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On the incomplete architecture of human ontogeny. Selection, optimization, and compensation as foundation of developmental theory.

Drawing on both evolutionary and ontogenetic perspectives, the basic biological-genetic and social-cultural architecture of human development is outlined. Three principles are involved. First, evolutionary selection pressure predicts a negative age correlation, and therefore, genome-based plasticity and biological potential decrease with age. Second, for growth aspects of human development to extend further into the life span, culture-based resources are required at ever-increasing levels. Third, because of age-related losses in biological plasticity, the efficiency of culture is reduced as life span development unfolds. Joint application of these principles suggests that the life span architecture becomes more and more incomplete with age. Degree of completeness can be defined as the ratio between gains and losses in functioning. Two examples illustrate the implications of the life span architecture proposed. The first is a general theory of development involving the orchestration of 3 component processes: selection, optimization, and compensation. The second considers the task of completing the life course in the sense of achieving a positive balance between gains and losses for all age levels. This goal is increasingly more difficult to attain as human development is extended into advanced old age.

Adolescent↗

Evaluation of tire-derived fuel for use in nitrogen oxide reduction by reburning.

Tire-derived fuel (TDF) was tested in a small-scale (44 kW or 150,000 Btu/hr) combustor to determine its feasibility as a fuel for use in reburning for control of nitrogen oxide (NO). TDF was gravity-fed into upward flowing combustion gases from a primary natural gas flame doped with ammonia to simulate a high NO combustion process. Emissions of NO, oxygen, carbon dioxide, carbon monoxide, and particulate matter were measured. The tests varied the nominal primary NO level from 600 to 1,200 ppm and the primary stoichiometry from 1.1 to 1.2, and used both natural gas and TDF as reburn fuels. The reburn injection rate was varied to achieve 8-20% of the total heat input from the reburn fuel. NO emissions reductions ranged between 20 and 63% when using TDF, depending upon the rate of TDF injection, primary NO, and primary stoichiometry. NO emission reductions when using natural gas as the reburn fuel were consistently higher than those when using TDF. While additional work remains to optimize the process and evaluate costs, TDF has been shown to have the potential to be a technically viable reburning fuel.

Air Pollution↗

Thermostable phytase production by Thermoascus aurantiacus in submerged fermentation.

Phytases act on phytic acid, an antinutrient factor present in animal feeds, and release inorganic phosphate. We optimized the production parameters for phytase production using Thermoascus aurantiacus (TUB F 43), a thermophilic fungal culture, by submerged fermentation. A semisynthetic medium containing glucose, starch, peptone, and minerals supplemented with 3.75% (w/v) wheat bran particles was found to be the best production medium among the various combinations tried. Further supplementation of this medium with surfactants such as Tween-20 and Tween-80 considerably enhanced the enzyme yield. A maximum phytase activity (468.22 U/mL) was obtained using this production medium containing 2% (v/v) Tween-20 after 72 h of fermentation at 45 degrees C in shake-flask cultures with a rotation of 150 rpm. Herein we present details of a few of the process parameter optimizations. The phytase enzyme was found to be thermostable, and the optimal temperature for phytase activity was found to be 55 degrees C. However, 80% of the activity still remained when the temperature was shifted to 70 degrees C.

6-Phytase↗

Measuring and improving performance in multicenter research consortia.

BACKGROUND: Some evidence suggests that the quality of the organization and management of research consortia influences productivity and staff satisfaction. Collaborators in a research consortium generally focus on developing and implementing studies and thus rarely assess the process of collaboration. We present an approach to evaluating and improving a research consortium, using the HMO Cancer Research Network (CRN) as an example. METHODS: Five domains are evaluated: extent of collaboration and quality of communication; performance of projects and infrastructure; data quality; scientific productivity; and impact on member organizations. The primary assessment tool is a survey of CRN scientists and project staff, undertaken annually. RESULTS: Each year, the evaluation has identified critical aspects of this collaboration that could be improved. Several tangible changes have been implemented to improve productivity of the consortium. The most important result of the CRN Evaluation is the ability to have open dialogue about ways to improve its overall performance. CONCLUSION: Optimizing the process of collaboration will contribute to achievement of the scientific goals. The experience of the CRN provides a useful framework and process for evaluating the structure of consortium-based research.

Biomedical Research↗

Sonication parameters for the preparation of biodegradable nanocapsules of controlled size by the double emulsion method.

The main goal of the present work was to study the influence of the sonication process on the characteristics of poly(lactide-co-glycolide) nanocapsules prepared by the water-in-oil-in-water solvent evaporation method. The duration and intensity of sonication were investigated with respect to their ability to modify the size and distribution of the nanocapsule population. It has been demonstrated that the duration of the second mixing step (leading to the w/o/w emulsion) is of greater influence than that of the first step (water-in-oil emulsion) on the final mean particle size. A three-dimensional response surface was drawn up to show that when the second emulsification time increased, the mean size decreased until reaching a plateau. A threshold in sonication intensity also exists, allowing optimization of both parameters and the formation of nanocapsules of controlled size with a rather narrow distribution. The use of a vortex mixer instead of a sonicator during the first mixing step led to nanocapsules with a similar response surface, supporting the idea that the second step is the decisive one. Finally, nanocapsules loaded with methylene blue, a hydrophilic model compound with a positive charge, were characterized and the encapsulation efficiency calculated. Their size and distribution were similar to that of the blank nanocapsules. Entrapment efficiency was independent of duration, intensity, and type of mixing. From these results, it was concluded that nanocapsules of controlled size could be obtained upon optimizing certain process parameters.

Biodegradation, Environmental↗

Goals and objectives in the management of metastatic breast cancer.

Patients with metastatic breast cancer consist of a heterogeneous group of patients whose prognoses and clinical courses can vary depending on host factors, such as comorbidity and age, and on tumor factors, such as hormone-receptor status, grade, and anatomical site of disease. Although the median survival time for patients with metastatic breast cancer is 2-4 years, subsets of patients with either indolent or limited metastatic disease may have prolonged survival times. Further, expectations of treatment, both in terms of efficacy and of toxicity, vary greatly based upon the specific treatment, patient characteristics, and tumor characteristics. Thus, the goals of treatment for patients with metastatic breast cancer are influenced by estimates of prognoses as well as a balance between physician and patient preferences regarding efficacy and toxicity considerations. Traditionally, objective measures of response and survival have been the targeted end points in clinical trial design and in physician selection of therapy for metastatic breast cancer. More recently, issues of quality of life have surfaced as important end points, especially from the perspective of the patient. The decision-making process in selecting the optimal treatment for patients with metastatic breast cancer is, therefore, a multidimensional process involving subjective as well as objective goals of treatment. Ultimately, the benefits of treatment must justify the risks and toxicities of the treatment, and the impact of treatment should be measured in relation to specified goals. Both physician and patient perspectives are important in establishing the objectives of treatment, and this process is optimally an interactive and ongoing process throughout the course of disease.

Breast Neoplasms↗

Mechanical properties of continuously spun fibers of carbon nanotubes.

We report on the mechanical properties of fibers consisting of pure carbon nanotube fibers directly spun from an aerogel formed during synthesis by chemical vapor deposition. The continuous withdrawal of product from the gas phase imparts a high commercial potential to the process, either for the production of particularly strong fibers or for the economic production of bulk quantities of carbon nanotubes. Tensile tests were performed on fibers produced from the dissociation of three different hydrocarbons, namely, ethanol, ethylene glycol, and hexane, with a range of iron (catalyst) concentrations. The conditions were chosen to lie within the range known to enable satisfactory continuous spinning, the iron concentration being varied within this range. Increasing proportions of single wall nanotubes were found as the iron concentration was decreased, conditions which also produced fibers of best strength and stiffness. The maximum tensile strength obtained was 1.46 GPa (equivalent to 0.70 N/tex assuming a density of 2.1 g/cm(3)). The experiments indicate that significant improvements in the mechanical properties can be accomplished by optimizing the process conditions.

Elasticity↗

Chronic neutrophilic leukemia and chronic myelomonocytic leukemia: WHO defined.

The World Health Organization (WHO) classification of myeloid disorders has provided updated parameters for the consistent diagnosis of two previously less than optimally defined chronic myeloid disorders, CNL and CMML. The classification of these disorders, which had been controversial, is now better defined and provides more clinically and biologically relevant disease definitions to enable uniform diagnosis and a framework to evaluate natural history and therapeutic interventions. CNL is now recognized as a distinct entity among the chronic myeloproliferative disorders and CMML is included within the new category of 'myelodysplastic/myeloproliferative diseases' (MDS/MPD). Predominant neutrophilia defines CNL whereas CMML is defined by predominant and monocytosis. In each case these defining features must be distinguished from reactive causes for the same in the absence of clear evidence of myeloid clonality (CNL and CMML) or dysplasia (CMML). The exclusion of underlying bcr/abl-driven oncogenesis is an essential component in the diagnosis of these chronic leukemic processes. The optimal therapy for both CNL and CMML remains uncertain. Current management decisions are based on small studies or extrapolated from therapeutic strategies that are effective in similar chronic, clonal myeloid disorders. Given the potential for evolution to acute leukemia or progressive refractory leucocytosis or cytopenias, allogeneic stem cell transplantation might be appropriate for younger patients. Continued reporting and investigation of specific therapeutic strategies and responses must be encouraged.

Humans↗

Effect of total sleep deprivation on the dimensional complexity of the waking EEG.

STUDY OBJECTIVES: Sleep deprivation can affect the waking EEG that may reflect information processing of the brain. We examined the effect of total sleep deprivation (TSD) on nonlinear dynamics of the waking EEG. DESIGN: Paired-group design. SETTING: A sleep disorders laboratory in a hospital. PARTICIPANTS: Twenty healthy male volunteers. INTERVENTIONS: Waking EEG data were recorded from subjects with eyes closed after (a) an 8-hour night's sleep and (b) TSD for 24 hours. The dimensional complexity (D2), as a nonlinear measure of complexity, of the EEG after a full night sleep were compared with those of the EEG after TSD. MEASUREMENTS AND RESULTS: The sleep-deprived states had lower D2 values at three channels (P4, O2, and C3) than normal states. CONCLUSIONS: TSD results in the decrease of complexity in the brain, which may imply sub-optimal information processing of the cerebral cortex. We suggest that the investigation of the relation between nonlinear dynamics of the waking EEG induced by TSD and cognitive performance may offer fruitful clues for understanding the role of sleep and the effects of sleep deprivation on brain function.

Adult↗

Optimized preembedding method improves the histologic yield of prostatic core needle biopsies.

BACKGROUND: The aim of this study was to optimize the core shape of prostatic core needle biopsies using a novel preembedding method, and to investigate the influence of the number of cores per tissue block on the histologic yield per section level. METHODS: Twenty-four core needle biopsies were taken from a fresh prostatectomy specimen, using an 18-gauge needle. Twelve core needle biopsies were conventionally fixed floating free in formalin-filled containers, whereas 12 biopsies were stretched between two nylon meshes, and placed in tissue cassettes before fixation. The total number of tissue sections per paraffin block necessary for complete workup of the tissue was determined. Using image analysis, the relation of the area of every fifth section level was calculated in relation to the total projected area of the biopsies. Both methods of tissue processing were compared for both parameters. RESULTS: In contrast to the curved biopsies after conventional processing, the optimized preembedding method generally led to stretched cores after fixation and embedding. This method led to a 100% decrease in total number of tissue sections necessary for complete workup and to higher percentages of the tissue amount per section level compared to the total projected core area. These parameters were also influenced by the number of cores per paraffin block, but to a minor degree. CONCLUSIONS: This study shows that optimized preembedding of prostatic needle biopsies improves the histologic yield per section level. The continuous occurrence of representative sections could improve diagnostic accuracy in the histological examination of prostatic core needle biopsies.

Biopsy, Needle↗

Formation of three-dimensional fetal myocardial tissue cultures from rat for long-term cultivation.

Three-dimensional cardiomyocyte cultures offer new possibilities for the analysis of cardiac cell differentiation, spatial cellular arrangement, and time-specific gene expression in a tissue-like environment. We present a new method for generating homogenous and robust cardiomyocyte tissue cultures with good long-term viability. Ventricular heart cells prepared from fetal rats at embryonic day 13 were cultured in a scaffold-free two-step process. To optimize the cell culture model, several digestion protocols and culture conditions were tested. After digestion of fetal cardiac ventricles, the resultant cell suspension of isolated cardiocytes was shaken to initialize cell aggregate formation. In the second step, these three-dimensional cell aggregates were transferred onto a microporous membrane to allow further microstructure formation. Autonomously beating cultures possessed more than 25 cell layers and a homogenous distribution of cardiomyocytes without central necrosis after 8 weeks in vitro. The cardiomyocytes showed contractile elements, desmosomes, and gap junctions analyzed by immunohistochemistry and electron microscopy. The beat frequency could be modulated by adrenergic agonist and antagonist. Adenoviral green fluorescent protein transfer into cardiomyocytes was possible and highly effective. This three-dimensional tissue model proved to be useful for studying cell-cell interactions and cell differentiation processes in a three-dimensional cell arrangement.

Adrenergic beta-Agonists↗

Optimization of a trypsin-bioreactor coupled with high-performance liquid chromatography-electrospray ionization tandem mass spectrometry for quality control of biotechnological drugs.

The optimization of a silica-based trypsin bioreactor and its use in the quality control of biotechnological drugs like peptides and proteins is described. Five bioreactors based on monolithic material have been prepared, with different amount of bound trypsin. The performances of these bioreactors were compared to the proteolytic activity of a bioreactor based on silica material. The trypsin-based chromatographic columns were coupled on-line with an LC/ESI/MS/MS system for digestion and identification of proteins. First, human serum albumin has been used as test protein to compare the ability of the bioreactors to hydrolyse high-molecular-weight proteins. The best chromatographic material (epoxy monolithic silica) and the optimum amount of enzyme bound (7.13 mg) have been identified to obtain the highest protein recovery and an analytical reproducibility of the whole digestion, separation and identification process. The optimized enzyme-reactor has been used for the on-line digestion of some biotechnological drugs such as somatotropin. Somatotropin for parentheral use has been analyzed, without sample pre-treatment, with both an on-line procedure and the traditional off-line procedure described in the European Pharmacopoeia. It was found that the cleavage efficiency (aminoacidic recovery, %AA) achieved within minutes by the developed protocol is at least comparable or even better than the conventional 4h consuming method.

Algorithms↗

A method for modifying the image quality parameters of digital radiographic images.

A new computer simulation approach is presented that is capable of modeling several varieties of digital radiographic systems by their image quality characteristics. In this approach, the resolution and noise characteristics of ideal supersampled input images are modified according to input modulation transfer functions (MTFs) and noise power spectra (NPS). The modification process is separated into two routines-one for modification of the resolution and another for modification of the noise characteristics of the input image. The resolution modification routine blurs the input image by applying a frequency filter described by the input MTF. The resulting blurred image is then reduced to its final size to account for the sampling process of the digital system. The noise modification routine creates colored noise by filtering the frequency components of a white noise spectrum according to the input noise power. This noise is then applied to the image by a moving region of interest to account for variations in noise due to differences in attenuation. In order to evaluate the efficacy of the modification routines, additional routines were developed to assess the resolution and noise of digital images. The MTFs measured from the output images of the resolution modification routine were within 3% of the input MTF The NPS measured from the output images of the noise modification routine were within 2% of the input NPS. The findings indicate that the developed modification routines provide a good means of simulating the resolution and noise characteristics of digital radiographic systems for optimization or processing purposes.

Algorithms↗

Processing and major histocompatibility complex class II presentation of Legionella pneumophila antigens by infected macrophages.

To better understand interactions between the intracellular pathogen Legionella pneumophila and macrophages (Mphis), host and bacterial determinants important for presentation of antigens on major histocompatibility complex class II molecules (MHC-II) were investigated. It was determined that immune CD4 T-cell responses to murine bone marrow-derived Mphis (BMphis) infected with wild-type L. pneumophila were higher than the responses to avirulent dotA mutant bacteria. Although this enhanced response by immune T cells required modulation of vacuole transport mediated by the Dot/Icm system, it did not require intracellular replication of L. pneumophila. Intracellular cytokine staining identified a population of immune CD4 T cells that produced gamma interferon upon incubation with BMphis infected with wild-type L. pneumophila that did not respond to Mphi infection with dotA mutant bacteria. Endocytic processing was required for presentation of L. pneumophila antigens on MHC-II as determined by a defect in CD4 T-cell responses when the pH of BMphi endosomes was neutralized with chloroquine. Investigation of MHC-II presentation of antigens by BMphis infected with L. pneumophila icmR, icmW, and icmS mutants indicated that these mutants have an intermediate presentation phenotype relative to those of wild-type and dotA mutant bacteria. In addition, it was found that antigens from dot and icm mutants are presented earlier than antigens from wild-type L. pneumophila. Although immune CD4 T-cell responses to proteins secreted by the L. pneumophila Lsp system were not detected, it was found that the Lsp system is important for priming L. pneumophila-specific T cells in vivo. These data indicate that optimal antigen processing and MHC-II presentation to immune CD4 T cells involves synthesis of L. pneumophila proteins in an endoplasmic reticulum-derived compartment followed by transport to lysosomes.

Animals↗

Automated washing with the Reliance Endoscope Processing System and its equivalence to optimal manual cleaning.

BACKGROUND: Manual cleaning of flexible endoscopes is prone to error. To date, attempts to automate this process have been unsuccessful. The aim of this project was to compare the efficacy of the washing phase in the new Reliance EPS (STERIS Corp, Mentor, OH) with that of optimal manual cleaning. METHODS: Using simulated-use testing, all channels in 3 different flexible endoscopes, including a bronchoscope (Pentax, Pentax Medical Company, Miami, FL), a side-viewing duodenoscope (Olympus, Olympus Corporation), and a colonoscope (Fujinon, Fujinon Corporation, Wayne, NJ) were evaluated. All of the channels in the flexible endoscope were soiled with artificial test soil (ATS) (test soil that mimics the worst case levels of hemoglobin, protein, carbohydrate, and endotoxin from patient-used flexible endoscopes) containing 10(8) cfu/mL of Enterococcus faecalis and Pseudomonas aeruginosa The soiled scopes were allowed to dry for 1 hour prior to processing. Hemoglobin, protein, and viable organism counts for the flexible endoscopes were determined before and after cleaning. RESULTS: Both the Reliance EPS washing phase and optimal manual cleaning achieved >90% reduction of hemoglobin and protein, resulting in <6.4 microg/cm2 after the cleaning cycle. The reduction factor for viable organisms was not significantly different between the 2 methods, which ranged from 2.06 to 6.21 for manual cleaning and from 2.1 to 5.93 for the Reliance EPS washing phase. The mean reduction factor (all tests) was 4.32 +/- 1.03 for manual cleaning compared with 4.24 +/- 1.11 for Reliance EPS washing phase. CONCLUSION: The efficacy of the Reliance EPS washing phase for flexible endoscopes was equivalent to optimal manual cleaning for all the makes and models of flexible endoscopes tested.

Bronchoscopes↗

Multiobjective optimization and multivariable control of the beer fermentation process with the use of evolutionary algorithms.

This paper describes empirical research on the model, optimization and supervisory control of beer fermentation. Conditions in the laboratory were made as similar as possible to brewery industry conditions. Since mathematical models that consider realistic industrial conditions were not available, a new mathematical model design involving industrial conditions was first developed. Batch fermentations are multiobjective dynamic processes that must be guided along optimal paths to obtain good results. The paper describes a direct way to apply a Pareto set approach with multiobjective evolutionary algorithms (MOEAs). Successful finding of optimal ways to drive these processes were reported. Once obtained, the mathematical fermentation model was used to optimize the fermentation process by using an intelligent control based on certain rules.

Algorithms↗

Discharge planning in rehabilitation following surgery for a stoma.

Discharge planning and establishing goals for rehabilitation after stoma surgery is an ongoing process, which should be preceded by an holistic assessment, ideally carried out by a specialist practitioner with knowledge and experience in this area. The practitioner needs to have effective listening skills to ensure that both practical and psychological care are patient-centred. The patient and his/her carers must be involved in all aspects of care planning and establishing goals for rehabilitation. The specialist practitioner should adopt an evidence-based approach to care, ensuring that important aspects of care, such as the early teaching of stoma management skills, are not neglected. The specialist practitioner may not be able to meet all the patient's needs and should refer on to other specialist staff where these services are available. Such multidisciplinary input, utilizing appropriate problem-solving approaches with the involvement of patients and their carers, can only enhance the quality of care delivered and optimize the process of rehabilitation.

Adaptation, Psychological↗

[Clinical evaluation, radiologic and histologic analysis in mandibular alveolar distraction procedures. Preliminary study].

BACKGROUND: Alveolar distraction osteogenesis is a process to form new alveolar bone to correct alveolar deformities in ridge height and width. Aim of this work is to study the bone processes to optimize the implantoprosthetic rehabilitation. METHODS: Alveolar distraction osteogenesis was applied in 7 patients with ridge deformities to obtain the desired ridge augmentation. Clinical and radiological evaluations were performed during the following 12 weeks, before implant insertion. Biopsies at 40, 60 and 88 days were studied after general, specific and histochemical staining of slides; microradiographs were analyzed to evaluate the trabecular bone volume. RESULTS: Forty days after the end of distraction, soft callus shows the start of ossification. Sixty days after the end of distraction, soft callus was widely converted into a network of trabecular woven bone; osteogenic activities were low; trabecular bone volume was about 50%. Eighty-eight days after the end of distraction bone amount appeared reduced, with a more ordered structure, further reduction of bone formation activity, whereas osteoclast erosion was active. CONCLUSIONS: Results show an almost steady-state bone deposition processes 60 days after the end of distraction and a regress with longer time. The results suggest the possibility of an early implant insertion to avoid bone loss due to mechanical unloading.

Adolescent↗