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Results for “Process optimization”

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PubMed1999

Mathematical models of tumour and normal tissue response.

The historical application of mathematics in the natural sciences and in radiotherapy is compared. The various forms of mathematical models and their limitations are discussed. The Linear Quadratic (LQ) model can be modified to include (i) radiobiological parameter changes that occur during fractionated radiotherapy, (ii) situations such as focal forms of radiotherapy, (iii) normal tissue responses, and (iv) to allow for the process of optimization. The inclusion of a variable cell loss factor in the LQ model repopulation term produces a more flexible clonogenic doubling time, which can simulate the phenomenon of 'accelerated repopulation'. Differential calculus can be applied to the LQ model after elimination of the fraction number integers. The optimum dose per fraction (maximum cell kill relative to a given normal tissue fractionation sensitivity) is then estimated from the clonogen doubling times and the radiosensitivity parameters (or alpha/beta ratios). Economic treatment optimization is described. Tumour volume studies during or following teletherapy are used to optimize brachytherapy. The radiation responses of both individual tumours and tumour populations (by random sampling 'Monte-Carlo' techniques from statistical ranges of radiobiological and physical parameters) can be estimated. Computerized preclinical trials can be used to guide choice of dose fractionation scheduling in clinical trials. The potential impact of gene and other biological therapies on the results of radical radiotherapy are testable. New and experimentally testable hypotheses are generated from limited clinical data by exploratory modelling exercises.

Brachytherapy↗

PubMed2002

Analysis of odontoblast gene expression using a novel approach, laser capture microdissection.

Studying the mechanisms of molecular interactions in developing tissues demands sensitive molecular biological in vivo and in vitro techniques. Laser capture microdissection (LCM) allows for the isolation of mRNA in histological sections even from single cells, thus enabling the identification of in vivo gene expression products in closely circumscribed tissue areas. The aims of this study were to assess the optimal fixation, processing, and staining conditions to retrieve RNA from microdissected odontoblasts. Fluorometric assays and RT-PCR analysis of alpha 1(I) collagen, dentin sialophosphoprotein (Dspp), and osteocalcin (OC) confirmed that the total RNA isolated from day 0 and day 3 captured odontoblasts was sufficient in quantity and quality. Our results indicate that individual odontoblasts obtained by LCM are morphologically intact and chemically unaltered, allowing accurate molecular and biochemical analyses.

Animals↗

PubMed2005

Development of novel interpenetrating network gellan gum-poly(vinyl alcohol) hydrogel microspheres for the controlled release of carvedilol.

Novel interpenetrating polymeric network microspheres of gellan gum and poly(vinyl alcohol) were prepared by the emulsion cross-linking method. Carvedilol, an antihypertensive drug, was successfully loaded into these microspheres prepared by changing the experimental variables such as ratio of gellan gum:poly(vinyl alcohol) and extent of cross-linking in order to optimize the process variables on drug encapsulation efficiency, release rates, size, and morphology of the microspheres. Formation of interpenetrating network and the chemical stability of carvedilol after preparing the microspheres was confirmed by Fourier transform infrared spectroscopy. Differential scanning calorimetry and x-ray diffraction studies were made on the drug-loaded microspheres to investigate the crystalline nature of the drug after encapsulation. Results indicated a crystalline dispersion of carvedilol in the polymer matrix. Scanning electron microscopy confirmed the spherical nature and smooth surface morphology of the microspheres produced. Mean particle size of the microspheres as measured by laser light scattering technique ranged between 230 and 346 microm. Carvedilol was successfully encapsulated up to 87% in the polymeric matrices. In vitro release studies were performed in the simulated gastric fluid or simulated intestinal fluid. The release of carvedilol was continued up to 12 h. Dynamic swelling studies were performed in the simulated gastric fluid or simulated intestinal fluid, and diffusion coefficients were calculated by considering the spherical geometry of the matrices. The release data were fitted to an empirical relation to estimate the transport parameters. The mechanical properties of interpenetrating polymeric networks prepared were investigated. Network parameters such as molar mass between cross-links and cross-linking density for interpenetrating polymeric networks were calculated.

Algorithms↗

PubMed1998

Artificial neural network for predicting intracranial haemorrhage in preterm neonates.

Intraventricular haemorrhage (IVH) incidence is used to assess peri-/neonatal therapy, and to make intra- and inter-hospital quality assessments. Unbiased assessment is complicated by the amount of confounding factors. Is an artificial neural network (ANN) able to early and accurately forecast the occurrence of severe IVH in an individual patient? Is it superior to classic multiple logistic regression? We conducted an observational study on pre-existing routine data. Admission data were available from 890 preterm neonates (gestational age < 32 weeks, birthweight < 1500 g). Patients were randomly assigned to either a training, or a validation set (50%/50%). Using the training set data an ANN was trained. A second predictive model was developed by stepwise multiple logistic regression analysis. Using the validation set input data both models delivered estimates of the probability for severe IVH to occur in each individual patient. Receiver operating characteristic (ROC) curves were used to compare prognostic performance. The optimal ANN processed 13 input variables, whereas stepwise logistic regression analysis only identified five independent predictor variables. The area under the ROC curve was 0.935 for the ANN and 0.884 for the logistic regression model (p = 0.001). Adjusted for 95%, 90%, 85%, 80% and 75% specificity, the sensitivity of the ANN was significantly superior to that of the logistic regression model. Due to its ability to give an accurate prognosis based solely on admission data, a trained ANN qualifies as a tool for local quality control.

Cerebral Hemorrhage↗

PubMed2005

Job level risk assessment using task level ACGIH hand activity level TLV scores: a pilot study.

Existing upper extremity musculoskeletal disorder analytical tools are primarily intended for single or mono-task jobs. However, many jobs contain more than 1 task and some include job rotation. This case/control study investigates methods of modifying an existing tool, the American Conference of Governmental Industrial Hygienists (ACGIH) Hand Activity Level (HAL) Threshold Limit Value (TLV), to assess the upper extremity risk of multi-task jobs. Various methods of combining the task differences and ratios into a job level assessment were explored. Two methods returned significant odds ratios, (p < .05) of 18.0 (95% CI 1.8-172) and 12.0 (95% CI 1.2-120). These results indicate that a modified ACGIH HAL TLV may provide insight into the work-related risk of multi-task jobs. Further research is needed to optimize this process.

Hand↗

PubMed2006

Development of a rapid infiltration system for wastewater and river water treatment in Japan using granulated materials.

A rapid infiltration (RI) system using granulated materials was developed for wastewater and river water treatment. Granules were processed by optimized procedures from soil and waste materials with high sorption of recalcitrant dissolved organic matter (DOM) and phosphorus. Granule performance was examined by laboratory column and pilot-scale tests. During the first year of the pilot test, removal of phosphorus was removed from livestock-farm effluent at the hydraulic loading rate of 2 m/day was 50-70% and that of refractory DOM was 10-30%.

Adsorption↗

PubMed2003

Encapsulating protein into preformed liposomes by ethanol-destabilized method.

This study describes a highly efficient method for encapsulating protein drugs into liposomes without using toxic solvents such as chloroform. Large unilamellar vesicles (LUVs) were formed by the ethanol injection method. The effects of composition of phospholipid, buffer concentration, incubation time, incubation temperature, drug loading, ethanol content, and the presence of poly(ethylene) glycol (PEG) lipids on the entrapment efficiency of protein were investigated. It was shown that these preformed LUVs could be induced to entrap protein drugs in the presence of ethanol. Protein could be efficiently encapsulated into liposomes. The interaction of the liposomes with proteins leads to the formation of multilamellar liposomes ranging in size from 70 to 120 nm, only slightly bigger than the parent LUVs from which they originated. Protein drugs were stable in the liposomal solution. There is no significant activity loss during the encapsulation process. The optimal encapsulation efficiency was achieved when 30% approximately 40% ethanol was used in encapsulating protein drugs. Due to the steric hindrance, LUVs containing a PEG coating will dramatically reduce the encapsulation efficiency, even in liposomes containing very low amount of PEG.

Buffers↗

PubMed2003

In vitro characterization of polyorthoester microparticles containing bupivacaine.

Laboratory-scale spray-congealing equipment was utilized to fabricate injectable microparticles consisting of polyorthoester and bupivacaine. Operating conditions for the spray-congealing process were optimized to produce microparticles with the desired shape and particle size to yield acceptable syringeability and injectability. Characterizations were performed to determine the chemico-physical properties of polyorthoester before and after microparticle fabrication. Microparticles with different drug loadings and comparable particle sizes were produced, and their in vitro drug-release profiles were determined. The in vitro drug release of microparticles with a high drug loading was markedly faster than those with a low drug loading. This is partially attributed to a more significant initial burst-drug release of the microparticles with a high drug loading. The microparticles have demonstrated the potential to be used for long-acting postsurgery pain management by local injection.

Bupivacaine↗

PubMed2004

Modular tube/plate-based sample management: a business model optimized for scalable storage and processing.

Modular approaches to sample management allow staged implementation and progressive expansion of libraries within existing laboratory space. A completely integrated, inert atmosphere system for the storage and processing of a variety of microplate and microtube formats is currently available as an integrated series of individual modules. Liquid handling for reformatting and replication into microplates, plus high-capacity cherry picking, can be performed within the inert environmental envelope to maximize compound integrity. Complete process automation provides ondemand access to samples and improved process control. Expansion of such a system provides a low-risk tactic for implementing a large-scale storage and processing system.

Automation↗

PubMed2002

The association between caregiver burden and sleep disturbances in partners of patients with Parkinson's disease.

OBJECTIVES: Caregivers of patients with various diseases frequently report sleep disturbances and depressive symptoms. Care intensity for individuals with Parkinson's disease is mainly influenced by the severity of their motor impairment. The latter is associated with sleep fragmentation, nocturnal pain and cramps. These disease-specific characteristics contribute to sleep-related problems in patients. However, little is known about prevalence and causes of sleep disturbances in caregivers of Parkinson's disease patients. DESIGN AND SETTING: Cross-sectional analysis, nested within the FAQT-Study, a prospective German cohort study evaluating determinants of quality of life in Parkinson's disease patients. PARTICIPANTS: We assessed 106 Parkinson's disease patients and their caregiving partners. MEASUREMENTS: Patients and partners were asked to fill in the Center for Epidemiologic Studies Depression Scale, the caregiver burden inventory, and the Giessener Beschwerdebogen of psychosomatic complaints. All instruments include questions about sleep related problems. Patients were examined by neurologists and classified according to established scales (UPDRS and Hoehn and Yahr scales). RESULTS: Frequent sleep disturbances were reported by 27% of all spouses. Relevant depressive symptoms were shown in 30% of spouses and 45% of Parkinson's disease patients (P<0.001). Depression scores in partners correlated with those in patients. Self-perceived bad night-time sleep in spouses was related to symptom severity, male gender, bad sleep in patients, and to the frequency of caregiving. Caregiver burden was identified as a mediator of the association between care intensity and bad sleep, while psychosomatic complaints were related to sleep problems independently. CONCLUSION: Sleep disturbances are prevalent in partners of Parkinson's disease patients and influenced by their engagement in the caregiving process. Treatment optimization for motor symptoms in patients may not only contribute to improved patient sleep but also to a lower prevalence of sleep disturbances in caregivers.

Aged↗

PubMed2025

Predicting coarse-grained representations of biogeochemical cycles from metabarcoding data.

MOTIVATION: Taxonomic analysis of environmental microbial communities is now routinely performed thanks to advances in DNA sequencing. Determining the role of these communities in global biogeochemical cycles requires the identification of their metabolic functions, such as hydrogen oxidation, sulfur reduction, and carbon fixation. These functions can be directly inferred from metagenomics data, but in many environmental applications metabarcoding is still the method of choice. The reconstruction of metabolic functions from metabarcoding data and their integration into coarse-grained representations of biogeochemical cycles remains a difficult bioinformatics problem today. RESULTS: We developed a pipeline, called Tabigecy, which exploits taxonomic affiliations to predict metabolic functions constituting biogeochemical cycles. In a first step, Tabigecy uses the tool EsMeCaTa to predict consensus proteomes from input affiliations. To optimize this process, we generated a precomputed database containing information about 2404 taxa from UniProt. The consensus proteomes are searched using bigecyhmm, a newly developed Python package relying on Hidden Markov Models to identify key enzymes involved in metabolic function of biogeochemical cycles. The metabolic functions are then projected on coarse-grained representation of the cycles. We applied Tabigecy to two salt cavern datasets and validated its predictions with microbial activity and hydrochemistry measurements performed on the samples. The results highlight the utility of the approach to investigate the impact of microbial communities on biogeochemical processes. AVAILABILITY AND IMPLEMENTATION: The Tabigecy pipeline is available at https://github.com/ArnaudBelcour/tabigecy. The Python package bigecyhmm and the precomputed EsMeCaTa database are also separately available at https://github.com/ArnaudBelcour/bigecyhmm and https://doi.org/10.5281/zenodo.13354073, respectively.

Metagenomics↗

PubMed2004

Catecholaminergic consolidation of motor cortical neuroplasticity in humans.

Amphetamine, a catecholaminergic re-uptake-blocker, is able to improve neuroplastic mechanisms in humans. However, so far not much is known about the underlying physiological mechanisms. Here, we study the impact of amphetamine on NMDA receptor-dependent long-lasting excitability modifications in the human motor cortex elicited by weak transcranial direct current stimulation (tDCS). Amphetamine significantly enhanced and prolonged increases in anodal, tDCS-induced, long-lasting excitability. Under amphetamine premedication, anodal tDCS resulted in an enhancement of excitability which lasted until the morning after tDCS, compared to approximately 1 h in the placebo condition. Prolongation of the excitability enhancement was most pronounced for long-term effects; the duration of short-term excitability enhancement was only slightly increased. Since the additional application of the NMDA receptor antagonist dextromethorphane blocked any enhancement of tDCS-driven excitability under amphetamine, we conclude that amphetamine consolidates the tDCS-induced neuroplastic effects, but does not initiate them. The fact that propanolol, a beta-adrenergic antagonist, diminished the duration of the tDCS-generated after-effects suggests that adrenergic receptors play a certain role in the consolidation of NMDA receptor-dependent motor cortical excitability modifications in humans. This result may enable researchers to optimize neuroplastic processes in the human brain on the rational basis of purpose-designed pharmacological interventions.

Adult↗

PubMed2004

Additive effects of emotional content and spatial selective attention on electrocortical facilitation.

Affectively arousing visual stimuli have been suggested to automatically attract attentional resources in order to optimize sensory processing. The present study crosses the factors of spatial selective attention and affective content, and examines the relationship between instructed (spatial) and automatic attention to affective stimuli. In addition to response times and error rate, electroencephalographic data from 129 electrodes were recorded during a covert spatial attention task. This task required silent counting of random-dot targets embedded in a 10 Hz flicker of colored pictures presented to both hemifields. Steady-state visual evoked potentials (ssVEPs) were obtained to determine amplitude and phase of electrocortical responses to pictures. An increase of ssVEP amplitude was observed as an additive function of spatial attention and emotional content. Statistical parametric mapping of this effect indicated occipito-temporal and parietal cortex activation contralateral to the attended visual hemifield in ssVEP amplitude modulation. This difference was most pronounced during selection of the left visual hemifield, at right temporal electrodes. In line with this finding, phase information revealed accelerated processing of aversive arousing, compared to affectively neutral pictures. The data suggest that affective stimulus properties modulate the spatiotemporal process along the ventral stream, encompassing amplitude amplification and timing changes of posterior and temporal cortex.

Adult↗

PubMed2002

Practical fast gas chromatography for contract laboratory program pesticide analyses.

An approach to shortening the analysis time for practical fast gas chromatography (GC) by using Method Translator software, which can be downloaded free from the Internet, is presented. This software simplifies the process of optimizing temperature programming while changing column dimensions, carrier gas type, and flow. Basic chromatographic theory is employed in a practical manner for adjusting column dimensions for optimal performance. In addition, electronic pneumatic control and high oven ramp rates make it easier to achieve fast analysis times without reproducibility problems. This practical approach is demonstrated using Contract Laboratory Program pesticide analytes. The factors found to be most important in decreasing the analysis time without a loss of performance are utilization of GC columns having smaller diameters and substitution of hydrogen for helium as the carrier gas.

Chromatography, Gas↗

PubMed1987

Some social and health policy requirements for the prevention of AIDS.

Given the present circumstances and considering the foreseeable development of medical knowledge, the primary prevention of AIDS is the sole field of health policy in which the spreading of the disease and the subsequent number of victims can be reduced. AIDS prevention as a time-stable behaviour control in potentially risky situations is therefore primarily a task which has to be tackled in a social scientific manner. It has to be handled on the basis of available medical knowledge of infectious disease situations. Viewed realistically, the prospective goal is not the elimination of the disease, but the greatest possible reduction and minimization of risk, both individually and epidemiologically. Proceeding from realistic estimates of the desired and undesired effects of health policy measures, this principle is being applied through the strategy (achieved through informational campaigns) of encouraging the use of condoms when having sexual intercourse in non-monogamous relationships and of informing intravenous drug abusers of the need to employ sterile hypodermic needles. Elements of this preventive strategy are discussed under four central questions: What should/must be learn? Who should/must learn? What objective and subjective factors facilitate or hinder this learning? How can this learning process most optimally be organized? The efficiency-reducing interference of other kinds of strategies (e.g. orientation toward zero risk concepts, repression, and mass screening for HIV-anti-bodies) is thereby worked out.

Acquired Immunodeficiency Syndrome↗

PubMed1998

Permeation of human ovarian tissue with cryoprotective agents in preparation for cryopreservation.

The recent improvements in the treatment of cancer by chemo- and radiotherapy have led to a significant increase in the survival rates of patients with malignant disease, but at the expense of distressing side effects. One major problem, especially for younger patients, is that aggressive therapy destroys a significant proportion of the follicular population, which can result in either temporary or permanent infertility. Freeze-banking pieces of ovarian cortex prior to treatment is one strategy for preserving fecundity. When the patient is in remission, fertility could, theoretically, be restored by autografting the thawed tissue at the orthotopic site or by growing isolated follicles to maturity in vitro. Recent studies have found good follicular survival in frozen-thawed human ovarian tissue but to optimize the process an effective cryopreservation method needs to be developed. An essential part of such a technique is to permeate the tissue with a cryoprotectant to minimize ice formation and the extent of this equilibration is an important determinant of post-thaw cellular survival. In the current study, we have investigated the diffusion of four cryoprotective agents into human tissue at both 4 degrees C and 37 degrees C. We have also studied the effect of adding different concentrations of the non penetrating cryoprotective agent, sucrose, to the freezing media using the release of lactate dehydrogenase as a measure of its protective effect. At 4 degrees C propylene glycol and glycerol penetrated the tissue significantly slower than either ethylene glycol or dimethyl sulphoxide. At the higher temperature of 37 degrees C all four cryoprotectants penetrated at a faster rate, however concern about enhanced toxicity prevents the use of these conditions in practice. Thus, the results suggest that the best method of preparing tissue for freezing is exposure for 30 min to 1.5 M solutions of ethylene glycol or dimethyl sulphoxide at 4 degrees C; this achieved a mean tissue concentration that was almost 80% that of the bathing solution. We also report that the addition of low concentrations of sucrose to the freezing medium does not have a significant protective effect against freezing injury.

Adult↗

PubMed2006

Parameter estimation of a respiratory control model from noninvasive carbon dioxide measurements during sleep.

A new method for estimating the parameters of a human gas exchange model is presented. Sensitivity analysis is used both to inspect the relative importance of the model parameters and to speed up the par-ameter estimation process. Multistart optimization is used to compensate for the effects of partial and noisy measurements. The validity of the method is first investigated with a test problem for which par-ameter identifiability is shown. The method is then applied to the estimation of sleep-related changes in the respiratory control system from the end-tidal and transcutaneous carbon dioxide measurements on human subjects. The results show that it is possible to gain insight into the behaviour of the rather complex physiological system using only a few noninvasive measurements and tractable computations.

Algorithms↗

PubMed2000

Development and implementation of a clinical pathway programme in an acute care general hospital in Singapore.

A critical or clinical pathway defines the optimal care process, sequencing and timing of interventions by doctors, nurses and other health care professionals for a particular diagnosis or procedure. Clinical pathways are developed through collaborative efforts of clinicians, case managers, nurses, pharmacists, physiotherapists and other allied health care professionals with the aim of improving the quality of patient care, while minimizing cost to the patient. The use of clinical pathways has increased over the past decade in the USA, the UK, Australia, and many other developed countries. However, its use in the developing nations and Asia has been sporadic. To the author's knowledge, there is to date, no published literature on the use and impact of clinical pathways on the quality and cost of patient care in the Asian health care setting. This paper provides a qualitative account of the development and implementation of a clinical pathway programme (using the example of patients with uncomplicated acute myocardial infarction) in an acute care general hospital in Singapore. The paper concludes that clinical pathways, when implemented in the context of an acute care hospital, can result in improvements in the care delivery process.

Cost-Benefit Analysis↗