Low tacrolimus concentrations and increased risk of early acute rejection in adult renal transplantation

Background. A retrospective analysis was performed on adult renal transplant recipients to evaluate the relationship between tacrolimus trough concentrations and the development of rejection in the first month after transplant. Methods. A total of 349 concentrations from 29 patients, measured by enzyme-linked immunosorbent assay (ELISA), were recorded. Based on an increased serum creatinine, 12 patients were considered to have organ rejection. Rejection was confirmed by biopsy in five of these. The median trough concentration of tacrolimus over the first month of therapy, or until the time of first rejection was compared in rejecters vs non-rejecters. Results. Median trough concentrations of tacrolimus were found to be lower in biopsy-proven rejecters vs non-rejecters (P=0.03) and all rejecters vs nonrejecters (P = 0.04). The average median concentration (+/- SD) in the biopsy-proven rejecter group was 5.09 +/-1.16 ng/ml, compared to 9.20 +/-3.52 ng/ml in the non-rejecter group. After exclusion of an outlier, the average median concentration in all rejecters was 5.57 +/-1.47 ng/rnl, compared with 9.20 +/-3.52 ng/ml in non-rejecters. A rejection rate of 55% was found for patients with a median trough concentration between 0 and 10 ng/ml. This compared with no observed rejection in patients with a median concentration between 10 and 15 ng/ml. Conclusion. A significant relationship exists between organ rejection and median tacrolimus trough concentrations in the first month post-transplant, with patients displaying low concentrations more likely to reject. In order to minimize rejection in the first month after renal transplantation, trough concentrations greater than 10 ng/ml must be achieved.

Long-term outcomes of genetic counseling in women at increased risk of developing hereditary breast cancer Information,

This multicenter study evaluated the impact of genetic counseling in 218 women at risk of developing hereditary breast cancer. Women were assessed prior to counseling and 12-month post-counseling using self-administered, mailed questionnaires. Compared to baseline, breast cancer genetics knowledge was increased significantly at follow-up. and greater increases in knowledge were associated with educational level. Breast cancer anxiety decreased significantly from baseline to follow-up, and these decreases were associated with improvements in perceived risk. A significant decrease in clinical breast examination was observed at the 12-month follow-up. Findings suggest that women with a family history of breast cancer benefit from attending familial cancer clinics as it leads to increases in breast cancer genetics knowledge and decreases in breast cancer anxiety. The lowered rates of clinical breast examination indicate that the content of genetic counseling may need to be reviewed to ensure that women receive and take away the right message. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Are pioneer axons guided by regulatory gene expression domains in the zebrafish forebrain? High-resolution analysis of the patterning of the zebrafish brain during axon tract formation

Although the principles of axon growth are well understood in vitro the mechanisms guiding axons in vivo are less clear. It has been postulated that growing axons in the vertebrate brain follow borders of neuroepithelial cells expressing specific regulatory genes. In the present study we reexamined this hypothesis by analysing the earliest growing axons in the forebrain of embryonic zebrafish. Confocal laser scanning microscopy was used to determine the spatiotemporal relationship between growing axons and the expression pattern of eight regulatory genes in zebrafish brain. Pioneer axons project either longitudinally or dorsoventrally to establish a scaffold of axon tracts during this developmental period. Each of the regulatory genes was expressed in stereotypical domains and the borders of some were oriented along dorsoventral and longitudinal planes. However, none of these borders clearly defined the trajectories of pioneer axons. In two cases axons coursed in proximity to the borders of shh and pax6, but only for a relatively short portion of their pathway. Only later growing axons were closely apposed to the borders of some gene expression domains. These results suggest that pioneer axons in the embryonic forebrain do not follow continuous pathways defined by the borders of regulatory gene expression domains, (C) 2000 Academic Press.

Gender stereotypes and drinking cognitions as indicators of moderate and high risk drinking among young women and men

The study examined differences in gender stereotypes, restrained drinking and self-efficacy for alcohol refusal between moderate and high risk drinkers among a university sample of 301 women and 118 men. Both female and male high risk drinkers displayed a response conflict, typified by high scores on restrained drinking but low scores on self-efficacy. This pattern of response conflict was more pronounced for high risk drinking women, who also identified poorly with feminine trails (e.g. 'nurturing', 'love children', 'appreciative'). The findings are discussed in relation to society's double standard that accepts intoxication in men but condemns it in women. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.

Urban birth and migrant status as risk factors for psychosis: An Australian case-control study

Background Urban birth and migrant status have been identified as risk factors for psychosis in North American and European studies. The aim of this study was to explore these variables in an Australian case-control study. Method Country of birth of subjects and their parents, and place of birth of Australian-born subjects, were examined in individuals with psychosis drawn from a prevalence study (n = 310) and well controls recruited from the same catchment area (n = 303). Results Migrant status was associated with a significantly decreased odds of having a psychotic disorder. For those born in Australia, neither migrant status of parents nor urban birth was associated with having a psychotic disorder. Conclusions The lack of effect for urban birth and second-generation migrant status may help generate candidate environmental risk factors that operate in Europe but not in Australia.

Does 'imprinting' with low prenatal vitamin D contribute to the risk of various adult disorders?

Hypovitaminosis D is a candidate risk-modifying factor for a diverse range of disorders apart from rickets and osteoporosis. Based on epidemiology, and on in vitro and animal experiment, vitamin D has been linked to multiple sclerosis, certain cancers (prostate, breast and colorectal), insulin-dependent diabetes mellitus and schizophrenia. I hypothesise that low pre- and perinatal vitamin D levels imprint on the functional characteristics of various tissues throughout the body, leaving the affected individual at increased risk of developing a range of adult-onset disorders. The hypothesis draws from recent advances in our understanding of the early origin of adult disease and proposes a 'critical window' during which vitamin D levels may have a persisting impact on adult health outcomes. Methods to test the hypothesis are outlined. If correct, the hypothesis has important implications for public health. Careful attention to maternal vitamin D status could translate into diverse improvements in health outcomes for the following generation. (C) 2001 Harcourt Publishers Ltd.

Adult mouse intrinsic laryngeal muscles express high levels of the myogenic regulatory factor, MYF-5

The intrinsic laryngeal muscles display unique structural and functional characteristics that distinguish them from the skeletal muscle of the trunk and limbs. These features include relatively small muscle fibers, super-fast contraction speed, and fatigue resistance. The molecular basis of tissue-specific functions and other characteristics is differential gene expression. Accordingly, we have investigated the molecular basis of the functional specialization of the intrinsic laryngeal muscles by examining the expression of two key genes in the larynx, known to be important for skeletal muscle development and function: (a) the muscle regulatory factor, Myf-5, and (b) the superfast-contracting myosin heavy chain (EO-MyHC). We have found that the adult thyroarytenoid muscles express much higher levels of both Myf-5 and EO-MyHC messenger ribonucleic acid (mRNA), compared to lower hindlimb skeletal muscle where Myf-5 mRNA levels are very low and EO-MyHC is not detectable. These findings suggest that the unique functional characteristics of the intrinsic laryngeal muscles may be based in laryngeal muscle-specific gene expression directed by a unique combination of muscle regulatory factors. Such laryngeal muscle-specific genes may allow the future development of new treatments for laryngeal muscle dysfunction.

Pest risk assessment of insects in sea cargo containers

A survey of the floors of 3001 empty sea cargo containers in storage was undertaken to estimate the quarantine risk of importing exotic insect pests into Australia, with special reference to pests of timber. More than 7400 live and dead insects were collected from 1174 containers. No live infestations of timber-feeding insects were recorded, but feeding damage detected in one floor indicates a low risk of importing colonies of timber pests in containers. The survey collection of dead insects demonstrates that containers are regularly exposed to economically important quarantinable insects, including timber pests (bostrichids, curculionids, cerambycids, siricids and termites), agricultural pests (including Adoretus sinicus, Adoretus sp., Carpophilus obsoletus and Philaenus spumarius), and nuisance pests (vespids and Solenopsis sp.). Stored product pests were found in more than 10% of containers. The assessment of pest risk associated with shipping containers is discussed in terms of the quantity and quality of opportunities for exotic insects to establish via this pathway.

Duck hepatitis B virus expresses a regulatory HBx-like protein from a hidden open reading frame

Duck hepatitis B viruses (DHBV), unlike mammalian hepadnaviruses, are thought to lack X genes, which encode transcription-regulatory proteins believed to contribute to the development of hepatocellular carcinoma. A lack of association of chronic DHBV infection with hepatocellular carcinoma development supports this belief. Here, we demonstrate that DHBV genomes have a hidden open reading frame from which a transcription-regulatory protein, designated DHBx, is expressed both in vitro and in vivo. We show that DHBx enhances neither viral protein expression, intracellular DNA synthesis, nor virion production when assayed in the full-length genome context in LMH cells. However, similar to mammalian hepadnavirus X proteins, DHBx activates cellular and viral promoters via the Raf-mitogen-activated protein kinase signaling pathway and localizes primarily in the cytoplasm. The functional similarities as,well as the weak sequence homologies of DHBx and the X proteins of mammalian hepadnaviruses strongly suggest a common ancestry of ortho- and avihepadnavirus X genes. In addition, our data disclose similar intracellular localization and transcription regulatory functions of the corresponding proteins, raise new questions as to their presumed role in hepatocarcinogenesis, and imply unique opportunities for deciphering of their still-enigmatic in vivo functions.

Body size and risk of extinction in Australian mammals

The link between body size and risk of extinction has been the focus of much recent attention. For Australian terrestrial mammals this link is of particular interest because it is widely believed that species in the intermediate size range of 35-5500 g (the critical weight range) have been the most prone to recent extinction. But the relationship between body size and extinction risk in Australian mammals has never been subject to a robust statistical analysis. Using a combination of randomization tests and phylogenetic comparative analyses, we found that Australian mammal extinctions and declines have been nonrandom with respect to body size, but we reject the hypothesis of a critical weight range at intermediate sizes. Small species appear to be the least prone to extinction, but extinctions have not been significantly clustered around intermediate sizes. Our results suggest that hypotheses linking intermediate body size with high risk of extinction in Australian mammals are misguided and that the focus of future research should shift to explaining why the smallest species are the most resistant to extinction.

Service guarantees: A strategic mechanism to minimise customers' perceived risk in service organisations

Service offerings are largely intangible in nature. Customers are thus unable to assess the purchase outcome prior to experience, rendering the risk of possible customer dissatisfaction very high. It is argued that the concept of service guarantees proposed by services management theory can be effectively utilised to reduce the perceived risk of dissatisfaction for the customer in service organisations. Additionally, it is suggested that service guarantees force management to undertake activities which elevate the superiority of the organisation in the eyes of the customer and, thus, the opportunity to transform one-time customers into loyal ones. The purpose of this paper is twofold: first, to illustrate how customers’ behavioural intentions can be influenced by the use of a service guarantee; and second, to outline a systematic process that can help service business managers to develop and implement an effective service guarantee. This research highlights the numerous benefits available to service organisations by utilising the service guarantee as a strategic tool. Some of the important management implications are also outlined.

Habitat complexity, spatial interference, and "minimum risk distribution": a framework for population stability

In the past century, the debate over whether or not density-dependent factors regulate populations has generally focused on changes in mean population density, ignoring the spatial variance around the mean as unimportant noise. In an attempt to provide a different framework for understanding population dynamics based on individual fitness, this paper discusses the crucial role of spatial variability itself on the stability of insect populations. The advantages of this method are the following: (1) it is founded on evolutionary principles rather than post hoc assumptions; (2) it erects hypotheses that can be tested; and (3) it links disparate ecological schools, including spatial dynamics, behavioral ecology, preference-performance, and plant apparency into an overall framework. At the core of this framework, habitat complexity governs insect spatial variance. which in turn determines population stability. First, the minimum risk distribution (MRD) is defined as the spatial distribution of individuals that results in the minimum number of premature deaths in a population given the distribution of mortality risk in the habitat (and, therefore, leading to maximized population growth). The greater the divergence of actual spatial patterns of individuals from the MRD, the greater the reduction of population growth and size from high, unstable levels. Then, based on extensive data from 29 populations of the processionary caterpillar, Ochrogaster lunifer, four steps are used to test the effect of habitat interference on population growth rates. (1) The costs (increasing the risk of scramble competition) and benefits (decreasing the risk of inverse density-dependent predation) of egg and larval aggregation are quantified. (2) These costs and benefits, along with the distribution of resources, are used to construct the MRD for each habitat. (3) The MRD is used as a benchmark against which the actual spatial pattern of individuals is compared. The degree of divergence of the actual spatial pattern from the MRD is quantified for each of the 29 habitats. (4) Finally, indices of habitat complexity are used to provide highly accurate predictions of spatial divergence from the MRD, showing that habitat interference reduces population growth rates from high, unstable levels. The reason for the divergence appears to be that high levels of background vegetation (vegetation other than host plants) interfere with female host-searching behavior. This leads to a spatial distribution of egg batches with high mortality risk, and therefore lower population growth. Knowledge of the MRD in other species should be a highly effective means of predicting trends in population dynamics. Species with high divergence between their actual spatial distribution and their MRD may display relatively stable dynamics at low population levels. In contrast, species with low divergence should experience high levels of intragenerational population growth leading to frequent habitat-wide outbreaks and unstable dynamics in the long term. Six hypotheses, erected under the framework of spatial interference, are discussed, and future tests are suggested.