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Novel system for classifying chromatographic applications, exemplified by comprehensive two-dimensional gas chromatography and multivariate analysis.

For practical chromatographers it is extremely difficult to judge the merits and limitations of new technological developments. On the other hand, it is nearly impossible for those at the forefront of technology to judge the implications of their efforts for all specific applications of chromatography. Both chromatographers and researchers can be aided by a classification of the numerous specific applications into a few well-defined categories. In this paper, we propose such a classification of all chemical analysis by chromatography into three generic types of applications, viz. target-compound analysis, group-type separation, and fingerprinting. The requirements for each type are discussed in general terms. The classification scheme is applied to assess the benefits and limitations of comprehensive two-dimensional gas chromatography (GC x GC) and the possible additional benefits of using multivariate-analysis (MVA) techniques for each type of application. The conclusions pertaining to the generic types of applications are indicative for the implications of new developments for specific chemical analysis by chromatography.

Chromatography, Gas↗

Genotyping single nucleotide polymorphisms by MALDI mass spectrometry in clinical applications.

Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry has become one of the most powerful and widely applied technologies for SNP scoring and determination of allele frequencies in the post-genome sequencing era. Although different strategies for allele discrimination combined with MALDI were devised, in practice only primer extension methods are nowadays routinely used. This combination enables the rapid, quantitative, and direct detection of several genetic markers simultaneously in a broad variety of biological samples. In the field of molecular diagnostics, MALDI has been applied to the discovery of genetic markers, that are associated with a phenotype like a disease susceptibility or drug response, as well as an alternative means for diagnostic testing of a range of diseases for which the responsible mutations are already known. It is one of the first techniques with which whole genome scans based on single nucleotide polymorphisms were carried out. It is equally well suited for pathogen identification and the detection of emerging mutant strains as well as for the characterization of the genetic identity and quantitative trait loci mapping in farm animals. MALDI can also be used as a detection platform for a range of novel applications that are more demanding than standard SNP genotyping such as mutation/polymorphism discovery, molecular haplotyping, analysis of DNA methylation, and expression profiling. This review gives an introduction to the application of mass spectrometry for DNA analysis, and provides an overview of most studies using SNPs as genetic markers and MALDI mass spectrometric detection that are related to clinical applications and molecular diagnostics. Further, it aims to show specialized applications that might lead to diagnostic applications in the future. It does not speculate on whether this methodology will ever reach the diagnostic market.

Animals↗

A pre-optimised dosimetry system using a rigid applicator for intracavitary treatment of cervical carcinoma.

AIMS: Tumour control and complication risk have been major concerns in the treatment of cervical carcinoma. A review of dose distribution for intracavitary treatment of cervical carcinoma revealed that modification of the Manchester dosimetry system is necessary for cases of narrow-sized vagina. A revised dosimetry system was introduced in the present study, with the objective of optimising the dose coverage for the parametrium while minimising the bladder and rectum dosage by restricting the rectal dose so as not to exceed 75% of the brachytherapy prescription dose. MATERIALS AND METHODS: A suitable-sized applicator was selected according to the patient's anatomy. The revised system is optimised based on the fixed geometry of the applicator. The system was therefore predefined and the distribution of the treatment dose already determined before application. The revised system was applied to 135 cases, involving 540 applications. The clinical outcome in terms of local tumour control and complication rates is reported. The differences between the revised system and the Manchester system in terms of dose coverage for the parametrium and the rectum dose were compared. RESULTS: The results showed that higher rectal and parametrial dosages were obtained with the Manchester system as compared with the revised system. Our study showed that over 50% of our patients would have received a rectal dose close to 100% of the point A dose if the Manchester system was applied, whereas it was restricted to below 75% using the revised system. Using the revised system, the significance of the parametrial dosage coverage in relation to local control was assessed: the mean dose to the rectum and the bladder as a percentage of point A was 65.7 +/- 5% (range 50-85%) and 66.4 +/- 14% (range 29-116%), respectively. The 5-year actuarial local failure-free survival rates were 90, 92.9, 86.8, 100, 69.7 and 0% for stages IB, IIA, IIB, IIIA, IIIB and IV (P < 0.0001), respectively. The 3-year actuarial complication rates (grade 3/4) for proctitis and cystitis were 1.4 and 0.5%, respectively. The dosage coverage for the parametrium was found to be significant (P = 0.029) in relation to local control for early-stage disease. CONCLUSIONS: The favourable local tumour control and low complication rates shown by our results indicate that the revised system presents an optimal dose distribution, particularly for the application of small ovoids, whereas morbidity was reduced to a lower level without compromising local control.

Brachytherapy↗

Practical application of aqueous two-phase partition to process development for the recovery of biological products.

The practical application of aqueous two-phase systems (ATPS) to process development has been exploited for several years for the recovery of biological products. Unfortunately, this has not resulted in an extensive presence of the technique in commercial processes. Some of the main identified reasons for such situation involve the full understanding of the mechanism governing phase formation and the behaviour of solute partitioning in ATPS processes, the cost of phase forming polymers and the necessary extended time to understand the technique for process development. In this review paper, some of the practical disadvantages attributed to ATPS are addressed. The practical approach exploited to design ATPS processes, the application to achieve process integration, the increasing use for the recovery of high-value products and the recent development of alternative low cost ATPS, are discussed. It is proposed that the potential trend in the application of ATPS processes for the recovery of biological products will involve the recovery of high-value bio-particulate products with medical applications. This proposed trend in the application of ATPS will address the urgent need to rapidly and economically bring new biopharmaceutical products to market using scaleable and efficient bioprocess technology.

Biological Products↗

Agronomic application of olive mill wastewaters with phosphate rock in a semi-arid Mediterranean soil modifies the soil properties and decreases the extractable soil phosphorus.

Olive mill wastewater (OMW), a by-product of the olive-mill industry, is produced in large amounts in Mediterranean countries. The presence of indigenous phosphate deposits in some countries like Tunisia provides an incentive for direct application or local chemical treatment at low cost to improve the solubility of low reactive phosphate rocks (PRs). The use of naturally occurring low-molecular weight organic acids (LMWOAs) that are present in OMW represents a new perspective in PR research and a possible solution for the recycling of the OMW. The present work was aimed at evaluating, under natural situations (field of olive trees), the effects of agronomic application of OMW (amounts applied: 30, 60 m(3) ha(-1)) with PR (amounts applied: 150 kg ha(-1)) on olive trees soil properties. We measured organic C, nitrogen (N), extractable phosphorus (P), exchangeable calcium (Ca), and exchangeable potassium (K), as well as other properties (pH and electrical conductivity). Our data provide evidence that agronomic application of OMW with PR has important effects on soil properties. Increases in organic C, total N, extractable P and exchangeable potassium (K) were found after the first agronomic application of OMW and PR. These increases were only temporary, following the second agronomic application of OMW and PR, significant reductions were detected in the extractable soil P (19.67 mg kg(-1) in the control soil vs. 8.99 mg kg(-1) in the amended soil). Changes in the extractable soil P could alter plant productivity and plant community structure because shifts in nutriment availability can affect the balance between limiting and non-limiting nutrients.

Industrial Waste↗

A single application of cyclic loading can accelerate matrix deposition and enhance the properties of tissue-engineered cartilage.

OBJECTIVE: Mechanical stimulation is a widely used method to enhance the formation and properties of tissue-engineered cartilage. While studies have evaluated the responsiveness of chondrocytes to mechanical stimuli, little is known about how much stimulation is actually required. Thus, the purpose of this study was to investigate the effect of a single application of cyclic loading to chondrocytes on the formation and properties of in vitro-formed tissue. DESIGN: Isolated bovine articular chondrocytes were seeded on ceramic substrates in 3D culture and subjected to a single application of compressive cyclic loading at 1, 8 or 15 days after seeding. Once the time at which the chondrocytes were most sensitive to mechanical loading was determined, the effect of a single application on the synthesis and accumulation of matrix molecules as well as the mechanical properties of the in vitro-formed cartilage tissue was evaluated. RESULTS: Chondrocytes were more responsive to cyclic loading applied early in culture. Cyclic forces applied 24 h after the cultures were established increased collagen and proteoglycan syntheses (48 +/- 11% and 49 +/- 11%, respectively). This single application of cyclic loading also increased the accumulation of collagen (stimulated: 207 +/- 20 microg, control: 173 +/- 9 microg) and proteoglycans (stimulated: 302 +/- 24 microg, control: 270 +/- 14 microg) as well as improved the mechanical properties of the in vitro-formed tissue (twofold increase in equilibrium stress and modulus) determined 4 weeks after the applied stimulus. CONCLUSIONS: A single application of cyclic loading to chondrocytes early in culture increased matrix accumulation and enhanced the mechanical properties of the in vitro-formed tissue. This suggests that mechanical forces do not have to be applied intermittently over long periods of time to accelerate in vitro tissue formation.

Animals↗

Does exogenous application of salicylic acid through the rooting medium modulate growth and photosynthetic capacity in two differently adapted spring wheat cultivars under salt stress?

In order to assess whether exogenous application of salicylic acid (SA) through the rooting medium could modulate the photosynthetic capacity of two wheat cultivars differing in salinity tolerance, a hydroponic experiment was conducted under greenhouse conditions. Seeds of a salt tolerant (S-24) and a moderately salt sensitive (MH-97) cultivar were germinated at 0 or 150 mM NaCl in Hoagland's nutrient solution containing different levels of salicylic acid (SA) (0, 0.25, 0.50, 0.75 and 1.00 mM) for 7d. Seven-day old wheat seedlings were transferred to hydroponics and grown at 0, or 150 mM NaCl for for further 30 d. Different levels of salicylic acid (SA) were also maintained in the solution culture. After 30 d, four plants out of six were harvested and the remaining plants were left for the estimation of yield attributes Salt stress reduced the growth and grain yield of both cultivars. However, cv. S-24 performed better than MH-97 under salt stress with respect to leaf area, and grain yield. Exogenous application of SA promoted growth and yield, and counteracted the salt stress-induced growth inhibition of salt tolerant S-24, whereas for MH-97 there was no improvement in growth or grain yield with SA application. Of the varying SA levels used, the most effective levels for promoting growth and grain yield were 0.75 and 0.25 mM under normal and saline conditions, respectively. The improvement in growth and grain yield of S-24 due to SA application was associated with improved photosynthetic capacity. Changes in photosynthetic rate due to SA application were not due to stomatal limitations, but were associated with metabolic factors, other than photosynthetic pigments and leaf carotenoids.

Adaptation, Physiological↗

Comparison of suture ligation and clip application for the treatment of patent ductus arteriosus in preterm neonates.

OBJECTIVE: We reviewed the experience of 2 centers performing surgical ligation of patent ductus arteriosus in preterm neonates to identify whether the choice of surgical technique--suture ligation or clip application--affected outcome. METHODS: Between 2000 and 2005, 67 newborn infants had open surgical closure of patent ductus arteriosus: 33 by suture ligation and 34 by clip application. The groups were similar in age and sex. RESULTS: The average length of the procedure was 55.8 +/- 13.7 minutes for suture ligation and 30.8 +/- 8.7 minutes for clip application (P < .05). Six neonates had intraoperative bleeding in the suture ligation group. Four patients had significant postoperative complications in the suture ligation group, compared with 2 in the clip application group. CONCLUSIONS: This study demonstrates that clip application results in a significant reduction in the operative time and, possibly, in less morbidity.

Cardiac Surgical Procedures↗

Breast cancer incidence and its possible spatial association with pesticide application in two counties of England.

BACKGROUND: This study examines the spatial distribution of breast cancer incidence in Lincolnshire and Leicestershire, and its association with the application of selected pesticides. METHODS: The Black-White (BW) join-count statistic and Moran I coefficient were used to investigate the localized distribution of breast cancer. Linear regression techniques were applied to examine the association between the breast cancer incidence rate and pesticide application. RESULTS: The results from the BW join-count test and the Moran I coefficient test showed no overall evidence of localized distribution, 'clusters', of breast cancer. The regression analyses showed no sign of spatial association between breast cancer and application of pesticides in the urban areas as expected. The findings, however, did reveal a spatial association between the breast cancer incidence rates and the application of three selected pesticides [Aldicarb, Atrazine and Lindane (thought to potentially mimic oestrogen)] in rural Leicestershire. No such association was seen in Lincolnshire. CONCLUSIONS: Pesticides vary significantly in their spatial application. Overall, consistent associations between breast cancer incidence rates and the selected pesticides were not found, although the ecological study design has limitations and these are discussed. This approach is able to rule out strong associations; assessment of smaller risk would require a large and expensive study in individuals. The results of this study, although derived in the UK, have significance to the debate concerning the possibility of environmental compounds that mimic oestrogen and their consequences for human health.

Aged↗

Field assessment of treatment efficacy by three methods of phosphoric acid application in lead-contaminated urban soil.

In situ soil treatment using phosphoric acid (H(3)PO(4)) may be an effective remedial technology for immobilizing soil Pb and reducing Pb risk to human health and ecosystem. The treatment efficacy of three H(3)PO(4) application methods was assessed in a smelter-contaminated urban soil located in the Jasper County Superfund Site, Missouri. Soil, with an average of 3529 mg Pb kg(-1) and in the 2- by 4-m plot size, was treated with H(3)PO(4) at a rate of 10 g P kg(-1) in four replicates by each of three methods: rototilling; surface application; pressure injection. Three soil cores, 2.5-cm diameter and 30-cm long, were taken from each plot before and 90 days after treatment and analyzed for soluble P, bioaccessible Pb and solid-Pb speciation. Applications of H(3)PO(4) induced the heterogeneity of soluble P in soil, with the highest concentrations in the surface. Three application methods mixed the H(3)PO(4) more effectively in the horizontals than the verticals of treated soil zone. The H(3)PO(4) applications significantly reduced Pb bioaccessibility in the soil, which was influenced by the concentrations of soil soluble P and solid-Pb species. The risk reductions of soil Pb were achieved by formation of pyromorphites or pyromorphite-like minerals. The rototilling appears to be the most effective treatment method in context of the homogeneity of soluble P and the reduction of Pb bioaccessibility in treated soil.

Cities↗

Findings and outcomes of psychological evaluations of gastric bypass applicants.

BACKGROUND: Among severely obese persons seeking surgical treatment, lifetime prevalence rates of Axis 1 psychiatric disorders range up to 50%; 27% to 42% have a diagnosable psychiatric disorder at the time of evaluation. Despite recommendations by the National Institutes of Health Consensus Development Panel that evaluation for surgery include a mental health component, little data are available on the outcomes of such evaluations. Similarly, there are also few data on the frequency and type of psychotropic medication use by these patients. The primary objective of this study was to describe the recommendations resulting from psychological evaluations of bariatric surgery applicants; a secondary purpose was to describe the point and lifetime prevalences of psychotropic medication use. METHODS: We examined the psychological evaluation recommendations of successive gastric bypass applicants at the Medical University of South Carolina. RESULTS: Results indicated that the overwhelming majority (81.5%) of gastric bypass applicants had no psychological contraindication to surgery. A smaller percentage (15.8%) required psychological treatment before surgery, and only 2.7% of all applicants were considered psychologically inappropriate for surgery. Results also indicate that 47.7% were using at least 1 psychotropic medication at the time of the evaluation, and that 9.2% were using more than 1. The overwhelming majority of medications used were antidepressants, followed by antianxiety medications and mood stabilizers. CONCLUSIONS: These results indicate that the vast majority of patients will not be denied surgery as the result of a psychological assessment, yet approximately 20% of patients may be considered, based on psychological evaluation, psychologically inappropriate for immediate surgery, at least without initial treatment. These data also suggest that pharmacologic treatment of psychiatric disorders is quite common among gastric bypass applicants.

Adult↗

Effect of composted sewage sludge application to soil on sweet pepper crop (Capsicum annuum var. annuum) grown under two exploitation regimes.

The aim of this study is to monitor the effect of the application of three increasing amounts of composted sewage sludge (3, 6 and 9 kg compost m(-2)) on the physico-chemical properties of a horticultural calcareous soil where sweet pepper plants (Capsicum annuum var. annuum) cv. California were grown. A comparative study of two different exploitation regimes was carried out; the first was an open-air field-grown plot and the second plot was kept under controlled conditions in a greenhouse. Changes in physical and chemical properties measured in soil and sweet pepper crop were recorded during crop growth in order to measure the evolution of these properties as a consequence of increasing compost applications. Organic matter, total nitrogen Kjeldahl and available phosphorus contents increased in soil after composted sewage sludge applications. The 9 kg compost m(-2) application promoted the appearance of deleterious effects on the properties of soil, such as salt accumulation, a significant increase in the electrical conductivity and an input of heavy metals (Pb>Cr>Cd). The 6 kg compost m(-2) application provided a supply of nutrients necessary to grow peppers plants under both exploitation regimes. Pepper fruit biomass production under greenhouse was almost 60% higher compared to that of the open-air plot. Lower contents of Ca and increased levels of Cu in fruit under greenhouse growing conditions compared to those of open-air grown peppers seemed to promote the occurrence of blossom-end rot, affecting more than 10% of the harvested fruits.

Biodegradation, Environmental↗

Is the quality of surgical residency applicants deteriorating?

BACKGROUND: Among directors of general surgery residencies, there is a concern that the quality of medical students applying to surgical residencies is declining. METHODS: Quality of surgical applicants was assessed by several methods including subjective opinions determined by survey and by objective data including student United States Medical Licensing Examination (USMLE) scores of matched candidates. The number of applicants interviewed, total interviews granted, proportion of Alpha Omega Alpha (AOA) students, and the rank order of the candidates matched was obtained by survey. The survey included data on postgraduate year 1 (PGY-1) residents from July 1996 to July 1999. Three mailings were made to 226 US surgical residency programs. RESULTS: Data were obtained from 90 programs. Surgery program directors disagreed with a survey statement that overall quality of applicants had declined (P <0.01), but agreed with a statement that activities of medical schools to enroll graduating students into primary care had hurt recruitment (P <0.001). Objective data revealed no change in mean USMLE part I scores of PGY-1 residents over the 4 years (P = 0.265, power = 0.81). There was no change in proportion of matched residents who were AOA over time. The mean score of all new PGY-1 residents, the rank of the first matched resident, the rank of the last ranked resident, and proportion of AOA students was higher in programs with five or more categorical spots when compared with programs of at most four (P <0.001). Across all programs, there was a trend to go lower on the rank list to fill categorical positions over time (P <0.001). CONCLUSIONS: There is a perception that medical school policies act to discourage recruitment of quality medical students into general surgery programs, and surgery programs are going deeper into their rank lists to fill categorical positions. However, the average USMLE part I score of applicants to surgical residencies and proportion of AOA applicants has not decreased.

Data Collection↗

Response of erupting human premolars to force application.

To test the hypothesis that human tooth eruption requires a critical time period during which no force is applied to the erupting tooth, the eruption of a maxillary second premolar in the prefunctional stage was recorded during the afternoon or evening hours in eight children, using an optical device based on the principle of Moiré magnification, while intermittent loads of 300-400 mN were applied to the teeth. When a tooth was erupting actively, light force applications either had no discernible effect or decreased the eruption rate for 2 min or less. When a tooth was intruding spontaneously rather than erupting, a varied response was observed, but the rate of intrusion never increased after force application. Often intrusion showed or halted, and especially during the evening, eruption was likely to occur after a force application during an initial period of intrusion. The conclusion is that, although light force applications significantly displace an erupting premolar, they have little or no effect on net eruption, and that a critical time period without force application is not necessary for eruption to occur.

Adolescent↗

Image restoration for confocal microscopy: improving the limits of deconvolution, with application to the visualization of the mammalian hearing organ.

Deconvolution algorithms have proven very effective in conventional (wide-field) fluorescence microscopy. Their application to confocal microscopy is hampered, in biological experiments, by the presence of important levels of noise in the images and by the lack of a precise knowledge of the point spread function (PSF) of the system. We investigate the application of wavelet-based processing tools to deal with these problems, in particular wavelet denoising methods, which turn out to be very effective in application to three-dimensional confocal images. When used in combination with more classical deconvolution algorithms, these methods provide a robust and efficient restoration scheme allowing one to deal with difficult imaging conditions. To make our approach applicable in practical situations, we measured the PSF of a Biorad-MRC1024 confocal microscope under a large set of imaging conditions, including in situ acquisitions. As a specific biological application, we present several examples of restorations of three-dimensional confocal images acquired inside an intact preparation of the hearing organ. We also provide a quantitative assessment of the gain in quality achieved by wavelet-aided restorations over classical deconvolution schemes, based on a set of numerical experiments that we performed with test images.

Algorithms↗

Cumulative radiation effect. Part VII: computer calculations and applications in clinical practice.

In five previous papers, the concept of the Cumulative Radiation Effect (CRE) has been presented as a scale of accumulative sub-tolerance radiation damage. The biological effect generated in normal connective tissue by fractionated or continuous radiation therapy given in any temporal arrangement is described by the CRE on a unified scale of assessment, so that a unique value of the CRE describes a specific level of radiation effect. The basic methods of evaluating CREs were shown in the papers to facilitate a full understanding of the fundamental aspects of the CRE-system, but these methods can be time-consuming and tedious for complex situations. In the previous papers in this series, one way of overcoming the difficulties in evaluating CRE problems was presented in simple nomographic and tabular methods for the solution of practical problems. An alternative way of overcoming the difficulties in the evaluation of CRE problems is to use computers and it is the purpose of this paper to outline computer calculations and applications in clinical practice in connection with the CRE-system. In a general appraisal of the applications of computers to the CRE-system, the various problems encountered in clinical radiotherapy are categorised into those involving the evaluation of a CRE at a point in tissue and those involving the calculation of CRE distributions. As a general guide, the computer techniques adopted at the Glasgow Institute of Radiotherapeutics for the solution of CRE problems are presented, and consist basically of a package of three interactive programs for point CRE calculations and a Fortan program which calculates CRE distributions for iso-effect treatment planning. Many examples are given to demonstrate the applications of these programs, and special emphasis has been laid on the problem of treating a point in tissue with different doses per fraction on alternate treatment days. The wide range of possible clinical applications of the CRE-system has been outlined and described under the categories of routine clinical applicatons, retrospective and prospective surveys of patient treatment, and experimental and theoretical research. Some of these applications such as the results of surveys and studies of time optimisation of treatment schedules could have far-reaching consequences and lead to significant improvements in treatment and cure rates with the minimum damage to normal tissue.

Computers↗

Workflow management with systems approach: anticipated and ad-hoc workflow for scientific applications.

While workflow management has mostly been considered in business applications so far, the focus of the Workflow Management with Systems Approach (WOMASA) is on scientific applications such as geoprocessing, molecular biology, or laboratory environments. In particular, WOMASA aims at flexible and platform-indepented workflow support, with respect to both specification and execution of workflows. It turns out that the modeling and execution of workflows in traditional and in scientific applications exhibit significant differences. In particular, the need for dynamic modifications of workflow models while workflows are running is an important feature in scientific applications. The conceptual design and functionality of a WOMASA prototype is outlined, in particular that of its core workflow engine, and it is shown how the requirements of flexibility in modeling and executing workflows, imposed by scientific applications, are met.

DNA↗

Ocular tissue concentrations of mitomycin C with variable dose and duration of application time in rabbits.

We measured mitomycin C (MMC) concentrations in ocular tissues in rabbits with variable dose (0.1, 0.2, or 0.4 mg) and duration of application time (1, 3, or 5 minutes) of MMC using high-performance liquid chromatography. Mitomycin C concentrations at the administered site after single subconjunctival application of MMC and after irrigation showed significant correlation with dose and duration of time of application. By multiple regression analysis, MMC concentrations (microg/g) at the conjunctiva were described as -6.73 + 67.4 x Dose (mg) + 1.66 x Time (minutes) (R2 0.65); at the sclera, -1.85 + 38.2 x Dose + 0.927 x Time (R2 0.63); at the cornea, -0.727 + 8.44 x Dose (R2 0.46). With a 0.2-mg MMC dose, in all three application times (1, 3, or 5 minutes), MMC concentrations in the conjunctiva at the administered quadrant were three times higher than in the neighboring quadrants and 6 to 7 times higher than in the opposite quadrant. In the sclera, MMC concentrations were 3.5 times higher than in the neighboring sites and over 8 to 9 times higher than in the opposite site. In the cornea, MMC concentrations were 2 to 3 times higher than in the neighboring sites and opposite site. In the iris-ciliary body, MMC concentrations were 0.61 microg/g at the administered site with 0.2 mg for 3-minute application, 2 times higher than in neighboring sites, and 2 times higher than in opposite sites.

Animals↗