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PubMed2006

Linking species-area and species-energy relationships in Drosophila microcosms.

Resource availability is an important constraint on community structure. Some authors have suggested it conceptually links two of the most basic patterns in ecology, the species-area relationship and the latitudinal gradient in species richness. I present the first experimental test of this conjecture, by manipulating both the area and resource concentration of artificial larval drosophilid fly habitats and then allowing colonization from a natural species pool. Both the abundance and species richness of these habitats depended upon the total quantity of resources available, regardless of whether those resources were contained within smaller high-quality habitats or larger poor-quality habitats. While the intercepts of species-area relationships varied with resource concentration, they all collapsed onto the same species-energy curve. These results support the view that energetic constraints are of fundamental importance in structuring ecological communities, and that such constraints may even help explain ecological patterns such as the species-area relationship that do not explicitly address resource availability.

Animals↗

PubMed2003

The cell-centered database: a database for multiscale structural and protein localization data from light and electron microscopy.

The creation of structured shared data repositories for molecular data in the form of web-accessible databases like GenBank has been a driving force behind the genomic revolution. These resources serve not only to organize and manage molecular data being created by researchers around the globe, but also provide the starting point for data mining operations to uncover interesting information present in the large amount of sequence and structural data. To realize the full impact of the genomic and proteomic efforts of the last decade, similar resources are needed for structural and biochemical complexity in biological systems beyond the molecular level, where proteins and macromolecular complexes are situated within their cellular and tissue environments. In this review, we discuss our efforts in the development of neuroinformatics resources for managing and mining cell level imaging data derived from light and electron microscopy. We describe the main features of our web-accessible database, the Cell Centered Database (CCDB; http://ncmir.ucsd.edu/CCDB/), designed for structural and protein localization information at scales ranging from large expanses of tissue to cellular microdomains with their associated macromolecular constituents. The CCDB was created to make 3D microscopic imaging data available to the scientific community and to serve as a resource for investigating structural and macromolecular complexity of cells and tissues, particularly in the rodent nervous system.

Brain↗

PubMed1980

Alternative to mental hospital treatment. II. Economic benefit-cost analysis.

A cost-benefit analysis should be seen not as a mechanism for deciding mechanically on the allocation of funds and resources among programs but as a structure for weighing advantages and disadvantages (that is, for organizing knowledge). Considering all the forms of benefits and costs that we were able to derive in monetary terms, the experimental program provided both additional benefits and additional costs as compared with the conventional treatment. However, the added benefits, some +1,200 per patient per year, are nearly +400 more per patient per year than the added costs. A number of the forms of benefits and costs that we have measured in quantitative but nonmonetary terms show additional advantages of the community-based experimental program. The generalizability of a single experiment is limited, but the methodologies developed may be useful if their proper role is appreciated.

Adult↗

PubMed1998

A partial solution: a local mental health authority for the UK.

BACKGROUND: the structural problems of the mental health system in the UK have been analyzed by a number of authors over the past several years as the "reforms" of the health and social service systems have continued (Kavanagh and Knapp, 1995; Mechanic, 1995). In a recent article, Hadley and Goldman (1995) suggest that one possible solution to some of these issues may be the creation of a local mental health authority. Such an authority would consolidate the funding, authority and responsibility in a single entity. We believe this model, which is typical of many local public mental health systems in the US, is at least part of the solution to the current problem of financial and service fragmentation of the current system in the UK. The numerous "reforms" of the health and social service systems (which include the Community Care Act, the development of the Internal Market, GP fundholding and the purchaser-provider split) were not designed for the care of the mentally ill (Han, 1996). These policy changes in the design of health and social services have created a complicated and difficult context in which services must be delivered. Too many agencies play a significant role in the delivery and management of mental health services. Health authorities, social service agencies and GP fundholders are direct and indirect funders of the system while community care trusts, social service agencies and GPs are service providers (Hadley, 1996a). RESULTS AND A PROPOSAL: We believe that the development of local mental health authorities may be part of the solution to the structural and economic problems of the current system in the UK. It is not the answer to limited resources or limited skills, but can create a new structure, which will permit and encourage the cooperation and innovation that is now possible only with unusual effort. Local mental health authorities have a number of crucial characteristics, but, most importantly, they refocus the system on the provision of care to the seriously mentally ill. This is the expressed priority of government, advocates and providers, alike.These new entities could be created at either the purchaser or provider level or, as exists in a number of jurisdictions in the US, at both levels, where a single purchaser may be responsible for multiple consolidated providers. This combination is now the emerging model for innovative services in the US. In the UK, the development of a local mental health authority at the purchaser and/or provider level might be relatively simple. Although the creation of a statutory authority would require primary legislation and is therefore probably not a short-term solution, there appears to be a variety of administrative options that would have the same effect. IMPLICATIONS FOR HEALTH POLICY FORMULATION: The creation of a local mental health authority may be a necessary first step towards the development of a coordinated and comprehensive system of care. It seems likely that there is currently more "political" support for the development of a purchaser model but the development of a sophisticated purchsaer is also likely to take considerable time and effort. Although all the structural and policy problems of the mental health system in the UK will not all be solved by local mental health authorities, they may be beneficial if responsibility for mental illness care is to be centralized and fragmentation is to be reduced. Without making structural changes, the best efforts by clinicians, policymakers and managers are most likely to be in vain. Without a clear point of ultimate purchasing and service responsibility, the fragmentation and inefficiency of the current system will remain (Hadley et al., 1996).

Journal Article↗

PubMed1990

Epilogue: agricultural occupational and environmental health policy strategies for the future.

Farmers' health and safety are critical public health problems that have historically been ignored in the United States and in many countries by health policy developers. The challenges to reduce the hazards are significant. However, by mobilizing the resources, the public will, and the structure to carry out preventive programs, progress is possible. Sweden has shown that research, education, engineering, and regulation have resulted in significant reductions of tractor rollover deaths, chainsaw injuries, and hearing loss.

Accidents, Occupational↗

PubMed2007

Recent progress in engineering alpha/beta hydrolase-fold family members.

The members of the alpha/beta hydrolase-fold family represent a functionally versatile group of enzymes with many important applications in biocatalysis. Given the technical significance of alpha/beta hydrolases in processes ranging from the kinetic resolution of enantiomeric precursors for pharmaceutical compounds to bulk products such as laundry detergent, optimizing and tailoring enzymes for these applications presents an ongoing challenge to chemists, biochemists, and engineers alike. A review of the recent literature on alpha/beta hydrolase engineering suggests that the early successes of "random processes" such as directed evolution are now being slowly replaced by more hypothesis-driven, focused library approaches. These developments reflect a better understanding of the enzymes' structure-function relationship and improved computational resources, which allow for more sophisticated search and prediction algorithms, as well as, in a very practical sense, the realization that bigger is not always better.

Epoxide Hydrolases↗

PubMedDate not supplied

Developing management systems with cross-cultural fit: assessing international differences in operational systems.

Experiences in the Yunnan Maternal and Child Health Project, a 6-year CAN 6 million dollars bilateral initiative implemented in 10 counties (population 2.4 million) in Yunnan, China, are used to illustrate management approaches that successfully bridge cross-cultural differences in operational systems between donor and recipient countries. Donor institutions, local implementing agencies, and partner executing organizations each operate within specific assumptions about how governance structures, financial and administrative systems, human resource infrastructure, communications systems, and monitoring and reporting mechanisms function. These 'system domains' vary across cultures and countries, and become more evident as projects deal with capacity constraints, concerns about accountability, and rapid socioeconomic and political change during implementation. Management teams must be able to identify areas of poor fit among operational systems and respond appropriately. An assessment tool is offered, which management partners can use, as a basis for joint reflections on potential risks, identification of mitigation strategies, and establishing operational systems that are a fit for the funder as well as for partner agencies responsible for executing the project.

Canada↗

PubMed2005

Histone acetylase inhibitor trichostatin A induces acetylcholinesterase expression and protects against organophosphate exposure.

The biological effects of organophosphorous (OP) chemical warfare nerve agents (CWNAs) are exerted by inhibition of acetylcholinesterase (AChE), which prevents the hydrolysis of the neurotransmitter acetylcholine, leading to hypercholinergy, seizures/status epilepticus, respiratory/cardiovascular failure, and potentially death. Current investigations show that bioscavenger therapy using purified fetal bovine AChE in rodents and non-human primates and the more recently tested human butyrylcholinesterase, is a promising treatment for protection against multiple LD(50) CWNA exposures. Potential impediments, due to the complex structure of the enzyme, purification effort, resources, and cost have necessitated alternative approaches. Therefore, we investigated the effects of transcriptional inducers to enhance the expression of AChE to achieve sufficient protection against OP poisoning. Trichostatin A (TSA), an inhibitor of histone deacetylase that de-condenses the chromatin, thereby increasing the binding of transcription factors and mRNA synthesis, was evaluated for induction of AChE expression in various neuronal cell lines. Dose-response curves showed that a concentration of 333 nM TSA was optimal in inducing AChE expression. In Neuro-2A cells, TSA at 333 nM increased the extracellular AChE activity approximately 3-4 fold and intracellular enzyme activity 10-fold. Correlating with the AChE induction, TSA pre-treatment significantly protected the cells against exposure to the organophosphate diisopropylfluorophosphate, a surrogate for the chemical warfare agents soman and sarin. These studies indicate that transcriptional inducers such as TSA up-regulate AChE, which then can bioscavenge any organophosphates present, thereby protecting the cells from OP-induced cytotoxicity. In conclusion, transcriptional inducers are prospective new methods to protect against CWNA exposure.

Acetylcholinesterase↗

PubMed1992

Multiple protein sequence alignment from tertiary structure comparison: assignment of global and residue confidence levels.

An algorithm is presented for the accurate and rapid generation of multiple protein sequence alignments from tertiary structure comparisons. A preliminary multiple sequence alignment is performed using sequence information, which then determines an initial superposition of the structures. A structure comparison algorithm is applied to all pairs of proteins in the superimposed set and a similarity tree calculated. Multiple sequence alignments are then generated by following the tree from the branches to the root. At each branchpoint of the tree, a structure-based sequence alignment and coordinate transformations are output, with the multiple alignment of all structures output at the root. The algorithm encoded in STAMP (STructural Alignment of Multiple Proteins) is shown to give alignments in good agreement with published structural accounts within the dehydrogenase fold domains, globins, and serine proteinases. In order to reduce the need for visual verification, two similarity indices are introduced to determine the quality of each generated structural alignment. Sc quantifies the global structural similarity between pairs or groups of proteins, whereas Pij' provides a normalized measure of the confidence in the alignment of each residue. STAMP alignments have the quality of each alignment characterized by Sc and Pij' values and thus provide a reproducible resource for studies of residue conservation within structural motifs.

Algorithms↗

PubMed1996

Mapping human telomere regions with YAC and P1 clones: chromosome-specific markers for 27 telomeres including 149 STSs and 24 polymorphisms for 14 proterminal regions.

A YAC library enriched for telomere clones was constructed and screened for the human telomere-specific repeat sequence (TTAGGG). Altogether 196 TYAC library clones were studied: 189 new TYAC clones were isolated, 149 STSs were developed for 132 different TY-ACs, and 39 P1 clones were identified using 19 STSs from 16 of the TYACs. A combination of mapping methods including fluorescence in situ hybridization, somatic cell hybrid panels, clamped homogeneous electric fields, meiotic linkage, and BLASTN sequence analysis was utilized to characterize the resource. Forty-five of the TYACs map to 31 specific telomere regions. Twenty-four linkage markers were developed and mapped within 14 proterminal regions (12 telomeres and 2 terminal bands). The polymorphic markers include 12 microsatellites for 10 telomeres (1q, 2p, 6q, 7q, 10p, 10q, 13q, 14q, 18p, 22q) and the terminal bands of 11q and 12p. Twelve RFLP markers were identified and meiotically mapped to the telomeres of 2q, 7q, 8p, and 14q. Chromosome-specific STSs for 27 telomeres were identified from the 196 TYACs. More than 30,000 nucleotides derived from the TYAC vector-insert junction regions or from regions flanking TYAC microsatellites were compared to reported sequences using BLASTN. In addition to identifying homology with previously reported telomere sequences and human repeat elements, gene sequences and a number of ESTs were found to be highly homologous to the TYAC sequences. These genes include human coagulation factor V (F5), Weel protein tyrosine kinase (WEE1), neurotropic protein tyrosine kinase type 2 (NTRE2), glutathione S-transferase (GST1), and beta tubulin (TUBB). The TYAC/P1 resource, derivative STSs, and polymorphisms constitute an enabling resource to further studies of telomere structure and function and a means for physical and genetic map integration and closure.

Animals↗

PubMedDate not supplied

A transformed human epithelial cell line that retains tight junctions post crisis.

The successful establishment of a postcrisis SV-40 T antigen transformed epithelial cell line, 1HAEo-, which retains tight junctions and vectorial ion transport, is described. Immunocytochemical analysis of 1HAEo- cells shows a defined pattern of cytokeratin staining and a characteristic pericellular localization of the adhesion molecule cellCAM 120/80, indicating the presence of junctional complexes. The presence of both tight junctions and desmosomes has been confirmed by electron microscopy. Cell monolayers have good transepithelial resistance measured in Ussing chambers. Cells increase chloride ion transport in response to addition of agents that raise either intracellular cAMP or calcium, measured either by 36Cl- efflux or whole-cell patch clamp. An increase in short-circuit current, in response to these agents, can be measured in Ussing chambers. The presence of a depolarization-induced outwardly rectifying 45 pS chloride channel has been demonstrated in single cell detached membrane patches. In addition, the cells have been found to express mucin mRNA. These cells therefore demonstrate that it is possible to select transformed cell clones with particular morphologic characteristics, i.e. the presence of tight junctions and cell polarity, which also retain useful epithelial cell-specific functions, including vectorial ion transport. They also provide a major resource for the study of the structure and function of human epithelia.

Base Sequence↗

PubMed1999

[Socioeconomic status and gender. Manifestations of social inequality in psychiatric diseases].

This paper is concerned with the relationship between social inequality and psychiatric disorders, an issue being neglected in German psychiatry for a long time. Social inequality will be discussed in it's dimensions "socioeconomic status" and "sex" referring to the present state of epidemiological and sociological knowledge. Because such macro-social factors offer little explanation for the association with psychiatric disorders by themselves micro-social concepts of burden and resources are necessary to link the structural and the individual level. These concepts are considered to be one pathway by which the mechanisms to disease may occur. A short review of empirical findings and analytic approaches show the complexity of these mechanisms requiring further research not only because of analytic deficiencies but also because of social change. Further research will concern in general the explanation of social patterns of diseases, in detail the link between individual stress and coping with the social structure, and last but not least a gender-sensitive approach to psychiatric disorders which is more differentiated.

Cost of Illness↗

PubMed2006

A discriminative method for remote homology detection based on n-peptide compositions with reduced amino acid alphabets.

In this study, n-peptide compositions are utilized for protein vectorization over a discriminative remote homology detection framework based on support vector machines (SVMs). The size of amino acid alphabet is gradually reduced for increasing values of n to make the method to conform with the memory resources in conventional workstations. A hash structure is implemented for accelerated search of n-peptides. The method is tested to see its ability to classify proteins into families on a subset of SCOP family database and compared against many of the existing homology detection methods including the most popular generative methods; SAM-98 and PSI-BLAST and the recent SVM methods; SVM-Fisher, SVM-BLAST and SVM-Pairwise. The results have demonstrated that the new method significantly outperforms SVM-Fisher, SVM-BLAST, SAM-98 and PSI-BLAST, while achieving a comparable accuracy with SVM-Pairwise. In terms of efficiency, it performs much better than SVM-Pairwise. It is shown that the information of n-peptide compositions with reduced amino acid alphabets provides an accurate and efficient means of protein vectorization for SVM-based sequence classification.

Amino Acid Sequence↗

PubMed2006

Running before we walk: how can we maximise the benefits from community service dietitians in KwaZulu-Natal, South Africa?

INTRODUCTION AND AIM: The Department of Health in South Africa, instituted compulsory community service (CS) as one strategy to overcome the chronic shortage of health professionals in underserved and rural areas. A number of articles have listed the reasons for the lack of willingness of health professionals to practice in rural areas. Amongst others they listed the lack of career opportunities, the recruitment of students into health professions from incongruous backgrounds, inappropriate training, bureaucratic problems, poorly equipped hospitals and social isolation. The aim of this study was to examine and explore the factors affecting the professional development of dietitians during CS. METHODS: Thirteen of the 15 community service dietitians (CSDs) currently (2005) undertaking CS in KwaZulu-Natal participated in focus group discussions. Each member of the group was also required to answer a short written questionnaire before the discussions to establish whether there was congruence between the written answers and the verbal discussions. The large group was divided into two sub groups and each session lasted one and a half hours. A list of topics was discussed by each group. The sessions were taped and transcribed and further analysed using the qualitative analysis programme, "QSR NVivo". RESULTS: Analysis of the transcripts revealed a number of thematic areas and included the evaluation of the placement process, obstructions and constraints, the developmental progress of the CSD and means of enhancing professional development. The discussion on the placement process was not contentious, with only three CSDs having reservations about the process. Many obstructions and constraints to service delivery and professional development were revealed and included the lack of supervision and support, the lack of preparedness of the institutions receiving CSDs and the lack of clarity of the CSDs' perception of community service, unhappiness of some CSDs being placed a long way from home, work and role overload, not being part of a team, lack of understanding the CSDs role and the under utilisation of their services. Developmental progress of the CSDs was enhanced by some positive aspects which included the social interactions experienced in the community setting, learning new skills and support that they received from other community service professionals. DISCUSSIONS AND RECOMMENDATIONS: Comparison of the written answers with verbal discussions showed the same results. A number of issues raised in this study have been recorded by other authors. It is recommended that the issue of supervision and support be addressed so that the professional development of CSDs is enhanced. The lack of preparedness of the receiving institutions is a problem that is relatively easy to address and should be made a priority. The training institutions also need to be more proactive in preparing dietetic students for CS. CONCLUSIONS: Compulsory community service as a method of addressing the problems of underserved population has merit. To maximise the benefits the DOH would do well to heed the recommendations by ensuring that there are structures in place to provide adequate resources for and support and supervision of CSDs.

Allied Health Personnel↗

PubMed2006

Limit cycles in a chemostat model for a single species with age structure.

We model an age-structured population feeding on an abiotic resource by combining the Gurtin-MacCamy [Math. Biosci. 43 (1979) 199] approach with a standard chemostat model. Limit cycles arise by Hopf bifurcations at low values of the chemostat dilution rate, even for simple maternity functions for which the original Gurtin-MacCamy model has no oscillatory solutions. We find the exact location in parameter space of the Hopf bifurcations for special cases of our model. The onset of cycling is largely independent of both the form of the resource uptake function and the shape of the maternity function.

Bioreactors↗

PubMed2005

Brain regions associated with successful and unsuccessful retrieval of verbal episodic memory as revealed by divided attention.

Which brain regions are implicated when words are retrieved under divided attention, and what does this tell us about attentional and memory processes needed for retrieval? To address these questions we used fMRI to examine brain regions associated with auditory recognition performed under full and divided attention (DA). We asked young adults to encode words presented auditorily under full attention (FA), and following this, asked them to recognize studied words while in the scanner. Attention was divided at retrieval by asking participants to perform either an animacy task to words, or odd-digit identification task to numbers presented visually, concurrently with the recognition task. Retrieval was disrupted significantly by the word-, but not number-based concurrent task. A corresponding decrease in brain activity was observed in right hippocampus, bilateral parietal cortex, and left precuneus, thus demonstrating, for the first time, involvement of these regions in recognition under DA at retrieval. Increases in activation of left prefrontal cortex (PFC), associated with phonological processing, were observed in the word- compared to number-based DA condition. Results suggest that the medial temporal lobe (MTL) and neo-cortical components of retrieval, believed to form the basis of episodic memory traces, are disrupted when phonological processing regions in left PFC are engaged simultaneously by another task. Results also support a component-process model of retrieval which posits that MTL-mediated retrieval does not compete for general cognitive resources but does compete for specific structural representations.

Acoustic Stimulation↗

PubMed2004

Incorporating Florence Nightingale's theory of nursing into teaching a group of preadolescent children about negative peer pressure.

Clinically based nurses often question the value of nursing theory, ultimately resulting in the reluctance to implement nursing theory into practice. This clinical practicum project successfully used Nightingale's primary tenets, such as building trust, self-assessment, and group leadership, as a theoretical framework in a nursing practice group for the purpose of teaching a group of preadolescent children about negative peer pressure. Preadolescent children are particularly vulnerable to peer group culture. Proactive strategies, as demonstrated through this project, can be used to positively influence children's behavior toward each other during the formative middle years. Group sessions addressed such topics as moral beliefs and values, bullying, and saying "no" to peer pressure and were structured using a variety of contemporary resources to develop interactive exercises that engaged the children and enhanced group communication. The children and their parents reported positive outcomes from the nurse-led group sessions.

Adolescent↗

PubMed2004

Governance in gridlock in the Russian health system; the case of Sverdlovsk oblast.

Epidemiological, demographic and environmental crises, transition to a new political regime and exceptionally severe economic crises were powerful stimuli to health sector reform in Russia. The Russian Federation responded by introducing medical insurance whilst decentralising public administration. Yet despite intense contextual pressures to do so and a new policy climate, Russian hospitals found it difficult to reprofile services and reallocate their resources. A case study analysing governance structures in Sverdlovsk oblast reveals that medical insurance created incentives to reduce costs by reducing bed-days, but if hospitals did so they would lose money under the formulae through which decentralised local government still allocated around three-quarters of hospital income. If instead hospitals tried to increase budgetary income by increasing numbers of bed-days, the insurance system would penalise them. This specific form of policy mess can be called 'governance in gridlock'. The juxtaposition of two overlapping but incompatible sets of governance structures practically immobilised official hospital management systems. It is as one-sided to blame residues of the Soviet system for this gridlock as it is to blame the medical insurance system. Gridlock resulted from the interaction of the two, a problem to which all health system reform is potentially vulnerable.

Bed Occupancy↗