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PubMed2001

The relevance of rooted vascular plants as indicators of estuarine sediment quality.

Toxicity assessments and numerical quality assessment guidelines for estuarine sediments are rarely based on information for aquatic plants. The effect of this lack of information on contaminated sediment toxicity evaluations is largely unknown. For this reason, the toxicities of whole sediments collected from 15 sites in three urbanized Florida bayou-estuaries were determined for the benthic invertebrates Mysidopsis bahia and Ampelisca abdita and the plants Scirpus robustus Pursh (saltmarsh bulrush) and Spartina alterniflora Loisel (saltmarsh cordgrass). The results of the bioassays, conducted for 7 to 28 days, were compared for interspecific differences and to effects-based, sediment quality assessment guidelines. A variety of inorganic and organic analytes were detected in the estuarine sediments, and concentrations of as many as 7 analytes exceeded the sediment guidelines at the 15 sampling locations. Toxicity occurred at 2 of the 15 sampling stations based on invertebrate survival. Twelve of the 15 sediments had either a significant stimulatory or inhibitory effect on early seedling growth relative to a reference sediment (p < 0.05). The phytoresponse was specific to the location, test species, and plant tissue. There was no consistent trend between the sensitivities of the plants and invertebrates exposed to the sediments collected from the same sites. Of the 12 sediments that significantly affected seedling growth, 10 were not acutely toxic to the invertebrates. Consequently, the plant test species provided information that would have been missing if only animal test species were used. For this reason, the phytotoxicity database needs to be expanded for contaminated sediments to further evaluate interspecific sensitivities and to provide perspective on the environmental relevancy of proposed sediment quality criteria and effects-based assessment guidelines for which this information is usually missing. However, additional test method development and field validation are needed to support this effort, which includes the identification of sensitive plant test species, response parameters, and the chemical and physical sediment factors that influence plant growth.

Animals↗

PubMed2002

[Prognostic factors in thin cutaneous malignant melanoma].

An increasing number of thin (< or = 1 mm) cutaneous malignant melanomas are currently diagnosed. The majority of thin lesions is associated with an excellent prognosis, however, some of them may develop local recurrences and/or distant metastases with fatal outcome. Although Breslow thickness is the single most significant prognostic factor in melanoma in general, for thin lesions the identification of other morphological, biological and/or molecular parameters which may have an impact on neoplastic progression is mandatory. At present, Clark's levels and ulceration are regarded as significant prognostic factors. Further studies are needed to confirm the prognostic value of other histopathological parameters, including the evaluation of regression, inflammatory infiltrate and mitotic activity.

Biomarkers, Tumor↗

PubMed1985

A simple algorithm for defining the mean cardiac cycle of aortic flow and pressure during steady state.

A fast procedure for defining a cardiac cycle using simultaneously recorded and digitized aortic flow and pressure is presented. A simple algorithm, based on a double-threshold method, initially involves singling the dicrotic notch of flow in order to separate contiguous cardiac cycles during a given steady state. The individual cycles are carried back to a common origin of time, then they are normalized to the mean length and averaged. As a result of an averaging operation the algorithm gives a "mean cycle" of both pulsatile aortic pressure and flow. An "a posteriori" analysis of the noise components in the data has been carried out in order to justify the averaging operation. The "mean cycle" of aortic flow and pressure are suitable to be used as the input quantities of the automatic identification procedures recently assessed to estimate the parameters of simple models of the arterial input impedance. Our algorithm was defined and implemented as a FORTRAN program for a digital PDP 11/24 computer. This algorithm was tested by using pressure and flow data measured in the ascending aorta of dogs. About 26 sec were necessary to select 10 cardiac cycles (each one being about 200 samples long) of both flow and pressure in sequences of 2500 samples per signal and to compute the respective "mean cycles." Total peripheral resistance, total arterial compliance, and aortic characteristic impedance were estimated by aid of the simple three-element windkessel model. The results obtained by our method of determining parameters on the "mean cycle" of aortic pressure and flow were compared to the results obtained by averaging the parameters determined on each heart cycle.

Animals↗

PubMed1995

Comparison of high dose-rate and low dose-rate dose distributions for vaginal cylinders.

PURPOSE: The identification of appropriate high dose-rate parameters required to produce a "uniform" dose distribution on the surface of a vaginal cylinder. The high dose-rate dose distribution is then compared to the traditional low dose-rate dose distributions obtained with Burnett cylinders. METHODS AND MATERIALS: Dose distributions were calculated for 2, 3, and 3.5 cm diameter Burnett cylinders with and without crossing sources. Three models for the high dose-rate cylinders were developed and compared. High dose-rate dose distributions were calculated for 2, 3, and 3.5 cm diameter cylinders with and without anisotropic corrections for various dose specification points. RESULTS: Low dose-rate distributions are not uniform over the surface of the applicator. The exact distribution depends upon cylinder diameter and upon the exact source loading. High dose rate dose distributions can be configured to provide for a "uniform" dose on the surface, if an apex dose specification point is used together with dose specification points on the surface of the applicator opposite each dwell position. CONCLUSIONS: The conversion of low dose rate techniques to high dose rate techniques for vaginal cylinders involves an appreciation of the details of dose distributions of both approaches. The comparison between traditional low dose-rate distributions and high dose-rate distributions shows that, unlike the low dose-rate distributions, a relatively uniform high dose-rate distribution can be obtained independent of cylinder diameter. The clinical significance of the differences in the low dose-rate and high dose-rate dose distributions remains to be determined by long-term follow up of patients treated with high dose-rate techniques.

Carcinoma↗

PubMed2006

Inner ear proteomics: a fad or hear to stay.

Proteomics, the large-scale analysis of the structure and function of proteins, as well as of protein-protein interactions, has evolved into a major component of 'systems analysis'. This requires the integration of information from different sources and at multiple levels, and involves two distinct parameters, (1) high-throughput protein separation, identification, and characterization, and (2) the extension of the obtained analytical data for the determination of the physiological function. The inner ear poses exceptional challenges to the study of proteomics because of its minute size, poor accessibility, association with complex fluid spaces, and diversity of cell types. Various approaches to the study of proteomics of the inner ear are presented, and success stories, noteworthy failures and what lies ahead, will be discussed.

Animals↗

PubMed2005

Modelling and optimization of a recombinant BHK-21 cultivation process using hybrid grey-box systems.

In this work a model-based optimization study of fed-batch BHK-21 cultures expressing the human fusion glycoprotein IgG1-IL2 was performed. It was concluded that due to the complexity of the BHK metabolism it is rather difficult to develop a kinetic model with sufficient accuracy for optimization studies. Many kinetic expressions and a large number of parameters are involved resulting in a complex identification problem. For this reason, an alternative more cost-effective methodology based on hybrid grey-box models was adopted. Several model structures combining the a priori reliable first principles knowledge with black-box models were investigated using data from batch and fed-batch experiments. It has been reported in previous studies that the BHK metabolism exhibits modulation particularities when compared to other mammalian cell lines. It was concluded that these mechanisms were effectively captured by the hybrid model, this being of crucial importance for the successful optimization of the process operation. A method was proposed to monitor the risk of hybrid model unreliability and to constraint the optimization results to acceptable risk levels. From the optimization study it was concluded that the process productivity may be considerably increased if the glutamine and glucose concentrations are maintained at low levels during the growth phase and then glutamine feeding is increased.

Animals↗

PubMed2002

Complete characterisation of lanolin steryl esters by sub-ambient pressure gas chromatography-mass spectrometry in the electron impact and chemical ionisation modes.

Steryl esters occurring in lanolin have been characterised by sub-ambient pressure gas chromatography coupled to mass spectrometry. Electron impact and chemical ionisation modes with different reagent gases have been evaluated in order to carry out unambiguous peak identification. Steryl esters with different sterol (i.e. cholesterol, lanosterol and dihydrolanosterol) and acid moieties either according to carbon number (i.e C10-C23) or isomeric forms (i.e. normal, iso and anteiso) have been identified. Identification of the sterol and acid moieties has been carried out by means of the mass spectral information obtained in the electron impact, chemical ionisation mode either in the positive or negative modes using methane, isobutane and ammonia as reagent gases. Isomeric identification has been achieved by chromatographic retention parameters (i.e. entire-chain length and fractional-chain length) and by the free fatty acid profile also present in lanolin.

Chromatography, Gas↗

PubMed2002

Beneficial influences of systemic cooperation and sociological behavior on longevity.

During his long research career in the field of aging, Dr Bernard Strehler developed a series of theories concerning the identity of genes that can promote longevity and their role in natural selection. As a tribute to Dr Strehler, we have taken this opportunity to summarize a selection of these theories and to illustrate how these insights have influenced our search for longevity genes within the immune system. The identification of longevity genes has proven difficult. We believe that, at least in part, this reflects the emphasis on the concept of survival of the 'physically' fittest. We have used the immune system as a model to demonstrate that, over and above the self-evident advantage of those genes that contribute the attributes commonly associated with survival of the 'physically' fittest, those genes that lead to a predisposition to cooperate also confer a competitive survival advantage. As the acquisition of cooperativity in a society is linked to support mechanisms provided by older individuals, the search for longevity genes should not be limited to those genes that are associated with extended expression of a youthful phenotype. Rather these studies should be expanded to include identification of those genes that regulate physiologic parameters that affect individual longevity, even if they do not correspond with the traditional view of reproductive competitiveness. At the societal level, longevity genes may encode attributes that regulate sociologic or psychological parameters that may contribute to a tendency to non-aggressive or cooperative behavior that leads to achievement of common goals necessary for the survival of the species. This view of the selection for longevity impacts the analysis of longevity genes and aging at the organismal level. Dr Strehler viewed organismal aging as an integrated functional state, in which he conceived the outcome as reflecting the net balance of functional decrementers and evolved compensatory features. We propose that, in more evolved species, the longevity genes will be those genes, or sets of genes, that counterbalance of age-related functional decrementers with the age-related manifestation of evolved compensatory features. Thus, as illustrated here through analysis of the immune system, the longevity genes may well be those genes that promote overall systemic cooperation and compensation within the immune system and associated systems, rather than the genes that prevent age-related alterations in only one or a limited number of pathways.

Aging↗

PubMed1999

Evaluation of focal defects of the nerve fiber layer using optical coherence tomography.

OBJECTIVE: To analyze glaucomatous eyes with known focal defects of the nerve fiber layer (NFL), relating optical coherence tomography (OCT) findings to clinical examination, NFL and stereoscopic optic nerve head (ONH) photography, and Humphrey 24-2 visual fields. DESIGN: Cross-sectional prevalence study. PARTICIPANTS: The authors followed 19 patients in the study group and 14 patients in the control group. INTERVENTION: Imaging with OCT was performed circumferentially around the ONH with a circle diameter of 3.4 mm using an internal fixation technique. One hundred OCT scan points taken within 2.5 seconds were analyzed. MAIN OUTCOME MEASURES: Measurements of NFL thickness using OCT were performed. RESULTS: In most eyes with focal NFL defects, OCTs showed significant thinning of the NFL in areas closely corresponding to focal defects visible on clinical examination, to red-free photographs, and to defects on the Humphrey visual fields. Optical coherence tomography enabled the detection of focal defects in the NFL with a sensitivity of 65% and a specificity of 81%. CONCLUSION: Analysis of NFL thickness in eyes with focal defects showed good structural and functional correlation with clinical parameters. Optical coherence tomography contributes to the identification of focal defects in the NFL that occur in early stages of glaucoma.

Cross-Sectional Studies↗

PubMed2004

Artificial neural network analysis for evaluation of peptide MS/MS spectra in proteomics.

The aim of the work was to explore usefulness of artificial neural network (ANN) analysis for the evaluation of proteomics data. The analysis was applied to the data generated by the widely used protein identification program Sequest, completed with several structural parameters readily calculated from peptide molecular formulas. Proteins from yeast cells were identified based on the MS/MS spectra of peptides. The constructed ANN was demonstrated to classify automatically as either "good" or "bad" the peptide MS/MS spectra otherwise classified manually. An appropriately trained ANN proves to be a high-throughput tool facilitating examination of Sequest's results. ANNs are recommended as a means of automatic processing of large amounts of MS/MS data, which normally must be considered in the analysis of complex mixtures of proteins in proteomics.

Artificial Intelligence↗

PubMed1993

Cancer Research Campaign review of radiobiology research.

The meeting was reviewed and summarised by Professor Herman Suit. He judged that the potential clinical gains from research in radiobiology were very great and likely to translate to improved cancer treatment in the near future. He was highly complimentary about the contribution of UK research in radiobiology and he indicated that this viewpoint was held widely in the United States, Europe and Japan. Radiobiological research was the basis for major clinical trials in radiotherapy undertaken by trial groups in all these countries. He felt that major contributions to current practice in radiotherapy had been the definition of dose response, the rationale for the use of radiotherapy against slowly responding tumours, and the understanding of repair differentials and of clonal proliferation in the design of clinical fractionation trials, leading to clear demonstration of benefit for altered fractionation in the treatment of head and neck cancer and in the treatment of bladder cancer. An important goal of research should be the development of predictive testing for radiation response employing multiple predictive tests of radiation sensitivity (survival at 2 Gy), cellular proliferation (potential doubling time) and identification of hypoxic cells, together with physiological parameters such as blood flow intratumoral pressure, thiol metabolism and activation and status of repair genes. In terms of improving differential response between tumour and normal tissues, further refinement of dose fractionation patterns would be needed, but also research should continue on the modification of response using drug/radiation protocols, targeting techniques, growth factors and other biological response modifiers to support normal tissues, and modulation of DNA repair. Professor Suit felt that the pace of research in radiobiology was most encouraging for the field of radiotherapy. There was a consensus that support for radiobiology needed to be matched by support for academic radiotherapy if potential research gains were to be translated into advances in treatment. He shared the view expressed by the Committee of Cancer Experts of the EORTC that improvements in cancer cure over the next decade were likely to derive from improvements in radiotherapy.

Cell Hypoxia↗

PubMed2006

Use of a novel FISH assay on paraffin-embedded tissues as an adjunct to diagnosis of alveolar rhabdomyosarcoma.

A valuable diagnostic adjunct and important prognostic parameter in alveolar rhabdomyosarcoma (ARMS) is the identification of translocations t(2;13)(q35;q14) and t(1;13)(p36;q14), and the associated PAX3-FKHR and PAX7-FKHR fusion transcripts, respectively. Most RMS fusion gene type studies have been based on reverse transcriptase-polymerase chain reaction (RT-PCR) detection of the fusion transcript, a technique limited by RNA quality and failure of devised primer sets to detect unusual variants. As an alternative approach, we developed a fluorescence in situ hybridization (FISH) assay that can: (1) distinguish between the two most common ARMS-associated fusion genes; (2) identify potential unusual variant translocations; (3) assess histologic components in mixed alveolar/embryonal RMS; and (4) be performed on paraffinized tissue. FISH analyses of 75 specimens (40 ARMS, 16 ERMS, 8 mixed ARMS/ERMS, and 11 non-RMS tumors) using selected cosmid clone, bacterial, P1-derived, and yeast artificial chromosome probe sets were successful in all but two cases. Among specimens with informative results for both FISH and RT-PCR or standard karyotyping, PAX/FKHR classification results were concordant in 94.6% (53/56). The three discordant cases included one exhibiting a t(2;13) by FISH that was subsequently confirmed by repeat RT-PCR, a second showing a rearrangement of the PAX3 locus only (consistent with the presence of a PAX3 variant translocation), and a third revealing a t(2;13) by FISH that lacked this translocation cytogenetically. Both alveolar and embryonal components of the mixed ARMS/ERMS subtype were negative for PAX3, PAX7, and FKHR rearrangements, a surprising finding confirmed by RT-PCR and/or conventional karyotyping. These data demonstrate that FISH with newly designed probe sets is a reliable and highly specific method of detecting t(1;13) and t(2;13) in routinely processed tissue and may be useful in differentiating ARMS from other small round cell tumors. The findings also suggest that FISH may be a more sensitive assay than RT-PCR in some settings, capable of revealing variant translocations.

Biological Assay↗

PubMed2000

Erythropoietic reconstitution, macrophages and reticulin fibrosis in bone marrow specimens of CML patients following allogeneic transplantation.

A clinicopathological study was conducted on 351 bone marrow trephine biopsies derived from 124 patients with chronic myeloid leukemia (CML) at standardized endpoints before and after allogeneic bone marrow transplantation (BMT). The purpose was to investigate quantitative changes of the nucleated erythroid precursor cell population and other associated features such as resident bone marrow macrophages and myelofibrosis and to elucidate their relevance on engraftment parameters. Monoclonal antibodies were applied for the identification of erythroid precursors and the labeling of mature macrophages; argyrophilic (reticulin-collagen) fibers were demonstrated by a silver impregnation technique. Following morphometric analysis of the pregraft bone marrow specimens statistical evaluation was in line with an adverse correlation between early to moderate reticulin fibrosis and amount of erythropoiesis. Moreover, a significant relationship was calculable between numbers of erythroid precursors and CD68+ macrophages. After myelo-ablative therapy and BMT a pronounced decrease in cellularity and in the quantity of erythropoiesis was found. Comparable with the pregraft samples, a significant association between erythroid precursors and macrophages could be determined in the regenerating donor bone marrow. A pretransplant relevant reduction of the red cell lineage and a manifest (reticulin) myelofibrosis indicating an advanced stage of disease were accompanied by a significant delay to reach transfusion independence. This result was further supported by comparable findings in trephine biopsies performed in the early post-transplant period (second month after BMT). Corresponding examinations revealed an enhancement of fiber density and a decrease in erythropoiesis in those patients who did not conform with the usually accepted criteria for successful engraftment. In conclusion, compelling evidence has been produced that a significantly reduced amount of erythroid precursors, which is usually associated with myelofibrosis in the pretransplant bone marrow, exerts an impairment to undisturbed hematopoietic reconstitution. Moreover, a close spatial and numerical relationship between the erythroid lineage and resident (mature) macrophages is observable, in particular in the state of regeneration after BMT.

Adolescent↗

PubMed2005

Characteristics of patients with stage T1b incidental prostate cancer.

OBJECTIVE: To study the characteristics of patients with incidental prostate cancer. MATERIAL AND METHODS: The proportion of incidentally diagnosed prostate cancer was investigated in patients who underwent transurethral resection of the prostate (TURP) at our clinic over a 5-year period. "True" incidental prostate cancer was defined as cases where the preoperative digital rectal examination (DRE) and the prostate-specific antigen (PSA) value were normal. Patients with known malignancy of the prostate were excluded, together with those with PSA >4 ng/ml and/or a positive DRE. The characteristics of these patients were compared to those of benign prostatic hyperplasia patients and the group as a whole. RESULTS: Of the 786 patients operated on between 1999 and 2003, 34 (4.3%) had a positive pathology report for "true" incidental prostate cancer. An increased frequency of poorly differentiated tumors (32.3%) was noted. Of the 34 patients, 17 were stage T1a and 17 T1b; 11 patients had a Gleason sum of 7-10, all of them in the T1b group. In the T1b group the mean age was 74 years, the mean PSA level 2.9 ng/ml and the mean weight of tissue resected 11.1 g. Corresponding values in the T1a patients were 70.1 years, 3.32 ng/ml and 18.2 g. CONCLUSIONS: Compared to previous studies, we noticed a low incidence of "true" incidental prostatic carcinoma but a high ratio of poorly differentiated tumors (all stage T1b). Compared to the group as a whole, patients with incidental prostate cancer were older and had smaller prostate and transition zone volumes. Further research is needed to identify parameters that may aid in the earlier identification of incidental prostate cancer, as patients may benefit from curative treatment.

Aged↗

PubMed1996

Evaluation of a chemical spot-test kit for the detection of airborne particulate lead in the workplace.

A commercial rhodizonate-based test kit was evaluated for its potential use in the detection of lead in airborne particulate samples at work sites. Over 350 air samples were collected at abrasive blasting lead paint abatement sites using cellulose ester membrane filters and personal sampling pumps. The filter samples were tested with the chemical spot test and then analyzed by graphite furnace atomic absorption spectrophotometry. No positive readings were recorded for lead masses below 1.3 micrograms Pb/filter, and no negative readings were observed for lead amounts above 8.1 micrograms Pb/filter. Experimental data were statistically molded in an effort to estimate the performance parameters of the spot test kit. The identification limit of the kit was found to be approximately 3.6 microgram/filter sample. For lead mass values above approximately 10 micrograms Pb/filter, 95% confidence of a positive reading was found, while 95% confidence of a negative reading was found for lead masses below approximately 0.6 micrograms Pb/filter. Based on the results of this study the rhodizonate-based test kit for lead demonstrates potential for use in field screening for lead in personal breathing zone and area air samples.

Air Pollution↗

PubMed1989

Evolution equations and ultrasonic wave propagation in biological tissues.

Fundamental research in ultrasonic diagnostics is often limited by the relatively simple models of propagation invoked in what is largely an empirical science. Careful discussion of the problem reveals the need for more sophisticated propagation theories as the basis of measurement techniques and for the interpretation of experimental results. It is thus important for dialogue between theoreticians and experimentalists in the field. The complexity of ultrasonic wave propagation in tissue arises from a combination of factors. First, there is the biochemical sophistication of the media concerned. Second, there is the variety of physical phenomena involved: the diffractive nature of the ultrasonic field, the presence of absorption, the presence of large scale inhomogeneities and small scale scatterers, and the possibility of finite amplitude propagation effects. It has tended to be the custom to deal with each of these problems on an individual basis with a second feature being introduced as a perturbation of the results obtained for the first. The present authors have been concerned to find a unified approach which will permit each of the effects to be taken into account in relation to the others. This approach is based on the application of two-dimensional evolution equations modelling ultrasonic propagation in non-cavitating soft tissues. The model incorporates all the propagation phenomena known from experimental studies, indicating a need for knowledge of nine material parameters for a complete description. It thus provides a basis for numerical investigation of the relative significance of the parameters under different conditions. This will permit identification of those that should be known experimentally with high precision and those that have a minor role in the propagation phenomena.

Biophysical Phenomena↗

PubMed1992

Clinical decision making for discharge planning in a changing psychiatric environment.

This article reviews the clinical decision-making process involved in planning for continuity of care following discharge from inpatient psychiatric services. The decision-making frame of reference requires the identification of the players in the process, parameters of their roles, performance expectations, and boundaries of rights and obligations; clear definition of objectives; collection of data and analysis of its relevancy; and study of possible alternatives, with evaluations of their consequences. The authors present an approach to clinical decision making that includes an analysis of modalities and practice skills and a critical review of practice in a psychiatric setting that emphasizes the role of the family; the importance of continuity of care; and the need to engage the patient, family, and care systems within briefer time frames.

Adult↗

PubMed1991

Prognostic significance of proliferation in endometrial adenocarcinomas: a multivariate analysis of clinical and flow cytometric variables.

In a prospective study, the prognostic significance of clinical and flow cytometric variables was evaluated in univariate and multivariate analyses of 489 cases of endometrial adenocarcinoma. Age, uterine cavity depth, stage, histopathologic grade, myometrial invasion, ploidy level, and S-phase fraction were of prognostic value in the univariate analysis. In a multivariate analysis of clinical variables, age and uterine cavity depth were insignificant. When adding flow cytometric variables (DNA content and S-phase fraction) separately to the clinical variables, the significance of myometrial invasion was reduced, and histopathologic grade became nonsignificant when S-phase fraction was included. When adding both DNA content and S-phase fraction, the DNA content became prognostically insignificant. S-phase fraction was, next to clinical stages III and IV, found to be the strongest predictor of outcome. It is concluded that S-phase fraction is a new, objective parameter that can be used for the identification of prognostically different subgroups of patients within a given stage and grade.

Adenocarcinoma↗