Literature review: potential non-thermal molecular effects of external radiofrequency electromagnetic fields on cancer.

INTRODUCTION: There is an ongoing scientific discussion, that anti-cancer effects induced by radiofrequency (RF)-hyperthermia might not be solely attributable to subsequent temperature elevations at the tumor site but also to non-temperature-induced effects. The exact molecular mechanisms behind said potential non-thermal RF effects remain largely elusive, however, limiting their therapeutical targetability. OBJECTIVE: Therefore, we aim to provide an overview of the current literature on potential non-temperature-induced molecular effects within cancer cells in response to RF-electromagnetic fields (RF-EMF). MATERIAL AND METHODS: This literature review was conducted following the PRISMA guidelines. For this purpose, a MeSH-term-defined literature search on MEDLINE (PubMed) and Scopus (Elsevier) was conducted on March 23rd, 2024. Essential criteria herein included the continuous wave RF-EMF nature (3 kHz - 300 GHz) of the source, the securing of temperature-controlled circumstances within the trials, and the preclinical nature of the trials. RESULTS: Analysis of the data processed in this review suggests that RF-EMF radiation of various frequencies seems to be able to induce significant non-temperature-induced anti-cancer effects. These effects span from mitotic arrest and growth inhibition to cancer cell death in the form of autophagy and apoptosis and appear to be mostly exclusive to cancer cells. Several cellular mechanisms were identified through which RF-EMF radiation potentially imposes its anti-cancer effects. Among those, by reviewing the included publications, we identified RF-EMF-induced ion channel activation, altered gene expression, altered membrane potentials, membrane oscillations, and blebbing, as well as changes in cytoskeletal structure and cell morphology. CONCLUSION: The existent literature points toward a yet untapped therapeutic potential of RF-EMF treatment, which might aid in damaging cancer cells through bio-electrical and electro-mechanical molecular mechanisms while minimizing adverse effects on healthy tissue cells. Further research is imperative to definitively confirm non-thermal EMF effects as well as to determine optimal cancer-type-specific RF-EMF frequencies, field intensities, and exposure intervals.

Regional hyperthermia for soft tissue sarcoma - a survey on current practice, controversies and consensus among 12 European centers.

PURPOSE: To analyze the current practice of regional hyperthermia (RHT) for soft tissue sarcoma (STS) at 12 European centers to provide an overview, find consensuses and identify controversies necessary for future guidelines and clinical trials. METHODS: In this cross-sectional survey study, a 27-item questionnaire assessing clinical subjects and procedural details on RHT for STS was distributed to 12 European cancer centers for RHT. RESULTS: We have identified seven controversies and five consensus points. Of 12 centers, 6 offer both, RHT with chemotherapy (CTX) or with radiotherapy (RT). Two centers only offer RHT with CTX and four centers only offer RHT with RT. All 12 centers apply RHT for localized, high-risk STS of the extremities, trunk wall and retroperitoneum. However, eight centers also use RHT in metastatic STS, five in palliative STS, eight for superficial STS and six for low-grade STS. Pretherapeutic imaging for RHT treatment planning is used by 10 centers, 9 centers set 40-43 °C as the intratumoral target temperature, and all centers use skin detectors or probes in body orifices for thermometry. DISCUSSION: There is disagreement regarding the integration of RHT in contemporary interdisciplinary care of STS patients. Many clinical controversies exist that require a standardized consensus guideline and innovative study ideas. At the same time, our data has shown that existing guidelines and decades of experience with the technique of RHT have mostly standardized procedural aspects. CONCLUSIONS: The provided results may serve as a basis for future guidelines and inform future clinical trials for RHT in STS patients.

Survey in radiation oncology departments in Germany, Austria, and Switzerland: state of digitalization by 2023.

PURPOSE: The aim of this work was to assess the current state of digitalization in radiation oncology departments in Germany, Austria, and Switzerland. METHODS: A comprehensive survey was conducted in a digital format, consisting of 53 questions that covered various aspects of digitalization including patient workflow, departmental organization, radiotherapy planning, and employee-related aspects. RESULTS: Overall, 120 forms were eligible for evaluation. Participants were mainly physicians or medical physicists responsible for digitalization aspects in their departments. Nearly 70% of the institutions used electronic patient records, with 50% being completely paperless. However, the use of smartphone apps for electronic patient reported outcomes (ePROMs) and digital health applications (DIGA) was limited (9% and 4.9%, respectively). In total, 70.8% of the radio-oncology departments had interfaces with diagnostic departments, and 36% had digital interchanges with other clinics. Communication with external partners was realized mainly through fax (72%), e­mails (55%), postal letters (63%), or other digital exchange formats (28%). Almost half of the institutions (49%) had dedicated IT staff for their operations. CONCLUSION: To the best of our knowledge, this survey is the first of its kind conducted in German-speaking radiation oncology departments within the medical field. The findings suggest that there is a varied level of digitalization implementation within these departments, with certain areas exhibiting lower rates of digitalization that could benefit from targeted improvement initiatives.

Natural Analogues in pH Variability and Predictability across the Coastal Pacific Estuaries: Extrapolation of the Increased Oyster Dissolution under Increased pH Amplitude and Low Predictability Related to Ocean Acidification.

Coastal-estuarine habitats are rapidly changing due to global climate change, with impacts influenced by the variability of carbonate chemistry conditions. However, our understanding of the responses of ecologically and economically important calcifiers to pH variability and temporal variation is limited, particularly with respect to shell-building processes. We investigated the mechanisms driving biomineralogical and physiological responses in juveniles of introduced (Pacific; Crassostrea gigas) and native (Olympia; Ostrea lurida) oysters under flow-through experimental conditions over a six-week period that simulate current and future conditions: static control and low pH (8.0 and 7.7); low pH with fluctuating (24-h) amplitude (7.7 ± 0.2 and 7.7 ± 0.5); and high-frequency (12-h) fluctuating (8.0 ± 0.2) treatment. The oysters showed physiological tolerance in vital processes, including calcification, respiration, clearance, and survival. However, shell dissolution significantly increased with larger amplitudes of pH variability compared to static pH conditions, attributable to the longer cumulative exposure to lower pH conditions, with the dissolution threshold of pH 7.7 with 0.2 amplitude. Moreover, the high-frequency treatment triggered significantly greater dissolution, likely because of the oyster's inability to respond to the unpredictable frequency of variations. The experimental findings were extrapolated to provide context for conditions existing in several Pacific coastal estuaries, with time series analyses demonstrating unique signatures of pH predictability and variability in these habitats, indicating potentially benefiting effects on fitness in these habitats. These implications are crucial for evaluating the suitability of coastal habitats for aquaculture, adaptation, and carbon dioxide removal strategies.

Experimental and computational evaluation of capacitive hyperthermia.

OBJECTIVE: Hyperthermia as an enhancer of radio- and/or chemotherapy has been confirmed by various trials. Quite a few positive randomized trials have been carried out with capacitive hyperthermia systems (CHS), even though specific absorption rates (SAR) in deep regions are known to be inferior to the established annular-phased array techniques. Due to a lack of systematic SAR measurements for current capacitive technology, we performed phantom measurements in combination with simulation studies. MATERIALS AND METHODS: According to the current guidelines, homogeneous and inhomogeneous agarose phantoms were manufactured for the commercial CHS Celsius42. Temperature/time curves were registered, and specific absorption rate (SAR) profiles and distributions were derived using the temperature gradient method. We implemented models for electrodes and phantom setups for simulation studies using Sim4Life. RESULTS: For a standard total power of 200 W, we measured effective SAR until depths of 6-8 cm in a homogeneous phantom, which indicates fair heating conditions for tumor diseases in superficial and intermediate depths. A fat layer of 1 cm strongly weakens the SAR, but 10-20 W/kg are still achieved in intermediate to deep regions (2-10 cm). In the phantom setup with integrated bone, we measured low SAR of 5-10 W/kg in the cancellous bone. Our simulations could fairly describe the measured SAR distributions, but predict tendentially higher SAR than measured. Additional simulations suggest that we would achieve higher SAR with vital fatty tissue and bone metastases in clinical situations. CONCLUSION: Capacitive systems are suitable to heat superficial and medium-deep tumors as well as some bone metastases, and CHS application is feasible for a specific class of patients with pelvic and abdominal tumors. These findings are consistent with positive clinical studies.

Tetramodal therapy with transurethral resection followed by chemoradiation in combination with hyperthermia for muscle-invasive bladder cancer: early results of a multicenter phase IIB study.

BACKGROUND: Transurethral resection of bladder tumor (TUR-BT) followed by chemoradiation (CRT) is a valid treatment option for patients with muscle-invasive bladder cancer (MIBC). This study aimed to investigate the efficacy of a tetramodal approach with additional regional hyperthermia (RHT). METHODS: Patients with stages T2-4 MIBC were recruited at two institutions. Treatment consisted of TUR-BT followed by radiotherapy at doses of 57-58.2 Gy with concurrent weekly platinum-based chemotherapy and weekly deep RHT (41-43 °C, 60 min) within two hours of radiotherapy. The primary endpoint was a complete response six weeks after the end of treatment. Further endpoints were cystectomy-free rate, progression-free survival (PFS), local recurrence-free survival (LRFS), overall survival (OS) and toxicity. Quality of life (QoL) was assessed at follow-up using the EORTC-QLQ-C30 and QLQ-BM30 questionnaires. Due to slow accrual, an interim analysis was performed after the first stage of the two-stage design. RESULTS: Altogether 27 patients were included in the first stage, of these 21 patients with a median age of 73 years were assessable. The complete response rate of evaluable patients six weeks after therapy was 93%. The 2-year cystectomy-free rate, PFS, LRFS and OS rates were 95%, 76%, 81% and 86%, respectively. Tetramodal treatment was well tolerated with acute and late G3-4 toxicities of 10% and 13%, respectively, and a tendency to improve symptom-related quality of life (QoL) one year after therapy. CONCLUSION: Tetramodal therapy of T2-T4 MIBC is promising with excellent local response, moderate toxicity and good QoL. This study deserves continuation into the second stage.

Multivariate Analysis of Sediment Toxicity in an Ocean Ecosystem: A Southern California Bight Case Study.

Contaminated sediments can negatively affect aquatic organisms and beneficial uses of coastal regions. Monitoring programs typically collect many indicators of sediment toxicity, yet multivariate approaches that comprehensively evaluate data across heterogeneous spatial environments are frequently not performed. In this paper, we explore a multivariate approach to show that a list of suspected drivers of sediment toxicity to native Mytilus galloprovincialis (mussel) and Eohaustorius estuarius (a marine amphipod) population can be narrowed down without excluding samples, and that redundancies in sampling sites can be identified and isolated. Using a 153 × 28 data matrix assembled from a southern California-wide bight monitoring program, we demonstrate by this approach that Port of Los Angeles (PLA) and San Diego Bay (SDB) contained the most toxic sediments in the bight in 2008, the nature of which was unique to each locality. (Note: Little toxicity was observed here in 2013 and 2018.) In PLA sediments, mussels were more affected than amphipods, with higher survivability associated with low Hg and Sn levels. Conversely, amphipods had higher mortality than mussel embryos in SDB sediments, with higher survivability associated with low Be and Co levels. Nitrogen, organic content, and finer sediment particles were not related to the survivability of these organisms.

Improved patient-specific hyperthermia planning based on parametrized electromagnetic and thermal models for the SIGMA-30 applicator.

OBJECTIVE: To create an improved planning method for pediatric regional hyperthermia (RHT) using the SIGMA-30 applicator (SIGMA-30). MATERIALS AND METHODS: An electromagnetic model of SIGMA-30 was generated for use with the finite-difference time-domain (FDTD) method. Applying special MATLAB-based algorithms, voxel models of a pediatric patient with pelvic rhabdomyosarcoma were created from Computed-Tomography (CT) contours for use with the FDTD method and the finite-difference (FD) method capable of using either temperature-independent or temperature-dependent perfusion models for solving the Bioheat Transfer Equation (BHTE). Patient models were parametrized regarding, first, the positioning in the applicator, second, the absorbed power range and, third, different perfusion models, resulting in the so-called Parametrized Treatment Models (PTMs). A novel dedicated optimization procedure was developed based on quantitative comparison of numerical calculations against temperature and power measurements from two RHT therapies. RESULTS: Using measured data, a realistic absorbed power range in the patient model was estimated. Within this range, several FDTD and BHTE runs were performed and, applying the aforementioned optimization scheme, the best PTMs and perfusion models were identified for each therapy via a retrospective comparison with measurements in 14 temperature sensor positions: 5 in the tumor, 8 in rectum and one in bladder. CONCLUSION: A novel dedicated optimization procedure for identification of suitable patient-specific electromagnetic and thermal models, which can be used for improved patient planning, was developed and evaluated by comparison with treatment-derived measurements using SIGMA-30. The optimization procedure can be extended to other hyperthermia applicators and to other patient types, including adults.

Combined tumor plus nontumor interim FDG-PET parameters are prognostic for response to chemoradiation in squamous cell esophageal cancer.

We have investigated the prognostic value of two novel interim 18 F-fluorodeoxyglucose positron emission tomography (FDG-PET) parameters in patients undergoing chemoradiation (CRT) for esophageal squamous cell carcinoma (ESCC): one tumor parameter (maximal standardized uptake ratio rSUR) and one normal tissue parameter (change of FDG uptake within irradiated nontumor-affected esophagus ∆SUVNTO ). PET data of 134 European and Chinese patients were analyzed. Parameter establishment was based on 36 patients undergoing preoperative CRT plus surgery, validation was performed in 98 patients receiving definitive CRT. Patients received PET imaging prior and during fourth week of CRT. Clinical parameters, baseline PET parameters, and interim PET parameters (rSUR and ∆SUVNTO ) were analyzed and compared to event-free survival (EFS), overall survival (OS), loco-regional control (LRC) and freedom from distant metastases (FFDM). Combining rSUR and ∆SUVNTO revealed a strong prognostic impact on EFS, OS, LRC and FFDM in patients undergoing preoperative CRT. In the definitive CRT cohort, univariate analysis with respect to EFS revealed several staging plus both previously established interim PET parameters as significant prognostic factors. Multivariate analyses revealed only rSUR and ∆SUVNTO as independent prognostic factors (p = 0.003, p = 0.008). Combination of these parameters with the cutoff established in preoperative CRT revealed excellent discrimination of patients with a long or short EFS (73% vs. 17% at 2 years, respectively) and significantly discriminated all other endpoints (OS, p < 0.001; LRC, p < 0.001; FFDM, p = 0.02), even in subgroups. Combined use of interim FDG-PET derived parameters ∆SUVNTO and rSUR seems to have predictive potential, allowing to select responders for definitive CRT and omission of surgery.

Image-guided dose-escalated radiation therapy for localized prostate cancer with helical tomotherapy.

PURPOSE: To evaluate treatment outcomes for patients with localized prostate cancer who were treated with dose-escalated primary image-guided radiation therapy (IGRT). METHODS: We retrospectively analyzed 88 consecutive patients treated using helical tomotherapy with daily megavoltage CTs (MVCT). Patients were prescribed daily doses of 1.8 Gy to the planning target volume (PTV) and 2 Gy to the clinical target volume (CTV). Low- and favorable intermediate-risk patients received a minimum total dose of 72 Gy to the PTV and up to 80 Gy to the CTV. Unfavorable intermediate-risk and high-risk patients received a minimum total dose of 75.6 Gy to the PTV and up to 84 Gy to the CTV. We assessed freedom from biochemical relapse (FFBF), 5­year biochemical recurrence-free survival (5-bRFS), distant metastasis-free survival (5-dMFS), and cancer-specific survival (5-CSS) as well as acute and late genitourinary (GU) and gastrointestinal (GI) toxicity. RESULTS: Among our cohort, 11.4% were low-risk, 50% intermediate-risk, and 38.6% high-risk patients according to the D'Amico criteria. Median follow-up was 66 months (range 8-83 months). FFBF was 100%, 97.7%, and 90.7%; 5­bRFS was 100%, 92.8%, and 70.4%; 5­dMFS was 100%, 92.7%, and 70.4%; and 5­CSS was 100%, 97.4%, and 89.8% for low-, intermediate-, and high-risk patients, respectively. Grades 2 and 3 toxicity occurred at the following rates: acute GU toxicity 39.8% and 1.1%, acute GI toxicity 12.5% and 0%, late GU toxicity 19.3% and 4.5%, and late GI toxicity 4.5% and 1.1% of patients, respectively. No toxicity >grade 3 was observed. CONCLUSION: Risk-adapted dose-escalated IGRT with helical tomotherapy of up to 84 Gy is a feasible and well-tolerable treatment scheme with promising oncological results.

Role of combined radiation and androgen deprivation therapy in intermediate-risk prostate cancer : Statement from the DEGRO working group on prostate cancer.

OBJECTIVE: This article aims to provide an overview of the role of combined radiation and androgen deprivation (ADT) therapy in patients with intermediate-risk prostate cancer. MATERIALS AND METHODS: The current German, European, and NCCN (National Comprehensive Cancer Network) guidelines as well as relevant literature in the PubMed database which provide information on sub-classification within the intermediate-risk group and the use of ADT in terms of oncological outcome were reviewed. RESULTS: Different recommendations for risk-group assessment of patients with localized prostate cancer are available. Subdivision of intermediate risk into a favorable and an unfavorable group seems to be justified to allow for a more individualized therapy in a quite heterogenous group of patients. So far, multiple randomized trials have shown a benefit when radiation therapy (RT) is combined with ADT. The use of dose-escalated RT without ADT also appears to be an adequate therapy associated with a very low rate of cancer-specific deaths. Therefore, taking into account the increased rate of toxicity associated with ADT, dose-escalated RT alone might be justified, especially in favorable intermediate-risk patients. CONCLUSION: Dose-escalated RT alone appears to be an appropriate treatment in favorable intermediate-risk patients. Addition of short course ADT (4-6 months) might improve outcomes in unfavorable intermediate-risk patients.

Radiofrequency applicator concepts for thermal magnetic resonance of brain tumors at 297 MHz (7.0 Tesla).

Purpose: Thermal intervention is a potent sensitizer of cells to chemo- and radiotherapy in cancer treatment. Glioblastoma multiforme (GBM) is a potential clinical target, given the cancer's aggressive nature and resistance to current treatment options. The annular phased array (APA) technique employing electromagnetic waves in the radiofrequency (RF) range allows for localized temperature increase in deep seated target volumes (TVs). Reports on clinical applications of the APA technique in the brain are still missing. Ultrahigh field magnetic resonance (MR) employs higher frequencies than conventional MR and has potential to provide focal temperature manipulation, high resolution imaging and noninvasive temperature monitoring using an integrated RF applicator (ThermalMR). This work examines the applicability of RF applicator concepts for ThermalMR of brain tumors at 297 MHz (7.0 Tesla).Methods: Electromagnetic field (EMF) simulations are performed for clinically realistic data based on GBM patients. Two algorithms are used for specific RF energy absorption rate based thermal intervention planning for small and large TVs in the brain, aiming at maximum RF power deposition or RF power uniformity in the TV for 10 RF applicator designs.Results: For both TVs , the power optimization outperformed the uniformity optimization. The best results for the small TV are obtained for the 16 element interleaved RF applicator using an elliptical antenna arrangement with water bolus. The two row elliptical RF applicator yielded the best result for the large TV.Discussion: This work investigates the capacity of ThermalMR to achieve targeted thermal interventions in model systems resembling human brain tissue and brain tumors.

Locoregional peritoneal hyperthermia to enhance the effectiveness of chemotherapy in patients with peritoneal carcinomatosis: a simulation study comparing different locoregional heating systems.

Introduction: Intravenous chemotherapy plus abdominal locoregional hyperthermia is explored as a noninvasive alternative to hyperthermic intraperitoneal chemotherapy (HIPEC) in treatment of peritoneal carcinomatosis (PC). First clinical results demonstrate feasibility, but survival data show mixed results and for pancreatic and gastric origin results are not better than expected for chemotherapy alone. In this study, computer simulations are performed to compare the effectiveness of peritoneal heating for five different locoregional heating systems.Methods: Simulations of peritoneal heating were performed for a phantom and two pancreatic cancer patients, using the Thermotron RF8, the AMC-4/ALBA-4D system, the BSD Sigma-60 and Sigma-Eye system, and the AMC-8 system. Specific absorption rate (SAR) distributions were optimized and evaluated. Next, to provide an indication of possible enhancement factors, the corresponding temperature distributions and thermal enhancement ratio (TER) of oxaliplatin were estimated.Results: Both phantom and patient simulations showed a relatively poor SAR coverage for the Thermotron RF8, a fairly good coverage for the AMC-4/ALBA-4D, Sigma-60, and Sigma-Eye systems, and the best and most homogeneous coverage for the AMC-8 system. In at least 50% of the peritoneum, 35-45 W/kg was predicted. Thermal simulations confirmed these favorable peritoneal heating properties of the AMC-8 system and TER values of ∼1.4-1.5 were predicted in at least 50% of the peritoneum.Conclusion: Locoregional peritoneal heating with the AMC-8 system yields more favorable heating patterns compared to other clinically used locoregional heating devices. Therefore, results of this study may promote the use of the AMC-8 system for locoregional hyperthermia in future multidisciplinary studies for treatment of PC.

Phytoplankton decline in the eastern North Pacific transition zone associated with atmospheric blocking.

Global climate change can significantly influence oceanic phytoplankton dynamics, and thus biogeochemical cycles and marine food webs. However, associative explanations based on the correlation between chlorophyll-a concentration (Chl-a) and climatic indices is inadequate to describe the mechanism of the connection between climate change, large-scale atmospheric dynamics, and phytoplankton variability. Here, by analyzing multiple satellite observations of Chl-a and atmospheric conditions from National Center for Environmental Prediction/National Center for Atmospheric Research reanalysis datasets, we show that high-latitude atmospheric blocking events over Alaska are the primary drivers of the recent decline of Chl-a in the eastern North Pacific transition zone. These blocking events were associated with the persistence of large-scale atmosphere pressure fields that decreased westerly winds and southward Ekman transport over the subarctic ocean gyre. Reduced southward Ekman transport leads to reductions in nutrient availability to phytoplankton in the transition zone. The findings describe a previously unidentified climatic factor that contributed to the recent decline of phytoplankton in this region and propose a mechanism of the top-down teleconnection between the high-latitude atmospheric circulation anomalies and the subtropical oceanic primary productivity. The results also highlight the importance of understanding teleconnection among atmosphere-ocean interactions as a means to anticipate future climate change impacts on oceanic primary production.

Physical analysis of temperature-dependent effects of amplitude-modulated electromagnetic hyperthermia.

Purpose: Preclinical studies and clinical observations suggest that amplitude modulation (AM) below 100 kHz may enhance the intratumoral power absorption of radiofrequency hyperthermia at 13.56 MHz; however, it remains unclear whether AM induces temperature-dependent effects.Methods: We established tumor models assuming typical tumor architectures or cell suspensions to analyze the effects of additional power dissipation. The preconditions for demodulation at cell membranes in situ were outlined. The bioheat transfer equation was solved analytically for the selected models and the possibility of circumscribed temperature increases (point heating) with dependency on the specific absorption rate (SAR) peaks was estimated for centimeter down to nanometer scales.Results: Very-low-frequency (VLF) AM radiofrequency can increase the SAR in the extracellular space or necrosis of tumors as compared to radiofrequencies alone. Such modulation-derived SAR peaks can induce higher temperatures (hot spots) in tumors with necrotic areas of millimeter to centimeter size. However, for lesions <1 cm, excessive (unrealistic) SAR > 1000, 10,000 and 1014 W/kg for diameters of ∼5 mm, ∼1 mm and ∼10 nm (nanoheating), respectively, would be required to explain the cell kill observed in pre-clinical and clinical data, even with VLF modulation.Conclusion: Our analysis suggests that VLF AM of radiofrequency hyperthermia for a theoretical tumor model cannot induce relevant temperature-dependent effects, as the associated temperature increases caused by the resultant SAR peaks are too small. Further investigation of possible non-temperature-dependent effects is recommended.

NeuralNetTools: Visualization and Analysis Tools for Neural Networks.

Supervised neural networks have been applied as a machine learning technique to identify and predict emergent patterns among multiple variables. A common criticism of these methods is the inability to characterize relationships among variables from a fitted model. Although several techniques have been proposed to "illuminate the black box", they have not been made available in an open-source programming environment. This article describes the NeuralNetTools package that can be used for the interpretation of supervised neural network models created in R. Functions in the package can be used to visualize a model using a neural network interpretation diagram, evaluate variable importance by disaggregating the model weights, and perform a sensitivity analysis of the response variables to changes in the input variables. Methods are provided for objects from many of the common neural network packages in R, including caret, neuralnet, nnet, and RSNNS. The article provides a brief overview of the theoretical foundation of neural networks, a description of the package structure and functions, and an applied example to provide a context for model development with NeuralNetTools. Overall, the package provides a toolset for neural networks that complements existing quantitative techniques for data-intensive exploration.

A novel imputation methodology for time series based on pattern sequence forecasting.

The Pattern Sequence Forecasting (PSF) algorithm is a previously described algorithm that identifies patterns in time series data and forecasts values using periodic characteristics of the observations. A new method for univariate time series is introduced that modifies the PSF algorithm to simultaneously forecast and backcast missing values for imputation. The imputePSF method extends PSF by characterizing repeating patterns of existing observations to provide a more precise estimate of missing values compared to more conventional methods, such as replacement with means or last observation carried forward. The imputation accuracy of imputePSF was evaluated by simulating varying amounts of missing observations with three univariate datasets. Comparisons of imputePSF with well-established methods using the same simulations demonstrated an overall reduction in error estimates. The imputePSF algorithm can produce more precise imputations on appropriate datasets, particularly those with periodic and repeating patterns.

Dosimetric implications of inter- and intrafractional prostate positioning errors during tomotherapy : Comparison of gold marker-based registrations with native MVCT.

INTRODUCTION: For high-dose radiation therapy (RT) of prostate cancer, image-guided (IGRT) and intensity-modulated RT (IMRT) approaches are standard. Less is known regarding comparisons of different IGRT techniques and the resulting residual errors, as well as regarding their influences on dose distributions. PATIENTS AND METHODS: A total of 58 patients who received tomotherapy-based RT up to 84 Gy for high-risk prostate cancer underwent IGRT based either on daily megavoltage CT (MVCT) alone (n = 43) or the additional use of gold markers (n = 15) under routine conditions. Planned Adaptive (Accuray Inc., Madison, WI, USA) software was used for elaborated offline analysis to quantify residual interfractional prostate positioning errors, along with systematic and random errors and the resulting safety margins after both IGRT approaches. Dosimetric parameters for clinical target volume (CTV) coverage and exposition of organs at risk (OAR) were also analyzed and compared. Interfractional as well as intrafractional displacements were determined. RESULTS: Particularly in the vertical direction, residual interfractional positioning errors were reduced using the gold marker-based approach, but dosimetric differences were moderate and the clinical relevance relatively small. Intrafractional prostate motion proved to be quite high, with displacements of 1-3 mm; however, these did not result in additional dosimetric impairments. CONCLUSION: Residual interfractional positioning errors were reduced using gold marker-based IGRT; however, this resulted in only slightly different final dose distributions. Therefore, daily MVCT-based IGRT without markers might be a valid alternative.

Parameter sensitivity and identifiability for a biogeochemical model of hypoxia in the northern Gulf of Mexico.

Local sensitivity analyses and identifiable parameter subsets were used to describe numerical constraints of a hypoxia model for bottom waters of the northern Gulf of Mexico. The sensitivity of state variables differed considerably with parameter changes, although most variables were responsive to changes in parameters that influenced planktonic growth rates and less sensitive to physical or chemical parameters. Variation in sensitivity had a direct correspondence with identifiability, such that only small subsets of the complete parameter set had unique effects on the model output. Selecting parameters by decreasing sensitivity demonstrated that only eight of 51 total parameters had a sufficiently unique effect on model output for accurate calibration. As a result, parameter selection heuristics were used to identify parameters for model calibration that depended on combined effects on output, relative sensitivity of each parameter, and ecological categories for the biogeochemical equations. The calibrated zero-dimensional (0-D) unit of the hypoxia model had improved fit to the observed data if sensitive phytoplankton parameters were included in an identifiable subset. Extension of results to a three-dimensional grid of the Gulf of Mexico showed that sensitive parameters for the 0-D model translated to non-trivial changes in the areal estimates of hypoxia.

Numerical and qualitative contrasts of two statistical models for water quality change in tidal waters.

Two statistical approaches, weighted regression on time, discharge, and season (WRTDS) and generalized additive models (GAMs), have recently been used to evaluate water quality trends in estuaries. Both models have been used in similar contexts despite differences in statistical foundations and products. This study provided an empirical and qualitative comparison of both models using 29 years of data for two discrete time series of chlorophyll-a (chl-a) in the Patuxent River Estuary. Empirical descriptions of each model were based on predictive performance against the observed data, ability to reproduce flow-normalized trends with simulated data, and comparisons of performance with validation datasets. Between-model differences were apparent but minor and both models had comparable abilities to remove flow effects from simulated time series. Both models similarly predicted observations for missing data with different characteristics. Trends from each model revealed distinct mainstem influences of the Chesapeake Bay with both models predicting a roughly 65% increase in chl-a over time in the lower estuary, whereas flow-normalized predictions for the upper estuary showed a more dynamic pattern, with a nearly 100% increase in chl-a in the last 10 years. Qualitative comparisons highlighted important differences in the statistical structure, available products, and characteristics of the data and desired analysis.