Purpose
To evaluate three different formulae for calculating the biologically effective dose (BED) by use of a multipopulation reaction–diffusion simulation to determine whether these formulae ...produce equivalent effects for different treatment regimes.
Methods
The standard BED formula, BEDs, was updated to account both for spacial nonuniformity in dose and for cellular regrowth between fractions, by creating two new formulae: BEDϕ and BEDϕT. These BED formulae were used to calculate dose per fraction values for two, three, and five fraction treatments and to compare the tumor volumes of those treatments to those of a single fraction. A spherical tumor model based on the reaction–diffusion equation was used to calculate the final volume of each tumor 185 days after the delivery of the first fraction. The percent difference in volume between single‐fraction and multiple‐fraction treatments was used as a measure to test the accuracy of each BED formula.
Results
Percent differences in volume between single‐ and multiple‐fraction treatment regimes varied up to approximately 18.5% if the dose per fraction was calculated using BEDs but the delivered dose was nonuniform. Proper application of spacial nonuniformity in dose and tumor regrowth correction factors modified the dose per fraction values by no more than 5%, but resulted in the improvement of simulated tumor volumes down to around 2% or lower difference in volume.
Conclusions
Treatment regimes with the same BED value should have the same effect. However, small changes in the dose per fraction delivered in multiple‐fraction treatments can have a large effect on the tumor volume of a treatment when the dose is delivered nonuniformly or when tumor regrowth between fractions is ignored. Inclusion of these correction factors is important for the underlying assumption that treatments with equal BED will have equal effects on the clinically observed tumor volume.
Mathematical modeling of biological processes is widely used to enhance quantitative understanding of bio-medical phenomena. This quantitative knowledge can be applied in both clinical and ...experimental settings. Recently, many investigators began studying mathematical models of tumor response to radiation therapy. We developed a simple mathematical model to simulate the growth of tumor volume and its response to a single fraction of high dose irradiation. The modelling study may provide clinicians important insights on radiation therapy strategies through identification of biological factors significantly influencing the treatment effectiveness.
We made several key assumptions of the model. Tumor volume is composed of proliferating (or dividing) cancer cells and non-dividing (or dead) cells. Tumor growth rate (or tumor volume doubling time) is proportional to the ratio of the volumes of tumor vasculature and the tumor. The vascular volume grows slower than the tumor by introducing the vascular growth retardation factor, θ. Upon irradiation, the proliferating cells gradually die over a fixed time period after irradiation. Dead cells are cleared away with cell clearance time. The model was applied to simulate pre-treatment growth and post-treatment radiation response of rat rhabdomyosarcoma tumors and metastatic brain tumors of five patients who were treated with Gamma Knife stereotactic radiosurgery (GKSRS).
By selecting appropriate model parameters, we showed the temporal variation of the tumors for both the rat experiment and the clinical GKSRS cases could be easily replicated by the simple model. Additionally, the application of our model to the GKSRS cases showed that the α-value, which is an indicator of radiation sensitivity in the LQ model, and the value of θ could be predictors of the post-treatment volume change.
The proposed model was successful in representing both the animal experimental data and the clinically observed tumor volume changes. We showed that the model can be used to find the potential biological parameters, which may be able to predict the treatment outcome. However, there is a large statistical uncertainty of the result due to the small sample size. Therefore, a future clinical study with a larger number of patients is needed to confirm the finding.
Based on the bestseller "3G Evolution - HSPA and LTE for mobile broadband" and reflecting the ongoing success of LTE throughout the world, this book focuses on LTE with full updates including ...LTE-Advanced to provide a complete picture of the LTE system. Overview and detailed explanations are given for the latest LTE standards for radio interface architecture, the physical layer, access procedures, broadcast, relaying, spectrum and RF characteristics, and system performance. Key technologies presented include multi-carrier transmission, advanced single-carrier transmission, advanced receivers, OFDM, MIMO and adaptive antenna solutions, advanced radio resource management and protocols, and different radio network architectures. Their role and use in the context of mobile broadband access in general is explained. Both a high-level overview and more detailed step-by-step explanations of the LTE/LTE-Advanced implementation are given. An overview of other related systems such as GSM/EDGE, HSPA, CDMA2000, and WIMAX is also provided.This book is a ‘must-have’ resource for engineers and other professionals in the telecommunications industry, working with cellular or wireless broadband technologies, giving an understanding of how to utilize the new technology in order to stay ahead of the competition.The authors of the book all work at Ericsson Research and have been deeply involved in 3G and 4G development and standardisation since the early days of 3G research. They are leading experts in the field and are today still actively contributing to the standardisation of LTE within 3GPP. Includes full details of the latest additions to the LTE Radio Access standards and technologies up to and including 3GPP Release 10Clear explanations of the role of the underlying technologies for LTE, including OFDM and MIMO Full coverage of LTE-Advanced, including LTE carrier aggregation, extended multi-antenna transmission, relaying functionality and heterogeneous deploymentsLTE radio interface architecture, physical layer, access procedures, MBMS, RF characteristics and system performance covered in detail
Excess ectopic fat storage is linked to type 2 diabetes. The importance of dietary fat composition for ectopic fat storage in humans is unknown. We investigated liver fat accumulation and body ...composition during overfeeding saturated fatty acids (SFAs) or polyunsaturated fatty acids (PUFAs). LIPOGAIN was a double-blind, parallel-group, randomized trial. Thirty-nine young and normal-weight individuals were overfed muffins high in SFAs (palm oil) or n-6 PUFAs (sunflower oil) for 7 weeks. Liver fat, visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (SAT), total adipose tissue, pancreatic fat, and lean tissue were assessed by magnetic resonance imaging. Transcriptomics were performed in SAT. Both groups gained similar weight. SFAs, however, markedly increased liver fat compared with PUFAs and caused a twofold larger increase in VAT than PUFAs. Conversely, PUFAs caused a nearly threefold larger increase in lean tissue than SFAs. Increase in liver fat directly correlated with changes in plasma SFAs and inversely with PUFAs. Genes involved in regulating energy dissipation, insulin resistance, body composition, and fat-cell differentiation in SAT were differentially regulated between diets, and associated with increased PUFAs in SAT. In conclusion, overeating SFAs promotes hepatic and visceral fat storage, whereas excess energy from PUFAs may instead promote lean tissue in healthy humans.
3G Evolution Erik Dahlman, Stefan Parkvall, Johan Skold, Per Beming
2010, 2007, 2007-12-31, c2007
eBook
This very up-to-date and practical book, written by engineers working closely in 3GPP, gives insight into the newest technologies and standards adopted by 3GPP, with detailed explanations of the ...specific solutions chosen and their implementation in HSPA and LTE. The key technologies presented include multi- carrier transmission, advanced single-carrier transmission, advanced receivers, OFDM, MIMO and adaptive antenna solutions, advanced radio resource management and protocols, and different radio network architectures. Their role and use in the context of mobile broadband access in general is explained. Both a high-level overview and more detailed step-by-step explanations of HSPA and LTE implementation are given. An overview of other related systems such as TD SCDMA, CDMA2000, and WIMAX is also provided.This is a 'must-have' resource for engineers and other professionals working with cellular or wireless broadband technologies who need to know how to utilize the new technology to stay ahead of the competition.The authors of the book all work at Ericsson Research and are deeply involved in 3G development and standardisation since the early days of 3G research. They are leading experts in the field and are today still actively contributing to the standardisation of both HSPA and LTE within 3GPP.* Gives the first explanation of the radio access technologies and key international standards for moving to the next stage of 3G evolution: fully operational mobile broadband * Describes the new technologies selected by the 3GPP to realise High Speed Packet Access (HSPA) and Long Term Evolution (LTE) for mobile broadband * Gives both higher-level overviews and detailed explanations of HSPA and LTE as specified by 3GPP
The move from reading to writing the human genome offers new opportunities to improve human health. The United States National Institutes of Health (NIH) Somatic Cell Genome Editing (SCGE) Consortium ...aims to accelerate the development of safer and more-effective methods to edit the genomes of disease-relevant somatic cells in patients, even in tissues that are difficult to reach. Here we discuss the consortium's plans to develop and benchmark approaches to induce and measure genome modifications, and to define downstream functional consequences of genome editing within human cells. Central to this effort is a rigorous and innovative approach that requires validation of the technology through third-party testing in small and large animals. New genome editors, delivery technologies and methods for tracking edited cells in vivo, as well as newly developed animal models and human biological systems, will be assembled-along with validated datasets-into an SCGE Toolkit, which will be disseminated widely to the biomedical research community. We visualize this toolkit-and the knowledge generated by its applications-as a means to accelerate the clinical development of new therapies for a wide range of conditions.
We developed a mathematical model to simulate the growth of tumor volume and its response to a single fraction of high dose irradiation. We made several key assumptions of the model. Tumor volume is ...composed of proliferating (or dividing) cancer cells and non-dividing (or dead) cells. Tumor growth rate (or tumor volume doubling time, Td) is proportional to the ratio of the volumes of tumor vasculature and the tumor. The vascular volume grows slower than the tumor by introducing the vascular growth retardation factor, theta. Upon irradiation the proliferating cells gradually die over a fixed time period after irradiation. Dead cells are cleared away with cell clearance time, Tcl. The model was applied to simulate pre-treatment growth and post-treatment radiation response of rat rhabdomyosarcoma tumor and metastatic brain tumors of five patients who were treated by Gamma Knife stereotactic radiosurgery (GKSRS). By selecting appropriate model parameters, we showed the temporal variation of the tumors for both the rat experiment and the clinical GKSRS cases could be easily replicated by the simple model. Additionally, the application of our model to the GKSRS cases showed that the alpha-value, which is an indicator of radiation sensitivity in the LQ model, and the retardation factor theta could be predictors of the post-treatment volume change. Since there is a large statistical uncertainty of this result due to the small sample size, a future clinical study with a larger number of patients is needed to confirm this finding.
Background
Different healthy food patterns may modify cardiometabolic risk. We investigated the effects of an isocaloric healthy Nordic diet on insulin sensitivity, lipid profile, blood pressure and ...inflammatory markers in people with metabolic syndrome.
Methods
We conducted a randomized dietary study lasting for 18–24 weeks in individuals with features of metabolic syndrome (mean age 55 years, BMI 31.6 kg m−2, 67% women). Altogether 309 individuals were screened, 200 started the intervention after 4‐week run‐in period, and 96 (proportion of dropouts 7.9%) and 70 individuals (dropouts 27%) completed the study, in the Healthy diet and Control diet groups, respectively. Healthy diet included whole‐grain products, berries, fruits and vegetables, rapeseed oil, three fish meals per week and low‐fat dairy products. An average Nordic diet served as a Control diet. Compliance was monitored by repeated 4‐day food diaries and fatty acid composition of serum phospholipids.
Results
Body weight remained stable, and no significant changes were observed in insulin sensitivity or blood pressure. Significant changes between the groups were found in non‐HDL cholesterol (−0.18, mmol L−1 95% CI −0.35; −0.01, P = 0.04), LDL to HDL cholesterol (−0.15, −0.28; −0.00, P = 0.046) and apolipoprotein B to apolipoprotein A1 ratios (−0.04, −0.07; −0.00, P = 0.025) favouring the Healthy diet. IL‐1 Ra increased during the Control diet (difference −84, −133; −37 ng L−1, P = 0.00053). Intakes of saturated fats (E%, beta estimate 4.28, 0.02; 8.53, P = 0.049) and magnesium (mg, −0.23, −0.41; −0.05, P = 0.012) were associated with IL‐1 Ra.
Conclusions
Healthy Nordic diet improved lipid profile and had a beneficial effect on low‐grade inflammation.
Multiple sclerosis (MS) is a chronic inflammatory and demyelinating disease of the central nervous system (CNS) with a complex etiology comprising a genetically determined predisposition and a ...suspected autoimmune pathogenesis. Experimental autoimmune encephalomyelitis (EAE) is an animal model for MS, which can be used to define susceptibility loci for autoimmune neuroinflammation. We have recently established a chronic relapsing EAE model characterized by inflammation and focal demyelination in the CNS by immunizing a variety of rat strains with the CNS-specific myelin oligodendrocyte glycoprotein (MOG). This model is more MS-like than any other rodent EAE model described up to now. Here we present the first systematic genome search for chromosomal regions linked to phenotypes of MOG-induced EAE in a (DA × ACI) F2 intercross. A genome-wide significant susceptibility locus linked to demyelination was identified on chromosome 18. This region has not been described in inflammatory diseases affecting other organs and the responsible gene or genes may thus be nervous system specific. Other chromosomal regions showing suggestive linkage to phenotypes of MOG-induced EAE were identified on chromosomes 10, 12 and 13. The chromo-some 10 and 12 regions have previously been linked to arthritis in DA rats, suggesting that they harbour immunoregulatory genes controlling general susceptibility to autoimmune diseases. We conclude that identification of susceptibility genes for MOG-induced EAE on rat chromosomes 10,12,13 and 18 may disclose important disease pathways for chronic inflammatory demyelinating diseases of the CNS such as MS.
We study how UE-to-UE interference impacts the performance, considering transmitter out-of-band (OOB) emissions and receiver blocking characteristics for homogenous 20 MHz LTE systems. For ...co-existing TDD systems on different carrier frequencies within the same band, UE-to-UE interference may occur in certain situations. The impact of such interference is evaluated for a hotspot scenario and compared to a uniform user distribution scenario, and is found to be significantly worse. When the number of scheduled users in the aggressor cell is high (e.g. >; 2), then receiver blocking impact, rather than the OOB emission, dominates the interference performance in hotspot scenario. Consequently, guard bands cannot be used to mitigate the receiver blocking impacts.
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