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Journal of Chromatography. A Mar 2008Since 1999, substantial research has been devoted to the development of liquid-phase microextraction (LPME) based on porous hollow fibers. With this technology, target... (Review)
Review
Since 1999, substantial research has been devoted to the development of liquid-phase microextraction (LPME) based on porous hollow fibers. With this technology, target analytes are extracted from aqueous samples, through a thin supported liquid membrane (SLM) sustained in the pores in the wall of a porous hollow fiber, and further into a microL volume of acceptor solution placed inside the lumen of the hollow fiber. After extraction, the acceptor solution is directly subjected to a final chemical analysis by liquid chromatography (HPLC), gas chromatography (GC), capillary electrophoresis (CE), or mass spectrometry (MS). In this review, LPME will be discussed with focus on extraction principles, historical development, fundamental theory, and performance. Also, major applications have been compiled, and recent forefront developments will be discussed.
Topics: Chemical Fractionation; Citalopram; Electrophoresis, Capillary; Methamphetamine; Models, Theoretical; Pharmaceutical Preparations; Solid Phase Microextraction
PubMed: 17889886
DOI: 10.1016/j.chroma.2007.08.088 -
SLAS Technology Dec 2019We describe the development of a high-resolution, noncontact fraction collector for liquid chromatography (LC) separations, allowing high-resolution fractionation in...
We describe the development of a high-resolution, noncontact fraction collector for liquid chromatography (LC) separations, allowing high-resolution fractionation in high-density well plates. The device is based on a low-dead-volume solenoid valve operated at 1-30 Hz for accurate collection of fractions of equal volume. The solenoid valve was implemented in a modified autosampler resulting in the so-called FractioMate fractionator. The influence of the solenoid supply voltage on solvent release was determined and the effect of the frequency, flow rate, and mobile phase composition was studied. For this purpose, droplet release was visually assessed for a wide range of frequencies and flow rates, followed by quantitative evaluation of a selection of promising settings for highly accurate, repeatable, and stable fraction collection. The potential of the new fraction collector for LC-based bioactivity screening was demonstrated by fractionating the LC eluent of a mixture of estrogenic and androgenic compounds, and a surface water sample (blank and spiked with bioactives) combining mass spectrometric detection and two reporter gene assays for bioactivity detection of the fractions. Additionally, a mixture of two compounds was repeatedly LC separated and fractionated to assess the feasibility of the system for analyte isolation followed by nuclear magnetic resonance analysis.
Topics: Biological Assay; Chemical Fractionation; Chromatography, High Pressure Liquid; Chromatography, Liquid; Genes, Reporter; Humans; MCF-7 Cells; Magnetic Resonance Spectroscopy; Mass Spectrometry; Solvents
PubMed: 31096846
DOI: 10.1177/2472630319848768 -
Physics in Medicine and Biology Aug 2021A mathematical tumor response model has been developed, encompassing the interplay between immune cells and cancer cells initiated by either partial or full tumor...
A mathematical tumor response model has been developed, encompassing the interplay between immune cells and cancer cells initiated by either partial or full tumor irradiation. The iterative four-compartment model employs the linear-quadratic radiation response theory for four cell types: active and inactive cytotoxic T lymphocytes (immune cells, CD8T cells in particular), viable cancer cells (undamaged and reparable cells) and doomed cells (irreparably damaged cells). The cell compartment interactions are calculated per day, with total tumor volume (TV) as the main quantity of interest. The model was fitted to previously published data on syngeneic xenografts (67NR breast carcinoma and Lewis lung carcinoma; (Markovsky2019697-708)) subjected to single doses of 10 or 15 Gy by 50% (partial) or 100% (full) TV irradiation. The experimental data included effects from anti-CD8antibodies and immunosuppressive drugs. Using a new optimization method, promising fits were obtained where the lowest and highest root-mean-squared error values were observed for anti-CD8treatment and unirradiated control data, respectively, for both cell types. Additionally, predictive capabilities of the model were tested by using the estimated model parameters to predict scenarios for higher doses and different TV irradiation fractions. Here, mean relative deviations in the range of 19%-34% from experimental data were found. However, more validation data is needed to conclude on the model's predictive capabilities. In conclusion, the model was found useful in evaluating the impact from partial and full TV irradiation on the immune response and subsequent tumor growth. The model shows potential to support and guide spatially fractionated radiotherapy in future pre-clinical and clinical studies.
Topics: Animals; Breast Neoplasms; Carcinoma, Lewis Lung; Dose Fractionation, Radiation; Humans; Immunity; Immunomodulation; Radiotherapy Dosage
PubMed: 34298527
DOI: 10.1088/1361-6560/ac176b -
Journal of Chromatography. A Apr 2010Dispersive liquid-liquid microextraction (DLLME) has become a very popular environmentally benign sample-preparation technique, because it is fast, inexpensive, easy to... (Review)
Review
Dispersive liquid-liquid microextraction (DLLME) has become a very popular environmentally benign sample-preparation technique, because it is fast, inexpensive, easy to operate with a high enrichment factor and consumes low volume of organic solvent. DLLME is a modified solvent extraction method in which acceptor-to-donor phase ratio is greatly reduced compared with other methods. In this review, in order to encourage further development of DLLME, its combination with different analytical techniques such as gas chromatography (GC), high-performance liquid chromatography (HPLC), inductively coupled plasma-optical emission spectrometry (ICP-OES) and electrothermal atomic absorption spectrometry (ET AAS) will be discussed. Also, its applications in conjunction with different extraction techniques such as solid-phase extraction (SPE), solidification of floating organic drop (SFO) and supercritical fluid extraction (SFE) are summarized. This review focuses on the extra steps in sample preparation for application of DLLME in different matrixes such as food, biological fluids and solid samples. Further, the recent developments in DLLME are presented. DLLME does have some limitations, which will also be discussed in detail. Finally, an outlook on the future of the technique will be given.
Topics: Body Fluids; Chemical Fractionation; Chromatography; Food Analysis; Humans
PubMed: 20005521
DOI: 10.1016/j.chroma.2009.11.088 -
International Journal of Radiation... Apr 2000To quantify the response of human lung to a course of fractionated radiotherapy based on a literature review of published clinical data. (Review)
Review
PURPOSE
To quantify the response of human lung to a course of fractionated radiotherapy based on a literature review of published clinical data.
MATERIALS AND METHODS
Quantitative clinical radiobiology is concerned with the estimation of parameters that describe the clinical outcome of radiotherapy as a function of patient and treatment characteristics. Here, parameters describing the steepness of the dose-response curve, the response to a change in dose per fraction and to a change in overall treatment time for early and late lung injury are compiled based on published clinical studies.
RESULTS
Two phases of lung injury are seen, radiation pneumonitis and lung fibrosis. The first signs of early lung changes are seen almost immediately after irradiation. This reaction peaks after 5 to 6 months, and settles partially before 9-10 months. Around that time, the late changes become manifest and these are stable in most cases. There is an important distinction between lung injury and radiotherapy-related morbidity, as even severe changes in a small volume may not give rise to any clinical symptoms. Many assays have been developed for lung damage, and these highlight various clinical and biological aspects of lung damage. Here, the literature on steepness of dose-response curves and fractionation sensitivity is reviewed and quantified by the alpha/beta ratio of the linear-quadratic model for both radiation pneumonitis and lung fibrosis. For the early phase a significant time factor exists. Current best estimates for these radiobiological parameters are derived. Other external factors affecting these estimates are briefly discussed.
CONCLUSIONS
Quantitative estimates of radiobiological characteristics of human lung are available for the pneumonitis phase where the fractionation sensitivity is in the same range as for most late-responding normal tissues. Short intensive schedules may also bear an added risk for pneumonitis as the dose recovered per day is around 0.5 Gy. For the later phase of lung fibrosis, the estimates are fewer and generally less precise. It is clear though, that the alpha/beta ratio is low, possibly 2-3 Gy. No time factor has been demonstrated for the late reaction. Due to the considerable physiological reserve capacity in the normal human lung, the relationship between damage and morbidity depends strongly on the lung volume affected. It therefore seems likely that for small volumes irradiated to high doses, the dose-limiting complications may not be due to restriction of lung function, but rather to haemorrhage and formation of fistulae.
Topics: Animals; Dose Fractionation, Radiation; Dose-Response Relationship, Radiation; Humans; Lung; Radiotherapy; Radiotherapy, Conformal; Risk Factors
PubMed: 10815624
DOI: 10.1080/095530000138448 -
Radiotherapy and Oncology : Journal of... Aug 2022For radiotherapy of thoracic and abdominal tumors safety margins are applied to address geometrical uncertainties caused by e.g. set-up errors, organ motion and... (Review)
Review
For radiotherapy of thoracic and abdominal tumors safety margins are applied to address geometrical uncertainties caused by e.g. set-up errors, organ motion and delineation variability. For pediatric patients no standardized margins are defined. Moreover, studies on these geometrical uncertainties are relatively scarce. Therefore, this systematic review presents an overview of organ motion, applied margin sizes and delineation variability in patients <18 years. A search from January 2000 to March 2021 in Medline, Embase, Web of Science, ClinicalTrials.gov and the International Trials Registry Platform resulted in the inclusion of 117 studies reporting on organ motion, margin sizes and/or delineation variability. Studies were heterogeneous concerning age, tumor types, the use of general anesthesia, imaging modalities; image guidance techniques were reported in 39% of the studies. Inter- and intrafractional motion as reported for different organs was largest in cranio-caudal direction and ranged from -9.1 to 10.0 mm and -4.4 to 19.5 mm, respectively. Motion quantification methodologies differed between studies regarding measures of displacement and definitions of motion direction. Reported CTV-PTV margins varied from 3 to 20 mm for both thoracic and abdominal targets, and for spinal and pelvic from 3to 15 mm and 3 to 10 mm, respectively. Studies reported wide variation in interobserver variability of target volume delineation, which may affect dose distributions to both target volumes and organs at risk. Results of this review indicate possible reduction of margin sizes for children, however, wide variation in organ motion and delineation variability caused by differences in methodologies and outcomes hamper the use of standardized margins.
Topics: Child; Dose Fractionation, Radiation; Humans; Organ Motion; Radiotherapy Dosage; Radiotherapy Planning, Computer-Assisted; Radiotherapy, Image-Guided
PubMed: 35640771
DOI: 10.1016/j.radonc.2022.05.021 -
International Journal of Radiation... Apr 2020The CHHiP trial randomized 3216 men with localized prostate cancer (1:1:1) to 3 radiation therapy fractionation schedules: 74 Gy in 37 fractions over 7.4 weeks; 60 Gy in... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The CHHiP trial randomized 3216 men with localized prostate cancer (1:1:1) to 3 radiation therapy fractionation schedules: 74 Gy in 37 fractions over 7.4 weeks; 60 Gy in 20 fractions over 4 weeks; and 57 Gy in 19 fractions over 3.8 weeks. Literature-based dose constraints were applied with arithmetic adjustment for the hypofractionated arms. This study aimed to derive anorectal dose constraints using prospectively collected clinician-reported outcomes (CROs) and patient-reported outcomes (PROs) and to assess the added predictive value of spatial dose metrics.
METHODS AND MATERIALS
A case-control study design was used; 7 CRO and 5 PRO bowel symptoms were evaluated. Cases experienced a moderate or worse symptom 1 to 5 years after-radiation therapy and did not have the symptom before radiation therapy. Controls did not experience the symptom at baseline or between 1 to 5 years after radiation therapy. The anorectum was recontoured from the anal verge to the rectosigmoid junction; dose/volume parameters were extracted. Univariate logistic regression, atlases of complication indices, and bootstrapped receiver-operating-characteristic analysis (1000 replicates, balanced outcomes) were used to derive dose constraints for the whole cohort (hypofractionated schedules were converted to 2-Gy equivalent schedules using α/β = 3 Gy) and separate hypofractionated/conventional fractionation cohorts. Only areas under the curve with 95% confidence interval lower limits >0.5 were considered statistically significant. Any constraint derived in <95% to 99% of bootstraps was excluded.
RESULTS
Statistically significant dose constraints were derived for CROs but not PROs. Intermediate to high doses were important for rectal bleeding, whereas intermediate doses were important for increased bowel frequency, fecal incontinence, and rectal pain. Spatial dose metrics did not improve prediction of CROs or PROs. A new panel of dose constraints for hypofractionated schedules to 60 Gy or 57 Gy are V20Gy <85%, V30Gy <57%, V40Gy <38%, V50Gy <22%, and V60Gy <0.01%.
CONCLUSIONS
Dose constraints differed among symptoms, indicating potentially different pathogenesis of radiation-induced side effects. Derived dose constraints were stricter than those used in CHHiP and may reduce bowel symptoms after radiation therapy.
Topics: Dose Fractionation, Radiation; Humans; Male; Patient Reported Outcome Measures; Prostatic Neoplasms; Rectum; Treatment Outcome
PubMed: 31987974
DOI: 10.1016/j.ijrobp.2020.01.003 -
Clinical Oncology (Royal College of... 2001There are many clinical situations in which radiobiological considerations can be usefully applied and all clinicians should be aware of the potential benefits of... (Review)
Review
There are many clinical situations in which radiobiological considerations can be usefully applied and all clinicians should be aware of the potential benefits of developing a quantitative radiobiological approach to their practice. The concept of biologically effective dose (BED) in particular is useful for quantifying treatment expectations, but clinical oncologists should recognize that careful interpretation of modelling results is required before clinical decisions can be made and that there is a lack of reliable human parameters for application in some situations. Correct use of the BED concept will, in more complex treatment situations, sometimes involve the use of multiple parameters and BED calculations. Examples include: 1. Where the dose per fraction is being altered and it is possible that normal tissue tolerance may be compromised, calculations should include two or more alpha/beta ratio values, some being less than 3 Gy, in order to estimate the 'worst case scenario'. 2. A single one-point BED calculation will not be representative of the biological effect throughout a large planning target volume where there are significant 'hot spots'. Multiple BED evaluations are then indicated. 3. Where there are combinations of radiotherapy treatments or phases of treatments, these can be quantitatively assessed by the addition of BEDs, although the volume of tissue is not inherently included in the BED calculation and any high-dose region needs to be separately assessed as in point 2. 4. Allowance for tumour clonogen repopulation during therapy is required for some tumour types. 5. Different histological classes of cancers require the use of different alpha/beta ratios. Where there is reasonable doubt regarding this parameter, a suitable range should be used. The principles involved are illustrated by worked examples. Attention to detail and the examination of ranges of possible results should offer a safer guide to alternative dose fractionation schedules, although the ultimate choice will be tempered by clinical circumstances.
Topics: Dose Fractionation, Radiation; Humans; Models, Theoretical; Neoplasms; Radiation Oncology
PubMed: 11373882
DOI: 10.1053/clon.2001.9221 -
Journal of Radiation Research Jan 2020The aim of the study was to evaluate inter-fractional dosimetric variations for high-dose rate breast brachytherapy using a strut-adjusted volume implant (SAVI). For the...
The aim of the study was to evaluate inter-fractional dosimetric variations for high-dose rate breast brachytherapy using a strut-adjusted volume implant (SAVI). For the nine patients included, dosimetric constraints for treatment were as follows: for the planning target volume for evaluation (PTV_Eval), the volume receiving 90, 150 and 200% of the prescribed dose (V90%,150%,200%) should be >90%, ≤50 cm3 and ≤20 cm3, respectively; the dose covering 1 cm3 (D1cc) of the organs at risk should be ≤110% of the prescribed dose; and the air volume should be ≤10% of PTV_Eval. Differences in V90%,150%,200%, D1cc and air volume ($\Delta V$ and $\Delta D$) as inter-fractional dosimetric variations and SAVI displacements were measured with pretreatment and planning computed tomography (CT) images. Inter-fractional dosimetric variations were analyzed for correlations with the SAVI displacements. The patients were divided into two groups based on the distance of the SAVI from the surface skin to assess the relationship between the insertion position of the SAVI and dosimetric parameters. The median ΔV90%,150%,200% for the PTV_Eval in all patients was -0.3%, 0.2 cm3 and 0.2 cm3, respectively. The median (range) ΔD1cc for the chest wall and surface skin was -0.8% (-18.9 to 9.4%) and 0.3% (-7.6 to 5.3%), respectively. SAVI displacement did not correlate with inter-fractional dosimetric variations. In conclusion, the dose constraints were satisfied in most cases. However, there were inter-fractional dosimetric changes due to SAVI displacement.
Topics: Adult; Aged; Aged, 80 and over; Breast Implants; Breast Neoplasms; Dose Fractionation, Radiation; Female; Humans; Image Processing, Computer-Assisted; Middle Aged; Radiometry
PubMed: 31665490
DOI: 10.1093/jrr/rrz061 -
Medical Physics Aug 2023Stereotactic radiosurgery (SRS) is an established treatment for patients with brain metastases (BMs). However, damage to the healthy brain may limit the tumor dose for...
BACKGROUND
Stereotactic radiosurgery (SRS) is an established treatment for patients with brain metastases (BMs). However, damage to the healthy brain may limit the tumor dose for patients with multiple lesions.
PURPOSE
In this study, we investigate the potential of spatiotemporal fractionation schemes to reduce the biological dose received by the healthy brain in SRS of multiple BMs, and also demonstrate a novel concept of spatiotemporal fractionation for polymetastatic cancer patients that faces less hurdles for clinical implementation.
METHODS
Spatiotemporal fractionation (STF) schemes aim at partial hypofractionation in the metastases along with more uniform fractionation in the healthy brain. This is achieved by delivering distinct dose distributions in different fractions, which are designed based on their cumulative biologically effective dose ( ) such that each fraction contributes with high doses to complementary parts of the target volume, while similar dose baths are delivered to the normal tissue. For patients with multiple brain metastases, a novel constrained approach to spatiotemporal fractionation (cSTF) is proposed, which is more robust against setup and biological uncertainties. The approach aims at irradiating entire metastases with possibly different doses, but spatially similar dose distributions in every fraction, where the optimal dose contribution of every fraction to each metastasis is determined using a new planning objective to be added to the BED-based treatment plan optimization problem. The benefits of spatiotemporal fractionation schemes are evaluated for three patients, each with >25 BMs.
RESULTS
For the same tumor BED and the same brain volume exposed to high doses in all plans, the mean brain BED can be reduced compared to uniformly fractionated plans by 9%-12% with the cSTF plans and by 13%-19% with the STF plans. In contrast to the STF plans, the cSTF plans avoid partial irradiation of the individual metastases and are less sensitive to misalignments of the fractional dose distributions when setup errors occur.
CONCLUSION
Spatiotemporal fractionation schemes represent an approach to lower the biological dose to the healthy brain in SRS-based treatments of multiple BMs. Although cSTF cannot achieve the full BED reduction of STF, it improves on uniform fractionation and is more robust against both setup errors and biological uncertainties related to partial tumor irradiation.
Topics: Humans; Radiosurgery; Brain; Brain Neoplasms; Dose Fractionation, Radiation; Uncertainty
PubMed: 37318898
DOI: 10.1002/mp.16457