Classification of drugs in absorption classes using the classification and regression trees (CART) methodology.

Classification and regression trees (CART) were evaluated for their potential use in a quantitative structure-activity relationship (QSAR) context. Models were build using the published absorption values for 141 drug-like molecules as response variable and over 1400 molecular descriptors as potential explanatory variables. Both the role of two- and three-dimensional descriptors and their relative importance were evaluated. For the used dataset, CART models showed high descriptive and predictive abilities. The predictive abilities were evaluated based on both cross-validation and an external test set. Application of the variable ranking method to the models showed high importances for the n-octanol/water partition coefficient (logP) and polar surface area (PSA). This shows that CART is capable of selecting the most important descriptors, as known from the literature, for the absorption process in the intestinal tract.

Evaluation of a rural community-based disability service in Queensland, Australia.

INTRODUCTION: The article outlines the evaluation framework devised for a semi-formal disability service project in central Queensland, Australia, which was implemented using a community-based, participatory model. Utilising a service framework known as Community-Based Rehabilitation and an implementation strategy adapted from Participatory Rural Appraisal, this model is presented as a potential alternative for rehabilitation and disability services in the light of concerns that such services are poorly tailored and inadequate in remote and rural areas of Australia. METHOD: In recognition of the difficulty of evaluating such participatory and community-based initiatives, this evaluation was based on the analysis of large amounts of qualitative data from multiple sources, which were categorised against key themes drawn from the literature, using a SWOT analysis (strengths, weaknesses, opportunities and threats). It is suggested that this innovative and multifaceted evaluation methodology may have broader application. RESULTS AND CONCLUSIONS: Findings of the service evaluation indicated positive informal, community and social outcomes. Formal structural and organisational outcomes were found to be limited with a possibility of compromising the long-term viability of the initiative. Suggestions are made regarding the process of implementing similar research initiatives. The model may have application in similar rural community-based initiatives internationally.

Developing a rural community-based disability service: (I) service framework and implementation strategy.

In response to widely recognised dilemmas associated with rehabilitation and disability service provision in remote and rural areas of Australia, a community-based, participatory approach to service development was adapted for a disability service project in central Queensland. The service framework, known as Community Based Rehabilitation (CBR), fosters the involvement of community members in disability service provision. Although this framework has been described previously, few guidelines exist regarding appropriate implementation of such an approach. Consequently, the implementation strategy known as Participatory Rural Appraisal (PRA) was adopted. Participatory Rural Appraisal has been reported to foster the participation and decision-making of community members in community projects. The present article describes the application of this implementation strategy to disability service provision in a relatively under-resourced rural shire. The rationale, framework and process of the pilot are described. A subsequent publication will document the service component, detail evaluation findings and describe the long-term outcomes of this research.

Effect of activity duration on recovery and metabolic costs in the desert iguana (Dipsosaurus dorsalis).

The majority of elevated O(2) consumption associated with short and vigorous activity occurs during recovery, thus an assessment of associated metabolic costs should also examine the excess post-exercise oxygen consumption (EPOC). This study examined O(2) uptake during exercise, EPOC and distance traveled during 5-, 15-, 60- and 300-s sprints at maximal treadmill intensity in Dipsosaurus (N=10; 74.3+/-2.1 g). EPOC (0.08, 0.14, 0.23 and 0.18 ml O(2) g(-1), respectively) was large (80-99% of total elevated O(2) consumption) and increased significantly between 5 and 60 s. The cost of activity (C(act); ml O(2) g(-1) x km(-1)), intended to reflect the total net costs associated with the activity, was calculated as the total elevated O(2) consumption per unit distance traveled. C(act) decreased with activity duration due to proportionally larger increases in distance traveled relative to EPOC volume, and is predicted by the equation C(act)=14.7 x activity duration (s)(-0.24). The inclusion of EPOC costs provides an ecologically relevant estimate of the total metabolic cost of locomotor activity. C(act) exceeds standard transport costs at all durations examined due to the addition of obligate recovery costs. The differences are large enough to impact energy budget analyses for ectotherms.

People, partnerships and human progress: building community capital.

The Victorian-era journal The Sanitarian used on its masthead the slogan 'A nation's health is a nation's wealth'. Today, we are re-discovering that wisdom, recognizing that health is indeed a form of wealth. Moreover, we are beginning to understand that wealth is not merely our economic capital, but includes three other forms of capital--social, natural and human capital. Health is one key element of human capital. A healthy community is one that has high levels of social, ecological, human and economic 'capital', the combination of which may be thought of as 'community capital'. The challenge for communities in the 21st century will be to increase all four forms of capital simultaneously. This means working with suitable partners in the private sector, making human development the central purpose of governance, and more closely integrating social, environmental and economic policy. Community gardens, sustainable transportation systems and energy conservation programmes in community housing projects are some of the ways in which we can build community capital.

Healthy communities must also be sustainable communities.

The author contends that healthy communities must be both environmentally and socially sustainable, given that health depends on the quality of the built and natural environments, and that global change resulting from the industrial economy is affecting the web of life. He argues that suburban sprawl wastes scarce resources and disproportionately places those resources in the hands of suburban dwellers. Urban areas can be made more environmentally sustainable, especially with respect to energy consumption, which will help reduce air pollution and climate change and contribute in other ways to improved health.

Whole-body systemic transcapillary filtration rates, coefficients, and isogravimetric capillary pressures in Bufo marinus and Rana catesbeiana.

Whole-body and organ-level transcapillary filtration rates and coefficients are virtually unexamined in ectothermal vertebrates. These filtration rates appear to be greater than in mammals when plasma volume shifts and lymphatic function are analyzed. Gravimetric techniques monitoring whole-body mass changes were used to estimate net systemic filtration in Bufo marinus and Rana catesbeiana while perfusing with low-protein Ringer's and manipulating venous pressure. Capillary pressures were estimated from arterial and venous pressures after measuring the venous to arterial resistance ratio of 0.23. The capillary filtration coefficient (CFC) for the two species was 25.2+/-1.47 mL min-1 kg-1 kPa-1. Isogravimetric capillary pressure (Pci), the pressure at which net fluid is neither filtered nor reabsorbed, was 1.12+/-0.054 kPa and was confirmed by an independent method. None of these variables showed a significant interspecific difference. The anuran CFC and Pci are significantly higher than those found using the same method on rats (7.6+/-2.04 mL min-1 kg-1 kPa-1 and 0.3+/-0.37 kPa, respectively) and those commonly reported in mammals. Despite the high CFC, the high Pci predicts that little net filtration will occur at resting in vivo capillary pressures.

Creating health and health promoting hospitals: a worthy challenge for the twenty-first century.

States that it seems self-evident that a hospital should be a healing environment, a healthy place to work, should not harm the health of the environment and should contribute to and be a source of health in the community, but argues that hospitals have not paid a great deal of attention to many of these issues until recently. Suggests that in recent years, a new and broader understanding of health promotion has led to a re-examination of the ways in which hospitals can be both healthy and health-promoting. Begins by exploring the broader concepts of health promotion that lay the foundation for the creation of healthy and health-promoting hospitals and provides some examples of how these approaches are being applied.

A comparison of HIV/AIDS knowledge among high school freshmen and senior students.

Statistical data show that heterosexual transmission of AIDS among teenagers is a significant problem. The purpose of this study was to assess and compare the level of knowledge concerning HIV/AIDS among high school freshmen- and senior-level students and to determine the association between certain demographic variables and the students' knowledge level. A convenience sample of 169 freshmen and 274 senior high school students were surveyed at a local area high school (N = 443). A 49-item knowledge questionnaire, used by the high school district HIV/Abstinence program, and a demographic questionnaire developed by the investigators were used to collect the data. The findings revealed that both the freshmen and senior students had several misconceptions about HIV/AIDS, including the modes of transmission, the sure way of preventing the sexual transmission, donating blood, and the usual causes of death for people with AIDS. A comparison of the mean knowledge scores among freshmen and senior students indicated there was no significant difference among the two groups. The mean knowledge score of the seniors was significantly affected by whether they had received HIV/AIDS education. However, this was not the case for the freshmen. African American students, especially the female students, had significantly lower knowledge scores than other ethnic groups.

Indicators that count! Measuring population health at the community level.

We begin with a discussion of some vitally important conceptual and methodological issues. These issues concern our understanding of community, of health, of population health and its determinants, of the concept of 'measurement' and the values that underlie it, and our reasons for wishing to measure these constructs. We then present a framework for indicator categories, propose some criteria for indicator selection and suggest an initial set of core indicators. This indicator set reflects not simply health status--no matter how broadly defined--but also the environmental, social and economic determinants of health and the "healthfulness" of the community itself. Our most important conclusion is that if the information that is contained in the data of the indicator set is to be transformed into knowledge that can empower and emancipate the community, it has to be developed in consultation with the local community and local users of the information.

Future directions in population health.

The long-term health of the population will be influenced by a number of major forces in the next century. In this brief review, particular emphasis is placed on environmental and economic forces. Major global environmental changes include climate change and global warming, resource depletion, ecotoxicity and reduced biodiversity. We do not yet know the impact on longevity of lifetime exposure to a mix of persistent toxic chemicals in our environment, since it has only been widespread in the past 40-50 years. The health impacts of global warming are only just beginning to be understood and could be profound. But perhaps the most profound threat to population health is economic growth, to the extent that it undermines environmental and social sustainability. We need a new form of capitalism, one that simultaneously increases environmental, social, economic and human capital, if population health is to be maintained in the 21st century.

Yield Loss Caused by Pratylenchus thornei on Wheat in South Australia.

A two-year field trial with 130 plots was conducted at Tanunda, South Australia. Ten cereal cultivars differing in susceptibility to Pratylenchus thornei, two poor host crops (non-leguminous), and a bare fallow treatment were used to manipulate the numbers of nematodes in the plots in the first year. Initial and final densities were determined for each plot and varied from 0 to 9,400 nematodes/200 g oven-dried soil at the beginning of the second year. A highly susceptible wheat cultivar, Warigal, and two wheat lines known to have some resistance to P. thornei, GS50A and AUS4930, were planted in the second year. High densities of P. thornei caused more extensive lesions and severe cortical degradation in roots of Warigal than in GS50A or AUS4930. There was a significant linear relationship between initial density of P. thornei and Warigal grain yield (t/ha), with the estimated regression equation Y = 1.86 - 0.0000557x, where Y is the grain yield in t/ha and x is the number of P. thornei/200 g oven-dried soil. High initial densities (9,000 P. thornei/200 g oven-dried soil) caused up to 27% yield loss of this commercial Australian wheat. In contrast, the yield of the two resistant lines was not affected by initial density, suggesting that both were tolerant as well as resistant in the field.

Strain IMB-1, a novel bacterium for the removal of methyl bromide in fumigated agricultural soils.

A facultatively methylotrophic bacterium, strain IMB-1, that has been isolated from agricultural soil grows on methyl bromide (MeBr), methyl iodide, methyl chloride, and methylated amines, as well as on glucose, pyruvate, or acetate. Phylogenetic analysis of its 16S rRNA gene sequence indicates that strain IMB-1 classes in the alpha subgroup of the class Proteobacteria and is closely related to members of the genus Rhizobium. The ability of strain IMB-1 to oxidize MeBr to CO2 is constitutive in cells regardless of the growth substrate. Addition of cell suspensions of strain IMB-1 to soils greatly accelerates the oxidation of MeBr, as does pretreatment of soils with low concentrations of methyl iodide. These results suggest that soil treatment strategies can be devised whereby bacteria can effectively consume MeBr during field fumigations, which would diminish or eliminate the outward flux of MeBr to the atmosphere.

Thermal stability studies of a globular protein in aqueous poly(ethylene glycol) by (1)H NMR.

The reversible folding destabilization of hen lysozyme has been confirmed by a melting temperature (T(m)) decrease in aqueous poly(ethylene glycol) (PEG). The percent denatured, extracted from the histidine 15 C2H (H15 C2H) native and denatured peak areas from 500-MHz one-dimensional proton nuclear magnetic resonance (1D (1)H NMR) spectra in D(2)O, was analyzed through denaturation temperatures at 0% and 20% (w/w) PEG 1000. The lysozyme (3.5 mM) T(m) decreased by 4.2 degrees C and 7.1 degrees C in 20% (w/w) PEG 1000 at pH 3.8 and 3.0, respectively. The T(m) decreased with increasing lysozyme concentration. Additionally, the temperature-induced resonance migrations of 17 protons from 8 residues indicate that the native lysozyme structure undergoes temperature-induced conformational changes. The changes were essentially identical in both 0% and 20% (w/w) PEG 1000 at both pH 3.0 and 3.8. This small, local restructuring of the hydrophobic box region may be a manifestation of temperature-dependent solution hydrophobicity, whereas active-site cleft fluctuations may be due to the inherent active-site flexibility. The lysozyme structure in PEG at 35 degrees C was determined to be essentially native from the (1)H nuclear Overhauser effect spectroscopy (NOESY) fingerprint regions. Additionally, lysozyme chemical shifts, from 1D spectra, in PEG 200, 300, and 1000 at 35 degrees C and various concentrations were essentially identical, further confirming that the conformation remains native in various PEG solutions. (c) 1996 John Wiley & Sons, Inc.

Bacterial lipopolysaccharide copurifies with plasmid DNA: implications for animal models and human gene therapy.

During the course of gene therapy experiments in rodents, using intramuscular injections of plasmid DNA derived from Escherichia coli, we noted dose-related toxicity. This observation prompted a search for possible contaminants of DNA samples. We used the highly specific and sensitive limulus amoebocyte lysate assay (LAL), to monitor endotoxin bioactivity in DNA samples, and found plasmid DNA derived from standard E. coli bacterial strains, using traditional DNA isolation protocols, to be heavily contaminated with endotoxin, or lipopolysaccharide (LPA). Standard DNA isolation procedures resulted in the copurification of up to 500 micrograms/ml of LPS. LPS is a potent inducer of cytokines and other inflammatory mediators, and may complicate the use of naked DNA in gene therapy. The copurification of endotoxin with plasmid DNA also has important implications for in vitro transfection studies and microinjection of DNA into embryos. A simple and efficient protocol to reduce LPS contamination of plasmid DNA was developed. The conversion of intact bacteria to spheroplasts prior to the isolation of plasmid DNA, incubation with lysozyme, treatment with the detergent n-octyl-beta-D-thioglucopyranoside (OSPG) and polymyxin-B (PMB) chromatography, allowed the isolation of plasmid DNA containing less than 50 ng/ml LPS. This represents a 10,000-fold reduction in LPS contamination, compared to conventional methods of plasmid DNA purification, avoids potentially toxic reagents such as ethidium bromide, and produces a higher yield of plasmid DNA.

Inheritance and linkage of isozyme loci in almond.

The segregation of seven isozyme marker genes was investigated using eight controlled crosses in almond. The cultivar 'Nonpareil' was the maternal parent in all crosses. Pollination was achieved using eight different cultivars, and a total of 3200 individual kernels were assessed. For each isozyme the goodness-of-fit test was used to test for departure from the expected frequencies assuming Mendelian inheritance. Given a higher than expected number of significant results for individual isozymes, independent segregation between pairs of isozymes was tested using the chi-square statistic on the resulting two-way contingency tables. In all crosses a highly significant association (P value< 0.001) was observed between (1) the AAT- 1 and IDH isozymes loci and (2) the LAP-1 and PGM-2 isozymes loci, which leads to the conclusion that the respective isozyme pairs are linked.In addition, a significant association (P value < 0.001) was observed between LAP-1 and GPI-2 when the pollen sources were 'Fritz', 'Mission', or 'Price', but this could not be tested for the remaining five pollen sources, 'Carmel', 'Grant', 'Keane', 'Ne plus Ultra', 'Peerless', because they are homozygous at these loci. If LAP-1 is linked with GPI-2 and PGM-2, it might be expected that we should find evidence of linkage between GPI-2 and PGM-2. The lack of a significant association between these two isozymes suggests that LAP-1 is located centrally on the chromosome. These three pairs of linked loci are the first to be reported in almond.

Transcriptional control of dacB, which encodes a major sporulation-specific penicillin-binding protein.

Sporulation-specific sigma factor E (sigma E) of Bacillus subtilis is both necessary and sufficient for transcription of the dacB gene, which encodes penicillin-binding protein 5*. Evidence in support of this conclusion was obtained by primer extension analysis of dacB transcripts and the induction of active sigma E with subsequent synthesis of PBP 5* in vegetative cells.

Effect of gamma carboxylation on prothrombinase inhibitory activity of catalytically inactive factor XA.

Recombinant catalytically inactive factor Xa (factor rXai) is capable of assembly into inactive prothrombinase complexes, thus serving as a competitive inhibitor (Ki = 0.3nM) of active factor Xa. In order to study the role of gamma carboxylation in prothrombinase complex assembly, we have prepared differentially gamma carboxylated factor rXai and have measured the activities of these proteins in prothrombinase complex inhibition and in extension of plasma clotting. A factor rXai preparation containing 8 out of a possible maximum of 11 g carboxyglutamic acid (GLA) residues was found to be as active as chemically inactivated plasma factor Xa which was fully gamma carboxylated. Loss of a single additional g carboxyglutamic acid in the recombinant protein, however lead to a marked loss in activity. Factor rXai preparation with 8 GLA residues is also detected by a monoclonal antibody specific for a GLA dependent epitope. Thus assembly of the factor Va/Xa complex on phospholipid membranes does not require the presence of all of the g carboxyglutamic acid residues present in the plasma protein.