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PubMed1980

Thalassaemia as a model of recessive genetic disease in the community.

In order to gain understanding of some of the problems of genetic counseling for a severe recessive disease in England, a Greek Cypriot extended family including 87 living members and known to be transmitting a beta-thalassaemia gene was investigated for the extent and the sources of their knowledge about thalassaemia. 42% of members tested carried beta-thalassaemia trait: nearly half were already aware of this, but only 10% of the non-carriers were aware of their status. The study illustrated many of the difficulties in conveying accurate counselling to a whole community and the need for active involvement of all health workers, especially general practitioners. This study is also relevant to the approaching possibility of genetic counseling for cystic fibrosis.

Cyprus↗
PubMed1998

Solar cycle variation of the low-altitude trapped proton flux.

Under NASA's Space Environment Effects (SEE) program, we are developing new models for the low-altitude (250-1000 km, L < 1.5) trapped radiation environment based on data from the TIROS/NOAA polar orbiting spacecraft. The unique features of this data base and model include the long time series (more than one complete solar cycle) obtained from the TIROS/NOAA data and the use of a coordinate system more applicable to the low-altitude environment. The data show a strong variation (as much as a factor of 10) over the solar cycle and a hysteresis effect between the rising and falling portions of the solar cycle. Both the solar cycle variation and the hysteresis are functions of L. In addition to the hysteresis effect, the flux during a given cycle appears to be a function of the previous cycle. Superimposed on the gradual variation over the solar cycle, transient effects, correlated with solar particle events (SPEs), can be clearly seen. Comparison with the AP8 models shows that the measured flux is a factor of 2-3 higher than the model. These data have important implications for the development and use of trapped radiation models, and will also contribute to our knowledge of the source and loss mechanisms at work in the inner zone

Atmosphere↗
PubMed1997

Hereditary ataxias and spastic paraplegias: methodological aspects of a prevalence study in Portugal.

A project for studying the prevalence of hereditary ataxias (HA) and familial spastic paraplegias (FSP) in Portugal was set up in 1993. The ascertainment of patients in previous prevalence studies relied mainly on the information of hospital admissions and out-patient contacts with the neurology and other related departments at central hospitals covering the whole region surveyed. Many patients might be overlooked if large populations were studied using this method, since registers at central hospitals are very incomplete and for most part not yet computerized. On the other hand HA and FSP are rare diseases appearing in family clusters, and it would be unreasonable to undertake a sample survey based upon a suitable frame of the Portuguese population. Therefore we decided to carry out a two-phase prevalence survey at district level, involving the collaboration of all physicians working in the district health institutions and the population, in the screening of eligible subjects in phase 1. All subjects screened as positive were examined by a neurologist in phase 2. This method provided a direct estimate of false positives and false negatives were all patients also examined in phase 2, who came to our knowledge using other sources of information. The prevalence of hereditary ataxias and spastic paraplegias in the pilot district was 6.4 per 100,000 inhabitants. The sensitivity of the screening procedure was 81.2% and the predictive value of a positive screening was 25%. Considering the geographically circumscribed district nature of the populations to be studied, the comprehensive sources of case identification used and the high adherence of the health professionals involved, we believe that this method can be widely used, particularly in countries with similar health care services.

Adult↗
PubMed2005

Analyzing and mining image databases.

Image mining is the application of computer-based techniques that extract and exploit information from large image sets to support human users in generating knowledge from these sources. This review focuses on biomedical applications, in particular automated imaging at the cellular level. An image database is an interactive software application that combines data management, image analysis and visual data mining. The main characteristic of such a system is a layer that represents objects within an image, and that represents a large spectrum of quantitative and semantic object features. The image analysis needs to be adapted to each particular experiment, so 'end-user programming' will be desirable to make the technology more widely applicable.

Humans↗
PubMed2005

PAX of mind for pathway researchers.

Scientists seeking to understand the inner workings of cells have access to a multitude of pathway data resources. However, the representations of pathway data within these resources are not consistent or interchangeable. To facilitate easy information retrieval from a wide variety of pathway resources, such as signal transduction, gene regulation, molecular interaction and metabolic pathway databases, a broad effort in the biopathways community called BioPAX was formed. New biological pathway software applications built using the BioPAX standard will be able to integrate knowledge from multiple sources in a coherent and reliable way. This article reports the progress that the BioPAX work-group has made towards building and deploying the BioPAX data-exchange format for biological pathway data.

Computational Biology↗
PubMed2001

Low-molecular weight dicarboxylic acids and glyoxylic acid: seasonal and air mass characteristics.

Low-molecular weight dicarboxylic acids are important constituents ofthe organic fraction of atmospheric particulate matter in remote and polluted regions. The knowledge on their sources is sparse, however, and organic aerosols in general need to be better characterized. Observations of C2-C5 alpha,omega-dicarboxylic acids (DCAs oxalic, malonic, succinic, and glutaric acid) and C2 oxomonocarboxylic acid (glyoxylic acid) from rural and urban sites in different seasons in Germany are reported using filter sampling and ion chromatography. The C2-C5 DCAs accounted for (by average) 0.07-0.51 microg m(-3) at the various sites corresponding to 3.4-23 mg g(-1) of total suspended particulate matter and glyoxylic acid for < 0.18-0.28 mg g(-1). Both, the transport of air masses over the continent and the summer season favored the occurrence of the acids. Secondary photochemical formation dominated the sources. It was found that for central Europe the anthropogenic emissions are more important than the biogenic emissions for all the acids determined and most important for oxalic acid. The biogenic precursors play a signifcant role for malonic acid. The influence of the marine sources was detectable for malonic and glutaric acid.

Air Pollutants↗
PubMed2006

QSAR modeling of human serum protein binding with several modeling techniques utilizing structure-information representation.

Four modeling techniques, using topological descriptors to represent molecular structure, were employed to produce models of human serum protein binding (% bound) on a data set of 1008 experimental values, carefully screened from publicly available sources. To our knowledge, this data is the largest set on human serum protein binding reported for QSAR modeling. The data was partitioned into a training set of 808 compounds and an external validation test set of 200 compounds. Partitioning was accomplished by clustering the compounds in a structure descriptor space so that random sampling of 20% of the whole data set produced an external test set that is a good representative of the training set with respect to both structure and protein binding values. The four modeling techniques include multiple linear regression (MLR), artificial neural networks (ANN), k-nearest neighbors (kNN), and support vector machines (SVM). With the exception of the MLR model, the ANN, kNN, and SVM QSARs were ensemble models. Training set correlation coefficients and mean absolute error ranged from r2=0.90 and MAE=7.6 for ANN to r2=0.61 and MAE=16.2 for MLR. Prediction results from the validation set yielded correlation coefficients and mean absolute errors which ranged from r2=0.70 and MAE=14.1 for ANN to a low of r2=0.59 and MAE=18.3 for the SVM model. Structure descriptors that contribute significantly to the models are discussed and compared with those found in other published models. For the ANN model, structure descriptor trends with respect to their affects on predicted protein binding can assist the chemist in structure modification during the drug design process.

Blood Proteins↗
PubMed1999

Parameter uncertainty and variability in evaluative fate and exposure models.

The human toxicity potential, a weighting scheme used to evaluate toxic emissions for life cycle assessment and toxics release inventories, is based on potential dose calculations and toxicity factors. This paper evaluates the variance in potential dose calculations that can be attributed to the uncertainty in chemical-specific input parameters as well as the variability in exposure factors and landscape parameters. A knowledge of the uncertainty allows us to assess the robustness of a decision based on the toxicity potential; a knowledge of the sources of uncertainty allows us to focus our resources if we want to reduce the uncertainty. The potential dose of 236 chemicals was assessed. The chemicals were grouped by dominant exposure route, and a Monte Carlo analysis was conducted for one representative chemical in each group. The variance is typically one to two orders of magnitude. For comparison, the point estimates in potential dose for 236 chemicals span ten orders of magnitude. Most of the variance in the potential dose is due to chemical-specific input parameters, especially half-lives, although exposure factors such as fish intake and the source of drinking water can be important for chemicals whose dominant exposure is through indirect routes. Landscape characteristics are generally of minor importance.

Animals↗
PubMed2003

Monitoring of diazinon concentrations and loadings, and identification of geographic origins consequent to stormwater runoff from orchards in the Sacramento River watershed, U.S.A.

Diazinon contamination of California's rivers has resulted in placing several rivers on the federal Clean Water Act 303d list of impaired waterways. Impaired water body listing requires the development of Total Maximum Daily Loads (TMDL). Previous studies identified stormwater related diazinon pulses in California rivers. This study was conducted to monitor diazinon concentrations in the Sacramento River watershed after rainfall events, to ascertain whether pulses could be identified and, if concentrations of concern were observed, to estimate loadings and determine geographic origins of the insecticide. TMDL development requires knowledge of contaminant sources, loadings, and geographic origins. Flow and diazinon concentrations peaked in the Sacramento River at Sacramento after the three largest storms during January and February 1994. Diazinon concentrations peaked consequent to each of three storms. Diazinon concentrations measured in the Sacramento River at Sacramento exceeded the California Department of Fish and Game acute and chronic criteria for protection of aquatic life during January and February for nine and nineteen days, respectively. Multiple exceedances were observed throughout the watershed. Diazinon loading and geographic origin differed with each of the three storms. The design of this study provides a useful template for others attempting to identify loadings and sources of contaminants in surface waters and to rectify aquatic ecosystem contamination from various land use practices.

Animals↗
PubMed2004

Red, distasteful water mites: did fish make them that way?

Water mites (Acari: Hydrachnida) are unusual among the typically cryptic freshwater fauna in that many species are brightly colored red or orange, and also appear to be distasteful to fish. This apparent aposematism (use of color to warn predators) has been previously explained as the evolutionary end-product of pressure from fish predation. The fish-predation argument has been supported by observations that fish spit out red mites, powder made from red water mites is more distasteful to fish than powder made from non-red mites, and red mites appear to be more abundant than non-red mites in water bodies where fish are present. In this paper, we challenge the hypothesis that fish were the sole driving force behind the evolution of aposematism in water mites. We show that non-red mites actually dominate in water bodies with fish, and that red mites are more abundant in temporary, fishless water bodies. We also demonstrate that powder made from red, terrestrial velvet mites (Trombidiidae) was as distasteful to fish as powder made from red water mites. We suggest that the main role of red and orange carotenoid pigments may be to act as photoprotectants, and hypothesize that redness originated in the terrestrial ancestors of water mites and has been retained in certain lineages of water mites after the invasion of the aquatic habitat. We also suggest that distastefulness evolved subsequent to bright coloration in response to increased conspicuousness to predators. Relaxed selection for redness has occurred when adults and/or larvae are less exposed to sunlight, either through occupying more protected habitats, parasitizing more nocturnal hosts, or parasitizing hosts for a short period of time. Our ability to test this alternative hypothesis is hampered by lack of knowledge of the source and mode of action of distastefulness, and of phylogenetic relationships among the Parasitengona.

Animals↗
PubMed2001

Comparison of key worker and patient assessment of needs in schizophrenic patients living in the community: a Nordic multicentre study.

OBJECTIVE: The present study is part of a Nordic multicentre study investigating the life and care situation of community samples of schizophrenic patients. The specific aim of the present part of the study was to examine the agreement between patients and their key worker concerning the presence of met and unmet needs in a number of life domains, and help or support given in these domains. METHOD: The comparisons were based on 300 matched pairs of assessments of need using the Camberwell Assessment of Need interview. RESULTS: The results showed that key workers identified slightly more needs, 6.17 vs. 5.76, a significant difference. There was a moderate or better agreement on the presence of a need in 17 of 22 life domains investigated, but in only 11 life domains concerning the presence of an unmet need. Disagreement concerning whether the patient was given the right kind of help or support was even more substantial. CONCLUSION: It is concluded that key workers and patients disagree particularly concerning unmet needs and that this is potentially related to a number of factors associated with the key worker and patient. It is also concluded that further research is needed to increase the knowledge concerning the sources of this disagreement if need assessment is to become a valid basis for service planning and individual treatment planning.

Adult↗
PubMed2003

Redistribution of energy available for ocean mixing by long-range propagation of internal waves.

Ocean mixing, which affects pollutant dispersal, marine productivity and global climate, largely results from the breaking of internal gravity waves--disturbances propagating along the ocean's internal stratification. A global map of internal-wave dissipation would be useful in improving climate models, but would require knowledge of the sources of internal gravity waves and their propagation. Towards this goal, I present here computations of horizontal internal-wave propagation from 60 historical moorings and relate them to the source terms of internal waves as computed previously. Analysis of the two most energetic frequency ranges--near-inertial frequencies and semidiurnal tidal frequencies--reveals that the fluxes in both frequency bands are of the order of 1 kW x m(-1) (that is, 15-50% of the energy input) and are directed away from their respective source regions. However, the energy flux due to near-inertial waves is stronger in winter, whereas the tidal fluxes are uniform throughout the year. Both varieties of internal waves can thus significantly affect the space-time distribution of energy available for global mixing.

Climate↗
PubMed1996

Reflex sympathetic dystrophy of the lower extremity in tetraplegia: case report.

Reflex sympathetic dystrophy (RSD) of the upper extremities has been reported to occur following complete and incomplete injuries of the cervical cord. Such reports describe the value of the three-phase radionuclide bone scan (TPBS) in differentiating RSD from pain of other sources. To our knowledge, RSD of the lower extremities has not been reported in a patient with tetraplegia. We report a case of lower extremity RSD in a patient with complete traumatic injury of the cervical cord. The case illustrates the use of the TPBS to differentiate RSD from heterotopic ossification (HO) in the lower extremities. THe successful use of the alpha-adrenergic blocker, phenoxybenzamine, in the treatment of RSD is described. Follow-up to 30 months has shown no evidence of recurrence, and complete resolution of the scintigraphic findings.

Adrenergic alpha-Antagonists↗
PubMed2003

The human sexuality education of physicians in North American medical schools.

Individuals seeking treatment for sexual problems frequently would like to turn to a source they consider knowledgeable and worthy of respect, their doctor. The objective was to assess how well the 125 schools of medicine in the United States and the 16 in Canada prepare physicians to diagnose and treat sexual problems. A prospective cohort study was carried out. The main outcome results were description of the medical educational experiences, teaching time, specific subject areas, clinical programs, clerkships, continuing education programs in the domain of human sexuality in North American medical schools. The results were as follows. There were 101 survey responses (71.6%) of a potential of 141 medical schools (74% of United States and 50% of Canadian medical schools). A total of 84 respondents (83.2%) for sexuality education used a lecture format. A single discipline was responsible for this teaching in 32 (31.7%) schools, but a multidisciplinary team was responsible in 64 (63.4%) schools (five schools failed to respond to the question). The majority (54.1%) of the schools provided 3-10 h of education. Causes of sexual dysfunction (94.1%), its treatment (85.2%) altered sexual identification (79.2%) and issues of sexuality in illness or disability (69.3%) were included in the curriculum of 96 respondents. Only 43 (42.6%) schools offered clinical programs, which included a focus on treating patients with sexual problems and dysfunctions, and 56 (55.5%) provided the students in their clerkships with supervision in dealing with sexual issues. In conclusion, expansion of human sexuality education in medical schools may be necessary to meet the public demand of an informed health provider.

Canada↗
PubMed2003

'I could have just done with a little more help': an analysis of women's help-seeking from health visitors in the context of domestic violence.

Domestic violence is a serious issue that adversely affects large numbers of women and children. Despite having an adverse impact upon health and welfare, women experiencing domestic violence face a number of difficulties seeking help about their situation from statutory health and welfare agencies. The present paper is based upon a study of British health visiting in relation to women experiencing domestic violence. Drawing upon interview data from 16 women who experienced domestic violence and were the mothers of small children, this paper explores their accounts of contact with the health visiting service. All of the 16 women who participated in this research described difficulties in seeking help about domestic violence. These included practical concerns such as fears for their own safety, lack of knowledge regarding appropriate sources of support and protection, and concerns about losing custody of their children. Given these concerns, some women concealed their experiences of domestic violence from their health visitors. For those who disclosed the domestic violence to their health visitors, they did not always receive appropriate support or protection. Of particular concern was the absence of information about accessing more specialist services. The research findings suggest that there is considerable scope for practice development in order to ensure that women experiencing domestic violence are able to receive safe and appropriate responses from health visitors.

Battered Women↗
PubMed2004

Ethical practice in nursing: working the in-betweens.

BACKGROUND: While contemporary ethical theory is of tremendous value to nursing, the extent to which such theory has been informed by the concerns and practices of nurses has been limited. PURPOSE: With a view to complementing extant ethical theory, a study was undertaken to explore, from the perspective of nurses, the meaning of ethics and the enactment of ethical practice in nursing. DESIGN AND METHODS: Located in the interpretive/constructivist paradigm, using an emergent design, this inquiry employed focus groups to collect the data. Eighty-seven nurses from a wide range of practice settings were interviewed in 19 focus groups of three to nine nurses each. FINDINGS: The nurses described ethics in their practice as both a way of being and a process of enactment. They described drawing on a wide range of sources of moral knowledge in a dynamic process of developing awareness of themselves as moral agents. Enacting moral agency involved working in a shifting moral context, and working in-between their own values and those of the organizations in which they worked, in-between their own values and those of others, and in-between competing values and interests. CONCLUSIONS: Analysis of the experiences and concerns of the nurses offered new understanding of ethics in nursing and direction for the development of ethical theory pertinent to nursing practice.

Adult↗
PubMed2001

Identification of TogMNAB, an ABC transporter which mediates the uptake of pectic oligomers in Erwinia chrysanthemi 3937.

The bacterium Erwinia chrysanthemi, which causes soft rot disease on various plants, is able to use pectin as a carbon source for growth. Knowledge of the critical step in pectin catabolism which allows the entry of pectic oligomers into the cells is scarce. We report here the first example of a transport system involved in the uptake of pectic oligomers. The TogMNAB transporter of E. chrysanthemi is a member of the ATP-binding cassette (ABC) superfamily. TogM and TogN are homologous to the inner membrane components, TogA exhibits the signature of ABC ATPases and TogB shows similarity with periplasmic ligand-binding proteins. The TogMNAB transporter is a new member of the carbohydrate uptake transporter-1 family (CUT1, TC no. 3.1.1), which is specialized in the transport of complex sugars. The four genes, togM, togN, togA and togB, are apparently co-transcribed in a large operon which also includes the pectate lyase gene pelW. The transcription of the tog operon is induced in the presence of pectic derivatives and is affected by catabolite repression. It is controlled by the KdgR repressor and the CRP activator. The TogMNAB system is able to provide Escherichia coli with the ability to transport oligogalacturonides. In E. chrysanthemi, the TogMNAB system seems to play a major role in switching on the induction of pectin catabolism. TogB also acts as a specific receptor for chemotaxis towards oligogalacturonides. The decreased capacity of maceration of a togM mutant indicates the importance of transport and/or attraction of oligogalacturonides for E. chrysanthemi pathogenicity.

ATP-Binding Cassette Transporters↗
PubMed2000

Bedside perspectives on the use of opioids: transferring results of clinical research into practice.

1. Transference of research findings to clinical practice has been a challenge for those managing chronic pain. Generally, pain is not well controlled in hospitals and steps need to be taken to make pain control more effective. 2. Clinical trials of opioids have shown that pain can be controlled in the great majority of patients. Apart from the use of the World Health Organization Analgesic Ladder, a 'pain diagnosis' should be made and a comprehensive view of pain needs to be considered by the clinician. This would include pain and other physical symptoms, psychological issues and social and spiritual stresses. 3. Respiratory depression and tolerance for opioids are often seen as negative aspects of opioids and, therefore, may lead to inadequate control of pain. The evidence cited suggests that, in the long-term treatment of cancer pain, respiratory depression almost never occurs. The only situation that warrants caution is when an anaesthetic block or similar procedure relieves pain treated by opioids, when that patient has been receiving large doses of opioids. Long-term studies with opioids show that tolerance may occur, but is not a clinical problem and should not impair their use in adequate doses to relieve the patient's pain. 4. The active morphine metabolites, morphine-3-glucuronide (M3G) and morphine-6-glucuronide (M6G) do need to be considered when administering morphine. There seems to be considerable interindividual variation in the production and elimination of metabolites. In cases of renal failure or in the elderly, the ratios of M3G and M6G to morphine accumulate exponentially, making opioid toxicity more likely. Even different routes of administration seem to be associated with different ratios of metabolites. A knowledge of these sources of pharmacokinetic variability may lead to more effective use of the opioids in clinical practice.

Analgesics, Opioid↗