A GPU-based multi-criteria optimization algorithm for HDR brachytherapy

Currently in HDR brachytherapy planning, a manual fine-tuning of an objective function is necessary to obtain case-specific valid plans. This study intends to facilitate this process by proposing a patient-specific inverse planning algorithm for HDR prostate brachytherapy: GPU-based multi-criteria optimization (gMCO). Two GPU-based optimization engines including simulated annealing (gSA) and a quasi-Newton optimizer (gL-BFGS) were implemented to compute multiple plans in parallel. After evaluating the equivalence and the computation performance of these two optimization engines, one preferred optimization engine was selected for the gMCO algorithm. Five hundred sixty-two previously treated prostate HDR cases were divided into validation set (100) and test set (462). In the validation set, the number of Pareto optimal plans to achieve the best plan quality was determined for the gMCO algorithm. In the test set, gMCO plans were compared with the physician-approved clinical plans. Over 462 cases, the number of clinically valid plans was 428 (92.6%) for clinical plans and 461 (99.8%) for gMCO plans. The number of valid plans with target V100 coverage greater than 95% was 288 (62.3%) for clinical plans and 414 (89.6%) for gMCO plans. The mean planning time was 9.4 s for the gMCO algorithm to generate 1000 Pareto optimal plans. In conclusion, gL-BFGS is able to compute thousands of SA equivalent treatment plans within a short time frame. Powered by gL-BFGS, an ultra-fast and robust multi-criteria optimization algorithm was implemented for HDR prostate brachytherapy. A large-scale comparison against physician approved clinical plans showed that treatment plan quality could be improved and planning time could be significantly reduced with the proposed gMCO algorithm.Comment: 18 pages, 7 figure

Retinal thickness in eyes with mild nonproliferative retinopathy in patients with type 2 diabetes mellitus: comparison of measurements obtained by retinal thickness analysis and optical coherence tomography

OBJECTIVE: To compare measurements of retinal thickness in eyes with mild nonproliferative retinopathy in patients with type 2 diabetes mellitus using 2 different techniques: the retinal thickness analyzer (RTA) and optical coherence tomography (OCT). METHODS: Twenty-eight eyes from 28 patients with type 2 diabetes mellitus and mild nonproliferative retinopathy were classified according to the Wisconsin grading system by 7-field stereoscopic fundus photography. Ten eyes were classified as level 10 (absence of visible lesions) and 18 as level 20 or 35 (minimal retinopathy). All eyes were examined by the RTA and OCT. Healthy populations were used to establish reference maps for the RTA (n = 14; mean age, 48 years; age range, 42-55 years) and OCT (n = 10; mean age, 56 years; age range, 43-68 years). Reference maps were computed using the means + 2 SDs of the values obtained for each location. Increases in thickness were computed as a percentage of increase over these reference maps. RESULTS: The RTA detected increases in thickness in 1 or more locations in 24 of the 28 diabetic eyes examined, whereas OCT detected increases in only 3 eyes. The percentages of increase detected by the RTA ranged from 0.3% to 73.5%, whereas OCT detected percentages of increase of 0.3% to 4.8%. CONCLUSION: Optical coherence tomography is less sensitive than the RTA in detecting localized increases in retinal thickness in the initial stages of diabetic retinal disease

A semiempirical computational study of aziridinone and diaziridinone reactivity.

The results of semiempirical molecular orbital calculations performed on aziridinone and diaziridinone employing the MNDO, AM1, and PM3 molecular models are presented. The AM1 method, which best reproduces ground-state molecular properties, is used to calculate electronic parameters and the use of these parameters for the evaluation of reactivity is discussed.221222

The inflammatory response in the regression of lumbar disc herniation

Lumbar disc herniation (LDH) is highly associated with inflammation in the context of low back pain. Currently, inflammation is associated with adverse symptoms related to the stimulation of nerve fibers that may lead to pain. However, inflammation has also been indicated as the main factor responsible for LDH regression. This apparent controversy places inflammation as a good prognostic indicator of spontaneous regression of LDH. This review addresses the molecular and cellular mechanisms involved in LDH regression, including matrix remodeling and neovascularization, in the scope of the clinical decision on conservative versus surgical intervention. Based on the evidence, a special focus on the inflammatory response in the LDH context is given, particularly in the monocyte/macrophage role. The phenomenon of spontaneous regression of LDH, extensively reported in the literature, is therefore analyzed here under the perspective of the modulatory role of inflammation.This work was financed by project “Bioengineered Therapies for infectious diseases and tissue regeneration” (NORTE-01-0145-FEDER-000012), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), by FEDER/COMPETE 2020 (POCI), Portugal 2020, and by Portuguese funds through FCT/MCTES in the framework of the project "Institute for Research and Innovation in Health Sciences" (POCI-01- 0145-FEDER-007274). Cunha C and Gonçalves RM acknowledge FCT by their postdoc fellowship (SFRH/BDP/87071/2012) and FCT Investigator Grant (IF/ 00638/2014), respectively. Silva AJ acknowledges her fellowship under the framework of the project Norte-01-0145-FEDER-000012

Topical and Systemic Cannabidiol Improves Trinitrobenzene Sulfonic Acid Colitis in Mice

Background/Aims: Compounds of Cannabis sativa are known to exert anti-inflammatory properties, some of them without inducing psychotropic side effects. Cannabidiol (CBD) is such a side effect-free phytocannabinoid that improves chemically induced colitis in rodents when given intraperitoneally. Here, we tested the possibility whether rectal and oral application of CBD would also ameliorate colonic inflammation, as these routes of application may represent a more appropriate way for delivering drugs in human colitis. Methods: Colitis was induced in CD1 mice by trinitrobenzene sulfonic acid. Individual groups were either treated with CBD intraperitoneally (10 mg/kg), orally (20 mg/kg) or intrarectally (20 mg/kg). Colitis was evaluated by macroscopic scoring, histopathology and the myeloperoxidase (MPO) assay. Results: Intraperitoneal treatment of mice with CBD led to improvement of colonic inflammation. Intrarectal treatment with CBD also led to a significant improvement of disease parameters and to a decrease in MPO activity while oral treatment, using the same dose as per rectum, had no ameliorating effect on colitis. Conclusion: The data of this study indicate that in addition to intraperitoneal application, intrarectal delivery of cannabinoids may represent a useful therapeutic administration route for the treatment of colonic inflammation. Copyright (C) 2012 S. Karger AG, Base

Catastrophic photometric redshift errors: weak lensing survey requirements

We study the sensitivity of weak lensing surveys to the effects of catastrophic redshift errors - cases where the true redshift is misestimated by a significant amount. To compute the biases in cosmological parameters, we adopt an efficient linearized analysis where the redshift errors are directly related to shifts in the weak lensing convergence power spectra. We estimate the number Nspec of unbiased spectroscopic redshifts needed to determine the catastrophic error rate well enough that biases in cosmological parameters are below statistical errors of weak lensing tomography. While the straightforward estimate of Nspec is ~10^6 we find that using only the photometric redshifts with z<=2.5 leads to a drastic reduction in Nspec to ~30,000 while negligibly increasing statistical errors in dark energy parameters. Therefore, the size of spectroscopic survey needed to control catastrophic errors is similar to that previously deemed necessary to constrain the core of the z_s-z_p distribution. We also study the efficacy of the recent proposal to measure redshift errors by cross-correlation between the photo-z and spectroscopic samples. We find that this method requires ~10% a priori knowledge of the bias and stochasticity of the outlier population, and is also easily confounded by lensing magnification bias. The cross-correlation method is therefore unlikely to supplant the need for a complete spectroscopic redshift survey of the source population.Comment: 14 pages, 3 figure

rASUDAS: A New Web-Based Application for Estimating Ancestry from Tooth Morphology

The use of crown and root morphology to estimate population relationships has a long history in dental anthropology. Over the past two decades, methods employing dental morphology within forensic anthropology have been formalized with the incorporation of statistical models. This paper presents a new web-based application (rASUDAS) that estimates the ancestry of unknown individuals based on their suite of tooth crown and root traits. The application utilizes 21 independent traits that were scored following the Arizona State University Dental Anthropology System (ASUDAS). The reference sample represents approximately 30,000 individuals from seven biogeographic regions. A naive Bayes classifier algorithm was created in the R open source programming language to assign posterior probabilities for individual group assignment. To test the application, 150 individuals were selected from the C. G. Turner II database with the proviso that an individual had to be scored for a minimum of 12 of the 21 traits. In a seven-group analysis, the model correctly assigned individuals to groups 51.8% of the time. In a four-group analysis, classification accuracy improved to 66.7%. With three groups, accuracy was at 72.7%. It is still necessary to validate the program using forensic cases and to augment the reference sample with modern skeletal data. However, results from the beta version of rASUDAS are presented as proof of concept on the potential of dental morphology in ancestry estimation in forensic contexts

The systemic immune response to collagen-induced arthritis and the impact of bone injury in inflammatory conditions

Rheumatoid arthritis (RA) is a systemic disease that affects the osteoarticular system, associated with bone fragility and increased risk of fractures. Herein, we aimed to characterize the systemic impact of the rat collagen-induced arthritis (CIA) model and explore its combination with femoral bone defect (FD). The impact of CIA on endogenous mesenchymal stem/stromal cells (MSC) was also investigated. CIA induction led to enlarged, more proliferative, spleen and draining lymph nodes, with altered proportion of lymphoid populations. Upon FD, CIA animals increased the systemic myeloid cell proportions, and their expression of co-stimulatory molecules CD40 and CD86. Screening plasma cytokine/chemokine levels showed increased tumor necrosis factor-a (TNF-a), Interleukin (IL)-17, IL-4, IL-5, and IL-12 in CIA, and IL-2 and IL-6 increased in CIA and CIA+FD, while Fractalkine and Leptin were decreased in both groups. CIA-derived MSC showed lower metabolic activity and proliferation, and significantly increased osteogenic and chondrogenic differentiation markers. Exposure of control-MSC to TNF-a partially mimicked the CIA-MSC phenotype in vitro. In conclusion, inflammatory conditions of CIA led to alterations in systemic immune cell proportions, circulating mediators, and in endogenous MSC. CIA animals respond to FD, and the combined model can be used to study the mechanisms of bone repair in inflammatory conditions.This research was funded by the project NORTE-01-0145-FEDER-000012, supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF), and AO Foundation-Switzerland (project S-15-83S). J.H.T, A.M.S, M.B.G, M.I.A and C.C were supported by FCT-Fundação para a Ciência e a Tecnologia, through the fellowships SFRH/BD/112832/2015, SFRH/BD/85968/2012, PD/BD/135489/2018, DL 57/2016/CP1360/CT0008 and DL 57/2016/CP1360/CT0004, respectively