A. There was no association with sunscreen use overall, however, never/rare use of sunscreen at home under the age of 5 years was associated with increased risk (OR = 2.2, 95%Cl = 0.7-7.1). There was no difference between cases and controls in cumulative sun exposure in this high-exposure environment. Factors indicating genetic susceptibility to melanoma, in particular, the propensity to develop nevi and freckles, red hair, blue eyes, inability to tan and a family history of the disease are the primary determinants of melanoma among adolescents in this high solar radiation environment. Lack of association with reported sun exposure is consistent with the high genetic susceptibility in this group. (C) 2002 Wiley-Liss, Inc.

Streptococcus pyogenes prtFII, but not sfbI, sfbII or fbp54, is represented more frequently among invasive-disease isolates of tropical Australia

Streptococcus pyogenes (group A streptococcus) strains may express several distinct fibronectin-binding proteins (FBPs) which are considered as major streptococcal adhesins. Of the FBPs, SfbI was shown in vitro to promote internalization of the bacterium into host cells and has been implicated in persistence. In the tropical Northern Territory, where group A streptococcal infection is common, multiple genotypes of the organism were found among isolates from invasive disease cases and no dominant strains were observed. To determine whether any FBPs is associated with invasive disease propensity of S. pyogenes, we have screened streptococcal isolates from bacteraemic and necrotizing fasciitis patients and isolates from uncomplicated infections for genetic endowment of 4 FBPs. No difference was observed in the distribution of sfbII, fbp54 and sfbI between the blood isolates' and isolates from uncomplicated infection. We conclude that the presence of sfbI does not appear to promote invasive diseases, despite its association with persistence. We also show a higher proportion of group A streptococcus strains isolated from invasive disease cases possess prtFII when compared to strains isolated from non-invasive disease cases. We suggest that S. pyogenes may recruit different FBPs for different purposes.

NAD-glycohydrolase production and speA and speC distribution in group A streptococcus (GAS) isolates do not correlate with severe GAS diseases in the Australian population

Streptococcus pyogenes isolates from a tropical region and a subtropical region of Australia with high and low incidences of severe streptococcal diseases, respectively, were analyzed for speA, speB, and speC gene distributions and NAD-glycohydrolase expression. No direct correlation of these characteristics with a propensity to cause invasive diseases was observed.

Synthesis and structural analysis of the N-terminal domain of the thyroid hormone-binding protein transthyretin

Transthyretin (TTR) is a 55 kDa protein responsible for the transport of thyroid hormones and retinol in human serum. Misfolded forms of the protein are implicated in the amyloid diseases familial amyloidotic polyneuropathy and senile systemic amyloidosis. Its folding properties and stabilization by ligands are of current interest due to their importance in understanding and combating these diseases. To assist in such studies we developed a method for the solid phase synthesis of the monomeric unit of a TTR analogue and its folding to form a functional 55 kDa tetramer. The monomeric unit of the protein was chemically synthesized in three parts, comprising amino acid residues 151, 5499 and 102127, and ligated using chemoselective thioether ligation chemistry. The synthetic protein was folded and assembled to a tetrameric structure in the presence of the TTRs native ligand, thyroxine, as shown by gel filtration chromatography, native gel electrophoresis, TTR antibody recognition and thyroid hormone binding. In the current study the solution structure of the first of these fragment peptides, TTR(151) is examined to determine its intrinsic propensity to form beta-sheet structure, potentially involved in amyloid fibril formation by TTR. Despite the presence of extensive beta-structure in the native form of the protein, the Nterminal fragment adopts an essentially random coil conformation in solution.

Kinetic parameters associated with self-heating of New Zealand coals under adiabatic conditions

Adiabatic self-heating tests were carried out on five New Zealand coal samples ranging in rank from lignite to high-volatile bituminous. Kinetic parameters of oxidation were obtained front the self-heating curves assuming Arrhenius behaviour. The activation energy E (kJ mol(-1)) and the pre-exponential factor A (s(-1)) were determined in the temperature range of 70-140 degreesC. The activation energy exhibited a definite rank relationship with a minimum E of 55 kJ mol(-1) occurring at a Suggate rank of similar to6.2 corresponding to subbituminous C. Either side of this rank there was a noticeable increase in the activation energy indicating lower reactivity of the coal. A similar rank trend was also observed in the R-70 self-heating rate index values that were taken from the initial portion of the self-heating curve front 40 to 70 degreesC. From these results it is clear that the adiabatic method is capable of providing reliable kinetic parameters of coal oxidation.

The role of morphine-6-glucuronide (M6G) in pain control

Morphine-6beta-D-glucuronide (M6G) is an analgesically active metabolite of morphine, accounting for approximate to10% of the morphine dose when administered by systemic routes to humans. Although M6G is more hydrophilic than morphine, it crosses the blood-brain barrier, albeit relatively slowly. For this reason, it is generally thought that, after chronic dosing, M6G contributes significantly to the analgesic effects of systemically administered morphine. Owing to its polar nature, M6G is cleared from the systemic circulation primarily via renal elimination. As M6G accumulates in patients with renal impairment, there is an increased risk of M6G-induced respiratory depression in renal failure patients who are being dosed chronically with systemic morphine. Consistent with its analgesic and respiratory depressant properties, M6G binds to the p-opioid receptor in a naloxone-reversible manner. Although the affinity of M6G for the mu-opioid receptor is similar to or slightly less than that of morphine, preclinical studies in rodents show that M6G is one to two orders of magnitude more potent than morphine when administered by central routes. This major discrepancy between the markedly higher intrinsic antinociceptive potency of M6G relative to morphine, despite their similar p-opioid receptor binding affinities, is difficult to reconcile. It has been proposed that M6G mediates its pain-relieving effects through a novel 'M6G opioid receptor', while others have argued that M6G may have higher efficacy than morphine for transduction of intracellular events. When administered by parenteral routes to rodents, M6G's antinociceptive potency is no more than twofold higher than morphine. In humans, the analgesic efficacy and respiratory depressant potency of M6G relative to morphine have been assessed in a number of short-term studies involving the intrathecal or intravenous routes of administration. For example, in hip replacement patients, intrathecal M6G provided excellent postoperative analgesia but the occurrence of late respiratory depression in 10% of these patients raised serious concern about safety. In postoperative patients, intravenous M6G administered by means of patient-controlled analgesia (PCA), or bolus plus PCA, produced no analgesia in one study and limited analgesia in another. Similarly, there was a lack of significant analgesia in healthy volunteers who received intravenous M6G for the alleviation of experimental pain (carbon dioxide applied to the nasal mucosa). In contrast, satisfactory analgesia was produced by bolus doses of intravenous M6G administered to patients with cancer pain, and to healthy volunteers with experimentally-induced ischaemic, electrical or thermal (ice water) pain. Studies to date in healthy volunteers suggest that intravenous M6G may be a less potent respiratory depressant and have a lower propensity for producing nausea and vomiting than morphine. However, it is unclear whether equi-analgesic doses of M6G and morphine were compared. Clearly, more extensive short-term trials, together with studies involving chronic M6G administration, are necessary before the potential clinical utility of M6G as an analgesic drug in its own right can be determined.

Merkel-cell carcinoma of the skin

Merkel-cell carcinoma (MCC) is a rare form of skin cancer of neuroendocrine origin that has been described as the most aggressive cutaneous malignancy. The cell of origin is thought to be the Merkel cell or skin-pressure receptor. It has the propensity for dermal-lymphatic invasion, and nodal and haematogenous spread. Factors that have been implicated in its cause include exposure to sunlight and immunosuppression. The tumour has many similarities to small-cell carcinoma of the lung, with intrinsic sensitivity to ionising radiation and chemotherapy, and an aggressive metastatic potential. The best treatment outcomes can be achieved with early diagnosis and the integration of surgery, radiation, and chemotherapy. The treatment challenges for the clinician are often enormous because many of the patients are elderly and because lesions occur in difficult sites such as the head and neck region and the lower leg.

The Migration of Doctors and Nurses from South Pacific Island Nations

Little is known of the structure of the international migration of skilled health professionals. Accelerated migration of doctors and nurses from the Pacific island states of Fiji, Samoa and Tonga to the Pacific periphery is part of the globalization of health care. The findings from a recent survey of 251 doctors and nurses from the three island countries are reported here. Key determinants of both present migration status and future migration intentions were analyzed using econometric methods. Nurses' and doctors' propensities to migrate are influenced by both income and non-income factors, including ownership of businesses and houses. Migrants also tend to have more close relatives overseas, to have trained there, and so experienced superior working conditions. Migration propensities vary between countries, and between nurses and doctors within countries. Tongan nurses have a higher propensity to migrate, mainly because of greater relative earnings differentials, but are also more likely to return home. The role of kinship ties, relative income differentials and working conditions is evident in other developing country contexts. Remittances and return migration, alongside business investment, bring some benefits to compensate for the skill drain. National development policies should focus on encouraging return migration, alongside retention and recruitment, but are unlikely to prevent out migration. (C) 2003 Elsevier Ltd. All rights reserved.

Relationship between ash content and R-70 self-heating rate of Callide Coal

Borecore samples from the Trap Gully pit at Callide have been assessed using the R-70 self-heating test. The highest R-70 self-heating rate value was 16.22 degrees C/h, which is consistent with the subbituminous rank of the coal. R-70 decreases significantly with increasing mineral matter content, as defined by the ash content of the coal. This effect is due to the mineral matter in the coal acting as a heat sink. A trendline equation has been fitted to the borecore data from the Trap Gully pit: R-70 = 0.0029 x ash(2) - 0.4889 x ash + 20.644, where all parameters are on a dry-basis. This relationship can be used to model the self-heating hazard of the pit, both vertically and laterally. (c) 2005 Elsevier B.V All rights reserved.

Comparison of the R-70 self-heating rate of New Zealand and Australian coals to Suggate rank parameter

Samples from New Zealand and Australia have been tested in an adiabatic oven to assess the effect of rank on the R-70 selfheating rate of coal. A non-linear relationship can be defined for coals from both countries using the revised Suggate rank (S-r) parameter. Subbituminous coals have the highest R-70 self-heating rate values, which are 20 times that of high volatile A bituminous coals on a dry mineral matter free basis (similar to 1 cf. 20 degrees C h(-1)). However, the moderating effects of moisture and mineral matter can reduce this difference to only 2-3 times for coal in-situ. (c) 2005 Elsevier B.V All rights reserved.

Morningness-eveningness orientation, optimal time-of-day and attitude change: Evidence for the systematic processing of a persuasive communication

This study investigates the effects of morningness-eveningness orientation and time-of-day on persuasion. In an attitude change paradigm, 120 female participants read a persuasive message that consisted of six counter-attitudinal arguments (anti-voluntary euthanasia) either in the morning (8:30 a.m.) or in the evening (7:00 p.m.). Attitude change was assessed by measuring attitudes towards the target issue before and after exposure to the message. Message processing was assessed by thought-listing and message recall tasks. Self-reported mood and arousal were monitored throughout. Participants were classified into M- and E-types according to their scores on the Horne and Ostberg (1976) MEQ questionnaire. When tested at their respective optimal time-of-day (i.e., morning for M-types/evening for E-types), M- and E-types reported higher energetic arousal, greater agreement with the message, greater message-congruent thinking, and a propensity for superior message recall compared to M- and E-types tested at their nonoptimal time-of-day (i.e., evening for M-types/morning for E-types). The attitude change in those tested at their optimal time-of-day was mediated by the level of message-congruent thinking. Results are interpreted in terms of the Elaboration Likelihood Model of persuasion. (c) 2005 Elsevier Ltd. All rights reserved.

Community perceptions of suspicious pigmented skin lesions: are they accurate when compared to general practitioners?

Community responses (n = 925, response rate = 71%) of a series of eight photographs of pigmented skin lesions were compared against those of general practitioners (n = 114, response rate = 77%), considered to be the most relevant gold standard. The eight photographs included three melanomas, two potentially malignant lesions and three benign pigmented lesions. Over the pool of lesions examined, the average probability that community members thought a lesion was likely to be skin cancer (0.68 [99% CI = 0.66-0.69]) was higher (p < 0.0001) than that of the comparison general practitioners 0.58 [99% CI = 0.55-0.62]. This reflects a general (but not consistent) inflated propensity to over-diagnose among community members. The average probability that respondents indicated they would seek medical advice for a lesion was 0.71 [99% CI = 0.70-0.73]. As expected, this was strongly associated with their perceptions of the skin lesion. These results suggest that the community can play a valuable role in assessing the need for medical evaluation of pigmented skin lesions. (c) 2004 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved.

Disulfide-linked dimers of human adrenaline synthesizing enzyme PNMT are catalytically active

The crystal structure of human phenylethanolamine N-methyltransferase (hPNMT) reveals a disulfide- linked dimer, despite the presence of reducing agent in the crystallisation conditions. By removing the reducing agent, hPNMT crystals grow more rapidly and at lower protein concentrations. However, it was unclear whether the disulfide bonds are only present in the crystal form or whether these affect enzyme activity. The solution oligomeric state of hPNMT was investigated using biochemical techniques and activity assays. We found that in the absence of reducing agent, hPNMT forms dimers in solution. Furthermore, the solution dimer of hPNMT incorporates disulfide bonds, since this form is sensitive to reducing agent. The C48A and C139A mutants of hPNMT, which are incapable of forming the disulfide bond observed in the crystal structure, have a decreased propensity to form dimer in solution. Those dimers that do form are also sensitive to reducing agent. Further, the C48A/C139A double mutant shows only monomeric behaviour. Both dimeric and monomeric hPNMT, as well as mutants have wildtype enzyme activity. These results show that a variety of disulfides, including those observed in the crystal structure, can form in solution. In addition, disulfide-linked dimers are as active as the monomeric enzyme indicating that the crystal structure of the protein is a valid target for inhibitor design. Crown Copyright (c) 2005 Published by Elsevier B.V. All rights reserved.