FastSVD-ML-ROM\textit{FastSVD-ML-ROM}: A Reduced-Order Modeling Framework based on Machine Learning for Real-Time Applications

Digital twins have emerged as a key technology for optimizing the performance of engineering products and systems. High-fidelity numerical simulations constitute the backbone of engineering design, providing an accurate insight into the performance of complex systems. However, large-scale, dynamic, non-linear models require significant computational resources and are prohibitive for real-time digital twin applications. To this end, reduced order models (ROMs) are employed, to approximate the high-fidelity solutions while accurately capturing the dominant aspects of the physical behavior. The present work proposes a new machine learning (ML) platform for the development of ROMs, to handle large-scale numerical problems dealing with transient nonlinear partial differential equations. Our framework, mentioned as $\textit{FastSVD-ML-ROM}$, utilizes $\textit{(i)}$ a singular value decomposition (SVD) update methodology, to compute a linear subspace of the multi-fidelity solutions during the simulation process, $\textit{(ii)}$ convolutional autoencoders for nonlinear dimensionality reduction, $\textit{(iii)}$ feed-forward neural networks to map the input parameters to the latent spaces, and $\textit{(iv)}$ long short-term memory networks to predict and forecast the dynamics of parametric solutions. The efficiency of the $\textit{FastSVD-ML-ROM}$ framework is demonstrated for a 2D linear convection-diffusion equation, the problem of fluid around a cylinder, and the 3D blood flow inside an arterial segment. The accuracy of the reconstructed results demonstrates the robustness and assesses the efficiency of the proposed approach.Comment: 35 pages, 22 figure

Normal bone turnover markers in a patient with active Paget’s disease of bone: response to treatment with zoledronic acid

Celem leczenia choroby kości Pageta (PDB) jest zahamowanie zwiększonego obrotu kostnego. Obecnie lekami z wyboru są bisfosfoniany. Do wskazań do stosowania leków antyresorpcyjnych u pacjentów z objawowa postacią PDB należą: bóle kostne i stawowe, powikłania neurologiczne, planowany zabieg chirurgiczny w rejonie aktywnych zmian chorobowych i hiperkalcemia spowodowana unieruchomieniem. Celem terapii antyresorpcyjnej jest uzyskanie poprawy stanu klinicznego i remisji biochemicznej, ocenianej na podstawie normalizacji stężeń biomarkerów obrotu kostnego. Przed podjęciem decyzji o wdrożeniu terapii u chorych w późnej, sklerotycznej fazie choroby (burned out) należy wziąć pod uwagę pogorszenie stanu klinicznego, a zwłaszcza występowanie bólów kostnych. U tych chorych duże znaczenie ma badanie scyntygraficzne kości, ponieważ może ono uwidocznić zwiększoną aktywność osteoblastyczną, której mogą nie wykazać markery obrotu kostnego. W niniejszej pracy przedstawiono przypadek chorego w późnym, sklerotycznym stadium PDB, u którego występowały nasilone objawy kliniczne, lecz stężenia markerów obrotu kostnego były prawidłowe. Po leczeniu kwasem zoledronowym nastąpiła istotna poprawa kliniczna.The treatment of Paget’s disease of bone (PDB) aims at the suppression of abnormal bone turnover; bisphosphonates are currently the treatment of choice. Indications for antiresorptive treatment in symptomatic patients with PDB include bone or joint pain, neurological complications, surgery planned at an active pagetic site and hypercalcaemia from immobilisation. The goals of antiresorptive treatment are clinical improvement and biochemical remission, as assessed by the normalisation of bone turnover markers. Clinical deterioration, especially bone pain, should be considered before deciding to treat patients with late sclerotic (burned-out) PDB. Bone scintigraphy may be of importance in these patients, because it depicts increased osteoblastic activity, when bone markers may not. We present a case of late sclerotic PDB with clinical deterioration but normal bone turnover markers, who experienced significant clinical improvement after treatment with zoledronic acid

Multi-disciplinary optimization of variable rotor speed and active blade twist rotorcraft: Trade-off between noise and emissions

The concepts of variable rotor speed and active blade twist are emerging technologies for the next generation of civil rotorcraft. Previous research has focused on the optimum implementation of these technologies for improved fuel economy and environmental impact. Within this work, an integrated approach is deployed to quantify the concurrent reductions in rotor noise and NOx emissions. A relaxation-based free-wake inflow model, coupled with unsteady blade aerodynamics modeling, resolves the flow-field around the main rotor. Aero-acoustic predictions are performed through an acoustic-analogy-based formulation. Gaseous emissions are then predicted via stirred-reactor modeling, coupled with zero-dimensional engine performance analysis method. This strategy is incorporated into a multi-disciplinary genetic algorithm optimization process based on surrogate modeling. Optimal schedules of combined variable rotor speed and active blade twist controls are derived for a twin-engine light helicopter in descent. The accrued schedules suggest NOx reductions between 6% and 21%, simultaneously with source-noise reductions of the order of 2–8 dB, relative to the non-morphing rotor case. The developed strategy constitutes an enabling methodology for the holistic and multi-disciplinary assessment of morphing helicopter rotor configurations

A new mathematical model for the interpretation of translational research evaluating six CTLA-4 polymorphisms in high-risk melanoma patients receiving adjuvant interferon

Adjuvant therapy of stage IIB/III melanoma with interferon reduces relapse and mortality by up to 33% but is accompanied by toxicity-related complications. Polymorphisms of the CTLA-4 gene associated with autoimmune diseases could help in identifying interferon treatment benefits. We previously genotyped 286 melanoma patients and 288 healthy (unrelated) individuals for six CTLA-4 polymorphisms (SNP). Previous analyses found no significant differences between the distributions of CTLA-4 polymorphisms in the melanoma population vs. controls, no significant difference in relapse free and overall survivals among patients and no correlation between autoimmunity and specific alleles. We report new analysis of these CTLA-4 genetic profiles, using Network Phenotyping Strategy (NPS). It is graph-theory based method, analyzing the SNP patterns. Application of NPS on CTLA-4 polymorphism captures allele relationship pattern for every patient into 6-partite mathematical graph P. Graphs P are combined into weighted 6-partite graph S, which subsequently decomposed into reference relationship profiles (RRP). Finally, every individual CTLA-4 genotype pattern is characterized by the graph distances of P from eight identified RRP's. RRP's are subgraphs of S, collecting equally frequent binary allele co-occurrences in all studied loci. If S topology represents the genetic "dominant model", the RRP's and their characteristic frequencies are identical to expectation-maximization derived haplotypes and maximal likelihood estimates of their frequencies. The graphrepresentation allows showing that patient CTLA-4 haplotypes are uniquely different from the controls by absence of specific SNP combinations. New function-related insight is derived when the 6-partite graph reflects allelic state of CTLA-4. We found that we can use differences between individual P and specific RRPs to identify patient subpopulations with clearly different polymorphic patterns relatively to controls as well as to identify patients with significantly different survival. © 2014 Pancoska et al

Serum Anti-Müllerian Hormone Is Significantly Altered by Downregulation With Daily Gonadotropin-Releasing Hormone Agonist: A Prospective Cohort Study

Research Question: What is the effect of gonadotropin-releasing hormone (GnRH)-agonist treatment on serum anti-Müllerian hormone (AMH)?Design: This prospective cohort study conducted in a tertiary university hospital comprised patients (n = 52) who self-administered daily triptorelin (0.1 mg/0.1 mL) subcutaneously for 14 days from menstrual cycle day 21 ± 3, between July 2015 and March 2016. Enrolled women were 18–43 years old, considered normal ovarian responders, with a planned GnRH agonist controlled ovarian stimulation protocol. The primary endpoint was to evaluate the effect of GnRH agonist on serum AMH levels after 7 and 14 days of treatment.Results: Under GnRH agonist treatment, serum AMH was significantly decreased vs. baseline on day 7 (mean change from baseline: −0.265 ng/mL; 95% confidence interval [CI], −0.395 to −0.135 ng/mL; p < 0.001). On day 14, serum AMH was significantly increased (mean change from baseline: 0.289 ng/mL; 95% CI, 0.140–0.439 ng/mL; p < 0.001). Although the median change in AMH from baseline was only −14.9% on day 7 and +17.4% on day 14, from day 7 to 14 AMH significantly increased by 0.55 ng/mL (43.8%; p < 0.001), which is of paramount clinical importance. A linear, mixed-effect model demonstrated that GnRH agonist treatment for 7 and 14 days had a highly significant effect on serum AMH concentration after adjustment for confounding factors (age, body mass index, baseline antral follicle count, and visit). AMH assay precision was excellent (four aliquots/sample); coefficient of variation was 1.2–1.4%.Conclusions: GnRH agonist treatment had a clinically significant effect on serum AMH, dependent on treatment duration. The clear V-shaped response of AMH level to daily GnRH agonist treatment has important clinical implications for assessing ovarian reserve and predicting ovarian response, thus AMH measurements under GnRH agonist downregulation should be interpreted with great caution

Guidelines on Chemotherapy in Advanced Stage Gynecological Malignancies: An Evaluation of 224 Professional Societies and Organizations

BACKGROUND: Clinical practice guidelines are important for guiding practice, but it is unclear if they are commensurate with the available evidence. METHODS: We examined guidelines produced by cancer and gynecological societies and organizations and evaluated their coverage of and stance towards chemotherapy for advanced stage disease among 4 gynecological malignancies (breast, ovarian, cervical, endometrial cancer) where the evidence for the use of chemotherapy is very different (substantial and conclusive for breast and ovarian cancer, limited and suggesting no major benefit for cervical and endometrial cancer). Eligible societies and organizations were identified through systematic internet searches (last update June 2009). Pertinent websites were scrutinized for presence of clinical practice guidelines, and relative guidelines were analyzed. RESULTS: Among 224 identified eligible societies and organizations, 69 (31%) provided any sort of guidelines, while recommendations for chemotherapy on advanced stage gynecological malignancies were available in 20 of them. Only 14 had developed their own guideline, and only 5 had developed guidelines for all 4 malignancies. Use of levels of evidence and grades of recommendations, and aspects of the production, implementation, and timeliness of the guidelines did not differ significantly across malignancies. Guidelines on breast and ovarian cancer utilized significantly more randomized trials and meta-analyses. Guidelines differed across malignancies on their coverage of disease-free survival (p = 0.033), response rates (p = 0.024), symptoms relief (p = 0.005), quality of life (p = 0.001) and toxicity (p = 0.039), with breast and ovarian cancer guidelines typically covering more frequently these outcomes. All guidelines explicitly or implicitly endorsed the use of chemotherapy. CONCLUSIONS: Clinical practice guidelines are provided by the minority of professional societies and organizations. Available guidelines tend to recommend chemotherapy even for diseases where the effect of chemotherapy is controversial and recommendations are based on scant evidence