Accumulation and toxicity of monophenyl arsenicals in rat endothelial cells

Clark 1 (diphenylarsine chloride) and Clark 2 ( diphenylarsine cyanide) were used as chemical weapon agents (CWA), and the soil contamination by these CWA and their degraded products, diphenyl and phenyl arsenicals, has been one of the most serious environmental issues. In a series of comparisons in toxicity between trivalent and pentavalent arsenicals we investigated differences in the accumulation and toxicity of phenylarsine oxide (PAO(3+)) and phenylarsonic acid (PAA(5+)) in rat heart microvascular endothelial cells. Both the cellular association and toxicity of PAO(3+) were much higher than those of PAA(5+), and LC50 values of PAO(3+) and PAA(5+) were calculated to be 0.295 muM and 1.93 mM, respectively. Buthionine sulfoximine, a glutathione depleter, enhanced the cytotoxicity of both PAO(3+) and PAA(5+). N-Acetyl-L-cysteine (NAC) reduced the cytotoxicity and induction of heme oxygenase-1 (HO-1) mRNA in PAO(3+)-exposed cells, while NAC affected neither the cytotoxicity nor the HO-1 mRNA level in PAA(5+)-exposed cells. The effect of NAC may be due to a strong affinity of PAO(3+) to thiol groups because both NAC and GSH inhibited the cellular accumulation of PAO(3+), but PAA(3+) increased tyrosine phosphorylation levels of cellular proteins. These results indicate that the inhibition of protein phosphatases as well as the high affinity to cellular components may confer PAO(3+) the high toxicity.

The combined SPE : ToxY-PAM phytotoxicity assay; application and appraisal of a novel biomonitoring tool for the aquatic environment

Mounting concerns regarding the environmental impact of herbicides has meant a growing requirement for accurate, timely information regarding herbicide residue contamination of, in particular, aquatic systems. Conventional methods of detection remain limited in terms of practicality due to high costs of operation and the specialised information that analysis provides. A new phytotoxicity bioassay was trialled for the detection of herbicide residues in filter-purified (Milli-Q) as well as natural waters. The performance of the system, which combines solid-phase extraction (SPE) with the ToxY-PAM dual-channel yield analyser (Heinz Walz GmbH), was tested alongside the traditional method of liquid chromatography-mass spectrometry (LC-MS). The assay methodology was found to be highly sensitive (LOD 0.1 ng L-1 diuron) with good reproducibility. The study showed that the assay protocol is time effective and can be employed for the aquatic screening of herbicide residues in purified as well as natural waters.

Sexual abuse in childhood and sexual dysfunction in adulthood: An Australian population-based study

This study examined self-reported adult sexual functioning in individuals reporting a history of childhood sexual abuse (CSA) in a representative sample of the Australian population. A sample of 1793 persons, aged 18-59 years, were randomly selected from the electoral roll for Australian states and territories in April 2000. Respondents were interviewed about their health status and sexual experiences, including unwanted sexual experiences before the age of 16 years. More than one-third of women and approximately one-sixth of men reported a history of CSA. Women were more likely than men to report both non-penetrative and penetrative experiences of CSA. For both sexes, there was a significant association between CSA and symptoms of sexual dysfunction. In assessing the specific nature of the relationship between sexual abuse and sexual dysfunction, statistically significant associations were, in general, evident for women only. CSA was not associated with the level of physical or emotional satisfaction respondents experienced with their sexual activity. The total number of lifetime sexual partners was significantly and positively associated with CSA for females, but not for males; however, the number of sexual partners in the last year was not related to CSA. CSA in the Australian population is common and contributes to significant impairment in the sexual functioning of adults, especially women. These consequences appear not to extend to the other areas of sexual activity considered in this study.

Cognitive fit between conceptual schemas and internal problem representations: The case of geospatio-temporal conceptual schema comprehension

Geospatio-temporal conceptual models provide a mechanism to explicitly represent geospatial and temporal aspects of applications. Such models, which focus on both what and when/where, need to be more expressive than conventional conceptual models (e.g., the ER model), which primarily focus on what is important for a given application. In this study, we view conceptual schema comprehension of geospatio-temporal data semantics in terms of matching the external problem representation (that is, the conceptual schema) to the problem-solving task (that is, syntactic and semantic comprehension tasks), an argument based on the theory of cognitive fit. Our theory suggests that an external problem representation that matches the problem solver's internal task representation will enhance performance, for example, in comprehending such schemas. To assess performance on geospatio-temporal schema comprehension tasks, we conducted a laboratory experiment using two semantically identical conceptual schemas, one of which mapped closely to the internal task representation while the other did not. As expected, we found that the geospatio-temporal conceptual schema that corresponded to the internal representation of the task enhanced the accuracy of schema comprehension; comprehension time was equivalent for both. Cognitive fit between the internal representation of the task and conceptual schemas with geospatio-temporal annotations was, therefore, manifested in accuracy of schema comprehension and not in time for problem solution. Our findings suggest that the annotated schemas facilitate understanding of data semantics represented on the schema.

Some considerations on the design of population pharmacokinetic studies

The goal of this manuscript is to introduce a framework for consideration of designs for population pharmacokinetic orpharmacokinetic-pharmacodynamic studies. A standard one compartment pharmacokinetic model with first-order input and elimination is considered. A series of theoretical designs are considered that explore the influence of optimizing the allocation of sampling times, allocating patients to elementary designs, consideration of sparse sampling and unbalanced designs and also the influence of single vs. multiple dose designs. It was found that what appears to be relatively sparse sampling (less blood samples per patient than the number of fixed effects parameters to estimate) can also be highly informative. Overall, it is evident that exploring the population design space can yield many parsimonious designs that are efficient for parameter estimation and that may not otherwise have been considered without the aid of optimal design theory.

Optimal design for model discrimination and parameter estimation for itraconazole population pharmacokinetics in cystic fibrosis patients

Optimal sampling times are found for a study in which one of the primary purposes is to develop a model of the pharmacokinetics of itraconazole in patients with cystic fibrosis for both capsule and solution doses. The optimal design is expected to produce reliable estimates of population parameters for two different structural PK models. Data collected at these sampling times are also expected to provide the researchers with sufficient information to reasonably discriminate between the two competing structural models.

Selecting optimal instantiations of data models - Theory and validation of an ex ante approach

The schema of an information system can significantly impact the ability of end users to efficiently and effectively retrieve the information they need. Obtaining quickly the appropriate data increases the likelihood that an organization will make good decisions and respond adeptly to challenges. This research presents and validates a methodology for evaluating, ex ante, the relative desirability of alternative instantiations of a model of data. In contrast to prior research, each instantiation is based on a different formal theory. This research theorizes that the instantiation that yields the lowest weighted average query complexity for a representative sample of information requests is the most desirable instantiation for end-user queries. The theory was validated by an experiment that compared end-user performance using an instantiation of a data structure based on the relational model of data with performance using the corresponding instantiation of the data structure based on the object-relational model of data. Complexity was measured using three different Halstead metrics: program length, difficulty, and effort. For a representative sample of queries, the average complexity using each instantiation was calculated. As theorized, end users querying the instantiation with the lower average complexity made fewer semantic errors, i.e., were more effective at composing queries. (c) 2005 Elsevier B.V. All rights reserved.

Evaluation of the Western Australian Department of Health telehealth project

In 1999, the Department of Health in Western Australia began a telehealth project, which finished in 2004. The 75 videoconferencing sites funded by the project were part of a total state-wide videoconference network of 104 sites. During the period from January 2002 to December 2003, a total of 3266 consultations, case reviews and patient education sessions took place. Clinical use grew to 30% of all telehealth activity. Educational use was approximately 40% (1416 sessions) and management use was about 30% (1031 sessions). The average overhead cost per telehealth session across all regions and usage types was $A192. Meaningful comparisons of the results of the present study with other public health providers were difficult, because many of the available Websites on telehealth were out of date. Despite the successful use of telehealth to deliver clinical services in Western Australia, sustaining the effort in the post-project phase will present significant challenges.

Realtime telemedicine for paediatric otolaryngology pre-admission screening

We conducted a feasibility study to examine whether a paediatric patient at a regional hospital could be assessed by an ear, nose and throat (ENT) specialist via videoconference, therefore saving at least one journey to the tertiary hospital for a pre-admission appointment. A video-otoscope was used with standard videoconference equipment, and realtime images were transmitted at a bandwidth of 384 kbit/s. In all, 13 telepaediatric ENT clinics were conducted between November 2003 and April 2005, and 98 consultations were facilitated for 64 patients. The main reasons for referral were recurrent tonsillitis (25%) and obstructive sleep apnoea (23%). Of the 64 patients examined by telemedicine, 42 (66%) were recommended for surgery and placed on the surgical waiting list. About 12 patients (19%) required travel to the tertiary centre for further investigations and tests not available locally, while four patients (6%) were reviewed via videoconference during a scheduled clinic. Six patients (9%) required no further follow-up after their initial telepaedliatric consultation. Videoconferencing is an effective method of assessing ENT conditions of paediatric patients and for pre-screening potential surgical admissions to a tertiary hospital. Careful consideration of a number of economic and logistical factors needs to be made before large investments are made to expand the service.

An e-health needs assessment of medical residents in Cameroon

Medical residents from Yaounde I University in Cameroon are required to spend periods of time in rural or remote locations to complete their training. To determine if e-health might lessen their isolation and enhance patient care, a needs assessment of the residents was performed using a brief questionnaire (five items) about the situation in which residents found themselves outside their medical school environment. We gave the questionnaires to 45 residents. Seventeen questionnaires had been returned at the time of the site visit, a response rate of 38%. Most residents indicated that the ability to contact a mentor would have either made them feel more confident (16, or 94%) or altered their handling of recent cases (15, or 88%). All residents had access to a mobile phone, and many (11, or 65%) had used it to contact a medical colleague for guidance. A low-cost and technologically simple telemedicine solution that maximized use of mobile phone capability, provided access to medical and health-care information, and permitted exchange of images would be an appropriate response to the identified needs.