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PubMed2005

Electrostatics of Cytochrome-c assemblies.

Electrostatic potentials along with computational mutagenesis are used to obtain atomic level insights into Cytochrome-c in order to design efficient bionanosensors. The electrostatic properties of wild type and mutant Cytochrome-c are examined in the context of their assembly, i.e. are examined in the absence and presence of neighboring molecules from the assembly. An intense increase in the positive potential ensues when the neighboring molecules are taken into account. This suggests that in the extrapolation of electric field effects upon the design of assemblies, considering the properties of only the central molecule may not be sufficient. Additionally, the influence of the uncharged residues becomes quite diminished when the molecule is considered in an assembly. This could pave the way for making mutants that might be more soluble in different media used in the construction of devices. [Figure: see text]. The electrostatic potential, calculated using the program DELPHI mapped on to the surface of Cytochrome-c when it is considered by itself (in the left column) and in the presence of the electrostatic field generated by the presence of the surrounding 4 molecules on the right. The potentials range from -10kT in red to +10kT in blue. The central figure shows the regions that have been mutated to positively charged residues by placing a unit positive charge at the terminal atom of the respective side chain. The figures range from the wild type in the first row, followed by the Gln12, Asn70, Asp50, Glu90 and Ala83 mutants.

Cytochromes c↗

PubMed2006

Evaluating the organization and delivery of breast cancer services: use of performance measures to identify knowledge gaps.

OBJECTIVES: This paper identifies gaps in our knowledge about the quality of breast cancer care in Canada to understand where programs and resources are required to enhance health services and research capacity. METHODS: A modified Delphi approach was employed involving a 15-member multidisciplinary panel of health professionals and two rounds of rating followed by deliberation to develop evidence- and consensus-based performance measures. A literature search for Canadian health services research in breast cancer was conducted based on the indicator topics. Eligible articles were identified in indexed databases of medical literature and funded research from 1995 to 2006. RESULTS: The multidisciplinary panel selected 34 indicators spanning access to services, patient outcomes, diagnosis and staging, surgery, adjuvant therapy, pathology, and follow-up care. A total of 78 articles (66 quantitative; 12 exploratory) on these topics were reviewed. Apart from two aspects of care (communication of treatment options, supportive care), the yield of Canadian breast cancer health services research did not increase subsequent to a review conducted 10 years ago which recommended greater efforts in this area. CONCLUSIONS: Research involving quantitative and qualitative methods is needed to increase our understanding about the organization and delivery of services for breast cancer diagnosis, treatment and follow-up care. Since it is unclear how to balance competing research demands, innovative strategies are required to assemble resources for health services research on breast cancer. This could include the promotion of partnerships between researchers and policy-makers across jurisdictions, and the pooling of resources between organizations, regions or networks.

Breast Neoplasms↗

PubMed2006

Manufacturing consensus.

The Food and Drug Administration (FDA) has declared that it would be illegal to advertise as or in any way claim your drug to be superior to competitors on the market, which are up to 30 times cheaper. How does a pharmaceutical company market such a product? The answer is to enlist academics to form expert panels to construct guidelines and algorithms, or participate in Delphi panels and other exercises, which can be expected to prove that newer, more costly drugs produce cost savings. These academics do so on the basis of the existing clinical trial evidence--which supposedly the FDA has used to come to its verdict that the newer compound is no better than its competitors. However, where the FDA has seen the raw data, academics later see the published data. In between intervenes a medical writing exercise, which produces the first and most important piece of advertising for any pharmaceutical product--the randomized controlled trial infomercial. This paper explores how pharmaceutical companies manufacture an apparent academic consensus and, in so doing, gives a case study of the recent controversies surrounding the marketing of selective serotonin reuptake inhibitor (SSRI) drugs for adolescent depression.

Adolescent↗

PubMed1990

Modeling of the electrostatic potential field of plastocyanin.

The DelPhi computer program is used to calculate the electrostatic potential field of the photosynthetic electron transport protein plastocyanin. Knowledge of the potential field is important for understanding the mechanisms by which plastocyanin interacts with other charged reagents. The program uses a macroscopic, continuum approach in which the protein and solvent are assigned different dielectric constants, the crystal structure of the protein defines the dielectric boundary, and the ionic strength of the solvent is taken into account. The potential field is determined by numerically solving the Poisson-Boltzmann equation. The field surrounding plastocyanin is characterized by a region of positive potential over the copper center active site, and a region of negative potential over the adjacent association site containing tyrosine 83. The shape and magnitude of the potential field shows a strong dependence on the ionic strength and pH of the solvent. The program is able to accurately predict the effect of the copper center oxidation state on the pKa of a tetranitromethane derivative of tyrosine 83 using an intrinsic protein dielectric constant of 2 to 4. Evidence is also presented that the glutamate 68 side chain is exposed to the solvent to a greater extent in the solution structure of plastocyanin than in the crystal structure.

Amino Acid Sequence↗

PubMed1982

Role of isovaleroyl lipids in channeling of sound in the porpoise melon.

Physical properties (e.g. specific gravity, adiabatic compressibility and sound velocity) of lipids isolated from tissues from contiguous areas of the fatty melon of an echo-locating porpoise (Delphinus delphis) were determined to elucidate relations between lipid composition and structure, and sound transmission in the head. Lipid content varied greatly within the melon (13.6-77.6% of the tissue weight) and triacylglycerols (80-100%) were the major lipid components. This lipid class was composed of diisovaleroylglycerides (triacylglycerols containing two isovaleroyl moieties and a long-chain acyl moiety), monoisovaleroyldiacylglycerols and triacylglycerols consisting of long-chain acids. The lipid-rich (greater than 45%) areas in the melon contained a high proportion (greater than 45% of total triacylglycerols) of diisovaleroylglycerides. There were gradations of sound velocities within the melon; the lowest sound velocities were associated with high concentrations of diisovaleroylglycerides (less than 1400 m/s) and the highest with high concentrations of long-chain triacylglycerols. Assuming an average sound frequency of 75 kHz, and considering dimensions of melon (path length and width of 12-14 cm and 5 cm, respectively), a forward radiating lobe of 15-25 degrees is produced. Thus, the deposition of lipids of different acoustic properties in a three-dimensional matrix within the porpoise melon results in a lens for the projection of sound into the marine environment.

Animals↗

PubMed1987

Influence of noise on wave boundary recognition by ECG measurement programs. Recommendations for preprocessing.

In the international cooperative project entitled "Common Standards for Quantitative Electrocardiography" (CSE) systematic noise tests have been performed in order to compare measurement results of electrocardiographic computer programs under degraded operational conditions and to develop recommendations for preprocessing and measurement strategies. The influence of seven different high- and low-frequency noise types on the recognition of P, QRS, and T wave onsets and offsets was investigated. The analysis was performed on 160 electrocardiograms derived from two sets of 10 cases each, by eight electrocardiographic and six vectorcardiographic computer programs. The stability and precision of these programs were tested with respect to the results obtained (1) in the noise-free recordings and (2) by a group of five cardiologists who have analyzed the recordings previously in a Delphi reviewing process. Increasing levels of high-frequency noise shifted the onsets and offsets of most programs outward. Programs analyzing an averaged beat showed significantly less variability than programs which measure every complex or a selected beat. On the basis of the findings of the present study, a measurement strategy based on selective averaging is recommended for diagnostic ECG computer programs. However, averaging should be performed only if proper alignment and precise waveform comparison have been performed beforehand in order to exclude dissimilar complexes.

Diagnosis, Computer-Assisted↗

PubMed1982

Scenarios, past, present and future.

A key point in considering strategic planning is that it is not forecasting. The future is unpredictable and is not a product of the past. This low opinion of forecasting has gained in influence recently. But such an approach creates a dilemma for the strategic planner. He needs to take into account potential future forces--but he can only do this with inadequate means. Forecasting methods, however, can suggest trends and it is possible to reduce the number of possible futures to a manageable number. This is, in effect, creating scenarios. The concept of using alternative scenarios in planning was popularized some 20 years back. The proviso was made that they should not be interpreted as forecasts. The methods have proved highly flexible and include the consensus technique, the iteration-through-synopsis technique, and the cross-impact method. Various studies using one or more of these have been implemented, perhaps the best known being by Meadows and by Mesarovic. These have been based on the so-called 'hard' method, using computers. 'Soft' methods are based more on the mind and use psychology and sociology, the most familiar being the Delphi method. A somewhat more sophisticated version is Cross-Impact Analysis.

Forecasting↗

PubMed1994

A review of heavy metal and organochlorine levels in marine mammals in Australia.

Study of toxic contaminants in marine mammal specimens collected around Australia is currently uncoordinated and piecemeal. Most states collect samples but there is little or no financial support for their analysis. This study combines data, published or unpublished, from 13 sources. Heavy metals have been analysed in about 676 specimens; over 400 were for mercury levels in P. macrocephalus taken at a whaling station. The remaining samples were mostly from toothed whales, a few baleen whales (< 20), pinnipeds (41) and dugongs (49). The most consistently analysed metals were lead, mercury and cadmium. Liver and kidney lead levels ranged from < 1-3 ppm; levels in bone were 0-418 ppm, with most less than 10 ppm. Mercury levels in a large sample of P. macrocephalus muscle were < 12.2 ppm. Mercury levels in the small number of samples from other species were 0.51-143 ppm (kidney), 1.52-479 ppm (liver) and < 0.1-36 ppm (muscle). Cadmium levels in liver (0-52 ppm) and kidney (0-106 ppm) were extremely variable. Levels greater than 10 ppm were recorded in many species and were especially high in Hydrurga leptonyx, Dugong dugon, Mesoplodon layardii and Pseudorca crassidens. Adult Tursiops truncatus inhabiting the inshore gulfs of South Australia had considerably higher levels of cadmium compared with other regions. Information on organochlorine levels is sparse (approximately 39 specimens) and suggest low levels when compared to other parts of the world. Total DDT was highest (28.4 ppm) in a neonatal Orcinus orca. Some high levels of DDT were recorded in Tursiops truncatus, Delphinus delphis and Arctocephalus pusillus doriferus. PCBs ranged from < 0.05 to 3.87 ppm. A comprehensive pathological assessment of marine mammals is needed in order to evaluate the effects of toxic contaminants.

Animals↗

PubMed1994

The cost of treatment dropout in depression. A cost-benefit analysis of fluoxetine vs. tricyclics.

In this study, we tried to estimate the economic potential benefit of the use of fluoxetine (PROZACR 20 mg, Lilly) versus tricyclic antidepressants (TCAs) in depression of mild to moderate intensity. Fluoxetine has demonstrated, in controlled studies, significantly lower rates of side-effects and treatment dropout than TCAs while showing similar efficacy. Treatment dropout, especially at an early stage of the therapy, can have profound consequences, including excessive lengthening of the depressive episode, symptomatic relapse, increase of repeated days out of work, even suicides or suicide attempts. We estimated the expected cost of treatment dropout using a Delphi expert panel. We then computed the economic benefit of fluoxetine by combining the dropout cost and the differential rate of total treatment dropout between fluoxetine and TCAs, as found in clinical trials. We thus showed that a 8 week fluoxetine could be beneficial to society provided society values a year of human life above a threshold varying from French Francs 23.800 to FF8.600 (respectively, about US$4500 and 1600) depending on the type of depression. As these values are extremely low compared to those found in the literature, we concluded that an apparently costly innovation such as fluoxetine may induce short-term financial savings for society.

Antidepressive Agents, Tricyclic↗

PubMed1988

Validating the certification process for infection control practice.

Approximately 5 years ago a task analysis was conducted by the Certification Board of Infection Control (CBIC) to describe infection control practice. This task analysis served as the basis for development of the certification examination. This article describes the process used to update and revalidate the original task analysis to ensure the continued validity and job relatedness of the certification process. Using a modified Delphi technique, several panels of representative expert infection control practitioners (ICPs), a total of 29 persons, participated in an iterative process to define the practice dimensions of infection control and to link these practice dimensions to the certification examination. In general, there was a high level of congruence between respondents on the original task analysis and the expert panels, although a few differences in practice were identified among ICPs in extended care facilities and a few new tasks were identified. In addition, a revised content outline for the examination was created by placing clusters of knowledge statements together around common themes.

Certification↗

PubMed1989

Automated assignment of behavioural states in the human near term fetus.

Thirty-five 2-h recordings of fetal heart rate and fetal movements, made at 38-39 weeks of gestational age, have been analyzed in a partly automated procedure. Involved were 17 nulliparous and 19 multiparous women. To minimize subjectivity the classification of the heart rate was performed in a Delphi group opinion procedure consisting of three rounds. In the third round, three independent investigators classified 89.1% of the total tracing time as pattern A through D. The investigators could not classify 6.1% of the tracing time in any of the available categories. The percentages of coincidence of state parameters did not differ significantly between the fetuses of nulli- and multiparous women. Fifty percent of the fetuses showed true behavioural states, both in the nulli and the multiparous women. The percentage of time spent in state 1F was higher in the multiparous group (P less than 0.05). The other percentages of states did not differ significantly, neither did the duration of the enclosed epochs. The advantages and disadvantages of the automated assignment of fetal behavioural states are discussed.

Computers↗

PubMed2005

Development of public health priorities for end-of-life initiatives.

OBJECTIVE: Recently, end-of-life (EOL) issues have captured the attention of the public health community. This study reports a project to help state health departments better understand their potential role in addressing EOL issues and develop initial priorities for EOL activities. METHODS: The project involved two studies. Study 1 (October 2002 to September 2003) involved a concept mapping process to solicit and organize recommendations from key stakeholders. Concept mapping integrates qualitative group processes with multivariate statistical analysis to represent the ideas of stakeholders visually through maps. A key-informant approach was used to identify stakeholder participants with expertise in aging, cancer, public health, and EOL. In two meetings, stakeholders used the maps to develop short-, intermediate-, and long-term recommendations for EOL initiatives. Study 2 (October 2003 to September 2004) involved a modified Delphi process with three iterations to prioritize recommendations for initial action from among a group of short-term recommendations. RESULTS: Study 1 resulted in 103 recommendations for EOL initiatives across nine domains. Study 2 resulted in consensus on five initial recommendations from three domains: identifying an EOL point of contact in state health departments, collecting and analyzing data about EOL, incorporating EOL principles into state comprehensive cancer control plans, educating the public about hospice and palliative care, and educating the public about the importance of advance directives. CONCLUSIONS: Diverse perspectives of key public health stakeholders resulted in a series of short- and longer-term recommendations for EOL action. These recommendations can guide future efforts by state health departments and other public health agencies to address EOL issues.

Humans↗

PubMed2005

Interobserver agreement and consensus over the esthetic evaluation of conservative treatment for breast cancer.

Twenty-four experts from 13 different countries were asked to evaluate photographs taken of 60 women following conservative breast cancer treatment. The esthetic result of each case was classified as poor, fair, good or excellent. Agreement was evaluated using the kappa (k) and weighted kappa (wk) statistics, for all observers, male and female participants, those younger and older than 50 years, those seeing more than 250 cases a year, and those with previous publications in this area. Consensus was obtained by way of a modified Delphi approach, when more than 50% of participants provided the same classification. In a second round, consensual cases were disclosed and a revised opinion was asked in non-consensual ones. Agreement between all participants was fair (k=0.24, wk=0.37) and remained within the same range (k=0.20-0.31, wk=0.31-0.45) in the subgroups analyzed. First round consensus was obtained in 46 out of 60 cases (77%) and in the second round in 59 out of 60 cases (98%). Evaluation of the esthetic results of conservative treatment for breast cancer is only fairly reproducible when performed by experts working in different geographical areas. Consensus is obtainable if a relatively low threshold of agreement is considered acceptable.

Adult↗

PubMed2006

Stratification and intra- and inter-specific differences in fatty acid composition of common dolphin (Delphinus sp.) blubber: implications for dietary analysis.

Sixty-five fatty acids were quantified in the blubber of common dolphins (Delphinus delphis, D. capensis) incidentally caught off the coast of southern California. Dolphins were grouped by sex, reproductive status and species, and a blubber sample was collected at a mid-lateral site located caudal to the trailing edge of the dorsal fin. Samples were divided horizontally into inner, middle and outer layers and gradients in fatty acid content (mass percent) were observed across the depth of the blubber. Levels of monounsaturated fatty acids were greatest in the outer layer, whereas levels of saturated and polyunsaturated fatty acids were greatest in the inner layer. Degree of stratification was greatest in sexually mature dolphins. Blubber of sexually immature, but physically mature, male dolphins was also highly stratified, suggesting that this difference may be attributed to differences in diet. Classification and regression tree analysis resulted in the fewest misclassifications when dolphins were grouped by species, possibly indicating that these closely related animals forage on different prey species. Dietary-derived fatty acids were typically selected as splitting criteria in classification and regression tree analyses, suggesting that the observed differences in fatty acid composition between the various groups of dolphins may be attributed to differences in diet.

Animals↗

PubMed2006

Clinically important drug-disease interactions and their prevalence in older adults.

BACKGROUND: Older adults may have decreased homeostatic reserve, have multiple chronic diseases, and take multiple medications. Therefore, they are at risk for adverse outcomes after receiving a drug that exacerbates a chronic disease. OBJECTIVES: The aims of this study were to compile a list of clinically important drug-disease interactions in older adults, obtain the consensus of a multidisciplinary panel of geriatric health care professionals on these interactions, and determine the prevalence of these interactions in a sample of outpatients. METHODS: This analysis included a 2-round modified Delphi survey and cross-sectional study. Possible drug-disease interactions in patients aged > or =65 years were identified through a search of the English-language literature indexed on MEDLINE and International Pharmaceutical Abstracts (1966-July 2004) using terms that included drug-disease interaction, medication errors, and inappropriate prescribing. Nine health care professionals with expertise in geriatrics (2 geriatricians, 7 geriatric clinical pharmacist specialists) were selected based on specialty training and continuing clinical work in geriatrics, academic appointments, and geographic location. The panel rated the importance of the potential drug-disease interactions using a 5-point Likert scale (from 1 = definitely not serious to 5 = definitely serious). Consensus on a drug-disease interaction was defined as a lower bound of the 95% CI > or =4.0. The prevalence of drug-disease interactions was determined by applying the consensus criteria to a convenience sample of frail older veterans at hospital discharge who were enrolled in a health services intervention trial. RESULTS: The panel reached consensus on 28 individual drug-disease interactions involving 14 diseases or conditions. Overall, 205 (15.3%) of the 1340 veterans in the sample had > or =1 drug-disease interaction. The 2 most common drug-disease interactions were use of first-generation calcium channel blockers in patients with congestive heart failure and use of aspirin in patients with peptic ulcer disease (both, 3.7%). CONCLUSIONS: A survey of multidisciplinary geriatric health care professionals resulted in a concise consensus list of clinically important drug-disease interactions in older adults. Further research is needed to examine the impact of these drug-disease interactions on health outcomes and their applicability as national measures for the prevention of drug-related problems.

Aged↗

PubMed2006

Methodology for the development of the ESPEN Guidelines on Enteral Nutrition.

Under the auspices of the European Society for Clinical Nutrition and Metabolism (ESPEN) clinical practice guidelines on enteral nutrition were systematically developed between spring 2004 and winter 2005 in a both evidence and consensus based process. A steering committee implemented 13 disease-specific working groups with a total of 88 experts in clinical nutrition from 20 countries. Evidence was gathered by conducting a structured literature search applying a defined search strategy, inclusion criteria and specified keywords. The quality and strength of the supporting evidence was then graded according to published standards. On this basis recommendations were spelled out which were not only based on the evidence levels of the studies but also on the judgement of the working groups concerning the consistency, clinical relevance and validity of the evidence. Preparation of the drafts was accomplished in interactive small group work processes. The voting of statements took place in a consensus conference and final refinements and voting were done using the Delphi technique. The ESPEN guidelines enteral nutrition reflect the current medical knowledge in the field of enteral nutrition therapy and summarize the evidence when enteral nutrition is indicated and which goals can be reached in regard to nutritional state, quality of life and outcome.

Enteral Nutrition↗

PubMed2006

Marine mammal strandings in the New Caledonia region, Southwest Pacific.

Four hundred twenty three marine mammals, in 72 stranding events, were recorded between 1877 and 2005 in New Caledonia, the Loyalty Islands, and Vanuatu in the southwest Pacific. Sixteen species were represented in this count, including: minke whale, Balaenoptera acutorostrata (1 single stranding), sei whale, B. borealis (1 single stranding), blue whale, B. musculus (1 single stranding), humpback whale, Megaptera novaeangliae (2 single strandings), giant sperm whale, Physeter macrocephalus (18 single strandings, 2 pair strandings), pygmy sperm whale, Kogia breviceps (5 single strandings), dwarf sperm whale, K. sima (2 single strandings, 1 triple stranding), Blainville's beaked whale, Mesoplodon densirostris (2 single strandings), short-finned pilot whale, Globicephala macrorhynchus (4 strandings, 56 individuals), melon-headed whale, Peponocephala electra (1 single stranding and 2 mass strandings totalling 231 individuals), common dolphin, Delphinus delphis (1 single stranding), spinner dolphin, Stenella longirostris (1 pair stranding and 2 mass strandings of groups of approximately 30 individuals each), Indian Ocean bottlenose dolphin, Tursiops aduncus (2 single strandings), dugong, Dugong dugon (14 single strandings), and New Zealand fur seal, Arctocephalus forsteri (3 single strandings). A stranded rorqual identified as an Antarctic minke whale (B. bonaerensis), with coloration patterns that did not match known descriptions, was also reported. Sei whale was recorded for the first time in the tropical Southwest Pacific region and Antarctic minke whale, melon-headed whale, and Indian Ocean bottlenose dolphin were recorded for the first time in New Caledonia. Strandings of sperm whales were most frequent in the spring, but also occurred in autumn months, suggesting a seasonal pattern of occurrence possibly related to seasonal migration. One stranded humpback whale bore the scars of a killer whale's attack and one dugong was injured by a shark. Scars left by propellers were noted on several stranded animals including one Antarctic minke whale, one pygmy sperm whale, one dwarf sperm whale, and four dugongs. Collisions with vessels were suspected to be a frequent cause of death for dugong.

Animals↗

PubMed2006

Evaluating complementary and alternative therapy services in primary and community care settings: a review of 25 service evaluations.

OBJECTIVES: To review evaluations of primary and community care complementary therapy services. To explore the impact evaluation reports may have had on funding decisions taken by NHS commissioners. DESIGN: We collected 32 reports for 25 services, principally in England. Reports were analysed for content using the structure-process-outcome model. Modified BESTCAM guidelines, which came out of a Delphi consensus exercise rating the ability of reports to address commissioners' priorities, were used to address the second objective. RESULTS: Most commonly, evaluators carried out data extraction of referral forms (10), costings of the service (9), patient satisfaction questionnaires (9) and patient health status questionnaires (8). Five service evaluations addressed NHS cost pressures, with another carrying out a cost effectiveness assessment with QALY. CONCLUSION: Addressing commissioners' priorities (e.g. GP consultations rates, prescription rates, secondary care referrals) in complementary therapy service evaluations may bolster chances of securing funding, but are unlikely to be enough on their own.

Biomedical Research↗